                           б

<110>  ٰ̩ҩɷ޹˾
 
<120>  һֿTIGITƼӦ

<130>  DSP1P202570J

<150>  PCT/CN2019/104258
<151>  2019-09-03

<160>  57    

<170>  PatentIn version 3.5

<210>  1
<211>  343
<212>  PRT
<213>  ˹

<220>
<223>  PVRCD155

<400>  1

Met Ala Arg Ala Met Ala Ala Ala Trp Pro Leu Leu Leu Val Ala Leu 
1               5                   10                  15      


Leu Val Leu Ser Trp Pro Pro Pro Gly Thr Gly Asp Val Val Val Gln 
            20                  25                  30          


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


Cys Tyr Leu Gln Val Pro Asn Met Glu Val Thr His Val Ser Gln Leu 
    50                  55                  60                  


Thr Trp Ala Arg His Gly Glu Ser Gly Ser Met Ala Val Phe His Gln 
65                  70                  75                  80  


Thr Gln Gly Pro Ser Tyr Ser Glu Ser Lys Arg Leu Glu Phe Val Ala 
                85                  90                  95      


Ala Arg Leu Gly Ala Glu Leu Arg Asn Ala Ser Leu Arg Met Phe Gly 
            100                 105                 110         


Leu Arg Val Glu Asp Glu Gly Asn Tyr Thr Cys Leu Phe Val Thr Phe 
        115                 120                 125             


Pro Gln Gly Ser Arg Ser Val Asp Ile Trp Leu Arg Val Leu Ala Lys 
    130                 135                 140                 


Pro Gln Asn Thr Ala Glu Val Gln Lys Val Gln Leu Thr Gly Glu Pro 
145                 150                 155                 160 


Val Pro Met Ala Arg Cys Val Ser Thr Gly Gly Arg Pro Pro Ala Gln 
                165                 170                 175     


Ile Thr Trp His Ser Asp Leu Gly Gly Met Pro Asn Thr Ser Gln Val 
            180                 185                 190         


Pro Gly Phe Leu Ser Gly Thr Val Thr Val Thr Ser Leu Trp Ile Leu 
        195                 200                 205             


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


His Glu Ser Phe Glu Lys Pro Gln Leu Leu Thr Val Asn Leu Thr Val 
225                 230                 235                 240 


Tyr Tyr Pro Pro Glu Val Ser Ile Ser Gly Tyr Asp Asn Asn Trp Tyr 
                245                 250                 255     


Leu Gly Gln Asn Glu Ala Thr Leu Thr Cys Asp Ala Arg Ser Asn Pro 
            260                 265                 270         


Glu Pro Thr Gly Tyr Asn Trp Ser Thr Thr Met Gly Pro Leu Pro Pro 
        275                 280                 285             


Phe Ala Val Ala Gln Gly Ala Gln Leu Leu Ile Arg Pro Val Asp Lys 
    290                 295                 300                 


Pro Ile Asn Thr Thr Leu Ile Cys Asn Val Thr Asn Ala Leu Gly Ala 
305                 310                 315                 320 


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


His Ser Gly Ile Ser Arg Asn 
            340             


<210>  2
<211>  1029
<212>  DNA
<213>  ˹

<220>
<223>  PVRCD155DNA

<400>  2
atggctagag ctatggctgc tgcttggcca ctgctgctgg tggccctgct ggtgctgtct       60

