                         SEQUENCE LISTING

<110>  Universitaet Zuerich
 
<120>  IL-12 PD-L1 Ligand Fusion Protein

<130>  uz411wo

<160>  38    

<170>  PatentIn version 3.5

<210>  1
<211>  197
<212>  PRT
<213>  Homo sapiens

<400>  1

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>  2
<211>  306
<212>  PRT
<213>  Homo sapiens

<400>  2

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>  3
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain variable region

<400>  3

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 Phe Thr Phe Ser Asp Ser 
            20                  25                  30          


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


Ala Trp Ile Ser Pro Tyr Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


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


Leu Val Thr Val Ser Ala 
        115             


<210>  4
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  heavy chain variable region

<400>  4

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 Phe Thr Phe Ser Asp Ser 
            20                  25                  30          


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


Ala Trp Ile Ser Pro Tyr Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


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


Leu Val Thr Val Ser Ala 
        115             


<210>  5
<211>  109
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain variable region

<400>  5

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 Asp Val Ser Thr Ala 
            20                  25                  30          


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


Tyr Ser Ala Ser Phe Leu Tyr 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 Leu Tyr His Pro Ala 
                85                  90                  95      


Thr Phe Cys Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 
            100                 105                 


<210>  6
<211>  108
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  light chain variable region

<400>  6

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 Asp Val Ser Thr Ala 
            20                  25                  30          


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


Tyr Ser Ala Ser Phe Leu Tyr 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 Leu Tyr His Pro Ala 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 
            100                 105             


<210>  7
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker peptide

<400>  7

Gly Ser Ala Asp Gly Gly 
1               5       


<210>  8
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker peptide

<400>  8

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10                  15  


<210>  9
<211>  479
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  single chain scFv 1

<400>  9

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 Phe Thr Phe Ser Asp Ser 
            20                  25                  30          


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


Ala Trp Ile Ser Pro Tyr Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


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


Leu Val Thr Val Ser Ala Gly Gly Ser Gly Gly Asp Ile Gln Met Thr 
        115                 120                 125             


Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile 
    130                 135                 140                 


Thr Cys Arg Ala Ser Gln Asp Val Ser Thr Ala Val Ala Trp Tyr Gln 
145                 150                 155                 160 


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


Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr 
            180                 185                 190         


Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr 
        195                 200                 205             


Tyr Tyr Cys Gln Gln Tyr Leu Tyr His Pro Ala Thr Phe Cys Gly Gln 
    210                 215                 220                 


Gly Thr Lys Val Glu Ile Lys Arg Ser Ser Ser Ser Gly Ser Ser Ser 
225                 230                 235                 240 


Ser Gly Ser Ser Ser Ser Gly Glu Val Gln Leu Val Glu Ser Gly Gly 
                245                 250                 255     


Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser 
            260                 265                 270         


Gly Phe Thr Phe Ser Asp Ser Trp Ile His Trp Val Arg Gln Ala Pro 
        275                 280                 285             


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


Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Ala Asp 
305                 310                 315                 320 


Thr Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu 
                325                 330                 335     


Asp Thr Ala Val Tyr Tyr Cys Ala Arg Arg Trp His Pro Gly Gly Phe 
            340                 345                 350         


Asp Tyr Trp Gln Gln Gly Thr Leu Val Thr Val Ser Ala Gly Gly Ser 
        355                 360                 365             


Gly Gly Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser 
    370                 375                 380                 


Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Ser 
385                 390                 395                 400 


Thr Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu 
                405                 410                 415     


Leu Ile Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe 
            420                 425                 430         


Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu 
        435                 440                 445             


Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Leu Tyr His 
    450                 455                 460                 


Pro Ala Thr Phe Cys Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 
465                 470                 475                 


<210>  10
<211>  477
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  single chain scFv 2

<400>  10

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 Phe Thr Phe Ser Asp Ser 
            20                  25                  30          


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


Ala Trp Ile Ser Pro Tyr Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


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


Leu Val Thr Val Ser Ala Gly Gly Ser Gly Gly Asp Ile Gln Met Thr 
        115                 120                 125             


Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile 
    130                 135                 140                 


Thr Cys Arg Ala Ser Gln Asp Val Ser Thr Ala Val Ala Trp Tyr Gln 
145                 150                 155                 160 


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


Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr 
            180                 185                 190         


Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr 
        195                 200                 205             


Tyr Tyr Cys Gln Gln Tyr Leu Tyr His Pro Ala Thr Phe Gly Gln Gly 
    210                 215                 220                 


Thr Lys Val Glu Ile Lys Arg Ser Ser Ser Ser Gly Ser Ser Ser Ser 
225                 230                 235                 240 


Gly Ser Ser Ser Ser Gly Glu Val Gln Leu Val Glu Ser Gly Gly Gly 
                245                 250                 255     


Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly 
            260                 265                 270         


Phe Thr Phe Ser Asp Ser Trp Ile His Trp Val Arg Gln Ala Pro Gly 
        275                 280                 285             


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


Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr 
305                 310                 315                 320 


Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp 
                325                 330                 335     


Thr Ala Val Tyr Tyr Cys Ala Arg Arg His Trp Pro Gly Gly Phe Asp 
            340                 345                 350         


Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala Gly Gly Ser Gly 
        355                 360                 365             


Gly 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 Asp Val Ser Thr 
385                 390                 395                 400 


Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu 
                405                 410                 415     


Ile Tyr Ser Ala Ser Phe Leu Tyr 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 Leu Tyr His Pro 
    450                 455                 460                 


Ala Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg 
465                 470                 475         


<210>  11
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker peptide

<400>  11

Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly 
1               5                   10                  15  


<210>  12
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  GGSGG

<400>  12

Gly Gly Ser Gly Gly 
1               5   


<210>  13
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  secretory leader signal

<400>  13

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Gly 
1               5                   10                  15      


Val His Ser 
            


<210>  14
<211>  1022
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hIL-12-PD-L1 ligand conjugate v1

<400>  14

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Gly 
1               5                   10                  15      


Val His Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu 
            20                  25                  30          


Asp Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp 
        35                  40                  45              


Thr Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu 
    50                  55                  60                  


Val Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly 
65                  70                  75                  80  


Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His 
                85                  90                  95      


Ser Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp 
            100                 105                 110         


Ile Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys 
        115                 120                 125             


Glu Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr 
    130                 135                 140                 


Ile Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser 
145                 150                 155                 160 


Asp Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg 
                165                 170                 175     


Val Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu 
            180                 185                 190         


Asp Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met 
        195                 200                 205             


Val Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe 
    210                 215                 220                 


Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu 
225                 230                 235                 240 


Lys Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro 
                245                 250                 255     


Asp Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val 
            260                 265                 270         


Gln Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr 
        275                 280                 285             


Asp Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser 
    290                 295                 300                 


Val Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala 
305                 310                 315                 320 


Ser Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
                325                 330                 335     


Gly Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met 
            340                 345                 350         


Phe Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn 
        355                 360                 365             


Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser 
    370                 375                 380                 


Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val 
385                 390                 395                 400 


Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn 
                405                 410                 415     


Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg 
            420                 425                 430         


Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp 
        435                 440                 445             


Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu 
    450                 455                 460                 


Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val 
465                 470                 475                 480 


Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro 
                485                 490                 495     


Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys 
            500                 505                 510         


Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp 
        515                 520                 525             


Arg Val Met Ser Tyr Leu Asn Ala Ser Gly Ser Ala Asp Gly Gly Glu 
    530                 535                 540                 


Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser 
545                 550                 555                 560 


Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Ser Trp 
                565                 570                 575     


Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala 
            580                 585                 590         


Trp Ile Ser Pro Tyr Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys 
        595                 600                 605             


Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala Tyr Leu 
    610                 615                 620                 


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
625                 630                 635                 640 


Arg Arg Trp His Pro Gly Gly Phe Asp Tyr Trp Gln Gln Gly Thr Leu 
                645                 650                 655     


Val Thr Val Ser Ala Gly Gly Ser Gly Gly Asp Ile Gln Met Thr Gln 
            660                 665                 670         


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


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


Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ser Ala Ser Phe Leu 
705                 710                 715                 720 


Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
                725                 730                 735     


Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr 
            740                 745                 750         


Tyr Cys Gln Gln Tyr Leu Tyr His Pro Ala Thr Phe Cys Gly Gln Gly 
        755                 760                 765             


Thr Lys Val Glu Ile Lys Arg Ser Ser Ser Ser Gly Ser Ser Ser Ser 
    770                 775                 780                 


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


Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly 
                805                 810                 815     


Phe Thr Phe Ser Asp Ser Trp Ile His Trp Val Arg Gln Ala Pro Gly 
            820                 825                 830         


Lys Gly Leu Glu Trp Val Ala Trp Ile Ser Pro Tyr Gly Gly Ser Thr 
        835                 840                 845             


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


Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp 
865                 870                 875                 880 


Thr Ala Val Tyr Tyr Cys Ala Arg Arg Trp His Pro Gly Gly Phe Asp 
                885                 890                 895     


Tyr Trp Gln Gln Gly Thr Leu Val Thr Val Ser Ala Gly Gly Ser Gly 
            900                 905                 910         


Gly Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val 
        915                 920                 925             


Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Ser Thr 
    930                 935                 940                 


Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu 
945                 950                 955                 960 


Ile Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser 
                965                 970                 975     


Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln 
            980                 985                 990         


Pro Glu Asp Phe Ala Thr Tyr Tyr  Cys Gln Gln Tyr Leu  Tyr His Pro 
        995                 1000                 1005             


Ala Thr  Phe Cys Gly Gln Gly  Thr Lys Val Glu Ile  Lys Arg 
    1010                 1015                 1020         


<210>  15
<211>  1020
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hIL-12-PD-L1 ligand conjugate

<400>  15

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Gly 
1               5                   10                  15      


Val His Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu 
            20                  25                  30          


