                         SEQUENCE LISTING

<110>  Biosion Inc.
 
<120>  PD-1 BINDING ANTIBODIES AND USES THEREOF

<130>  55532 00039

<150>  US 63/072,421
<151>  2020-08-31

<160>  42    

<170>  PatentIn version 3.5

<210>  1
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH CDR1 of mouse, chimeric and humanized E1A9C8A7 antibodies, and
       mouse E2G4E10B7

<400>  1

Asp Tyr Val Met His 
1               5   


<210>  2
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH CDR1 of mouse E1G5D1H1

<400>  2

Asp Phe Tyr Met Tyr 
1               5   


<210>  3
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH CDR2 of mouse, chimeric and humanized E1A9C8A7 antibodies

<400>  3

Val Ile Ser Thr Tyr His Ile Pro Ala Val Tyr Asn Gln Lys Phe Lys 
1               5                   10                  15      


Gly 
    


<210>  4
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH CDR2 of mouse E2G4E10B7

<400>  4

Val Ile Ser Thr His Phe Gly Asp Gly Val Tyr Asn Gln Lys Phe Lys 
1               5                   10                  15      


Gly 
    


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

<220>
<223>  VH CDR2 of mouse E1G5D1H1

<400>  5

Thr Ile Ser Asn Ser Gly Thr Gln Thr Tyr Tyr Leu Asp Ser Val Lys 
1               5                   10                  15      


Gly 
    


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

<220>
<223>  VH CDR3 of mouse, chimeric and humanized E1A9C8A7 antibodies, and
       mouse E2G4E10B7


<220>
<221>  misc_feature
<222>  (5)..(5)
<223>  Xaa can be Asp or Glu

<220>
<221>  misc_feature
<222>  (7)..(7)
<223>  Xaa can be Tyr or Trp

<400>  6

Glu Val Tyr Gly Xaa Ser Xaa Tyr Phe Asp Val 
1               5                   10      


<210>  7
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH CDR3 of mouse E1G5D1H1

<400>  7

Asp Tyr Tyr Arg Tyr Asp Ser Trp Tyr Phe Asp Val 
1               5                   10          


<210>  8
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VL CDR1 of mouse, chimeric and humanized E1A9C8A7 antibodies, and
       mouse E2G4E10B7


<220>
<221>  misc_feature
<222>  (6)..(6)
<223>  Xaa can be Ile or Leu

<220>
<221>  misc_feature
<222>  (10)..(10)
<223>  Xaa can be Asn, Ala, or Asp

<400>  8

Arg Ser Ser Gln Ser Xaa Val His Ser Xaa Gly Asn Thr Tyr Leu Glu 
1               5                   10                  15      


<210>  9
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VL CDR1 of mouse E1G5D1H1

<400>  9

Arg Ala Ser Glu Ser Val Asp Phe Tyr Gly Thr Ser Leu Met Gln 
1               5                   10                  15  


<210>  10
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VL CDR2 of mouse, chimeric and humanized E1A9C8A7 antibodies, and
       mouse E2G4E10B7

<400>  10

Lys Val Ser Asn Arg Phe Ser 
1               5           


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

<220>
<223>  VL CDR2 of mouse E1G5D1H1

<400>  11

Ala Ala Ser Asn Val Glu Ser 
1               5           


<210>  12
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VL CDR3 of mouse, chimeric and humanized E1A9C8A7 antibodies, and
       mouse E2G4E10B7

<400>  12

Phe Gln Gly Ser His Val Pro Tyr Thr 
1               5                   


<210>  13
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VL CDR3 of mouse E1G5D1H1

<400>  13

Gln Gln Ser Arg Lys Val Pro Trp Thr 
1               5                   


<210>  14
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH of mouse and chimeric E1A9C8A7 antibodies

<400>  14

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


Ser Val Arg Ile Ser Cys Lys Gly Ser Gly Tyr Thr Phe Ser Asp Tyr 
            20                  25                  30          