tggccccctc caggaaccgg cgacgtggtg gtgcaggctc caacccaggt gcctggcttc      120

ctgggcgatt ccgtgacact gccttgctac ctgcaggtgc caaacatgga ggtgacacac      180

gtgagccagc tgacatgggc tagacatgga gagtctggct ccatggccgt gttccaccag      240

acccagggcc ctagctactc tgagtccaag cgcctggagt ttgtggctgc tagactggga      300

gctgagctga ggaatgcttc cctgcggatg tttggcctga gagtggagga cgagggcaat      360

tatacatgcc tgttcgtgac ctttccacag ggcagccggt ctgtggatat ctggctgaga      420

gtgctggcca agccccagaa cacagctgag gtgcagaagg tgcagctgac aggagagcct      480

gtgccaatgg ctagatgcgt gtccacaggc ggcaggcccc ctgctcagat cacctggcac      540

tctgacctgg gcggcatgcc caatacatct caggtcccag gcttcctgtc cggcaccgtg      600

acagtgacca gcctgtggat tctggtgcct tccagccagg tggatggcaa gaacgtgacc      660

tgcaaggtgg agcatgagag ctttgagaag ccacagctgc tgacagtgaa tctgaccgtg      720

tactatccac ccgaggtgtc catcagcggc tacgacaaca attggtatct gggccagaat      780

gaggccacac tgacctgtga tgctaggtct aaccctgagc caaccggcta taattggtcc      840

accacaatgg gcccactgcc tccattcgct gtggctcagg gagctcagct gctgatcaga      900

ccagtggaca agcccatcaa caccacactg atctgtaacg tgacaaatgc tctgggcgcc      960

agacaggctg agctgaccgt gcaggtgaag gagggccctc catctgagca ttccggcatc     1020

agccgcaat                                                             1029


<210>  3
<211>  141
<212>  PRT
<213>  ˹

<220>
<223>  TIGIT

<400>  3

Met Arg Trp Cys Leu Leu Leu Ile Trp Ala Gln Gly Leu Arg Gln Ala 
1               5                   10                  15      


Pro Leu Ala Ser Gly Met Met Thr Gly Thr Ile Glu Thr Thr Gly Asn 
            20                  25                  30          


Ile Ser Ala Glu Lys Gly Gly Ser Ile Ile Leu Gln Cys His Leu Ser 
        35                  40                  45              


Ser Thr Thr Ala Gln Val Thr Gln Val Asn Trp Glu Gln Gln Asp Gln 
    50                  55                  60                  


Leu Leu Ala Ile Cys Asn Ala Asp Leu Gly Trp His Ile Ser Pro Ser 
65                  70                  75                  80  


Phe Lys Asp Arg Val Ala Pro Gly Pro Gly Leu Gly Leu Thr Leu Gln 
                85                  90                  95      


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


Tyr Pro Asp Gly Thr Tyr Thr Gly Arg Ile Phe Leu Glu Val Leu Glu 
        115                 120                 125             


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


<210>  4
<211>  245
<212>  PRT
<213>  ˹

<220>
<223>  TIGIT

<400>  4

Met Arg Trp Cys Leu Phe Leu Ile Trp Ala Gln Gly Leu Arg Gln Ala 
1               5                   10                  15      


Pro Leu Ala Ser Gly Met Met Thr Gly Thr Ile Glu Thr Thr Gly Asn 
            20                  25                  30          


Ile Ser Ala Lys Lys Gly Gly Ser Val Ile Leu Gln Cys His Leu Ser 
        35                  40                  45              


Ser Thr Met Ala Gln Val Thr Gln Val Asn Trp Glu Gln His Asp His 
    50                  55                  60                  


Ser Leu Leu Ala Ile Arg Asn Ala Glu Leu Gly Trp His Ile Tyr Pro 
65                  70                  75                  80  


Ala Phe Lys Asp Arg Val Ala Pro Gly Pro Gly Leu Gly Leu Thr Leu 
                85                  90                  95      


Gln Ser Leu Thr Met Asn Asp Thr Gly Glu Tyr Phe Cys Thr Tyr His 
            100                 105                 110         


Thr Tyr Pro Asp Gly Thr Tyr Arg Gly Arg Ile Phe Leu Glu Val Leu 
        115                 120                 125             


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


Gly Ala Met Ala Met Met Leu Val Val Ile Cys Ile Ala Val Ile Val 
145                 150                 155                 160 


Val Val Val Leu Ala Arg Lys Lys Lys Ser Leu Arg Ile His Ser Val 
                165                 170                 175     


Glu Ser Gly Leu Gln Arg Lys Ser Thr Gly Gln Glu Glu Gln Ile Pro 
            180                 185                 190         


Ser Ala Pro Ser Pro Pro Gly Ser Cys Val Gln Ala Glu Ala Ala Pro 
        195                 200                 205             


Ala Gly Leu Cys Gly Glu Gln Gln Gly Asp Asp Cys Ala Glu Leu His 
    210                 215                 220                 


Asp Tyr Phe Asn Val Leu Ser Tyr Arg Ser Leu Gly Ser Cys Ser Phe 
225                 230                 235                 240 


Phe Thr Glu Thr Gly 
                245 


<210>  5
<211>  249
<212>  PRT
<213>  ˹

<220>
<223>  СTIGIT

<400>  5

Met His Gly Trp Leu Leu Leu Val Trp Val Gln Gly Leu Ile Gln Ala 
1               5                   10                  15      


