                         SEQUENCE LISTING

<110>  WuXi Biologics (Shanghai) CO., LTD
       WuXi Biologics Ireland Limited
 
<120>  Bispecific antibodies against PD-1 and LAG-3

<130>  AJ3297PCT2002

<160>  27    

<170>  PatentIn version 3.3

<210>  1
<211>  10
<212>  PRT
<213>  Artificial

<220>
<223>  HCDR3 of Anti-LAG-3 binding domain

<400>  1

Met Gln Leu Trp Ser Tyr Asp Val Asp Val 
1               5                   10  


<210>  2
<211>  16
<212>  PRT
<213>  Artificial

<220>
<223>  HCDR2 of Anti-LAG-3 binding domain

<400>  2

Ser Phe Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser 
1               5                   10                  15      


<210>  3
<211>  12
<212>  PRT
<213>  Artificial

<220>
<223>  HCDR1 of Anti-LAG-3 binding domain

<400>  3

Gly Asp Ser Ile Ser Ser Thr Ser Tyr Tyr Trp Gly 
1               5                   10          


<210>  4
<211>  10
<212>  PRT
<213>  Artificial

<220>
<223>  HCDR3 of Anti-PD-1 binding domain

<400>  4

Asn Arg Ala Gly Glu Gly Tyr Phe Asp Tyr 
1               5                   10  


<210>  5
<211>  17
<212>  PRT
<213>  Artificial

<220>
<223>  HCDR2 of Anti-PD-1 binding domain

<400>  5

Thr Ile Thr Gly Gly Gly Gly Ser Ile Tyr Tyr Ala Asp Ser Val Lys 
1               5                   10                  15      


Gly 
    


<210>  6
<211>  10
<212>  PRT
<213>  Artificial

<220>
<223>  HCDR1of Anti-PD-1 binding domain

<400>  6

Gly Phe Thr Phe Ser Ser His Ala Met Ser 
1               5                   10  


<210>  7
<211>  11
<212>  PRT
<213>  Artificial

<220>
<223>  LCDR3 of Anti-LAG-3 binding domain

<400>  7

Ser Ser Tyr Thr Ser Thr Thr Thr Leu Val Val 
1               5                   10      


<210>  8
<211>  7
<212>  PRT
<213>  Artificial

<220>
<223>  LCDR2 of Anti- LAG-3 binding domain

<400>  8

Asp Val Ser Glu Arg Pro Ser 
1               5           


<210>  9
<211>  14
<212>  PRT
<213>  Artificial

<220>
<223>  LCDR1of Anti- LAG-3 binding domain

<400>  9

Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asp Tyr Val Ala 
1               5                   10                  


<210>  10
<211>  8
<212>  PRT
<213>  Artificial

<220>
<223>  LCDR3 of Anti-PD-1 domain

<400>  10

Gln Val Trp Asp Ser Ile Trp Val 
1               5               


<210>  11
<211>  7
<212>  PRT
<213>  Artificial

<220>
<223>  LCDR2 of Anti-PD-1 domain

<400>  11

Arg Asp Ser Asn Arg Pro Ser 
1               5           


<210>  12
<211>  11
<212>  PRT
<213>  Artificial

<220>
<223>  LCDR1 of Anti-PD-1 binding domain

<400>  12

Gly Gly Asp Asn Ile Gly Asn Lys Asp Val His 
1               5                   10      


<210>  13
<211>  120
<212>  PRT
<213>  Artificial

<220>
<223>  VH of anti-LAG-3 binding domain

<400>  13

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


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


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


Trp Ile Gly Ser Phe Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser 
    50                  55                  60                  


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


Ser Leu Lys Leu Asn Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Met Gln Leu Trp Ser Tyr Asp Val Asp Val Trp Gly Gln 
            100                 105                 110         