Asp Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp 
        35                  40                  45              


Thr Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu 
    50                  55                  60                  


Val Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly 
65                  70                  75                  80  


Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His 
                85                  90                  95      


Ser Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp 
            100                 105                 110         


Ile Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys 
        115                 120                 125             


Glu Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr 
    130                 135                 140                 


Ile Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser 
145                 150                 155                 160 


Asp Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg 
                165                 170                 175     


Val Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu 
            180                 185                 190         


Asp Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met 
        195                 200                 205             


Val Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe 
    210                 215                 220                 


Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu 
225                 230                 235                 240 


Lys Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro 
                245                 250                 255     


Asp Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val 
            260                 265                 270         


Gln Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr 
        275                 280                 285             


Asp Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser 
    290                 295                 300                 


Val Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala 
305                 310                 315                 320 


Ser Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
                325                 330                 335     


Gly Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met 
            340                 345                 350         


Phe Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn 
        355                 360                 365             


Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser 
    370                 375                 380                 


Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val 
385                 390                 395                 400 


Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn 
                405                 410                 415     


Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg 
            420                 425                 430         


Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp 
        435                 440                 445             


Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu 
    450                 455                 460                 


Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val 
465                 470                 475                 480 


Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro 
                485                 490                 495     


Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys 
            500                 505                 510         


Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp 
        515                 520                 525             


Arg Val Met Ser Tyr Leu Asn Ala Ser Gly Ser Ala Asp Gly Gly Glu 
    530                 535                 540                 


Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser 
545                 550                 555                 560 


Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Ser Trp 
                565                 570                 575     


Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala 
            580                 585                 590         


Trp Ile Ser Pro Tyr Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys 
        595                 600                 605             


Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala Tyr Leu 
    610                 615                 620                 


Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
625                 630                 635                 640 


Arg Arg His Trp Pro Gly Gly Phe Asp Tyr Trp Gly Gln Gly Thr Leu 
                645                 650                 655     


Val Thr Val Ser Ala Gly Gly Ser Gly Gly Asp Ile Gln Met Thr Gln 
            660                 665                 670         


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


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


Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ser Ala Ser Phe Leu 
705                 710                 715                 720 


Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp 
                725                 730                 735     


Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr 
            740                 745                 750         


Tyr Cys Gln Gln Tyr Leu Tyr His Pro Ala Thr Phe Gly Gln Gly Thr 
        755                 760                 765             


Lys Val Glu Ile Lys Arg Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly 
    770                 775                 780                 


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


Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe 
                805                 810                 815     


Thr Phe Ser Asp Ser Trp Ile His Trp Val Arg Gln Ala Pro Gly Lys 
            820                 825                 830         


Gly Leu Glu Trp Val Ala Trp Ile Ser Pro Tyr Gly Gly Ser Thr Tyr 
        835                 840                 845             


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


Lys Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr 
865                 870                 875                 880 


Ala Val Tyr Tyr Cys Ala Arg Arg His Trp Pro Gly Gly Phe Asp Tyr 
                885                 890                 895     


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala Gly Gly Ser Gly Gly 
            900                 905                 910         


Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
        915                 920                 925             


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Ser Thr Ala 
    930                 935                 940                 


Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
945                 950                 955                 960 


Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly 
                965                 970                 975     


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
            980                 985                 990         


Glu Asp Phe Ala Thr Tyr Tyr Cys  Gln Gln Tyr Leu Tyr  His Pro Ala 
        995                 1000                 1005             


Thr Phe  Gly Gln Gly Thr Lys  Val Glu Ile Lys Arg  
    1010                 1015                 1020 


<210>  16
<211>  591
<212>  DNA
<213>  Homo sapiens

<400>  16
agaaacctcc ccgtggccac tccagaccca ggaatgttcc catgccttca ccactcccaa       60

aacctgctga gggccgtcag caacatgctc cagaaggcca gacaaactct agaattttac      120

ccttgcactt ctgaagagat tgatcatgaa gatatcacaa aagataaaac cagcacagtg      180

gaggcctgtt taccattgga attaaccaag aatgagagtt gcctaaattc cagagagacc      240

tctttcataa ctaatgggag ttgcctggcc tccagaaaga cctcttttat gatggccctg      300

tgccttagta gtatttatga agacttgaag atgtaccagg tggagttcaa gaccatgaat      360

gcaaagcttc tgatggatcc taagaggcag atctttctag atcaaaacat gctggcagtt      420

attgatgagc tgatgcaggc cctgaatttc aacagtgaga ctgtgccaca aaaatcctcc      480

cttgaagaac cggattttta taaaactaaa atcaagctct gcatacttct tcatgctttc      540

agaattcggg cagtgactat tgatagagtg atgagctatc tgaatgcttc c               591


<210>  17
<211>  918
<212>  DNA
<213>  Homo sapiens

<400>  17
atatgggaac tgaagaaaga tgtttatgtc gtagaattgg attggtatcc ggatgcccct       60

ggagaaatgg tggtcctcac ctgtgacacc cctgaagaag atggtatcac ctggaccttg      120

gaccagagca gtgaggtctt aggctctggc aaaaccctga ccatccaagt caaagagttt      180

ggagatgctg gccagtacac ctgtcacaaa ggaggcgagg ttctaagcca ttcgctcctg      240

ctgcttcaca aaaaggaaga tggaatttgg tccactgata ttttaaagga ccagaaagaa      300

cccaaaaata agacctttct aagatgcgag gccaagaatt attctggacg tttcacctgc      360

tggtggctga cgacaatcag tactgatttg acattcagtg tcaaaagcag cagaggctct      420

tctgaccccc aaggggtgac gtgcggagct gctacactct ctgcagagag agtcagaggg      480

gacaacaagg agtatgagta ctcagtggag tgccaggagg acagtgcctg cccagctgct      540

gaggagagtc tgcccattga ggtcatggtg gatgccgttc acaagctcaa gtatgaaaac      600

tacaccagca gcttcttcat cagggacatc atcaaacctg acccacccaa gaacttgcag      660

ctgaagccat taaagaattc tcggcaggtg gaggtcagct gggagtaccc tgacacctgg      720

agtactccac attcctactt ctccctgaca ttctgcgttc aggtccaggg caagagcaag      780

agagaaaaga aagatagagt cttcacggac aagacctcag ccacggtcat ctgccgcaaa      840

aatgccagca ttagcgtgcg ggcccaggac cgctactata gctcatcttg gagcgaatgg      900

gcatctgtgc cctgcagt                                                    918


<210>  18
<211>  354
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  heavy chain variable region

<400>  18
gaggtgcagc tggtggagag cggcggcggc ctggtgcagc ctggcggcag cctgagactg       60

agctgcgccg ccagcggctt caccttcagc gacagctgga tccactgggt gagacaggcc      120

cctggcaagg gcctggagtg ggtggcctgg atcagccctt acggcggcag cacctactac      180

gccgacagcg tgaagggcag attcaccatc agcgccgaca ccagcaagaa caccgcctac      240

ctgcagatga acagcctgag agccgaggac accgccgtgt actactgcgc cagaagatgg      300

caccctggcg gcttcgacta ctggcagcag ggcaccctgg tgaccgtgag cgcc            354


<210>  19
<211>  354
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  VH commercial anti PD-L1 AB

<400>  19
gaggtgcagc tggtggagag cggcggcggc ctggtgcagc ctggcggcag cctgagactg       60

agctgcgccg ccagcggctt caccttcagc gacagctgga tccactgggt gagacaggcc      120

cctggcaagg gcctggagtg ggtggcctgg atcagccctt acggcggcag cacctactac      180

gccgacagcg tgaagggcag attcaccatc agcgccgaca ccagcaagaa caccgcctac      240

ctgcagatga acagcctgag agccgaggac accgccgtgt actactgcgc cagaagacac      300

tggcctggcg gcttcgacta ctggggccag ggcaccctgg tgaccgtgag cgcc            354


<210>  20
<211>  327
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  light chain variable region

<400>  20
gacatccaga tgacccagag ccctagcagc ctgagcgcca gcgtgggcga cagagtgacc       60

atcacctgca gagccagcca ggacgtgagc accgccgtgg cctggtacca gcagaagcct      120

ggcaaggccc ctaagctgct gatctacagc gccagcttcc tgtacagcgg cgtgcctagc      180

agattcagcg gcagcggcag cggcaccgac ttcaccctga ccatcagcag cctgcagcct      240

gaggacttcg ccacctacta ctgccagcag tacctgtacc accctgccac cttctgcggc      300

cagggcacca aggtggagat caagaga                                          327


<210>  21
<211>  324
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  VL commercial anti PD-L1 AB

<400>  21
gacatccaga tgacccagag ccctagcagc ctgagcgcca gcgtgggcga cagagtgacc       60

atcacctgca gagccagcca ggacgtgagc accgccgtgg cctggtacca gcagaagcct      120

ggcaaggccc ctaagctgct gatctacagc gccagcttcc tgtacagcgg cgtgcctagc      180

agattcagcg gcagcggcag cggcaccgac ttcaccctga ccatcagcag cctgcagcct      240

gaggacttcg ccacctacta ctgccagcag tacctgtacc accctgccac cttcggccag      300

ggcaccaagg tggagatcaa gaga                                             324


<210>  22
<211>  18
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  linker

<400>  22
ggtagtgctg acggagga                                                     18


<210>  23
<211>  45
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  linker

<400>  23
gggggaggcg gaagcggggg aggcggaagc gggggaggcg gaagc                       45


<210>  24
<211>  1437
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PD-L1 ligand v1

