                         SEQUENCE LISTING

<110>  NANJING LEADS BIOLABS CO., LTD.
 
<120>  RECOMBINANT PROTEIN TARGETING PD-1 AND TGF

<130>  PF 200614PCT

<150>  US 62/924,154
<151>  2019-10-21

<160>  25    

<170>  PatentIn version 3.3

<210>  1
<211>  136
<212>  PRT
<213>  Artificial

<220>
<223>  TGFRII extracellular domain

<400>  1

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


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


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


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


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


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


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


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


Glu Tyr Asn Thr Ser Asn Pro Asp 
    130                 135     


<210>  2
<211>  126
<212>  PRT
<213>  Artificial

<220>
<223>  Anti-PD-1 antibody Heavy chain variable region

<400>  2

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


Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Pro Phe Gln Ser Tyr 
            20                  25                  30          


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


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


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


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


Ala Arg Gly Ser Tyr Ser Ser Gly Trp Asp Tyr Tyr Tyr Tyr Tyr Gly 
            100                 105                 110         


Met Asp Val Trp Gly Lys Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125     


<210>  3
<211>  112
<212>  PRT
<213>  Artificial

<220>
<223>  Anti-PD-1 antibody Light chain variable region

<400>  3

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


Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser 
            20                  25                  30          


Gln Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


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


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala 
                85                  90                  95      


Leu Gln Thr Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105                 110         


<210>  4
<211>  456
<212>  PRT
<213>  Artificial

<220>
<223>  Anti-PD-1 antibody Heavy chain

<400>  4

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


Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Pro Phe Gln Ser Tyr 
            20                  25                  30          


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


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


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


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


Ala Arg Gly Ser Tyr Ser Ser Gly Trp Asp Tyr Tyr Tyr Tyr Tyr Gly 
            100                 105                 110         


Met Asp Val Trp Gly Lys Gly Thr Leu Val Thr Val Ser Ser Ala Ser 
        115                 120                 125             


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


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


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


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


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


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


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


Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
                245                 250                 255     


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


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


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


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


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


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


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


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


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
385                 390                 395                 400 


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


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


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


Ser Leu Ser Leu Ser Pro Gly Ala 
    450                 455     


<210>  5
<211>  219
<212>  PRT
<213>  Artificial

<220>
<223>  Anti-PD-1 antibody Light chain

<400>  5

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


Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser 
            20                  25                  30          


Gln Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


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


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala 
                85                  90                  95      


Leu Gln Thr Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105                 110         


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


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


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


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


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


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


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


<210>  6
<211>  11
<212>  PRT
<213>  Artificial

<220>
<223>  Linker

<400>  6

Ser Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser 
1               5                   10      


<210>  7
<211>  19
<212>  PRT
<213>  Artificial

<220>
<223>  Linker

<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 
            


<210>  8
<211>  14
<212>  PRT
<213>  Artificial

<220>
<223>  Linker

<400>  8

Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Gly Gly Pro Ser 
1               5                   10                  


<210>  9
<211>  20
<212>  PRT
<213>  Artificial

<220>
<223>  Linker

<400>  9

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


Gly Gly Gly Ser 
            20  


<210>  10
<211>  603
<212>  PRT
<213>  Artificial

<220>
<223>  Heavy chain-linker-TGFRII extracellular domain

<400>  10

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


Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Pro Phe Gln Ser Tyr 
            20                  25                  30          


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


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


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


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


Ala Arg Gly Ser Tyr Ser Ser Gly Trp Asp Tyr Tyr Tyr Tyr Tyr Gly 
            100                 105                 110         


Met Asp Val Trp Gly Lys Gly Thr Leu Val Thr Val Ser Ser Ala Ser 
        115                 120                 125             


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


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


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


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


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


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


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


Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
                245                 250                 255     


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


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


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


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


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


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


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


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


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
385                 390                 395                 400 


