                         SEQUENCE LISTING

<110>  AskGene
 
<120>  Human TIGIT Specific Single Domain Antibodies and Methods of Use

<130>  AG3-021WO

<140>  63012221
<141>  2020-04-19

<160>  46    

<170>  PatentIn version 3.5

<210>  1
<211>  123
<212>  PRT
<213>  artificial

<220>
<223>  clone 379-D1; Single Domain Antibody Protein Sequence

<400>  1

Gln Val Gln Val Val Glu Ser Gly Gly Gly Ser Val Gln Ala Gly Gly 
1               5                   10                  15      


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


Pro Val Gly Trp Phe Arg Gln Ala Pro Gly Lys Asp Arg Glu Pro Ile 
        35                  40                  45              


Ala Ala Ile Thr Arg Gly Ala Arg Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


Leu His Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Ala Ala Thr Trp Gly Thr Thr Pro Pro Val Gln Pro Ile Ala Asp Phe 
            100                 105                 110         


Trp Asn Gln Gly Thr Gln Val Thr Val Ser Ser 
        115                 120             


<210>  2
<211>  123
<212>  PRT
<213>  artificial

<220>
<223>  clone 379-D11; Single Domain Antibody Protein Sequence

<400>  2

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


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


Pro Ile Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Pro Ile 
        35                  40                  45              


Ala Ala Ile Thr Arg Gly Ser Arg Gly Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys 
                85                  90                  95      


Ala Ala Thr Trp Gly Thr Thr His Pro Val Arg Pro Ile Val Asp Ser 
            100                 105                 110         


Trp Gly Gln Gly Thr His Val Thr Val Thr Ser 
        115                 120             


<210>  3
<211>  123
<212>  PRT
<213>  artificial

<220>
<223>  clone 379-B4; Single Domain Antibody Protein Sequence

<400>  3

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


Ser Leu Arg Leu Ser Cys Val Val Ser Gly Gly Arg Phe Ser Ile Asn 
            20                  25                  30          


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


Ala Arg Ala Thr Asn Thr Gly Arg Thr Thr Thr Thr Asn Tyr Ala Asp 
    50                  55                  60                  


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


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


Tyr Cys His Ala Asp Ile Ile Ser Asp Gly Lys Thr Val Asn Arg Tyr 
            100                 105                 110         


Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser 
        115                 120             


<210>  4
<211>  125
<212>  PRT
<213>  artificial

<220>
<223>  clone 379-D6; Single Domain Antibody Protein Sequence

<400>  4

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


Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Arg Thr Phe Gly Val Met 
            20                  25                  30          


Ser Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val 
        35                  40                  45              


Ala Ala Val Ser Arg Gly Gly Gly Gly Thr Phe Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Ala Asp Ser Lys Arg Gly Ala His Met Met Ser Ala His Ala Ser 
            100                 105                 110         


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


<210>  5
<211>  123
<212>  PRT
<213>  artificial

<220>
<223>  clone 379-B4 mutein; Single Domain Antibody Protein Sequence

<400>  5

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


Ser Leu Arg Leu Ser Cys Val Val Ser Gly Gly Arg Phe Ser Ile Asn 
            20                  25                  30          


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


Ala Arg Ala Thr Asn Thr Gly Arg Thr Thr Thr Thr Asn Tyr Ala Asp 
    50                  55                  60                  


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


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


Tyr Cys His Ala Asp Ile Ile Ser Asp Gly Lys Thr Val Asn Arg Tyr 
            100                 105                 110         


Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser 
        115                 120             


<210>  6
<211>  125
<212>  PRT
<213>  artificial

<220>
<223>  clone 379-D6 mutein; Single Domain Antibody Protein Sequence

<400>  6

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


Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Arg Thr Phe Gly Val Met 
            20                  25                  30          


Ser Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val 
        35                  40                  45              


Ala Ala Val Ser Arg Gly Gly Gly Gly Thr Phe Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Ala Asp Ser Lys Arg Gly Ala His Met Met Ser Ala His Ala Ser 
            100                 105                 110         


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


<210>  7
<211>  227
<212>  PRT
<213>  artificial

<220>
<223>  IgG1 Fc - Single Domain Antibody Protein Sequences

<400>  7

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


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


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


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


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


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


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


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


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


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


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


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


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


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


Pro Gly Lys 
225         


<210>  8
<211>  15
<212>  PRT
<213>  artificial

<220>
<223>  peptide linker

<400>  8

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


<210>  9
<211>  209
<212>  PRT
<213>  artificial

<220>
<223>  Fragment of VEGFR2 extracellular domain comprising the second and
       third Ig-like C2-type (immunoglobulin-like) domains of VEGF 
       receptor II

<400>  9

Gln Asp Tyr Arg Ser Pro Phe Ile Ala Ser Val Ser Asp Gln His Gly 
1               5                   10                  15      


Val Val Tyr Ile Thr Glu Asn Lys Asn Lys Thr Val Val Ile Pro Cys 
            20                  25                  30          


Leu Gly Ser Ile Ser Asn Leu Asn Val Ser Leu Cys Ala Arg Tyr Pro 
        35                  40                  45              


Glu Lys Arg Phe Val Pro Asp Gly Asn Arg Ile Ser Trp Asp Ser Lys 
    50                  55                  60                  


Lys Gly Phe Thr Ile Pro Ser Tyr Met Ile Ser Tyr Ala Gly Met Val 
65                  70                  75                  80  


Phe Cys Glu Ala Lys Ile Asn Asp Glu Ser Tyr Gln Ser Ile Met Tyr 
                85                  90                  95      


Ile Val Val Val Val Gly Tyr Arg Ile Tyr Asp Val Val Leu Ser Pro 
            100                 105                 110         


Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys 
        115                 120                 125             


Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr 
    130                 135                 140                 


Pro Ser Ser Lys His Gln His Lys Lys Leu Val Asn Arg Asp Leu Lys 
145                 150                 155                 160 


Thr Gln Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile 
                165                 170                 175     


Asp Gly Val Thr Arg Ser Asp Gln Gly Leu Tyr Thr Cys Ala Ala Ser 
            180                 185                 190         


Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu 
        195                 200                 205             


Lys 
    


<210>  10
<211>  205
<212>  PRT
<213>  artificial

<220>
<223>  VEGF-binding moiety comprises the second Ig-like C2-type 
       (immunoglobulin-like) domains of VEGF receptor I and third 
       Ig-like C2-type (immunoglobulin-like) domains of VEGF receptor II

<400>  10

Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu 
1               5                   10                  15      


Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val 
            20                  25                  30          


Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr 
        35                  40                  45              


Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe 
    50                  55                  60                  


Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu 
65                  70                  75                  80  


Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg 
                85                  90                  95      


Gln Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile 
            100                 105                 110         


Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr 
        115                 120                 125             


Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys 
    130                 135                 140                 


His Gln His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gln Ser Gly 
145                 150                 155                 160 


Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr 
                165                 170                 175     


Arg Ser Asp Gln Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met 
            180                 185                 190         


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


<210>  11
<211>  137
<212>  PRT
<213>  artificial

<220>
<223>  Extracellular domain (ECD) of TGF-beta Receptor II (TGF?RII)

<400>  11

Gly Ile Pro Pro His Val Gln Lys Ser Val Asn Asn Asp Met Ile Val 
1               5                   10                  15      


Thr Asp Asn Asn Gly Ala Val Lys Phe Pro Gln Leu Cys Lys Phe Cys 
            20                  25                  30          


Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn 
        35                  40                  45              


Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala 
    50                  55                  60                  


Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His 
65                  70                  75                  80  


Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser 
                85                  90                  95      


Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe 
            100                 105                 110         


Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser 
        115                 120                 125             


Glu Glu Tyr Asn Thr Ser Asn Pro Asp 
    130                 135         


<210>  12
<211>  117
<212>  PRT
<213>  artificial

<220>
<223>  TGF-beta1-binding moiety comprise a fragment of the extracellular
       domain of TGF-beta Receptor II

<400>  12

Gly Ala Val Lys Phe Pro Gln Leu Cys Lys Phe Cys Asp Val Arg Phe 
1               5                   10                  15      


Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr 
            20                  25                  30          


Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys 
        35                  40                  45              


Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu 
    50                  55                  60                  


Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile 
65                  70                  75                  80  


Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys 
                85                  90                  95      


Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn 
            100                 105                 110         


Thr Ser Asn Pro Asp 
        115         


<210>  13
<211>  112
<212>  PRT
<213>  artificial

<220>
<223>  TGF-beta1-binding moiety comprise a fragment of the extracellular
       domain of TGF-beta Receptor II

<400>  13

Pro Gln Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr Cys Asp Asn 
1               5                   10                  15      


Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys 
            20                  25                  30          


Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn Asp Glu Asn Ile 
        35                  40                  45              


Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His Asp Phe 
    50                  55                  60                  


Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys 
65                  70                  75                  80  


Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser Asp Glu Cys 
                85                  90                  95      


Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp 
            100                 105                 110         


<210>  14
<211>  279
<212>  PRT
<213>  artificial

<220>
<223>  TGF-beta1-binding moiety comprise two copies of a fragment of the
       extracellular domain of TGF-beta Receptor II


<220>
<221>  REPEAT
<222>  (138)..(142)
<223>  n = 1, 2, 3, 4 or 5

<400>  14

Gly Ile Pro Pro His Val Gln Lys Ser Val Asn Asn Asp Met Ile Val 
1               5                   10                  15      


Thr Asp Asn Asn Gly Ala Val Lys Phe Pro Gln Leu Cys Lys Phe Cys 
            20                  25                  30          


Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn 
        35                  40                  45              


Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala 
    50                  55                  60                  


Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His 
65                  70                  75                  80  


Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser 
                85                  90                  95      


Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe 
            100                 105                 110         


Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser 
        115                 120                 125             


Glu Glu Tyr Asn Thr Ser Asn Pro Asp Gly Gly Gly Gly Ser Gly Ile 
    130                 135                 140                 


Pro Pro His Val Gln Lys Ser Val Asn Asn Asp Met Ile Val Thr Asp 
145                 150                 155                 160 


Asn Asn Gly Ala Val Lys Phe Pro Gln Leu Cys Lys Phe Cys Asp Val 
                165                 170                 175     


Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser 
            180                 185                 190         


Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp 
        195                 200                 205             


Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro 
    210                 215                 220                 


Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys 
225                 230                 235                 240 


Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys 
                245                 250                 255     


Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu 
            260                 265                 270         


Tyr Asn Thr Ser Asn Pro Asp 
        275                 


<210>  15
<211>  214
<212>  PRT
<213>  artificial

<220>
<223>  Light Chain of PD-1 Antibody Nivolumab

<400>  15

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


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr 
            20                  25                  30          


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


Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly 
    50                  55                  60                  


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


Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Ser Asn Trp Pro Arg 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 
            100                 105                 110         


Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             


Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 


Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 


Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     


Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         


Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  16
<211>  440
<212>  PRT
<213>  artificial

<220>
<223>  PD-1 Antibody Nivolumab Heavy Chain Amino Acid Sequence

<400>  16

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


Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Ser 
            20                  25                  30          


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


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


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


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


Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser 
            100                 105                 110         


Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser 
        115                 120                 125             


Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp 
    130                 135                 140                 


Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr 
145                 150                 155                 160 


Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr 
                165                 170                 175     


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


Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp 
        195                 200                 205             


Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala 
    210                 215                 220                 


Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
225                 230                 235                 240 


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
                245                 250                 255     


Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val 
            260                 265                 270         


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
        275                 280                 285             


Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
    290                 295                 300                 


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly 
305                 310                 315                 320 


Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
                325                 330                 335     


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr 
            340                 345                 350         


Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
        355                 360                 365             


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
    370                 375                 380                 


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
385                 390                 395                 400 


Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe 
                405                 410                 415     


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
            420                 425                 430         


Ser Leu Ser Leu Ser Leu Gly Lys 
        435                 440 


<210>  17
<211>  218
<212>  PRT
<213>  artificial

<220>
<223>  PD-1 Antibody Pembrolizumab Light Chain Sequence

<400>  17

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


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Lys Gly Val Ser Thr Ser 
            20                  25                  30          


Gly Tyr Ser Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro 
        35                  40                  45              


Arg Leu Leu Ile Tyr Leu Ala Ser Tyr Leu Glu Ser Gly Val Pro Ala 
    50                  55                  60                  


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


Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Ser Arg 
                85                  90                  95      


Asp Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 
            100                 105                 110         


Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
        115                 120                 125             


Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
    130                 135                 140                 


Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
145                 150                 155                 160 


Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                165                 170                 175     


Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
            180                 185                 190         


His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
        195                 200                 205             


Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
    210                 215             


<210>  18
<211>  447
<212>  PRT
<213>  artificial

<220>
<223>  Antibody Pembrolizumab Heavy Chain Sequence

<400>  18

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


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
            20                  25                  30          


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


Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe 
    50                  55                  60                  


Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


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


Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 
        115                 120                 125             


Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala 
    130                 135                 140                 


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


Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 
                165                 170                 175     


Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 
            180                 185                 190         


Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys 
        195                 200                 205             


Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro 
    210                 215                 220                 


Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val 
225                 230                 235                 240 


Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                245                 250                 255     


Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu 
            260                 265                 270         


Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
        275                 280                 285             


Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser 
    290                 295                 300                 


Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
305                 310                 315                 320 


Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile 
                325                 330                 335     


Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
            340                 345                 350         


Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
        355                 360                 365             


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
    370                 375                 380                 


Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
385                 390                 395                 400 


Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg 
                405                 410                 415     


Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
            420                 425                 430         


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 
        435                 440                 445         


<210>  19
<211>  214
<212>  PRT
<213>  artificial

<220>
<223>  Light Chain of PD-L1 Antibody ASKB1296

<400>  19

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


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr 
            20                  25                  30          


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


Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly 
    50                  55                  60                  


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


Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Ser Asn Trp Pro Arg 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala 
            100                 105                 110         


Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             


Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 


Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 


Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     


Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         


Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  20
<211>  453
<212>  PRT
<213>  artificial

<220>
<223>  Heavy Chain of PD-L1 Antibody ASKB1296

<400>  20

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


Thr Val Lys Ile Ser Cys Thr Ala Ser Gly Phe Asn Ile Lys Asp Asp 
            20                  25                  30          


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


Gly Arg Ile Asp Pro Ala Asn Ala Asn Thr Lys Tyr Ala Pro Lys Phe 
    50                  55                  60                  


Gln Asp Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asn Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Ala Arg Phe Gly Tyr Phe Tyr Gly Ser Ser Phe Tyr Ala Val Ala 
            100                 105                 110         


Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys 
        115                 120                 125             


Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly 
    130                 135                 140                 


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


Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr 
                165                 170                 175     


Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val 
            180                 185                 190         


Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn 
        195                 200                 205             


Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro 
    210                 215                 220                 


Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
225                 230                 235                 240 


Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                245                 250                 255     


Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
            260                 265                 270         


Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
        275                 280                 285             


Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn 
    290                 295                 300                 


Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
305                 310                 315                 320 


Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                325                 330                 335     


Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
            340                 345                 350         


Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn 
        355                 360                 365             


Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
    370                 375                 380                 


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
385                 390                 395                 400 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                405                 410                 415     


Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
            420                 425                 430         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        435                 440                 445             


Ser Leu Ser Pro Lys 
    450             


<210>  21
<211>  453
<212>  PRT
<213>  artificial

<220>
<223>  Heavy Chain of PD-L1 Antibody ASKB1296

<400>  21

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


Thr Val Lys Ile Ser Cys Thr Ala Ser Gly Phe Asn Ile Lys Glu Asp 
            20                  25                  30          


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


Gly Arg Ile Asp Pro Ala Asn Ala Asn Thr Lys Tyr Ala Pro Lys Phe 
    50                  55                  60                  


Gln Asp Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asn Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Ala Arg Phe Gly Tyr Phe Tyr Gly Ser Ser Phe Tyr Ala Val Ala 
            100                 105                 110         


Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys 
        115                 120                 125             


Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly 
    130                 135                 140                 


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


Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr 
                165                 170                 175     


Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val 
            180                 185                 190         


Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn 
        195                 200                 205             


Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro 
    210                 215                 220                 


Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
225                 230                 235                 240 


Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                245                 250                 255     


Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
            260                 265                 270         


Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
        275                 280                 285             


Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn 
    290                 295                 300                 


Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
305                 310                 315                 320 


Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                325                 330                 335     


Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
            340                 345                 350         


Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn 
        355                 360                 365             


Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
    370                 375                 380                 


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
385                 390                 395                 400 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                405                 410                 415     


Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
            420                 425                 430         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        435                 440                 445             


Ser Leu Ser Pro Lys 
    450             


<210>  22
<211>  214
<212>  PRT
<213>  artificial

<220>
<223>  Atezolizumab Light Chain Sequence

<400>  22

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 Thr Val Ala Ala 
            100                 105                 110         


Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             


Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 


Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 


Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     


Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         


Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  23
<211>  448
<212>  PRT
<213>  artificial

<220>
<223>  Atezolizumab Heavy Chain Sequence

<400>  23

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 Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 
        115                 120                 125             


Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 
    130                 135                 140                 


Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 
145                 150                 155                 160 


Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 
                165                 170                 175     


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


Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 
        195                 200                 205             


Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr 
    210                 215                 220                 


His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser 
225                 230                 235                 240 


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
                245                 250                 255     


Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
            260                 265                 270         


Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
        275                 280                 285             


Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val 
    290                 295                 300                 


Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
305                 310                 315                 320 


Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
                325                 330                 335     


Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
            340                 345                 350         


Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys 
        355                 360                 365             


Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
    370                 375                 380                 


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
385                 390                 395                 400 


Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 
                405                 410                 415     


Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
            420                 425                 430         


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
        435                 440                 445             


<210>  24
<211>  596
<212>  PRT
<213>  artificial

<220>
<223>  PD-L1 Antibody Heavy Chain Polypeptide Chain


<220>
<221>  MISC_FEATURE
<222>  (31)..(31)
<223>  X is E or D

<220>
<221>  REPEAT
<222>  (455)..(459)
<223>  n is 1, 2, 3, 4 or 5

<400>  24

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


Thr Val Lys Ile Ser Cys Thr Ala Ser Gly Phe Asn Ile Lys Xaa Asp 
            20                  25                  30          


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


Gly Arg Ile Asp Pro Ala Asn Ala Asn Thr Lys Tyr Ala Pro Lys Phe 
    50                  55                  60                  


Gln Asp Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asn Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Ala Arg Phe Gly Tyr Phe Tyr Gly Ser Ser Phe Tyr Ala Val Ala 
            100                 105                 110         


Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys 
        115                 120                 125             


Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly 
    130                 135                 140                 


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


Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr 
                165                 170                 175     


Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val 
            180                 185                 190         


Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn 
        195                 200                 205             


Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro 
    210                 215                 220                 


Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
225                 230                 235                 240 


Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                245                 250                 255     


Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
            260                 265                 270         


Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
        275                 280                 285             


Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn 
    290                 295                 300                 


Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
305                 310                 315                 320 


Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                325                 330                 335     


Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
            340                 345                 350         


Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn 
        355                 360                 365             


Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
    370                 375                 380                 


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
385                 390                 395                 400 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                405                 410                 415     


Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
            420                 425                 430         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        435                 440                 445             


Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gly Ile Pro Pro His 
    450                 455                 460                 


Val Gln Lys Ser Val Asn Asn Asp Met Ile Val Thr Asp Asn Asn Gly 
465                 470                 475                 480 


Ala Val Lys Phe Pro Gln Leu Cys Lys Phe Cys Asp Val Arg Phe Ser 
                485                 490                 495     


Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser 
            500                 505                 510         


Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn 
        515                 520                 525             


Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro 
    530                 535                 540                 


Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met 
545                 550                 555                 560 


Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser 
                565                 570                 575     


Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr 
            580                 585                 590         


Ser Asn Pro Asp 
        595     


<210>  25
<211>  582
<212>  PRT
<213>  artificial

<220>
<223>  PD-1 Antibody Heavy Chain Polypeptide Chain


<220>
<221>  REPEAT
<222>  (441)..(445)
<223>  n is 1, 2, 3, 4 or 5

<400>  25

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


Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Ser 
            20                  25                  30          


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


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


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


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


Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser 
            100                 105                 110         


Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser 
        115                 120                 125             


Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp 
    130                 135                 140                 


Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr 
145                 150                 155                 160 


Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr 
                165                 170                 175     


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


Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp 
        195                 200                 205             


Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala 
    210                 215                 220                 


Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
225                 230                 235                 240 


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
                245                 250                 255     


Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val 
            260                 265                 270         


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
        275                 280                 285             


Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
    290                 295                 300                 


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly 
305                 310                 315                 320 


Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
                325                 330                 335     


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr 
            340                 345                 350         


Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
        355                 360                 365             


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
    370                 375                 380                 


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
385                 390                 395                 400 


Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe 
                405                 410                 415     


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
            420                 425                 430         


Ser Leu Ser Leu Ser Leu Gly Ala Gly Gly Gly Gly Ser Gly Ile Pro 
        435                 440                 445             


Pro His Val Gln Lys Ser Val Asn Asn Asp Met Ile Val Thr Asp Asn 
    450                 455                 460                 


Asn Gly Ala Val Lys Phe Pro Gln Leu Cys Lys Phe Cys Asp Val Arg 
465                 470                 475                 480 


Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile 
                485                 490                 495     


Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg 
            500                 505                 510         


Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys 
        515                 520                 525             


Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys 
    530                 535                 540                 


Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser 
545                 550                 555                 560 


Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr 
                565                 570                 575     


Asn Thr Ser Asn Pro Asp 
            580         


<210>  26
<211>  719
<212>  PRT
<213>  artificial

<220>
<223>  hPD1(IgG1)-(G4S)4G-2xshorterTGFbRIIECD

<400>  26

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


Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Ser 
            20                  25                  30          


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


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


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


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


Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser 
            100                 105                 110         


Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser 
        115                 120                 125             


Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp 
    130                 135                 140                 


Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr 
145                 150                 155                 160 


Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr 
                165                 170                 175     


Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln 
            180                 185                 190         


Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp 
        195                 200                 205             


Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro 
    210                 215                 220                 


Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro 
225                 230                 235                 240 


Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr 
                245                 250                 255     


Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn 
            260                 265                 270         


Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 
        275                 280                 285             


Glu Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 
    290                 295                 300                 


Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 
305                 310                 315                 320 


Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys 
                325                 330                 335     


Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu 
            340                 345                 350         


Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe 
        355                 360                 365             


Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
    370                 375                 380                 


Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 
385                 390                 395                 400 


Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 
                405                 410                 415     


Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
            420                 425                 430         


Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser 
        435                 440                 445             


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
    450                 455                 460                 


Gly Ala Val Lys Phe Pro Gln Leu Cys Lys Phe Cys Asp Val Arg Phe 
465                 470                 475                 480 


Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr 
                485                 490                 495     


Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys 
            500                 505                 510         


Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu 
        515                 520                 525             


Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile 
    530                 535                 540                 


Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys 
545                 550                 555                 560 


Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn 
                565                 570                 575     


Thr Ser Asn Pro Asp Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
            580                 585                 590         


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Ala Val Lys Phe Pro 
        595                 600                 605             


Gln Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr Cys Asp Asn Gln 
    610                 615                 620                 


Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro 
625                 630                 635                 640 


Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn Asp Glu Asn Ile Thr 
                645                 650                 655     


Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His Asp Phe Ile 
            660                 665                 670         


Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys Lys 
        675                 680                 685             


Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser Asp Glu Cys Asn 
    690                 695                 700                 


Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp 
705                 710                 715                 


<210>  27
<211>  600
<212>  PRT
<213>  artificial

<220>
<223>  hPD1(IgG1)-(G4S)4G-1xTGFbRIIECD

<400>  27

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


Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Ser 
            20                  25                  30          


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


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


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


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


Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser 
            100                 105                 110         


Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser 
        115                 120                 125             


Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp 
    130                 135                 140                 


Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr 
145                 150                 155                 160 


Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr 
                165                 170                 175     


Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln 
            180                 185                 190         


Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp 
        195                 200                 205             


Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro 
    210                 215                 220                 


Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro 
225                 230                 235                 240 


Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr 
                245                 250                 255     


Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn 
            260                 265                 270         


Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 
        275                 280                 285             


Glu Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 
    290                 295                 300                 


Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 
305                 310                 315                 320 


Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys 
                325                 330                 335     


Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu 
            340                 345                 350         


Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe 
        355                 360                 365             


Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
    370                 375                 380                 


Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 
385                 390                 395                 400 


Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 
                405                 410                 415     


Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
            420                 425                 430         


Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser 
        435                 440                 445             


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
    450                 455                 460                 


Ile Pro Pro His Val Gln Lys Ser Val Asn Asn Asp Met Ile Val Thr 
465                 470                 475                 480 


Asp Asn Asn Gly Ala Val Lys Phe Pro Gln Leu Cys Lys Phe Cys Asp 
                485                 490                 495     


Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys 
            500                 505                 510         


Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val 
        515                 520                 525             


Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp 
    530                 535                 540                 


Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro 
545                 550                 555                 560 


Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met 
                565                 570                 575     


Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu 
            580                 585                 590         


Glu Tyr Asn Thr Ser Asn Pro Asp 
        595                 600 


<210>  28
<211>  581
<212>  PRT
<213>  artificial

<220>
<223>  hPD1(IgG1)-(G4S)4G-1xshorterTGFbRIIECD

<400>  28

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


Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Ser 
            20                  25                  30          


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


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


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


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


Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser 
            100                 105                 110         


Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser 
        115                 120                 125             


Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp 
    130                 135                 140                 


Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr 
145                 150                 155                 160 


Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr 
                165                 170                 175     


Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln 
            180                 185                 190         


Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp 
        195                 200                 205             


Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro 
    210                 215                 220                 


Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro 
225                 230                 235                 240 


Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr 
                245                 250                 255     


Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn 
            260                 265                 270         


Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 
        275                 280                 285             


Glu Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 
    290                 295                 300                 


Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 
305                 310                 315                 320 


Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys 
                325                 330                 335     


Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu 
            340                 345                 350         


Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe 
        355                 360                 365             


Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
    370                 375                 380                 


Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 
385                 390                 395                 400 


Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 
                405                 410                 415     


Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
            420                 425                 430         


Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser 
        435                 440                 445             


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
    450                 455                 460                 


Gly Ala Val Lys Phe Pro Gln Leu Cys Lys Phe Cys Asp Val Arg Phe 
465                 470                 475                 480 


Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr 
                485                 490                 495     


Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys 
            500                 505                 510         


Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu 
        515                 520                 525             


Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile 
    530                 535                 540                 


Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys 
545                 550                 555                 560 


Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn 
                565                 570                 575     


Thr Ser Asn Pro Asp 
            580     


<210>  29
<211>  582
<212>  PRT
<213>  artificial

<220>
<223>  PD-1 Antibody Heavy Chain Polypeptide Chain


<220>
<221>  REPEAT
<222>  (445)..(449)

<400>  29

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


Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Ser 
            20                  25                  30          


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


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


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


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


Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser 
            100                 105                 110         


Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser 
        115                 120                 125             


Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp 
    130                 135                 140                 


Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr 
145                 150                 155                 160 


Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr 
                165                 170                 175     


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


Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp 
        195                 200                 205             


Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala 
    210                 215                 220                 


Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
225                 230                 235                 240 


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
                245                 250                 255     


Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val 
            260                 265                 270         


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
        275                 280                 285             


Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
    290                 295                 300                 


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly 
305                 310                 315                 320 


Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
                325                 330                 335     


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr 
            340                 345                 350         


Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
        355                 360                 365             


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
    370                 375                 380                 


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
385                 390                 395                 400 


Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe 
                405                 410                 415     


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
            420                 425                 430         


Ser Leu Ser Leu Ser Leu Gly Ala Gly Gly Gly Gly Ser Gly Ile Pro 
        435                 440                 445             


Pro His Val Gln Lys Ser Val Asn Asn Asp Met Ile Val Thr Asp Asn 
    450                 455                 460                 


Asn Gly Ala Val Lys Phe Pro Gln Leu Cys Lys Phe Cys Asp Val Arg 
465                 470                 475                 480 


Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile 
                485                 490                 495     


Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg 
            500                 505                 510         


Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys 
        515                 520                 525             


Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys 
    530                 535                 540                 


Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser 
545                 550                 555                 560 


Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr 
                565                 570                 575     


Asn Thr Ser Asn Pro Asp 
            580         


<210>  30
<211>  592
<212>  PRT
<213>  artificial

<220>
<223>  PD-1 Antibody Heavy Chain Polypeptide Chain

<400>  30

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


Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Ser 
            20                  25                  30          


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


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


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


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


Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser 
            100                 105                 110         


Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser 
        115                 120                 125             


Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp 
    130                 135                 140                 


Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr 
145                 150                 155                 160 


Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr 
                165                 170                 175     


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


Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp 
        195                 200                 205             


Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala 
    210                 215                 220                 


Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
225                 230                 235                 240 


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
                245                 250                 255     


Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val 
            260                 265                 270         


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
        275                 280                 285             


Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
    290                 295                 300                 


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly 
305                 310                 315                 320 


Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
                325                 330                 335     


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr 
            340                 345                 350         


Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
        355                 360                 365             


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
    370                 375                 380                 


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
385                 390                 395                 400 


Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe 
                405                 410                 415     


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
            420                 425                 430         


Ser Leu Ser Leu Ser Leu Gly Lys Gly Gly Gly Gly Ser Gly Gly Gly 
        435                 440                 445             


Gly Ser Gly Gly Gly Gly Ser Gly Ile Pro Pro His Val Gln Lys Ser 
    450                 455                 460                 


Val Asn Asn Asp Met Ile Val Thr Asp Asn Asn Gly Ala Val Lys Phe 
465                 470                 475                 480 


Pro Gln Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr Cys Asp Asn 
                485                 490                 495     


Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys 
            500                 505                 510         


Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn Asp Glu Asn Ile 
        515                 520                 525             


Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His Asp Phe 
    530                 535                 540                 


Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys 
545                 550                 555                 560 


Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser Asp Glu Cys 
                565                 570                 575     


Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp 
            580                 585                 590         


<210>  31
<211>  744
<212>  PRT
<213>  artificial

<220>
<223>  hPD1(IgG4)-2xTGFBRIIECD

<400>  31

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


Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Ser 
            20                  25                  30          


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


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


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


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


Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser 
            100                 105                 110         


Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser 
        115                 120                 125             


Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp 
    130                 135                 140                 


Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr 
145                 150                 155                 160 


Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr 
                165                 170                 175     


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


Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp 
        195                 200                 205             


Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala 
    210                 215                 220                 


Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
225                 230                 235                 240 


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
                245                 250                 255     


Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val 
            260                 265                 270         


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
        275                 280                 285             


Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
    290                 295                 300                 


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly 
305                 310                 315                 320 


Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
                325                 330                 335     


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr 
            340                 345                 350         


Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
        355                 360                 365             


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
    370                 375                 380                 


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
385                 390                 395                 400 


Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe 
                405                 410                 415     


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
            420                 425                 430         


Ser Leu Ser Leu Ser Leu Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly 
        435                 440                 445             


Gly Ser Gly Gly Gly Gly Ser Gly Ile Pro Pro His Val Gln Lys Ser 
    450                 455                 460                 


Val Asn Asn Asp Met Ile Val Thr Asp Asn Asn Gly Ala Val Lys Phe 
465                 470                 475                 480 


Pro Gln Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr Cys Asp Asn 
                485                 490                 495     


Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys 
            500                 505                 510         


Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn Asp Glu Asn Ile 
        515                 520                 525             


Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His Asp Phe 
    530                 535                 540                 


Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys 
545                 550                 555                 560 


Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser Asp Glu Cys 
                565                 570                 575     


Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp 
            580                 585                 590         


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
        595                 600                 605             


Ile Pro Pro His Val Gln Lys Ser Val Asn Asn Asp Met Ile Val Thr 
    610                 615                 620                 


Asp Asn Asn Gly Ala Val Lys Phe Pro Gln Leu Cys Lys Phe Cys Asp 
625                 630                 635                 640 


Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys 
                645                 650                 655     


Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val 
            660                 665                 670         


Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp 
        675                 680                 685             


Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro 
    690                 695                 700                 


Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met 
705                 710                 715                 720 


Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu 
                725                 730                 735     


Glu Tyr Asn Thr Ser Asn Pro Asp 
            740                 


<210>  32
<211>  215
<212>  PRT
<213>  artificial

<220>
<223>  Ipilimumab light chain amino acid sequence

<400>  32

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 
1               5                   10                  15      


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser 
            20                  25                  30          


Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 
        35                  40                  45              


Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 
    50                  55                  60                  


Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 
65                  70                  75                  80  


Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 
                85                  90                  95      


Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala 
            100                 105                 110         


Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser 
        115                 120                 125             


Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu 
    130                 135                 140                 


Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser 
145                 150                 155                 160 


Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu 
                165                 170                 175     


Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val 
            180                 185                 190         


Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys 
        195                 200                 205             


Ser Phe Asn Arg Gly Glu Cys 
    210                 215 


<210>  33
<211>  448
<212>  PRT
<213>  artificial

<220>
<223>  Ipilimumab heavy chain amino acid sequence

<400>  33

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


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


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


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


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


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


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


Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 
        115                 120                 125             


Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 
    130                 135                 140                 


Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 
145                 150                 155                 160 


Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 
                165                 170                 175     


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


Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 
        195                 200                 205             


Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr 
    210                 215                 220                 


His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser 
225                 230                 235                 240 


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
                245                 250                 255     


Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
            260                 265                 270         


Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
        275                 280                 285             


Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 
    290                 295                 300                 


Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
305                 310                 315                 320 


Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
                325                 330                 335     


Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
            340                 345                 350         


Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys 
        355                 360                 365             


Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
    370                 375                 380                 


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
385                 390                 395                 400 


Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 
                405                 410                 415     


Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
            420                 425                 430         


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
        435                 440                 445             


<210>  34
<211>  123
<212>  PRT
<213>  artificial

<220>
<223>  Amino acid sequence of humanized 379D1, V1

<400>  34

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


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


Pro Val Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg Glu Pro Val 
        35                  40                  45              


Ala Ala Ile Thr Arg Gly Ala Arg Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Glu Ser Lys Asn Thr Val 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 Ala Thr Trp Gly Thr Thr Pro Pro Val Gln Pro Ile Ala Asp Phe 
            100                 105                 110         


Trp Asn Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120             


<210>  35
<211>  123
<212>  PRT
<213>  artificial

<220>
<223>  Amino acid sequence of humanized 379D1, V2

<400>  35

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


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


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


Ala Ala Ile Thr Arg Gly Ala Arg Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Glu Ser Lys Asn Thr Val 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 Ala Thr Trp Gly Thr Thr Pro Pro Val Gln Pro Ile Ala Asp Phe 
            100                 105                 110         


Trp Asn Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120             


<210>  36
<211>  123
<212>  PRT
<213>  artificial

<220>
<223>  Amino acid sequence of humanized 379D1, V3

<400>  36

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


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


Pro Val Gly Trp Phe Arg Gln Ala Pro Gly Lys Asp Arg Glu Pro Ile 
        35                  40                  45              


Ala Ala Ile Thr Arg Gly Ala Arg Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Glu Ser Lys Asn Thr Val 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 Ala Thr Trp Gly Thr Thr Pro Pro Val Gln Pro Ile Ala Asp Phe 
            100                 105                 110         


Trp Asn Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120             


<210>  37
<211>  123
<212>  PRT
<213>  artificial

<220>
<223>  Amino acid sequence of humanized 379D1, V4

<400>  37

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


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


Pro Val Gly Trp Phe Arg Gln Ala Pro Gly Lys Asp Arg Glu Pro Ile 
        35                  40                  45              


Ala Ala Ile Thr Arg Gly Ala Arg Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Ala Thr Trp Gly Thr Thr Pro Pro Val Gln Pro Ile Ala Asp Phe 
            100                 105                 110         


Trp Asn Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120             


<210>  38
<211>  123
<212>  PRT
<213>  artificial

<220>
<223>  Amino acid sequence of humanized 379D1, V5


<220>
<221>  MISC_FEATURE
<222>  (3)..(3)
<223>  X is L or V

<220>
<221>  MISC_FEATURE
<222>  (44)..(44)
<223>  X is G or D

<220>
<221>  MISC_FEATURE
<222>  (48)..(48)
<223>  X is V or I

<220>
<221>  MISC_FEATURE
<222>  (88)..(88)
<223>  X is A or P

<400>  38

Gln Val Xaa Val Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly 
1               5                   10                  15      


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


Pro Val Gly Trp Phe Arg Gln Ala Pro Gly Lys Xaa Arg Glu Pro Xaa 
        35                  40                  45              


Ala Ala Ile Thr Arg Gly Ala Arg Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Ala Thr Trp Gly Thr Thr Pro Pro Val Gln Pro Ile Ala Asp Phe 
            100                 105                 110         


Trp Asn Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120             


<210>  39
<211>  584
<212>  PRT
<213>  artificial

<220>
<223>  Amino acid sequence of ASKB1296 HV_379D1 fusion molecule


<220>
<221>  MISC_FEATURE
<222>  (31)..(31)
<223>  X is E or D

<220>
<221>  REPEAT
<222>  (455)..(459)
<223>  n is 0, 1, 2, 3, 4 or 5

<220>
<221>  MISC_FEATURE
<222>  (462)..(462)
<223>  X is L or V

<220>
<221>  MISC_FEATURE
<222>  (503)..(503)
<223>  X is G or D

<220>
<221>  MISC_FEATURE
<222>  (509)..(509)
<223>  X is V or I

<220>
<221>  MISC_FEATURE
<222>  (549)..(549)
<223>  X is A or P

<400>  39

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


Thr Val Lys Ile Ser Cys Thr Ala Ser Gly Phe Asn Ile Lys Xaa Asp 
            20                  25                  30          


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


Gly Arg Ile Asp Pro Ala Asn Ala Asn Thr Lys Tyr Ala Pro Lys Phe 
    50                  55                  60                  


Gln Asp Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asn Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Ala Arg Phe Gly Tyr Phe Tyr Gly Ser Ser Phe Tyr Ala Val Ala 
            100                 105                 110         


Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys 
        115                 120                 125             


Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly 
    130                 135                 140                 


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


Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr 
                165                 170                 175     


Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val 
            180                 185                 190         


Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn 
        195                 200                 205             


Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro 
    210                 215                 220                 


Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
225                 230                 235                 240 


Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
                245                 250                 255     


Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
            260                 265                 270         


Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
        275                 280                 285             


Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn 
    290                 295                 300                 


Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
305                 310                 315                 320 


Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
                325                 330                 335     


Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
            340                 345                 350         


Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn 
        355                 360                 365             


Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
    370                 375                 380                 


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
385                 390                 395                 400 


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
                405                 410                 415     


Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
            420                 425                 430         


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
        435                 440                 445             


Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly Ser Gln Val Xaa Val Val 
    450                 455                 460                 


Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly Ser Leu Arg Leu Ser 
465                 470                 475                 480 


Cys Ala Gly Ser Glu Arg Thr Phe Ser Ser Tyr Pro Val Gly Trp Phe 
                485                 490                 495     


