                         SEQUENCE LISTING

<110>  AskGene Pharma Inc.
 
<120>  CHIMERIC MOLECULES COMPRISING IL-12 AGONIST POLYPEPTIDE

<130>  AG3-026WO

<140>  63/136,640
<141>  2021-01-12

<160>  137   

<170>  PatentIn version 3.5

<210>  1
<211>  241
<212>  PRT
<213>  artificial

<220>
<223>  VL-VH scFv derived from Ustekinumab

<400>  1

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Trp 
            20                  25                  30          


Leu Ala Trp Tyr Gln Gln Lys Pro Glu Lys Ala Pro Lys Ser Leu Ile 
        35                  40                  45              


Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ile Tyr Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser 
            100                 105                 110         


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Gln 
        115                 120                 125             


Ser Gly Ala Glu Val Lys Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys 
    130                 135                 140                 


Lys Gly Ser Gly Tyr Ser Phe Thr Thr Tyr Trp Leu Gly Trp Val Arg 
145                 150                 155                 160 


Gln Met Pro Gly Lys Gly Leu Asp Trp Ile Gly Ile Met Ser Pro Val 
                165                 170                 175     


Asp Ser Asp Ile Arg Tyr Ser Pro Ser Phe Gln Gly Gln Val Thr Met 
            180                 185                 190         


Ser Val Asp Lys Ser Ile Thr Thr Ala Tyr Leu Gln Trp Asn Ser Leu 
        195                 200                 205             


Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys Ala Arg Arg Arg Pro Gly 
    210                 215                 220                 


Gln Gly Tyr Phe Asp Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser 
225                 230                 235                 240 


Ser 
    


<210>  2
<211>  241
<212>  PRT
<213>  artificial

<220>
<223>  VH-VL scFv derived from Ustekinumab

<400>  2

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu 
1               5                   10                  15      


Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Tyr 
            20                  25                  30          


Trp Leu Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Asp Trp Ile 
        35                  40                  45              


Gly Ile Met Ser Pro Val Asp Ser Asp Ile Arg Tyr Ser Pro Ser Phe 
    50                  55                  60                  


Gln Gly Gln Val Thr Met Ser Val Asp Lys Ser Ile Thr Thr Ala Tyr 
65                  70                  75                  80  


Leu Gln Trp Asn Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Arg Arg Pro Gly Gln Gly Tyr Phe Asp Phe Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        115                 120                 125             


Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser 
    130                 135                 140                 


Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser 
145                 150                 155                 160 


Gln Gly Ile Ser Ser Trp Leu Ala Trp Tyr Gln Gln Lys Pro Glu Lys 
                165                 170                 175     


Ala Pro Lys Ser Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val 
            180                 185                 190         


Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
        195                 200                 205             


Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln 
    210                 215                 220                 


Tyr Asn Ile Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
225                 230                 235                 240 


Lys 
    


<210>  3
<211>  241
<212>  PRT
<213>  artificial

<220>
<223>  VL-VH scFv derived from Briakinnumab

<400>  3

Gln Ser Val Leu Thr Gln Pro Pro Ser Val Ser Gly Ala Pro Gly Gln 
1               5                   10                  15      


Arg Val Thr Ile Ser Cys Ser Gly Ser Arg Ser Asn Ile Gly Ser Asn 
            20                  25                  30          


Thr Val Lys Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 
        35                  40                  45              


Ile Tyr Tyr Asn Asp Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 
    50                  55                  60                  


Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Thr Gly Leu Gln 
65                  70                  75                  80  


Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Gln Ser Tyr Asp Arg Tyr Thr 
                85                  90                  95      


His Pro Ala Leu Leu Phe Gly Thr Gly Thr Lys Val Thr Val Leu Gly 
            100                 105                 110         


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val 
        115                 120                 125             


Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu 
    130                 135                 140                 


Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Gly Met 
145                 150                 155                 160 


His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Phe 
                165                 170                 175     


Ile Arg Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val Lys Gly 
            180                 185                 190         


Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln 
        195                 200                 205             


Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Lys Thr 
    210                 215                 220                 


His Gly Ser His Asp Asn Trp Gly Gln Gly Thr Met Val Thr Val Ser 
225                 230                 235                 240 


Ser 
    


<210>  4
<211>  241
<212>  PRT
<213>  artificial

<220>
<223>  VH-VL scFv derived from Briakinnumab

<400>  4

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          


Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ala Phe Ile Arg Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  


Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Lys Thr His Gly Ser His Asp Asn Trp Gly Gln Gly Thr Met Val Thr 
            100                 105                 110         


Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
        115                 120                 125             


Gly Ser Gln Ser Val Leu Thr Gln Pro Pro Ser Val Ser Gly Ala Pro 
    130                 135                 140                 


Gly Gln Arg Val Thr Ile Ser Cys Ser Gly Ser Arg Ser Asn Ile Gly 
145                 150                 155                 160 


Ser Asn Thr Val Lys Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys 
                165                 170                 175     


Leu Leu Ile Tyr Tyr Asn Asp Gln Arg Pro Ser Gly Val Pro Asp Arg 
            180                 185                 190         


Phe Ser Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Thr Gly 
        195                 200                 205             


Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Gln Ser Tyr Asp Arg 
    210                 215                 220                 


Tyr Thr His Pro Ala Leu Leu Phe Gly Thr Gly Thr Lys Val Thr Val 
225                 230                 235                 240 


Leu 
    


<210>  5
<211>  306
<212>  PRT
<213>  artificial

<220>
<223>  P40 subunit of IL-12

<400>  5

Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr 
1               5                   10                  15      


Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu 
            20                  25                  30          


Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly 
        35                  40                  45              


Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly 
    50                  55                  60                  


Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu 
65                  70                  75                  80  


Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys 
                85                  90                  95      


Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys 
            100                 105                 110         


Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr 
        115                 120                 125             


Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln 
    130                 135                 140                 


Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly 
145                 150                 155                 160 


Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala 
                165                 170                 175     


Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala 
            180                 185                 190         


Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg 
        195                 200                 205             


Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu 
    210                 215                 220                 


Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp 
225                 230                 235                 240 


Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln 
                245                 250                 255     


Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr 
            260                 265                 270         


Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala 
        275                 280                 285             


Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro 
    290                 295                 300                 


Cys Ser 
305     


<210>  6
<211>  197
<212>  PRT
<213>  artificial

<220>
<223>  P35 subunit of IL-12

<400>  6

Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro Cys Leu 
1               5                   10                  15      


His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu Gln Lys 
            20                  25                  30          


Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu Glu Ile Asp 
        35                  40                  45              


His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala Cys Leu 
    50                  55                  60                  


Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu Thr 
65                  70                  75                  80  


Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser Phe 
                85                  90                  95      


Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met Tyr 
            100                 105                 110         


Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp Pro Lys 
        115                 120                 125             


Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp Glu Leu 
    130                 135                 140                 


Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys Ser Ser 
145                 150                 155                 160 


Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile Leu 
                165                 170                 175     


Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val Met Ser 
            180                 185                 190         


Tyr Leu Asn Ala Ser 
        195         


<210>  7
<211>  146
<212>  PRT
<213>  artificial

<220>
<223>  CD40L ectodomain (aa 116-261)

<400>  7

Gly Asp Gln Asn Pro Gln Ile Ala Ala His Val Ile Ser Glu Ala Ser 
1               5                   10                  15      


Ser Lys Thr Thr Ser Val Leu Gln Trp Ala Glu Lys Gly Tyr Tyr Thr 
            20                  25                  30          


Met Ser Asn Asn Leu Val Thr Leu Glu Asn Gly Lys Gln Leu Thr Val 
        35                  40                  45              


Lys Arg Gln Gly Leu Tyr Tyr Ile Tyr Ala Gln Val Thr Phe Cys Ser 
    50                  55                  60                  


Asn Arg Glu Ala Ser Ser Gln Ala Pro Phe Ile Ala Ser Leu Cys Leu 
65                  70                  75                  80  


Lys Ser Pro Gly Arg Phe Glu Arg Ile Leu Leu Arg Ala Ala Asn Thr 
                85                  90                  95      


His Ser Ser Ala Lys Pro Cys Gly Gln Gln Ser Ile His Leu Gly Gly 
            100                 105                 110         


Val Phe Glu Leu Gln Pro Gly Ala Ser Val Phe Val Asn Val Thr Asp 
        115                 120                 125             


Pro Ser Gln Val Ser His Gly Thr Gly Phe Thr Ser Phe Gly Leu Leu 
    130                 135                 140                 


Lys Leu 
145     


<210>  8
<211>  548
<212>  PRT
<213>  artificial

<220>
<223>  Fc - IL-12 P40 with knobs mutations

<400>  8

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp 
                245                 250                 255     


Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr 
            260                 265                 270         


Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val 
        275                 280                 285             


Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp 
    290                 295                 300                 


Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser 
305                 310                 315                 320 


Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile 
                325                 330                 335     


Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu 
            340                 345                 350         


Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile 
        355                 360                 365             


Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp 
    370                 375                 380                 


Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val 
385                 390                 395                 400 


Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp 
                405                 410                 415     


Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val 
            420                 425                 430         


Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe 
        435                 440                 445             


Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys 
    450                 455                 460                 


Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp 
465                 470                 475                 480 


Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln 
                485                 490                 495     


Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp 
            500                 505                 510         


Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val 
        515                 520                 525             


Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser 
    530                 535                 540                 


Val Pro Cys Ser 
545             


<210>  9
<211>  548
<212>  PRT
<213>  artificial

<220>
<223>  IL-12 P40-Fc with knobs mutations

<400>  9

Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr 
1               5                   10                  15      


Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu 
            20                  25                  30          


Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly 
        35                  40                  45              


Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly 
    50                  55                  60                  


Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu 
65                  70                  75                  80  


Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys 
                85                  90                  95      


Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys 
            100                 105                 110         


Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr 
        115                 120                 125             


Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln 
    130                 135                 140                 


Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly 
145                 150                 155                 160 


Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala 
                165                 170                 175     


Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala 
            180                 185                 190         


Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg 
        195                 200                 205             


Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu 
    210                 215                 220                 


Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp 
225                 230                 235                 240 


Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln 
                245                 250                 255     


Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr 
            260                 265                 270         


Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala 
        275                 280                 285             


Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro 
    290                 295                 300                 


Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
305                 310                 315                 320 


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
                325                 330                 335     


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
            340                 345                 350         


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
        355                 360                 365             


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
    370                 375                 380                 


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr 
385                 390                 395                 400 


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
                405                 410                 415     


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
            420                 425                 430         


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
        435                 440                 445             


Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val 
    450                 455                 460                 


Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
465                 470                 475                 480 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
                485                 490                 495     


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
            500                 505                 510         


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
        515                 520                 525             


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
    530                 535                 540                 


Ser Pro Gly Lys 
545             


<210>  10
<211>  760
<212>  PRT
<213>  artificial

<220>
<223>  Fc - IL-12 (P40-P35) with knobs mutations

<400>  10

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp 
                245                 250                 255     


Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr 
            260                 265                 270         


Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val 
        275                 280                 285             


Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp 
    290                 295                 300                 


Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser 
305                 310                 315                 320 


Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile 
                325                 330                 335     


Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu 
            340                 345                 350         


Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile 
        355                 360                 365             


Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp 
    370                 375                 380                 


Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val 
385                 390                 395                 400 


Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp 
                405                 410                 415     


Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val 
            420                 425                 430         


Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe 
        435                 440                 445             


Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys 
    450                 455                 460                 


Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp 
465                 470                 475                 480 


Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln 
                485                 490                 495     


Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp 
            500                 505                 510         


Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val 
        515                 520                 525             


Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser 
    530                 535                 540                 


Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
545                 550                 555                 560 


Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe 
                565                 570                 575     


Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met 
            580                 585                 590         


Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu 
        595                 600                 605             


Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu 
    610                 615                 620                 


Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser 
625                 630                 635                 640 


Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys 
                645                 650                 655     


Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu 
            660                 665                 670         


Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met 
        675                 680                 685             


Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile 
    690                 695                 700                 


Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln 
705                 710                 715                 720 


Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu 
                725                 730                 735     


Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg 
            740                 745                 750         


Val Met Ser Tyr Leu Asn Ala Ser 
        755                 760 


<210>  11
<211>  921
<212>  PRT
<213>  artificial

<220>
<223>  CD40L - Fc - IL-12 (P40-P35) with knobs mutations


<220>
<221>  variant
<222>  (1)..(161)
<223>  n = 1, 2 or 3

<400>  11

Gly Asp Gln Asn Pro Gln Ile Ala Ala His Val Ile Ser Glu Ala Ser 
1               5                   10                  15      


Ser Lys Thr Thr Ser Val Leu Gln Trp Ala Glu Lys Gly Tyr Tyr Thr 
            20                  25                  30          


Met Ser Asn Asn Leu Val Thr Leu Glu Asn Gly Lys Gln Leu Thr Val 
        35                  40                  45              


Lys Arg Gln Gly Leu Tyr Tyr Ile Tyr Ala Gln Val Thr Phe Cys Ser 
    50                  55                  60                  


Asn Arg Glu Ala Ser Ser Gln Ala Pro Phe Ile Ala Ser Leu Cys Leu 
65                  70                  75                  80  


Lys Ser Pro Gly Arg Phe Glu Arg Ile Leu Leu Arg Ala Ala Asn Thr 
                85                  90                  95      


His Ser Ser Ala Lys Pro Cys Gly Gln Gln Ser Ile His Leu Gly Gly 
            100                 105                 110         


Val Phe Glu Leu Gln Pro Gly Ala Ser Val Phe Val Asn Val Thr Asp 
        115                 120                 125             


Pro Ser Gln Val Ser His Gly Thr Gly Phe Thr Ser Phe Gly Leu Leu 
    130                 135                 140                 


Lys Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
145                 150                 155                 160 


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
                165                 170                 175     


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
            180                 185                 190         


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
        195                 200                 205             


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
    210                 215                 220                 


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr 
225                 230                 235                 240 


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
                245                 250                 255     


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
            260                 265                 270         


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
        275                 280                 285             


Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val 
    290                 295                 300                 


Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
305                 310                 315                 320 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
                325                 330                 335     


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
            340                 345                 350         


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
        355                 360                 365             


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
    370                 375                 380                 


Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
385                 390                 395                 400 


Gly Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu 
                405                 410                 415     


Asp Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp 
            420                 425                 430         


Thr Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu 
        435                 440                 445             


Val Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly 
    450                 455                 460                 


Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His 
465                 470                 475                 480 


Ser Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp 
                485                 490                 495     


Ile Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys 
            500                 505                 510         


Glu Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr 
        515                 520                 525             


Ile Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser 
    530                 535                 540                 


Asp Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg 
545                 550                 555                 560 


Val Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu 
                565                 570                 575     


Asp Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met 
            580                 585                 590         


Val Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe 
        595                 600                 605             


Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu 
    610                 615                 620                 


Lys Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro 
625                 630                 635                 640 


Asp Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val 
                645                 650                 655     


Gln Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr 
            660                 665                 670         


Asp Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser 
        675                 680                 685             


Val Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala 
    690                 695                 700                 


Ser Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
705                 710                 715                 720 


Gly Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met 
                725                 730                 735     


Phe Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn 
            740                 745                 750         


Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser 
        755                 760                 765             


Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val 
    770                 775                 780                 


Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn 
785                 790                 795                 800 


Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg 
                805                 810                 815     


Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp 
            820                 825                 830         


Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu 
        835                 840                 845             


Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val 
    850                 855                 860                 


Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro 
865                 870                 875                 880 


Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys 
                885                 890                 895     


Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp 
            900                 905                 910         


Arg Val Met Ser Tyr Leu Asn Ala Ser 
        915                 920     


<210>  12
<211>  921
<212>  PRT
<213>  artificial

<220>
<223>  IL-12 (P40-P35) - Fc - CD40L with knobs mutations


<220>
<221>  variant
<222>  (761)..(921)
<223>  sequence from positions 761 to 921 may be absent or present in 
       1-3 copies (n=0, 1, 2 or 3)

<400>  12

Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr 
1               5                   10                  15      


Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu 
            20                  25                  30          


Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly 
        35                  40                  45              


Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly 
    50                  55                  60                  


Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu 
65                  70                  75                  80  


Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys 
                85                  90                  95      


Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys 
            100                 105                 110         


Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr 
        115                 120                 125             


Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln 
    130                 135                 140                 


Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly 
145                 150                 155                 160 


Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala 
                165                 170                 175     


Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala 
            180                 185                 190         


Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg 
        195                 200                 205             


Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu 
    210                 215                 220                 


Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp 
225                 230                 235                 240 


Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln 
                245                 250                 255     


Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr 
            260                 265                 270         


Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala 
        275                 280                 285             


Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro 
    290                 295                 300                 


Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
305                 310                 315                 320 


Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro Cys 
                325                 330                 335     


Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu Gln 
            340                 345                 350         


Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu Glu Ile 
        355                 360                 365             


Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala Cys 
    370                 375                 380                 


Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu 
385                 390                 395                 400 


Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser 
                405                 410                 415     


Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met 
            420                 425                 430         


Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp Pro 
        435                 440                 445             


Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp Glu 
    450                 455                 460                 


Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys Ser 
465                 470                 475                 480 


Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile 
                485                 490                 495     


Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val Met 
            500                 505                 510         


Ser Tyr Leu Asn Ala Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
        515                 520                 525             


Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 
    530                 535                 540                 


Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
545                 550                 555                 560 


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
                565                 570                 575     


Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
            580                 585                 590         


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
        595                 600                 605             


Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
    610                 615                 620                 


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
625                 630                 635                 640 


Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
                645                 650                 655     


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr 
            660                 665                 670         


Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser 
        675                 680                 685             


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
    690                 695                 700                 


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
705                 710                 715                 720 


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
                725                 730                 735     


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
            740                 745                 750         


Ser Leu Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly 
        755                 760                 765             


Gly Ser Gly Gly Gly Gly Ser Gly Asp Gln Asn Pro Gln Ile Ala Ala 
    770                 775                 780                 


His Val Ile Ser Glu Ala Ser Ser Lys Thr Thr Ser Val Leu Gln Trp 
785                 790                 795                 800 


Ala Glu Lys Gly Tyr Tyr Thr Met Ser Asn Asn Leu Val Thr Leu Glu 
                805                 810                 815     


Asn Gly Lys Gln Leu Thr Val Lys Arg Gln Gly Leu Tyr Tyr Ile Tyr 
            820                 825                 830         


Ala Gln Val Thr Phe Cys Ser Asn Arg Glu Ala Ser Ser Gln Ala Pro 
        835                 840                 845             


Phe Ile Ala Ser Leu Cys Leu Lys Ser Pro Gly Arg Phe Glu Arg Ile 
    850                 855                 860                 


Leu Leu Arg Ala Ala Asn Thr His Ser Ser Ala Lys Pro Cys Gly Gln 
865                 870                 875                 880 


Gln Ser Ile His Leu Gly Gly Val Phe Glu Leu Gln Pro Gly Ala Ser 
                885                 890                 895     


Val Phe Val Asn Val Thr Asp Pro Ser Gln Val Ser His Gly Thr Gly 
            900                 905                 910         


Phe Thr Ser Phe Gly Leu Leu Lys Leu 
        915                 920     


<210>  13
<211>  770
<212>  PRT
<213>  artificial

<220>
<223>  Fc- scFV which binds to IL-12-VL-VH Ustekinumab-Briakinnumab 
       [ASKGD111_CX10__1]

<400>  13

Met Gly Val Lys Val Leu Phe Ala Leu Ile Cys Ile Ala Val Ala Glu 
1               5                   10                  15      


Ala Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
            20                  25                  30          


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
        35                  40                  45              


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
    50                  55                  60                  


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
65                  70                  75                  80  


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
                85                  90                  95      


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
            100                 105                 110         


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
        115                 120                 125             


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
    130                 135                 140                 


Val Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val 
145                 150                 155                 160 


Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
                165                 170                 175     


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
            180                 185                 190         


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr 
        195                 200                 205             


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
    210                 215                 220                 


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
225                 230                 235                 240 


Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Ala 
                245                 250                 255     


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln 
            260                 265                 270         


Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr 
        275                 280                 285             


Cys Arg Ala Ser Gln Gly Ile Ser Ser Trp Leu Ala Trp Tyr Gln Gln 
    290                 295                 300                 


Lys Pro Glu Lys Ala Pro Lys Ser Leu Ile Tyr Ala Ala Ser Ser Leu 
305                 310                 315                 320 


Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
                325                 330                 335     


Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr 
            340                 345                 350         


Tyr Cys Gln Gln Tyr Asn Ile Tyr Pro Tyr Thr Phe Gly Gln Gly Thr 
        355                 360                 365             


Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
    370                 375                 380                 


Gly Gly Gly Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 
385                 390                 395                 400 


Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser 
                405                 410                 415     


Phe Thr Thr Tyr Trp Leu Gly Trp Val Arg Gln Met Pro Gly Lys Gly 
            420                 425                 430         


Leu Asp Trp Ile Gly Ile Met Ser Pro Val Asp Ser Asp Ile Arg Tyr 
        435                 440                 445             


Ser Pro Ser Phe Gln Gly Gln Val Thr Met Ser Val Asp Lys Ser Ile 
    450                 455                 460                 


Thr Thr Ala Tyr Leu Gln Trp Asn Ser Leu Lys Ala Ser Asp Thr Ala 
465                 470                 475                 480 


Met Tyr Tyr Cys Ala Arg Arg Arg Pro Gly Gln Gly Tyr Phe Asp Phe 
                485                 490                 495     


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser 
            500                 505                 510         


Gly Gly Gly Gly Ser Ala Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        515                 520                 525             


Ser Gln Ser Val Leu Thr Gln Pro Pro Ser Val Ser Gly Ala Pro Gly 
    530                 535                 540                 


Gln Arg Val Thr Ile Ser Cys Ser Gly Ser Arg Ser Asn Ile Gly Ser 
545                 550                 555                 560 


Asn Thr Val Lys Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu 
                565                 570                 575     


Leu Ile Tyr Tyr Asn Asp Gln Arg Pro Ser Gly Val Pro Asp Arg Phe 
            580                 585                 590         


Ser Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Thr Gly Leu 
        595                 600                 605             


Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Gln Ser Tyr Asp Arg Tyr 
    610                 615                 620                 


Thr His Pro Ala Leu Leu Phe Gly Thr Gly Thr Lys Val Thr Val Leu 
625                 630                 635                 640 


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln 
                645                 650                 655     


Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser 
            660                 665                 670         


Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Gly 
        675                 680                 685             


Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala 
    690                 695                 700                 


Phe Ile Arg Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val Lys 
705                 710                 715                 720 


Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
                725                 730                 735     


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Lys 
            740                 745                 750         


Thr His Gly Ser His Asp Asn Trp Gly Gln Gly Thr Met Val Thr Val 
        755                 760                 765             


Ser Ser 
    770 


<210>  14
<211>  753
<212>  PRT
<213>  artificial

<220>
<223>  Fc-scFV which binds to IL-12-VL-VH Briakinnumab- Ustekinumab

<400>  14

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Ala Gly 
225                 230                 235                 240 


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Val Leu Thr Gln Pro 
                245                 250                 255     


Pro Ser Val Ser Gly Ala Pro Gly Gln Arg Val Thr Ile Ser Cys Ser 
            260                 265                 270         


Gly Ser Arg Ser Asn Ile Gly Ser Asn Thr Val Lys Trp Tyr Gln Gln 
        275                 280                 285             


Leu Pro Gly Thr Ala Pro Lys Leu Leu Ile Tyr Tyr Asn Asp Gln Arg 
    290                 295                 300                 


Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Lys Ser Gly Thr Ser 
305                 310                 315                 320 


Ala Ser Leu Ala Ile Thr Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr 
                325                 330                 335     


Tyr Cys Gln Ser Tyr Asp Arg Tyr Thr His Pro Ala Leu Leu Phe Gly 
            340                 345                 350         


Thr Gly Thr Lys Val Thr Val Leu Gly Gly Gly Gly Ser Gly Gly Gly 
        355                 360                 365             


Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly 
    370                 375                 380                 


Gly Val Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser 
385                 390                 395                 400 


Gly Phe Thr Phe Ser Ser Tyr Gly Met His Trp Val Arg Gln Ala Pro 
                405                 410                 415     


Gly Lys Gly Leu Glu Trp Val Ala Phe Ile Arg Tyr Asp Gly Ser Asn 
            420                 425                 430         


Lys Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp 
        435                 440                 445             


Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu 
    450                 455                 460                 


Asp Thr Ala Val Tyr Tyr Cys Lys Thr His Gly Ser His Asp Asn Trp 
465                 470                 475                 480 


Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly 
                485                 490                 495     


Gly Gly Gly Ser Ala Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
            500                 505                 510         


Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
        515                 520                 525             


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Trp 
    530                 535                 540                 


Leu Ala Trp Tyr Gln Gln Lys Pro Glu Lys Ala Pro Lys Ser Leu Ile 
545                 550                 555                 560 


Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 
                565                 570                 575     


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
            580                 585                 590         


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ile Tyr Pro Tyr 
        595                 600                 605             


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser 
    610                 615                 620                 


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Gln 
625                 630                 635                 640 


Ser Gly Ala Glu Val Lys Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys 
                645                 650                 655     


Lys Gly Ser Gly Tyr Ser Phe Thr Thr Tyr Trp Leu Gly Trp Val Arg 
            660                 665                 670         


Gln Met Pro Gly Lys Gly Leu Asp Trp Ile Gly Ile Met Ser Pro Val 
        675                 680                 685             


Asp Ser Asp Ile Arg Tyr Ser Pro Ser Phe Gln Gly Gln Val Thr Met 
    690                 695                 700                 


Ser Val Asp Lys Ser Ile Thr Thr Ala Tyr Leu Gln Trp Asn Ser Leu 
705                 710                 715                 720 


Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys Ala Arg Arg Arg Pro Gly 
                725                 730                 735     


Gln Gly Tyr Phe Asp Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser 
            740                 745                 750         


Ser 
    


<210>  15
<211>  752
<212>  PRT
<213>  artificial

<220>
<223>  Fc - scFV which binds to IL-12-VL-VH Briakinnumab- Ustekinumab 
       with cleavable linker

<400>  15

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Ala Gly 
225                 230                 235                 240 


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Val Leu Thr Gln Pro 
                245                 250                 255     


Pro Ser Val Ser Gly Ala Pro Gly Gln Arg Val Thr Ile Ser Cys Ser 
            260                 265                 270         


Gly Ser Arg Ser Asn Ile Gly Ser Asn Thr Val Lys Trp Tyr Gln Gln 
        275                 280                 285             


Leu Pro Gly Thr Ala Pro Lys Leu Leu Ile Tyr Tyr Asn Asp Gln Arg 
    290                 295                 300                 


Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Lys Ser Gly Thr Ser 
305                 310                 315                 320 


Ala Ser Leu Ala Ile Thr Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr 
                325                 330                 335     


Tyr Cys Gln Ser Tyr Asp Arg Tyr Thr His Pro Ala Leu Leu Phe Gly 
            340                 345                 350         


Thr Gly Thr Lys Val Thr Val Leu Gly Gly Gly Gly Ser Gly Gly Gly 
        355                 360                 365             


Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly 
    370                 375                 380                 


Gly Val Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser 
385                 390                 395                 400 


Gly Phe Thr Phe Ser Ser Tyr Gly Met His Trp Val Arg Gln Ala Pro 
                405                 410                 415     


Gly Lys Gly Leu Glu Trp Val Ala Phe Ile Arg Tyr Asp Gly Ser Asn 
            420                 425                 430         


Lys Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp 
        435                 440                 445             


Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu 
    450                 455                 460                 


Asp Thr Ala Val Tyr Tyr Cys Lys Thr His Gly Ser His Asp Asn Trp 
465                 470                 475                 480 


Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly 
                485                 490                 495     


Gly Gly Gly Ser Gly Pro Leu Gly Val Arg Gly Gly Gly Gly Ser Asp 
            500                 505                 510         


Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp 
        515                 520                 525             


Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Trp Leu 
    530                 535                 540                 


Ala Trp Tyr Gln Gln Lys Pro Glu Lys Ala Pro Lys Ser Leu Ile Tyr 
545                 550                 555                 560 


Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser 
                565                 570                 575     


Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 
            580                 585                 590         


Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ile Tyr Pro Tyr Thr 
        595                 600                 605             


Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly 
    610                 615                 620                 


Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Gln Ser 
625                 630                 635                 640 


Gly Ala Glu Val Lys Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys Lys 
                645                 650                 655     


Gly Ser Gly Tyr Ser Phe Thr Thr Tyr Trp Leu Gly Trp Val Arg Gln 
            660                 665                 670         


Met Pro Gly Lys Gly Leu Asp Trp Ile Gly Ile Met Ser Pro Val Asp 
        675                 680                 685             


Ser Asp Ile Arg Tyr Ser Pro Ser Phe Gln Gly Gln Val Thr Met Ser 
    690                 695                 700                 


Val Asp Lys Ser Ile Thr Thr Ala Tyr Leu Gln Trp Asn Ser Leu Lys 
705                 710                 715                 720 


Ala Ser Asp Thr Ala Met Tyr Tyr Cys Ala Arg Arg Arg Pro Gly Gln 
                725                 730                 735     


Gly Tyr Phe Asp Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
            740                 745                 750         


<210>  16
<211>  914
<212>  PRT
<213>  artificial

<220>
<223>  CD40L - Fc - scFV which binds to IL-12-VL-VH 
       Ustekinumab-Briakinnumab


<220>
<221>  variant
<222>  (1)..(161)
<223>  sequence from positions 1 to 161 may be present in 1-3 copies 
       (n=1, 2 or 3)

<400>  16

Gly Asp Gln Asn Pro Gln Ile Ala Ala His Val Ile Ser Glu Ala Ser 
1               5                   10                  15      


Ser Lys Thr Thr Ser Val Leu Gln Trp Ala Glu Lys Gly Tyr Tyr Thr 
            20                  25                  30          


Met Ser Asn Asn Leu Val Thr Leu Glu Asn Gly Lys Gln Leu Thr Val 
        35                  40                  45              


Lys Arg Gln Gly Leu Tyr Tyr Ile Tyr Ala Gln Val Thr Phe Cys Ser 
    50                  55                  60                  


Asn Arg Glu Ala Ser Ser Gln Ala Pro Phe Ile Ala Ser Leu Cys Leu 
65                  70                  75                  80  


Lys Ser Pro Gly Arg Phe Glu Arg Ile Leu Leu Arg Ala Ala Asn Thr 
                85                  90                  95      


His Ser Ser Ala Lys Pro Cys Gly Gln Gln Ser Ile His Leu Gly Gly 
            100                 105                 110         


Val Phe Glu Leu Gln Pro Gly Ala Ser Val Phe Val Asn Val Thr Asp 
        115                 120                 125             


Pro Ser Gln Val Ser His Gly Thr Gly Phe Thr Ser Phe Gly Leu Leu 
    130                 135                 140                 


Lys Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
145                 150                 155                 160 


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
                165                 170                 175     


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
            180                 185                 190         


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
        195                 200                 205             


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
    210                 215                 220                 


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
225                 230                 235                 240 


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
                245                 250                 255     


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
            260                 265                 270         


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
        275                 280                 285             


Val Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val 
    290                 295                 300                 


Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
305                 310                 315                 320 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
                325                 330                 335     


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr 
            340                 345                 350         


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
        355                 360                 365             


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
    370                 375                 380                 


Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Ala 
385                 390                 395                 400 


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln 
                405                 410                 415     


Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr 
            420                 425                 430         


Cys Arg Ala Ser Gln Gly Ile Ser Ser Trp Leu Ala Trp Tyr Gln Gln 
        435                 440                 445             


Lys Pro Glu Lys Ala Pro Lys Ser Leu Ile Tyr Ala Ala Ser Ser Leu 
    450                 455                 460                 


Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
465                 470                 475                 480 


Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr 
                485                 490                 495     


Tyr Cys Gln Gln Tyr Asn Ile Tyr Pro Tyr Thr Phe Gly Gln Gly Thr 
            500                 505                 510         


Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
        515                 520                 525             


Gly Gly Gly Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 
    530                 535                 540                 


Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser 
545                 550                 555                 560 


Phe Thr Thr Tyr Trp Leu Gly Trp Val Arg Gln Met Pro Gly Lys Gly 
                565                 570                 575     


Leu Asp Trp Ile Gly Ile Met Ser Pro Val Asp Ser Asp Ile Arg Tyr 
            580                 585                 590         


Ser Pro Ser Phe Gln Gly Gln Val Thr Met Ser Val Asp Lys Ser Ile 
        595                 600                 605             


Thr Thr Ala Tyr Leu Gln Trp Asn Ser Leu Lys Ala Ser Asp Thr Ala 
    610                 615                 620                 


Met Tyr Tyr Cys Ala Arg Arg Arg Pro Gly Gln Gly Tyr Phe Asp Phe 
625                 630                 635                 640 


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser 
                645                 650                 655     


Gly Gly Gly Gly Ser Ala Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly 
            660                 665                 670         


Ser Gln Ser Val Leu Thr Gln Pro Pro Ser Val Ser Gly Ala Pro Gly 
        675                 680                 685             


Gln Arg Val Thr Ile Ser Cys Ser Gly Ser Arg Ser Asn Ile Gly Ser 
    690                 695                 700                 


Asn Thr Val Lys Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu 
705                 710                 715                 720 


Leu Ile Tyr Tyr Asn Asp Gln Arg Pro Ser Gly Val Pro Asp Arg Phe 
                725                 730                 735     


Ser Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Thr Gly Leu 
            740                 745                 750         


Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Gln Ser Tyr Asp Arg Tyr 
        755                 760                 765             


Thr His Pro Ala Leu Leu Phe Gly Thr Gly Thr Lys Val Thr Val Leu 
    770                 775                 780                 


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln 
785                 790                 795                 800 


Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser 
                805                 810                 815     


Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Gly 
            820                 825                 830         


Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala 
        835                 840                 845             


Phe Ile Arg Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val Lys 
    850                 855                 860                 


Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
865                 870                 875                 880 


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Lys 
                885                 890                 895     


Thr His Gly Ser His Asp Asn Trp Gly Gln Gly Thr Met Val Thr Val 
            900                 905                 910         


Ser Ser 
        


<210>  17
<211>  913
<212>  PRT
<213>  artificial

<220>
<223>  CD40L - Fc - scFV which binds to IL-12-VL-VH Briakinnumab- 
       Ustekinumab with cleavable linker


<220>
<221>  repeat
<222>  (1)..(161)
<223>  sequence from positions 1 to 161 may be present in 1-3 copies 
       (n=1, 2 or 3)

<400>  17

Gly Asp Gln Asn Pro Gln Ile Ala Ala His Val Ile Ser Glu Ala Ser 
1               5                   10                  15      


Ser Lys Thr Thr Ser Val Leu Gln Trp Ala Glu Lys Gly Tyr Tyr Thr 
            20                  25                  30          


Met Ser Asn Asn Leu Val Thr Leu Glu Asn Gly Lys Gln Leu Thr Val 
        35                  40                  45              


Lys Arg Gln Gly Leu Tyr Tyr Ile Tyr Ala Gln Val Thr Phe Cys Ser 
    50                  55                  60                  


Asn Arg Glu Ala Ser Ser Gln Ala Pro Phe Ile Ala Ser Leu Cys Leu 
65                  70                  75                  80  


Lys Ser Pro Gly Arg Phe Glu Arg Ile Leu Leu Arg Ala Ala Asn Thr 
                85                  90                  95      


His Ser Ser Ala Lys Pro Cys Gly Gln Gln Ser Ile His Leu Gly Gly 
            100                 105                 110         


Val Phe Glu Leu Gln Pro Gly Ala Ser Val Phe Val Asn Val Thr Asp 
        115                 120                 125             


Pro Ser Gln Val Ser His Gly Thr Gly Phe Thr Ser Phe Gly Leu Leu 
    130                 135                 140                 


Lys Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
145                 150                 155                 160 


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
                165                 170                 175     


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
            180                 185                 190         


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
        195                 200                 205             


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
    210                 215                 220                 


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
225                 230                 235                 240 


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
                245                 250                 255     


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
            260                 265                 270         


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
        275                 280                 285             


Val Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val 
    290                 295                 300                 


Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
305                 310                 315                 320 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
                325                 330                 335     


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr 
            340                 345                 350         


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
        355                 360                 365             


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
    370                 375                 380                 


Ser Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Ala 
385                 390                 395                 400 


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Val Leu Thr Gln 
                405                 410                 415     


Pro Pro Ser Val Ser Gly Ala Pro Gly Gln Arg Val Thr Ile Ser Cys 
            420                 425                 430         


Ser Gly Ser Arg Ser Asn Ile Gly Ser Asn Thr Val Lys Trp Tyr Gln 
        435                 440                 445             


Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu Ile Tyr Tyr Asn Asp Gln 
    450                 455                 460                 


Arg Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Lys Ser Gly Thr 
465                 470                 475                 480 


Ser Ala Ser Leu Ala Ile Thr Gly Leu Gln Ala Glu Asp Glu Ala Asp 
                485                 490                 495     


Tyr Tyr Cys Gln Ser Tyr Asp Arg Tyr Thr His Pro Ala Leu Leu Phe 
            500                 505                 510         


Gly Thr Gly Thr Lys Val Thr Val Leu Gly Gly Gly Gly Ser Gly Gly 
        515                 520                 525             


Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly 
    530                 535                 540                 


Gly Gly Val Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala 
545                 550                 555                 560 


Ser Gly Phe Thr Phe Ser Ser Tyr Gly Met His Trp Val Arg Gln Ala 
                565                 570                 575     


Pro Gly Lys Gly Leu Glu Trp Val Ala Phe Ile Arg Tyr Asp Gly Ser 
            580                 585                 590         


Asn Lys Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg 
        595                 600                 605             


Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala 
    610                 615                 620                 


Glu Asp Thr Ala Val Tyr Tyr Cys Lys Thr His Gly Ser His Asp Asn 
625                 630                 635                 640 


Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser 
                645                 650                 655     


Gly Gly Gly Gly Ser Gly Pro Leu Gly Val Arg Gly Gly Gly Gly Ser 
            660                 665                 670         


Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
        675                 680                 685             


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Trp 
    690                 695                 700                 


Leu Ala Trp Tyr Gln Gln Lys Pro Glu Lys Ala Pro Lys Ser Leu Ile 
705                 710                 715                 720 


Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 
                725                 730                 735     


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
            740                 745                 750         


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ile Tyr Pro Tyr 
        755                 760                 765             


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser 
    770                 775                 780                 


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Gln 
785                 790                 795                 800 


Ser Gly Ala Glu Val Lys Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys 
                805                 810                 815     


Lys Gly Ser Gly Tyr Ser Phe Thr Thr Tyr Trp Leu Gly Trp Val Arg 
            820                 825                 830         


Gln Met Pro Gly Lys Gly Leu Asp Trp Ile Gly Ile Met Ser Pro Val 
        835                 840                 845             


Asp Ser Asp Ile Arg Tyr Ser Pro Ser Phe Gln Gly Gln Val Thr Met 
    850                 855                 860                 


Ser Val Asp Lys Ser Ile Thr Thr Ala Tyr Leu Gln Trp Asn Ser Leu 
865                 870                 875                 880 


Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys Ala Arg Arg Arg Pro Gly 
                885                 890                 895     


Gln Gly Tyr Phe Asp Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser 
            900                 905                 910         


Ser 
    


<210>  18
<211>  914
<212>  PRT
<213>  artificial

<220>
<223>  scFV which binds to IL-12-VL-VH Ustekinumab-Briakinnumab - Fc - 
       CD40L


<220>
<221>  variant
<222>  (754)..(914)
<223>  sequence from positions 754 to 914 may be absent or present in 
       1-3 copies (n=0, 1, 2 or 3)

<400>  18

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Trp 
            20                  25                  30          


Leu Ala Trp Tyr Gln Gln Lys Pro Glu Lys Ala Pro Lys Ser Leu Ile 
        35                  40                  45              


Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ile Tyr Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser 
            100                 105                 110         


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Gln 
        115                 120                 125             


Ser Gly Ala Glu Val Lys Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys 
    130                 135                 140                 


Lys Gly Ser Gly Tyr Ser Phe Thr Thr Tyr Trp Leu Gly Trp Val Arg 
145                 150                 155                 160 


Gln Met Pro Gly Lys Gly Leu Asp Trp Ile Gly Ile Met Ser Pro Val 
                165                 170                 175     


Asp Ser Asp Ile Arg Tyr Ser Pro Ser Phe Gln Gly Gln Val Thr Met 
            180                 185                 190         


Ser Val Asp Lys Ser Ile Thr Thr Ala Tyr Leu Gln Trp Asn Ser Leu 
        195                 200                 205             


Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys Ala Arg Arg Arg Pro Gly 
    210                 215                 220                 


Gln Gly Tyr Phe Asp Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser 
225                 230                 235                 240 


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Ala Gly Gly Gly 
                245                 250                 255     


Gly Ser Gly Gly Gly Gly Ser Gln Ser Val Leu Thr Gln Pro Pro Ser 
            260                 265                 270         


Val Ser Gly Ala Pro Gly Gln Arg Val Thr Ile Ser Cys Ser Gly Ser 
        275                 280                 285             


Arg Ser Asn Ile Gly Ser Asn Thr Val Lys Trp Tyr Gln Gln Leu Pro 
    290                 295                 300                 


Gly Thr Ala Pro Lys Leu Leu Ile Tyr Tyr Asn Asp Gln Arg Pro Ser 
305                 310                 315                 320 


Gly Val Pro Asp Arg Phe Ser Gly Ser Lys Ser Gly Thr Ser Ala Ser 
                325                 330                 335     


Leu Ala Ile Thr Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys 
            340                 345                 350         


Gln Ser Tyr Asp Arg Tyr Thr His Pro Ala Leu Leu Phe Gly Thr Gly 
        355                 360                 365             


Thr Lys Val Thr Val Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    370                 375                 380                 


Gly Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val 
385                 390                 395                 400 


Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe 
                405                 410                 415     


Thr Phe Ser Ser Tyr Gly Met His Trp Val Arg Gln Ala Pro Gly Lys 
            420                 425                 430         


Gly Leu Glu Trp Val Ala Phe Ile Arg Tyr Asp Gly Ser Asn Lys Tyr 
        435                 440                 445             


Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser 
    450                 455                 460                 


Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr 
465                 470                 475                 480 


Ala Val Tyr Tyr Cys Lys Thr His Gly Ser His Asp Asn Trp Gly Gln 
                485                 490                 495     


Gly Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly 
            500                 505                 510         


Gly Ser Ala Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys 
        515                 520                 525             


Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 
    530                 535                 540                 


Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
545                 550                 555                 560 


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
                565                 570                 575     


Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
            580                 585                 590         


Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 
        595                 600                 605             


Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 
    610                 615                 620                 


Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys 
625                 630                 635                 640 


Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr 
                645                 650                 655     


Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser 
            660                 665                 670         


Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
        675                 680                 685             


Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
    690                 695                 700                 


Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys 
705                 710                 715                 720 


Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
                725                 730                 735     


Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
            740                 745                 750         


Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
        755                 760                 765             


Gly Asp Gln Asn Pro Gln Ile Ala Ala His Val Ile Ser Glu Ala Ser 
    770                 775                 780                 


Ser Lys Thr Thr Ser Val Leu Gln Trp Ala Glu Lys Gly Tyr Tyr Thr 
785                 790                 795                 800 


Met Ser Asn Asn Leu Val Thr Leu Glu Asn Gly Lys Gln Leu Thr Val 
                805                 810                 815     


Lys Arg Gln Gly Leu Tyr Tyr Ile Tyr Ala Gln Val Thr Phe Cys Ser 
            820                 825                 830         


Asn Arg Glu Ala Ser Ser Gln Ala Pro Phe Ile Ala Ser Leu Cys Leu 
        835                 840                 845             


Lys Ser Pro Gly Arg Phe Glu Arg Ile Leu Leu Arg Ala Ala Asn Thr 
    850                 855                 860                 


His Ser Ser Ala Lys Pro Cys Gly Gln Gln Ser Ile His Leu Gly Gly 
865                 870                 875                 880 


Val Phe Glu Leu Gln Pro Gly Ala Ser Val Phe Val Asn Val Thr Asp 
                885                 890                 895     


Pro Ser Gln Val Ser His Gly Thr Gly Phe Thr Ser Phe Gly Leu Leu 
            900                 905                 910         


Lys Leu 
        


<210>  19
<211>  913
<212>  PRT
<213>  artificial

<220>
<223>  scFV which binds to IL-12-VL-VH Ustekinumab-Briakinnumab - Fc - 
       CD40L, with a cleavable linker


<220>
<221>  repeat
<222>  (753)..(913)
<223>  sequence from positions 753 to 913 may be absent or present in 
       1-3 copies (n=0, 1, 2 or 3)

<400>  19

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Trp 
            20                  25                  30          


Leu Ala Trp Tyr Gln Gln Lys Pro Glu Lys Ala Pro Lys Ser Leu Ile 
        35                  40                  45              


Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ile Tyr Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser 
            100                 105                 110         


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Gln 
        115                 120                 125             


Ser Gly Ala Glu Val Lys Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys 
    130                 135                 140                 


Lys Gly Ser Gly Tyr Ser Phe Thr Thr Tyr Trp Leu Gly Trp Val Arg 
145                 150                 155                 160 


Gln Met Pro Gly Lys Gly Leu Asp Trp Ile Gly Ile Met Ser Pro Val 
                165                 170                 175     


Asp Ser Asp Ile Arg Tyr Ser Pro Ser Phe Gln Gly Gln Val Thr Met 
            180                 185                 190         


Ser Val Asp Lys Ser Ile Thr Thr Ala Tyr Leu Gln Trp Asn Ser Leu 
        195                 200                 205             


Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys Ala Arg Arg Arg Pro Gly 
    210                 215                 220                 


Gln Gly Tyr Phe Asp Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser 
225                 230                 235                 240 


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Pro Leu Gly Val 
                245                 250                 255     


Arg Gly Gly Gly Gly Ser Gln Ser Val Leu Thr Gln Pro Pro Ser Val 
            260                 265                 270         


Ser Gly Ala Pro Gly Gln Arg Val Thr Ile Ser Cys Ser Gly Ser Arg 
        275                 280                 285             


Ser Asn Ile Gly Ser Asn Thr Val Lys Trp Tyr Gln Gln Leu Pro Gly 
    290                 295                 300                 


Thr Ala Pro Lys Leu Leu Ile Tyr Tyr Asn Asp Gln Arg Pro Ser Gly 
305                 310                 315                 320 


Val Pro Asp Arg Phe Ser Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu 
                325                 330                 335     


Ala Ile Thr Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Gln 
            340                 345                 350         


Ser Tyr Asp Arg Tyr Thr His Pro Ala Leu Leu Phe Gly Thr Gly Thr 
        355                 360                 365             


Lys Val Thr Val Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
    370                 375                 380                 


Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val 
385                 390                 395                 400 


Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr 
                405                 410                 415     


Phe Ser Ser Tyr Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly 
            420                 425                 430         


Leu Glu Trp Val Ala Phe Ile Arg Tyr Asp Gly Ser Asn Lys Tyr Tyr 
        435                 440                 445             


Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys 
    450                 455                 460                 


Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala 
465                 470                 475                 480 


Val Tyr Tyr Cys Lys Thr His Gly Ser His Asp Asn Trp Gly Gln Gly 
                485                 490                 495     


Thr Met Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
            500                 505                 510         


Ser Ala Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr 
        515                 520                 525             


His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser 
    530                 535                 540                 


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
545                 550                 555                 560 


Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
                565                 570                 575     


Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
            580                 585                 590         


Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 
        595                 600                 605             


Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
    610                 615                 620                 


Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
625                 630                 635                 640 


Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu 
                645                 650                 655     


Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys 
            660                 665                 670         


Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
        675                 680                 685             


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
    690                 695                 700                 


Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser 
705                 710                 715                 720 


Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
                725                 730                 735     


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Ala 
            740                 745                 750         


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
        755                 760                 765             


Asp Gln Asn Pro Gln Ile Ala Ala His Val Ile Ser Glu Ala Ser Ser 
    770                 775                 780                 


Lys Thr Thr Ser Val Leu Gln Trp Ala Glu Lys Gly Tyr Tyr Thr Met 
785                 790                 795                 800 


Ser Asn Asn Leu Val Thr Leu Glu Asn Gly Lys Gln Leu Thr Val Lys 
                805                 810                 815     


Arg Gln Gly Leu Tyr Tyr Ile Tyr Ala Gln Val Thr Phe Cys Ser Asn 
            820                 825                 830         


Arg Glu Ala Ser Ser Gln Ala Pro Phe Ile Ala Ser Leu Cys Leu Lys 
        835                 840                 845             


Ser Pro Gly Arg Phe Glu Arg Ile Leu Leu Arg Ala Ala Asn Thr His 
    850                 855                 860                 


Ser Ser Ala Lys Pro Cys Gly Gln Gln Ser Ile His Leu Gly Gly Val 
865                 870                 875                 880 


Phe Glu Leu Gln Pro Gly Ala Ser Val Phe Val Asn Val Thr Asp Pro 
                885                 890                 895     


Ser Gln Val Ser His Gly Thr Gly Phe Thr Ser Phe Gly Leu Leu Lys 
            900                 905                 910         


Leu 
    


<210>  20
<211>  914
<212>  PRT
<213>  artificial

<220>
<223>  scFV which binds to IL-12-VL-VH Briakinnumab - Ustekinumab - Fc -
       CD40L


<220>
<221>  repeat
<222>  (753)..(914)
<223>  sequence from positions 753 to 914 may be absent or present in 
       1-3 copies (n=0, 1, 2 or 3)

<400>  20

Gln Ser Val Leu Thr Gln Pro Pro Ser Val Ser Gly Ala Pro Gly Gln 
1               5                   10                  15      


Arg Val Thr Ile Ser Cys Ser Gly Ser Arg Ser Asn Ile Gly Ser Asn 
            20                  25                  30          


Thr Val Lys Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 
        35                  40                  45              


Ile Tyr Tyr Asn Asp Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 
    50                  55                  60                  


Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Thr Gly Leu Gln 
65                  70                  75                  80  


Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Gln Ser Tyr Asp Arg Tyr Thr 
                85                  90                  95      


His Pro Ala Leu Leu Phe Gly Thr Gly Thr Lys Val Thr Val Leu Gly 
            100                 105                 110         


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val 
        115                 120                 125             


Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg Ser Leu 
    130                 135                 140                 


Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Gly Met 
145                 150                 155                 160 


His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Phe 
                165                 170                 175     


Ile Arg Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val Lys Gly 
            180                 185                 190         


Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln 
        195                 200                 205             


Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Lys Thr 
    210                 215                 220                 


His Gly Ser His Asp Asn Trp Gly Gln Gly Thr Met Val Thr Val Ser 
225                 230                 235                 240 


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Ala Gly Gly Gly 
                245                 250                 255     


Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser 
            260                 265                 270         


Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala 
        275                 280                 285             


Ser Gln Gly Ile Ser Ser Trp Leu Ala Trp Tyr Gln Gln Lys Pro Glu 
    290                 295                 300                 


Lys Ala Pro Lys Ser Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly 
305                 310                 315                 320 


Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 
                325                 330                 335     


Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln 
            340                 345                 350         


Gln Tyr Asn Ile Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu 
        355                 360                 365             


Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
    370                 375                 380                 


Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly 
385                 390                 395                 400 


Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr 
                405                 410                 415     


Tyr Trp Leu Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Asp Trp 
            420                 425                 430         


Ile Gly Ile Met Ser Pro Val Asp Ser Asp Ile Arg Tyr Ser Pro Ser 
        435                 440                 445             


Phe Gln Gly Gln Val Thr Met Ser Val Asp Lys Ser Ile Thr Thr Ala 
    450                 455                 460                 


Tyr Leu Gln Trp Asn Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr 
465                 470                 475                 480 


Cys Ala Arg Arg Arg Pro Gly Gln Gly Tyr Phe Asp Phe Trp Gly Gln 
                485                 490                 495     


Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly 
            500                 505                 510         


Gly Ser Ala Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys 
        515                 520                 525             


Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 
    530                 535                 540                 


Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
545                 550                 555                 560 


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
                565                 570                 575     


Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
            580                 585                 590         


Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 
        595                 600                 605             


Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 
    610                 615                 620                 


Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys 
625                 630                 635                 640 


Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr 
                645                 650                 655     


Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser 
            660                 665                 670         


Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
        675                 680                 685             


Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
    690                 695                 700                 


Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys 
705                 710                 715                 720 


Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
                725                 730                 735     


Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
            740                 745                 750         


Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
        755                 760                 765             


Gly Asp Gln Asn Pro Gln Ile Ala Ala His Val Ile Ser Glu Ala Ser 
    770                 775                 780                 


Ser Lys Thr Thr Ser Val Leu Gln Trp Ala Glu Lys Gly Tyr Tyr Thr 
785                 790                 795                 800 


Met Ser Asn Asn Leu Val Thr Leu Glu Asn Gly Lys Gln Leu Thr Val 
                805                 810                 815     


Lys Arg Gln Gly Leu Tyr Tyr Ile Tyr Ala Gln Val Thr Phe Cys Ser 
            820                 825                 830         


Asn Arg Glu Ala Ser Ser Gln Ala Pro Phe Ile Ala Ser Leu Cys Leu 
        835                 840                 845             


Lys Ser Pro Gly Arg Phe Glu Arg Ile Leu Leu Arg Ala Ala Asn Thr 
    850                 855                 860                 


His Ser Ser Ala Lys Pro Cys Gly Gln Gln Ser Ile His Leu Gly Gly 
865                 870                 875                 880 


Val Phe Glu Leu Gln Pro Gly Ala Ser Val Phe Val Asn Val Thr Asp 
                885                 890                 895     


Pro Ser Gln Val Ser His Gly Thr Gly Phe Thr Ser Phe Gly Leu Leu 
            900                 905                 910         


Lys Leu 
        


<210>  21
<211>  860
<212>  PRT
<213>  artificial

<220>
<223>  SIRP alpha ECD - Fc - IL-12 (P40-P35) with knobs mutations


<220>
<221>  variant
<222>  (1)..(100)
<223>  sequence from positions 1 to 100 may be present in 1-3 copies 
       (n=1, 2 or 3)

<400>  21

Glu Glu Glu Leu Gln Val Ile Gln Pro Asp Lys Ser Val Leu Val Ala 
1               5                   10                  15      


Ala Gly Glu Thr Ala Thr Leu Arg Cys Thr Ala Thr Ser Leu Ile Pro 
            20                  25                  30          


Val Gly Pro Ile Gln Trp Phe Arg Gly Ala Gly Pro Gly Arg Glu Leu 
        35                  40                  45              


Ile Tyr Asn Gln Lys Glu Gly His Phe Pro Arg Val Thr Thr Val Ser 
    50                  55                  60                  


Asp Leu Thr Lys Arg Asn Asn Met Asp Phe Ser Ile Arg Ile Gly Asn 
65                  70                  75                  80  


Ile Thr Pro Ala Asp Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
                85                  90                  95      


Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
            100                 105                 110         


Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
        115                 120                 125             


Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
    130                 135                 140                 


Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
145                 150                 155                 160 


Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
                165                 170                 175     


Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
            180                 185                 190         


Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
        195                 200                 205             


Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
    210                 215                 220                 


Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys 
225                 230                 235                 240 


Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
                245                 250                 255     


Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
            260                 265                 270         


Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
        275                 280                 285             


Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
    290                 295                 300                 


Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
305                 310                 315                 320 


Leu Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly 
                325                 330                 335     


Ser Gly Gly Gly Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val 
            340                 345                 350         


Val Glu Leu Asp Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu 
        355                 360                 365             


Thr Cys Asp Thr Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln 
    370                 375                 380                 


Ser Ser Glu Val Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys 
385                 390                 395                 400 


Glu Phe Gly Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val 
                405                 410                 415     


Leu Ser His Ser Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp 
            420                 425                 430         


Ser Thr Asp Ile Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe 
        435                 440                 445             


Leu Arg Cys Glu Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp 
    450                 455                 460                 


Leu Thr Thr Ile Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg 
465                 470                 475                 480 


Gly Ser Ser Asp Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser 
                485                 490                 495     


Ala Glu Arg Val Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu 
            500                 505                 510         


Cys Gln Glu Asp Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile 
        515                 520                 525             


Glu Val Met Val Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr 
    530                 535                 540                 


Ser Ser Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn 
545                 550                 555                 560 


Leu Gln Leu Lys Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp 
                565                 570                 575     


Glu Tyr Pro Asp Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr 
            580                 585                 590         


Phe Cys Val Gln Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg 
        595                 600                 605             


Val Phe Thr Asp Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala 
    610                 615                 620                 


Ser Ile Ser Val Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser 
625                 630                 635                 640 


Glu Trp Ala Ser Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly 
                645                 650                 655     


Gly Ser Gly Gly Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp 
            660                 665                 670         


Pro Gly Met Phe Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala 
        675                 680                 685             


Val Ser Asn Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro 
    690                 695                 700                 


Cys Thr Ser Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr 
705                 710                 715                 720 


Ser Thr Val Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser 
                725                 730                 735     


Cys Leu Asn Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu 
            740                 745                 750         


Ala Ser Arg Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile 
        755                 760                 765             


Tyr Glu Asp Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala 
    770                 775                 780                 


Lys Leu Leu Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met 
785                 790                 795                 800 


Leu Ala Val Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu 
                805                 810                 815     


Thr Val Pro Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr 
            820                 825                 830         


Lys Ile Lys Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val 
        835                 840                 845             


Thr Ile Asp Arg Val Met Ser Tyr Leu Asn Ala Ser 
    850                 855                 860 


<210>  22
<211>  860
<212>  PRT
<213>  artificial

<220>
<223>  IL-12 (P40-P35)-Fc- SIRP alpha ECD with knobs mutations


<220>
<221>  variant
<222>  (761)..(860)
<223>  sequence from positions 761 to 860 may be present in 1-3 copies 
       (n=1, 2 or 3)

<400>  22

Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr 
1               5                   10                  15      


Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu 
            20                  25                  30          


Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly 
        35                  40                  45              


Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly 
    50                  55                  60                  


Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu 
65                  70                  75                  80  


Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys 
                85                  90                  95      


Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys 
            100                 105                 110         


Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr 
        115                 120                 125             


Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln 
    130                 135                 140                 


Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly 
145                 150                 155                 160 


Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala 
                165                 170                 175     


Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala 
            180                 185                 190         


Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg 
        195                 200                 205             


Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu 
    210                 215                 220                 


Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp 
225                 230                 235                 240 


Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln 
                245                 250                 255     


Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr 
            260                 265                 270         


Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala 
        275                 280                 285             


Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro 
    290                 295                 300                 


Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
305                 310                 315                 320 


Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro Cys 
                325                 330                 335     


Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu Gln 
            340                 345                 350         


Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu Glu Ile 
        355                 360                 365             


Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala Cys 
    370                 375                 380                 


Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu 
385                 390                 395                 400 


Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser 
                405                 410                 415     


Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met 
            420                 425                 430         


Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp Pro 
        435                 440                 445             


Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp Glu 
    450                 455                 460                 


Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys Ser 
465                 470                 475                 480 


Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile 
                485                 490                 495     


Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val Met 
            500                 505                 510         


Ser Tyr Leu Asn Ala Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
        515                 520                 525             


Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 
    530                 535                 540                 


Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
545                 550                 555                 560 


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
                565                 570                 575     


Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
            580                 585                 590         


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
        595                 600                 605             


Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
    610                 615                 620                 


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
625                 630                 635                 640 


Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
                645                 650                 655     


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr 
            660                 665                 670         


Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser 
        675                 680                 685             


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
    690                 695                 700                 


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
705                 710                 715                 720 


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
                725                 730                 735     


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
            740                 745                 750         


Ser Leu Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly 
        755                 760                 765             


Gly Ser Gly Gly Gly Gly Ser Glu Glu Glu Leu Gln Val Ile Gln Pro 
    770                 775                 780                 


Asp Lys Ser Val Leu Val Ala Ala Gly Glu Thr Ala Thr Leu Arg Cys 
785                 790                 795                 800 


Thr Ala Thr Ser Leu Ile Pro Val Gly Pro Ile Gln Trp Phe Arg Gly 
                805                 810                 815     


Ala Gly Pro Gly Arg Glu Leu Ile Tyr Asn Gln Lys Glu Gly His Phe 
            820                 825                 830         


Pro Arg Val Thr Thr Val Ser Asp Leu Thr Lys Arg Asn Asn Met Asp 
        835                 840                 845             


Phe Ser Ile Arg Ile Gly Asn Ile Thr Pro Ala Asp 
    850                 855                 860 


<210>  23
<211>  906
<212>  PRT
<213>  artificial

<220>
<223>  CD47 ECD - Fc - IL-12 (P40-P35) with knobs mutations


<220>
<221>  variant
<222>  (1)..(146)
<223>  sequence from positions 1 to 146 may be present in 1-3 copies 
       (n=1, 2 or 3)

<400>  23

Gln Leu Leu Phe Asn Lys Thr Lys Ser Val Glu Phe Thr Phe Cys Asn 
1               5                   10                  15      


Asp Thr Val Val Ile Pro Cys Phe Val Thr Asn Met Glu Ala Gln Asn 
            20                  25                  30          


Thr Thr Glu Val Tyr Val Lys Trp Lys Phe Lys Gly Arg Asp Ile Tyr 
        35                  40                  45              


Thr Phe Asp Gly Ala Leu Asn Lys Ser Thr Val Pro Thr Asp Phe Ser 
    50                  55                  60                  


Ser Ala Lys Ile Glu Val Ser Gln Leu Leu Lys Gly Asp Ala Ser Leu 
65                  70                  75                  80  


Lys Met Asp Lys Ser Asp Ala Val Ser His Thr Gly Asn Tyr Thr Cys 
                85                  90                  95      


Glu Val Thr Glu Leu Thr Arg Glu Gly Glu Thr Ile Ile Glu Leu Lys 
            100                 105                 110         


Tyr Arg Val Val Ser Trp Phe Ser Pro Asn Glu Asn Ile Leu Ile Val 
        115                 120                 125             


Ile Phe Pro Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
    130                 135                 140                 


Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu 
145                 150                 155                 160 


Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
                165                 170                 175     


Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
            180                 185                 190         


Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 
        195                 200                 205             


Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser 
    210                 215                 220                 


Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
225                 230                 235                 240 


Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 
                245                 250                 255     


Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
            260                 265                 270         


Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln 
        275                 280                 285             


Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
    290                 295                 300                 


Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
305                 310                 315                 320 


Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 
                325                 330                 335     


Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 
            340                 345                 350         


Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
        355                 360                 365             


Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
    370                 375                 380                 


Gly Gly Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu 
385                 390                 395                 400 


Leu Asp Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys 
                405                 410                 415     


Asp Thr Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser 
            420                 425                 430         


Glu Val Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe 
        435                 440                 445             


Gly Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser 
    450                 455                 460                 


His Ser Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr 
465                 470                 475                 480 


Asp Ile Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg 
                485                 490                 495     


Cys Glu Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr 
            500                 505                 510         


Thr Ile Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser 
        515                 520                 525             


Ser Asp Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu 
    530                 535                 540                 


Arg Val Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln 
545                 550                 555                 560 


Glu Asp Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val 
                565                 570                 575     


Met Val Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser 
            580                 585                 590         


Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln 
        595                 600                 605             


Leu Lys Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr 
    610                 615                 620                 


Pro Asp Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys 
625                 630                 635                 640 


Val Gln Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe 
                645                 650                 655     


Thr Asp Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile 
            660                 665                 670         


Ser Val Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp 
        675                 680                 685             


Ala Ser Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    690                 695                 700                 


Gly Gly Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly 
705                 710                 715                 720 


Met Phe Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser 
                725                 730                 735     


Asn Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr 
            740                 745                 750         


Ser Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr 
        755                 760                 765             


Val Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu 
    770                 775                 780                 


Asn Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser 
785                 790                 795                 800 


