                         SEQUENCE LISTING

<110>  Merck Sharp & Dohme Corp.
       Williams, Sybil M. G.
       Han, Jin-Hwan
       LaFace, Drake Maurice
       Pinheiro, Elaine
       Seghezzi, Wolfgang
 
<120>  BIOMARKERS FOR ANTI-TIGIT ANTIBODY TREATMENT

<130>  25112-WO-PCT

<150>  US 62/909,021
<151>  2019-10-01

<160>  29    

<170>  PatentIn version 3.5

<210>  1
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  31C6 heavy chain variable domain

<400>  1

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


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


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


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


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


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


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


Thr Thr Val Thr Val Ser Ser 
        115                 


<210>  2
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  31C6 light chain variable domain

<400>  2

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


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


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


Tyr Asn Ala Lys Thr Leu Ala Glu Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


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


Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys 
            100                 105         


<210>  3
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  31C6 CDR-H1

<400>  3

Ser Tyr Val Met His 
1               5   


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

<220>
<223>  31C6 CDR-H2

<400>  4

Tyr Ile Asp Pro Tyr Asn Asp Gly Ala Lys Tyr Ala Gln Lys Phe Gln 
1               5                   10                  15      


Gly 
    


<210>  5
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  31C6 CDR-H3

<400>  5

Gly Gly Pro Tyr Gly Trp Tyr Phe Asp Val 
1               5                   10  


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

<220>
<223>  31C6 CDR-L1

<400>  6

Arg Ala Ser Glu His Ile Tyr Ser Tyr Leu Ser 
1               5                   10      


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

<220>
<223>  31C6 CDR-L2

<400>  7

Asn Ala Lys Thr Leu Ala Glu 
1               5           


<210>  8
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  31C6 CDR-L3

<400>  8

Gln His His Phe Gly Ser Pro Leu Thr 
1               5                   


<210>  9
<211>  449
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  31C6 heavy chain immunoglobulin

<400>  9

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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Lys 
    


<210>  10
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  31C6 light chain immunoglobulin

<400>  10

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


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


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


Tyr Asn Ala Lys Thr Leu Ala Glu Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


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


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


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


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


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


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


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


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


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  11
<211>  116
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  18G10 - rat anti-murine VH sequence

<400>  11

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


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Phe Pro Leu Thr Ser Tyr 
            20                  25                  30          


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


Gly Ala Ile Trp Ser Ser Gly Ser Thr Asp Tyr Asn Ser Ala Leu Lys 
    50                  55                  60                  


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


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


Lys Ser Gly Trp Ala Phe Phe Asp Tyr Trp Gly Gln Gly Val Met Val 
            100                 105                 110         


Thr Val Ser Ser 
        115     


<210>  12
<211>  106
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  18G10 - rat anti-murine VL sequence

<400>  12

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


Asp Arg Val Thr Leu Asn Cys Ile Ala Ser Gln Asn Ile Tyr Lys Ser 
            20                  25                  30          


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


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


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


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


Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys 
            100                 105     


<210>  13
<211>  324
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Murine mIgG1-[D265A]

<400>  13

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


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


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


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


Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val 
65                  70                  75                  80  


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


Ile Val Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro 
            100                 105                 110         


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


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


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


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


Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn 
            180                 185                 190         


Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro 
        195                 200                 205             


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


Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val 
225                 230                 235                 240 


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


Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln 
            260                 265                 270         


Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn 
        275                 280                 285             


Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val 
    290                 295                 300                 


Leu His Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His 
305                 310                 315                 320 


Ser Pro Gly Lys 
                


<210>  14
<211>  330
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Murine IgG2a heavy chain constant domain

<400>  14

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


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


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


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


Ser Ser Ser Val Thr Val Thr Ser Ser Thr Trp Pro Ser Gln Ser Ile 
65                  70                  75                  80  


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


Ile Glu Pro Arg Gly Pro Thr Ile Lys Pro Cys Pro Pro Cys Lys Cys 
            100                 105                 110         


Pro Ala Pro Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro 
        115                 120                 125             


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


Val Val Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp 
145                 150                 155                 160 


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


Glu Asp Tyr Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro Ile Gln 
            180                 185                 190         


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


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


Ser Val Arg Ala Pro Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu 
225                 230                 235                 240 


Met Thr Lys Lys Gln Val Thr Leu Thr Cys Met Val Thr Asp Phe Met 
                245                 250                 255     


Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr Glu Leu 
            260                 265                 270         


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


Met Tyr Ser Lys Leu Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn 
    290                 295                 300                 


Ser Tyr Ser Cys Ser Val Val His Glu Gly Leu His Asn His His Thr 
305                 310                 315                 320 


Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys 
                325                 330 


<210>  15
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Murine kappa light chain constant domain