<400>  24
gaggtgcagc tggtggagag cggcggcggc ctggtgcagc ctggcggcag cctgagactg       60

agctgcgccg ccagcggctt caccttcagc gacagctgga tccactgggt gagacaggcc      120

cctggcaagg gcctggagtg ggtggcctgg atcagccctt acggcggcag cacctactac      180

gccgacagcg tgaagggcag attcaccatc agcgccgaca ccagcaagaa caccgcctac      240

ctgcagatga acagcctgag agccgaggac accgccgtgt actactgcgc cagaagatgg      300

caccctggcg gcttcgacta ctggcagcag ggcaccctgg tgaccgtgag cgccggcggc      360

agcggcggcg acatccagat gacccagagc cctagcagcc tgagcgccag cgtgggcgac      420

agagtgacca tcacctgcag agccagccag gacgtgagca ccgccgtggc ctggtaccag      480

cagaagcctg gcaaggcccc taagctgctg atctacagcg ccagcttcct gtacagcggc      540

gtgcctagca gattcagcgg cagcggcagc ggcaccgact tcaccctgac catcagcagc      600

ctgcagcctg aggacttcgc cacctactac tgccagcagt acctgtacca ccctgccacc      660

ttctgcggcc agggcaccaa ggtggagatc aagagaagca gcagcagcgg cagcagcagc      720

agcggcagca gcagcagcgg cgaggtgcag ctggtggaga gcggcggcgg cctggtgcag      780

cctggcggca gcctgagact gagctgcgcc gccagcggct tcaccttcag cgacagctgg      840

atccactggg tgagacaggc ccctggcaag ggcctggagt gggtggcctg gatcagccct      900

tacggcggca gcacctacta cgccgacagc gtgaagggca gattcaccat cagcgccgac      960

accagcaaga acaccgccta cctgcagatg aacagcctga gagccgagga caccgccgtg     1020

tactactgcg ccagaagatg gcaccctggc ggcttcgact actggcagca gggcaccctg     1080

gtgaccgtga gcgccggcgg cagcggcggc gacatccaga tgacccagag ccctagcagc     1140

ctgagcgcca gcgtgggcga cagagtgacc atcacctgca gagccagcca ggacgtgagc     1200

accgccgtgg cctggtacca gcagaagcct ggcaaggccc ctaagctgct gatctacagc     1260

gccagcttcc tgtacagcgg cgtgcctagc agattcagcg gcagcggcag cggcaccgac     1320

ttcaccctga ccatcagcag cctgcagcct gaggacttcg ccacctacta ctgccagcag     1380

tacctgtacc accctgccac cttctgcggc cagggcacca aggtggagat caagaga        1437


<210>  25
<211>  1431
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  PD-L1 ligand v2 (commercial anti PD-L1 AB)

<400>  25
gaggtgcagc tggtggagag cggcggcggc ctggtgcagc ctggcggcag cctgagactg       60

agctgcgccg ccagcggctt caccttcagc gacagctgga tccactgggt gagacaggcc      120

cctggcaagg gcctggagtg ggtggcctgg atcagccctt acggcggcag cacctactac      180

gccgacagcg tgaagggcag attcaccatc agcgccgaca ccagcaagaa caccgcctac      240

ctgcagatga acagcctgag agccgaggac accgccgtgt actactgcgc cagaagacac      300

tggcctggcg gcttcgacta ctggggccag ggcaccctgg tgaccgtgag cgccggcggc      360

agcggcggcg acatccagat gacccagagc cctagcagcc tgagcgccag cgtgggcgac      420

agagtgacca tcacctgcag agccagccag gacgtgagca ccgccgtggc ctggtaccag      480

cagaagcctg gcaaggcccc taagctgctg atctacagcg ccagcttcct gtacagcggc      540

gtgcctagca gattcagcgg cagcggcagc ggcaccgact tcaccctgac catcagcagc      600

ctgcagcctg aggacttcgc cacctactac tgccagcagt acctgtacca ccctgccacc      660

ttcggccagg gcaccaaggt ggagatcaag agaagcagca gcagcggcag cagcagcagc      720

ggcagcagca gcagcggcga ggtgcagctg gtggagagcg gcggcggcct ggtgcagcct      780

ggcggcagcc tgagactgag ctgcgccgcc agcggcttca ccttcagcga cagctggatc      840

cactgggtga gacaggcccc tggcaagggc ctggagtggg tggcctggat cagcccttac      900

ggcggcagca cctactacgc cgacagcgtg aagggcagat tcaccatcag cgccgacacc      960

agcaagaaca ccgcctacct gcagatgaac agcctgagag ccgaggacac cgccgtgtac     1020

tactgcgcca gaagacactg gcctggcggc ttcgactact ggggccaggg caccctggtg     1080

accgtgagcg ccggcggcag cggcggcgac atccagatga cccagagccc tagcagcctg     1140

agcgccagcg tgggcgacag agtgaccatc acctgcagag ccagccagga cgtgagcacc     1200

gccgtggcct ggtaccagca gaagcctggc aaggccccta agctgctgat ctacagcgcc     1260

agcttcctgt acagcggcgt gcctagcaga ttcagcggca gcggcagcgg caccgacttc     1320

accctgacca tcagcagcct gcagcctgag gacttcgcca cctactactg ccagcagtac     1380

ctgtaccacc ctgccacctt cggccagggc accaaggtgg agatcaagag a              1431


<210>  26
<211>  45
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  first intra PDL1 Linker element DNA

<400>  26
agcagcagca gcggcagcag cagcagcggc agcagcagca gcggc                       45


<210>  27
<211>  15
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  second intra PDL1 Linker element DNA

<400>  27
ggcggcagcg gcggc                                                        15


<210>  28
<211>  57
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  secretory leader signal

<400>  28
atgggctgga gcctgatcct cctgttcctc gtcgctgtgg ctacaggtgt gcactcg          57


<210>  29
<211>  3084
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  IL-12-PD-L1 ligand conjugate

<400>  29
atgggctgga gcctgatcct cctgttcctc gtcgctgtgg ctacaggtgt gcactcgata       60