Val Met His Trp Met Lys Gln Ser His Gly Glu Ser Leu Glu Trp Ile 
        35                  40                  45              


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


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


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


Ala Arg Glu Val Tyr Gly Asp Ser Tyr Tyr Phe Asp Val Trp Gly Ala 
            100                 105                 110         


Gly Thr Thr Val Thr Val Ser Ser 
        115                 120 


<210>  15
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH of huE1A9C8A7-V1 to huE1A9C8A7-V5


<220>
<221>  misc_feature
<222>  (30)..(30)
<223>  Xaa can be Ser or Thr

<220>
<221>  misc_feature
<222>  (37)..(37)
<223>  Xaa can be Met or Val

<220>
<221>  misc_feature
<222>  (74)..(74)
<223>  Xaa can be Lys or Thr

<400>  15

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


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


Val Met His Trp Xaa Arg Gln Ala Pro Gly Gln Ser Leu Glu Trp Ile 
        35                  40                  45              


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


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


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


Ala Arg Glu Val Tyr Gly Asp Ser Tyr Tyr Phe Asp Val Trp Gly Gln 
            100                 105                 110         


Gly Thr Thr Val Thr Val Ser Ser 
        115                 120 


<210>  16
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH of huE1A9C8A7-V6 to huE1A9C8A7-V8


<220>
<221>  misc_feature
<222>  (20)..(20)
<223>  Xaa can be Val or Ile

<220>
<221>  misc_feature
<222>  (44)..(44)
<223>  Xaa can be Ser or Gly

<220>
<221>  misc_feature
<222>  (48)..(48)
<223>  Xaa can be Ile or Met

<400>  16

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


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


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


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


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


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


Ala Arg Glu Val Tyr Gly Asp Ser Tyr Tyr Phe Asp Val Trp Gly Gln 
            100                 105                 110         


Gly Thr Thr Val Thr Val Ser Ser 
        115                 120 


<210>  17
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH of huE1A9C8A7-V9 to huE1A9C8A7-V11


<220>
<221>  misc_feature
<222>  (67)..(67)
<223>  Xaa can be Arg or Lys

<220>
<221>  misc_feature
<222>  (68)..(68)
<223>  Xaa can be Ala or Val

<220>
<221>  misc_feature
<222>  (72)..(72)
<223>  Xaa can be Val or Arg

<400>  17

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


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


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


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


Lys Gly Xaa Xaa Thr Met Thr Xaa Asp Thr Ser Thr Ser Thr Val Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Val Tyr Gly Asp Ser Tyr Tyr Phe Asp Val Trp Gly Gln 
            100                 105                 110         


Gly Thr Thr Val Thr Val Ser Ser 
        115                 120 


<210>  18
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH of mouse E2G4E10B7

<400>  18

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


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


Val Met His Trp Val Arg Gln Ser His Ala Lys Ser Leu Glu Trp Ile 
        35                  40                  45              


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


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


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


Ala Arg Glu Val Tyr Gly Asp Ser Trp Tyr Phe Asp Val Trp Gly Ala 
            100                 105                 110         


Gly Thr Thr Val Thr Val Ser Ser 
        115                 120 


<210>  19
<211>  121
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH of mouse E1G5D1H1

<400>  19

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


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


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


Ala Thr Ile Ser Asn Ser Gly Thr Gln Thr Tyr Tyr Leu Asp Ser Val 
    50                  55                  60                  


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


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


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


Ala Gly Thr Thr Val Thr Val Ser Ser 
        115                 120     


<210>  20
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VL for mouse and chimeric E1A9C8A7

<400>  20

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


Asp Gln Val Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His Ser 
            20                  25                  30          


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


Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe 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 Leu Gly Val Tyr Tyr Cys Phe Gln Gly 
                85                  90                  95      


Ser His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


<210>  21
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VL of huE1A9C8A7-V1 - huE1A9C8A7-V11, and huE1A9C8A7-V8-3