<400>  15

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


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


Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg 
        35                  40                  45              


Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser 
    50                  55                  60                  


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


Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser 
                85                  90                  95      


Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys 
            100                 105         


<210>  16
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  11A11 - rat anti-murine VH sequence

<400>  16

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


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


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


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


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


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


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


Thr Leu Val Ile Val Ser Ser 
        115                 


<210>  17
<211>  106
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  11A11 - rat anti-murine VL sequence

<400>  17

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


Asp Arg Val Thr Met Asn Cys Lys Ala Ser Gln Asn Val Asp Asn Asn 
            20                  25                  30          


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


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


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


Glu Asp Ala Ala Phe Tyr Tyr Cys Gln Arg Ile Tyr Asn Phe Pro Thr 
                85                  90                  95      


Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys 
            100                 105     


<210>  18
<211>  330
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Murine IgG2a heavy chain constant domain

<400>  18

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


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


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


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


Ser Ser Ser Val Thr Val Thr Ser Ser Thr Trp Pro Ser Gln Ser Ile 
65                  70                  75                  80  


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


Ile Glu Pro Arg Gly Pro Thr Ile Lys Pro Cys Pro Pro Cys Lys Cys 
            100                 105                 110         


Pro Ala Pro Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro 
        115                 120                 125             


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


Val Val Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp 
145                 150                 155                 160 


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


Glu Asp Tyr Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro Ile Gln 
            180                 185                 190         


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


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


Ser Val Arg Ala Pro Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu 
225                 230                 235                 240 


Met Thr Lys Lys Gln Val Thr Leu Thr Cys Met Val Thr Asp Phe Met 
                245                 250                 255     


Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr Glu Leu 
            260                 265                 270         


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


Met Tyr Ser Lys Leu Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn 
    290                 295                 300                 


Ser Tyr Ser Cys Ser Val Val His Glu Gly Leu His Asn His His Thr 
305                 310                 315                 320 


Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys 
                325                 330 


<210>  19
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Murine kappa light chain constant domain

<400>  19

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


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


Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg 
        35                  40                  45              


Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser 
    50                  55                  60                  


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


Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser 
                85                  90                  95      


Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys 
            100                 105         


<210>  20
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DX400 VH sequence

<400>  20

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


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


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


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


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


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


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


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  21
<211>  324
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DX400 heavy chain sequence

<400>  21

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


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


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


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


Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val 
65                  70                  75                  80  


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


Ile Val Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro 
            100                 105                 110         


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


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


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


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


Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn 
            180                 185                 190         


Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro 
        195                 200                 205             


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


Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val 
225                 230                 235                 240 


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


Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln 
            260                 265                 270         


Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn 
        275                 280                 285             


Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val 
    290                 295                 300                 


Leu His Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His 
305                 310                 315                 320 


Ser Pro Gly Lys 
                


<210>  22
<211>  111
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DX400 VL sequence

<400>  22

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


Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Gln Ser Val Thr Ile Ser 
            20                  25                  30          


Arg Tyr Thr Leu Met His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 
        35                  40                  45              


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


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


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


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


<210>  23
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  DX400 light chain sequence

<400>  23

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


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


Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg 
        35                  40                  45              


Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser 
    50                  55                  60                  


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


Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser 
                85                  90                  95      


Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys 
            100                 105         


<210>  24
<211>  447
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Pembrolizumab Heavy chain

<400>  24

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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  25
<211>  218
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Pembrolizumab Light chain

<400>  25

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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  26
<211>  440
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Nivolumab heavy chain

<400>  26

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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Ser Leu Ser Leu Ser Leu Gly Lys 
        435                 440 


<210>  27
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Nivolumab light chain

<400>  27

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


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


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


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


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


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


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


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


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


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


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


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


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


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  28
<211>  333
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD226_MOUSE

<400>  28

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


Leu Cys Glu Glu Thr Leu Trp Asp Thr Thr Val Arg Leu Ser Glu Thr 
            20                  25                  30          


Met Thr Leu Glu Cys Val Tyr Pro Leu Thr His Asn Leu Thr Gln Val 
        35                  40                  45              


Glu Trp Thr Lys Asn Thr Gly Thr Lys Thr Val Ser Ile Ala Val Tyr 
    50                  55                  60                  


Asn Pro Asn His Asn Met His Ile Glu Ser Asn Tyr Leu His Arg Val 
65                  70                  75                  80  


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


Tyr Asn Ala Ser Glu Ala Asp Ile Gly Ile Tyr Ser Cys Leu Phe His 
            100                 105                 110         


Ala Phe Pro Asn Gly Pro Trp Glu Lys Lys Ile Lys Val Val Trp Ser 
        115                 120                 125             