tgggaactga agaaagatgt ttatgtcgta gaattggatt ggtatccgga tgcccctgga      120

gaaatggtgg tcctcacctg tgacacccct gaagaagatg gtatcacctg gaccttggac      180

cagagcagtg aggtcttagg ctctggcaaa accctgacca tccaagtcaa agagtttgga      240

gatgctggcc agtacacctg tcacaaagga ggcgaggttc taagccattc gctcctgctg      300

cttcacaaaa aggaagatgg aatttggtcc actgatattt taaaggacca gaaagaaccc      360

aaaaataaga cctttctaag atgcgaggcc aagaattatt ctggacgttt cacctgctgg      420

tggctgacga caatcagtac tgatttgaca ttcagtgtca aaagcagcag aggctcttct      480

gacccccaag gggtgacgtg cggagctgct acactctctg cagagagagt cagaggggac      540

aacaaggagt atgagtactc agtggagtgc caggaggaca gtgcctgccc agctgctgag      600

gagagtctgc ccattgaggt catggtggat gccgttcaca agctcaagta tgaaaactac      660

accagcagct tcttcatcag ggacatcatc aaacctgacc cacccaagaa cttgcagctg      720

aagccattaa agaattctcg gcaggtggag gtcagctggg agtaccctga cacctggagt      780

actccacatt cctacttctc cctgacattc tgcgttcagg tccagggcaa gagcaagaga      840

gaaaagaaag atagagtctt cacggacaag acctcagcca cggtcatctg ccgcaaaaat      900

gccagcatta gcgtgcgggc ccaggaccgc tactatagct catcttggag cgaatgggca      960

tctgtgccct gcagtggggg aggcggaagc gggggaggcg gaagcggggg aggcggaagc     1020

agaaacctcc ccgtggccac tccagaccca ggaatgttcc catgccttca ccactcccaa     1080

aacctgctga gggccgtcag caacatgctc cagaaggcca gacaaactct agaattttac     1140

ccttgcactt ctgaagagat tgatcatgaa gatatcacaa aagataaaac cagcacagtg     1200

gaggcctgtt taccattgga attaaccaag aatgagagtt gcctaaattc cagagagacc     1260

tctttcataa ctaatgggag ttgcctggcc tccagaaaga cctcttttat gatggccctg     1320

tgccttagta gtatttatga agacttgaag atgtaccagg tggagttcaa gaccatgaat     1380

gcaaagcttc tgatggatcc taagaggcag atctttctag atcaaaacat gctggcagtt     1440

attgatgagc tgatgcaggc cctgaatttc aacagtgaga ctgtgccaca aaaatcctcc     1500

cttgaagaac cggattttta taaaactaaa atcaagctct gcatacttct tcatgctttc     1560

agaattcggg cagtgactat tgatagagtg atgagctatc tgaatgcttc cggtagtgct     1620

gacggaggag aggtgcagct ggtggagagc ggcggcggcc tggtgcagcc tggcggcagc     1680

ctgagactga gctgcgccgc cagcggcttc accttcagcg acagctggat ccactgggtg     1740

agacaggccc ctggcaaggg cctggagtgg gtggcctgga tcagccctta cggcggcagc     1800

acctactacg ccgacagcgt gaagggcaga ttcaccatca gcgccgacac cagcaagaac     1860

accgcctacc tgcagatgaa cagcctgaga gccgaggaca ccgccgtgta ctactgcgcc     1920

agaagatggc accctggcgg cttcgactac tggcagcagg gcaccctggt gaccgtgagc     1980

gccggcggca gcggcggcga catccagatg acccagagcc ctagcagcct gagcgccagc     2040

gtgggcgaca gagtgaccat cacctgcaga gccagccagg acgtgagcac cgccgtggcc     2100

tggtaccagc agaagcctgg caaggcccct aagctgctga tctacagcgc cagcttcctg     2160

tacagcggcg tgcctagcag attcagcggc agcggcagcg gcaccgactt caccctgacc     2220

atcagcagcc tgcagcctga ggacttcgcc acctactact gccagcagta cctgtaccac     2280

cctgccacct tctgcggcca gggcaccaag gtggagatca agagaagcag cagcagcggc     2340

agcagcagca gcggcagcag cagcagcggc gaggtgcagc tggtggagag cggcggcggc     2400

ctggtgcagc ctggcggcag cctgagactg agctgcgccg ccagcggctt caccttcagc     2460

gacagctgga tccactgggt gagacaggcc cctggcaagg gcctggagtg ggtggcctgg     2520

atcagccctt acggcggcag cacctactac gccgacagcg tgaagggcag attcaccatc     2580

agcgccgaca ccagcaagaa caccgcctac ctgcagatga acagcctgag agccgaggac     2640

accgccgtgt actactgcgc cagaagatgg caccctggcg gcttcgacta ctggcagcag     2700

ggcaccctgg tgaccgtgag cgccggcggc agcggcggcg acatccagat gacccagagc     2760

cctagcagcc tgagcgccag cgtgggcgac agagtgacca tcacctgcag agccagccag     2820

gacgtgagca ccgccgtggc ctggtaccag cagaagcctg gcaaggcccc taagctgctg     2880

atctacagcg ccagcttcct gtacagcggc gtgcctagca gattcagcgg cagcggcagc     2940

ggcaccgact tcaccctgac catcagcagc ctgcagcctg aggacttcgc cacctactac     3000

tgccagcagt acctgtacca ccctgccacc ttctgcggcc agggcaccaa ggtggagatc     3060

aagagacacc atcatcacca ccat                                            3084


<210>  30
<211>  3078
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  IL-12-PD-L1 ligand conjugate v2, long linker

<400>  30
atgggctgga gcctgatcct cctgttcctc gtcgctgtgg ctacaggtgt gcactcgata       60

tgggaactga agaaagatgt ttatgtcgta gaattggatt ggtatccgga tgcccctgga      120

gaaatggtgg tcctcacctg tgacacccct gaagaagatg gtatcacctg gaccttggac      180

cagagcagtg aggtcttagg ctctggcaaa accctgacca tccaagtcaa agagtttgga      240

gatgctggcc agtacacctg tcacaaagga ggcgaggttc taagccattc gctcctgctg      300

cttcacaaaa aggaagatgg aatttggtcc actgatattt taaaggacca gaaagaaccc      360

aaaaataaga cctttctaag atgcgaggcc aagaattatt ctggacgttt cacctgctgg      420

tggctgacga caatcagtac tgatttgaca ttcagtgtca aaagcagcag aggctcttct      480

gacccccaag gggtgacgtg cggagctgct acactctctg cagagagagt cagaggggac      540

aacaaggagt atgagtactc agtggagtgc caggaggaca gtgcctgccc agctgctgag      600

gagagtctgc ccattgaggt catggtggat gccgttcaca agctcaagta tgaaaactac      660

accagcagct tcttcatcag ggacatcatc aaacctgacc cacccaagaa cttgcagctg      720

aagccattaa agaattctcg gcaggtggag gtcagctggg agtaccctga cacctggagt      780

actccacatt cctacttctc cctgacattc tgcgttcagg tccagggcaa gagcaagaga      840

gaaaagaaag atagagtctt cacggacaag acctcagcca cggtcatctg ccgcaaaaat      900

gccagcatta gcgtgcgggc ccaggaccgc tactatagct catcttggag cgaatgggca      960

tctgtgccct gcagtggggg aggcggaagc gggggaggcg gaagcggggg aggcggaagc     1020

agaaacctcc ccgtggccac tccagaccca ggaatgttcc catgccttca ccactcccaa     1080

aacctgctga gggccgtcag caacatgctc cagaaggcca gacaaactct agaattttac     1140

ccttgcactt ctgaagagat tgatcatgaa gatatcacaa aagataaaac cagcacagtg     1200

gaggcctgtt taccattgga attaaccaag aatgagagtt gcctaaattc cagagagacc     1260

tctttcataa ctaatgggag ttgcctggcc tccagaaaga cctcttttat gatggccctg     1320

tgccttagta gtatttatga agacttgaag atgtaccagg tggagttcaa gaccatgaat     1380

gcaaagcttc tgatggatcc taagaggcag atctttctag atcaaaacat gctggcagtt     1440

attgatgagc tgatgcaggc cctgaatttc aacagtgaga ctgtgccaca aaaatcctcc     1500

cttgaagaac cggattttta taaaactaaa atcaagctct gcatacttct tcatgctttc     1560

agaattcggg cagtgactat tgatagagtg atgagctatc tgaatgcttc cggtagtgct     1620

gacggaggag aggtgcagct ggtggagagc ggcggcggcc tggtgcagcc tggcggcagc     1680

ctgagactga gctgcgccgc cagcggcttc accttcagcg acagctggat ccactgggtg     1740

agacaggccc ctggcaaggg cctggagtgg gtggcctgga tcagccctta cggcggcagc     1800

acctactacg ccgacagcgt gaagggcaga ttcaccatca gcgccgacac cagcaagaac     1860

accgcctacc tgcagatgaa cagcctgaga gccgaggaca ccgccgtgta ctactgcgcc     1920

agaagacact ggcctggcgg cttcgactac tggggccagg gcaccctggt gaccgtgagc     1980

gccggcggca gcggcggcga catccagatg acccagagcc ctagcagcct gagcgccagc     2040

gtgggcgaca gagtgaccat cacctgcaga gccagccagg acgtgagcac cgccgtggcc     2100

tggtaccagc agaagcctgg caaggcccct aagctgctga tctacagcgc cagcttcctg     2160

tacagcggcg tgcctagcag attcagcggc agcggcagcg gcaccgactt caccctgacc     2220

atcagcagcc tgcagcctga ggacttcgcc acctactact gccagcagta cctgtaccac     2280

cctgccacct tcggccaggg caccaaggtg gagatcaaga gaagcagcag cagcggcagc     2340

agcagcagcg gcagcagcag cagcggcgag gtgcagctgg tggagagcgg cggcggcctg     2400

gtgcagcctg gcggcagcct gagactgagc tgcgccgcca gcggcttcac cttcagcgac     2460

agctggatcc actgggtgag acaggcccct ggcaagggcc tggagtgggt ggcctggatc     2520

agcccttacg gcggcagcac ctactacgcc gacagcgtga agggcagatt caccatcagc     2580

gccgacacca gcaagaacac cgcctacctg cagatgaaca gcctgagagc cgaggacacc     2640

gccgtgtact actgcgccag aagacactgg cctggcggct tcgactactg gggccagggc     2700

accctggtga ccgtgagcgc cggcggcagc ggcggcgaca tccagatgac ccagagccct     2760

agcagcctga gcgccagcgt gggcgacaga gtgaccatca cctgcagagc cagccaggac     2820

gtgagcaccg ccgtggcctg gtaccagcag aagcctggca aggcccctaa gctgctgatc     2880

tacagcgcca gcttcctgta cagcggcgtg cctagcagat tcagcggcag cggcagcggc     2940

accgacttca ccctgaccat cagcagcctg cagcctgagg acttcgccac ctactactgc     3000

cagcagtacc tgtaccaccc tgccaccttc ggccagggca ccaaggtgga gatcaagaga     3060

caccatcatc accaccat                                                   3078


<210>  31
<211>  3156
<212>  DNA
<213>  Mus musculus

<400>  31
atgggctgga gcctgatcct cctgttcctc gtcgctgtgg ctacaggtgt gcactcgtgt       60