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


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


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


Ser Leu Ser Leu Ser Pro Gly Ala Ser Pro Ala Pro Glu Leu Leu Gly 
    450                 455                 460                 


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


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


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


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


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


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


Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr 
                565                 570                 575     


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


Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp 
        595                 600             


<210>  11
<211>  611
<212>  PRT
<213>  Artificial

<220>
<223>  Heavy chain-linker-TGFRII extracellular domain

<400>  11

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


Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Pro Phe Gln Ser Tyr 
            20                  25                  30          


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


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


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


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


Ala Arg Gly Ser Tyr Ser Ser Gly Trp Asp Tyr Tyr Tyr Tyr Tyr Gly 
            100                 105                 110         


Met Asp Val Trp Gly Lys Gly Thr Leu Val Thr Val Ser Ser Ala Ser 
        115                 120                 125             


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


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


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


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


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


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


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


Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
                245                 250                 255     


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


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


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


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


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


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


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


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


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
385                 390                 395                 400 


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


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


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


Ser Leu Ser Leu Ser Pro Gly Ala Asp Lys Thr His Thr Cys Pro Pro 
    450                 455                 460                 


Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Ile Pro Pro His Val 
465                 470                 475                 480 


Gln Lys Ser Val Asn Asn Asp Met Ile Val Thr Asp Asn Asn Gly Ala 
                485                 490                 495     


Val Lys Phe Pro Gln Leu Cys Lys Phe Cys Asp Val Arg Phe Ser Thr 
            500                 505                 510         


Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile 
        515                 520                 525             


Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn Asp 
    530                 535                 540                 


Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr 
545                 550                 555                 560 


His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys 
                565                 570                 575     


Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser 
            580                 585                 590         


Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser 
        595                 600                 605             


Asn Pro Asp 
    610     


<210>  12
<211>  606
<212>  PRT
<213>  Artificial

<220>
<223>  Heavy chain-linker-TGFRII extracellular domain

<400>  12

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


Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Pro Phe Gln Ser Tyr 
            20                  25                  30          


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


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


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


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


Ala Arg Gly Ser Tyr Ser Ser Gly Trp Asp Tyr Tyr Tyr Tyr Tyr Gly 
            100                 105                 110         


Met Asp Val Trp Gly Lys Gly Thr Leu Val Thr Val Ser Ser Ala Ser 
        115                 120                 125             


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


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


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


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


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


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


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


Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
                245                 250                 255     


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


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


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


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


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


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


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


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


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
385                 390                 395                 400 


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


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


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


Ser Leu Ser Leu Ser Pro Gly Ala Ser Lys Tyr Gly Pro Pro Cys Pro 
    450                 455                 460                 


Pro Cys Gly Gly Pro Ser Ile Pro Pro His Val Gln Lys Ser Val Asn 
465                 470                 475                 480 


Asn Asp Met Ile Val Thr Asp Asn Asn Gly Ala Val Lys Phe Pro Gln 
                485                 490                 495     


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


Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln 
        515                 520                 525             


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


Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu 
545                 550                 555                 560 


Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro 
                565                 570                 575     


Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp 
            580                 585                 590         


Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp 
        595                 600                 605     


<210>  13
<211>  612
<212>  PRT
<213>  Artificial

<220>
<223>  Heavy chain-linker-TGFRII extracellular domain

<400>  13

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


Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Pro Phe Gln Ser Tyr 
            20                  25                  30          


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


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


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


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


Ala Arg Gly Ser Tyr Ser Ser Gly Trp Asp Tyr Tyr Tyr Tyr Tyr Gly 
            100                 105                 110         


Met Asp Val Trp Gly Lys Gly Thr Leu Val Thr Val Ser Ser Ala Ser 
        115                 120                 125             


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


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


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


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


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


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


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


Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
                245                 250                 255     


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


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


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


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


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


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


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


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


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
385                 390                 395                 400 


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


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


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


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


Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile Pro Pro His 
465                 470                 475                 480 