Arg Gln Ala Pro Gly Lys Xaa Ala Ala Arg Glu Pro Xaa Ala Ala Ile 
            500                 505                 510         


Thr Arg Gly Ala Arg Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg 
        515                 520                 525             


Phe Thr Ile Ser Arg Asp Glu Ser Lys Asn Thr Val Tyr Leu Gln Met 
    530                 535                 540                 


Asn Ser Leu Arg Xaa Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala Thr 
545                 550                 555                 560 


Trp Gly Thr Thr Pro Pro Val Gln Pro Ile Ala Asp Phe Trp Asn Gln 
                565                 570                 575     


Gly Thr Leu Val Thr Val Ser Ser 
            580                 


<210>  40
<211>  355
<212>  PRT
<213>  artificial

<220>
<223>  Amino acid sequence of 379D1- IgG1 Fc fusion molecule, V1


<220>
<221>  MISC_FEATURE
<222>  (3)..(3)
<223>  X is L or V

<220>
<221>  MISC_FEATURE
<222>  (44)..(44)
<223>  X is G or D

<220>
<221>  MISC_FEATURE
<222>  (48)..(48)
<223>  X is V or I

<220>
<221>  MISC_FEATURE
<222>  (88)..(88)
<223>  X is A or P

<220>
<221>  REPEAT
<222>  (124)..(128)
<223>  n is 0, 1, 2, 3, 4 or 5

<400>  40

Gln Val Xaa Val Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly 
1               5                   10                  15      


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


Pro Val Gly Trp Phe Arg Gln Ala Pro Gly Lys Xaa Arg Glu Pro Xaa 
        35                  40                  45              


Ala Ala Ile Thr Arg Gly Ala Arg Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Ala Thr Trp Gly Thr Thr Pro Pro Val Gln Pro Ile Ala Asp Phe 
            100                 105                 110         


Trp Asn Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser 
        115                 120                 125             


Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
    130                 135                 140                 


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
145                 150                 155                 160 


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                165                 170                 175     


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
            180                 185                 190         


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
        195                 200                 205             


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
    210                 215                 220                 


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
225                 230                 235                 240 


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                245                 250                 255     


Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
            260                 265                 270         


Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
        275                 280                 285             


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
    290                 295                 300                 


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
305                 310                 315                 320 


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                325                 330                 335     


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
            340                 345                 350         


Pro Gly Lys 
        355 


<210>  41
<211>  483
<212>  PRT
<213>  artificial

<220>
<223>  Amino acid sequence of 379D1- IgG1 Fc fusion molecule, V2


<220>
<221>  MISC_FEATURE
<222>  (3)..(3)
<223>  X is L or V

<220>
<221>  MISC_FEATURE
<222>  (44)..(44)
<223>  X is G or D

<220>
<221>  MISC_FEATURE
<222>  (48)..(48)
<223>  X is G or D

<220>
<221>  MISC_FEATURE
<222>  (88)..(88)
<223>  X is A or P

<220>
<221>  REPEAT
<222>  (124)..(128)
<223>  n = 0, 1, 2, 3, 4 or 5

<220>
<221>  MISC_FEATURE
<222>  (131)..(131)
<223>  X is L or V

<220>
<221>  MISC_FEATURE
<222>  (172)..(172)
<223>  X is G or D

<220>
<221>  MISC_FEATURE
<222>  (176)..(176)
<223>  X is V or I

<220>
<221>  MISC_FEATURE
<222>  (216)..(216)
<223>  X is A or P

<220>
<221>  REPEAT
<222>  (254)..(258)
<223>  n = 0, 1, 2, 3, 4 or 5

<400>  41

Gln Val Xaa Val Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly 
1               5                   10                  15      


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


Pro Val Gly Trp Phe Arg Gln Ala Pro Gly Lys Xaa Arg Glu Pro Xaa 
        35                  40                  45              


Ala Ala Ile Thr Arg Gly Ala Arg Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Ala Thr Trp Gly Thr Thr Pro Pro Val Gln Pro Ile Ala Asp Phe 
            100                 105                 110         


Trp Asn Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser 
        115                 120                 125             


Gln Val Xaa Val Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly 
    130                 135                 140                 


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


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


Ala Ala Ile Thr Arg Gly Ala Arg Ser Thr Tyr Tyr Ala Asp Ser Val 
            180                 185                 190         


Lys Gly Arg Phe Thr Ile Ser Arg Asp Glu Ser Lys Asn Thr Val Tyr 
        195                 200                 205             


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


Ala Ala Thr Trp Gly Thr Thr Pro Pro Val Gln Pro Ile Ala Asp Phe 
225                 230                 235                 240 


Trp Asn Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser 
                245                 250                 255     


Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
            260                 265                 270         


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
        275                 280                 285             


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
    290                 295                 300                 


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
305                 310                 315                 320 


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
                325                 330                 335     


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
            340                 345                 350         


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
        355                 360                 365             


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
    370                 375                 380                 


Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
385                 390                 395                 400 


Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
                405                 410                 415     


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
            420                 425                 430         


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
        435                 440                 445             


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
    450                 455                 460                 


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
465                 470                 475                 480 


Pro Gly Lys 
            


<210>  42
<211>  355
<212>  PRT
<213>  artificial

<220>
<223>  Amino acid sequence of 379D1- IgG1 Fc fusion molecule, with knob 
       mutations, V3


<220>
<221>  MISC_FEATURE
<222>  (3)..(3)
<223>  X is L or V

<220>
<221>  MISC_FEATURE
<222>  (44)..(44)
<223>  X is G or D

<220>
<221>  MISC_FEATURE
<222>  (48)..(48)
<223>  X is V or I

<220>
<221>  MISC_FEATURE
<222>  (88)..(88)
<223>  X is A or P

<220>
<221>  REPEAT
<222>  (124)..(128)
<223>  n is 0, 1, 2, 3, 4 or 5

<400>  42

Gln Val Xaa Val Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly 
1               5                   10                  15      


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


Pro Val Gly Trp Phe Arg Gln Ala Pro Gly Lys Xaa Arg Glu Pro Xaa 
        35                  40                  45              


Ala Ala Ile Thr Arg Gly Ala Arg Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Ala Thr Trp Gly Thr Thr Pro Pro Val Gln Pro Ile Ala Asp Phe 
            100                 105                 110         


Trp Asn Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser 
        115                 120                 125             


Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
    130                 135                 140                 


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
145                 150                 155                 160 


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
                165                 170                 175     


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
            180                 185                 190         


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
        195                 200                 205             


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
    210                 215                 220                 


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
225                 230                 235                 240 