cctcagaagc taaccatctc ctggtttgcc atcgttttgc tggtgtctcc actcatggcc      120

atgtgggagc tggagaaaga cgtttatgtt gtagaggtgg actggactcc cgatgcccct      180

ggagaaacag tgaacctcac ctgtgacacg cctgaagaag atgacatcac ctggacctca      240

gaccagagac atggagtcat aggctctgga aagaccctga ccatcactgt caaagagttt      300

ctagatgctg gccagtacac ctgccacaaa ggaggcgaga ctctgagcca ctcacatctg      360

ctgctccaca agaaggaaaa tggaatttgg tccactgaaa ttttaaaaaa tttcaaaaac      420

aagactttcc tgaagtgtga agcaccaaat tactccggac ggttcacgtg ctcatggctg      480

gtgcaaagaa acatggactt gaagttcaac atcaagagca gtagcagttc ccctgactct      540

cgggcagtga catgtggaat ggcgtctctg tctgcagaga aggtcacact ggaccaaagg      600

gactatgaga agtattcagt gtcctgccag gaggatgtca cctgcccaac tgccgaggag      660

accctgccca ttgaactggc gttggaagca cggcagcaga ataaatatga gaactacagc      720

accagcttct tcatcaggga catcatcaaa ccagacccgc ccaagaactt gcagatgaag      780

cctttgaaga actcacaggt ggaggtcagc tgggagtacc ctgactcctg gagcactccc      840

cattcctact tctccctcaa gttctttgtt cgaatccagc gcaagaaaga aaagatgaag      900

gagacagagg aggggtgtaa ccagaaaggt gcgttcctcg tagagaagac atctaccgaa      960

gtccaatgca aaggcgggaa tgtctgcgtg caagctcagg atcgctatta caattcctca     1020

tgcagcaagt gggcatgtgt tccctgcagg gtccgatccg ggggaggcgg aagcggggga     1080

ggcggaagcg ggggaggcgg aagcagggtc attccagtct ctggacctgc caggtgtctt     1140

agccagtccc gaaacctgct gaagaccaca gatgacatgg tgaagacggc cagagaaaaa     1200

ctgaaacatt attcctgcac tgctgaagac atcgatcatg aagacatcac acgggaccaa     1260

accagcacat tgaagacctg tttaccactg gaactacaca agaacgagag ttgcctggct     1320

actagagaga cttcttccac aacaagaggg agctgcctgc ccccacagaa gacgtctttg     1380

atgatgaccc tgtgccttgg tagcatctat gaggacttga agatgtacca gacagagttc     1440

caggccatca acgcagcact tcagaatcac aaccatcagc agatcattct agacaagggc     1500

atgctggtgg ccatcgatga gctgatgcag tctctgaatc ataatggcga gactctgcgc     1560

cagaaacctc ctgtgggaga agcagaccct tacagagtga aaatgaagct ctgcatcctg     1620

cttcacgcct tcagcacccg cgtcgtgacc atcaacaggg tgatgggcta tctgagctcc     1680

gccggtagtg ctgacggagg agaggtgcag ctggtggaga gcggcggcgg cctggtgcag     1740

cctggcggca gcctgagact gagctgcgcc gccagcggct tcaccttcag cgacagctgg     1800

atccactggg tgagacaggc ccctggcaag ggcctggagt gggtggcctg gatcagccct     1860

tacggcggca gcacctacta cgccgacagc gtgaagggca gattcaccat cagcgccgac     1920

accagcaaga acaccgccta cctgcagatg aacagcctga gagccgagga caccgccgtg     1980

tactactgcg ccagaagatg gcaccctggc ggcttcgact actggcagca gggcaccctg     2040

gtgaccgtga gcgccggcgg cagcggcggc gacatccaga tgacccagag ccctagcagc     2100

ctgagcgcca gcgtgggcga cagagtgacc atcacctgca gagccagcca ggacgtgagc     2160

accgccgtgg cctggtacca gcagaagcct ggcaaggccc ctaagctgct gatctacagc     2220

gccagcttcc tgtacagcgg cgtgcctagc agattcagcg gcagcggcag cggcaccgac     2280

ttcaccctga ccatcagcag cctgcagcct gaggacttcg ccacctacta ctgccagcag     2340

tacctgtacc accctgccac cttctgcggc cagggcacca aggtggagat caagagaagc     2400

agcagcagcg gcagcagcag cagcggcagc agcagcagcg gcgaggtgca gctggtggag     2460

agcggcggcg gcctggtgca gcctggcggc agcctgagac tgagctgcgc cgccagcggc     2520

ttcaccttca gcgacagctg gatccactgg gtgagacagg cccctggcaa gggcctggag     2580

tgggtggcct ggatcagccc ttacggcggc agcacctact acgccgacag cgtgaagggc     2640

agattcacca tcagcgccga caccagcaag aacaccgcct acctgcagat gaacagcctg     2700

agagccgagg acaccgccgt gtactactgc gccagaagat ggcaccctgg cggcttcgac     2760

tactggcagc agggcaccct ggtgaccgtg agcgccggcg gcagcggcgg cgacatccag     2820

atgacccaga gccctagcag cctgagcgcc agcgtgggcg acagagtgac catcacctgc     2880

agagccagcc aggacgtgag caccgccgtg gcctggtacc agcagaagcc tggcaaggcc     2940

cctaagctgc tgatctacag cgccagcttc ctgtacagcg gcgtgcctag cagattcagc     3000

ggcagcggca gcggcaccga cttcaccctg accatcagca gcctgcagcc tgaggacttc     3060

gccacctact actgccagca gtacctgtac caccctgcca ccttctgcgg ccagggcacc     3120

aaggtggaga tcaagagaca ccatcatcac caccat                               3156


<210>  32
<211>  1052
<212>  PRT
<213>  Mus musculus

<400>  32

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Gly 
1               5                   10                  15      


Val His Ser Cys Pro Gln Lys Leu Thr Ile Ser Trp Phe Ala Ile Val 
            20                  25                  30          


Leu Leu Val Ser Pro Leu Met Ala Met Trp Glu Leu Glu Lys Asp Val 
        35                  40                  45              


Tyr Val Val Glu Val Asp Trp Thr Pro Asp Ala Pro Gly Glu Thr Val 
    50                  55                  60                  


Asn Leu Thr Cys Asp Thr Pro Glu Glu Asp Asp Ile Thr Trp Thr Ser 
65                  70                  75                  80  


Asp Gln Arg His Gly Val Ile Gly Ser Gly Lys Thr Leu Thr Ile Thr 
                85                  90                  95      


Val Lys Glu Phe Leu Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly 
            100                 105                 110         


Glu Thr Leu Ser His Ser His Leu Leu Leu His Lys Lys Glu Asn Gly 
        115                 120                 125             


Ile Trp Ser Thr Glu Ile Leu Lys Asn Phe Lys Asn Lys Thr Phe Leu 
    130                 135                 140                 


Lys Cys Glu Ala Pro Asn Tyr Ser Gly Arg Phe Thr Cys Ser Trp Leu 
145                 150                 155                 160 


Val Gln Arg Asn Met Asp Leu Lys Phe Asn Ile Lys Ser Ser Ser Ser 
                165                 170                 175     


Ser Pro Asp Ser Arg Ala Val Thr Cys Gly Met Ala Ser Leu Ser Ala 
            180                 185                 190         


Glu Lys Val Thr Leu Asp Gln Arg Asp Tyr Glu Lys Tyr Ser Val Ser 
        195                 200                 205             


Cys Gln Glu Asp Val Thr Cys Pro Thr Ala Glu Glu Thr Leu Pro Ile 
    210                 215                 220                 


Glu Leu Ala Leu Glu Ala Arg Gln Gln Asn Lys Tyr Glu Asn Tyr Ser 
225                 230                 235                 240 


Thr Ser Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn 
                245                 250                 255     


Leu Gln Met Lys Pro Leu Lys Asn Ser Gln Val Glu Val Ser Trp Glu 
            260                 265                 270         


Tyr Pro Asp Ser Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Lys Phe 
        275                 280                 285             


Phe Val Arg Ile Gln Arg Lys Lys Glu Lys Met Lys Glu Thr Glu Glu 
    290                 295                 300                 


Gly Cys Asn Gln Lys Gly Ala Phe Leu Val Glu Lys Thr Ser Thr Glu 
305                 310                 315                 320 


Val Gln Cys Lys Gly Gly Asn Val Cys Val Gln Ala Gln Asp Arg Tyr 
                325                 330                 335     


Tyr Asn Ser Ser Cys Ser Lys Trp Ala Cys Val Pro Cys Arg Val Arg 
            340                 345                 350         


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
        355                 360                 365             


Arg Val Ile Pro Val Ser Gly Pro Ala Arg Cys Leu Ser Gln Ser Arg 
    370                 375                 380                 


Asn Leu Leu Lys Thr Thr Asp Asp Met Val Lys Thr Ala Arg Glu Lys 
385                 390                 395                 400 


Leu Lys His Tyr Ser Cys Thr Ala Glu Asp Ile Asp His Glu Asp Ile 
                405                 410                 415     


Thr Arg Asp Gln Thr Ser Thr Leu Lys Thr Cys Leu Pro Leu Glu Leu 
            420                 425                 430         


His Lys Asn Glu Ser Cys Leu Ala Thr Arg Glu Thr Ser Ser Thr Thr 
        435                 440                 445             


Arg Gly Ser Cys Leu Pro Pro Gln Lys Thr Ser Leu Met Met Thr Leu 
    450                 455                 460                 


Cys Leu Gly Ser Ile Tyr Glu Asp Leu Lys Met Tyr Gln Thr Glu Phe 
465                 470                 475                 480 


Gln Ala Ile Asn Ala Ala Leu Gln Asn His Asn His Gln Gln Ile Ile 
                485                 490                 495     


Leu Asp Lys Gly Met Leu Val Ala Ile Asp Glu Leu Met Gln Ser Leu 
            500                 505                 510         


Asn His Asn Gly Glu Thr Leu Arg Gln Lys Pro Pro Val Gly Glu Ala 
        515                 520                 525             


Asp Pro Tyr Arg Val Lys Met Lys Leu Cys Ile Leu Leu His Ala Phe 
    530                 535                 540                 


Ser Thr Arg Val Val Thr Ile Asn Arg Val Met Gly Tyr Leu Ser Ser 
545                 550                 555                 560 


Ala Gly Ser Ala Asp Gly Gly Glu Val Gln Leu Val Glu Ser Gly Gly 
                565                 570                 575     


Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser 
            580                 585                 590         


Gly Phe Thr Phe Ser Asp Ser Trp Ile His Trp Val Arg Gln Ala Pro 
        595                 600                 605             


Gly Lys Gly Leu Glu Trp Val Ala Trp Ile Ser Pro Tyr Gly Gly Ser 
    610                 615                 620                 


Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Ala Asp 
625                 630                 635                 640 


Thr Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu 
                645                 650                 655     


Asp Thr Ala Val Tyr Tyr Cys Ala Arg Arg Trp His Pro Gly Gly Phe 
            660                 665                 670         


Asp Tyr Trp Gln Gln Gly Thr Leu Val Thr Val Ser Ala Gly Gly Ser 
        675                 680                 685             


Gly Gly Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser 
    690                 695                 700                 


Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Ser 
705                 710                 715                 720 


Thr Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu 
                725                 730                 735     


Leu Ile Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe 
            740                 745                 750         


Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu 
        755                 760                 765             


Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Leu Tyr His 
    770                 775                 780                 


Pro Ala Thr Phe Cys Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Ser 
785                 790                 795                 800 


Ser Ser Ser Gly Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly Glu Val 
                805                 810                 815     


Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 
            820                 825                 830         


Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Ser Trp Ile 
        835                 840                 845             


His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Trp 
    850                 855                 860                 


Ile Ser Pro Tyr Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly 
865                 870                 875                 880 


Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala Tyr Leu Gln 
                885                 890                 895     


Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg 
            900                 905                 910         


Arg Trp His Pro Gly Gly Phe Asp Tyr Trp Gln Gln Gly Thr Leu Val 
        915                 920                 925             