Ala Phe Leu Ala Thr Ala Ile Gly Ala Thr Ala Gly Thr Ile Asp Thr 
            20                  25                  30          


Lys Arg Asn Ile Ser Ala Glu Glu Gly Gly Ser Val Ile Leu Gln Cys 
        35                  40                  45              


His Phe Ser Ser Asp Thr Ala Glu Val Thr Gln Val Asp Trp Lys Gln 
    50                  55                  60                  


Gln Asp Gln Leu Leu Ala Ile Tyr Ser Val Asp Leu Gly Trp His Val 
65                  70                  75                  80  


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


Thr Phe Gln Ser Leu Thr Met Asn Asp Thr Gly Glu Tyr Phe Cys Thr 
            100                 105                 110         


Tyr His Thr Tyr Pro Gly Gly Ile Tyr Lys Gly Arg Ile Phe Leu Lys 
        115                 120                 125             


Val Gln Glu Ser Ser Asp Asp Arg Asn Gly Leu Ala Gln Phe Gln Thr 
    130                 135                 140                 


Ala Pro Leu Gly Gly Thr Met Ala Ala Val Leu Gly Leu Ile Cys Leu 
145                 150                 155                 160 


Met Val Thr Gly Val Thr Val Leu Ala Arg Lys Asp Lys Ser Ile Arg 
                165                 170                 175     


Met His Ser Ile Glu Ser Gly Leu Gly Arg Thr Glu Ala Glu Pro Gln 
            180                 185                 190         


Glu Trp Asn Leu Arg Ser Leu Ser Ser Pro Gly Ser Pro Val Gln Thr 
        195                 200                 205             


Gln Thr Ala Pro Ala Gly Pro Cys Gly Glu Gln Ala Glu Asp Asp Tyr 
    210                 215                 220                 


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


Ser Phe Ile Ala Val Ser Lys Thr Gly 
                245                 


<210>  6
<211>  6
<212>  PRT
<213>  ˹

<220>
<223>  ںϵ

<400>  6

Ile Glu Gly Arg Met Asp 
1               5       


<210>  7
<211>  18
<212>  DNA
<213>  ˹

<220>
<223>  ںϵDNA

<400>  7
attgaaggta gaatggat                                                     18


<210>  8
<211>  126
<212>  PRT
<213>  ˹

<220>
<223>  Զտ壨Tiragolumabɱ

<400>  8

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


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


Ser Ala Ala Trp Asn Trp Ile Arg Gln Ser Pro Ser Arg Gly Leu Glu 
        35                  40                  45              


Trp Leu Gly Lys Thr Tyr Tyr Arg Phe Lys Trp Tyr Ser Asp Tyr Ala 
    50                  55                  60                  


Val Ser Val Lys Gly Arg Ile Thr Ile Asn Pro Asp Thr Ser Lys Asn 
65                  70                  75                  80  


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


Phe Tyr Cys Thr Arg Glu Ser Thr Thr Tyr Asp Leu Leu Ala Gly Pro 
            100                 105                 110         


Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125     


<210>  9
<211>  113
<212>  PRT
<213>  ˹

<220>
<223>  Զտ壨Tiragolumabɱ

<400>  9

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


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


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


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


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


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


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


Lys 
    


<210>  10
<211>  119
<212>  PRT
<213>  ˹

<220>
<223>  TIGIT Կ壨10A7ɱ

<400>  10

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


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


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


Ala Phe Ile Arg Ser Gly Ser Gly Ile Val Phe Tyr Ala Asp Ala Val 
    50                  55                  60                  


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


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


Ala Arg Arg Pro Leu Gly His Asn Thr Phe Asp Ser Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  11
<211>  114
<212>  PRT
<213>  ˹

<220>
<223>  TIGIT Կ壨10A7ɱ

<400>  11

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


Glu Lys Val Thr Met Thr Cys Lys Ser Ser Gln Ser Leu Tyr Tyr Ser 
            20                  25                  30          


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


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


Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr 
65                  70                  75                  80  


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


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


Lys Arg 
        


<210>  12
<211>  19
<212>  PRT
<213>  ˹

<220>
<223>  Դź

<400>  12

Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala Ile Leu Lys Gly 
1               5                   10                  15      