Arg Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu 
                805                 810                 815     


Asp Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu 
            820                 825                 830         


Leu Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala 
        835                 840                 845             


Val Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val 
    850                 855                 860                 


Pro Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile 
865                 870                 875                 880 


Lys Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile 
                885                 890                 895     


Asp Arg Val Met Ser Tyr Leu Asn Ala Ser 
            900                 905     


<210>  24
<211>  906
<212>  PRT
<213>  artificial

<220>
<223>  IL-12 (P40-P35)-Fc- CD47 ECD with knobs mutations


<220>
<221>  variant
<222>  (761)..(906)
<223>  sequence from positions 761 to 906 may be present in 1-3 copies 
       (n=1, 2 or 3)

<400>  24

Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr 
1               5                   10                  15      


Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu 
            20                  25                  30          


Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly 
        35                  40                  45              


Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly 
    50                  55                  60                  


Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu 
65                  70                  75                  80  


Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys 
                85                  90                  95      


Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys 
            100                 105                 110         


Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr 
        115                 120                 125             


Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln 
    130                 135                 140                 


Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly 
145                 150                 155                 160 


Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala 
                165                 170                 175     


Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala 
            180                 185                 190         


Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg 
        195                 200                 205             


Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu 
    210                 215                 220                 


Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp 
225                 230                 235                 240 


Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln 
                245                 250                 255     


Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr 
            260                 265                 270         


Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala 
        275                 280                 285             


Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro 
    290                 295                 300                 


Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
305                 310                 315                 320 


Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro Cys 
                325                 330                 335     


Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu Gln 
            340                 345                 350         


Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu Glu Ile 
        355                 360                 365             


Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala Cys 
    370                 375                 380                 


Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu 
385                 390                 395                 400 


Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser 
                405                 410                 415     


Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met 
            420                 425                 430         


Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp Pro 
        435                 440                 445             


Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp Glu 
    450                 455                 460                 


Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys Ser 
465                 470                 475                 480 


Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile 
                485                 490                 495     


Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val Met 
            500                 505                 510         


Ser Tyr Leu Asn Ala Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
        515                 520                 525             


Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 
    530                 535                 540                 


Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
545                 550                 555                 560 


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
                565                 570                 575     


Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
            580                 585                 590         


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
        595                 600                 605             


Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
    610                 615                 620                 


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
625                 630                 635                 640 


Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
                645                 650                 655     


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr 
            660                 665                 670         


Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser 
        675                 680                 685             


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
    690                 695                 700                 


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
705                 710                 715                 720 


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
                725                 730                 735     


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
            740                 745                 750         


Ser Leu Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly 
        755                 760                 765             


Gly Ser Gly Gly Gly Gly Ser Gln Leu Leu Phe Asn Lys Thr Lys Ser 
    770                 775                 780                 


Val Glu Phe Thr Phe Cys Asn Asp Thr Val Val Ile Pro Cys Phe Val 
785                 790                 795                 800 


Thr Asn Met Glu Ala Gln Asn Thr Thr Glu Val Tyr Val Lys Trp Lys 
                805                 810                 815     


Phe Lys Gly Arg Asp Ile Tyr Thr Phe Asp Gly Ala Leu Asn Lys Ser 
            820                 825                 830         


Thr Val Pro Thr Asp Phe Ser Ser Ala Lys Ile Glu Val Ser Gln Leu 
        835                 840                 845             


Leu Lys Gly Asp Ala Ser Leu Lys Met Asp Lys Ser Asp Ala Val Ser 
    850                 855                 860                 


His Thr Gly Asn Tyr Thr Cys Glu Val Thr Glu Leu Thr Arg Glu Gly 
865                 870                 875                 880 


Glu Thr Ile Ile Glu Leu Lys Tyr Arg Val Val Ser Trp Phe Ser Pro 
                885                 890                 895     


Asn Glu Asn Ile Leu Ile Val Ile Phe Pro 
            900                 905     


<210>  25
<211>  16
<212>  PRT
<213>  artificial

<220>
<223>  cleavable peptide linker

<400>  25

Gly Gly Ser Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Gly Ser 
1               5                   10                  15      


<210>  26
<211>  13
<212>  PRT
<213>  artificial

<220>
<223>  cleavable peptide linker

<400>  26

Gly Gly Ser Leu Ser Gly Arg Ser Asp Asn His Gly Ser 
1               5                   10              


<210>  27
<211>  42
<212>  PRT
<213>  artificial

<220>
<223>  GGGGSGGGGS GGGGSISSGL LSSGGSGGSL SGRSDNHGGG GS

<400>  27

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile 
1               5                   10                  15      


Ser Ser Gly Leu Leu Ser Ser Gly Gly Ser Gly Gly Ser Leu Ser Gly 
            20                  25                  30          


Arg Ser Asp Asn His Gly Gly Gly Gly Ser 
        35                  40          


<210>  28
<211>  6
<212>  PRT
<213>  artificial

<220>
<223>  MMP-2/MMP-9 Cleavable peptide linkers

<400>  28

Gly Pro Leu Gly Val Arg 
1               5       


<210>  29
<211>  7
<212>  PRT
<213>  artificial

<220>
<223>  PLGMWSR

<400>  29

Pro Leu Gly Met Trp Ser Arg 
1               5           


<210>  30
<211>  7
<212>  PRT
<213>  artificial

<220>
<223>  MMP-2/MMP-9 Cleavable peptide linkers

<400>  30

Pro Leu Gly Leu Trp Ala Arg 
1               5           


<210>  31
<211>  8
<212>  PRT
<213>  artificial

<220>
<223>  PQGIAGQR

<400>  31

Pro Gln Gly Ile Ala Gly Gln Arg 
1               5               


<210>  32
<211>  6
<212>  PRT
<213>  artificial

<220>
<223>  PLGLAG

<400>  32

Pro Leu Gly Leu Ala Gly 
1               5       


<210>  33
<211>  6
<212>  PRT
<213>  artificial

<220>
<223>  MMP-2/MMP-9 Cleavable peptide linkers

<400>  33

Leu Ala Leu Gly Pro Arg 
1               5       


<210>  34
<211>  10
<212>  PRT
<213>  artificial

<220>
<223>  MMP-2/MMP-9 Cleavable peptide linkers

<400>  34

Gly Gly Pro Leu Gly Met Leu Ser Gln Ser 
1               5                   10  


<210>  35
<211>  9
<212>  PRT
<213>  artificial

<220>
<223>  urokinase plasminogen activator (uPA) Cleavable peptide linkers

<400>  35

Gly Gly Gly Gly Arg Arg Gly Gly Ser 
1               5                   


<210>  36
<211>  8
<212>  PRT
<213>  artificial

<220>
<223>  urokinase plasminogen activator (uPA) Cleavable peptide linkers

<400>  36

Thr Gly Arg Gly Pro Ser Trp Val 
1               5               


<210>  37
<211>  8
<212>  PRT
<213>  artificial

<220>
<223>  urokinase plasminogen activator (uPA) Cleavable peptide linkers

<400>  37

Ser Ala Arg Gly Pro Ser Arg Trp 
1               5               


<210>  38
<211>  8
<212>  PRT
<213>  artificial

<220>
<223>  urokinase plasminogen activator (uPA) Cleavable peptide linkers

<400>  38

Thr Ala Arg Gly Pro Ser Phe Lys 
1               5               


<210>  39
<211>  7
<212>  PRT
<213>  artificial

<220>
<223>  urokinase plasminogen activator (uPA) Cleavable peptide linkers

<400>  39

Thr Ala Arg Gly Pro Ser Trp 
1               5           


<210>  40
<211>  8
<212>  PRT
<213>  artificial

<220>
<223>  urokinase plasminogen activator (uPA) Cleavable peptide linkers

<400>  40

Gly Gly Trp His Thr Gly Arg Asn 
1               5               


<210>  41
<211>  8
<212>  PRT
<213>  artificial

<220>
<223>  urokinase plasminogen activator (uPA) Cleavable peptide linkers

<400>  41

His Thr Gly Arg Ser Gly Ala Leu 
1               5               


<210>  42
<211>  8
<212>  PRT
<213>  artificial

<220>
<223>  urokinase plasminogen activator (uPA) Cleavable peptide linkers

<400>  42

Pro Leu Thr Gly Arg Ser Gly Gly 
1               5               


<210>  43
<211>  7
<212>  PRT
<213>  artificial

<220>
<223>  urokinase plasminogen activator (uPA) Cleavable peptide linkers

<400>  43

Leu Thr Gly Arg Ser Gly Ala 
1               5           


<210>  44
<211>  8
<212>  PRT
<213>  artificial

<220>
<223>  matriptase cleavable peptide linker

<400>  44

Arg Gln Ala Arg Val Val Asn Gly 
1               5               


<210>  45
<211>  18
<212>  PRT
<213>  artificial

<220>
<223>  matriptase-MMP2/9 dual cleavable peptide linker

<400>  45

Val His Met Pro Leu Gly Phe Leu Gly Pro Arg Gln Ala Arg Val Val 
1               5                   10                  15      


Asn Ala 
        


<210>  46
<211>  306
<212>  PRT
<213>  artificial

<220>
<223>  Mutants of P40 subunit of IL-12


<220>
<221>  variant
<222>  (260)..(260)
<223>  X is absent, K or A

<220>
<221>  variant
<222>  (261)..(261)
<223>  X is absent, R or A

<400>  46

Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr 
1               5                   10                  15      


Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu 
            20                  25                  30          


Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly 
        35                  40                  45              


Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly 
    50                  55                  60                  


Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu 
65                  70                  75                  80  


Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys 
                85                  90                  95      


Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys 
            100                 105                 110         


Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr 
        115                 120                 125             


Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln 
    130                 135                 140                 


Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly 
145                 150                 155                 160 


Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala 
                165                 170                 175     


Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala 
            180                 185                 190         


Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg 
        195                 200                 205             


Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu 
    210                 215                 220                 


Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp 
225                 230                 235                 240 


Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln 
                245                 250                 255     


Gly Lys Ser Xaa Xaa Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr 
            260                 265                 270         


Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala 
        275                 280                 285             


Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro 
    290                 295                 300                 


Cys Ser 
305     


<210>  47
<211>  548
<212>  PRT
<213>  artificial

<220>
<223>  Fc - IL-12 P40 mutant with knobs mutations

<400>  47

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp 
                245                 250                 255     


Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr 
            260                 265                 270         


Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val 
        275                 280                 285             


Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp 
    290                 295                 300                 


Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser 
305                 310                 315                 320 


Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile 
                325                 330                 335     


Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu 
            340                 345                 350         


Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile 
        355                 360                 365             


Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp 
    370                 375                 380                 


Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val 
385                 390                 395                 400 


Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp 
                405                 410                 415     


Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val 
            420                 425                 430         


Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe 
        435                 440                 445             


Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys 
    450                 455                 460                 


Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp 
465                 470                 475                 480 


Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln 
                485                 490                 495     


Val Gln Gly Lys Ser Ala Ala Glu Lys Lys Asp Arg Val Phe Thr Asp 
            500                 505                 510         


Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val 
        515                 520                 525             


Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser 
    530                 535                 540                 


Val Pro Cys Ser 
545             


<210>  48
<211>  548
<212>  PRT
<213>  artificial

<220>
<223>  IL-12 P40 mutant-Fc with knobs mutations

<400>  48

Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr 
1               5                   10                  15      


Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu 
            20                  25                  30          


Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly 
        35                  40                  45              


Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly 
    50                  55                  60                  


Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu 
65                  70                  75                  80  


Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys 
                85                  90                  95      


Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys 
            100                 105                 110         


Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr 
        115                 120                 125             


Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln 
    130                 135                 140                 


Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly 
145                 150                 155                 160 


Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala 
                165                 170                 175     


Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala 
            180                 185                 190         


Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg 
        195                 200                 205             


Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu 
    210                 215                 220                 


Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp 
225                 230                 235                 240 


Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln 
                245                 250                 255     


Gly Lys Ser Ala Ala Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr 
            260                 265                 270         


Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala 
        275                 280                 285             


Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro 
    290                 295                 300                 


Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
305                 310                 315                 320 


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
                325                 330                 335     


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
            340                 345                 350         


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
        355                 360                 365             


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
    370                 375                 380                 


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr 
385                 390                 395                 400 


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
                405                 410                 415     


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
            420                 425                 430         


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
        435                 440                 445             


Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val 
    450                 455                 460                 


Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
465                 470                 475                 480 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
                485                 490                 495     


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
            500                 505                 510         


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
        515                 520                 525             


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
    530                 535                 540                 


Ser Pro Gly Lys 
545             


<210>  49
<211>  548
<212>  PRT
<213>  artificial

<220>
<223>  Fc - IL-12 mutant P40 with knobs mutations

<400>  49

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp 
                245                 250                 255     


Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr 
            260                 265                 270         


Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val 
        275                 280                 285             


Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp 
    290                 295                 300                 


Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser 
305                 310                 315                 320 


Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile 
                325                 330                 335     


Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu 
            340                 345                 350         


Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile 
        355                 360                 365             


Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp 
    370                 375                 380                 


Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val 
385                 390                 395                 400 


Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp 
                405                 410                 415     


Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val 
            420                 425                 430         


Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe 
        435                 440                 445             


Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys 
    450                 455                 460                 


Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp 
465                 470                 475                 480 


Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln 
                485                 490                 495     


Val Gln Gly Gln Asp Gln Asp Glu Ser Gly Asp Arg Val Phe Thr Asp 
            500                 505                 510         


Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val 
        515                 520                 525             


Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser 
    530                 535                 540                 


Val Pro Cys Ser 
545             


<210>  50
<211>  548
<212>  PRT
<213>  artificial

<220>
<223>  IL-12 P40 mutant-Fc with knobs mutations

<400>  50

Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr 
1               5                   10                  15      


Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu 
            20                  25                  30          


Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly 
        35                  40                  45              


Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly 
    50                  55                  60                  


Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu 
65                  70                  75                  80  


Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys 
                85                  90                  95      


Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys 
            100                 105                 110         


Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr 
        115                 120                 125             


Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln 
    130                 135                 140                 


Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly 
145                 150                 155                 160 


Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala 
                165                 170                 175     


Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala 
            180                 185                 190         


Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg 
        195                 200                 205             


Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu 
    210                 215                 220                 


Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp 
225                 230                 235                 240 


Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln 
                245                 250                 255     


Gly Gln Asp Gln Asp Glu Ser Gly Asp Arg Val Phe Thr Asp Lys Thr 
            260                 265                 270         


Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala 
        275                 280                 285             


Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro 
    290                 295                 300                 


Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
305                 310                 315                 320 


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
                325                 330                 335     


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
            340                 345                 350         


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
        355                 360                 365             


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
    370                 375                 380                 


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr 
385                 390                 395                 400 


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
                405                 410                 415     


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
            420                 425                 430         


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
        435                 440                 445             


Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val 
    450                 455                 460                 


Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
465                 470                 475                 480 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
                485                 490                 495     


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
            500                 505                 510         


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
        515                 520                 525             


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
    530                 535                 540                 


Ser Pro Gly Lys 
545             


<210>  51
<211>  760
<212>  PRT
<213>  artificial

<220>
<223>  Fc - IL-12 (P40-P35) mutant with knobs mutations

<400>  51

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp 
                245                 250                 255     


Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr 
            260                 265                 270         


Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val 
        275                 280                 285             


Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp 
    290                 295                 300                 


Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser 
305                 310                 315                 320 


Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile 
                325                 330                 335     


Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu 
            340                 345                 350         


Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile 
        355                 360                 365             


Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp 
    370                 375                 380                 


Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val 
385                 390                 395                 400 


Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp 
                405                 410                 415     


Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val 
            420                 425                 430         


Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe 
        435                 440                 445             


Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys 
    450                 455                 460                 


Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp 
465                 470                 475                 480 


Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln 
                485                 490                 495     


Val Gln Gly Lys Ser Ala Ala Glu Lys Lys Asp Arg Val Phe Thr Asp 
            500                 505                 510         


Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val 
        515                 520                 525             


Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser 
    530                 535                 540                 


Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
545                 550                 555                 560 


Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe 
                565                 570                 575     


Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met 
            580                 585                 590         


Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu 
        595                 600                 605             


Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu 
    610                 615                 620                 


Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser 
625                 630                 635                 640 


Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys 
                645                 650                 655     


Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu 
            660                 665                 670         


Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met 
        675                 680                 685             


Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile 
    690                 695                 700                 


Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln 
705                 710                 715                 720 


Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu 
                725                 730                 735     


Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg 
            740                 745                 750         


Val Met Ser Tyr Leu Asn Ala Ser 
        755                 760 


<210>  52
<211>  921
<212>  PRT
<213>  artificial

<220>
<223>  CD40L - Fc - IL-12 (P40-P35) mutant with knobs mutations


<220>
<221>  variant
<222>  (1)..(161)
<223>  sequence from positions 1 to 161 may be present in 1-3 copies 
       (n=1, 2 or 3)

<400>  52

Gly Asp Gln Asn Pro Gln Ile Ala Ala His Val Ile Ser Glu Ala Ser 
1               5                   10                  15      


Ser Lys Thr Thr Ser Val Leu Gln Trp Ala Glu Lys Gly Tyr Tyr Thr 
            20                  25                  30          


Met Ser Asn Asn Leu Val Thr Leu Glu Asn Gly Lys Gln Leu Thr Val 
        35                  40                  45              


Lys Arg Gln Gly Leu Tyr Tyr Ile Tyr Ala Gln Val Thr Phe Cys Ser 
    50                  55                  60                  


Asn Arg Glu Ala Ser Ser Gln Ala Pro Phe Ile Ala Ser Leu Cys Leu 
65                  70                  75                  80  


Lys Ser Pro Gly Arg Phe Glu Arg Ile Leu Leu Arg Ala Ala Asn Thr 
                85                  90                  95      


His Ser Ser Ala Lys Pro Cys Gly Gln Gln Ser Ile His Leu Gly Gly 
            100                 105                 110         


Val Phe Glu Leu Gln Pro Gly Ala Ser Val Phe Val Asn Val Thr Asp 
        115                 120                 125             


Pro Ser Gln Val Ser His Gly Thr Gly Phe Thr Ser Phe Gly Leu Leu 
    130                 135                 140                 


Lys Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
145                 150                 155                 160 


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
                165                 170                 175     


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
            180                 185                 190         


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
        195                 200                 205             


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
    210                 215                 220                 


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr 
225                 230                 235                 240 


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
                245                 250                 255     


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
            260                 265                 270         


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
        275                 280                 285             


Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val 
    290                 295                 300                 


Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
305                 310                 315                 320 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
                325                 330                 335     


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
            340                 345                 350         


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
        355                 360                 365             


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
    370                 375                 380                 


Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
385                 390                 395                 400 


Gly Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu 
                405                 410                 415     


Asp Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp 
            420                 425                 430         


Thr Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu 
        435                 440                 445             


Val Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly 
    450                 455                 460                 


Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His 
465                 470                 475                 480 


Ser Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp 
                485                 490                 495     


Ile Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys 
            500                 505                 510         


Glu Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr 
        515                 520                 525             


Ile Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser 
    530                 535                 540                 


Asp Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg 
545                 550                 555                 560 


Val Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu 
                565                 570                 575     


Asp Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met 
            580                 585                 590         


Val Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe 
        595                 600                 605             


Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu 
    610                 615                 620                 


Lys Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro 
625                 630                 635                 640 


Asp Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val 
                645                 650                 655     


Gln Val Gln Gly Lys Ser Ala Ala Glu Lys Lys Asp Arg Val Phe Thr 
            660                 665                 670         


Asp Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser 
        675                 680                 685             


Val Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala 
    690                 695                 700                 


Ser Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
705                 710                 715                 720 


Gly Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met 
                725                 730                 735     


Phe Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn 
            740                 745                 750         


Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser 
        755                 760                 765             


Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val 
    770                 775                 780                 


Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn 
785                 790                 795                 800 


Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg 
                805                 810                 815     


Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp 
            820                 825                 830         


Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu 
        835                 840                 845             


Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val 
    850                 855                 860                 


Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro 
865                 870                 875                 880 


Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys 
                885                 890                 895     


Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp 
            900                 905                 910         


Arg Val Met Ser Tyr Leu Asn Ala Ser 
        915                 920     


<210>  53
<211>  921
<212>  PRT
<213>  artificial

<220>
<223>  IL-12 (P40-P35) mutant - Fc - CD40L with knobs mutations


<220>
<221>  variant
<222>  (761)..(921)
<223>  sequence from positions 761 to 921 may be absent or present in 
       1-3 copies (n=0, 1, 2 or 3)

<400>  53

Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr 
1               5                   10                  15      


Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu 
            20                  25                  30          


Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly 
        35                  40                  45              


Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly 
    50                  55                  60                  


Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu 
65                  70                  75                  80  


Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys 
                85                  90                  95      


Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys 
            100                 105                 110         


Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr 
        115                 120                 125             


Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln 
    130                 135                 140                 


Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly 
145                 150                 155                 160 


Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala 
                165                 170                 175     


Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala 
            180                 185                 190         


Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg 
        195                 200                 205             


Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu 
    210                 215                 220                 


Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp 
225                 230                 235                 240 


Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln 
                245                 250                 255     


Gly Lys Ser Ala Ala Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr 
            260                 265                 270         


Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala 
        275                 280                 285             


Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro 
    290                 295                 300                 


Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
305                 310                 315                 320 


Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro Cys 
                325                 330                 335     


Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu Gln 
            340                 345                 350         


Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu Glu Ile 
        355                 360                 365             


Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala Cys 
    370                 375                 380                 


Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu 
385                 390                 395                 400 


Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser 
                405                 410                 415     


Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met 
            420                 425                 430         


Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp Pro 
        435                 440                 445             


Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp Glu 
    450                 455                 460                 


Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys Ser 
465                 470                 475                 480 


Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile 
                485                 490                 495     


Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val Met 
            500                 505                 510         


Ser Tyr Leu Asn Ala Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
        515                 520                 525             


Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 
    530                 535                 540                 


Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
545                 550                 555                 560 


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
                565                 570                 575     


Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
            580                 585                 590         


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
        595                 600                 605             


Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
    610                 615                 620                 


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
625                 630                 635                 640 


Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
                645                 650                 655     


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr 
            660                 665                 670         


Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser 
        675                 680                 685             


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
    690                 695                 700                 


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
705                 710                 715                 720 


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
                725                 730                 735     


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
            740                 745                 750         


Ser Leu Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly 
        755                 760                 765             


Gly Ser Gly Gly Gly Gly Ser Gly Asp Gln Asn Pro Gln Ile Ala Ala 
    770                 775                 780                 


His Val Ile Ser Glu Ala Ser Ser Lys Thr Thr Ser Val Leu Gln Trp 
785                 790                 795                 800 


Ala Glu Lys Gly Tyr Tyr Thr Met Ser Asn Asn Leu Val Thr Leu Glu 
                805                 810                 815     


Asn Gly Lys Gln Leu Thr Val Lys Arg Gln Gly Leu Tyr Tyr Ile Tyr 
            820                 825                 830         


Ala Gln Val Thr Phe Cys Ser Asn Arg Glu Ala Ser Ser Gln Ala Pro 
        835                 840                 845             


Phe Ile Ala Ser Leu Cys Leu Lys Ser Pro Gly Arg Phe Glu Arg Ile 
    850                 855                 860                 


Leu Leu Arg Ala Ala Asn Thr His Ser Ser Ala Lys Pro Cys Gly Gln 
865                 870                 875                 880 


Gln Ser Ile His Leu Gly Gly Val Phe Glu Leu Gln Pro Gly Ala Ser 
                885                 890                 895     


Val Phe Val Asn Val Thr Asp Pro Ser Gln Val Ser His Gly Thr Gly 
            900                 905                 910         


Phe Thr Ser Phe Gly Leu Leu Lys Leu 
        915                 920     


<210>  54
<211>  760
<212>  PRT
<213>  artificial

<220>
<223>  Fc - IL-12 (P40-P35) mutant with knobs mutations

<400>  54

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp 
                245                 250                 255     


Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr 
            260                 265                 270         


Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val 
        275                 280                 285             


Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp 
    290                 295                 300                 


Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser 
305                 310                 315                 320 


Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile 
                325                 330                 335     


Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu 
            340                 345                 350         


Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile 
        355                 360                 365             


Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp 
    370                 375                 380                 


Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val 
385                 390                 395                 400 


Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp 
                405                 410                 415     


Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val 
            420                 425                 430         


Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe 
        435                 440                 445             


Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys 
    450                 455                 460                 


Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp 
465                 470                 475                 480 


Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln 
                485                 490                 495     


Val Gln Gly Gln Asp Gln Asp Glu Ser Gly Asp Arg Val Phe Thr Asp 
            500                 505                 510         


Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val 
        515                 520                 525             


Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser 
    530                 535                 540                 


Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
545                 550                 555                 560 


Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe 
                565                 570                 575     


Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met 
            580                 585                 590         


Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu 
        595                 600                 605             


Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu 
    610                 615                 620                 


Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser 
625                 630                 635                 640 


Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys 
                645                 650                 655     


Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu 
            660                 665                 670         


Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met 
        675                 680                 685             


Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile 
    690                 695                 700                 


Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln 
705                 710                 715                 720 


Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu 
                725                 730                 735     


Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg 
            740                 745                 750         


Val Met Ser Tyr Leu Asn Ala Ser 
        755                 760 


<210>  55
<211>  921
<212>  PRT
<213>  artificial

<220>
<223>  Fc - IL-12 (P40-P35) mutant with knobs mutations


<220>
<221>  variant
<222>  (1)..(161)
<223>  sequence from positions 1 to 161 may be present in 1-3 copies 
       (n=1, 2 or 3)

<400>  55

Gly Asp Gln Asn Pro Gln Ile Ala Ala His Val Ile Ser Glu Ala Ser 
1               5                   10                  15      


Ser Lys Thr Thr Ser Val Leu Gln Trp Ala Glu Lys Gly Tyr Tyr Thr 
            20                  25                  30          


Met Ser Asn Asn Leu Val Thr Leu Glu Asn Gly Lys Gln Leu Thr Val 
        35                  40                  45              


Lys Arg Gln Gly Leu Tyr Tyr Ile Tyr Ala Gln Val Thr Phe Cys Ser 
    50                  55                  60                  


Asn Arg Glu Ala Ser Ser Gln Ala Pro Phe Ile Ala Ser Leu Cys Leu 
65                  70                  75                  80  


Lys Ser Pro Gly Arg Phe Glu Arg Ile Leu Leu Arg Ala Ala Asn Thr 
                85                  90                  95      


His Ser Ser Ala Lys Pro Cys Gly Gln Gln Ser Ile His Leu Gly Gly 
            100                 105                 110         


Val Phe Glu Leu Gln Pro Gly Ala Ser Val Phe Val Asn Val Thr Asp 
        115                 120                 125             


Pro Ser Gln Val Ser His Gly Thr Gly Phe Thr Ser Phe Gly Leu Leu 
    130                 135                 140                 


Lys Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
145                 150                 155                 160 


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
                165                 170                 175     


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
            180                 185                 190         


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
        195                 200                 205             


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
    210                 215                 220                 


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr 
225                 230                 235                 240 


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
                245                 250                 255     


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
            260                 265                 270         


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
        275                 280                 285             


Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val 
    290                 295                 300                 


Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
305                 310                 315                 320 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
                325                 330                 335     


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
            340                 345                 350         


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
        355                 360                 365             


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
    370                 375                 380                 


Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
385                 390                 395                 400 


Gly Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu 
                405                 410                 415     


Asp Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp 
            420                 425                 430         


Thr Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu 
        435                 440                 445             


Val Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly 
    450                 455                 460                 


Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His 
465                 470                 475                 480 


Ser Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp 
                485                 490                 495     


Ile Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys 
            500                 505                 510         


Glu Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr 
        515                 520                 525             


Ile Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser 
    530                 535                 540                 


Asp Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg 
545                 550                 555                 560 


Val Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu 
                565                 570                 575     


Asp Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met 
            580                 585                 590         


Val Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe 
        595                 600                 605             


Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu 
    610                 615                 620                 


Lys Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro 
625                 630                 635                 640 


Asp Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val 
                645                 650                 655     


Gln Val Gln Gly Gln Asp Gln Asp Glu Ser Gly Asp Arg Val Phe Thr 
            660                 665                 670         


Asp Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser 
        675                 680                 685             


Val Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala 
    690                 695                 700                 


Ser Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
705                 710                 715                 720 


Gly Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met 
                725                 730                 735     


Phe Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn 
            740                 745                 750         


Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser 
        755                 760                 765             


Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val 
    770                 775                 780                 


Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn 
785                 790                 795                 800 


Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg 
                805                 810                 815     


Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp 
            820                 825                 830         


Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu 
        835                 840                 845             


Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val 
    850                 855                 860                 


Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro 
865                 870                 875                 880 


Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys 
                885                 890                 895     


Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp 
            900                 905                 910         


Arg Val Met Ser Tyr Leu Asn Ala Ser 
        915                 920     


<210>  56
<211>  921
<212>  PRT
<213>  artificial

<220>
<223>  IL-12 (P40-P35) mutant - Fc - CD40L with knobs mutations


<220>
<221>  variant
<222>  (761)..(921)
<223>  sequence from positions 761 to 921 may be absent or present in 
       1-3 copies (n=0, 1, 2 or 3)

<400>  56

Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr 
1               5                   10                  15      


Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu 
            20                  25                  30          


Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly 
        35                  40                  45              


Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly 
    50                  55                  60                  


Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu 
65                  70                  75                  80  


Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys 
                85                  90                  95      


Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys 
            100                 105                 110         


Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr 
        115                 120                 125             


Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln 
    130                 135                 140                 


Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly 
145                 150                 155                 160 


Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala 
                165                 170                 175     


Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala 
            180                 185                 190         


Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg 
        195                 200                 205             


Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu 
    210                 215                 220                 


Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp 
225                 230                 235                 240 


Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln 
                245                 250                 255     


Gly Gln Asp Gln Asp Glu Ser Gly Asp Arg Val Phe Thr Asp Lys Thr 
            260                 265                 270         


Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala 
        275                 280                 285             


Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro 
    290                 295                 300                 


Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
305                 310                 315                 320 


Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro Cys 
                325                 330                 335     


Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu Gln 
            340                 345                 350         


Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu Glu Ile 
        355                 360                 365             


Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala Cys 
    370                 375                 380                 


Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu 
385                 390                 395                 400 


Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser 
                405                 410                 415     


Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met 
            420                 425                 430         


Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp Pro 
        435                 440                 445             


Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp Glu 
    450                 455                 460                 


Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys Ser 
465                 470                 475                 480 


Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile 
                485                 490                 495     


Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val Met 
            500                 505                 510         


Ser Tyr Leu Asn Ala Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
        515                 520                 525             


Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 
    530                 535                 540                 


Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
545                 550                 555                 560 


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
                565                 570                 575     


Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
            580                 585                 590         


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
        595                 600                 605             


Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
    610                 615                 620                 


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
625                 630                 635                 640 


Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
                645                 650                 655     


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr 
            660                 665                 670         


Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser 
        675                 680                 685             


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
    690                 695                 700                 


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
705                 710                 715                 720 


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
                725                 730                 735     


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
            740                 745                 750         


Ser Leu Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly 
        755                 760                 765             


Gly Ser Gly Gly Gly Gly Ser Gly Asp Gln Asn Pro Gln Ile Ala Ala 
    770                 775                 780                 


His Val Ile Ser Glu Ala Ser Ser Lys Thr Thr Ser Val Leu Gln Trp 
785                 790                 795                 800 


Ala Glu Lys Gly Tyr Tyr Thr Met Ser Asn Asn Leu Val Thr Leu Glu 
                805                 810                 815     


Asn Gly Lys Gln Leu Thr Val Lys Arg Gln Gly Leu Tyr Tyr Ile Tyr 
            820                 825                 830         


Ala Gln Val Thr Phe Cys Ser Asn Arg Glu Ala Ser Ser Gln Ala Pro 
        835                 840                 845             


Phe Ile Ala Ser Leu Cys Leu Lys Ser Pro Gly Arg Phe Glu Arg Ile 
    850                 855                 860                 


Leu Leu Arg Ala Ala Asn Thr His Ser Ser Ala Lys Pro Cys Gly Gln 
865                 870                 875                 880 