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
                245                 250                 255     


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
            260                 265                 270         


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
        275                 280                 285             


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
    290                 295                 300                 


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
305                 310                 315                 320 


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
                325                 330                 335     


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
            340                 345                 350         


Pro Gly Lys 
        355 


<210>  43
<211>  483
<212>  PRT
<213>  artificial

<220>
<223>  Amino acid sequence of 379D1- IgG1 Fc fusion molecule with knob 
       mutations, V4


<220>
<221>  MISC_FEATURE
<222>  (3)..(3)
<223>  X is L or V

<220>
<221>  MISC_FEATURE
<222>  (44)..(44)
<223>  X is G or D

<220>
<221>  MISC_FEATURE
<222>  (48)..(48)
<223>  X is V or I

<220>
<221>  MISC_FEATURE
<222>  (88)..(88)
<223>  X is A or P

<220>
<221>  REPEAT
<222>  (124)..(128)
<223>  n is 0, 1, 2, 3, 4 or 5

<220>
<221>  MISC_FEATURE
<222>  (131)..(131)
<223>  X is L or V

<220>
<221>  MISC_FEATURE
<222>  (172)..(172)
<223>  X is G or D

<220>
<221>  MISC_FEATURE
<222>  (176)..(176)
<223>  X is V or I

<220>
<221>  MISC_FEATURE
<222>  (216)..(216)
<223>  X is A or P

<220>
<221>  REPEAT
<222>  (252)..(256)
<223>  n is 0, 1, 2, 3, 4 or 5

<400>  43

Gln Val Xaa Val Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly 
1               5                   10                  15      


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


Pro Val Gly Trp Phe Arg Gln Ala Pro Gly Lys Xaa Arg Glu Pro Xaa 
        35                  40                  45              


Ala Ala Ile Thr Arg Gly Ala Arg Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Ala Thr Trp Gly Thr Thr Pro Pro Val Gln Pro Ile Ala Asp Phe 
            100                 105                 110         


Trp Asn Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser 
        115                 120                 125             


Gln Val Xaa Val Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Gly 
    130                 135                 140                 


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


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


Ala Ala Ile Thr Arg Gly Ala Arg Ser Thr Tyr Tyr Ala Asp Ser Val 
            180                 185                 190         


Lys Gly Arg Phe Thr Ile Ser Arg Asp Glu Ser Lys Asn Thr Val Tyr 
        195                 200                 205             


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


Ala Ala Thr Trp Gly Thr Thr Pro Pro Val Gln Pro Ile Ala Asp Phe 
225                 230                 235                 240 


Trp Asn Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser 
                245                 250                 255     


Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
            260                 265                 270         


Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
        275                 280                 285             


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
    290                 295                 300                 


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
305                 310                 315                 320 


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
                325                 330                 335     


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
            340                 345                 350         


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
        355                 360                 365             


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
    370                 375                 380                 


Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
385                 390                 395                 400 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
                405                 410                 415     


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
            420                 425                 430         


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
        435                 440                 445             


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
    450                 455                 460                 


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
465                 470                 475                 480 


Pro Gly Lys 
            


<210>  44
<211>  448
<212>  PRT
<213>  artificial

<220>
<223>  Ipilimumab heavy chain amino acid sequence with hole mutations

<400>  44

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


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


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


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


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


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


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


Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 
        115                 120                 125             


Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 
    130                 135                 140                 


Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 
145                 150                 155                 160 


Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 
                165                 170                 175     


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


Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 
        195                 200                 205             


Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr 
    210                 215                 220                 


His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser 
225                 230                 235                 240 


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
                245                 250                 255     


Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
            260                 265                 270         


Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
        275                 280                 285             


Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 
    290                 295                 300                 


Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
305                 310                 315                 320 


Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
                325                 330                 335     


Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu 
            340                 345                 350         


Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Ser Cys 
        355                 360                 365             


Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
    370                 375                 380                 


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
385                 390                 395                 400 


Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser 
                405                 410                 415     


Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
            420                 425                 430         


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
        435                 440                 445             


<210>  45
<211>  448
<212>  PRT
<213>  artificial

<220>
<223>  Ipilimumab heavy chain amino acid sequence with Knob mutations

<400>  45

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


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


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


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


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


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


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


Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 
        115                 120                 125             


Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 
    130                 135                 140                 


Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 
145                 150                 155                 160 


Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 
                165                 170                 175     


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


Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 
        195                 200                 205             


Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr 
    210                 215                 220                 


His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser 
225                 230                 235                 240 


Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
                245                 250                 255     


Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
            260                 265                 270         


Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
        275                 280                 285             


Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val 
    290                 295                 300                 


Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
305                 310                 315                 320 


Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr 
                325                 330                 335     


Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
            340                 345                 350         


Pro Pro Cys Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys 
        355                 360                 365             


Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
    370                 375                 380                 


Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
385                 390                 395                 400 


Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 
                405                 410                 415     


Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
            420                 425                 430         


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
        435                 440                 445             


<210>  46
<211>  485
<212>  PRT
<213>  artificial

<220>
<223>  (D1-V1)2-Fc, Hole

<400>  46

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


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


Pro Val Gly Trp Phe Arg Gln Ala Pro Gly Lys Gly Arg Glu Pro Val 
        35                  40                  45              


Ala Ala Ile Thr Arg Gly Ala Arg Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Glu Ser Lys Asn Thr Val 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 Ala Thr Trp Gly Thr Thr Pro Pro Val Gln Pro Ile Ala Asp Phe 
            100                 105                 110         


Trp Asn Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser 
        115                 120                 125             


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


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


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


Ala Ala Ile Thr Arg Gly Ala Arg Ser Thr Tyr Tyr Ala Asp Ser Val 
            180                 185                 190         


Lys Gly Arg Phe Thr Ile Ser Arg Asp Glu Ser Lys Asn Thr Val Tyr 
        195                 200                 205             


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


Ala Ala Thr Trp Gly Thr Thr Pro Pro Val Gln Pro Ile Ala Asp Phe 
225                 230                 235                 240 


Trp Asn Gln Gly Thr Leu Val Thr Val Ser Ser Gly Ser Glu Pro Lys 
                245                 250                 255     


Ser Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu 
            260                 265                 270         


Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
        275                 280                 285             


Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
    290                 295                 300                 


Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 
305                 310                 315                 320 


Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 
                325                 330                 335     


Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
            340                 345                 350         


Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 
        355                 360                 365             


Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
    370                 375                 380                 


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


Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
                405                 410                 415     


Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
            420                 425                 430         


Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu 
        435                 440                 445             


Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 
    450                 455                 460                 


Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
465                 470                 475                 480 


Leu Ser Pro Gly Lys 
                485 