<220>
<221>  misc_feature
<222>  (33)..(33)
<223>  Xaa can be Asn or Ala

<400>  21

Asp Ile Val Met Thr Gln Thr 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 Ile Val His Ser 
            20                  25                  30          


Xaa Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


Pro Gln Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe 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 Phe Gln Gly 
                85                  90                  95      


Ser His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105                 110         


<210>  22
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VL of mouse E2G4E10B7

<400>  22

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


Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 
            20                  25                  30          


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


Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe 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 Leu Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Phe Gln Gly 
                85                  90                  95      


Ser His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


<210>  23
<211>  111
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VL of mouse E1G5D1H1

<400>  23

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


Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser Val Asp Phe Tyr 
            20                  25                  30          


Gly Thr Ser Leu Met Gln Trp Phe Gln Leu Lys Pro Gly Gln Pro Pro 
        35                  40                  45              


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


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


Pro Val Glu Glu Asp Asp Ile Ala Met Tyr Phe Cys Gln Gln Ser Arg 
                85                  90                  95      


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


<210>  24
<211>  327
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Heavy chain constant region for chimeric and humanized antibodies

<400>  24

Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg 
1               5                   10                  15      


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


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


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


Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr 
65                  70                  75                  80  


Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys 
                85                  90                  95      


Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro 
            100                 105                 110         


Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
        115                 120                 125             


Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
    130                 135                 140                 


Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp 
145                 150                 155                 160 


Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe 
                165                 170                 175     


Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
            180                 185                 190         


Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu 
        195                 200                 205             


Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
    210                 215                 220                 


Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys 
225                 230                 235                 240 


Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
                245                 250                 255     


Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
            260                 265                 270         


Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
        275                 280                 285             


Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser 
    290                 295                 300                 


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


Leu Ser Leu Ser Leu Gly Lys 
                325         


<210>  25
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Light chain constant region for chimeric and humanized antibodies

<400>  25

Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 
1               5                   10                  15      


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


Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 
        35                  40                  45              


Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 
    50                  55                  60                  


Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 
65                  70                  75                  80  


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


Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
            100                 105         


<210>  26
<211>  382
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human PD1-Fc protein

<400>  26

Leu Asp Ser Pro Asp Arg Pro Trp Asn Pro Pro Thr Phe Ser Pro Ala 
1               5                   10                  15      


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


Ser Asn Thr Ser Glu Ser Phe Val Leu Asn Trp Tyr Arg Met Ser Pro 
        35                  40                  45              


Ser Asn Gln Thr Asp Lys Leu Ala Ala Phe Pro Glu Asp Arg Ser Gln 
    50                  55                  60                  


Pro Gly Gln Asp Cys Arg Phe Arg Val Thr Gln Leu Pro Asn Gly Arg 
65                  70                  75                  80  


Asp Phe His Met Ser Val Val Arg Ala Arg Arg Asn Asp Ser Gly Thr 
                85                  90                  95      


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


Ser Leu Arg Ala Glu Leu Arg Val Thr Glu Arg Arg Ala Glu Val Pro 
        115                 120                 125             


Thr Ala His Pro Ser Pro Ser Pro Arg Pro Ala Gly Gln Phe Gln Glu 
    130                 135                 140                 


Asn Leu Tyr Phe Gln Gly Glu Pro Lys Ser Cys Asp Lys Thr His Thr 
145                 150                 155                 160 


Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 
                165                 170                 175     


Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
            180                 185                 190         


Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
        195                 200                 205             


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


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


Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
                245                 250                 255     


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


Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
        275                 280                 285             


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


Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 
305                 310                 315                 320 


Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp 
                325                 330                 335     


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


Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
        355                 360                 365             


Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    370                 375                 380         


<210>  27
<211>  294
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Mouse PD-1-his

<400>  27

Met Trp Val Arg Gln Val Pro Trp Ser Phe Thr Trp Ala Val Leu Gln 
1               5                   10                  15      