Gln Ser Ile His Leu Gly Gly Val Phe Glu Leu Gln Pro Gly Ala Ser 
                885                 890                 895     


Val Phe Val Asn Val Thr Asp Pro Ser Gln Val Ser His Gly Thr Gly 
            900                 905                 910         


Phe Thr Ser Phe Gly Leu Leu Lys Leu 
        915                 920     


<210>  57
<211>  507
<212>  PRT
<213>  artificial

<220>
<223>  Fc- scFV which binds to IL-12-VL-VH Ustekinumab

<400>  57

Met Gly Val Lys Val Leu Phe Ala Leu Ile Cys Ile Ala Val Ala Glu 
1               5                   10                  15      


Ala Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
            20                  25                  30          


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
        35                  40                  45              


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
    50                  55                  60                  


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
65                  70                  75                  80  


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
                85                  90                  95      


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
            100                 105                 110         


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
        115                 120                 125             


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
    130                 135                 140                 


Val Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val 
145                 150                 155                 160 


Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
                165                 170                 175     


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
            180                 185                 190         


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr 
        195                 200                 205             


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
    210                 215                 220                 


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
225                 230                 235                 240 


Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Ala 
                245                 250                 255     


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln 
            260                 265                 270         


Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr 
        275                 280                 285             


Cys Arg Ala Ser Gln Gly Ile Ser Ser Trp Leu Ala Trp Tyr Gln Gln 
    290                 295                 300                 


Lys Pro Glu Lys Ala Pro Lys Ser Leu Ile Tyr Ala Ala Ser Ser Leu 
305                 310                 315                 320 


Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
                325                 330                 335     


Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr 
            340                 345                 350         


Tyr Cys Gln Gln Tyr Asn Ile Tyr Pro Tyr Thr Phe Gly Gln Gly Thr 
        355                 360                 365             


Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
    370                 375                 380                 


Gly Gly Gly Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 
385                 390                 395                 400 


Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser 
                405                 410                 415     


Phe Thr Thr Tyr Trp Leu Gly Trp Val Arg Gln Met Pro Gly Lys Gly 
            420                 425                 430         


Leu Asp Trp Ile Gly Ile Met Ser Pro Val Asp Ser Asp Ile Arg Tyr 
        435                 440                 445             


Ser Pro Ser Phe Gln Gly Gln Val Thr Met Ser Val Asp Lys Ser Ile 
    450                 455                 460                 


Thr Thr Ala Tyr Leu Gln Trp Asn Ser Leu Lys Ala Ser Asp Thr Ala 
465                 470                 475                 480 


Met Tyr Tyr Cys Ala Arg Arg Arg Pro Gly Gln Gly Tyr Phe Asp Phe 
                485                 490                 495     


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
            500                 505         


<210>  58
<211>  489
<212>  PRT
<213>  artificial

<220>
<223>  Fc - scFV which binds to IL-12-VL-VH Ustekinumab with cleavable 
       linker

<400>  58

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Pro Leu 
225                 230                 235                 240 


Gly Val Arg Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro 
                245                 250                 255     


Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg 
            260                 265                 270         


Ala Ser Gln Gly Ile Ser Ser Trp Leu Ala Trp Tyr Gln Gln Lys Pro 
        275                 280                 285             


Glu Lys Ala Pro Lys Ser Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser 
    290                 295                 300                 


Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 
305                 310                 315                 320 


Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys 
                325                 330                 335     


Gln Gln Tyr Asn Ile Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu 
            340                 345                 350         


Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
        355                 360                 365             


Gly Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro 
    370                 375                 380                 


Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr 
385                 390                 395                 400 


Thr Tyr Trp Leu Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Asp 
                405                 410                 415     


Trp Ile Gly Ile Met Ser Pro Val Asp Ser Asp Ile Arg Tyr Ser Pro 
            420                 425                 430         


Ser Phe Gln Gly Gln Val Thr Met Ser Val Asp Lys Ser Ile Thr Thr 
        435                 440                 445             


Ala Tyr Leu Gln Trp Asn Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr 
    450                 455                 460                 


Tyr Cys Ala Arg Arg Arg Pro Gly Gln Gly Tyr Phe Asp Phe Trp Gly 
465                 470                 475                 480 


Gln Gly Thr Leu Val Thr Val Ser Ser 
                485                 


<210>  59
<211>  651
<212>  PRT
<213>  artificial

<220>
<223>  CD40L - Fc - scFV which binds to IL-12-VL-VH Ustekinumab


<220>
<221>  variant
<222>  (1)..(161)
<223>  sequence from positions 1 to 161 may be present in 1-3 copies 
       (n=1, 2 or 3)

<400>  59

Gly Asp Gln Asn Pro Gln Ile Ala Ala His Val Ile Ser Glu Ala Ser 
1               5                   10                  15      


Ser Lys Thr Thr Ser Val Leu Gln Trp Ala Glu Lys Gly Tyr Tyr Thr 
            20                  25                  30          


Met Ser Asn Asn Leu Val Thr Leu Glu Asn Gly Lys Gln Leu Thr Val 
        35                  40                  45              


Lys Arg Gln Gly Leu Tyr Tyr Ile Tyr Ala Gln Val Thr Phe Cys Ser 
    50                  55                  60                  


Asn Arg Glu Ala Ser Ser Gln Ala Pro Phe Ile Ala Ser Leu Cys Leu 
65                  70                  75                  80  


Lys Ser Pro Gly Arg Phe Glu Arg Ile Leu Leu Arg Ala Ala Asn Thr 
                85                  90                  95      


His Ser Ser Ala Lys Pro Cys Gly Gln Gln Ser Ile His Leu Gly Gly 
            100                 105                 110         


Val Phe Glu Leu Gln Pro Gly Ala Ser Val Phe Val Asn Val Thr Asp 
        115                 120                 125             


Pro Ser Gln Val Ser His Gly Thr Gly Phe Thr Ser Phe Gly Leu Leu 
    130                 135                 140                 


Lys Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
145                 150                 155                 160 


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
                165                 170                 175     


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
            180                 185                 190         


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
        195                 200                 205             


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
    210                 215                 220                 


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
225                 230                 235                 240 


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
                245                 250                 255     


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
            260                 265                 270         


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
        275                 280                 285             


Val Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val 
    290                 295                 300                 


Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
305                 310                 315                 320 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
                325                 330                 335     


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr 
            340                 345                 350         


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
        355                 360                 365             


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
    370                 375                 380                 


Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Ala 
385                 390                 395                 400 


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln 
                405                 410                 415     


Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr 
            420                 425                 430         


Cys Arg Ala Ser Gln Gly Ile Ser Ser Trp Leu Ala Trp Tyr Gln Gln 
        435                 440                 445             


Lys Pro Glu Lys Ala Pro Lys Ser Leu Ile Tyr Ala Ala Ser Ser Leu 
    450                 455                 460                 


Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
465                 470                 475                 480 


Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr 
                485                 490                 495     


Tyr Cys Gln Gln Tyr Asn Ile Tyr Pro Tyr Thr Phe Gly Gln Gly Thr 
            500                 505                 510         


Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
        515                 520                 525             


Gly Gly Gly Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys 
    530                 535                 540                 


Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser 
545                 550                 555                 560 


Phe Thr Thr Tyr Trp Leu Gly Trp Val Arg Gln Met Pro Gly Lys Gly 
                565                 570                 575     


Leu Asp Trp Ile Gly Ile Met Ser Pro Val Asp Ser Asp Ile Arg Tyr 
            580                 585                 590         


Ser Pro Ser Phe Gln Gly Gln Val Thr Met Ser Val Asp Lys Ser Ile 
        595                 600                 605             


Thr Thr Ala Tyr Leu Gln Trp Asn Ser Leu Lys Ala Ser Asp Thr Ala 
    610                 615                 620                 


Met Tyr Tyr Cys Ala Arg Arg Arg Pro Gly Gln Gly Tyr Phe Asp Phe 
625                 630                 635                 640 


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
                645                 650     


<210>  60
<211>  650
<212>  PRT
<213>  artificial

<220>
<223>  CD40L - Fc - scFV which binds to IL-12-VL-VH Briakinnumab- 
       Ustekinumab with cleavable linker


<220>
<221>  variant
<222>  (1)..(161)
<223>  sequence from positions 1 to 161 may be present in 1-3 copies 
       (n=1, 2 or 3)

<400>  60

Gly Asp Gln Asn Pro Gln Ile Ala Ala His Val Ile Ser Glu Ala Ser 
1               5                   10                  15      


Ser Lys Thr Thr Ser Val Leu Gln Trp Ala Glu Lys Gly Tyr Tyr Thr 
            20                  25                  30          


Met Ser Asn Asn Leu Val Thr Leu Glu Asn Gly Lys Gln Leu Thr Val 
        35                  40                  45              


Lys Arg Gln Gly Leu Tyr Tyr Ile Tyr Ala Gln Val Thr Phe Cys Ser 
    50                  55                  60                  


Asn Arg Glu Ala Ser Ser Gln Ala Pro Phe Ile Ala Ser Leu Cys Leu 
65                  70                  75                  80  


Lys Ser Pro Gly Arg Phe Glu Arg Ile Leu Leu Arg Ala Ala Asn Thr 
                85                  90                  95      


His Ser Ser Ala Lys Pro Cys Gly Gln Gln Ser Ile His Leu Gly Gly 
            100                 105                 110         


Val Phe Glu Leu Gln Pro Gly Ala Ser Val Phe Val Asn Val Thr Asp 
        115                 120                 125             


Pro Ser Gln Val Ser His Gly Thr Gly Phe Thr Ser Phe Gly Leu Leu 
    130                 135                 140                 


Lys Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
145                 150                 155                 160 


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
                165                 170                 175     


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
            180                 185                 190         


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
        195                 200                 205             


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
    210                 215                 220                 


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
225                 230                 235                 240 


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
                245                 250                 255     


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
            260                 265                 270         


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
        275                 280                 285             


Val Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val 
    290                 295                 300                 


Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
305                 310                 315                 320 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
                325                 330                 335     


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr 
            340                 345                 350         


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
        355                 360                 365             


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
    370                 375                 380                 


Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Pro 
385                 390                 395                 400 


Leu Gly Val Arg Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser 
                405                 410                 415     


Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys 
            420                 425                 430         


Arg Ala Ser Gln Gly Ile Ser Ser Trp Leu Ala Trp Tyr Gln Gln Lys 
        435                 440                 445             


Pro Glu Lys Ala Pro Lys Ser Leu Ile Tyr Ala Ala Ser Ser Leu Gln 
    450                 455                 460                 


Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 
465                 470                 475                 480 


Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 
                485                 490                 495     


Cys Gln Gln Tyr Asn Ile Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys 
            500                 505                 510         


Leu Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
        515                 520                 525             


Gly Gly Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys 
    530                 535                 540                 


Pro Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe 
545                 550                 555                 560 


Thr Thr Tyr Trp Leu Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu 
                565                 570                 575     


Asp Trp Ile Gly Ile Met Ser Pro Val Asp Ser Asp Ile Arg Tyr Ser 
            580                 585                 590         


Pro Ser Phe Gln Gly Gln Val Thr Met Ser Val Asp Lys Ser Ile Thr 
        595                 600                 605             


Thr Ala Tyr Leu Gln Trp Asn Ser Leu Lys Ala Ser Asp Thr Ala Met 
    610                 615                 620                 


Tyr Tyr Cys Ala Arg Arg Arg Pro Gly Gln Gly Tyr Phe Asp Phe Trp 
625                 630                 635                 640 


Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
                645                 650 


<210>  61
<211>  651
<212>  PRT
<213>  artificial

<220>
<223>  scFV which binds to IL-12-VL-VH Ustekinumab - Fc - CD40L


<220>
<221>  variant
<222>  (491)..(651)
<223>  sequence from positions 491 to 651 may be absent or present in 
       1-3 copies (n=0, 1, 2 or 3)

<400>  61

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Trp 
            20                  25                  30          


Leu Ala Trp Tyr Gln Gln Lys Pro Glu Lys Ala Pro Lys Ser Leu Ile 
        35                  40                  45              


Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ile Tyr Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser 
            100                 105                 110         


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Gln 
        115                 120                 125             


Ser Gly Ala Glu Val Lys Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys 
    130                 135                 140                 


Lys Gly Ser Gly Tyr Ser Phe Thr Thr Tyr Trp Leu Gly Trp Val Arg 
145                 150                 155                 160 


Gln Met Pro Gly Lys Gly Leu Asp Trp Ile Gly Ile Met Ser Pro Val 
                165                 170                 175     


Asp Ser Asp Ile Arg Tyr Ser Pro Ser Phe Gln Gly Gln Val Thr Met 
            180                 185                 190         


Ser Val Asp Lys Ser Ile Thr Thr Ala Tyr Leu Gln Trp Asn Ser Leu 
        195                 200                 205             


Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys Ala Arg Arg Arg Pro Gly 
    210                 215                 220                 


Gln Gly Tyr Phe Asp Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser 
225                 230                 235                 240 


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Ala Gly Gly Gly 
                245                 250                 255     


Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys 
            260                 265                 270         


Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
        275                 280                 285             


Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
    290                 295                 300                 


Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
305                 310                 315                 320 


Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
                325                 330                 335     


Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
            340                 345                 350         


His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
        355                 360                 365             


Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
    370                 375                 380                 


Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser Arg Asp Glu 
385                 390                 395                 400 


Leu Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr 
                405                 410                 415     


Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
            420                 425                 430         


Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
        435                 440                 445             


Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
    450                 455                 460                 


Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
465                 470                 475                 480 


Gln Lys Ser Leu Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly 
                485                 490                 495     


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Asp Gln Asn Pro Gln Ile 
            500                 505                 510         


Ala Ala His Val Ile Ser Glu Ala Ser Ser Lys Thr Thr Ser Val Leu 
        515                 520                 525             


Gln Trp Ala Glu Lys Gly Tyr Tyr Thr Met Ser Asn Asn Leu Val Thr 
    530                 535                 540                 


Leu Glu Asn Gly Lys Gln Leu Thr Val Lys Arg Gln Gly Leu Tyr Tyr 
545                 550                 555                 560 


Ile Tyr Ala Gln Val Thr Phe Cys Ser Asn Arg Glu Ala Ser Ser Gln 
                565                 570                 575     


Ala Pro Phe Ile Ala Ser Leu Cys Leu Lys Ser Pro Gly Arg Phe Glu 
            580                 585                 590         


Arg Ile Leu Leu Arg Ala Ala Asn Thr His Ser Ser Ala Lys Pro Cys 
        595                 600                 605             


Gly Gln Gln Ser Ile His Leu Gly Gly Val Phe Glu Leu Gln Pro Gly 
    610                 615                 620                 


Ala Ser Val Phe Val Asn Val Thr Asp Pro Ser Gln Val Ser His Gly 
625                 630                 635                 640 


Thr Gly Phe Thr Ser Phe Gly Leu Leu Lys Leu 
                645                 650     


<210>  62
<211>  650
<212>  PRT
<213>  artificial

<220>
<223>  scFV which binds to IL-12-VL-VH Ustekinumab  - Fc - CD40L, with a
       cleavable linker


<220>
<221>  variant
<222>  (490)..(650)
<223>  sequence from positions 490 to 650 may be absent or present in 
       1-3 copies (n=0, 1, 2 or 3)

<400>  62

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Trp 
            20                  25                  30          


Leu Ala Trp Tyr Gln Gln Lys Pro Glu Lys Ala Pro Lys Ser Leu Ile 
        35                  40                  45              


Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ile Tyr Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Gly Gly Gly Gly Ser 
            100                 105                 110         


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Gln 
        115                 120                 125             


Ser Gly Ala Glu Val Lys Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys 
    130                 135                 140                 


Lys Gly Ser Gly Tyr Ser Phe Thr Thr Tyr Trp Leu Gly Trp Val Arg 
145                 150                 155                 160 


Gln Met Pro Gly Lys Gly Leu Asp Trp Ile Gly Ile Met Ser Pro Val 
                165                 170                 175     


Asp Ser Asp Ile Arg Tyr Ser Pro Ser Phe Gln Gly Gln Val Thr Met 
            180                 185                 190         


Ser Val Asp Lys Ser Ile Thr Thr Ala Tyr Leu Gln Trp Asn Ser Leu 
        195                 200                 205             


Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys Ala Arg Arg Arg Pro Gly 
    210                 215                 220                 


Gln Gly Tyr Phe Asp Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser 
225                 230                 235                 240 


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Pro Leu Gly Val 
                245                 250                 255     


Arg Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
            260                 265                 270         


Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
        275                 280                 285             


Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
    290                 295                 300                 


Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
305                 310                 315                 320 


Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
                325                 330                 335     


Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
            340                 345                 350         


Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
        355                 360                 365             


Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
    370                 375                 380                 


Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu 
385                 390                 395                 400 


Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro 
                405                 410                 415     


Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
            420                 425                 430         


Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
        435                 440                 445             


Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
    450                 455                 460                 


Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
465                 470                 475                 480 


Lys Ser Leu Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly 
                485                 490                 495     


Gly Gly Ser Gly Gly Gly Gly Ser Gly Asp Gln Asn Pro Gln Ile Ala 
            500                 505                 510         


Ala His Val Ile Ser Glu Ala Ser Ser Lys Thr Thr Ser Val Leu Gln 
        515                 520                 525             


Trp Ala Glu Lys Gly Tyr Tyr Thr Met Ser Asn Asn Leu Val Thr Leu 
    530                 535                 540                 


Glu Asn Gly Lys Gln Leu Thr Val Lys Arg Gln Gly Leu Tyr Tyr Ile 
545                 550                 555                 560 


Tyr Ala Gln Val Thr Phe Cys Ser Asn Arg Glu Ala Ser Ser Gln Ala 
                565                 570                 575     


Pro Phe Ile Ala Ser Leu Cys Leu Lys Ser Pro Gly Arg Phe Glu Arg 
            580                 585                 590         


Ile Leu Leu Arg Ala Ala Asn Thr His Ser Ser Ala Lys Pro Cys Gly 
        595                 600                 605             


Gln Gln Ser Ile His Leu Gly Gly Val Phe Glu Leu Gln Pro Gly Ala 
    610                 615                 620                 


Ser Val Phe Val Asn Val Thr Asp Pro Ser Gln Val Ser His Gly Thr 
625                 630                 635                 640 


Gly Phe Thr Ser Phe Gly Leu Leu Lys Leu 
                645                 650 


<210>  63
<211>  306
<212>  PRT
<213>  artificial

<220>
<223>  IL-12 subunit P40 mutant

<400>  63

Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr 
1               5                   10                  15      


Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu 
            20                  25                  30          


Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly 
        35                  40                  45              


Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly 
    50                  55                  60                  


Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu 
65                  70                  75                  80  


Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys 
                85                  90                  95      


Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys 
            100                 105                 110         


Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr 
        115                 120                 125             


Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln 
    130                 135                 140                 


Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly 
145                 150                 155                 160 


Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala 
                165                 170                 175     


Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala 
            180                 185                 190         


Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg 
        195                 200                 205             


Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu 
    210                 215                 220                 


Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp 
225                 230                 235                 240 


Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln 
                245                 250                 255     


Gly Gln Asp Gln Asp Glu Ser Gly Asp Arg Val Phe Thr Asp Lys Thr 
            260                 265                 270         


Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala 
        275                 280                 285             


Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro 
    290                 295                 300                 


Cys Ser 
305     


<210>  64
<211>  65
<212>  PRT
<213>  artificial

<220>
<223>  Amino acid sequence of IL-15 receptor alpha Sushi domain

<400>  64

Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val 
1               5                   10                  15      


Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly 
            20                  25                  30          


Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn 
        35                  40                  45              


Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile 
    50                  55                  60                  


Arg 
65  


<210>  65
<211>  113
<212>  PRT
<213>  artificial

<220>
<223>  NWVNVISDLK KIEDLIQSMH IDATLYTESD VHPSCKVTAM KCFLLELQVI SLESGDASIH
       DTVENLIILA NNSLSSNGNV TESGCKECEE LEEKNIKEFL QSFVHIVQMF INT

<400>  65

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn 
            100                 105                 110         


Thr 
    


<210>  66
<211>  113
<212>  PRT
<213>  artificial

<220>
<223>  Human IL-15 mutant S58K

<400>  66

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Lys Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn 
            100                 105                 110         


Thr 
    


<210>  67
<211>  238
<212>  PRT
<213>  artificial

<220>
<223>  anti-IL-15 scFv1 ver2

<400>  67

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu 
1               5                   10                  15      


Ser Leu Lys Ile Ser Cys Lys Val Ser Gly Tyr Phe Phe Thr Thr Tyr 
            20                  25                  30          


Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Tyr Met 
        35                  40                  45              


Gly Ile Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe 
    50                  55                  60                  


Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr 
65                  70                  75                  80  


Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Gly Gly Asn Trp Asn Cys Phe Asp Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
        115                 120                 125             


Gly Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu 
    130                 135                 140                 


Ser Leu Ser Pro Gly Arg Glu Ala Thr Leu Ser Cys Arg Ala Ser Gln 
145                 150                 155                 160 


Ser Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
                165                 170                 175     


Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Arg Arg Ala Thr Gly Ile 
            180                 185                 190         


Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
        195                 200                 205             


Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Arg 
    210                 215                 220                 


Tyr Gly Ser Ser His Thr Phe Gly Gln Gly Thr Lys Leu Glu 
225                 230                 235             


<210>  68
<211>  274
<212>  PRT
<213>  artificial

<220>
<223>  ectodomain of a NKG2D ligand

<400>  68

Glu Pro His Ser Leu Arg Tyr Asn Leu Thr Val Leu Ser Trp Asp Gly 
1               5                   10                  15      


Ser Val Gln Ser Gly Phe Leu Thr Glu Val His Leu Asp Gly Gln Pro 
            20                  25                  30          


Phe Leu Arg Cys Asp Arg Gln Lys Cys Arg Ala Lys Pro Gln Gly Gln 
        35                  40                  45              


Trp Ala Glu Asp Val Leu Gly Asn Lys Thr Trp Asp Arg Glu Thr Arg 
    50                  55                  60                  


Asp Leu Thr Gly Asn Gly Lys Asp Leu Arg Met Thr Leu Ala His Ile 
65                  70                  75                  80  


Lys Asp Gln Lys Glu Gly Leu His Ser Leu Gln Glu Ile Arg Val Cys 
                85                  90                  95      


Glu Ile His Glu Asp Asn Ser Thr Arg Ser Ser Gln His Phe Tyr Tyr 
            100                 105                 110         


Asp Gly Glu Leu Phe Leu Ser Gln Asn Leu Glu Thr Lys Glu Trp Thr 
        115                 120                 125             


Met Pro Gln Ser Ser Arg Ala Gln Thr Leu Ala Met Asn Val Arg Asn 
    130                 135                 140                 


Phe Leu Lys Glu Asp Ala Met Lys Thr Lys Thr His Tyr His Ala Met 
145                 150                 155                 160 


His Ala Asp Cys Leu Gln Glu Leu Arg Arg Tyr Leu Lys Ser Gly Val 
                165                 170                 175     


Val Leu Arg Arg Thr Val Pro Pro Met Val Asn Val Thr Arg Ser Glu 
            180                 185                 190         


Ala Ser Glu Gly Asn Ile Thr Val Thr Cys Arg Ala Ser Gly Phe Tyr 
        195                 200                 205             


Pro Trp Asn Ile Thr Leu Ser Trp Arg Gln Asp Gly Val Ser Leu Ser 
    210                 215                 220                 


His Asp Thr Gln Gln Trp Gly Asp Val Leu Pro Asp Gly Asn Gly Thr 
225                 230                 235                 240 


Tyr Gln Thr Trp Val Ala Thr Arg Ile Cys Gln Gly Glu Glu Gln Arg 
                245                 250                 255     


Phe Thr Cys Tyr Met Glu His Ser Gly Asn His Ser Thr His Pro Val 
            260                 265                 270         


Pro Ser 
        


<210>  69
<211>  124
<212>  PRT
<213>  artificial

<220>
<223>  AS20592VH10 sdAb amino acid sequence

<400>  69

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ile Ile Ser Ser Tyr 
            20                  25                  30          


Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu Glu Gly Val 
        35                  40                  45              


Ala Ala Ile Asp Ser Asp Gly Gly Thr Ser Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Met Tyr Tyr Cys Ala 
                85                  90                  95      


Ala Asp Phe Cys Trp Val Asp Glu Asp Arg His Leu Tyr Glu Tyr Asn 
            100                 105                 110         


Ser Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 


<210>  70
<211>  124
<212>  PRT
<213>  artificial

<220>
<223>  AS20592VH10M1 sdAb amino acid sequence

<400>  70

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ile Ile Ser Ser Tyr 
            20                  25                  30          


Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu Glu Gly Val 
        35                  40                  45              


Ala Ala Ile Asp Ser Ser Gly Gly Thr Ser Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Met Tyr Tyr Cys Ala 
                85                  90                  95      


Ala Asp Phe Cys Trp Val Asp Glu Asp Arg His Leu Tyr Glu Tyr Asn 
            100                 105                 110         


Ser Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 


<210>  71
<211>  121
<212>  PRT
<213>  artificial

<220>
<223>  AS20594VH10 sdAb amino acid sequence

<400>  71

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Ile Ser Ser Tyr 
            20                  25                  30          


Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu Glu Gly Val 
        35                  40                  45              


Ala Ala Ile Asp Ser Asp Gly Ser Thr Ser Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      


Ala Asp Phe Cys Trp Val Asp Asp Phe Tyr Glu Tyr Asn Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


<210>  72
<211>  121
<212>  PRT
<213>  artificial

<220>
<223>  AS20594VH10M1 sdAb amino acid sequence

<400>  72

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Ile Ser Ser Tyr 
            20                  25                  30          


Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu Glu Gly Val 
        35                  40                  45              


Ala Ala Ile Asp Ser Ser Gly Ser Thr Ser Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      


Ala Asp Phe Cys Trp Val Asp Asp Phe Tyr Glu Tyr Asn Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


<210>  73
<211>  122
<212>  PRT
<213>  artificial

<220>
<223>  AS20846VH12 sdAb amino acid sequence

<400>  73

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Val Ser Ser Tyr 
            20                  25                  30          


Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg Glu Gly Val 
        35                  40                  45              


Ser Ala Ile Asp Ser Asp Gly Ser Val Ser Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Ala 
                85                  90                  95      


Ala Asp Leu Cys Trp Val Asp Gln Asp Gln Gly Glu Tyr Asn Thr Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120         


<210>  74
<211>  122
<212>  PRT
<213>  artificial

<220>
<223>  AS20846VH12M1 sdAb amino acid sequence

<400>  74

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Val Ser Ser Tyr 
            20                  25                  30          


Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg Glu Gly Val 
        35                  40                  45              


Ser Ala Ile Asp Ser Ser Gly Ser Val Ser Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Ala 
                85                  90                  95      


Ala Asp Leu Cys Trp Val Asp Gln Asp Gln Gly Glu Tyr Asn Thr Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120         


<210>  75
<211>  126
<212>  PRT
<213>  artificial

<220>
<223>  AS20601VH4 sdAb amino acid sequence

<400>  75

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Tyr Gly Gly Tyr 
            20                  25                  30          


Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu Glu Gly Val 
        35                  40                  45              


Ser Thr Ile Asn Ser Asp Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      


Val Asp Leu Ala Pro Cys Trp Val Ala Gly Pro Ile Glu Ala Ala Asp 
            100                 105                 110         


Phe Gly Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125     


<210>  76
<211>  126
<212>  PRT
<213>  artificial

<220>
<223>  AS20601VH4.M6 sdAb amino acid sequence

<400>  76

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Tyr Gly Gly Tyr 
            20                  25                  30          


Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu Glu Gly Val 
        35                  40                  45              


Ser Thr Ile Ala Ser Glu Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      


Val Asp Leu Ala Pro Cys Trp Val Ala Gly Pro Ile Glu Ala Ala Asp 
            100                 105                 110         


Phe Gly Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125     


<210>  77
<211>  126
<212>  PRT
<213>  artificial

<220>
<223>  AS20601VH4.M7 sdAb amino acid sequence

<400>  77

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Tyr Gly Gly Tyr 
            20                  25                  30          


Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Leu Glu Gly Val 
        35                  40                  45              


Ser Thr Ile Ala Ser Ser Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      


Val Asp Leu Ala Pro Cys Trp Val Ala Gly Pro Ile Glu Ala Ala Asp 
            100                 105                 110         


Phe Gly Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125     


<210>  78
<211>  117
<212>  PRT
<213>  artificial

<220>
<223>  VH of a 5T4 antibody

<400>  78

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu 
1               5                   10                  15      


Thr Leu Ser Ile Thr Cys Thr Val Ser Gly Val Ser Ile Ser Ser Tyr 
            20                  25                  30          


Gly Leu His Trp Ile Arg Gln Pro Pro Gly Lys Ser Leu Glu Trp Leu 
        35                  40                  45              


Gly Val Ile Trp Ala Ser Gly Arg Thr Asn Tyr Asn Pro Ala Leu Lys 
    50                  55                  60                  


Ser Arg Val Thr Ile Ser Gly Asp Thr Ser Lys Asn Gln Val Ser Leu 
65                  70                  75                  80  


Lys Leu Ser Gly Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      


Gly Ser Asn Trp Gly Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  79
<211>  107
<212>  PRT
<213>  artificial

<220>
<223>  VL of a 5T4 antibody

<400>  79

Ala Ile Arg Met Thr Gln Ser Pro Ser Ser Phe Ser Ala Ser Ala Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Asn Ile Tyr Ser Tyr 
            20                  25                  30          


Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ser Pro Lys Leu Leu Ile 
        35                  40                  45              


Tyr Asn Ala Lys Thr Leu Ala Glu Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln His His Tyr Ala Ile Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105         


<210>  80
<211>  490
<212>  PRT
<213>  artificial

<220>
<223>  Fc-scFV which binds to IL-12 - Briakinnumab (ASKGD111_CX10_64_2)

<400>  80

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Ala Gly 
225                 230                 235                 240 


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Val Leu Thr Gln Pro 
                245                 250                 255     


Pro Ser Val Ser Gly Ala Pro Gly Gln Arg Val Thr Ile Ser Cys Ser 
            260                 265                 270         


Gly Ser Arg Ser Asn Ile Gly Ser Asn Thr Val Lys Trp Tyr Gln Gln 
        275                 280                 285             


Leu Pro Gly Thr Ala Pro Lys Leu Leu Ile Tyr Tyr Asn Asp Gln Arg 
    290                 295                 300                 


Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Lys Ser Gly Thr Ser 
305                 310                 315                 320 


Ala Ser Leu Ala Ile Thr Gly Leu Gln Ala Glu Asp Glu Ala Asp Tyr 
                325                 330                 335     


Tyr Cys Gln Ser Tyr Asp Arg Tyr Thr His Pro Ala Leu Leu Phe Gly 
            340                 345                 350         


Thr Gly Thr Lys Val Thr Val Leu Gly Gly Gly Gly Ser Gly Gly Gly 
        355                 360                 365             


Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly 
    370                 375                 380                 


Gly Val Val Gln Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser 
385                 390                 395                 400 


Gly Phe Thr Phe Ser Ser Tyr Gly Met His Trp Val Arg Gln Ala Pro 
                405                 410                 415     


Gly Lys Gly Leu Glu Trp Val Ala Phe Ile Arg Tyr Asp Gly Ser Asn 
            420                 425                 430         


Lys Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp 
        435                 440                 445             


Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu 
    450                 455                 460                 


Asp Thr Ala Val Tyr Tyr Cys Lys Thr His Gly Ser His Asp Asn Trp 
465                 470                 475                 480 


Gly Gln Gly Thr Met Val Thr Val Ser Ser 
                485                 490 


<210>  81
<211>  760
<212>  PRT
<213>  artificial

<220>
<223>  Fc - IL-12 (P40-P35) with knobs mutations (ASKG111_CX5_43_1)

<400>  81

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp 
                245                 250                 255     


Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr 
            260                 265                 270         


Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val 
        275                 280                 285             


Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp 
    290                 295                 300                 


Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser 
305                 310                 315                 320 


Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile 
                325                 330                 335     


Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu 
            340                 345                 350         


Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile 
        355                 360                 365             


Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp 
    370                 375                 380                 


Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val 
385                 390                 395                 400 


Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp 
                405                 410                 415     


Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val 
            420                 425                 430         


Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe 
        435                 440                 445             


Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys 
    450                 455                 460                 


Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp 
465                 470                 475                 480 


Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln 
                485                 490                 495     


Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp 
            500                 505                 510         


Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val 
        515                 520                 525             


Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser 
    530                 535                 540                 


Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
545                 550                 555                 560 


Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe 
                565                 570                 575     


Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met 
            580                 585                 590         


Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu 
        595                 600                 605             


Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu 
    610                 615                 620                 


Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser 
625                 630                 635                 640 


Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys 
                645                 650                 655     


Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu 
            660                 665                 670         


Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met 
        675                 680                 685             


Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile 
    690                 695                 700                 


Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln 
705                 710                 715                 720 


Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu 
                725                 730                 735     


Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg 
            740                 745                 750         


Val Met Ser Tyr Leu Asn Ala Ser 
        755                 760 


<210>  82
<211>  760
<212>  PRT
<213>  artificial

<220>
<223>  Fc - IL-12 (P40-P35A1-K128N) with knobs (ASKGC111_CX14_25_1)

<400>  82

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp 
                245                 250                 255     


Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr 
            260                 265                 270         


Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val 
        275                 280                 285             


Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp 
    290                 295                 300                 


Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser 
305                 310                 315                 320 


Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile 
                325                 330                 335     


Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu 
            340                 345                 350         


Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile 
        355                 360                 365             


Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp 
    370                 375                 380                 


Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val 
385                 390                 395                 400 


Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp 
                405                 410                 415     


Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val 
            420                 425                 430         


Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe 
        435                 440                 445             


Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys 
    450                 455                 460                 


Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp 
465                 470                 475                 480 


Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln 
                485                 490                 495     


Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp 
            500                 505                 510         


Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val 
        515                 520                 525             


Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser 
    530                 535                 540                 


Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
545                 550                 555                 560 


Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe 
                565                 570                 575     


Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met 
            580                 585                 590         


Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu 
        595                 600                 605             


Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu 
    610                 615                 620                 


Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser 
625                 630                 635                 640 


Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys 
                645                 650                 655     


Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu 
            660                 665                 670         


Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met 
        675                 680                 685             


Asp Pro Asn Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile 
    690                 695                 700                 


Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln 
705                 710                 715                 720 


Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu 
                725                 730                 735     


Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg 
            740                 745                 750         


Val Met Ser Tyr Leu Asn Ala Ser 
        755                 760 


<210>  83
<211>  760
<212>  PRT
<213>  artificial

<220>
<223>  Fc - IL-12 (P40-P35A2-K128A) with knobs (ASKGC111_CX14_25_2)

<400>  83

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp 
                245                 250                 255     


Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr 
            260                 265                 270         


Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val 
        275                 280                 285             


Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp 
    290                 295                 300                 


Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser 
305                 310                 315                 320 


Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile 
                325                 330                 335     


Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu 
            340                 345                 350         


Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile 
        355                 360                 365             


Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp 
    370                 375                 380                 


Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val 
385                 390                 395                 400 


Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp 
                405                 410                 415     


Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val 
            420                 425                 430         


Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe 
        435                 440                 445             


Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys 
    450                 455                 460                 


Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp 
465                 470                 475                 480 


Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln 
                485                 490                 495     


Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp 
            500                 505                 510         


Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val 
        515                 520                 525             


Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser 
    530                 535                 540                 


Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
545                 550                 555                 560 


Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe 
                565                 570                 575     


Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met 
            580                 585                 590         


Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu 
        595                 600                 605             


Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu 
    610                 615                 620                 


Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser 
625                 630                 635                 640 


Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys 
                645                 650                 655     


Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu 
            660                 665                 670         


Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met 
        675                 680                 685             


Asp Pro Ala Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile 
    690                 695                 700                 


Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln 
705                 710                 715                 720 


Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu 
                725                 730                 735     


Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg 
            740                 745                 750         


Val Met Ser Tyr Leu Asn Ala Ser 
        755                 760 


<210>  84
<211>  760
<212>  PRT
<213>  artificial

<220>
<223>  Fc - IL-12 (P40-P35D-Y40A) with knobs (ASKGC111_CX14_25_3)

<400>  84

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp 
                245                 250                 255     


Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr 
            260                 265                 270         


Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val 
        275                 280                 285             


Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp 
    290                 295                 300                 


Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser 
305                 310                 315                 320 


Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile 
                325                 330                 335     


Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu 
            340                 345                 350         


Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile 
        355                 360                 365             


Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp 
    370                 375                 380                 


Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val 
385                 390                 395                 400 


Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp 
                405                 410                 415     


Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val 
            420                 425                 430         


Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe 
        435                 440                 445             


Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys 
    450                 455                 460                 


Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp 
465                 470                 475                 480 


Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln 
                485                 490                 495     


Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp 
            500                 505                 510         


Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val 
        515                 520                 525             


Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser 
    530                 535                 540                 


Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
545                 550                 555                 560 


Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe 
                565                 570                 575     


Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met 
            580                 585                 590         


Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Ala Pro Cys Thr Ser Glu 
        595                 600                 605             


Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu 
    610                 615                 620                 


Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser 
625                 630                 635                 640 


Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys 
                645                 650                 655     


Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu 
            660                 665                 670         


Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met 
        675                 680                 685             


Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile 
    690                 695                 700                 


Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln 
705                 710                 715                 720 


Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu 
                725                 730                 735     


Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg 
            740                 745                 750         


Val Met Ser Tyr Leu Asn Ala Ser 
        755                 760 


<210>  85
<211>  760
<212>  PRT
<213>  artificial

<220>
<223>  Fc - IL-12(P40-P35F-E45A/E46A) with knobs (ASKGC111_CX14_25_4)

<400>  85

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp 
                245                 250                 255     


Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr 
            260                 265                 270         


Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val 
        275                 280                 285             


Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp 
    290                 295                 300                 


Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser 
305                 310                 315                 320 


Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile 
                325                 330                 335     


Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu 
            340                 345                 350         


Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile 
        355                 360                 365             


Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp 
    370                 375                 380                 


Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val 
385                 390                 395                 400 


Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp 
                405                 410                 415     


Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val 
            420                 425                 430         


Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe 
        435                 440                 445             


Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys 
    450                 455                 460                 


Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp 
465                 470                 475                 480 


Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln 
                485                 490                 495     


Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp 
            500                 505                 510         


Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val 
        515                 520                 525             


Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser 
    530                 535                 540                 


Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
545                 550                 555                 560 


Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe 
                565                 570                 575     


Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met 
            580                 585                 590         


Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Ala 
        595                 600                 605             


Ala Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu 
    610                 615                 620                 


Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser 
625                 630                 635                 640 


Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys 
                645                 650                 655     


Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu 
            660                 665                 670         


Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met 
        675                 680                 685             


Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile 
    690                 695                 700                 


Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln 
705                 710                 715                 720 


Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu 
                725                 730                 735     


Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg 
            740                 745                 750         


Val Met Ser Tyr Leu Asn Ala Ser 
        755                 760 


<210>  86
<211>  760
<212>  PRT
<213>  artificial

<220>
<223>  Fc - IL-12 (P40-P35G-D48A/H49A) with knobs (ASKGC111_CX14_25_5)

<400>  86

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp 
                245                 250                 255     


Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr 
            260                 265                 270         


Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val 
        275                 280                 285             


Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp 
    290                 295                 300                 


Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser 
305                 310                 315                 320 


Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile 
                325                 330                 335     


Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu 
            340                 345                 350         


Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile 
        355                 360                 365             


Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp 
    370                 375                 380                 


Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val 
385                 390                 395                 400 


Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp 
                405                 410                 415     


Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val 
            420                 425                 430         


Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe 
        435                 440                 445             


Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys 
    450                 455                 460                 


Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp 
465                 470                 475                 480 


Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln 
                485                 490                 495     


Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp 
            500                 505                 510         


Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val 
        515                 520                 525             


Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser 
    530                 535                 540                 


Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
545                 550                 555                 560 


Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe 
                565                 570                 575     


Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met 
            580                 585                 590         


Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu 
        595                 600                 605             


Glu Ile Ala Ala Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu 
    610                 615                 620                 


Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser 
625                 630                 635                 640 


Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys 
                645                 650                 655     


Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu 
            660                 665                 670         


Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met 
        675                 680                 685             


Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile 
    690                 695                 700                 


Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln 
705                 710                 715                 720 


Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu 
                725                 730                 735     


Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg 
            740                 745                 750         


Val Met Ser Tyr Leu Asn Ala Ser 
        755                 760 


<210>  87
<211>  760
<212>  PRT
<213>  artificial

<220>
<223>  Fc - IL-12 (P40-P35I-E79A/T80A) with knobs (ASKGC111_CX14_25_6)

<400>  87

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp 
                245                 250                 255     


Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr 
            260                 265                 270         


Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val 
        275                 280                 285             


Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp 
    290                 295                 300                 


Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser 
305                 310                 315                 320 


Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile 
                325                 330                 335     


Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu 
            340                 345                 350         


Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile 
        355                 360                 365             


Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp 
    370                 375                 380                 


Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val 
385                 390                 395                 400 


Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp 
                405                 410                 415     


Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val 
            420                 425                 430         


Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe 
        435                 440                 445             


Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys 
    450                 455                 460                 


Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp 
465                 470                 475                 480 


Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln 
                485                 490                 495     


Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp 
            500                 505                 510         


Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val 
        515                 520                 525             


Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser 
    530                 535                 540                 


Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
545                 550                 555                 560 


Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe 
                565                 570                 575     


Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met 
            580                 585                 590         


Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu 
        595                 600                 605             


Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu 
    610                 615                 620                 


Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser 
625                 630                 635                 640 


Arg Ala Ala Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys 
                645                 650                 655     


Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu 
            660                 665                 670         


Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met 
        675                 680                 685             


Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile 
    690                 695                 700                 


Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln 
705                 710                 715                 720 


Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu 
                725                 730                 735     


Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg 
            740                 745                 750         


Val Met Ser Tyr Leu Asn Ala Ser 
        755                 760 


<210>  88
<211>  760
<212>  PRT
<213>  artificial

<220>
<223>  Fc - IL-12 (P40-P35K-F82A) with knobs (ASKGC111_CX14_25_7)

<400>  88

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp 
                245                 250                 255     


Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr 
            260                 265                 270         


Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val 
        275                 280                 285             


Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp 
    290                 295                 300                 


Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser 
305                 310                 315                 320 


Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile 
                325                 330                 335     


Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu 
            340                 345                 350         


Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile 
        355                 360                 365             


Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp 
    370                 375                 380                 


Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val 
385                 390                 395                 400 


Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp 
                405                 410                 415     


Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val 
            420                 425                 430         


Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe 
        435                 440                 445             


Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys 
    450                 455                 460                 


Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp 
465                 470                 475                 480 


Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln 
                485                 490                 495     


Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp 
            500                 505                 510         


Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val 
        515                 520                 525             


Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser 
    530                 535                 540                 


Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
545                 550                 555                 560 


Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe 
                565                 570                 575     


Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met 
            580                 585                 590         


Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu 
        595                 600                 605             


Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu 
    610                 615                 620                 


Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser 
625                 630                 635                 640 


Arg Glu Thr Ser Ala Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys 
                645                 650                 655     


Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu 
            660                 665                 670         


Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met 
        675                 680                 685             


Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile 
    690                 695                 700                 


Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln 
705                 710                 715                 720 


Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu 
                725                 730                 735     


Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg 
            740                 745                 750         


Val Met Ser Tyr Leu Asn Ala Ser 
        755                 760 


<210>  89
<211>  760
<212>  PRT
<213>  artificial

<220>
<223>  Fc - IL-12 (P40-P35M-N71Q) with knobs (ASKGC111_CX14_25_8)

<400>  89

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp 
                245                 250                 255     


Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr 
            260                 265                 270         


Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val 
        275                 280                 285             


Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp 
    290                 295                 300                 


Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser 
305                 310                 315                 320 


Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile 
                325                 330                 335     


Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu 
            340                 345                 350         


Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile 
        355                 360                 365             


Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp 
    370                 375                 380                 


Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val 
385                 390                 395                 400 


Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp 
                405                 410                 415     


Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val 
            420                 425                 430         


Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe 
        435                 440                 445             


Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys 
    450                 455                 460                 


Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp 
465                 470                 475                 480 


Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln 
                485                 490                 495     


Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp 
            500                 505                 510         


Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val 
        515                 520                 525             


Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser 
    530                 535                 540                 


Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
545                 550                 555                 560 


Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe 
                565                 570                 575     


Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met 
            580                 585                 590         


Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu 
        595                 600                 605             


Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu 
    610                 615                 620                 


Ala Cys Leu Pro Leu Glu Leu Thr Lys Gln Glu Ser Cys Leu Asn Ser 
625                 630                 635                 640 


Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys 
                645                 650                 655     


Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu 
            660                 665                 670         


Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met 
        675                 680                 685             


Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile 
    690                 695                 700                 


Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln 
705                 710                 715                 720 


Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu 
                725                 730                 735     


Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg 
            740                 745                 750         


Val Met Ser Tyr Leu Asn Ala Ser 
        755                 760 


<210>  90
<211>  760
<212>  PRT
<213>  artificial

<220>
<223>  Fc - IL-12 (P40-P35B-F166K) with knobs mutations 
       (ASKGC111_CX14_25_9)

<400>  90

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp 
                245                 250                 255     


Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr 
            260                 265                 270         


Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val 
        275                 280                 285             


Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp 
    290                 295                 300                 


Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser 
305                 310                 315                 320 


Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile 
                325                 330                 335     


Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu 
            340                 345                 350         


Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile 
        355                 360                 365             


Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp 
    370                 375                 380                 


Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val 
385                 390                 395                 400 


Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp 
                405                 410                 415     


Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val 
            420                 425                 430         


Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe 
        435                 440                 445             


Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys 
    450                 455                 460                 


Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp 
465                 470                 475                 480 


Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln 
                485                 490                 495     


Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp 
            500                 505                 510         


Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val 
        515                 520                 525             


Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser 
    530                 535                 540                 


Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
545                 550                 555                 560 


Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe 
                565                 570                 575     


Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met 
            580                 585                 590         


Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu 
        595                 600                 605             


Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu 
    610                 615                 620                 


Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser 
625                 630                 635                 640 


Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys 
                645                 650                 655     


Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu 
            660                 665                 670         


Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met 
        675                 680                 685             


Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile 
    690                 695                 700                 


Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln 
705                 710                 715                 720 


Lys Ser Ser Leu Glu Glu Pro Asp Lys Tyr Lys Thr Lys Ile Lys Leu 
                725                 730                 735     


Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg 
            740                 745                 750         


Val Met Ser Tyr Leu Asn Ala Ser 
        755                 760 


<210>  91
<211>  760
<212>  PRT
<213>  artificial

<220>
<223>  Fc - IL-12 (P40-P35E-T43A/S44G) with knobs mutations 
       (ASKGC111_CX14_25_11)

<400>  91

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp 
                245                 250                 255     


Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr 
            260                 265                 270         


Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val 
        275                 280                 285             


Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp 
    290                 295                 300                 


Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser 
305                 310                 315                 320 


Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile 
                325                 330                 335     


Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu 
            340                 345                 350         


Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile 
        355                 360                 365             


Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp 
    370                 375                 380                 


Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val 
385                 390                 395                 400 


Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp 
                405                 410                 415     


Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val 
            420                 425                 430         


Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe 
        435                 440                 445             


Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys 
    450                 455                 460                 


Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp 
465                 470                 475                 480 


Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln 
                485                 490                 495     


Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp 
            500                 505                 510         


Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val 
        515                 520                 525             


Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser 
    530                 535                 540                 


Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
545                 550                 555                 560 


Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe 
                565                 570                 575     


Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met 
            580                 585                 590         


Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Ala Gly Glu 
        595                 600                 605             


Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu 
    610                 615                 620                 


Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser 
625                 630                 635                 640 


Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys 
                645                 650                 655     


Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu 
            660                 665                 670         


Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met 
        675                 680                 685             


Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile 
    690                 695                 700                 


Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln 
705                 710                 715                 720 


Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu 
                725                 730                 735     


Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg 
            740                 745                 750         


Val Met Ser Tyr Leu Asn Ala Ser 
        755                 760 


<210>  92
<211>  760
<212>  PRT
<213>  artificial

<220>
<223>  Fc - IL-12 (P40-P35H-E50A) with knobs mutations 
       (ASKGC111_CX14_25_12)

<400>  92

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp 
                245                 250                 255     


Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr 
            260                 265                 270         


Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val 
        275                 280                 285             


Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp 
    290                 295                 300                 


Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser 
305                 310                 315                 320 


Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile 
                325                 330                 335     


Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu 
            340                 345                 350         


Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile 
        355                 360                 365             


Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp 
    370                 375                 380                 


Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val 
385                 390                 395                 400 


Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp 
                405                 410                 415     


Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val 
            420                 425                 430         


Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe 
        435                 440                 445             


Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys 
    450                 455                 460                 


Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp 
465                 470                 475                 480 


Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln 
                485                 490                 495     


Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp 
            500                 505                 510         


Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val 
        515                 520                 525             


Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser 
    530                 535                 540                 


Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
545                 550                 555                 560 


Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe 
                565                 570                 575     


Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met 
            580                 585                 590         


Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu 
        595                 600                 605             


Glu Ile Asp His Ala Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu 
    610                 615                 620                 


Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser 
625                 630                 635                 640 


Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys 
                645                 650                 655     


Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu 
            660                 665                 670         


Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met 
        675                 680                 685             


Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile 
    690                 695                 700                 


Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln 
705                 710                 715                 720 


Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu 
                725                 730                 735     


Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg 
            740                 745                 750         


Val Met Ser Tyr Leu Asn Ala Ser 
        755                 760 


<210>  93
<211>  752
<212>  PRT
<213>  artificial

<220>
<223>  Fc - IL-12 (P40-P35) with knobs mutations P40 Deletion258-265 
       (ASKGD111_CX14_4_1)

<400>  93

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp 
                245                 250                 255     


Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr 
            260                 265                 270         


Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val 
        275                 280                 285             


Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp 
    290                 295                 300                 


Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser 
305                 310                 315                 320 


Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile 
                325                 330                 335     


Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu 
            340                 345                 350         


Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile 
        355                 360                 365             


Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp 
    370                 375                 380                 


Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val 
385                 390                 395                 400 


Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp 
                405                 410                 415     


Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val 
            420                 425                 430         


Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe 
        435                 440                 445             


Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys 
    450                 455                 460                 


Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp 
465                 470                 475                 480 


Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln 
                485                 490                 495     


Val Gln Gly Arg Val Phe Thr Asp Lys Thr Ser Ala Thr Val Ile Cys 
            500                 505                 510         


Arg Lys Asn Ala Ser Ile Ser Val Arg Ala Gln Asp Arg Tyr Tyr Ser 
        515                 520                 525             


Ser Ser Trp Ser Glu Trp Ala Ser Val Pro Cys Ser Gly Gly Gly Gly 
    530                 535                 540                 


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Asn Leu Pro Val 
545                 550                 555                 560 


Ala Thr Pro Asp Pro Gly Met Phe Pro Cys Leu His His Ser Gln Asn 
                565                 570                 575     


Leu Leu Arg Ala Val Ser Asn Met Leu Gln Lys Ala Arg Gln Thr Leu 
            580                 585                 590         


Glu Phe Tyr Pro Cys Thr Ser Glu Glu Ile Asp His Glu Asp Ile Thr 
        595                 600                 605             


Lys Asp Lys Thr Ser Thr Val Glu Ala Cys Leu Pro Leu Glu Leu Thr 
    610                 615                 620                 


Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu Thr Ser Phe Ile Thr Asn 
625                 630                 635                 640 


Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser Phe Met Met Ala Leu Cys 
                645                 650                 655     


Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met Tyr Gln Val Glu Phe Lys 
            660                 665                 670         


Thr Met Asn Ala Lys Leu Leu Met Asp Pro Lys Arg Gln Ile Phe Leu 
        675                 680                 685             


Asp Gln Asn Met Leu Ala Val Ile Asp Glu Leu Met Gln Ala Leu Asn 
    690                 695                 700                 


Phe Asn Ser Glu Thr Val Pro Gln Lys Ser Ser Leu Glu Glu Pro Asp 
705                 710                 715                 720 


Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile Leu Leu His Ala Phe Arg 
                725                 730                 735     


Ile Arg Ala Val Thr Ile Asp Arg Val Met Ser Tyr Leu Asn Ala Ser 
            740                 745                 750         


<210>  94
<211>  757
<212>  PRT
<213>  artificial

<220>
<223>  - Fc - IL-12 (P40-P35) with knobs mutations P40v1 
       (ASKGD111_CX14_4_2)

<400>  94

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp 
                245                 250                 255     


Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr 
            260                 265                 270         


Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val 
        275                 280                 285             


Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp 
    290                 295                 300                 


Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser 
305                 310                 315                 320 


Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile 
                325                 330                 335     


Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu 
            340                 345                 350         


Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile 
        355                 360                 365             


Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp 
    370                 375                 380                 


Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val 
385                 390                 395                 400 


Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp 
                405                 410                 415     


Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val 
            420                 425                 430         


Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe 
        435                 440                 445             


Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys 
    450                 455                 460                 


Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp 
465                 470                 475                 480 


Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln 
                485                 490                 495     


Val Gln Gly Lys Asp Asn Thr Glu Arg Val Phe Thr Asp Lys Thr Ser 
            500                 505                 510         


Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala Gln 
        515                 520                 525             


Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro Cys 
    530                 535                 540                 


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
545                 550                 555                 560 


Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro Cys Leu 
                565                 570                 575     


His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu Gln Lys 
            580                 585                 590         


Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu Glu Ile Asp 
        595                 600                 605             


His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala Cys Leu 
    610                 615                 620                 


Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu Thr 
625                 630                 635                 640 


Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser Phe 
                645                 650                 655     


Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met Tyr 
            660                 665                 670         


Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp Pro Lys 
        675                 680                 685             


Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp Glu Leu 
    690                 695                 700                 


Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys Ser Ser 
705                 710                 715                 720 


Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile Leu 
                725                 730                 735     


Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val Met Ser 
            740                 745                 750         


Tyr Leu Asn Ala Ser 
        755         


<210>  95
<211>  760
<212>  PRT
<213>  artificial

<220>
<223>  Fc - IL-12 (P40-P35) with knobs mutations P40v3 
       (ASKGD111_CX14_4_3)

<400>  95

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp 
                245                 250                 255     


Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr 
            260                 265                 270         


Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val 
        275                 280                 285             


Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp 
    290                 295                 300                 


Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser 
305                 310                 315                 320 


Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile 
                325                 330                 335     


Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu 
            340                 345                 350         


Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile 
        355                 360                 365             


Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp 
    370                 375                 380                 


Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val 
385                 390                 395                 400 


Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp 
                405                 410                 415     


Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val 
            420                 425                 430         


Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe 
        435                 440                 445             


Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys 
    450                 455                 460                 


Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp 
465                 470                 475                 480 


Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln 
                485                 490                 495     


Val Gln Gly Gln Asp Gln Asp Glu Lys Lys Asp Arg Val Phe Thr Asp 
            500                 505                 510         


Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val 
        515                 520                 525             


Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser 
    530                 535                 540                 


Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
545                 550                 555                 560 


Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe 
                565                 570                 575     


Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met 
            580                 585                 590         


Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu 
        595                 600                 605             


Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu 
    610                 615                 620                 


Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser 
625                 630                 635                 640 


Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys 
                645                 650                 655     


Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu 
            660                 665                 670         


Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met 
        675                 680                 685             


Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile 
    690                 695                 700                 


Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln 
705                 710                 715                 720 


Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu 
                725                 730                 735     


Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg 
            740                 745                 750         


Val Met Ser Tyr Leu Asn Ala Ser 
        755                 760 


<210>  96
<211>  760
<212>  PRT
<213>  artificial

<220>
<223>  Fc - IL-12 (P40-P35) with knobs mutations P40v6_AA mutation 
       (ASKGD111_CX14_4_4)

<400>  96

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp 
                245                 250                 255     


Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr 
            260                 265                 270         


Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val 
        275                 280                 285             


Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp 
    290                 295                 300                 


Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser 
305                 310                 315                 320 


Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile 
                325                 330                 335     


Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu 
            340                 345                 350         


Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile 
        355                 360                 365             


Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp 
    370                 375                 380                 


Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val 
385                 390                 395                 400 


Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp 
                405                 410                 415     


Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val 
            420                 425                 430         


Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe 
        435                 440                 445             


Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys 
    450                 455                 460                 


Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp 
465                 470                 475                 480 


Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln 
                485                 490                 495     


Val Gln Gly Lys Ser Ala Ala Glu Lys Lys Asp Arg Val Phe Thr Asp 
            500                 505                 510         


Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val 
        515                 520                 525             


Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser 
    530                 535                 540                 


Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
545                 550                 555                 560 


Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe 
                565                 570                 575     


Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met 
            580                 585                 590         


Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu 
        595                 600                 605             


Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu 
    610                 615                 620                 


Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser 
625                 630                 635                 640 


Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys 
                645                 650                 655     


Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu 
            660                 665                 670         


Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met 
        675                 680                 685             


Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile 
    690                 695                 700                 


Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln 
705                 710                 715                 720 


Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu 
                725                 730                 735     


Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg 
            740                 745                 750         


Val Met Ser Tyr Leu Asn Ala Ser 
        755                 760 


<210>  97
<211>  494
<212>  PRT
<213>  artificial

<220>
<223>  scFV which binds to IL-12-VL-VH-4linker (ASKGD111_CX5_47_4)

<400>  97

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Pro Leu 
225                 230                 235                 240 


Gly Val Arg Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro 
                245                 250                 255     


Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg 
            260                 265                 270         


Ala Ser Gln Gly Ile Ser Ser Trp Leu Ala Trp Tyr Gln Gln Lys Pro 
        275                 280                 285             


Glu Lys Ala Pro Lys Ser Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser 
    290                 295                 300                 


Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 
305                 310                 315                 320 


Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys 
                325                 330                 335     


Gln Gln Tyr Asn Ile Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu 
            340                 345                 350         


Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
        355                 360                 365             


Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Gln Ser Gly Ala 
    370                 375                 380                 


Glu Val Lys Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser 
385                 390                 395                 400 


Gly Tyr Ser Phe Thr Thr Tyr Trp Leu Gly Trp Val Arg Gln Met Pro 
                405                 410                 415     


Gly Lys Gly Leu Asp Trp Ile Gly Ile Met Ser Pro Val Asp Ser Asp 
            420                 425                 430         


Ile Arg Tyr Ser Pro Ser Phe Gln Gly Gln Val Thr Met Ser Val Asp 
        435                 440                 445             


Lys Ser Ile Thr Thr Ala Tyr Leu Gln Trp Asn Ser Leu Lys Ala Ser 
    450                 455                 460                 


Asp Thr Ala Met Tyr Tyr Cys Ala Arg Arg Arg Pro Gly Gln Gly Tyr 
465                 470                 475                 480 


Phe Asp Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
                485                 490                 


<210>  98
<211>  298
<212>  PRT
<213>  artificial

<220>
<223>  P40 subunit of IL-12

<400>  98

Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr 
1               5                   10                  15      


Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu 
            20                  25                  30          


Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly 
        35                  40                  45              


Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly 
    50                  55                  60                  


Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu 
65                  70                  75                  80  


Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys 
                85                  90                  95      


Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys 
            100                 105                 110         


Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr 
        115                 120                 125             


Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln 
    130                 135                 140                 


Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly 
145                 150                 155                 160 


Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala 
                165                 170                 175     


Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala 
            180                 185                 190         


Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg 
        195                 200                 205             


Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu 
    210                 215                 220                 


Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp 
225                 230                 235                 240 


Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln 
                245                 250                 255     


Gly Arg Val Phe Thr Asp Lys Thr Ser Ala Thr Val Ile Cys Arg Lys 
            260                 265                 270         


Asn Ala Ser Ile Ser Val Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser 
        275                 280                 285             


Trp Ser Glu Trp Ala Ser Val Pro Cys Ser 
    290                 295             


<210>  99
<211>  760
<212>  PRT
<213>  artificial

<220>
<223>  Fc - IL-12 (P40-P35C-E38A/F39A) with knobs mutations 
       (ASKGC111_CX14_25_10)

<400>  99

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
225                 230                 235                 240 


Gly Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp 
                245                 250                 255     


Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr 
            260                 265                 270         


Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val 
        275                 280                 285             


Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp 
    290                 295                 300                 


Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser 
305                 310                 315                 320 


Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile 
                325                 330                 335     


Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu 
            340                 345                 350         


Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile 
        355                 360                 365             


Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp 
    370                 375                 380                 


Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val 
385                 390                 395                 400 


Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp 
                405                 410                 415     


Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val 
            420                 425                 430         


Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe 
        435                 440                 445             


Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys 
    450                 455                 460                 


Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp 
465                 470                 475                 480 


Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln 
                485                 490                 495     


Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp 
            500                 505                 510         


Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val 
        515                 520                 525             


Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser 
    530                 535                 540                 


Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
545                 550                 555                 560 


Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe 
                565                 570                 575     


Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met 
            580                 585                 590         


Leu Gln Lys Ala Arg Gln Thr Leu Ala Ala Tyr Pro Cys Thr Ser Glu 
        595                 600                 605             


Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu 
    610                 615                 620                 


Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser 
625                 630                 635                 640 


Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys 
                645                 650                 655     


Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu 
            660                 665                 670         


Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met 
        675                 680                 685             


Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile 
    690                 695                 700                 


Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln 
705                 710                 715                 720 


Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu 
                725                 730                 735     


Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg 
            740                 745                 750         


Val Met Ser Tyr Leu Asn Ala Ser 
        755                 760 


<210>  100
<211>  227
<212>  PRT
<213>  artificial

<220>
<223>  Fc Pembrolizumab

<400>  100

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
1               5                   10                  15      


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Lys 
225         


<210>  101
<211>  120
<212>  PRT
<213>  artificial

<220>
<223>  Pembrolizumab VH

<400>  101

Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
            20                  25                  30          


Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe 
    50                  55                  60                  


Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Thr Val Thr Val Ser Ser 
        115                 120 


<210>  102
<211>  111
<212>  PRT
<213>  artificial

<220>
<223>  Pembrolizumab VL

<400>  102

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly 
1               5                   10                  15      


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Lys Gly Val Ser Thr Ser 
            20                  25                  30          


Gly Tyr Ser Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 
        35                  40                  45              


Arg Leu Leu Ile Tyr Leu Ala Ser Tyr Leu Glu Ser Gly Val Pro Ala 
    50                  55                  60                  


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
65                  70                  75                  80  


Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Ser Arg 
                85                  90                  95      


Asp Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105                 110     


<210>  103
<211>  1011
<212>  PRT
<213>  artificial

<220>
<223>  Seq1-scFv-PD1-HC-LALA, G237A, IL-12wt Knob (ASKG129_CX14_100_1)

<400>  103

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly 
1               5                   10                  15      


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Lys Gly Val Ser Thr Ser 
            20                  25                  30          


Gly Tyr Ser Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 
        35                  40                  45              


Arg Leu Leu Ile Tyr Leu Ala Ser Tyr Leu Glu Ser Gly Val Pro Ala 
    50                  55                  60                  


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
65                  70                  75                  80  


Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Ser Arg 
                85                  90                  95      


Asp Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly 
            100                 105                 110         


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val 
        115                 120                 125             


Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala Ser Val 
    130                 135                 140                 


Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr Tyr Met 
145                 150                 155                 160 


Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Gly 
                165                 170                 175     


Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe Lys Asn 
            180                 185                 190         


Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr Met Glu 
        195                 200                 205             


Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg 
    210                 215                 220                 


Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln Gly Thr 
225                 230                 235                 240 


Thr Val Thr Val Ser Ser Gly Ser Glu Pro Lys Ser Ser Asp Lys Thr 
                245                 250                 255     


His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro Ser 
            260                 265                 270         


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg 
        275                 280                 285             


Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
    290                 295                 300                 


Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
305                 310                 315                 320 


Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 
                325                 330                 335     


Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
            340                 345                 350         


Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
        355                 360                 365             


Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
    370                 375                 380                 


Pro Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys 
385                 390                 395                 400 


Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
                405                 410                 415     


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
            420                 425                 430         


Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 
        435                 440                 445             


Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
    450                 455                 460                 


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly 
465                 470                 475                 480 


Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile Trp Glu 
                485                 490                 495     


Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr Pro Asp Ala 
            500                 505                 510         


Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu Glu Asp Gly 
        515                 520                 525             


Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly Ser Gly Lys 
    530                 535                 540                 


Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly Gln Tyr Thr 
545                 550                 555                 560 


Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu Leu Leu His 
                565                 570                 575     


Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys Asp Gln Lys 
            580                 585                 590         


Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys Asn Tyr Ser 
        595                 600                 605             


Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr Asp Leu Thr 
    610                 615                 620                 


Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln Gly Val Thr 
625                 630                 635                 640 


Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly Asp Asn Lys 
                645                 650                 655     


Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala Cys Pro Ala 
            660                 665                 670         


Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala Val His Lys 
        675                 680                 685             


Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg Asp Ile Ile 
    690                 695                 700                 


Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu Lys Asn Ser 
705                 710                 715                 720 


Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp Ser Thr Pro 
                725                 730                 735     


His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln Gly Lys Ser 
            740                 745                 750         


Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr Ser Ala Thr 
        755                 760                 765             


Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala Gln Asp Arg 
    770                 775                 780                 


Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro Cys Ser Gly 
785                 790                 795                 800 


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Asn 
                805                 810                 815     


Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro Cys Leu His His 
            820                 825                 830         


Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu Gln Lys Ala Arg 
        835                 840                 845             


Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu Glu Ile Asp His Glu 
    850                 855                 860                 


Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala Cys Leu Pro Leu 
865                 870                 875                 880 


Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu Thr Ser Phe 
                885                 890                 895     


Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser Phe Met Met 
            900                 905                 910         


Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met Tyr Gln Val 
        915                 920                 925             


Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp Pro Lys Arg Gln 
    930                 935                 940                 


Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp Glu Leu Met Gln 
945                 950                 955                 960 


Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys Ser Ser Leu Glu 
                965                 970                 975     


Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile Leu Leu His 
            980                 985                 990         


Ala Phe Arg Ile Arg Ala Val Thr  Ile Asp Arg Val Met  Ser Tyr Leu 
        995                 1000                 1005             


Asn Ala  Ser 
    1010     


<210>  104
<211>  1011
<212>  PRT
<213>  artificial

<220>
<223>  Seq2- scFv-PD1-HC-LALA, G237A, IL-12-P35Y40A-Knob 
       (ASKG129_CX14_100_2)

<400>  104

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly 
1               5                   10                  15      


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Lys Gly Val Ser Thr Ser 
            20                  25                  30          


Gly Tyr Ser Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 
        35                  40                  45              


Arg Leu Leu Ile Tyr Leu Ala Ser Tyr Leu Glu Ser Gly Val Pro Ala 
    50                  55                  60                  


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
65                  70                  75                  80  


Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Ser Arg 
                85                  90                  95      


Asp Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly 
            100                 105                 110         


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val 
        115                 120                 125             


Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala Ser Val 
    130                 135                 140                 


Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr Tyr Met 
145                 150                 155                 160 


Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Gly 
                165                 170                 175     


Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe Lys Asn 
            180                 185                 190         


Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr Met Glu 
        195                 200                 205             


Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg 
    210                 215                 220                 


Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln Gly Thr 
225                 230                 235                 240 


Thr Val Thr Val Ser Ser Gly Ser Glu Pro Lys Ser Ser Asp Lys Thr 
                245                 250                 255     


His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro Ser 
            260                 265                 270         


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg 
        275                 280                 285             


Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
    290                 295                 300                 


Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
305                 310                 315                 320 


Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 
                325                 330                 335     


Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
            340                 345                 350         


Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
        355                 360                 365             


Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
    370                 375                 380                 


Pro Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys 
385                 390                 395                 400 


Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
                405                 410                 415     


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
            420                 425                 430         


Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 
        435                 440                 445             


Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
    450                 455                 460                 


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly 
465                 470                 475                 480 


Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile Trp Glu 
                485                 490                 495     


Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr Pro Asp Ala 
            500                 505                 510         


Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu Glu Asp Gly 
        515                 520                 525             


Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly Ser Gly Lys 
    530                 535                 540                 


Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly Gln Tyr Thr 
545                 550                 555                 560 


Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu Leu Leu His 
                565                 570                 575     


Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys Asp Gln Lys 
            580                 585                 590         


Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys Asn Tyr Ser 
        595                 600                 605             


Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr Asp Leu Thr 
    610                 615                 620                 


Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln Gly Val Thr 
625                 630                 635                 640 


Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly Asp Asn Lys 
                645                 650                 655     


Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala Cys Pro Ala 
            660                 665                 670         


Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala Val His Lys 
        675                 680                 685             


Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg Asp Ile Ile 
    690                 695                 700                 


Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu Lys Asn Ser 
705                 710                 715                 720 


Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp Ser Thr Pro 
                725                 730                 735     


His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln Gly Lys Ser 
            740                 745                 750         


Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr Ser Ala Thr 
        755                 760                 765             


Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala Gln Asp Arg 
    770                 775                 780                 


Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro Cys Ser Gly 
785                 790                 795                 800 


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Asn 
                805                 810                 815     


Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro Cys Leu His His 
            820                 825                 830         


Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu Gln Lys Ala Arg 
        835                 840                 845             


Gln Thr Leu Glu Phe Ala Pro Cys Thr Ser Glu Glu Ile Asp His Glu 
    850                 855                 860                 


Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala Cys Leu Pro Leu 
865                 870                 875                 880 


Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu Thr Ser Phe 
                885                 890                 895     


Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser Phe Met Met 
            900                 905                 910         


Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met Tyr Gln Val 
        915                 920                 925             


Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp Pro Lys Arg Gln 
    930                 935                 940                 


Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp Glu Leu Met Gln 
945                 950                 955                 960 


Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys Ser Ser Leu Glu 
                965                 970                 975     


Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile Leu Leu His 
            980                 985                 990         


Ala Phe Arg Ile Arg Ala Val Thr  Ile Asp Arg Val Met  Ser Tyr Leu 
        995                 1000                 1005             


Asn Ala  Ser 
    1010     


<210>  105
<211>  1011
<212>  PRT
<213>  artificial

<220>
<223>  Seq3- scFv-PD1-HC-LALA, G237A, IL-12-P40AA-knob 
       (ASKG129_CX14_100_3)

<400>  105

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly 
1               5                   10                  15      


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Lys Gly Val Ser Thr Ser 
            20                  25                  30          


Gly Tyr Ser Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 
        35                  40                  45              


Arg Leu Leu Ile Tyr Leu Ala Ser Tyr Leu Glu Ser Gly Val Pro Ala 
    50                  55                  60                  


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
65                  70                  75                  80  


Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Ser Arg 
                85                  90                  95      


Asp Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly 
            100                 105                 110         


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val 
        115                 120                 125             


Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala Ser Val 
    130                 135                 140                 


Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr Tyr Met 
145                 150                 155                 160 


Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Gly 
                165                 170                 175     


Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe Lys Asn 
            180                 185                 190         


Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr Met Glu 
        195                 200                 205             


Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg 
    210                 215                 220                 


Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln Gly Thr 
225                 230                 235                 240 


Thr Val Thr Val Ser Ser Gly Ser Glu Pro Lys Ser Ser Asp Lys Thr 
                245                 250                 255     


His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro Ser 
            260                 265                 270         


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg 
        275                 280                 285             


Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
    290                 295                 300                 


Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
305                 310                 315                 320 


Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 
                325                 330                 335     


Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
            340                 345                 350         


Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
        355                 360                 365             


Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
    370                 375                 380                 


Pro Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys 
385                 390                 395                 400 


Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
                405                 410                 415     


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
            420                 425                 430         


Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 
        435                 440                 445             


Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
    450                 455                 460                 


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly 
465                 470                 475                 480 


Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile Trp Glu 
                485                 490                 495     


Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr Pro Asp Ala 
            500                 505                 510         


Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu Glu Asp Gly 
        515                 520                 525             


Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly Ser Gly Lys 
    530                 535                 540                 


Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly Gln Tyr Thr 
545                 550                 555                 560 


Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu Leu Leu His 
                565                 570                 575     


Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys Asp Gln Lys 
            580                 585                 590         


Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys Asn Tyr Ser 
        595                 600                 605             


Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr Asp Leu Thr 
    610                 615                 620                 


Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln Gly Val Thr 
625                 630                 635                 640 


Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly Asp Asn Lys 
                645                 650                 655     


Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala Cys Pro Ala 
            660                 665                 670         


Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala Val His Lys 
        675                 680                 685             


Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg Asp Ile Ile 
    690                 695                 700                 


Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu Lys Asn Ser 
705                 710                 715                 720 


Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp Ser Thr Pro 
                725                 730                 735     


His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln Gly Lys Ser 
            740                 745                 750         


Ala Ala Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr Ser Ala Thr 
        755                 760                 765             


Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala Gln Asp Arg 
    770                 775                 780                 


Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro Cys Ser Gly 
785                 790                 795                 800 


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Asn 
                805                 810                 815     


Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro Cys Leu His His 
            820                 825                 830         


Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu Gln Lys Ala Arg 
        835                 840                 845             


Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu Glu Ile Asp His Glu 
    850                 855                 860                 


Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala Cys Leu Pro Leu 
865                 870                 875                 880 


Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu Thr Ser Phe 
                885                 890                 895     


Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser Phe Met Met 
            900                 905                 910         


Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met Tyr Gln Val 
        915                 920                 925             


Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp Pro Lys Arg Gln 
    930                 935                 940                 


Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp Glu Leu Met Gln 
945                 950                 955                 960 


Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys Ser Ser Leu Glu 
                965                 970                 975     


Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile Leu Leu His 
            980                 985                 990         


Ala Phe Arg Ile Arg Ala Val Thr  Ile Asp Arg Val Met  Ser Tyr Leu 
        995                 1000                 1005             


Asn Ala  Ser 
    1010     


<210>  106
<211>  1006
<212>  PRT
<213>  artificial

<220>
<223>  Seq1-scFv-PD1-HC-LALA, G237A, IL-12wt Knob; short linker

<400>  106

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly 
1               5                   10                  15      


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Lys Gly Val Ser Thr Ser 
            20                  25                  30          


Gly Tyr Ser Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 
        35                  40                  45              


Arg Leu Leu Ile Tyr Leu Ala Ser Tyr Leu Glu Ser Gly Val Pro Ala 
    50                  55                  60                  


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
65                  70                  75                  80  


Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Ser Arg 
                85                  90                  95      


Asp Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly 
            100                 105                 110         


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val 
        115                 120                 125             


Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala Ser Val 
    130                 135                 140                 


Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr Tyr Met 
145                 150                 155                 160 


Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Gly 
                165                 170                 175     


Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe Lys Asn 
            180                 185                 190         


Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr Met Glu 
        195                 200                 205             


Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg 
    210                 215                 220                 


Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln Gly Thr 
225                 230                 235                 240 


Thr Val Thr Val Ser Ser Gly Ser Glu Pro Lys Ser Ser Asp Lys Thr 
                245                 250                 255     


His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro Ser 
            260                 265                 270         


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg 
        275                 280                 285             


Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
    290                 295                 300                 


Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
305                 310                 315                 320 


Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 
                325                 330                 335     


Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
            340                 345                 350         


Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
        355                 360                 365             


Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
    370                 375                 380                 


Pro Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys 
385                 390                 395                 400 


Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
                405                 410                 415     


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
            420                 425                 430         


Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 
        435                 440                 445             


Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
    450                 455                 460                 


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly 
465                 470                 475                 480 


Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile Trp Glu 
                485                 490                 495     


Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr Pro Asp Ala 
            500                 505                 510         


Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu Glu Asp Gly 
        515                 520                 525             


Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly Ser Gly Lys 
    530                 535                 540                 


Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly Gln Tyr Thr 
545                 550                 555                 560 


Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu Leu Leu His 
                565                 570                 575     


Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys Asp Gln Lys 
            580                 585                 590         


Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys Asn Tyr Ser 
        595                 600                 605             


Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr Asp Leu Thr 
    610                 615                 620                 


Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln Gly Val Thr 
625                 630                 635                 640 


Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly Asp Asn Lys 
                645                 650                 655     


Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala Cys Pro Ala 
            660                 665                 670         


Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala Val His Lys 
        675                 680                 685             


Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg Asp Ile Ile 
    690                 695                 700                 


Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu Lys Asn Ser 
705                 710                 715                 720 


Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp Ser Thr Pro 
                725                 730                 735     


His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln Gly Lys Ser 
            740                 745                 750         


Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr Ser Ala Thr 
        755                 760                 765             


Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala Gln Asp Arg 
    770                 775                 780                 


Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro Cys Ser Gly 
785                 790                 795                 800 


Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Asn Leu Pro Val Ala Thr 
                805                 810                 815     


Pro Asp Pro Gly Met Phe Pro Cys Leu His His Ser Gln Asn Leu Leu 
            820                 825                 830         


Arg Ala Val Ser Asn Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe 
        835                 840                 845             


Tyr Pro Cys Thr Ser Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp 
    850                 855                 860                 


Lys Thr Ser Thr Val Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn 
865                 870                 875                 880 


Glu Ser Cys Leu Asn Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser 
                885                 890                 895     


Cys Leu Ala Ser Arg Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser 
            900                 905                 910         


Ser Ile Tyr Glu Asp Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met 
        915                 920                 925             


Asn Ala Lys Leu Leu Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln 
    930                 935                 940                 


Asn Met Leu Ala Val Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn 
945                 950                 955                 960 


Ser Glu Thr Val Pro Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr 
                965                 970                 975     


Lys Thr Lys Ile Lys Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg 
            980                 985                 990         


Ala Val Thr Ile Asp Arg Val Met  Ser Tyr Leu Asn Ala  Ser 
        995                 1000                 1005     


<210>  107
<211>  1006
<212>  PRT
<213>  artificial

<220>
<223>  Seq2- scFv-PD1-HC-LALA, G237A, IL-12-P35Y40A-Knob 
       (ASKG129_CX14_100_2)

<400>  107

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly 
1               5                   10                  15      


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Lys Gly Val Ser Thr Ser 
            20                  25                  30          


Gly Tyr Ser Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 
        35                  40                  45              


Arg Leu Leu Ile Tyr Leu Ala Ser Tyr Leu Glu Ser Gly Val Pro Ala 
    50                  55                  60                  


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
65                  70                  75                  80  


Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Ser Arg 
                85                  90                  95      


Asp Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly 
            100                 105                 110         


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val 
        115                 120                 125             


Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala Ser Val 
    130                 135                 140                 


Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr Tyr Met 
145                 150                 155                 160 


Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Gly 
                165                 170                 175     


Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe Lys Asn 
            180                 185                 190         


Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr Met Glu 
        195                 200                 205             


Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg 
    210                 215                 220                 


Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln Gly Thr 
225                 230                 235                 240 


Thr Val Thr Val Ser Ser Gly Ser Glu Pro Lys Ser Ser Asp Lys Thr 
                245                 250                 255     


His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro Ser 
            260                 265                 270         


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg 
        275                 280                 285             


Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
    290                 295                 300                 


Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
305                 310                 315                 320 


Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 
                325                 330                 335     


Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
            340                 345                 350         


Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
        355                 360                 365             


Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
    370                 375                 380                 


Pro Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys 
385                 390                 395                 400 


Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
                405                 410                 415     


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
            420                 425                 430         


Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 
        435                 440                 445             


Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
    450                 455                 460                 


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly 
465                 470                 475                 480 


Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile Trp Glu 
                485                 490                 495     


Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr Pro Asp Ala 
            500                 505                 510         


Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu Glu Asp Gly 
        515                 520                 525             


Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly Ser Gly Lys 
    530                 535                 540                 


Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly Gln Tyr Thr 
545                 550                 555                 560 


Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu Leu Leu His 
                565                 570                 575     


Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys Asp Gln Lys 
            580                 585                 590         


Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys Asn Tyr Ser 
        595                 600                 605             


Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr Asp Leu Thr 
    610                 615                 620                 


Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln Gly Val Thr 
625                 630                 635                 640 


Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly Asp Asn Lys 
                645                 650                 655     


Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala Cys Pro Ala 
            660                 665                 670         


Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala Val His Lys 
        675                 680                 685             


Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg Asp Ile Ile 
    690                 695                 700                 


Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu Lys Asn Ser 
705                 710                 715                 720 


Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp Ser Thr Pro 
                725                 730                 735     


His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln Gly Lys Ser 
            740                 745                 750         


Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr Ser Ala Thr 
        755                 760                 765             


Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala Gln Asp Arg 
    770                 775                 780                 


Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro Cys Ser Gly 
785                 790                 795                 800 


Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Asn Leu Pro Val Ala Thr 
                805                 810                 815     


Pro Asp Pro Gly Met Phe Pro Cys Leu His His Ser Gln Asn Leu Leu 
            820                 825                 830         


Arg Ala Val Ser Asn Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe 
        835                 840                 845             


Ala Pro Cys Thr Ser Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp 
    850                 855                 860                 


Lys Thr Ser Thr Val Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn 
865                 870                 875                 880 


Glu Ser Cys Leu Asn Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser 
                885                 890                 895     


Cys Leu Ala Ser Arg Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser 
            900                 905                 910         


Ser Ile Tyr Glu Asp Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met 
        915                 920                 925             


Asn Ala Lys Leu Leu Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln 
    930                 935                 940                 


Asn Met Leu Ala Val Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn 
945                 950                 955                 960 


Ser Glu Thr Val Pro Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr 
                965                 970                 975     


Lys Thr Lys Ile Lys Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg 
            980                 985                 990         


Ala Val Thr Ile Asp Arg Val Met  Ser Tyr Leu Asn Ala  Ser 
        995                 1000                 1005     


<210>  108
<211>  1006
<212>  PRT
<213>  artificial

<220>
<223>  Seq3- scFv-PD1-HC-LALA, G237A, IL-12-P40AA-knob 
       (ASKG129_CX14_100_3)

<400>  108

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly 
1               5                   10                  15      


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Lys Gly Val Ser Thr Ser 
            20                  25                  30          


Gly Tyr Ser Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 
        35                  40                  45              


Arg Leu Leu Ile Tyr Leu Ala Ser Tyr Leu Glu Ser Gly Val Pro Ala 
    50                  55                  60                  


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
65                  70                  75                  80  


Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Ser Arg 
                85                  90                  95      


Asp Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly 
            100                 105                 110         


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val 
        115                 120                 125             


Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala Ser Val 
    130                 135                 140                 


Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr Tyr Met 
145                 150                 155                 160 


Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Gly 
                165                 170                 175     


Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe Lys Asn 
            180                 185                 190         


Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr Met Glu 
        195                 200                 205             


Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg 
    210                 215                 220                 


Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln Gly Thr 
225                 230                 235                 240 


Thr Val Thr Val Ser Ser Gly Ser Glu Pro Lys Ser Ser Asp Lys Thr 
                245                 250                 255     


His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro Ser 
            260                 265                 270         


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg 
        275                 280                 285             


Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
    290                 295                 300                 


Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
305                 310                 315                 320 


Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 
                325                 330                 335     


Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
            340                 345                 350         


Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
        355                 360                 365             


Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
    370                 375                 380                 


Pro Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys 
385                 390                 395                 400 


Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
                405                 410                 415     


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
            420                 425                 430         


Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 
        435                 440                 445             


Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
    450                 455                 460                 


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly 
465                 470                 475                 480 


Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile Trp Glu 
                485                 490                 495     


Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr Pro Asp Ala 
            500                 505                 510         


Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu Glu Asp Gly 
        515                 520                 525             


Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly Ser Gly Lys 
    530                 535                 540                 


Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly Gln Tyr Thr 
545                 550                 555                 560 


Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu Leu Leu His 
                565                 570                 575     


Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys Asp Gln Lys 
            580                 585                 590         


Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys Asn Tyr Ser 
        595                 600                 605             


Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr Asp Leu Thr 
    610                 615                 620                 


Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln Gly Val Thr 
625                 630                 635                 640 


Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly Asp Asn Lys 
                645                 650                 655     


Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala Cys Pro Ala 
            660                 665                 670         


Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala Val His Lys 
        675                 680                 685             


Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg Asp Ile Ile 
    690                 695                 700                 


Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu Lys Asn Ser 
705                 710                 715                 720 


Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp Ser Thr Pro 
                725                 730                 735     


His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln Gly Lys Ser 
            740                 745                 750         


Ala Ala Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr Ser Ala Thr 
        755                 760                 765             


Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala Gln Asp Arg 
    770                 775                 780                 


Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro Cys Ser Gly 
785                 790                 795                 800 


Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Asn Leu Pro Val Ala Thr 
                805                 810                 815     


Pro Asp Pro Gly Met Phe Pro Cys Leu His His Ser Gln Asn Leu Leu 
            820                 825                 830         


Arg Ala Val Ser Asn Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe 
        835                 840                 845             


Tyr Pro Cys Thr Ser Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp 
    850                 855                 860                 


Lys Thr Ser Thr Val Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn 
865                 870                 875                 880 


Glu Ser Cys Leu Asn Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser 
                885                 890                 895     


Cys Leu Ala Ser Arg Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser 
            900                 905                 910         


Ser Ile Tyr Glu Asp Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met 
        915                 920                 925             


Asn Ala Lys Leu Leu Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln 
    930                 935                 940                 


Asn Met Leu Ala Val Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn 
945                 950                 955                 960 


Ser Glu Thr Val Pro Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr 
                965                 970                 975     


Lys Thr Lys Ile Lys Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg 
            980                 985                 990         


Ala Val Thr Ile Asp Arg Val Met  Ser Tyr Leu Asn Ala  Ser 
        995                 1000                 1005     


<210>  109
<211>  742
<212>  PRT
<213>  artificial

<220>
<223>  Seq4- scFv-PD1-HC-LALA, G237A- mask-hole (ASKG129_CX14_100_4)

<400>  109

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly 
1               5                   10                  15      


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Lys Gly Val Ser Thr Ser 
            20                  25                  30          


Gly Tyr Ser Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 
        35                  40                  45              


Arg Leu Leu Ile Tyr Leu Ala Ser Tyr Leu Glu Ser Gly Val Pro Ala 
    50                  55                  60                  


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
65                  70                  75                  80  


Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Ser Arg 
                85                  90                  95      


Asp Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly 
            100                 105                 110         


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val 
        115                 120                 125             


Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala Ser Val 
    130                 135                 140                 


Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr Tyr Met 
145                 150                 155                 160 


Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Gly 
                165                 170                 175     


Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe Lys Asn 
            180                 185                 190         


Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr Met Glu 
        195                 200                 205             


Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg 
    210                 215                 220                 


Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln Gly Thr 
225                 230                 235                 240 


Thr Val Thr Val Ser Ser Gly Ser Glu Pro Lys Ser Ser Asp Lys Thr 
                245                 250                 255     


His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro Ser 
            260                 265                 270         


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg 
        275                 280                 285             


Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
    290                 295                 300                 


Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
305                 310                 315                 320 


Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 
                325                 330                 335     


Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
            340                 345                 350         


Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
        355                 360                 365             


Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu 
    370                 375                 380                 


Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Ser Cys 
385                 390                 395                 400 


Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
                405                 410                 415     


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
            420                 425                 430         


Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser 
        435                 440                 445             


Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
    450                 455                 460                 


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly 
465                 470                 475                 480 


Gly Gly Ser Gly Gly Gly Gly Ser Ala Ala Gly Gly Gly Gly Ser Gly 
                485                 490                 495     


Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser 
            500                 505                 510         


Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly 
        515                 520                 525             


Ile Ser Ser Trp Leu Ala Trp Tyr Gln Gln Lys Pro Glu Lys Ala Pro 
    530                 535                 540                 


Lys Ser Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser 
545                 550                 555                 560 


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
                565                 570                 575     


Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn 
            580                 585                 590         


Ile Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Ser 
        595                 600                 605             


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu 
    610                 615                 620                 


Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu Ser 
625                 630                 635                 640 


Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Tyr Trp 
                645                 650                 655     


Leu Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Asp Trp Ile Gly 
            660                 665                 670         


Ile Met Ser Pro Val Asp Ser Asp Ile Arg Tyr Ser Pro Ser Phe Gln 
        675                 680                 685             


Gly Gln Val Thr Met Ser Val Asp Lys Ser Ile Thr Thr Ala Tyr Leu 
    690                 695                 700                 


Gln Trp Asn Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys Ala 
705                 710                 715                 720 


Arg Arg Arg Pro Gly Gln Gly Tyr Phe Asp Phe Trp Gly Gln Gly Thr 
                725                 730                 735     


Leu Val Thr Val Ser Ser 
            740         


<210>  110
<211>  725
<212>  PRT
<213>  artificial

<220>
<223>  Seq4- scFv-PD1-HC-LALA, G237A- mask-hole (ASKG129_CX14_100_4); 
       short linker


<220>
<221>  variant
<222>  (479)..(483)
<223>  sequence from positions 479 to 483 may be absent or present in 
       1-3 copies (n=0, 1, 2 or 3)

<400>  110

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly 
1               5                   10                  15      


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Lys Gly Val Ser Thr Ser 
            20                  25                  30          


Gly Tyr Ser Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 
        35                  40                  45              


Arg Leu Leu Ile Tyr Leu Ala Ser Tyr Leu Glu Ser Gly Val Pro Ala 
    50                  55                  60                  


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
65                  70                  75                  80  


Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Ser Arg 
                85                  90                  95      


Asp Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly 
            100                 105                 110         


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val 
        115                 120                 125             


Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala Ser Val 
    130                 135                 140                 


Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr Tyr Met 
145                 150                 155                 160 


Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Gly 
                165                 170                 175     


Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe Lys Asn 
            180                 185                 190         


Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr Met Glu 
        195                 200                 205             


Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg 
    210                 215                 220                 


Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln Gly Thr 
225                 230                 235                 240 


Thr Val Thr Val Ser Ser Gly Ser Glu Pro Lys Ser Ser Asp Lys Thr 
                245                 250                 255     


His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro Ser 
            260                 265                 270         


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg 
        275                 280                 285             


Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
    290                 295                 300                 


Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
305                 310                 315                 320 


Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 
                325                 330                 335     


Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
            340                 345                 350         


Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
        355                 360                 365             


Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu 
    370                 375                 380                 


Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Ser Cys 
385                 390                 395                 400 


Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
                405                 410                 415     


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
            420                 425                 430         


Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser 
        435                 440                 445             


Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
    450                 455                 460                 


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly 
465                 470                 475                 480 


Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala 
                485                 490                 495     


Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile 
            500                 505                 510         


Ser Ser Trp Leu Ala Trp Tyr Gln Gln Lys Pro Glu Lys Ala Pro Lys 
        515                 520                 525             


Ser Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg 
    530                 535                 540                 


Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser 
545                 550                 555                 560 


Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ile 
                565                 570                 575     


Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Ser Gly 
            580                 585                 590         


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val 
        595                 600                 605             


Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu Ser Leu 
    610                 615                 620                 


Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Tyr Trp Leu 
625                 630                 635                 640 


Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Asp Trp Ile Gly Ile 
                645                 650                 655     


Met Ser Pro Val Asp Ser Asp Ile Arg Tyr Ser Pro Ser Phe Gln Gly 
            660                 665                 670         


Gln Val Thr Met Ser Val Asp Lys Ser Ile Thr Thr Ala Tyr Leu Gln 
        675                 680                 685             


Trp Asn Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys Ala Arg 
    690                 695                 700                 


Arg Arg Pro Gly Gln Gly Tyr Phe Asp Phe Trp Gly Gln Gly Thr Leu 
705                 710                 715                 720 


Val Thr Val Ser Ser 
                725 


<210>  111
<211>  611
<212>  PRT
<213>  artificial

<220>
<223>  LAG3-IGG1-YTE-LALA- scFv-U non clv _ 3xG4S (ASKG129_CX14_72_1)

<400>  111

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Val Ser Ser Tyr 
            20                  25                  30          


Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg Glu Gly Val 
        35                  40                  45              


Ser Ala Ile Asp Ser Asp Gly Ser Val Ser Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Ala 
                85                  90                  95      


Ala Asp Leu Cys Trp Val Asp Gln Asp Gln Gly Glu Tyr Asn Thr Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Ser Glu Pro Lys Ser 
        115                 120                 125             


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 
    130                 135                 140                 


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
145                 150                 155                 160 


Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                165                 170                 175     


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
            180                 185                 190         


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
        195                 200                 205             


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    210                 215                 220                 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
225                 230                 235                 240 


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                245                 250                 255     


Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
            260                 265                 270         


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        275                 280                 285             


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    290                 295                 300                 


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
305                 310                 315                 320 


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
                325                 330                 335     


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            340                 345                 350         


Ser Pro Gly Gly Ser Ala Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        355                 360                 365             


Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val 
    370                 375                 380                 


Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser 
385                 390                 395                 400 


Trp Leu Ala Trp Tyr Gln Gln Lys Pro Glu Lys Ala Pro Lys Ser Leu 
                405                 410                 415     


Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser 
            420                 425                 430         


Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln 
        435                 440                 445             


Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ile Tyr Pro 
    450                 455                 460                 


Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Ser Gly Gly Gly 
465                 470                 475                 480 


Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu 
                485                 490                 495     


Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu Ser Leu Lys Ile 
            500                 505                 510         


Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Tyr Trp Leu Gly Trp 
        515                 520                 525             


Val Arg Gln Met Pro Gly Lys Gly Leu Asp Trp Ile Gly Ile Met Ser 
    530                 535                 540                 


Pro Val Asp Ser Asp Ile Arg Tyr Ser Pro Ser Phe Gln Gly Gln Val 
545                 550                 555                 560 


Thr Met Ser Val Asp Lys Ser Ile Thr Thr Ala Tyr Leu Gln Trp Asn 
                565                 570                 575     


Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys Ala Arg Arg Arg 
            580                 585                 590         


Pro Gly Gln Gly Tyr Phe Asp Phe Trp Gly Gln Gly Thr Leu Val Thr 
        595                 600                 605             


Val Ser Ser 
    610     


<210>  112
<211>  606
<212>  PRT
<213>  artificial

<220>
<223>  LAG3-IGG1-YTE-LALA- scFv-U non clv _2xG4S (ASKG129_CX14_72_2)

<400>  112

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Val Ser Ser Tyr 
            20                  25                  30          


Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg Glu Gly Val 
        35                  40                  45              


Ser Ala Ile Asp Ser Asp Gly Ser Val Ser Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Ala 
                85                  90                  95      


Ala Asp Leu Cys Trp Val Asp Gln Asp Gln Gly Glu Tyr Asn Thr Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Ser Glu Pro Lys Ser 
        115                 120                 125             


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 
    130                 135                 140                 


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
145                 150                 155                 160 


Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                165                 170                 175     


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
            180                 185                 190         


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
        195                 200                 205             


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    210                 215                 220                 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
225                 230                 235                 240 


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                245                 250                 255     


Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
            260                 265                 270         


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        275                 280                 285             


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    290                 295                 300                 


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
305                 310                 315                 320 


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
                325                 330                 335     


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            340                 345                 350         


Ser Pro Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met 
        355                 360                 365             


Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr 
    370                 375                 380                 


Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Trp Leu Ala Trp Tyr 
385                 390                 395                 400 


Gln Gln Lys Pro Glu Lys Ala Pro Lys Ser Leu Ile Tyr Ala Ala Ser 
                405                 410                 415     


Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly 
            420                 425                 430         


Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala 
        435                 440                 445             


Thr Tyr Tyr Cys Gln Gln Tyr Asn Ile Tyr Pro Tyr Thr Phe Gly Gln 
    450                 455                 460                 


Gly Thr Lys Leu Glu Ile Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly 
465                 470                 475                 480 


Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Gln Ser Gly Ala 
                485                 490                 495     


Glu Val Lys Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser 
            500                 505                 510         


Gly Tyr Ser Phe Thr Thr Tyr Trp Leu Gly Trp Val Arg Gln Met Pro 
        515                 520                 525             


Gly Lys Gly Leu Asp Trp Ile Gly Ile Met Ser Pro Val Asp Ser Asp 
    530                 535                 540                 


Ile Arg Tyr Ser Pro Ser Phe Gln Gly Gln Val Thr Met Ser Val Asp 
545                 550                 555                 560 


Lys Ser Ile Thr Thr Ala Tyr Leu Gln Trp Asn Ser Leu Lys Ala Ser 
                565                 570                 575     