Gly Thr Thr Val Thr Val Ser Ser 
        115                 120 


<210>  14
<211>  118
<212>  PRT
<213>  Artificial

<220>
<223>  VH of anti-PD-1 binding domain

<400>  14

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 His 
            20                  25                  30          


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


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


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


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


Ala Lys Asn Arg Ala Gly Glu Gly Tyr Phe Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Leu 
        115             


<210>  15
<211>  111
<212>  PRT
<213>  Artificial

<220>
<223>  VL of anti-LAG-3 binding domain

<400>  15

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          


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


Met Ile Tyr Asp Val Ser Glu 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 Thr 
                85                  90                  95      


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


<210>  16
<211>  105
<212>  PRT
<213>  Artificial

<220>
<223>  VL of anti-PD-1 binding domain

<400>  16

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


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


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


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


Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Ala Gln Ala Gly 
65                  70                  75                  80  


Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Ile Trp Val Phe 
                85                  90                  95      


Gly Gly Gly Thr Lys Leu Thr Val Leu 
            100                 105 


<210>  17
<211>  702
<212>  PRT
<213>  Artificial

<220>
<223>  first polypeptide

<400>  17

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 His 
            20                  25                  30          


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


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


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


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


Ala Lys Asn Arg Ala Gly Glu Gly Tyr Phe Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         


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


Val Ala Val Phe Glu Pro Ser Glu Ala Glu Ile Ser His Thr Gln Lys 
    130                 135                 140                 


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


Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr 
                165                 170                 175     


Asp Pro Gln Pro Leu Lys Glu Gln Pro Ala Leu Gln Asp Ser Arg Tyr 
            180                 185                 190         


Ala Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp Gln Asn Pro 
        195                 200                 205             


Arg Asn His Phe Arg Cys Gln Val Gln Phe Tyr Gly Leu Ser Glu Asn 
    210                 215                 220                 


Asp Glu Trp Thr Gln Asp Arg Ala Lys Pro Val Thr Gln Ile Val Ser 
225                 230                 235                 240 


Ala Glu Ala Trp Gly Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
                245                 250                 255     


Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu 
            260                 265                 270         


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


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


Trp Ile Gly Ser Phe Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser 
305                 310                 315                 320 


Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe 
                325                 330                 335     


Ser Leu Lys Leu Asn Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
            340                 345                 350         


Cys Ala Arg Met Gln Leu Trp Ser Tyr Asp Val Asp Val Trp Gly Gln 
        355                 360                 365             


Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 
    370                 375                 380                 


Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala 
385                 390                 395                 400 


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


Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 
            420                 425                 430         


Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 
        435                 440                 445             


Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys 
    450                 455                 460                 


Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro 
465                 470                 475                 480 


Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val 
                485                 490                 495     


Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
            500                 505                 510         


Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu 
        515                 520                 525             


Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
    530                 535                 540                 


Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser 
545                 550                 555                 560 


Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                565                 570                 575     


Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile 
            580                 585                 590         


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


Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
    610                 615                 620                 


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
625                 630                 635                 640 


Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                645                 650                 655     


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


Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
        675                 680                 685             


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 
    690                 695                 700         


<210>  18
<211>  200
<212>  PRT
<213>  Artificial

<220>
<223>  second polypeptide

<400>  18

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


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


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


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


Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Ala Gln Ala Gly 
65                  70                  75                  80  


Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Ile Trp Val Phe 
                85                  90                  95      


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


Pro Ala Val Tyr Gln Leu Arg Asp Ser Lys Ser Ser Asp Lys Ser Val 
        115                 120                 125             


Cys Leu Phe Thr Asp Phe Asp Ser Gln Thr Gln Val Ser Gln Ser Lys 
    130                 135                 140                 


Asp Ser Asp Val Tyr Ile Thr Asp Lys Cys Val Leu Asp Met Arg Ser 
145                 150                 155                 160 


Met Asp Phe Lys Ser Asn Ser Ala Val Ala Trp Ser Gln Lys Ser Asp 
                165                 170                 175     