Leu Ser Trp Gln Ser Gly Trp Leu Leu Glu Val Pro Asn Gly Pro Trp 
            20                  25                  30          


Arg Ser Leu Thr Phe Tyr Pro Ala Trp Leu Thr Val Ser Glu Gly Ala 
        35                  40                  45              


Asn Ala Thr Phe Thr Cys Ser Leu Ser Asn Trp Ser Glu Asp Leu Met 
    50                  55                  60                  


Leu Asn Trp Asn Arg Leu Ser Pro Ser Asn Gln Thr Glu Lys Gln Ala 
65                  70                  75                  80  


Ala Phe Cys Asn Gly Leu Ser Gln Pro Val Gln Asp Ala Arg Phe Gln 
                85                  90                  95      


Ile Ile Gln Leu Pro Asn Arg His Asp Phe His Met Asn Ile Leu Asp 
            100                 105                 110         


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


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


Thr Glu Arg Ile Leu Glu Thr Ser Thr Arg Tyr Pro Ser Pro Ser Pro 
145                 150                 155                 160 


Lys Pro Glu Gly Arg Phe Gln Gly Met Val Ile Gly Ile Met Ser Ala 
                165                 170                 175     


Leu Val Gly Ile Pro Val Leu Leu Leu Leu Ala Trp Ala Leu Ala Val 
            180                 185                 190         


Phe Cys Ser Thr Ser Met Ser Glu Ala Arg Gly Ala Gly Ser Lys Asp 
        195                 200                 205             


Asp Thr Leu Lys Glu Glu Pro Ser Ala Ala Pro Val Pro Ser Val Ala 
    210                 215                 220                 


Tyr Glu Glu Leu Asp Phe Gln Gly Arg Glu Lys Thr Pro Glu Leu Pro 
225                 230                 235                 240 


Thr Ala Cys Val His Thr Glu Tyr Ala Thr Ile Val Phe Thr Glu Gly 
                245                 250                 255     


Leu Gly Ala Ser Ala Met Gly Arg Arg Gly Ser Ala Asp Gly Leu Gln 
            260                 265                 270         


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


His His His His His His 
    290                 


<210>  28
<211>  453
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human PDL1-Fc protein

<400>  28

Phe Thr Val Thr Val Pro Lys Asp Leu Tyr Val Val Glu Tyr Gly Ser 
1               5                   10                  15      


Asn Met Thr Ile Glu Cys Lys Phe Pro Val Glu Lys Gln Leu Asp Leu 
            20                  25                  30          


Ala Ala Leu Ile Val Tyr Trp Glu Met Glu Asp Lys Asn Ile Ile Gln 
        35                  40                  45              


Phe Val His Gly Glu Glu Asp Leu Lys Val Gln His Ser Ser Tyr Arg 
    50                  55                  60                  


Gln Arg Ala Arg Leu Leu Lys Asp Gln Leu Ser Leu Gly Asn Ala Ala 
65                  70                  75                  80  


Leu Gln Ile Thr Asp Val Lys Leu Gln Asp Ala Gly Val Tyr Arg Cys 
                85                  90                  95      


Met Ile Ser Tyr Gly Gly Ala Asp Tyr Lys Arg Ile Thr Val Lys Val 
            100                 105                 110         


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


Val Thr Ser Glu His Glu Leu Thr Cys Gln Ala Glu Gly Tyr Pro Lys 
    130                 135                 140                 


Ala Glu Val Ile Trp Thr Ser Ser Asp His Gln Val Leu Ser Gly Lys 
145                 150                 155                 160 


Thr Thr Thr Thr Asn Ser Lys Arg Glu Glu Lys Leu Phe Asn Val Thr 
                165                 170                 175     


Ser Thr Leu Arg Ile Asn Thr Thr Thr Asn Glu Ile Phe Tyr Cys Thr 
            180                 185                 190         


Phe Arg Arg Leu Asp Pro Glu Glu Asn His Thr Ala Glu Leu Val Ile 
        195                 200                 205             