Asp Thr Ala Met Tyr Tyr Cys Ala Arg Arg Arg Pro Gly Gln Gly Tyr 
            580                 585                 590         


Phe Asp Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        595                 600                 605     


<210>  113
<211>  601
<212>  PRT
<213>  artificial

<220>
<223>  LAG3-IGG1-YTE-LALA- scFv-U non clv _1xG4S (ASKG129_CX14_72_3)

<400>  113

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Val Ser Ser Tyr 
            20                  25                  30          


Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg Glu Gly Val 
        35                  40                  45              


Ser Ala Ile Asp Ser Asp Gly Ser Val Ser Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Ala 
                85                  90                  95      


Ala Asp Leu Cys Trp Val Asp Gln Asp Gln Gly Glu Tyr Asn Thr Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Ser Glu Pro Lys Ser 
        115                 120                 125             


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 
    130                 135                 140                 


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
145                 150                 155                 160 


Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                165                 170                 175     


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
            180                 185                 190         


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
        195                 200                 205             


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    210                 215                 220                 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
225                 230                 235                 240 


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                245                 250                 255     


Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
            260                 265                 270         


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        275                 280                 285             


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    290                 295                 300                 


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
305                 310                 315                 320 


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
                325                 330                 335     


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            340                 345                 350         


Ser Pro Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser 
        355                 360                 365             


Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala 
    370                 375                 380                 


Ser Gln Gly Ile Ser Ser Trp Leu Ala Trp Tyr Gln Gln Lys Pro Glu 
385                 390                 395                 400 


Lys Ala Pro Lys Ser Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly 
                405                 410                 415     


Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu 
            420                 425                 430         


Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln 
        435                 440                 445             


Gln Tyr Asn Ile Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu 
    450                 455                 460                 


Ile Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
465                 470                 475                 480 


Gly Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro 
                485                 490                 495     


Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr 
            500                 505                 510         


Thr Tyr Trp Leu Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Asp 
        515                 520                 525             


Trp Ile Gly Ile Met Ser Pro Val Asp Ser Asp Ile Arg Tyr Ser Pro 
    530                 535                 540                 


Ser Phe Gln Gly Gln Val Thr Met Ser Val Asp Lys Ser Ile Thr Thr 
545                 550                 555                 560 


Ala Tyr Leu Gln Trp Asn Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr 
                565                 570                 575     


Tyr Cys Ala Arg Arg Arg Pro Gly Gln Gly Tyr Phe Asp Phe Trp Gly 
            580                 585                 590         


Gln Gly Thr Leu Val Thr Val Ser Ser 
        595                 600     


<210>  114
<211>  596
<212>  PRT
<213>  artificial

<220>
<223>  LAG3-IGG1-YTE-LALA- scFv-U non clv _0xG4S (ASKG129_CX14_72_4)

<400>  114

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Val Ser Ser Tyr 
            20                  25                  30          


Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg Glu Gly Val 
        35                  40                  45              


Ser Ala Ile Asp Ser Asp Gly Ser Val Ser Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Ala 
                85                  90                  95      


Ala Asp Leu Cys Trp Val Asp Gln Asp Gln Gly Glu Tyr Asn Thr Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Ser Glu Pro Lys Ser 
        115                 120                 125             


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 
    130                 135                 140                 


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
145                 150                 155                 160 


Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                165                 170                 175     


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
            180                 185                 190         


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
        195                 200                 205             


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    210                 215                 220                 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
225                 230                 235                 240 


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                245                 250                 255     


Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
            260                 265                 270         


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        275                 280                 285             


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    290                 295                 300                 


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
305                 310                 315                 320 


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
                325                 330                 335     


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            340                 345                 350         


Ser Pro Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser 
        355                 360                 365             


Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser 
    370                 375                 380                 


Ser Trp Leu Ala Trp Tyr Gln Gln Lys Pro Glu Lys Ala Pro Lys Ser 
385                 390                 395                 400 


Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe 
                405                 410                 415     


Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu 
            420                 425                 430         


Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ile Tyr 
        435                 440                 445             


Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Ser Gly Gly 
    450                 455                 460                 


Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln 
465                 470                 475                 480 


Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu Ser Leu Lys 
                485                 490                 495     


Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr Tyr Trp Leu Gly 
            500                 505                 510         


Trp Val Arg Gln Met Pro Gly Lys Gly Leu Asp Trp Ile Gly Ile Met 
        515                 520                 525             


Ser Pro Val Asp Ser Asp Ile Arg Tyr Ser Pro Ser Phe Gln Gly Gln 
    530                 535                 540                 


Val Thr Met Ser Val Asp Lys Ser Ile Thr Thr Ala Tyr Leu Gln Trp 
545                 550                 555                 560 


Asn Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys Ala Arg Arg 
                565                 570                 575     


Arg Pro Gly Gln Gly Tyr Phe Asp Phe Trp Gly Gln Gly Thr Leu Val 
            580                 585                 590         


Thr Val Ser Ser 
        595     


<210>  115
<211>  618
<212>  PRT
<213>  artificial

<220>
<223>  LAG3-IGG1-YTE-LALA- scFv-U non clv _ 4xG4S (ASKG129_CX14_51_1)

<400>  115

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Val Ser Ser Tyr 
            20                  25                  30          


Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg Glu Gly Val 
        35                  40                  45              


Ser Ala Ile Asp Ser Asp Gly Ser Val Ser Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Ala 
                85                  90                  95      


Ala Asp Leu Cys Trp Val Asp Gln Asp Gln Gly Glu Tyr Asn Thr Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Ser Glu Pro Lys Ser 
        115                 120                 125             


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 
    130                 135                 140                 


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
145                 150                 155                 160 


Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                165                 170                 175     


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
            180                 185                 190         


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
        195                 200                 205             


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    210                 215                 220                 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
225                 230                 235                 240 


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                245                 250                 255     


Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
            260                 265                 270         


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        275                 280                 285             


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    290                 295                 300                 


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
305                 310                 315                 320 


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
                325                 330                 335     


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            340                 345                 350         


Ser Pro Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Ala Gly Gly 
        355                 360                 365             


Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro 
    370                 375                 380                 


Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg 
385                 390                 395                 400 


Ala Ser Gln Gly Ile Ser Ser Trp Leu Ala Trp Tyr Gln Gln Lys Pro 
                405                 410                 415     


Glu Lys Ala Pro Lys Ser Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser 
            420                 425                 430         


Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 
        435                 440                 445             


Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys 
    450                 455                 460                 


Gln Gln Tyr Asn Ile Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu 
465                 470                 475                 480 


Glu Ile Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly 
                485                 490                 495     


Gly Gly Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys 
            500                 505                 510         


Pro Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe 
        515                 520                 525             


Thr Thr Tyr Trp Leu Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu 
    530                 535                 540                 


Asp Trp Ile Gly Ile Met Ser Pro Val Asp Ser Asp Ile Arg Tyr Ser 
545                 550                 555                 560 


Pro Ser Phe Gln Gly Gln Val Thr Met Ser Val Asp Lys Ser Ile Thr 
                565                 570                 575     


Thr Ala Tyr Leu Gln Trp Asn Ser Leu Lys Ala Ser Asp Thr Ala Met 
            580                 585                 590         


Tyr Tyr Cys Ala Arg Arg Arg Pro Gly Gln Gly Tyr Phe Asp Phe Trp 
        595                 600                 605             


Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
    610                 615             


<210>  116
<211>  882
<212>  PRT
<213>  artificial

<220>
<223>  LAG3-IGG1-YTE-LALA-IL12P40AA_2xG4S (ASKG129_CX14_74_1)

<400>  116

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Val Ser Ser Tyr 
            20                  25                  30          


Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg Glu Gly Val 
        35                  40                  45              


Ser Ala Ile Asp Ser Asp Gly Ser Val Ser Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Ala 
                85                  90                  95      


Ala Asp Leu Cys Trp Val Asp Gln Asp Gln Gly Glu Tyr Asn Thr Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Ser Glu Pro Lys Ser 
        115                 120                 125             


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 
    130                 135                 140                 


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
145                 150                 155                 160 


Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                165                 170                 175     


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
            180                 185                 190         


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
        195                 200                 205             


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    210                 215                 220                 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
225                 230                 235                 240 


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                245                 250                 255     


Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
            260                 265                 270         


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        275                 280                 285             


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    290                 295                 300                 


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
305                 310                 315                 320 


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
                325                 330                 335     


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            340                 345                 350         


Ser Pro Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        355                 360                 365             


Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp 
    370                 375                 380                 


Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro 
385                 390                 395                 400 


Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu 
                405                 410                 415     


Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala 
            420                 425                 430         


Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu 
        435                 440                 445             


Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu 
    450                 455                 460                 


Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala 
465                 470                 475                 480 


Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser 
                485                 490                 495     


Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro 
            500                 505                 510         


Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg 
        515                 520                 525             


Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser 
    530                 535                 540                 


Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp 
545                 550                 555                 560 


Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile 
                565                 570                 575     


Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro 
            580                 585                 590         


Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr 
        595                 600                 605             


Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val 
    610                 615                 620                 


Gln Gly Lys Ser Ala Ala Glu Lys Lys Asp Arg Val Phe Thr Asp Lys 
625                 630                 635                 640 


Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg 
                645                 650                 655     


Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val 
            660                 665                 670         


Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Asn Leu 
        675                 680                 685             


Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro Cys Leu His His Ser 
    690                 695                 700                 


Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu Gln Lys Ala Arg Gln 
705                 710                 715                 720 


Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu Glu Ile Asp His Glu Asp 
                725                 730                 735     


Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala Cys Leu Pro Leu Glu 
            740                 745                 750         


Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu Thr Ser Phe Ile 
        755                 760                 765             


Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser Phe Met Met Ala 
    770                 775                 780                 


Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met Tyr Gln Val Glu 
785                 790                 795                 800 


Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp Pro Lys Arg Gln Ile 
                805                 810                 815     


Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp Glu Leu Met Gln Ala 
            820                 825                 830         


Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys Ser Ser Leu Glu Glu 
        835                 840                 845             


Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile Leu Leu His Ala 
    850                 855                 860                 


Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val Met Ser Tyr Leu Asn 
865                 870                 875                 880 


Ala Ser 
        


<210>  117
<211>  877
<212>  PRT
<213>  artificial

<220>
<223>  LAG3-IGG1-YTE-LALA-IL12P40AA_1xG4S (ASKG129_CX14_74_2)

<400>  117

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Val Ser Ser Tyr 
            20                  25                  30          


Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg Glu Gly Val 
        35                  40                  45              


Ser Ala Ile Asp Ser Asp Gly Ser Val Ser Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Ala 
                85                  90                  95      


Ala Asp Leu Cys Trp Val Asp Gln Asp Gln Gly Glu Tyr Asn Thr Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Ser Glu Pro Lys Ser 
        115                 120                 125             


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 
    130                 135                 140                 


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
145                 150                 155                 160 


Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                165                 170                 175     


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
            180                 185                 190         


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
        195                 200                 205             


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    210                 215                 220                 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
225                 230                 235                 240 


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                245                 250                 255     


Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
            260                 265                 270         


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        275                 280                 285             


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    290                 295                 300                 


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
305                 310                 315                 320 


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
                325                 330                 335     


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            340                 345                 350         


Ser Pro Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        355                 360                 365             


Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp 
    370                 375                 380                 


Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro 
385                 390                 395                 400 


Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu 
                405                 410                 415     


Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala 
            420                 425                 430         


Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu 
        435                 440                 445             


Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu 
    450                 455                 460                 


Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala 
465                 470                 475                 480 


Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser 
                485                 490                 495     


Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro 
            500                 505                 510         


Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg 
        515                 520                 525             


Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser 
    530                 535                 540                 


Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp 
545                 550                 555                 560 


Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile 
                565                 570                 575     


Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro 
            580                 585                 590         


Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr 
        595                 600                 605             


Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val 
    610                 615                 620                 


Gln Gly Lys Ser Ala Ala Glu Lys Lys Asp Arg Val Phe Thr Asp Lys 
625                 630                 635                 640 


Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg 
                645                 650                 655     


Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val 
            660                 665                 670         


Pro Cys Ser Gly Gly Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro 
        675                 680                 685             


Asp Pro Gly Met Phe Pro Cys Leu His His Ser Gln Asn Leu Leu Arg 
    690                 695                 700                 


Ala Val Ser Asn Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr 
705                 710                 715                 720 


Pro Cys Thr Ser Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys 
                725                 730                 735     


Thr Ser Thr Val Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu 
            740                 745                 750         


Ser Cys Leu Asn Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys 
        755                 760                 765             


Leu Ala Ser Arg Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser 
    770                 775                 780                 


Ile Tyr Glu Asp Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn 
785                 790                 795                 800 


Ala Lys Leu Leu Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn 
                805                 810                 815     


Met Leu Ala Val Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser 
            820                 825                 830         


Glu Thr Val Pro Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys 
        835                 840                 845             


Thr Lys Ile Lys Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala 
    850                 855                 860                 


Val Thr Ile Asp Arg Val Met Ser Tyr Leu Asn Ala Ser 
865                 870                 875         


<210>  118
<211>  887
<212>  PRT
<213>  artificial

<220>
<223>  LAG3-IGG1-YTE-LALA-IL12P40AA (ASKG129_CX14_51_5)

<400>  118

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Val Ser Ser Tyr 
            20                  25                  30          


Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg Glu Gly Val 
        35                  40                  45              


Ser Ala Ile Asp Ser Asp Gly Ser Val Ser Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Ala 
                85                  90                  95      


Ala Asp Leu Cys Trp Val Asp Gln Asp Gln Gly Glu Tyr Asn Thr Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Ser Glu Pro Lys Ser 
        115                 120                 125             


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 
    130                 135                 140                 


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
145                 150                 155                 160 


Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                165                 170                 175     


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
            180                 185                 190         


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
        195                 200                 205             


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    210                 215                 220                 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
225                 230                 235                 240 


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                245                 250                 255     


Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
            260                 265                 270         


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        275                 280                 285             


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    290                 295                 300                 


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
305                 310                 315                 320 


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
                325                 330                 335     


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            340                 345                 350         


Ser Pro Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        355                 360                 365             


Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp 
    370                 375                 380                 


Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro 
385                 390                 395                 400 


Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu 
                405                 410                 415     


Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala 
            420                 425                 430         


Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu 
        435                 440                 445             


Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu 
    450                 455                 460                 


Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala 
465                 470                 475                 480 


Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser 
                485                 490                 495     


Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro 
            500                 505                 510         


Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg 
        515                 520                 525             


Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser 
    530                 535                 540                 


Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp 
545                 550                 555                 560 


Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile 
                565                 570                 575     


Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro 
            580                 585                 590         


Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr 
        595                 600                 605             


Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val 
    610                 615                 620                 


Gln Gly Lys Ser Ala Ala Glu Lys Lys Asp Arg Val Phe Thr Asp Lys 
625                 630                 635                 640 


Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg 
                645                 650                 655     


Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val 
            660                 665                 670         


Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
        675                 680                 685             


Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro 
    690                 695                 700                 


Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu 
705                 710                 715                 720 


Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu Glu 
                725                 730                 735     


Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala 
            740                 745                 750         


Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg 
        755                 760                 765             


Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr 
    770                 775                 780                 


Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys 
785                 790                 795                 800 


Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp 
                805                 810                 815     


Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp 
            820                 825                 830         


Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys 
        835                 840                 845             


Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys 
    850                 855                 860                 


Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val 
865                 870                 875                 880 


Met Ser Tyr Leu Asn Ala Ser 
                885         


<210>  119
<211>  887
<212>  PRT
<213>  artificial

<220>
<223>  LAG3-IGG1-YTE-LALA-IL12-T36A (ASKG129_CX14_70_1)

<400>  119

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Val Ser Ser Tyr 
            20                  25                  30          


Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg Glu Gly Val 
        35                  40                  45              


Ser Ala Ile Asp Ser Asp Gly Ser Val Ser Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Ala 
                85                  90                  95      


Ala Asp Leu Cys Trp Val Asp Gln Asp Gln Gly Glu Tyr Asn Thr Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Ser Glu Pro Lys Ser 
        115                 120                 125             


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 
    130                 135                 140                 


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
145                 150                 155                 160 


Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                165                 170                 175     


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
            180                 185                 190         


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
        195                 200                 205             


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    210                 215                 220                 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
225                 230                 235                 240 


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                245                 250                 255     


Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
            260                 265                 270         


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        275                 280                 285             


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    290                 295                 300                 


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
305                 310                 315                 320 


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
                325                 330                 335     


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            340                 345                 350         


Ser Pro Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        355                 360                 365             


Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp 
    370                 375                 380                 


Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro 
385                 390                 395                 400 


Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu 
                405                 410                 415     


Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala 
            420                 425                 430         


Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu 
        435                 440                 445             


Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu 
    450                 455                 460                 


Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala 
465                 470                 475                 480 


Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser 
                485                 490                 495     


Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro 
            500                 505                 510         


Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg 
        515                 520                 525             


Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser 
    530                 535                 540                 


Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp 
545                 550                 555                 560 


Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile 
                565                 570                 575     


Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro 
            580                 585                 590         


Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr 
        595                 600                 605             


Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val 
    610                 615                 620                 


Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys 
625                 630                 635                 640 


Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg 
                645                 650                 655     


Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val 
            660                 665                 670         


Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
        675                 680                 685             


Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro 
    690                 695                 700                 


Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu 
705                 710                 715                 720 


Gln Lys Ala Arg Gln Ala Leu Glu Phe Tyr Pro Cys Thr Ser Glu Glu 
                725                 730                 735     


Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala 
            740                 745                 750         


Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg 
        755                 760                 765             


Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr 
    770                 775                 780                 


Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys 
785                 790                 795                 800 


Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp 
                805                 810                 815     


Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp 
            820                 825                 830         


Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys 
        835                 840                 845             


Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys 
    850                 855                 860                 


Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val 
865                 870                 875                 880 


Met Ser Tyr Leu Asn Ala Ser 
                885         


<210>  120
<211>  887
<212>  PRT
<213>  artificial

<220>
<223>  LAG3-IGG1-YTE-LALA-IL12-L37E (ASKG129_CX14_70_2)

<400>  120

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Val Ser Ser Tyr 
            20                  25                  30          


Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg Glu Gly Val 
        35                  40                  45              


Ser Ala Ile Asp Ser Asp Gly Ser Val Ser Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Ala 
                85                  90                  95      


Ala Asp Leu Cys Trp Val Asp Gln Asp Gln Gly Glu Tyr Asn Thr Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Ser Glu Pro Lys Ser 
        115                 120                 125             


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 
    130                 135                 140                 


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
145                 150                 155                 160 


Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                165                 170                 175     


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
            180                 185                 190         


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
        195                 200                 205             


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    210                 215                 220                 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
225                 230                 235                 240 


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                245                 250                 255     


Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
            260                 265                 270         


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        275                 280                 285             


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    290                 295                 300                 


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
305                 310                 315                 320 


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
                325                 330                 335     


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            340                 345                 350         


Ser Pro Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        355                 360                 365             


Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp 
    370                 375                 380                 


Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro 
385                 390                 395                 400 


Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu 
                405                 410                 415     


Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala 
            420                 425                 430         


Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu 
        435                 440                 445             


Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu 
    450                 455                 460                 


Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala 
465                 470                 475                 480 


Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser 
                485                 490                 495     


Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro 
            500                 505                 510         


Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg 
        515                 520                 525             


Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser 
    530                 535                 540                 


Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp 
545                 550                 555                 560 


Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile 
                565                 570                 575     


Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro 
            580                 585                 590         


Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr 
        595                 600                 605             


Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val 
    610                 615                 620                 


Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys 
625                 630                 635                 640 


Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg 
                645                 650                 655     


Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val 
            660                 665                 670         


Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
        675                 680                 685             


Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro 
    690                 695                 700                 


Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu 
705                 710                 715                 720 


Gln Lys Ala Arg Gln Thr Glu Glu Phe Tyr Pro Cys Thr Ser Glu Glu 
                725                 730                 735     


Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala 
            740                 745                 750         


Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg 
        755                 760                 765             


Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr 
    770                 775                 780                 


Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys 
785                 790                 795                 800 


Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp 
                805                 810                 815     


Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp 
            820                 825                 830         


Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys 
        835                 840                 845             


Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys 
    850                 855                 860                 


Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val 
865                 870                 875                 880 


Met Ser Tyr Leu Asn Ala Ser 
                885         


<210>  121
<211>  887
<212>  PRT
<213>  artificial

<220>
<223>  LAG3-IGG1-YTE-LALA-IL12-E38A (ASKG129_CX14_70_3)

<400>  121

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Val Ser Ser Tyr 
            20                  25                  30          


Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg Glu Gly Val 
        35                  40                  45              


Ser Ala Ile Asp Ser Asp Gly Ser Val Ser Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Ala 
                85                  90                  95      


Ala Asp Leu Cys Trp Val Asp Gln Asp Gln Gly Glu Tyr Asn Thr Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Ser Glu Pro Lys Ser 
        115                 120                 125             


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 
    130                 135                 140                 


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
145                 150                 155                 160 


Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                165                 170                 175     


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
            180                 185                 190         


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
        195                 200                 205             


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    210                 215                 220                 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
225                 230                 235                 240 


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                245                 250                 255     


Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
            260                 265                 270         


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        275                 280                 285             


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    290                 295                 300                 


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
305                 310                 315                 320 


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
                325                 330                 335     


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            340                 345                 350         


Ser Pro Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        355                 360                 365             


Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp 
    370                 375                 380                 


Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro 
385                 390                 395                 400 


Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu 
                405                 410                 415     


Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala 
            420                 425                 430         


Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu 
        435                 440                 445             


Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu 
    450                 455                 460                 


Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala 
465                 470                 475                 480 


Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser 
                485                 490                 495     


Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro 
            500                 505                 510         


Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg 
        515                 520                 525             


Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser 
    530                 535                 540                 


Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp 
545                 550                 555                 560 


Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile 
                565                 570                 575     


Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro 
            580                 585                 590         


Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr 
        595                 600                 605             


Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val 
    610                 615                 620                 


Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys 
625                 630                 635                 640 


Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg 
                645                 650                 655     


Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val 
            660                 665                 670         


Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
        675                 680                 685             


Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro 
    690                 695                 700                 


Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu 
705                 710                 715                 720 


Gln Lys Ala Arg Gln Thr Leu Ala Phe Tyr Pro Cys Thr Ser Glu Glu 
                725                 730                 735     


Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala 
            740                 745                 750         


Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg 
        755                 760                 765             


Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr 
    770                 775                 780                 


Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys 
785                 790                 795                 800 


Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp 
                805                 810                 815     


Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp 
            820                 825                 830         


Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys 
        835                 840                 845             


Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys 
    850                 855                 860                 


Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val 
865                 870                 875                 880 


Met Ser Tyr Leu Asn Ala Ser 
                885         


<210>  122
<211>  887
<212>  PRT
<213>  artificial

<220>
<223>  LAG3-IGG1-YTE-LALA-IL12-F39A (ASKG129_CX14_70_4)

<400>  122

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Val Ser Ser Tyr 
            20                  25                  30          


Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg Glu Gly Val 
        35                  40                  45              


Ser Ala Ile Asp Ser Asp Gly Ser Val Ser Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Ala 
                85                  90                  95      


Ala Asp Leu Cys Trp Val Asp Gln Asp Gln Gly Glu Tyr Asn Thr Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Ser Glu Pro Lys Ser 
        115                 120                 125             


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 
    130                 135                 140                 


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
145                 150                 155                 160 


Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                165                 170                 175     


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
            180                 185                 190         


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
        195                 200                 205             


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    210                 215                 220                 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
225                 230                 235                 240 


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                245                 250                 255     


Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
            260                 265                 270         


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        275                 280                 285             


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    290                 295                 300                 


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
305                 310                 315                 320 


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
                325                 330                 335     


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            340                 345                 350         


Ser Pro Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        355                 360                 365             


Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp 
    370                 375                 380                 


Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro 
385                 390                 395                 400 


Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu 
                405                 410                 415     


Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala 
            420                 425                 430         


Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu 
        435                 440                 445             


Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu 
    450                 455                 460                 


Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala 
465                 470                 475                 480 


Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser 
                485                 490                 495     


Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro 
            500                 505                 510         


Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg 
        515                 520                 525             


Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser 
    530                 535                 540                 


Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp 
545                 550                 555                 560 


Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile 
                565                 570                 575     


Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro 
            580                 585                 590         


Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr 
        595                 600                 605             


Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val 
    610                 615                 620                 


Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys 
625                 630                 635                 640 


Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg 
                645                 650                 655     


Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val 
            660                 665                 670         


Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
        675                 680                 685             


Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro 
    690                 695                 700                 


Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu 
705                 710                 715                 720 


Gln Lys Ala Arg Gln Thr Leu Glu Ala Tyr Pro Cys Thr Ser Glu Glu 
                725                 730                 735     


Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala 
            740                 745                 750         


Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg 
        755                 760                 765             


Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr 
    770                 775                 780                 


Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys 
785                 790                 795                 800 


Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp 
                805                 810                 815     


Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp 
            820                 825                 830         


Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys 
        835                 840                 845             


Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys 
    850                 855                 860                 


Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val 
865                 870                 875                 880 


Met Ser Tyr Leu Asn Ala Ser 
                885         


<210>  123
<211>  887
<212>  PRT
<213>  artificial

<220>
<223>  LAG3-IGG1-YTE-LALA-IL12-P41G (ASKG129_CX14_70_5)

<400>  123

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Val Ser Ser Tyr 
            20                  25                  30          


Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg Glu Gly Val 
        35                  40                  45              


Ser Ala Ile Asp Ser Asp Gly Ser Val Ser Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Ala 
                85                  90                  95      


Ala Asp Leu Cys Trp Val Asp Gln Asp Gln Gly Glu Tyr Asn Thr Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Ser Glu Pro Lys Ser 
        115                 120                 125             


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 
    130                 135                 140                 


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
145                 150                 155                 160 


Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                165                 170                 175     


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
            180                 185                 190         


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
        195                 200                 205             


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    210                 215                 220                 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
225                 230                 235                 240 


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                245                 250                 255     


Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
            260                 265                 270         


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        275                 280                 285             


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    290                 295                 300                 


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
305                 310                 315                 320 


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
                325                 330                 335     


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            340                 345                 350         


Ser Pro Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        355                 360                 365             


Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp 
    370                 375                 380                 


Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro 
385                 390                 395                 400 


Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu 
                405                 410                 415     


Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala 
            420                 425                 430         


Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu 
        435                 440                 445             


Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu 
    450                 455                 460                 


Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala 
465                 470                 475                 480 


Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser 
                485                 490                 495     


Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro 
            500                 505                 510         


Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg 
        515                 520                 525             


Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser 
    530                 535                 540                 


Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp 
545                 550                 555                 560 


Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile 
                565                 570                 575     


Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro 
            580                 585                 590         


Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr 
        595                 600                 605             


Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val 
    610                 615                 620                 


Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys 
625                 630                 635                 640 


Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg 
                645                 650                 655     


Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val 
            660                 665                 670         


Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
        675                 680                 685             


Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro 
    690                 695                 700                 


Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu 
705                 710                 715                 720 


Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Gly Cys Thr Ser Glu Glu 
                725                 730                 735     


Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala 
            740                 745                 750         


Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg 
        755                 760                 765             


Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr 
    770                 775                 780                 


Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys 
785                 790                 795                 800 


Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp 
                805                 810                 815     


Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp 
            820                 825                 830         


Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys 
        835                 840                 845             


Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys 
    850                 855                 860                 


Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val 
865                 870                 875                 880 


Met Ser Tyr Leu Asn Ala Ser 
                885         


<210>  124
<211>  887
<212>  PRT
<213>  artificial

<220>
<223>  LAG3-IGG1-YTE-LALA-IL12-wt (ASKG129_CX14_51_3)

<400>  124

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Val Ser Ser Tyr 
            20                  25                  30          


Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg Glu Gly Val 
        35                  40                  45              


Ser Ala Ile Asp Ser Asp Gly Ser Val Ser Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Ala 
                85                  90                  95      


Ala Asp Leu Cys Trp Val Asp Gln Asp Gln Gly Glu Tyr Asn Thr Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Ser Glu Pro Lys Ser 
        115                 120                 125             


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 
    130                 135                 140                 


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
145                 150                 155                 160 


Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                165                 170                 175     


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
            180                 185                 190         


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
        195                 200                 205             


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    210                 215                 220                 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
225                 230                 235                 240 


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                245                 250                 255     


Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
            260                 265                 270         


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        275                 280                 285             


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    290                 295                 300                 


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
305                 310                 315                 320 


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
                325                 330                 335     


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            340                 345                 350         


Ser Pro Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        355                 360                 365             


Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp 
    370                 375                 380                 


Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro 
385                 390                 395                 400 


Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu 
                405                 410                 415     


Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala 
            420                 425                 430         


Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu 
        435                 440                 445             


Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu 
    450                 455                 460                 


Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala 
465                 470                 475                 480 


Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser 
                485                 490                 495     


Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro 
            500                 505                 510         


Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg 
        515                 520                 525             


Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser 
    530                 535                 540                 


Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp 
545                 550                 555                 560 


Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile 
                565                 570                 575     


Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro 
            580                 585                 590         


Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr 
        595                 600                 605             


Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val 
    610                 615                 620                 


Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys 
625                 630                 635                 640 


Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg 
                645                 650                 655     


Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val 
            660                 665                 670         


Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
        675                 680                 685             


Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro 
    690                 695                 700                 


Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu 
705                 710                 715                 720 


Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu Glu 
                725                 730                 735     


Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala 
            740                 745                 750         


Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg 
        755                 760                 765             


Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr 
    770                 775                 780                 


Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys 
785                 790                 795                 800 


Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp 
                805                 810                 815     


Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp 
            820                 825                 830         


Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys 
        835                 840                 845             


Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys 
    850                 855                 860                 


Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val 
865                 870                 875                 880 


Met Ser Tyr Leu Asn Ala Ser 
                885         


<210>  125
<211>  981
<212>  PRT
<213>  artificial

<220>
<223>  PD-1-Antibody - IL-12 WT (ASKG129_CX14_77_1)

<400>  125

Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
            20                  25                  30          


Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe 
    50                  55                  60                  


Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 
        115                 120                 125             


Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 
    130                 135                 140                 


Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 
145                 150                 155                 160 


Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 
                165                 170                 175     


Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 
            180                 185                 190         


Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
        195                 200                 205             


Pro Ser Asn Thr Lys Val Asp Lys Lys Ala Glu Pro Lys Ser Cys Asp 
    210                 215                 220                 


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala 
225                 230                 235                 240 


Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile 
                245                 250                 255     


Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
            260                 265                 270         


Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
        275                 280                 285             


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
    290                 295                 300                 


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
305                 310                 315                 320 


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                325                 330                 335     


Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
            340                 345                 350         


Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
        355                 360                 365             


Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
    370                 375                 380                 


Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
385                 390                 395                 400 


Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                405                 410                 415     


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
            420                 425                 430         


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
        435                 440                 445             


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile 
    450                 455                 460                 


Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr Pro 
465                 470                 475                 480 


Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu Glu 
                485                 490                 495     


Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly Ser 
            500                 505                 510         


Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly Gln 
        515                 520                 525             


Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu Leu 
    530                 535                 540                 


Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys Asp 
545                 550                 555                 560 


Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys Asn 
                565                 570                 575     


Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr Asp 
            580                 585                 590         


Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln Gly 
        595                 600                 605             


Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly Asp 
    610                 615                 620                 


Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala Cys 
625                 630                 635                 640 


Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala Val 
                645                 650                 655     


His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg Asp 
            660                 665                 670         


Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu Lys 
        675                 680                 685             


Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp Ser 
    690                 695                 700                 


Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln Gly 
705                 710                 715                 720 


Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr Ser 
                725                 730                 735     


Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala Gln 
            740                 745                 750         


Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro Cys 
        755                 760                 765             


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    770                 775                 780                 


Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro Cys Leu 
785                 790                 795                 800 


His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu Gln Lys 
                805                 810                 815     


Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu Glu Ile Asp 
            820                 825                 830         


His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala Cys Leu 
        835                 840                 845             


Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu Thr 
    850                 855                 860                 


Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser Phe 
865                 870                 875                 880 


Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met Tyr 
                885                 890                 895     


Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp Pro Lys 
            900                 905                 910         


Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp Glu Leu 
        915                 920                 925             


Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys Ser Ser 
    930                 935                 940                 


Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile Leu 
945                 950                 955                 960 


Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val Met Ser 
                965                 970                 975     


Tyr Leu Asn Ala Ser 
            980     


<210>  126
<211>  981
<212>  PRT
<213>  artificial

<220>
<223>  129K-PD1-IL-12-P35-Y40A (ASKG129_CX14_77_2)

<400>  126

Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
            20                  25                  30          


Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe 
    50                  55                  60                  


Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 
        115                 120                 125             


Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 
    130                 135                 140                 


Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 
145                 150                 155                 160 


Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 
                165                 170                 175     


Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 
            180                 185                 190         


Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
        195                 200                 205             


Pro Ser Asn Thr Lys Val Asp Lys Lys Ala Glu Pro Lys Ser Cys Asp 
    210                 215                 220                 


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala 
225                 230                 235                 240 


Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile 
                245                 250                 255     


Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
            260                 265                 270         


Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
        275                 280                 285             


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
    290                 295                 300                 


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
305                 310                 315                 320 


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                325                 330                 335     


Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
            340                 345                 350         


Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
        355                 360                 365             


Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
    370                 375                 380                 


Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
385                 390                 395                 400 


Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                405                 410                 415     


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
            420                 425                 430         


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
        435                 440                 445             


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile 
    450                 455                 460                 


Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr Pro 
465                 470                 475                 480 


Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu Glu 
                485                 490                 495     


Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly Ser 
            500                 505                 510         


Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly Gln 
        515                 520                 525             


Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu Leu 
    530                 535                 540                 


Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys Asp 
545                 550                 555                 560 


Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys Asn 
                565                 570                 575     


Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr Asp 
            580                 585                 590         


Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln Gly 
        595                 600                 605             


Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly Asp 
    610                 615                 620                 


Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala Cys 
625                 630                 635                 640 


Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala Val 
                645                 650                 655     


His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg Asp 
            660                 665                 670         


Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu Lys 
        675                 680                 685             


Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp Ser 
    690                 695                 700                 


Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln Gly 
705                 710                 715                 720 


Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr Ser 
                725                 730                 735     


Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala Gln 
            740                 745                 750         


Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro Cys 
        755                 760                 765             


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    770                 775                 780                 


Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro Cys Leu 
785                 790                 795                 800 


His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu Gln Lys 
                805                 810                 815     


Ala Arg Gln Thr Leu Glu Phe Ala Pro Cys Thr Ser Glu Glu Ile Asp 
            820                 825                 830         


His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala Cys Leu 
        835                 840                 845             


Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu Thr 
    850                 855                 860                 


Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser Phe 
865                 870                 875                 880 


Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met Tyr 
                885                 890                 895     


Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp Pro Lys 
            900                 905                 910         


Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp Glu Leu 
        915                 920                 925             


Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys Ser Ser 
    930                 935                 940                 


Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile Leu 
945                 950                 955                 960 


Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val Met Ser 
                965                 970                 975     


Tyr Leu Asn Ala Ser 
            980     


<210>  127
<211>  981
<212>  PRT
<213>  artificial

<220>
<223>  129K-PD1-IL-12P40AA (ASKG129_CX14_77_3)

<400>  127

Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
            20                  25                  30          


Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe 
    50                  55                  60                  


Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 
        115                 120                 125             


Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 
    130                 135                 140                 


Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 
145                 150                 155                 160 


Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 
                165                 170                 175     


Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 
            180                 185                 190         


Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
        195                 200                 205             


Pro Ser Asn Thr Lys Val Asp Lys Lys Ala Glu Pro Lys Ser Cys Asp 
    210                 215                 220                 


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala 
225                 230                 235                 240 


Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile 
                245                 250                 255     


Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
            260                 265                 270         


Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
        275                 280                 285             


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
    290                 295                 300                 


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
305                 310                 315                 320 


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                325                 330                 335     


Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
            340                 345                 350         


Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
        355                 360                 365             


Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
    370                 375                 380                 


Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
385                 390                 395                 400 


Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                405                 410                 415     


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
            420                 425                 430         


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
        435                 440                 445             


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile 
    450                 455                 460                 


Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr Pro 
465                 470                 475                 480 


Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu Glu 
                485                 490                 495     


Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly Ser 
            500                 505                 510         


Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly Gln 
        515                 520                 525             


Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu Leu 
    530                 535                 540                 


Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys Asp 
545                 550                 555                 560 


Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys Asn 
                565                 570                 575     


Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr Asp 
            580                 585                 590         


Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln Gly 
        595                 600                 605             


Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly Asp 
    610                 615                 620                 


Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala Cys 
625                 630                 635                 640 


Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala Val 
                645                 650                 655     


His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg Asp 
            660                 665                 670         


Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu Lys 
        675                 680                 685             


Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp Ser 
    690                 695                 700                 


Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln Gly 
705                 710                 715                 720 


Lys Ser Ala Ala Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr Ser 
                725                 730                 735     


Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala Gln 
            740                 745                 750         


Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro Cys 
        755                 760                 765             


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    770                 775                 780                 


Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro Cys Leu 
785                 790                 795                 800 


His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu Gln Lys 
                805                 810                 815     


Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu Glu Ile Asp 
            820                 825                 830         


His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala Cys Leu 
        835                 840                 845             


Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu Thr 
    850                 855                 860                 


Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser Phe 
865                 870                 875                 880 


Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met Tyr 
                885                 890                 895     


Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp Pro Lys 
            900                 905                 910         


Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp Glu Leu 
        915                 920                 925             


Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys Ser Ser 
    930                 935                 940                 


Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile Leu 
945                 950                 955                 960 


Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val Met Ser 
                965                 970                 975     


Tyr Leu Asn Ala Ser 
            980     


<210>  128
<211>  712
<212>  PRT
<213>  artificial

<220>
<223>  129K-PD1-Umask (ASKG129_CX14_77_4)

<400>  128

Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
            20                  25                  30          


Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe 
    50                  55                  60                  


Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 
        115                 120                 125             


Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 
    130                 135                 140                 


Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 
145                 150                 155                 160 


Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 
                165                 170                 175     


Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 
            180                 185                 190         


Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
        195                 200                 205             


Pro Ser Asn Thr Lys Val Asp Lys Lys Ala Glu Pro Lys Ser Cys Asp 
    210                 215                 220                 


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala 
225                 230                 235                 240 


Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile 
                245                 250                 255     


Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
            260                 265                 270         


Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
        275                 280                 285             


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
    290                 295                 300                 


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
305                 310                 315                 320 


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                325                 330                 335     


Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
            340                 345                 350         


Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
        355                 360                 365             


Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
    370                 375                 380                 


Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
385                 390                 395                 400 


Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                405                 410                 415     


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
            420                 425                 430         


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
        435                 440                 445             


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Ala Gly Gly Gly Gly 
    450                 455                 460                 


Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser 
465                 470                 475                 480 


Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser 
                485                 490                 495     


Gln Gly Ile Ser Ser Trp Leu Ala Trp Tyr Gln Gln Lys Pro Glu Lys 
            500                 505                 510         


Ala Pro Lys Ser Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val 
        515                 520                 525             


Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
    530                 535                 540                 


Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln 
545                 550                 555                 560 


Tyr Asn Ile Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
                565                 570                 575     


Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
            580                 585                 590         


Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly 
        595                 600                 605             


Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr 
    610                 615                 620                 


Tyr Trp Leu Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Asp Trp 
625                 630                 635                 640 


Ile Gly Ile Met Ser Pro Val Asp Ser Asp Ile Arg Tyr Ser Pro Ser 
                645                 650                 655     


Phe Gln Gly Gln Val Thr Met Ser Val Asp Lys Ser Ile Thr Thr Ala 
            660                 665                 670         


Tyr Leu Gln Trp Asn Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr 
        675                 680                 685             


Cys Ala Arg Arg Arg Pro Gly Gln Gly Tyr Phe Asp Phe Trp Gly Gln 
    690                 695                 700                 


Gly Thr Leu Val Thr Val Ser Ser 
705                 710         


<210>  129
<211>  218
<212>  PRT
<213>  artificial

<220>
<223>  LC (CX11_135_1)

<400>  129

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly 
1               5                   10                  15      


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Lys Gly Val Ser Thr Ser 
            20                  25                  30          


Gly Tyr Ser Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 
        35                  40                  45              


Arg Leu Leu Ile Tyr Leu Ala Ser Tyr Leu Glu Ser Gly Val Pro Ala 
    50                  55                  60                  


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
65                  70                  75                  80  


Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Ser Arg 
                85                  90                  95      


Asp Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 
            100                 105                 110         


Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
        115                 120                 125             


Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
    130                 135                 140                 


Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
145                 150                 155                 160 


Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                165                 170                 175     


Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
            180                 185                 190         


His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
        195                 200                 205             


Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
    210                 215             


<210>  130
<211>  981
<212>  PRT
<213>  artificial

<220>
<223>  Seq1-PD1-HC-LALA, G237A, IL-12wt Knob (ASKG129_CX14_98_1)

<400>  130

Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
            20                  25                  30          


Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe 
    50                  55                  60                  


Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 
        115                 120                 125             


Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 
    130                 135                 140                 


Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 
145                 150                 155                 160 


Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 
                165                 170                 175     


Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 
            180                 185                 190         


Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
        195                 200                 205             


Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp 
    210                 215                 220                 


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala 
225                 230                 235                 240 


Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                245                 250                 255     


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
            260                 265                 270         


Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
        275                 280                 285             


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
    290                 295                 300                 


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
305                 310                 315                 320 


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                325                 330                 335     


Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
            340                 345                 350         


Thr Leu Pro Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
        355                 360                 365             


Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
    370                 375                 380                 


Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
385                 390                 395                 400 


Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                405                 410                 415     


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
            420                 425                 430         


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
        435                 440                 445             


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile 
    450                 455                 460                 


Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr Pro 
465                 470                 475                 480 


Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu Glu 
                485                 490                 495     


Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly Ser 
            500                 505                 510         


Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly Gln 
        515                 520                 525             


Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu Leu 
    530                 535                 540                 


Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys Asp 
545                 550                 555                 560 


Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys Asn 
                565                 570                 575     


Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr Asp 
            580                 585                 590         


Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln Gly 
        595                 600                 605             


Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly Asp 
    610                 615                 620                 


Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala Cys 
625                 630                 635                 640 


Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala Val 
                645                 650                 655     


His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg Asp 
            660                 665                 670         


Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu Lys 
        675                 680                 685             


Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp Ser 
    690                 695                 700                 


Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln Gly 
705                 710                 715                 720 


Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr Ser 
                725                 730                 735     


Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala Gln 
            740                 745                 750         


Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro Cys 
        755                 760                 765             


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    770                 775                 780                 


Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro Cys Leu 
785                 790                 795                 800 


His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu Gln Lys 
                805                 810                 815     


Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu Glu Ile Asp 
            820                 825                 830         


His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala Cys Leu 
        835                 840                 845             


Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu Thr 
    850                 855                 860                 


Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser Phe 
865                 870                 875                 880 


Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met Tyr 
                885                 890                 895     


Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp Pro Lys 
            900                 905                 910         


Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp Glu Leu 
        915                 920                 925             


Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys Ser Ser 
    930                 935                 940                 


Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile Leu 
945                 950                 955                 960 


Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val Met Ser 
                965                 970                 975     


Tyr Leu Asn Ala Ser 
            980     


<210>  131
<211>  981
<212>  PRT
<213>  artificial

<220>
<223>  Seq2-PD1-HC-LALA, G237A, IL-12-P35Y40A-Knob (ASKG129_CX14_98_2)

<400>  131

Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
            20                  25                  30          


Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe 
    50                  55                  60                  


Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 
        115                 120                 125             


Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 
    130                 135                 140                 


Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 
145                 150                 155                 160 


Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 
                165                 170                 175     


Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 
            180                 185                 190         


Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
        195                 200                 205             


Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp 
    210                 215                 220                 


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala 
225                 230                 235                 240 


Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                245                 250                 255     


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
            260                 265                 270         


Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
        275                 280                 285             


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
    290                 295                 300                 


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
305                 310                 315                 320 


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                325                 330                 335     


Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
            340                 345                 350         


Thr Leu Pro Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
        355                 360                 365             


Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
    370                 375                 380                 


Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
385                 390                 395                 400 


Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                405                 410                 415     


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
            420                 425                 430         


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
        435                 440                 445             


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile 
    450                 455                 460                 


Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr Pro 
465                 470                 475                 480 


Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu Glu 
                485                 490                 495     


Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly Ser 
            500                 505                 510         


Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly Gln 
        515                 520                 525             


Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu Leu 
    530                 535                 540                 


Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys Asp 
545                 550                 555                 560 


Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys Asn 
                565                 570                 575     


Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr Asp 
            580                 585                 590         


Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln Gly 
        595                 600                 605             


Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly Asp 
    610                 615                 620                 


Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala Cys 
625                 630                 635                 640 


Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala Val 
                645                 650                 655     


His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg Asp 
            660                 665                 670         


Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu Lys 
        675                 680                 685             


Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp Ser 
    690                 695                 700                 


Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln Gly 
705                 710                 715                 720 


Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr Ser 
                725                 730                 735     


Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala Gln 
            740                 745                 750         


Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro Cys 
        755                 760                 765             


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    770                 775                 780                 


Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro Cys Leu 
785                 790                 795                 800 


His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu Gln Lys 
                805                 810                 815     


Ala Arg Gln Thr Leu Glu Phe Ala Pro Cys Thr Ser Glu Glu Ile Asp 
            820                 825                 830         


His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala Cys Leu 
        835                 840                 845             


Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu Thr 
    850                 855                 860                 


Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser Phe 
865                 870                 875                 880 


Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met Tyr 
                885                 890                 895     


Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp Pro Lys 
            900                 905                 910         


Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp Glu Leu 
        915                 920                 925             


Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys Ser Ser 
    930                 935                 940                 


Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile Leu 
945                 950                 955                 960 


Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val Met Ser 
                965                 970                 975     


Tyr Leu Asn Ala Ser 
            980     


<210>  132
<211>  981
<212>  PRT
<213>  artificial

<220>
<223>  Seq3-PD1-HC-LALA, G237A, IL-12-P40AA-knob (ASKG129_CX14_98_3)

<400>  132

Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
            20                  25                  30          


Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe 
    50                  55                  60                  


Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 
        115                 120                 125             


Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 
    130                 135                 140                 


Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 
145                 150                 155                 160 


Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 
                165                 170                 175     


Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 
            180                 185                 190         


Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
        195                 200                 205             


Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp 
    210                 215                 220                 


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala 
225                 230                 235                 240 


Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                245                 250                 255     


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
            260                 265                 270         


Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
        275                 280                 285             


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
    290                 295                 300                 


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
305                 310                 315                 320 


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                325                 330                 335     


Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
            340                 345                 350         


Thr Leu Pro Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
        355                 360                 365             


Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
    370                 375                 380                 


Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
385                 390                 395                 400 


Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                405                 410                 415     


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
            420                 425                 430         


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
        435                 440                 445             


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile 
    450                 455                 460                 


Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr Pro 
465                 470                 475                 480 


Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu Glu 
                485                 490                 495     


Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly Ser 
            500                 505                 510         


Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly Gln 
        515                 520                 525             


Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu Leu 
    530                 535                 540                 


Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys Asp 
545                 550                 555                 560 


Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys Asn 
                565                 570                 575     


Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr Asp 
            580                 585                 590         


Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln Gly 
        595                 600                 605             


Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly Asp 
    610                 615                 620                 


Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala Cys 
625                 630                 635                 640 


Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala Val 
                645                 650                 655     


His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg Asp 
            660                 665                 670         


Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu Lys 
        675                 680                 685             


Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp Ser 
    690                 695                 700                 


Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln Gly 
705                 710                 715                 720 


Lys Ser Ala Ala Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr Ser 
                725                 730                 735     


Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala Gln 
            740                 745                 750         


Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro Cys 
        755                 760                 765             


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
    770                 775                 780                 


Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro Cys Leu 
785                 790                 795                 800 


His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu Gln Lys 
                805                 810                 815     


Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser Glu Glu Ile Asp 
            820                 825                 830         


His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala Cys Leu 
        835                 840                 845             


Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu Thr 
    850                 855                 860                 


Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser Phe 
865                 870                 875                 880 


Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met Tyr 
                885                 890                 895     


Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp Pro Lys 
            900                 905                 910         


Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp Glu Leu 
        915                 920                 925             


Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys Ser Ser 
    930                 935                 940                 


Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile Leu 
945                 950                 955                 960 


Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val Met Ser 
                965                 970                 975     


Tyr Leu Asn Ala Ser 
            980     


<210>  133
<211>  976
<212>  PRT
<213>  artificial

<220>
<223>  Seq1-PD1-HC-LALA, G237A, IL-12wt Knob with Shorter Linker in 
       IL-12

<400>  133

Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
            20                  25                  30          


Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe 
    50                  55                  60                  


Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 
        115                 120                 125             


Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 
    130                 135                 140                 


Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 
145                 150                 155                 160 


Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 
                165                 170                 175     


Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 
            180                 185                 190         


Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
        195                 200                 205             


Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp 
    210                 215                 220                 


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala 
225                 230                 235                 240 


Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                245                 250                 255     


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
            260                 265                 270         


Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
        275                 280                 285             


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
    290                 295                 300                 


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
305                 310                 315                 320 


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                325                 330                 335     


Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
            340                 345                 350         


Thr Leu Pro Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
        355                 360                 365             


Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
    370                 375                 380                 


Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
385                 390                 395                 400 


Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                405                 410                 415     


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
            420                 425                 430         


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
        435                 440                 445             


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile 
    450                 455                 460                 


Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr Pro 
465                 470                 475                 480 


Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu Glu 
                485                 490                 495     


Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly Ser 
            500                 505                 510         


Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly Gln 
        515                 520                 525             


Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu Leu 
    530                 535                 540                 


Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys Asp 
545                 550                 555                 560 


Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys Asn 
                565                 570                 575     


Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr Asp 
            580                 585                 590         


Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln Gly 
        595                 600                 605             


Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly Asp 
    610                 615                 620                 


Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala Cys 
625                 630                 635                 640 


Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala Val 
                645                 650                 655     


His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg Asp 
            660                 665                 670         


Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu Lys 
        675                 680                 685             


Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp Ser 
    690                 695                 700                 


Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln Gly 
705                 710                 715                 720 


Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr Ser 
                725                 730                 735     


Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala Gln 
            740                 745                 750         


Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro Cys 
        755                 760                 765             


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Asn Leu Pro Val 
    770                 775                 780                 


Ala Thr Pro Asp Pro Gly Met Phe Pro Cys Leu His His Ser Gln Asn 
785                 790                 795                 800 


Leu Leu Arg Ala Val Ser Asn Met Leu Gln Lys Ala Arg Gln Thr Leu 
                805                 810                 815     


Glu Phe Tyr Pro Cys Thr Ser Glu Glu Ile Asp His Glu Asp Ile Thr 
            820                 825                 830         


Lys Asp Lys Thr Ser Thr Val Glu Ala Cys Leu Pro Leu Glu Leu Thr 
        835                 840                 845             


Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu Thr Ser Phe Ile Thr Asn 
    850                 855                 860                 


Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser Phe Met Met Ala Leu Cys 
865                 870                 875                 880 


Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met Tyr Gln Val Glu Phe Lys 
                885                 890                 895     


Thr Met Asn Ala Lys Leu Leu Met Asp Pro Lys Arg Gln Ile Phe Leu 
            900                 905                 910         


Asp Gln Asn Met Leu Ala Val Ile Asp Glu Leu Met Gln Ala Leu Asn 
        915                 920                 925             


Phe Asn Ser Glu Thr Val Pro Gln Lys Ser Ser Leu Glu Glu Pro Asp 
    930                 935                 940                 


Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile Leu Leu His Ala Phe Arg 
945                 950                 955                 960 


Ile Arg Ala Val Thr Ile Asp Arg Val Met Ser Tyr Leu Asn Ala Ser 
                965                 970                 975     


<210>  134
<211>  976
<212>  PRT
<213>  artificial

<220>
<223>  Seq2-PD1-HC-LALA, G237A, IL-12-P35Y40A-Knob with Shorter Linker 
       in IL-12

<400>  134

Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
            20                  25                  30          


Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe 
    50                  55                  60                  


Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 
        115                 120                 125             


Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 
    130                 135                 140                 


Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 
145                 150                 155                 160 


Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 
                165                 170                 175     


Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 
            180                 185                 190         


Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
        195                 200                 205             


Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp 
    210                 215                 220                 


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala 
225                 230                 235                 240 


Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                245                 250                 255     


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
            260                 265                 270         


Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
        275                 280                 285             


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
    290                 295                 300                 


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
305                 310                 315                 320 


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                325                 330                 335     


Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
            340                 345                 350         


Thr Leu Pro Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
        355                 360                 365             


Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
    370                 375                 380                 


Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
385                 390                 395                 400 


Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                405                 410                 415     


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
            420                 425                 430         


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
        435                 440                 445             


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile 
    450                 455                 460                 


Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr Pro 
465                 470                 475                 480 


Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu Glu 
                485                 490                 495     


Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly Ser 
            500                 505                 510         


Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly Gln 
        515                 520                 525             


Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu Leu 
    530                 535                 540                 


Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys Asp 
545                 550                 555                 560 


Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys Asn 
                565                 570                 575     


Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr Asp 
            580                 585                 590         


Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln Gly 
        595                 600                 605             


Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly Asp 
    610                 615                 620                 


Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala Cys 
625                 630                 635                 640 


Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala Val 
                645                 650                 655     


His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg Asp 
            660                 665                 670         


Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu Lys 
        675                 680                 685             


Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp Ser 
    690                 695                 700                 


Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln Gly 
705                 710                 715                 720 


Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr Ser 
                725                 730                 735     


Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala Gln 
            740                 745                 750         


Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro Cys 
        755                 760                 765             


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Asn Leu Pro Val 
    770                 775                 780                 


Ala Thr Pro Asp Pro Gly Met Phe Pro Cys Leu His His Ser Gln Asn 
785                 790                 795                 800 


Leu Leu Arg Ala Val Ser Asn Met Leu Gln Lys Ala Arg Gln Thr Leu 
                805                 810                 815     


Glu Phe Ala Pro Cys Thr Ser Glu Glu Ile Asp His Glu Asp Ile Thr 
            820                 825                 830         


Lys Asp Lys Thr Ser Thr Val Glu Ala Cys Leu Pro Leu Glu Leu Thr 
        835                 840                 845             


Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu Thr Ser Phe Ile Thr Asn 
    850                 855                 860                 


Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser Phe Met Met Ala Leu Cys 
865                 870                 875                 880 


Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met Tyr Gln Val Glu Phe Lys 
                885                 890                 895     


Thr Met Asn Ala Lys Leu Leu Met Asp Pro Lys Arg Gln Ile Phe Leu 
            900                 905                 910         


Asp Gln Asn Met Leu Ala Val Ile Asp Glu Leu Met Gln Ala Leu Asn 
        915                 920                 925             


Phe Asn Ser Glu Thr Val Pro Gln Lys Ser Ser Leu Glu Glu Pro Asp 
    930                 935                 940                 


Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile Leu Leu His Ala Phe Arg 
945                 950                 955                 960 


Ile Arg Ala Val Thr Ile Asp Arg Val Met Ser Tyr Leu Asn Ala Ser 
                965                 970                 975     


<210>  135
<211>  976
<212>  PRT
<213>  artificial

<220>
<223>  Seq3-PD1-HC-LALA, G237A, IL-12-P40AA-knob with Shorter Linker in 
       IL-12

<400>  135

Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
            20                  25                  30          


Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe 
    50                  55                  60                  


Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 
        115                 120                 125             


Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 
    130                 135                 140                 


Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 
145                 150                 155                 160 


Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 
                165                 170                 175     


Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 
            180                 185                 190         


Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
        195                 200                 205             


Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp 
    210                 215                 220                 


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala 
225                 230                 235                 240 


Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                245                 250                 255     


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
            260                 265                 270         


Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
        275                 280                 285             


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
    290                 295                 300                 


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
305                 310                 315                 320 


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                325                 330                 335     


Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
            340                 345                 350         


Thr Leu Pro Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
        355                 360                 365             


Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
    370                 375                 380                 


Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
385                 390                 395                 400 


Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
                405                 410                 415     


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
            420                 425                 430         


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
        435                 440                 445             


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile 
    450                 455                 460                 


Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp Tyr Pro 
465                 470                 475                 480 


Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro Glu Glu 
                485                 490                 495     


Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu Gly Ser 
            500                 505                 510         


Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala Gly Gln 
        515                 520                 525             


Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu Leu Leu 
    530                 535                 540                 


Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu Lys Asp 
545                 550                 555                 560 


Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala Lys Asn 
                565                 570                 575     


Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser Thr Asp 
            580                 585                 590         


Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro Gln Gly 
        595                 600                 605             


Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg Gly Asp 
    610                 615                 620                 


Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser Ala Cys 
625                 630                 635                 640 


Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp Ala Val 
                645                 650                 655     


His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile Arg Asp 
            660                 665                 670         


Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro Leu Lys 
        675                 680                 685             


Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr Trp Ser 
    690                 695                 700                 


Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val Gln Gly 
705                 710                 715                 720 


Lys Ser Ala Ala Glu Lys Lys Asp Arg Val Phe Thr Asp Lys Thr Ser 
                725                 730                 735     


Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg Ala Gln 
            740                 745                 750         


Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro Cys 
        755                 760                 765             


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Arg Asn Leu Pro Val 
    770                 775                 780                 


Ala Thr Pro Asp Pro Gly Met Phe Pro Cys Leu His His Ser Gln Asn 
785                 790                 795                 800 


Leu Leu Arg Ala Val Ser Asn Met Leu Gln Lys Ala Arg Gln Thr Leu 
                805                 810                 815     


Glu Phe Tyr Pro Cys Thr Ser Glu Glu Ile Asp His Glu Asp Ile Thr 
            820                 825                 830         


Lys Asp Lys Thr Ser Thr Val Glu Ala Cys Leu Pro Leu Glu Leu Thr 
        835                 840                 845             


Lys Asn Glu Ser Cys Leu Asn Ser Arg Glu Thr Ser Phe Ile Thr Asn 
    850                 855                 860                 


Gly Ser Cys Leu Ala Ser Arg Lys Thr Ser Phe Met Met Ala Leu Cys 
865                 870                 875                 880 


Leu Ser Ser Ile Tyr Glu Asp Leu Lys Met Tyr Gln Val Glu Phe Lys 
                885                 890                 895     


Thr Met Asn Ala Lys Leu Leu Met Asp Pro Lys Arg Gln Ile Phe Leu 
            900                 905                 910         


Asp Gln Asn Met Leu Ala Val Ile Asp Glu Leu Met Gln Ala Leu Asn 
        915                 920                 925             


Phe Asn Ser Glu Thr Val Pro Gln Lys Ser Ser Leu Glu Glu Pro Asp 
    930                 935                 940                 


Phe Tyr Lys Thr Lys Ile Lys Leu Cys Ile Leu Leu His Ala Phe Arg 
945                 950                 955                 960 


Ile Arg Ala Val Thr Ile Asp Arg Val Met Ser Tyr Leu Asn Ala Ser 
                965                 970                 975     


<210>  136
<211>  712
<212>  PRT
<213>  artificial

<220>
<223>  Seq4-PD1-HC-LALA, G237A- mask-hole?ASKG129_CX14_98_4?

<400>  136

Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
            20                  25                  30          


Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe 
    50                  55                  60                  


Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 
        115                 120                 125             


Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 
    130                 135                 140                 


Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 
145                 150                 155                 160 


Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 
                165                 170                 175     


Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 
            180                 185                 190         


Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
        195                 200                 205             


Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp 
    210                 215                 220                 


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala 
225                 230                 235                 240 


Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
                245                 250                 255     


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
            260                 265                 270         


Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
        275                 280                 285             


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
    290                 295                 300                 


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
305                 310                 315                 320 


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                325                 330                 335     


Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys 
            340                 345                 350         


Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
        355                 360                 365             


Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
    370                 375                 380                 


Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val 
385                 390                 395                 400 


Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp 
                405                 410                 415     


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
            420                 425                 430         


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
        435                 440                 445             


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Ala Gly Gly Gly Gly 
    450                 455                 460                 


Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser 
465                 470                 475                 480 


Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser 
                485                 490                 495     


Gln Gly Ile Ser Ser Trp Leu Ala Trp Tyr Gln Gln Lys Pro Glu Lys 
            500                 505                 510         


Ala Pro Lys Ser Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val 
        515                 520                 525             


Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
    530                 535                 540                 


Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln 
545                 550                 555                 560 


Tyr Asn Ile Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile 
                565                 570                 575     


Lys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
            580                 585                 590         


Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly 
        595                 600                 605             


Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Thr 
    610                 615                 620                 


Tyr Trp Leu Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Asp Trp 
625                 630                 635                 640 


Ile Gly Ile Met Ser Pro Val Asp Ser Asp Ile Arg Tyr Ser Pro Ser 
                645                 650                 655     


Phe Gln Gly Gln Val Thr Met Ser Val Asp Lys Ser Ile Thr Thr Ala 
            660                 665                 670         


Tyr Leu Gln Trp Asn Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr 
        675                 680                 685             


Cys Ala Arg Arg Arg Pro Gly Gln Gly Tyr Phe Asp Phe Trp Gly Gln 
    690                 695                 700                 


Gly Thr Leu Val Thr Val Ser Ser 
705                 710         


<210>  137
<211>  887
<212>  PRT
<213>  artificial

<220>
<223>   LAG3-IGG1-YTE-LALA-IL12-Y40A (ASKG129_CX14_51_4)

<400>  137

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Thr Val Ser Ser Tyr 
            20                  25                  30          


Cys Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg Glu Gly Val 
        35                  40                  45              


Ser Ala Ile Asp Ser Asp Gly Ser Val Ser Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  


Gly Arg Phe Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe Cys Ala 
                85                  90                  95      


Ala Asp Leu Cys Trp Val Asp Gln Asp Gln Gly Glu Tyr Asn Thr Trp 
            100                 105                 110         


Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Ser Glu Pro Lys Ser 
        115                 120                 125             


Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala 
    130                 135                 140                 


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
145                 150                 155                 160 


Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                165                 170                 175     


His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
            180                 185                 190         


Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
        195                 200                 205             


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    210                 215                 220                 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
225                 230                 235                 240 


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                245                 250                 255     


Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
            260                 265                 270         


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        275                 280                 285             


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    290                 295                 300                 


Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
305                 310                 315                 320 


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
                325                 330                 335     


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            340                 345                 350         


Ser Pro Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        355                 360                 365             


Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu Asp Trp 
    370                 375                 380                 


Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp Thr Pro 
385                 390                 395                 400 


Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu Val Leu 
                405                 410                 415     


Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly Asp Ala 
            420                 425                 430         


Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His Ser Leu 
        435                 440                 445             


Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp Ile Leu 
    450                 455                 460                 


Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys Glu Ala 
465                 470                 475                 480 


Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr Ile Ser 
                485                 490                 495     


Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser Asp Pro 
            500                 505                 510         


Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg Val Arg 
        515                 520                 525             


Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu Asp Ser 
    530                 535                 540                 


Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met Val Asp 
545                 550                 555                 560 


Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe Phe Ile 
                565                 570                 575     


Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu Lys Pro 
            580                 585                 590         


Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro Asp Thr 
        595                 600                 605             


Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val Gln Val 
    610                 615                 620                 


Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr Asp Lys 
625                 630                 635                 640 


Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser Val Arg 
                645                 650                 655     


Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val 
            660                 665                 670         


Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly 
        675                 680                 685             


Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met Phe Pro 
    690                 695                 700                 


Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn Met Leu 
705                 710                 715                 720 


Gln Lys Ala Arg Gln Thr Leu Glu Phe Ala Pro Cys Thr Ser Glu Glu 
                725                 730                 735     


Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val Glu Ala 
            740                 745                 750         


Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn Ser Arg 
        755                 760                 765             


Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg Lys Thr 
    770                 775                 780                 


Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp Leu Lys 
785                 790                 795                 800 


Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu Met Asp 
                805                 810                 815     


Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val Ile Asp 
            820                 825                 830         


Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro Gln Lys 
        835                 840                 845             


Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys Leu Cys 
    850                 855                 860                 


Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp Arg Val 
865                 870                 875                 880 


Met Ser Tyr Leu Asn Ala Ser 
                885         