Phe Ala Cys Ala Asn Ala Phe Gln Asn Ser Ile Ile Pro Glu Asp Thr 
            180                 185                 190         


Phe Phe Pro Ser Pro Glu Ser Ser 
        195                 200 


<210>  19
<211>  217
<212>  PRT
<213>  Artificial

<220>
<223>  third polypeptide

<400>  19

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          


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


Met Ile Tyr Asp Val Ser Glu 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 Thr 
                85                  90                  95      


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


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


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


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


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


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


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


Lys Thr Val Ala Pro Thr Glu Cys Ser 
    210                 215         


<210>  20
<211>  703
<212>  PRT
<213>  Artificial

<220>
<223>  first polypeptide of WBP3658-U6T1.G25-1.uIgG4.SP (YTE)

<400>  20

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 His 
            20                  25                  30          


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


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


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


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


Ala Lys Asn Arg Ala Gly Glu Gly Tyr Phe Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         


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


Val Ala Val Phe Glu Pro Ser Glu Ala Glu Ile Ser His Thr Gln Lys 
    130                 135                 140                 


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


Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys Thr 
                165                 170                 175     


Asp Pro Gln Pro Leu Lys Glu Gln Pro Ala Leu Gln Asp Ser Arg Tyr 
            180                 185                 190         


Ala Leu Ser Ser Arg Leu Arg Val Ser Ala Thr Phe Trp Gln Asn Pro 
        195                 200                 205             


Arg Asn His Phe Arg Cys Gln Val Gln Phe Tyr Gly Leu Ser Glu Asn 
    210                 215                 220                 


Asp Glu Trp Thr Gln Asp Arg Ala Lys Pro Val Thr Gln Ile Val Ser 
225                 230                 235                 240 


Ala Glu Ala Trp Gly Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
                245                 250                 255     


Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu 
            260                 265                 270         


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


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


Trp Ile Gly Ser Phe Tyr Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser 
305                 310                 315                 320 


Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe 
                325                 330                 335     


Ser Leu Lys Leu Asn Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
            340                 345                 350         


Cys Ala Arg Met Gln Leu Trp Ser Tyr Asp Val Asp Val Trp Gly Gln 
        355                 360                 365             


Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 
    370                 375                 380                 


Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala 
385                 390                 395                 400 


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


Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 
            420                 425                 430         


Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 
        435                 440                 445             


Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys 
    450                 455                 460                 


Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro 
465                 470                 475                 480 


Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val 
                485                 490                 495     


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


Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu 
        515                 520                 525             


Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
    530                 535                 540                 


Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser 
545                 550                 555                 560 


Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
                565                 570                 575     


Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile 
            580                 585                 590         


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


Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
    610                 615                 620                 


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
625                 630                 635                 640 


Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
                645                 650                 655     


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


Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
        675                 680                 685             


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 
    690                 695                 700             


<210>  21
<211>  127
<212>  PRT
<213>  Artificial

<220>
<223>  Engineered TCR beta domain

<400>  21

Asp Leu Lys Asn Val Phe Pro Pro Glu Val Ala Val Phe Glu Pro Ser 
1               5                   10                  15      


Glu Ala Glu Ile Ser His Thr Gln Lys Ala Thr Leu Val Cys Leu Ala 
            20                  25                  30          


Thr Gly Phe Tyr Pro Asp His Val Glu Leu Ser Trp Trp Val Asn Gly 
        35                  40                  45              


Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln Pro Leu Lys Glu 
    50                  55                  60                  


Gln Pro Ala Leu Gln Asp Ser Arg Tyr Ala Leu Ser Ser Arg Leu Arg 
65                  70                  75                  80  


Val Ser Ala Thr Phe Trp Gln Asn Pro Arg Asn His Phe Arg Cys Gln 
                85                  90                  95      