Pro Glu Leu Pro Leu Ala His Pro Pro Asn Glu Arg Thr Glu Pro Lys 
    210                 215                 220                 


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Leu Ser Pro Gly Lys 
    450             


<210>  29
<211>  151
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human PD1-his

<400>  29

Leu Asp Ser Pro Asp Arg Pro Trp Asn Pro Pro Thr Phe Ser Pro Ala 
1               5                   10                  15      


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


Ser Asn Thr Ser Glu Ser Phe Val Leu Asn Trp Tyr Arg Met Ser Pro 
        35                  40                  45              


Ser Asn Gln Thr Asp Lys Leu Ala Ala Phe Pro Glu Asp Arg Ser Gln 
    50                  55                  60                  


Pro Gly Gln Asp Cys Arg Phe Arg Val Thr Gln Leu Pro Asn Gly Arg 
65                  70                  75                  80  


Asp Phe His Met Ser Val Val Arg Ala Arg Arg Asn Asp Ser Gly Thr 
                85                  90                  95      


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


Ser Leu Arg Ala Glu Leu Arg Val Thr Glu Arg Arg Ala Glu Val Pro 
        115                 120                 125             


Thr Ala His Pro Ser Pro Ser Pro Arg Pro Ala Gly Gln Phe Gln His 
    130                 135                 140                 


His His His His His His His 
145                 150     


<210>  30
<211>  360
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  VH of mouse E1A9C8A7

<400>  30
caggtccagc tgcagcagtc tggggctgag gtggtgaggc ctggggtctc agtgaggatt       60

tcctgcaagg gttctggcta cacattctct gattatgtta tgcactggat gaagcagagt      120

catggagaga gcctagagtg gattggggtt atcagtactt accatattcc tgctgtctac      180

aaccagaagt tcaagggcaa ggccacaatg actgtagaca aatcctccag tacagtctat      240

ctggaacttg ccagactgac atctgaggat tctgccatct attactgtgc aagagaggtc      300

tatggtgact cttactactt cgatgtctgg ggcgcgggga ccacggtcac cgtctcctca      360


<210>  31
<211>  361
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  VH of chimeric E1A9C8A7

<400>  31
caagtgcagc tgcagcagag cggcgccgaa gtggtgagac ccggcgtgag cgtgaggatc       60

agctgcaagg gcagcggcta taccttcagc gactacgtga tgcactggat gaagcagagc      120

cacggcgagt ctctggagtg gatcggagtg atcagcacct accacatccc cgccgtgtac      180

aaccagaagt tcaagggcaa ggccaccatg accgtggaca agagcagcag caccgtgtat      240

ctggagctgg ctagactgac ctccgaggat agcgccatct actactgcgc cagagaggtg      300

tacggcgata gctactactt cgacgtgtgg ggcgccggaa ccacagtgac cgtgagcagc      360

g                                                                      361


<210>  32
<211>  360
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  VH of huE1A9C8A7-V8

<400>  32
caagtgcagc tggtgcagag cggagccgaa gtggtgaaac ccggcgccag cgtgaagatc       60

agctgcaagg ccagcggcta caccttcacc gactacgtga tgcactgggt gagacaagcc      120

cccggccagt ctctggagtg gatgggcgtg atcagcacct accacatccc cgccgtgtac      180

aaccagaagt tcaagggcaa ggccaccatg accgtggaca ccagcaccag caccgtgtat      240

ctggagctgt cctctctgag gagcgaggac accgccgtgt actactgcgc cagagaggtg      300

tacggcgaca gctactactt cgacgtgtgg ggccaaggca ccacagtgac cgtgagcagc      360


<210>  33
<211>  336
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  VL of mouse E1A9C8A7