Asp Ser Phe Glu Ile Ala Ala Pro Ser Asp Ser Tyr Leu Ser Ala Glu 
    130                 135                 140                 


Pro Gly Gln Asp Val Thr Leu Thr Cys Gln Leu Pro Arg Thr Trp Pro 
145                 150                 155                 160 


Val Gln Gln Val Ile Trp Glu Lys Val Gln Pro His Gln Val Asp Ile 
                165                 170                 175     


Leu Ala Ser Cys Asn Leu Ser Gln Glu Thr Arg Tyr Thr Ser Lys Tyr 
            180                 185                 190         


Leu Arg Gln Thr Arg Ser Asn Cys Ser Gln Gly Ser Met Lys Ser Ile 
        195                 200                 205             


Leu Ile Ile Pro Asn Ala Met Ala Ala Asp Ser Gly Leu Tyr Arg Cys 
    210                 215                 220                 


Arg Ser Glu Ala Ile Thr Gly Lys Asn Lys Ser Phe Val Ile Arg Leu 
225                 230                 235                 240 


Ile Ile Thr Asp Gly Gly Thr Asn Lys His Phe Ile Leu Pro Ile Val 
                245                 250                 255     


Gly Gly Leu Val Ser Leu Leu Leu Val Ile Leu Ile Ile Ile Ile Phe 
            260                 265                 270         


Ile Leu Tyr Asn Arg Lys Arg Arg Arg Gln Val Arg Ile Pro Leu Lys 
        275                 280                 285             


Glu Pro Arg Asp Lys Gln Ser Lys Val Ala Thr Asn Cys Arg Ser Pro 
    290                 295                 300                 


Thr Ser Pro Ile Gln Ser Thr Asp Asp Glu Lys Glu Asp Ile Tyr Val 
305                 310                 315                 320 


Asn Tyr Pro Thr Phe Ser Arg Arg Pro Lys Pro Arg Leu 
                325                 330             


<210>  29
<211>  336
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CD226_HUMAN

<400>  29

Met Asp Tyr Pro Thr Leu Leu Leu Ala Leu Leu His Val Tyr Arg Ala 
1               5                   10                  15      


Leu Cys Glu Glu Val Leu Trp His Thr Ser Val Pro Phe Ala Glu Asn 
            20                  25                  30          


Met Ser Leu Glu Cys Val Tyr Pro Ser Met Gly Ile Leu Thr Gln Val 
        35                  40                  45              


Glu Trp Phe Lys Ile Gly Thr Gln Gln Asp Ser Ile Ala Ile Phe Ser 
    50                  55                  60                  


Pro Thr His Gly Met Val Ile Arg Lys Pro Tyr Ala Glu Arg Val Tyr 
65                  70                  75                  80  


Phe Leu Asn Ser Thr Met Ala Ser Asn Asn Met Thr Leu Phe Phe Arg 
                85                  90                  95      


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


Tyr Pro Gln Gly Thr Trp Gln Lys Val Ile Gln Val Val Gln Ser Asp 
        115                 120                 125             


Ser Phe Glu Ala Ala Val Pro Ser Asn Ser His Ile Val Ser Glu Pro 
    130                 135                 140                 


Gly Lys Asn Val Thr Leu Thr Cys Gln Pro Gln Met Thr Trp Pro Val 
145                 150                 155                 160 


Gln Ala Val Arg Trp Glu Lys Ile Gln Pro Arg Gln Ile Asp Leu Leu 
                165                 170                 175     


Thr Tyr Cys Asn Leu Val His Gly Arg Asn Phe Thr Ser Lys Phe Pro 
            180                 185                 190         


Arg Gln Ile Val Ser Asn Cys Ser His Gly Arg Trp Ser Val Ile Val 
        195                 200                 205             


Ile Pro Asp Val Thr Val Ser Asp Ser Gly Leu Tyr Arg Cys Tyr Leu 
    210                 215                 220                 


Gln Ala Ser Ala Gly Glu Asn Glu Thr Phe Val Met Arg Leu Thr Val 
225                 230                 235                 240 


Ala Glu Gly Lys Thr Asp Asn Gln Tyr Thr Leu Phe Val Ala Gly Gly 
                245                 250                 255     


Thr Val Leu Leu Leu Leu Phe Val Ile Ser Ile Thr Thr Ile Ile Val 
            260                 265                 270         


Ile Phe Leu Asn Arg Arg Arg Arg Arg Glu Arg Arg Asp Leu Phe Thr 
        275                 280                 285             


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


Ser Thr Ser Gln Pro Thr Asn Gln Ser Met Asp Asp Thr Arg Glu Asp 
305                 310                 315                 320 


Ile Tyr Val Asn Tyr Pro Thr Phe Ser Arg Arg Pro Lys Thr Arg Val 
                325                 330                 335     