Val Gln Phe Tyr Gly Leu Ser Glu Asn Asp Glu Trp Thr Gln Asp Arg 
            100                 105                 110         


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


<210>  22
<211>  93
<212>  PRT
<213>  Artificial

<220>
<223>  Engineered TCR alpha domain

<400>  22

Ile Gln Asn Pro Asp Pro Ala Val Tyr Gln Leu Arg Asp Ser Lys Ser 
1               5                   10                  15      


Ser Asp Lys Ser Val Cys Leu Phe Thr Asp Phe Asp Ser Gln Thr Gln 
            20                  25                  30          


Val Ser Gln Ser Lys Asp Ser Asp Val Tyr Ile Thr Asp Lys Cys Val 
        35                  40                  45              


Leu Asp Met Arg Ser Met Asp Phe Lys Ser Asn Ser Ala Val Ala Trp 
    50                  55                  60                  


Ser Gln Lys Ser Asp Phe Ala Cys Ala Asn Ala Phe Gln Asn Ser Ile 
65                  70                  75                  80  


Ile Pro Glu Asp Thr Phe Phe Pro Ser Pro Glu Ser Ser 
                85                  90              


<210>  23
<211>  10
<212>  PRT
<213>  Artificial

<220>
<223>  Linker between TCR beta domain and VH of anti-LAG-3

       binding domain

<400>  23

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


<210>  24
<211>  1
<212>  PRT
<213>  Artificial

<220>
<223>  Linker between TCR beta domain and VH of anti-PD-1

       binding domain

<400>  24

Glu 
1   


<210>  25
<211>  2
<212>  PRT
<213>  Artificial

<220>
<223>  Linker between VL of anti-PD-1

       binding domain and TCR alpha domain

<400>  25

Pro Asp 
1       


<210>  26
<211>  93
<212>  PRT
<213>  Homo sapiens

<400>  26

Ile Gln Asn Pro Asp Pro Ala Val Tyr Gln Leu Arg Asp Ser Lys Ser 
1               5                   10                  15      


Ser Asp Lys Ser Val Cys Leu Phe Thr Asp Phe Asp Ser Gln Thr Asn 
            20                  25                  30          


Val Ser Gln Ser Lys Asp Ser Asp Val Tyr Ile Thr Asp Lys Thr Val 
        35                  40                  45              


Leu Asp Met Arg Ser Met Asp Phe Lys Ser Asn Ser Ala Val Ala Trp 
    50                  55                  60                  


Ser Asn Lys Ser Asp Phe Ala Cys Ala Asn Ala Phe Asn Asn Ser Ile 
65                  70                  75                  80  


Ile Pro Glu Asp Thr Phe Phe Pro Ser Pro Glu Ser Ser 
                85                  90              


<210>  27
<211>  127
<212>  PRT
<213>  Homo sapiens

<400>  27

Asp Leu Lys Asn Val Phe Pro Pro Lys Val Ala Val Phe Glu Pro Ser 
1               5                   10                  15      


Glu Ala Glu Ile Ser His Thr Gln Lys Ala Thr Leu Val Cys Leu Ala 
            20                  25                  30          


Thr Gly Phe Tyr Pro Asp His Val Glu Leu Ser Trp Trp Val Asn Gly 
        35                  40                  45              


Lys Glu Val His Ser Gly Val Ser Thr Asp Pro Gln Pro Leu Lys Glu 
    50                  55                  60                  


Gln Pro Ala Leu Asn Asp Ser Arg Tyr Cys Leu Ser Ser Arg Leu Arg 
65                  70                  75                  80  


Val Ser Ala Thr Phe Trp Gln Asn Pro Arg Asn His Phe Arg Cys Gln 
                85                  90                  95      


Val Gln Phe Tyr Gly Leu Ser Glu Asn Asp Glu Trp Thr Gln Asp Arg 
            100                 105                 110         


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