<400>  33
gatgttttga tgacccaaat tccactctcc ctgcctgtta gtcttggaga tcaagtctcc       60

atctcttgca gatctagtca gagcattgta catagtaatg gaaacaccta tttagaatgg      120

tacctgcaga aaccaggcca gtctccaaag ctcctgatct acaaagtttc caaccgattt      180

tctggggtcc cagacaggtt cagtggcagt ggatcaggga cagatttcac actcaagatc      240

agcagagtgg aggctgagga tctgggagtt tattactgct ttcaaggttc acatgttccg      300

tacacgttcg gaggggggac caagctggaa ataaaa                                336


<210>  34
<211>  336
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  VL of chimeric E1A9C8A7

<400>  34
gacgtgctga tgacccagat ccctctgtct ctgcccgtgt ctctgggaga tcaagtgagc       60

atcagctgca gatccagcca gagcatcgtg cacagcaacg gcaacaccta tctggagtgg      120

tatctgcaga agcccggcca gagccccaag ctgctgatct acaaggtctc caatagattc      180

tccggcgtgc ccgatagatt cagcggaagc ggcagcggca ccgacttcac actgaagatc      240

tccagagtgg aggccgagga tctgggcgtg tactactgct ttcaaggcag ccacgtgccc      300

tacacctttg gcggcggcac caaactggag atcaag                                336


<210>  35
<211>  336
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  VL of huE1A9C8A7-V1 - huE1A9C8A7-V11

<400>  35
gacatcgtga tgacccagac acctctgtct ctgcccgtga cacccggcga gcccgccagc       60

atcagctgca gaagcagcca gagcatcgtg cacagcaacg gcaacaccta tctggagtgg      120

tatctgcaga agcccggcca gagccctcag ctgctgatct acaaggtgtc caatagattc      180

agcggcgtgc ccgacagatt cagcggcagc ggaagcggca cagacttcac actgaagatc      240

tccagagtgg aggccgagga cgtgggcgtg tactactgct tccaaggcag ccacgtgcct      300

tacaccttcg gcggcggcac caaggtggag atcaag                                336


<210>  36
<211>  360
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  VH of mouse E2G4E10B7

<400>  36
caggtccagc tgcagcagtc tggggctgag ctggtgaggc ctggggtctc agtgaagatt       60

tcctgcaagg gttctggcta cacattcact gattatgtta tgcactgggt gaggcagagc      120

catgcaaaga gtctagagtg gattggagtt atcagtactc actttggtga tggtgtttac      180

aaccagaagt tcaagggcaa ggccacaatg actgtagaca aatcctccag cacagcctat      240

atggaacttg ccagactgac atctgaggat tctgccatct attactgtgc aagagaggtc      300

tatggtgact cttggtactt cgatgtctgg ggcgcaggga ccacggtcac cgtctcctca      360


<210>  37
<211>  336
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  VL of mouse E2G4E10B7

<400>  37
gatgttttga tgacccaaac tccactctcc ctgcctgtca gtcttggaga tcaagcctcc       60

atctcttgca gatctagtca gagccttgta catagtgatg gaaacaccta tttagaatgg      120

tacctgcaga aaccaggcca gtctccaaag ctcctgatct acaaagtttc caaccgattt      180

tctggggtcc cagacaggtt cagtggcagt ggatcaggga cagatttcac actcaagatc      240

agcagactgg aggctgagga tctgggagtt tattactgct ttcaaggttc acatgttccg      300

tacacgttcg gaggggggac caagctggaa ataaaa                                336


<210>  38
<211>  363
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  VH of mouse E1G5D1H1

<400>  38
gaagtgcagt tggtggagtc tgggggaggc ttagtgaagc ctggagggtc tctgaagctc       60

tcctgtgcag cctctggatt cactttcagt gacttttaca tgtattgggt tcgccagact      120

ccggaaaaga ggctggagtg ggtcgcaacc attagtaata gtggtactca aacctactat      180

ctagacagtg tgaaggggcg attcaccatc tccagagaca atgccaagaa taacctgtac      240

ctgcaaatga gcagtctgaa gtctgaggac acagccatgt actattgtgc tagagactac      300

tataggtacg acagctggta cttcgatgtc tggggcgcag ggaccacggt caccgtctcc      360

tca                                                                    363


<210>  39
<211>  333
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  VL of mouse E1G5D1H1