Val Gln Cys 
            


<210>  13
<211>  57
<212>  DNA
<213>  ˹

<220>
<223>  ԴźDNA

<400>  13
atggagtttg ggctgagctg ggttttcctt gttgctatat taaaaggtgt ccagtgt          57


<210>  14
<211>  22
<212>  PRT
<213>  ˹

<220>
<223>  Դźİ

<400>  14

Met Asp Met Arg Val Leu Ala Gln Leu Leu Gly Leu Leu Leu Leu Cys 
1               5                   10                  15      


Phe Pro Gly Ala Arg Cys 
            20          


<210>  15
<211>  66
<212>  DNA
<213>  ˹

<220>
<223>  ԴźDNA

<400>  15
atggacatga gggtgctggc ccagctgctg ggactgctgc tgctgtgctt cccaggcgcc       60

agatgc                                                                  66


<210>  16
<211>  19
<212>  PRT
<213>  ˹

<220>
<223>  TIGITźİ

<400>  16

Met Lys Leu Pro Val Arg Leu Leu Val Leu Met Phe Trp Ile Pro Ala 
1               5                   10                  15      


Ser Ser Ser 
            


<210>  17
<211>  60
<212>  DNA
<213>  ˹

<220>
<223>  TIGITźDNA

<400>  17
atggagacag acacactcct gctatgggta ctgctgctct gggttccagg ttccactggt       60


<210>  18
<211>  19
<212>  PRT
<213>  ˹

<220>
<223>  TIGITźİ

<400>  18

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


Val His Ser 
            


<210>  19
<211>  57
<212>  DNA
<213>  ˹

<220>
<223>  TIGITźDNA

<400>  19
atggagcggc actggatctt cctgttcctg ttctccgtga ccgccggcgt gcactcc          57


<210>  20
<211>  119
<212>  PRT
<213>  ˹

<220>
<223>  TIGIT m10D8ɱ

<400>  20

Glu Val Lys Leu Gln 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 Ser Tyr 
            20                  25                  30          


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


Ala Thr Ile Asn Ser Asn Gly Gly Ser Thr Tyr Tyr Pro 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 Lys Ser Glu Asp Thr Ala Met Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Leu Gly Thr Gly Thr Leu Gly Phe Ala Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  21
<211>  6
<212>  PRT
<213>  ˹

<220>
<223>  m10D8 HCDR1

<400>  21

Ser Ser Tyr Gly Met Ser 
1               5       


<210>  22
<211>  17
<212>  PRT
<213>  ˹

<220>
<223>  m10D8 HCDR2

<400>  22

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


Gly 
    


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

<220>
<223>  m10D8 HCDR3

<400>  23

Leu Gly Thr Gly Thr Leu Gly Phe Ala Tyr 
1               5                   10  


<210>  24
<211>  108
<212>  PRT
<213>  ˹

<220>
<223>  TIGIT m10D8ɱ

<400>  24

Asp Ile Val Met Thr Gln Ala His Lys Phe Met Ser Thr Ser Gly Gly 
1               5                   10                  15      


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


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


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


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


Glu Asp Leu Ala Leu Tyr Tyr Cys Gln Gln His Tyr Ser Thr Pro Trp 
                85                  90                  95      


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


<210>  25
<211>  11
<212>  PRT
<213>  ˹

<220>
<223>  m10D8 LCDR1

<400>  25

Lys Ala Ser Gln Asp Val Lys Thr Ala Val Ser 
1               5                   10      


<210>  26
<211>  7
<212>  PRT
<213>  ˹

<220>
<223>  m10D8 LCDR2

<400>  26

Trp Ala Ser Thr Arg His Thr 
1               5           


<210>  27
<211>  9
<212>  PRT
<213>  ˹

<220>
<223>  m10D8 LCDR3

<400>  27

Gln Gln His Tyr Ser Thr Pro Trp Thr 
1               5                   


<210>  28
<211>  330
<212>  PRT
<213>  ˹

<220>
<223>  IgG1㶨

<400>  28

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


Ser Thr Ser Gly Gly 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 Gln Thr 
65                  70                  75                  80  


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


Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys 
            100                 105                 110         


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


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


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


Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
                165                 170                 175     


Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
            180                 185                 190         


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


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


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


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


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


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


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


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


Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                325                 330 