Thr Val Ser Ala Gly Gly Ser Gly Gly Asp Ile Gln Met Thr Gln Ser 
    930                 935                 940                 


Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys 
945                 950                 955                 960 


Arg Ala Ser Gln Asp Val Ser Thr Ala Val Ala Trp Tyr Gln Gln Lys 
                965                 970                 975     


Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ser Ala Ser Phe Leu Tyr 
            980                 985                 990         


Ser Gly Val Pro Ser Arg Phe Ser  Gly Ser Gly Ser Gly  Thr Asp Phe 
        995                 1000                 1005             


Thr Leu  Thr Ile Ser Ser Leu  Gln Pro Glu Asp Phe  Ala Thr Tyr 
    1010                 1015                 1020             


Tyr Cys  Gln Gln Tyr Leu Tyr  His Pro Ala Thr Phe  Cys Gly Gln 
    1025                 1030                 1035             


Gly Thr  Lys Val Glu Ile Lys  Arg His His His His  His His 
    1040                 1045                 1050         


<210>  33
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  linker

<400>  33

Gly Ser Ala Asp Gly 
1               5   


<210>  34
<211>  3147
<212>  DNA
<213>  Mus musculus

<400>  34
atgggctgga gcctgatcct cctgttcctc gtcgctgtgg ctacaggtgt gcactcgtgt       60

cctcagaagc taaccatctc ctggtttgcc atcgttttgc tggtgtctcc actcatggcc      120

atgtgggagc tggagaaaga cgtttatgtt gtagaggtgg actggactcc cgatgcccct      180

ggagaaacag tgaacctcac ctgtgacacg cctgaagaag atgacatcac ctggacctca      240

gaccagagac atggagtcat aggctctgga aagaccctga ccatcactgt caaagagttt      300

ctagatgctg gccagtacac ctgccacaaa ggaggcgaga ctctgagcca ctcacatctg      360

ctgctccaca agaaggaaaa tggaatttgg tccactgaaa ttttaaaaaa tttcaaaaac      420

aagactttcc tgaagtgtga agcaccaaat tactccggac ggttcacgtg ctcatggctg      480

gtgcaaagaa acatggactt gaagttcaac atcaagagca gtagcagttc ccctgactct      540

cgggcagtga catgtggaat ggcgtctctg tctgcagaga aggtcacact ggaccaaagg      600

gactatgaga agtattcagt gtcctgccag gaggatgtca cctgcccaac tgccgaggag      660

accctgccca ttgaactggc gttggaagca cggcagcaga ataaatatga gaactacagc      720

accagcttct tcatcaggga catcatcaaa ccagacccgc ccaagaactt gcagatgaag      780

cctttgaaga actcacaggt ggaggtcagc tgggagtacc ctgactcctg gagcactccc      840

cattcctact tctccctcaa gttctttgtt cgaatccagc gcaagaaaga aaagatgaag      900

gagacagagg aggggtgtaa ccagaaaggt gcgttcctcg tagagaagac atctaccgaa      960

gtccaatgca aaggcgggaa tgtctgcgtg caagctcagg atcgctatta caattcctca     1020

tgcagcaagt gggcatgtgt tccctgcagg gtccgatccg ggggaggcgg aagcggggga     1080

ggcggaagcg ggggaggcgg aagcagggtc attccagtct ctggacctgc caggtgtctt     1140

agccagtccc gaaacctgct gaagaccaca gatgacatgg tgaagacggc cagagaaaaa     1200

ctgaaacatt attcctgcac tgctgaagac atcgatcatg aagacatcac acgggaccaa     1260

accagcacat tgaagacctg tttaccactg gaactacaca agaacgagag ttgcctggct     1320

actagagaga cttcttccac aacaagaggg agctgcctgc ccccacagaa gacgtctttg     1380

atgatgaccc tgtgccttgg tagcatctat gaggacttga agatgtacca gacagagttc     1440

caggccatca acgcagcact tcagaatcac aaccatcagc agatcattct agacaagggc     1500

atgctggtgg ccatcgatga gctgatgcag tctctgaatc ataatggcga gactctgcgc     1560

cagaaacctc ctgtgggaga agcagaccct tacagagtga aaatgaagct ctgcatcctg     1620

cttcacgcct tcagcacccg cgtcgtgacc atcaacaggg tgatgggcta tctgagctcc     1680

gccggtagtg ctgacggaga ggtgcagctg gtggagagcg gcggcggcct ggtgcagcct     1740

ggcggcagcc tgagactgag ctgcgccgcc agcggcttca ccttcagcga cagctggatc     1800

cactgggtga gacaggcccc tggcaagggc ctggagtggg tggcctggat cagcccttac     1860

ggcggcagca cctactacgc cgacagcgtg aagggcagat tcaccatcag cgccgacacc     1920

agcaagaaca ccgcctacct gcagatgaac agcctgagag ccgaggacac cgccgtgtac     1980

tactgcgcca gaagacactg gcctggcggc ttcgactact ggggccaggg caccctggtg     2040

accgtgagcg ccggcggcag cggcggcgac atccagatga cccagagccc tagcagcctg     2100

agcgccagcg tgggcgacag agtgaccatc acctgcagag ccagccagga cgtgagcacc     2160

gccgtggcct ggtaccagca gaagcctggc aaggccccta agctgctgat ctacagcgcc     2220

agcttcctgt acagcggcgt gcctagcaga ttcagcggca gcggcagcgg caccgacttc     2280

accctgacca tcagcagcct gcagcctgag gacttcgcca cctactactg ccagcagtac     2340

ctgtaccacc ctgccacctt cggccagggc accaaggtgg agatcaagag aagcagcagc     2400

agcggcagca gcagcagcgg cagcagcagc agcggcgagg tgcagctggt ggagagcggc     2460

ggcggcctgg tgcagcctgg cggcagcctg agactgagct gcgccgccag cggcttcacc     2520

ttcagcgaca gctggatcca ctgggtgaga caggcccctg gcaagggcct ggagtgggtg     2580

gcctggatca gcccttacgg cggcagcacc tactacgccg acagcgtgaa gggcagattc     2640

accatcagcg ccgacaccag caagaacacc gcctacctgc agatgaacag cctgagagcc     2700

gaggacaccg ccgtgtacta ctgcgccaga agacactggc ctggcggctt cgactactgg     2760

ggccagggca ccctggtgac cgtgagcgcc ggcggcagcg gcggcgacat ccagatgacc     2820

cagagcccta gcagcctgag cgccagcgtg ggcgacagag tgaccatcac ctgcagagcc     2880

agccaggacg tgagcaccgc cgtggcctgg taccagcaga agcctggcaa ggcccctaag     2940

ctgctgatct acagcgccag cttcctgtac agcggcgtgc ctagcagatt cagcggcagc     3000

ggcagcggca ccgacttcac cctgaccatc agcagcctgc agcctgagga cttcgccacc     3060

tactactgcc agcagtacct gtaccaccct gccaccttcg gccagggcac caaggtggag     3120

atcaagagac accatcatca ccaccat                                         3147


<210>  35
<211>  1049
<212>  PRT
<213>  Mus musculus

<400>  35

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Gly 
1               5                   10                  15      


Val His Ser Cys Pro Gln Lys Leu Thr Ile Ser Trp Phe Ala Ile Val 
            20                  25                  30          


Leu Leu Val Ser Pro Leu Met Ala Met Trp Glu Leu Glu Lys Asp Val 
        35                  40                  45              


Tyr Val Val Glu Val Asp Trp Thr Pro Asp Ala Pro Gly Glu Thr Val 
    50                  55                  60                  


Asn Leu Thr Cys Asp Thr Pro Glu Glu Asp Asp Ile Thr Trp Thr Ser 
65                  70                  75                  80  


Asp Gln Arg His Gly Val Ile Gly Ser Gly Lys Thr Leu Thr Ile Thr 
                85                  90                  95      


Val Lys Glu Phe Leu Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly 
            100                 105                 110         


Glu Thr Leu Ser His Ser His Leu Leu Leu His Lys Lys Glu Asn Gly 
        115                 120                 125             


Ile Trp Ser Thr Glu Ile Leu Lys Asn Phe Lys Asn Lys Thr Phe Leu 
    130                 135                 140                 


Lys Cys Glu Ala Pro Asn Tyr Ser Gly Arg Phe Thr Cys Ser Trp Leu 
145                 150                 155                 160 


Val Gln Arg Asn Met Asp Leu Lys Phe Asn Ile Lys Ser Ser Ser Ser 
                165                 170                 175     


Ser Pro Asp Ser Arg Ala Val Thr Cys Gly Met Ala Ser Leu Ser Ala 
            180                 185                 190         


Glu Lys Val Thr Leu Asp Gln Arg Asp Tyr Glu Lys Tyr Ser Val Ser 
        195                 200                 205             


Cys Gln Glu Asp Val Thr Cys Pro Thr Ala Glu Glu Thr Leu Pro Ile 
    210                 215                 220                 


Glu Leu Ala Leu Glu Ala Arg Gln Gln Asn Lys Tyr Glu Asn Tyr Ser 
225                 230                 235                 240 


Thr Ser Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn 
                245                 250                 255     


Leu Gln Met Lys Pro Leu Lys Asn Ser Gln Val Glu Val Ser Trp Glu 
            260                 265                 270         


Tyr Pro Asp Ser Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Lys Phe 
        275                 280                 285             


Phe Val Arg Ile Gln Arg Lys Lys Glu Lys Met Lys Glu Thr Glu Glu 
    290                 295                 300                 


Gly Cys Asn Gln Lys Gly Ala Phe Leu Val Glu Lys Thr Ser Thr Glu 
305                 310                 315                 320 


Val Gln Cys Lys Gly Gly Asn Val Cys Val Gln Ala Gln Asp Arg Tyr 
                325                 330                 335     