Val Gln Lys Ser Val Asn Asn Asp Met Ile Val Thr Asp Asn Asn Gly 
                485                 490                 495     


Ala Val Lys Phe Pro Gln Leu Cys Lys Phe Cys Asp Val Arg Phe Ser 
            500                 505                 510         


Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser 
        515                 520                 525             


Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn 
    530                 535                 540                 


Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro 
545                 550                 555                 560 


Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met 
                565                 570                 575     


Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser 
            580                 585                 590         


Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr 
        595                 600                 605             


Ser Asn Pro Asp 
    610         


<210>  14
<211>  456
<212>  PRT
<213>  Artificial

<220>
<223>  Positive control- anti-PD-1 antibody 21F12-1F6 Heavy chain

<400>  14

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


Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Ile Phe Gln Ser Tyr 
            20                  25                  30          


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


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


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


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


Ala Arg Gly Ser Tyr Ser Ser Gly Trp Asp Tyr Tyr Tyr Tyr Tyr Gly 
            100                 105                 110         


Met Asp Val Trp Gly Lys Gly Thr Leu Val Thr Val Ser Ser Ala Ser 
        115                 120                 125             


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


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


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


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


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


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


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


Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
                245                 250                 255     


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


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


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


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


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


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


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


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


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
385                 390                 395                 400 


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


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


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


Ser Leu Ser Leu Ser Pro Gly Lys 
    450                 455     


<210>  15
<211>  607
<212>  PRT
<213>  Artificial

<220>
<223>  Anti-PD-L1 antibody M7824 Heavy chain

<400>  15

Glu Val Gln Leu Leu 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 Ser Tyr 
            20                  25                  30          


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


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


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


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


Ala Arg Ile Lys Leu Gly Thr Val Thr Thr Val Asp Tyr Trp Gly Gln 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Ser Gly Gly Gly Gly Ser Gly Ile Pro Pro His Val Gln Lys Ser Val 
465                 470                 475                 480 


Asn Asn Asp Met Ile Val Thr Asp Asn Asn Gly Ala Val Lys Phe Pro 
                485                 490                 495     


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


Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro 
        515                 520                 525             


Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn Asp Glu Asn Ile Thr 
    530                 535                 540                 


Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro Tyr His Asp Phe Ile 
545                 550                 555                 560 


Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys Lys 
                565                 570                 575     


Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser Ser Asp Glu Cys Asn 
            580                 585                 590         


Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp 
        595                 600                 605         


<210>  16
<211>  216
<212>  PRT
<213>  Artificial

<220>
<223>  Anti-PD-L1 antibody M7824 Light chain

<400>  16

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


Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr 
            20                  25                  30          


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


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


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


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


Ser Thr Arg Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu Gly Gln 
            100                 105                 110         


Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Pro Ser Ser Glu Glu 
        115                 120                 125             


Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr 
    130                 135                 140                 


Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro Val Lys 
145                 150                 155                 160 


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


Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His 
            180                 185                 190         


Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys 
        195                 200                 205             


Thr Val Ala Pro Thr Glu Cys Ser 
    210                 215     


<210>  17
<211>  290
<212>  PRT
<213>  Artificial

<220>
<223>  Human PD-L1

<400>  17

Met Arg Ile Phe Ala Val Phe Ile Phe Met Thr Tyr Trp His Leu Leu 
1               5                   10                  15      


Asn Ala Phe Thr Val Thr Val Pro Lys Asp Leu Tyr Val Val Glu Tyr 
            20                  25                  30          


Gly Ser Asn Met Thr Ile Glu Cys Lys Phe Pro Val Glu Lys Gln Leu 
        35                  40                  45              


Asp Leu Ala Ala Leu Ile Val Tyr Trp Glu Met Glu Asp Lys Asn Ile 
    50                  55                  60                  


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


Tyr Arg Gln Arg Ala Arg Leu Leu Lys Asp Gln Leu Ser Leu Gly Asn 
                85                  90                  95      