<400>  39
gacattgtat taacccaatc tccagcttct ttggctgtgt ctcaagggca gagagccacc       60

atctcctgca gagccagtga aagtgttgat ttttatggca caagtttaat gcagtggttc      120

caactgaaac caggacagcc acccaaactc ctcatctatg ctgcatccaa cgtcgaatct      180

ggagtccctg ccaggtttag tggcagtggg tctgggacaa acttcagcct caacatccat      240

cctgtggagg aggatgatat tgccatgtat ttctgtcagc aaagtaggaa ggttccgtgg      300

acattcggtg gaggcaccaa ccttgaaatc aaa                                   333


<210>  40
<211>  984
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Heavy chain constant region for chimeric and humanized antibodies

<400>  40
gccagcacaa agggcccttc cgtgtttccc ctggccccct gcagcaggag cacctctgag       60

tccaccgccg ccctgggctg tctggtgaag gactactttc ccgagcccgt gaccgtgagc      120

tggaattccg gcgccctgac atccggcgtg cacaccttcc ccgccgtgct gcagtcctcc      180

ggcctgtaca gcctgagctc cgtggtgaca gtgccttcct cctccctggg caccaagacc      240

tacacatgta atgtggatca caagcccagc aacacaaagg tggataagag agtggagtcc      300

aagtacggcc ctccttgccc tccctgtcct gccccagagt tcctgggcgg cccctctgtg      360

ttcctgttcc cccctaagcc caaggacaca ctgatgatct ccaggacccc tgaggtgacc      420

tgcgtggtgg tggacgtgag ccaggaggac cctgaggtgc agttcaattg gtacgtggat      480

ggcgtggagg tgcacaatgc caagacaaag cccagagagg agcagtttaa ttccacatac      540

agggtggtgt ccgtgctgac cgtgctgcac caggattggc tgaacggcaa ggagtacaag      600

tgtaaggtga gcaacaaggg cctgccttcc tccatcgaga agacaatcag caaggccaag      660

ggccagccta gggagcccca ggtgtacaca ctgcctccca gccaggagga gatgaccaag      720

aaccaggtga gcctgacctg cctggtgaag ggcttctacc ctagcgacat cgccgtggag      780

tgggagtcca acggccagcc cgagaataac tacaagacaa caccccccgt gctggattcc      840

gatggcagct tctttctgta ctccaggctg accgtggata agagcaggtg gcaggagggc      900

aatgtgttca gctgctccgt gatgcacgag gccctgcaca atcactacac ccagaagagc      960

ctgtccctga gcctgggcaa gtga                                             984


<210>  41
<211>  324
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Light chain constant region for chimeric and humanized antibodies

<400>  41
cgtacggtgg ctgcaccatc tgtcttcatc ttcccgccat ctgatgagca gttgaaatct       60

ggaactgcct ctgttgtgtg cctgctgaat aacttctatc ccagagaggc caaagtacag      120

tggaaggtgg ataacgccct ccaatcgggt aactcccagg agagtgtcac agagcaggac      180

agcaaggaca gcacctacag cctcagcagc accctgacgc tgagcaaagc agactacgag      240

aaacacaaag tctacgcctg cgaagtcacc catcagggcc tgagctcgcc cgtcacaaag      300

agcttcaaca ggggagagtg ttag                                             324


<210>  42
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH of huE1A9C8A7-V8-3

<400>  42

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


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


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


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


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


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


Ala Arg Glu Val Tyr Gly Glu Ser Tyr Tyr Phe Asp Val Trp Gly Gln 
            100                 105                 110         


Gly Thr Thr Val Thr Val Ser Ser 
        115                 120 