Tyr Asn Ser Ser Cys Ser Lys Trp Ala Cys Val Pro Cys Arg Val Arg 
            340                 345                 350         


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
        355                 360                 365             


Arg Val Ile Pro Val Ser Gly Pro Ala Arg Cys Leu Ser Gln Ser Arg 
    370                 375                 380                 


Asn Leu Leu Lys Thr Thr Asp Asp Met Val Lys Thr Ala Arg Glu Lys 
385                 390                 395                 400 


Leu Lys His Tyr Ser Cys Thr Ala Glu Asp Ile Asp His Glu Asp Ile 
                405                 410                 415     


Thr Arg Asp Gln Thr Ser Thr Leu Lys Thr Cys Leu Pro Leu Glu Leu 
            420                 425                 430         


His Lys Asn Glu Ser Cys Leu Ala Thr Arg Glu Thr Ser Ser Thr Thr 
        435                 440                 445             


Arg Gly Ser Cys Leu Pro Pro Gln Lys Thr Ser Leu Met Met Thr Leu 
    450                 455                 460                 


Cys Leu Gly Ser Ile Tyr Glu Asp Leu Lys Met Tyr Gln Thr Glu Phe 
465                 470                 475                 480 


Gln Ala Ile Asn Ala Ala Leu Gln Asn His Asn His Gln Gln Ile Ile 
                485                 490                 495     


Leu Asp Lys Gly Met Leu Val Ala Ile Asp Glu Leu Met Gln Ser Leu 
            500                 505                 510         


Asn His Asn Gly Glu Thr Leu Arg Gln Lys Pro Pro Val Gly Glu Ala 
        515                 520                 525             


Asp Pro Tyr Arg Val Lys Met Lys Leu Cys Ile Leu Leu His Ala Phe 
    530                 535                 540                 


Ser Thr Arg Val Val Thr Ile Asn Arg Val Met Gly Tyr Leu Ser Ser 
545                 550                 555                 560 


Ala Gly Ser Ala Asp Gly Glu Val Gln Leu Val Glu Ser Gly Gly Gly 
                565                 570                 575     


Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly 
            580                 585                 590         


Phe Thr Phe Ser Asp Ser Trp Ile His Trp Val Arg Gln Ala Pro Gly 
        595                 600                 605             


Lys Gly Leu Glu Trp Val Ala Trp Ile Ser Pro Tyr Gly Gly Ser Thr 
    610                 615                 620                 


Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr 
625                 630                 635                 640 


Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp 
                645                 650                 655     


Thr Ala Val Tyr Tyr Cys Ala Arg Arg His Trp Pro Gly Gly Phe Asp 
            660                 665                 670         


Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala Gly Gly Ser Gly 
        675                 680                 685             


Gly Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val 
    690                 695                 700                 


Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Ser Thr 
705                 710                 715                 720 


Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu 
                725                 730                 735     


Ile Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser 
            740                 745                 750         


Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln 
        755                 760                 765             


Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Leu Tyr His Pro 
    770                 775                 780                 


Ala Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Ser Ser Ser 
785                 790                 795                 800 


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


Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu 
            820                 825                 830         


Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Ser Trp Ile His Trp 
        835                 840                 845             


Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Trp Ile Ser 
    850                 855                 860                 


Pro Tyr Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe 
865                 870                 875                 880 


Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn 
                885                 890                 895     


Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Arg His 
            900                 905                 910         


Trp Pro Gly Gly Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val 
        915                 920                 925             


Ser Ala Gly Gly Ser Gly Gly Asp Ile Gln Met Thr Gln Ser Pro Ser 
    930                 935                 940                 


Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala 
945                 950                 955                 960 


Ser Gln Asp Val Ser Thr Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly 
                965                 970                 975     


Lys Ala Pro Lys Leu Leu Ile Tyr Ser Ala Ser Phe Leu Tyr Ser Gly 
            980                 985                 990         


Val Pro Ser Arg Phe Ser Gly Ser  Gly Ser Gly Thr Asp  Phe Thr Leu 
        995                 1000                 1005             


Thr Ile  Ser Ser Leu Gln Pro  Glu Asp Phe Ala Thr  Tyr Tyr Cys 
    1010                 1015                 1020             


Gln Gln  Tyr Leu Tyr His Pro  Ala Thr Phe Gly Gln  Gly Thr Lys 
    1025                 1030                 1035             


Val Glu  Ile Lys Arg His His  His His His His 
    1040                 1045                 


<210>  36
<211>  1021
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hIL-12-PD-L1 ligand conjugate v3

<400>  36

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Gly 
1               5                   10                  15      


Val His Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu 
            20                  25                  30          


Asp Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp 
        35                  40                  45              


Thr Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu 
    50                  55                  60                  


Val Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly 
65                  70                  75                  80  


Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His 
                85                  90                  95      


Ser Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp 
            100                 105                 110         


Ile Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys 
        115                 120                 125             


Glu Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr 
    130                 135                 140                 


Ile Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser 
145                 150                 155                 160 


Asp Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg 
                165                 170                 175     


Val Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu 
            180                 185                 190         


Asp Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met 
        195                 200                 205             


Val Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe 
    210                 215                 220                 


Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu 
225                 230                 235                 240 


Lys Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro 
                245                 250                 255     


Asp Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val 
            260                 265                 270         


Gln Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr 
        275                 280                 285             


Asp Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser 
    290                 295                 300                 


Val Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala 
305                 310                 315                 320 


Ser Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
                325                 330                 335     


Gly Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met 
            340                 345                 350         


Phe Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn 
        355                 360                 365             


Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser 
    370                 375                 380                 


Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val 
385                 390                 395                 400 


Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn 
                405                 410                 415     


Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg 
            420                 425                 430         


Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp 
        435                 440                 445             


Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu 
    450                 455                 460                 


Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val 
465                 470                 475                 480 


Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro 
                485                 490                 495     


Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys 
            500                 505                 510         


Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp 
        515                 520                 525             


Arg Val Met Ser Tyr Leu Asn Ala Ser Gly Ser Ala Asp Gly Glu Val 
    530                 535                 540                 


Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 
545                 550                 555                 560 


Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Ser Trp Ile 
                565                 570                 575     


His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Trp 
            580                 585                 590         


Ile Ser Pro Tyr Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly 
        595                 600                 605             


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


Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg 
625                 630                 635                 640 


Arg Trp His Pro Gly Gly Phe Asp Tyr Trp Gln Gln Gly Thr Leu Val 
                645                 650                 655     


Thr Val Ser Ala Gly Gly Ser Gly Gly Asp Ile Gln Met Thr Gln Ser 
            660                 665                 670         


Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys 
        675                 680                 685             


Arg Ala Ser Gln Asp Val Ser Thr Ala Val Ala Trp Tyr Gln Gln Lys 
    690                 695                 700                 


Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ser Ala Ser Phe Leu Tyr 
705                 710                 715                 720 


Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 
                725                 730                 735     


Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 
            740                 745                 750         


Cys Gln Gln Tyr Leu Tyr His Pro Ala Thr Phe Cys Gly Gln Gly Thr 
        755                 760                 765             


Lys Val Glu Ile Lys Arg Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly 
    770                 775                 780                 


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


Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe 
                805                 810                 815     


Thr Phe Ser Asp Ser Trp Ile His Trp Val Arg Gln Ala Pro Gly Lys 
            820                 825                 830         


Gly Leu Glu Trp Val Ala Trp Ile Ser Pro Tyr Gly Gly Ser Thr Tyr 
        835                 840                 845             


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


Lys Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr 
865                 870                 875                 880 


Ala Val Tyr Tyr Cys Ala Arg Arg Trp His Pro Gly Gly Phe Asp Tyr 
                885                 890                 895     


Trp Gln Gln Gly Thr Leu Val Thr Val Ser Ala Gly Gly Ser Gly Gly 
            900                 905                 910         


Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
        915                 920                 925             


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Ser Thr Ala 
    930                 935                 940                 


Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
945                 950                 955                 960 


Tyr Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly 
                965                 970                 975     


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
            980                 985                 990         


Glu Asp Phe Ala Thr Tyr Tyr Cys  Gln Gln Tyr Leu Tyr  His Pro Ala 
        995                 1000                 1005             


Thr Phe  Cys Gly Gln Gly Thr  Lys Val Glu Ile Lys  Arg 
    1010                 1015                 1020     


<210>  37
<211>  1019
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hIL-12-PD-L1 ligand conjugate v4

<400>  37

Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Gly 
1               5                   10                  15      


Val His Ser Ile Trp Glu Leu Lys Lys Asp Val Tyr Val Val Glu Leu 
            20                  25                  30          


Asp Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu Thr Cys Asp 
        35                  40                  45              


Thr Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln Ser Ser Glu 
    50                  55                  60                  


Val Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys Glu Phe Gly 
65                  70                  75                  80  


Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val Leu Ser His 
                85                  90                  95      


Ser Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp Ser Thr Asp 
            100                 105                 110         


Ile Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe Leu Arg Cys 
        115                 120                 125             


Glu Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp Leu Thr Thr 
    130                 135                 140                 


Ile Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg Gly Ser Ser 
145                 150                 155                 160 


Asp Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser Ala Glu Arg 
                165                 170                 175     


Val Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu Cys Gln Glu 
            180                 185                 190         


Asp Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile Glu Val Met 
        195                 200                 205             


Val Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr Ser Ser Phe 
    210                 215                 220                 


Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln Leu 
225                 230                 235                 240 


Lys Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp Glu Tyr Pro 
                245                 250                 255     


Asp Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr Phe Cys Val 
            260                 265                 270         


Gln Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg Val Phe Thr 
        275                 280                 285             


Asp Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala Ser Ile Ser 
    290                 295                 300                 


Val Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala 
305                 310                 315                 320 


Ser Val Pro Cys Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
                325                 330                 335     


Gly Gly Gly Ser Arg Asn Leu Pro Val Ala Thr Pro Asp Pro Gly Met 
            340                 345                 350         