Ala Ala Leu Gln Ile Thr Asp Val Lys Leu Gln Asp Ala Gly Val Tyr 
            100                 105                 110         


Arg Cys Met Ile Ser Tyr Gly Gly Ala Asp Tyr Lys Arg Ile Thr Val 
        115                 120                 125             


Lys Val Asn Ala Pro Tyr Asn Lys Ile Asn Gln Arg Ile Leu Val Val 
    130                 135                 140                 


Asp Pro Val Thr Ser Glu His Glu Leu Thr Cys Gln Ala Glu Gly Tyr 
145                 150                 155                 160 


Pro Lys Ala Glu Val Ile Trp Thr Ser Ser Asp His Gln Val Leu Ser 
                165                 170                 175     


Gly Lys Thr Thr Thr Thr Asn Ser Lys Arg Glu Glu Lys Leu Phe Asn 
            180                 185                 190         


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


Cys Thr Phe Arg Arg Leu Asp Pro Glu Glu Asn His Thr Ala Glu Leu 
    210                 215                 220                 


Val Ile Pro Glu Leu Pro Leu Ala His Pro Pro Asn Glu Arg Thr His 
225                 230                 235                 240 


Leu Val Ile Leu Gly Ala Ile Leu Leu Cys Leu Gly Val Ala Leu Thr 
                245                 250                 255     


Phe Ile Phe Arg Leu Arg Lys Gly Arg Met Met Asp Val Lys Lys Cys 
            260                 265                 270         


Gly Ile Gln Asp Thr Asn Ser Lys Lys Gln Ser Asp Thr His Leu Glu 
        275                 280                 285             


Glu Thr 
    290 


<210>  18
<211>  367
<212>  PRT
<213>  Artificial

<220>
<223>  OKT3-scFv

<400>  18

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


Val His Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Ala Arg 
            20                  25                  30          


Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe 
        35                  40                  45              


Thr Arg Tyr Thr Met His Trp Val Lys Gln Arg Pro Gly Gln Gly Leu 
    50                  55                  60                  


Glu Trp Ile Gly Tyr Ile Asn Pro Ser Arg Gly Tyr Thr Asn Tyr Asn 
65                  70                  75                  80  


Gln Lys Phe Lys Asp Lys Ala Thr Leu Thr Thr Asp Lys Ser Ser Ser 
                85                  90                  95      


Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val 
            100                 105                 110         


Tyr Tyr Cys Ala Arg Tyr Tyr Asp Asp His Tyr Cys Leu Asp Tyr Trp 
        115                 120                 125             


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


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ile Val Leu Thr Gln Ser 
145                 150                 155                 160 


Pro Ala Ile Met Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys 
                165                 170                 175     


Ser Ala Ser Ser Ser Val Ser Tyr Met Asn Trp Tyr Gln Gln Lys Ser 
            180                 185                 190         


Gly Thr Ser Pro Lys Arg Trp Ile Tyr Asp Thr Ser Lys Leu Ala Ser 
        195                 200                 205             


Gly Val Pro Ala His Phe Arg Gly Ser Gly Ser Gly Thr Ser Tyr Ser 
    210                 215                 220                 


Leu Thr Ile Ser Gly Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys 
225                 230                 235                 240 


Gln Gln Trp Ser Ser Asn Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu 
                245                 250                 255     


Glu Ile Asn Ser Ser Val Val Pro Val Leu Gln Lys Val Asn Ser Thr 
            260                 265                 270         


Thr Thr Lys Pro Val Leu Arg Thr Pro Ser Pro Val His Pro Thr Gly 
        275                 280                 285             


Thr Ser Gln Pro Gln Arg Pro Glu Asp Cys Arg Pro Arg Gly Ser Val 
    290                 295                 300                 


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


Leu Ala Gly Ile Cys Val Ala Leu Leu Leu Ser Leu Ile Ile Thr Leu 
                325                 330                 335     


Ile Cys Tyr His Arg Ser Arg Lys Arg Val Cys Lys Cys Pro Arg Pro 
            340                 345                 350         


