                         SEQUENCE LISTING

<110>  ASTRAZENECA (MEDIMMUNE)
 
<120>  BISPECIFIC ANTIBODY TARGETING PD-1 AND TIM-3

<130>  PDTM-200-US-PSP

<160>  30    

<170>  PatentIn version 3.5

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

<220>
<223>  AZD 7789 TIM-3 VH CDR1

<400>  1

Ser Tyr Ala Met Ser 
1               5   


<210>  2
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  AZD 7789 TIM-3 VH CDR2

<400>  2

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


Gly 
    


<210>  3
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  AZD 7789 TIM-3 VH CDR3

<400>  3

Gly Ser Tyr Gly Thr Tyr Tyr Gly Asn Tyr Phe Glu Tyr 
1               5                   10              


<210>  4
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  AZD 7789 PD-1 VH CDR1

<400>  4

Asp Tyr Gly Met His 
1               5   


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

<220>
<223>  AZD 7789 PD-1 VH CDR2

<400>  5

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


Gly 
    


<210>  6
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  AZD 7789 PD-1 VH CDR3

<400>  6

Arg Ala Pro Asn Ser Phe Tyr Glu Tyr Tyr Phe Asp Tyr 
1               5                   10              


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

<220>
<223>  AZD 7789 TIM-3 VL CDR1

<400>  7

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


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

<220>
<223>  AZD 7789 TIM-3 VL CDR2

<400>  8

Tyr Asp Ser Asp Arg Pro Ser 
1               5           


<210>  9
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  AZD 7789 TIM-3 VL CDR3

<400>  9

Gln Val Leu Asp Arg Arg Ser Asp His Phe Leu 
1               5                   10      


<210>  10
<211>  18
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  AZD 7789 PD-1 VL CDR1

<400>  10

Ser Ala Ser Ser Lys His Thr Asn Leu Tyr Trp Ser Arg His Met Tyr 
1               5                   10                  15      


Trp Tyr 
        


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

<220>
<223>  AZD 7789 PD-1 VL CDR2

<400>  11

Leu Thr Ser Asn Arg Ala Thr 
1               5           


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

<220>
<223>  AZD 7789 PD-1 VL CDR3

<400>  12

Gln Gln Trp Ser Ser Asn Pro 
1               5           


<210>  13
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TIM-3 (#62) VL CDR3

<400>  13

Gln Val Leu Asp Arg Arg Ser Asp His Trp Leu 
1               5                   10      


<210>  14
<211>  122
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  AZD 7789 TIM-3 VH

<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 Tyr 
            20                  25                  30          


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


Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr 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 Arg Gly Ser Tyr Gly Thr Tyr Tyr Gly Asn Tyr Phe Glu Tyr Trp 
            100                 105                 110         


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


<210>  15
<211>  452
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  AZD 7789 TIM-3 HC

<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          


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


Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr 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 Arg Gly Ser Tyr Gly Thr Tyr Tyr Gly Asn Tyr Phe Glu Tyr Trp 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Ser Pro Gly Lys 
    450         


<210>  16
<211>  108
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TIM3 (#62) Variable Light VL

<400>  16

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


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


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


Tyr Asp Ser Asp Arg Pro Ser Gly Ile Pro Gln Arg Phe Ser Gly Ser 
    50                  55                  60                  


Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile His Arg Val Glu Ala Gly 
65                  70                  75                  80  


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


Trp Leu Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
            100                 105             


<210>  17
<211>  108
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  AZD 7789 TIM-3 VL

<400>  17

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


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


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


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


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


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


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


<210>  18
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  AZD 7789 TIM-3 LC

<400>  18

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


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


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


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


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


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


Phe Leu Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys 
            100                 105                 110         


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


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


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


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


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


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


Ala Pro Thr Glu Val Ser 
    210                 


<210>  19
<211>  122
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  AZD 7789 PD-1 VH

<400>  19

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


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


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


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


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


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


<210>  20
<211>  452
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  AZD 7789 PD-1 HC

<400>  20

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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Ser Pro Gly Lys 
    450         


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

<220>
<223>  AZD 7789 PD-1 VL

<400>  21

Gln 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 Ser Ala Ser Ser Lys His Thr Asn Leu 
            20                  25                  30          