Phe Pro Cys Leu His His Ser Gln Asn Leu Leu Arg Ala Val Ser Asn 
        355                 360                 365             


Met Leu Gln Lys Ala Arg Gln Thr Leu Glu Phe Tyr Pro Cys Thr Ser 
    370                 375                 380                 


Glu Glu Ile Asp His Glu Asp Ile Thr Lys Asp Lys Thr Ser Thr Val 
385                 390                 395                 400 


Glu Ala Cys Leu Pro Leu Glu Leu Thr Lys Asn Glu Ser Cys Leu Asn 
                405                 410                 415     


Ser Arg Glu Thr Ser Phe Ile Thr Asn Gly Ser Cys Leu Ala Ser Arg 
            420                 425                 430         


Lys Thr Ser Phe Met Met Ala Leu Cys Leu Ser Ser Ile Tyr Glu Asp 
        435                 440                 445             


Leu Lys Met Tyr Gln Val Glu Phe Lys Thr Met Asn Ala Lys Leu Leu 
    450                 455                 460                 


Met Asp Pro Lys Arg Gln Ile Phe Leu Asp Gln Asn Met Leu Ala Val 
465                 470                 475                 480 


Ile Asp Glu Leu Met Gln Ala Leu Asn Phe Asn Ser Glu Thr Val Pro 
                485                 490                 495     


Gln Lys Ser Ser Leu Glu Glu Pro Asp Phe Tyr Lys Thr Lys Ile Lys 
            500                 505                 510         


Leu Cys Ile Leu Leu His Ala Phe Arg Ile Arg Ala Val Thr Ile Asp 
        515                 520                 525             


Arg Val Met Ser Tyr Leu Asn Ala Ser Gly Ser Ala Asp Gly Glu Val 
    530                 535                 540                 


Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu 
545                 550                 555                 560 


Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Ser Trp Ile 
                565                 570                 575     


His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Trp 
            580                 585                 590         


Ile Ser Pro Tyr Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly 
        595                 600                 605             


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


Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg 
625                 630                 635                 640 


Arg His Trp Pro Gly Gly Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val 
                645                 650                 655     


Thr Val Ser Ala Gly Gly Ser Gly Gly Asp Ile Gln Met Thr Gln Ser 
            660                 665                 670         


Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys 
        675                 680                 685             


Arg Ala Ser Gln Asp Val Ser Thr Ala Val Ala Trp Tyr Gln Gln Lys 
    690                 695                 700                 


Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ser Ala Ser Phe Leu Tyr 
705                 710                 715                 720 


Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe 
                725                 730                 735     


Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr 
            740                 745                 750         


Cys Gln Gln Tyr Leu Tyr His Pro Ala Thr Phe Gly Gln Gly Thr Lys 
        755                 760                 765             


Val Glu Ile Lys Arg Ser Ser Ser Ser Gly Ser Ser Ser Ser Gly Ser 
    770                 775                 780                 


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


Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr 
                805                 810                 815     


Phe Ser Asp Ser Trp Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly 
            820                 825                 830         


Leu Glu Trp Val Ala Trp Ile Ser Pro Tyr Gly Gly Ser Thr Tyr Tyr 
        835                 840                 845             


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


Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala 
865                 870                 875                 880 


Val Tyr Tyr Cys Ala Arg Arg His Trp Pro Gly Gly Phe Asp Tyr Trp 
                885                 890                 895     


Gly Gln Gly Thr Leu Val Thr Val Ser Ala Gly Gly Ser Gly Gly Asp 
            900                 905                 910         


Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp 
        915                 920                 925             


Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Ser Thr Ala Val 
    930                 935                 940                 


Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 
945                 950                 955                 960 


Ser Ala Ser Phe Leu Tyr Ser Gly Val Pro Ser Arg Phe Ser Gly Ser 
                965                 970                 975     


Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 
            980                 985                 990         


Asp Phe Ala Thr Tyr Tyr Cys Gln  Gln Tyr Leu Tyr His  Pro Ala Thr 
        995                 1000                 1005             


Phe Gly  Gln Gly Thr Lys Val  Glu Ile Lys Arg 
    1010                 1015                 


<210>  38
<211>  3060
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  hIL-12-PD-L1 ligand conjugate v2

<400>  38
atgggctgga gcctgatcct cctgttcctc gtcgctgtgg ctacaggtgt gcactcgata       60

tgggaactga agaaagatgt ttatgtcgta gaattggatt ggtatccgga tgcccctgga      120

gaaatggtgg tcctcacctg tgacacccct gaagaagatg gtatcacctg gaccttggac      180

cagagcagtg aggtcttagg ctctggcaaa accctgacca tccaagtcaa agagtttgga      240

gatgctggcc agtacacctg tcacaaagga ggcgaggttc taagccattc gctcctgctg      300

cttcacaaaa aggaagatgg aatttggtcc actgatattt taaaggacca gaaagaaccc      360

aaaaataaga cctttctaag atgcgaggcc aagaattatt ctggacgttt cacctgctgg      420

tggctgacga caatcagtac tgatttgaca ttcagtgtca aaagcagcag aggctcttct      480

gacccccaag gggtgacgtg cggagctgct acactctctg cagagagagt cagaggggac      540

aacaaggagt atgagtactc agtggagtgc caggaggaca gtgcctgccc agctgctgag      600

gagagtctgc ccattgaggt catggtggat gccgttcaca agctcaagta tgaaaactac      660

accagcagct tcttcatcag ggacatcatc aaacctgacc cacccaagaa cttgcagctg      720

aagccattaa agaattctcg gcaggtggag gtcagctggg agtaccctga cacctggagt      780

actccacatt cctacttctc cctgacattc tgcgttcagg tccagggcaa gagcaagaga      840

gaaaagaaag atagagtctt cacggacaag acctcagcca cggtcatctg ccgcaaaaat      900

gccagcatta gcgtgcgggc ccaggaccgc tactatagct catcttggag cgaatgggca      960

tctgtgccct gcagtggggg aggcggaagc gggggaggcg gaagcggggg aggcggaagc     1020

agaaacctcc ccgtggccac tccagaccca ggaatgttcc catgccttca ccactcccaa     1080

aacctgctga gggccgtcag caacatgctc cagaaggcca gacaaactct agaattttac     1140

ccttgcactt ctgaagagat tgatcatgaa gatatcacaa aagataaaac cagcacagtg     1200

gaggcctgtt taccattgga attaaccaag aatgagagtt gcctaaattc cagagagacc     1260

tctttcataa ctaatgggag ttgcctggcc tccagaaaga cctcttttat gatggccctg     1320

tgccttagta gtatttatga agacttgaag atgtaccagg tggagttcaa gaccatgaat     1380

gcaaagcttc tgatggatcc taagaggcag atctttctag atcaaaacat gctggcagtt     1440

attgatgagc tgatgcaggc cctgaatttc aacagtgaga ctgtgccaca aaaatcctcc     1500

cttgaagaac cggattttta taaaactaaa atcaagctct gcatacttct tcatgctttc     1560

agaattcggg cagtgactat tgatagagtg atgagctatc tgaatgcttc cggtagtgct     1620

gacggaggag aggtgcagct ggtggagagc ggcggcggcc tggtgcagcc tggcggcagc     1680

ctgagactga gctgcgccgc cagcggcttc accttcagcg acagctggat ccactgggtg     1740

agacaggccc ctggcaaggg cctggagtgg gtggcctgga tcagccctta cggcggcagc     1800

acctactacg ccgacagcgt gaagggcaga ttcaccatca gcgccgacac cagcaagaac     1860

accgcctacc tgcagatgaa cagcctgaga gccgaggaca ccgccgtgta ctactgcgcc     1920

agaagacact ggcctggcgg cttcgactac tggggccagg gcaccctggt gaccgtgagc     1980

gccggcggca gcggcggcga catccagatg acccagagcc ctagcagcct gagcgccagc     2040

gtgggcgaca gagtgaccat cacctgcaga gccagccagg acgtgagcac cgccgtggcc     2100

tggtaccagc agaagcctgg caaggcccct aagctgctga tctacagcgc cagcttcctg     2160

tacagcggcg tgcctagcag attcagcggc agcggcagcg gcaccgactt caccctgacc     2220

atcagcagcc tgcagcctga ggacttcgcc acctactact gccagcagta cctgtaccac     2280

cctgccacct tcggccaggg caccaaggtg gagatcaaga gaagcagcag cagcggcagc     2340

agcagcagcg gcagcagcag cagcggcgag gtgcagctgg tggagagcgg cggcggcctg     2400

gtgcagcctg gcggcagcct gagactgagc tgcgccgcca gcggcttcac cttcagcgac     2460

agctggatcc actgggtgag acaggcccct ggcaagggcc tggagtgggt ggcctggatc     2520

agcccttacg gcggcagcac ctactacgcc gacagcgtga agggcagatt caccatcagc     2580

gccgacacca gcaagaacac cgcctacctg cagatgaaca gcctgagagc cgaggacacc     2640

gccgtgtact actgcgccag aagacactgg cctggcggct tcgactactg gggccagggc     2700

accctggtga ccgtgagcgc cggcggcagc ggcggcgaca tccagatgac ccagagccct     2760

agcagcctga gcgccagcgt gggcgacaga gtgaccatca cctgcagagc cagccaggac     2820

gtgagcaccg ccgtggcctg gtaccagcag aagcctggca aggcccctaa gctgctgatc     2880

tacagcgcca gcttcctgta cagcggcgtg cctagcagat tcagcggcag cggcagcggc     2940

accgacttca ccctgaccat cagcagcctg cagcctgagg acttcgccac ctactactgc     3000

cagcagtacc tgtaccaccc tgccaccttc ggccagggca ccaaggtgga gatcaagaga     3060