Leu Val Arg Gln Glu Gly Lys Pro Arg Pro Ser Glu Lys Ile Val 
        355                 360                 365         


<210>  19
<211>  288
<212>  PRT
<213>  Artificial

<220>
<223>  Human PD-1

<400>  19

Met Gln Ile Pro Gln Ala Pro Trp Pro Val Val Trp Ala Val Leu Gln 
1               5                   10                  15      


Leu Gly Trp Arg Pro Gly Trp Phe Leu Asp Ser Pro Asp Arg Pro Trp 
            20                  25                  30          


Asn Pro Pro Thr Phe Ser Pro Ala Leu Leu Val Val Thr Glu Gly Asp 
        35                  40                  45              


Asn Ala Thr Phe Thr Cys Ser Phe Ser Asn Thr Ser Glu Ser Phe Val 
    50                  55                  60                  


Leu Asn Trp Tyr Arg Met Ser Pro Ser Asn Gln Thr Asp Lys Leu Ala 
65                  70                  75                  80  


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


Val Thr Gln Leu Pro Asn Gly Arg Asp Phe His Met Ser Val Val Arg 
            100                 105                 110         


Ala Arg Arg Asn Asp Ser Gly Thr Tyr Leu Cys Gly Ala Ile Ser Leu 
        115                 120                 125             


Ala Pro Lys Ala Gln Ile Lys Glu Ser Leu Arg Ala Glu Leu Arg Val 
    130                 135                 140                 


Thr Glu Arg Arg Ala Glu Val Pro Thr Ala His Pro Ser Pro Ser Pro 
145                 150                 155                 160 


Arg Pro Ala Gly Gln Phe Gln Thr Leu Val Val Gly Val Val Gly Gly 
                165                 170                 175     


Leu Leu Gly Ser Leu Val Leu Leu Val Trp Val Leu Ala Val Ile Cys 
            180                 185                 190         


Ser Arg Ala Ala Arg Gly Thr Ile Gly Ala Arg Arg Thr Gly Gln Pro 
        195                 200                 205             


Leu Lys Glu Asp Pro Ser Ala Val Pro Val Phe Ser Val Asp Tyr Gly 
    210                 215                 220                 


Glu Leu Asp Phe Gln Trp Arg Glu Lys Thr Pro Glu Pro Pro Val Pro 
225                 230                 235                 240 


Cys Val Pro Glu Gln Thr Glu Tyr Ala Thr Ile Val Phe Pro Ser Gly 
                245                 250                 255     


Met Gly Thr Ser Ser Pro Ala Arg Arg Gly Ser Ala Asp Gly Pro Arg 
            260                 265                 270         


Ser Ala Gln Pro Leu Arg Pro Glu Asp Gly His Cys Ser Trp Pro Leu 
        275                 280                 285             


<210>  20
<211>  440
<212>  PRT
<213>  Artificial

<220>
<223>  Heavy chain for Nivolumab

<400>  20

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>  21
<211>  214
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain for Nivolumab

<400>  21

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>  22
<211>  446
<212>  PRT
<213>  Artificial

<220>
<223>  Heavy chain of IgG Control

<400>  22

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


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


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


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


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


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


Ala Lys Val Ala Val Ala Gly Thr His Phe Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  23
<211>  214
<212>  PRT
<213>  Artificial

<220>
<223>  Light chain of IgG Control

<400>  23

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


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


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


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


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


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


Thr Phe Gly Gly 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>  24
<211>  446
<212>  PRT
<213>  Artificial

<220>
<223>  IgG4 control heavy chain

<400>  24

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


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


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


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


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


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


Ala Lys Val Ala Val Ala Gly Thr His Phe Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  25
<211>  214
<212>  PRT
<213>  Artificial

<220>
<223>  IgG4 control Light chain

<400>  25

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


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


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


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


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


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


Thr Phe Gly Gly 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                 