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


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


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


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


Ser Ser Asn Pro Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


<210>  22
<211>  219
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  AZD 7789 PD-1 LC

<400>  22

Gln 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 Ser Ala Ser Ser Lys His Thr Asn Leu 
            20                  25                  30          


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


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


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


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


Ser Ser Asn Pro Phe Thr Phe Gly Gln Gly Thr Lys Leu 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>  23
<211>  710
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TIM-3 Heavy Chain

<400>  23

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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Arg Trp 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 Ser 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 Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu 
    450                 455                 460                 


Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu 
465                 470                 475                 480 


Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Ala Met Ser Trp 
                485                 490                 495     


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


Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe 
        515                 520                 525             


Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn 
    530                 535                 540                 


Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Gly Ser 
545                 550                 555                 560 


Tyr Gly Thr Tyr Tyr Gly Asn Tyr Phe Glu Tyr Trp Gly Gln Gly Thr 
                565                 570                 575     


Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
            580                 585                 590         


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ser Tyr Val Leu Thr Gln 
        595                 600                 605             


Pro Pro Ser Val Ser Val Ala Pro Gly Lys Thr Ala Arg Ile Thr Cys 
    610                 615                 620                 


Gly Gly Asp Asn Ile Gly Gly Lys Ser Val His Trp Tyr Gln Gln Lys 
625                 630                 635                 640 


Pro Gly Gln Ala Pro Val Leu Val Ile Tyr Tyr Asp Ser Asp Arg Pro 
                645                 650                 655     


Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser Asn Ser Gly Asn Thr Ala 
            660                 665                 670         


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


Cys Gln Val Leu Asp Arg Arg Ser Asp His Phe Leu Phe Gly Cys Gly 
    690                 695                 700                 


Thr Lys Leu Thr Val Leu 
705                 710 


<210>  24
<211>  218
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TIM-3 Light Chain Variable Region

<400>  24

Gln 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 Ser Ala Ser Ser Lys His Thr Asn Leu 
            20                  25                  30          


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


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


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


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


Ser Ser Asn Pro Phe Thr Phe Gly Gln Gly Thr Lys Leu 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 Trp Cys Leu Leu Asn Asn Phe Tyr 
    130                 135                 140                 


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


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


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


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


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


<210>  25
<211>  720
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TIM-3 Heavy Chain

<400>  25

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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Arg Trp 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 Ser 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 Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln 
385                 390                 395                 400 


Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg 
                405                 410                 415     


Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Ala Met Ser 
            420                 425                 430         


Trp Val Arg Gln Ala Pro Gly Lys Cys Leu Glu Trp Val Ser Ala Ile 
        435                 440                 445             


Ser Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg 
    450                 455                 460                 


Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met 
465                 470                 475                 480 


Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Gly 
                485                 490                 495     


Ser Tyr Gly Thr Tyr Tyr Gly Asn Tyr Phe Glu Tyr Trp Gly Gln Gly 
            500                 505                 510         


Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        515                 520                 525             


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ser Tyr Val Leu Thr 
    530                 535                 540                 


Gln Pro Pro Ser Val Ser Val Ala Pro Gly Lys Thr Ala Arg Ile Thr 
545                 550                 555                 560 


Cys Gly Gly Asp Asn Ile Gly Gly Lys Ser Val His Trp Tyr Gln Gln 
                565                 570                 575     


Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr Tyr Asp Ser Asp Arg 
            580                 585                 590         


Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser Asn Ser Gly Asn Thr 
        595                 600                 605             


Ala Thr Leu Thr Ile Ser Arg Val Glu Ala Gly Asp Glu Ala Asp Tyr 
    610                 615                 620                 


Tyr Cys Gln Val Leu Asp Arg Arg Ser Asp His Phe Leu Phe Gly Cys 
625                 630                 635                 640 


Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Ser Gly Gly Gly Gly 
                645                 650                 655     


Ser Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
            660                 665                 670         


Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 
        675                 680                 685             


Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
    690                 695                 700                 


Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
705                 710                 715                 720 


<210>  26
<211>  218
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TIM-3 Light Chain

<400>  26

Gln 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 Ser Ala Ser Ser Lys His Thr Asn Leu 
            20                  25                  30          


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


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


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


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


Ser Ser Asn Pro Phe Thr Phe Gly Gln Gly Thr Lys Leu 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 Trp Cys Leu Leu Asn Asn Phe Tyr 
    130                 135                 140                 


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


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


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


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


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


<210>  27
<211>  122
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  TIM3 (#62) Variable Heavy VH

<400>  27

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          


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


Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr 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 Arg Gly Ser Tyr Gly Thr Tyr Tyr Gly Asn Tyr Phe Glu Tyr Trp 
            100                 105                 110         


Gly Arg Gly Thr Leu Val Thr Val Ser Ser 
        115                 120         


<210>  28
<211>  288
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Amino acid sequence of human PD-1 protein

<400>  28

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>  29
<211>  109
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human TIM-3 IgV domain

<400>  29

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


Cys Phe Tyr Thr Pro Ala Ala Pro Gly Asn Leu Val Pro Val Cys Trp 
            20                  25                  30          


Gly Lys Gly Ala Cys Pro Val Phe Glu Cys Gly Asn Val Val Leu Arg 
        35                  40                  45              


Thr Asp Glu Arg Asp Val Asn Tyr Trp Thr Ser Arg Tyr Trp Leu Asn 
    50                  55                  60                  


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


Leu Ala Asp Ser Gly Ile Tyr Cys Cys Arg Ile Gln Ile Pro Gly Ile 
                85                  90                  95      


Met Asn Asp Glu Lys Phe Asn Leu Lys Leu Val Ile Lys 
            100                 105                 


<210>  30
<211>  301
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human TIM-3 protein

<400>  30

Met Phe Ser His Leu Pro Phe Asp Cys Val Leu Leu Leu Leu Leu Leu 
1               5                   10                  15      


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


Asn Ala Tyr Leu Pro Cys Phe Tyr Thr Pro Ala Ala Pro Gly Asn Leu 
        35                  40                  45              


Val Pro Val Cys Trp Gly Lys Gly Ala Cys Pro Val Phe Glu Cys Gly 
    50                  55                  60                  


Asn Val Val Leu Arg Thr Asp Glu Arg Asp Val Asn Tyr Trp Thr Ser 
65                  70                  75                  80  


Arg Tyr Trp Leu Asn Gly Asp Phe Arg Lys Gly Asp Val Ser Leu Thr 
                85                  90                  95      


Ile Glu Asn Val Thr Leu Ala Asp Ser Gly Ile Tyr Cys Cys Arg Ile 
            100                 105                 110         


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


Ile Lys Pro Ala Lys Val Thr Pro Ala Pro Thr Arg Gln Arg Asp Phe 
    130                 135                 140                 


Thr Ala Ala Phe Pro Arg Met Leu Thr Thr Arg Gly His Gly Pro Ala 
145                 150                 155                 160 


Glu Thr Gln Thr Leu Gly Ser Leu Pro Asp Ile Asn Leu Thr Gln Ile 
                165                 170                 175     


Ser Thr Leu Ala Asn Glu Leu Arg Asp Ser Arg Leu Ala Asn Asp Leu 
            180                 185                 190         


Arg Asp Ser Gly Ala Thr Ile Arg Ile Gly Ile Tyr Ile Gly Ala Gly 
        195                 200                 205             


Ile Cys Ala Gly Leu Ala Leu Ala Leu Ile Phe Gly Ala Leu Ile Phe 
    210                 215                 220                 


Lys Trp Tyr Ser His Ser Lys Glu Lys Ile Gln Asn Leu Ser Leu Ile 
225                 230                 235                 240 


Ser Leu Ala Asn Leu Pro Pro Ser Gly Leu Ala Asn Ala Val Ala Glu 
                245                 250                 255     


Gly Ile Arg Ser Glu Glu Asn Ile Tyr Thr Ile Glu Glu Asn Val Tyr 
            260                 265                 270         


Glu Val Glu Glu Pro Asn Glu Tyr Tyr Cys Tyr Val Ser Ser Arg Gln 
        275                 280                 285             


Gln Pro Ser Gln Pro Leu Gly Cys Arg Phe Ala Met Pro 
    290                 295                 300     