<210>  29
<211>  330
<212>  PRT
<213>  ˹

<220>
<223>  IgG1㶨2

<400>  29

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


Ser Thr Ser Gly Gly 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 Gln Thr 
65                  70                  75                  80  


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


Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys 
            100                 105                 110         


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


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


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


Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
                165                 170                 175     


Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
            180                 185                 190         


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


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


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


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


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


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


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


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


Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                325                 330 


<210>  30
<211>  107
<212>  PRT
<213>  ˹

<220>
<223>  IgG1㶨

<400>  30

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>  31
<211>  330
<212>  PRT
<213>  ˹

<220>
<223>  СIgG2a㶨

<400>  31

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>  32
<211>  107
<212>  PRT
<213>  ˹

<220>
<223>  СIgG2a㶨

<400>  32

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>  33
<211>  119
<212>  PRT
<213>  ˹

<220>
<223>  h10D8V1V

<400>  33

Gln Val Gln Leu Gln Glu Ser Gly Gly Glu Leu Gly Lys 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          


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


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


Ala Arg Leu Gly Thr Gly Thr Leu Gly Phe Ala Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  34
<211>  107
<212>  PRT
<213>  ˹

<220>
<223>  h10D8V1V

<400>  34

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


Asp Thr Ile Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Lys Thr Ala 
            20                  25                  30          


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


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


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


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


Thr Phe Gly Gln Gly Thr Lys Val Asp Ile Lys 
            100                 105         


<210>  35
<211>  119
<212>  PRT
<213>  ˹

<220>
<223>  h10D8OFV

<400>  35

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 Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          


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


Ala Thr Ile Asn Ser Asn Gly Gly Ser Thr Tyr Tyr Pro 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 Arg Leu Gly Thr Gly Thr Leu Gly Phe Ala Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  36
<211>  107
<212>  PRT
<213>  ˹

<220>
<223>  h10D8OFV

<400>  36

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


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


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


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


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


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


Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105         


<210>  37
<211>  119
<212>  PRT
<213>  ˹

<220>
<223>  h10D8V3V

<400>  37

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 Ser Tyr 
            20                  25                  30          


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


Ala Thr Ile Asn Ser Asn Gly Gly Ser Thr Tyr Tyr Pro 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 Leu Gly Thr Gly Thr Leu Gly Phe Ala Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  38
<211>  107
<212>  PRT
<213>  ˹

<220>
<223>  h10D8V3V

<400>  38

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 Lys Ala Ser Gln Asp Val Lys Thr Ala 
            20                  25                  30          


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


Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Tyr Ser Thr Pro Trp 
                85                  90                  95      


Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105         


<210>  39
<211>  119
<212>  PRT
<213>  ˹

<220>
<223>  h10D8V4V

<400>  39

Gln Val Gln Leu Gln 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          


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


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


Ala Arg Leu Gly Thr Gly Thr Leu Gly Phe Ala Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  40
<211>  107
<212>  PRT
<213>  ˹

<220>
<223>  h10D8V4V

<400>  40

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


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


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


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


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


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


Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105         


<210>  41
<211>  119
<212>  PRT
<213>  ˹

<220>
<223>  h10D8V5V

<400>  41

Gln Val Gln Leu Gln 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          


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


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


Ala Arg Leu Gly Thr Gly Thr Leu Gly Phe Ala Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  42
<211>  107
<212>  PRT
<213>  ˹

<220>
<223>  h10D8V5V

<400>  42

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


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


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


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


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


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


Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105         


<210>  43
<211>  7
<212>  PRT
<213>  ˹

<220>
<223>  LCDR2 ͻ

<400>  43

Trp Ala Ser Thr Arg Ala Thr 
1               5           


<210>  44
<211>  449
<212>  PRT
<213>  ˹

<220>
<223>  h10D8OF

<400>  44

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 Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          


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


Ala Thr Ile Asn Ser Asn Gly Gly Ser Thr Tyr Tyr Pro 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 Arg Leu Gly Thr Gly Thr Leu Gly Phe Ala Tyr Trp Gly Gln Gly 
            100                 105                 110         


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


Pro Leu Ala Pro 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>  45
<211>  214
<212>  PRT
<213>  ˹

<220>
<223>  h10D8OF

<400>  45

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


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


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


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


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


Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln His Tyr Ser Thr Pro Trp 
                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>  46
<211>  1350
<212>  DNA
<213>  ˹

<220>
<223>  h10D8OF

<400>  46
caggtgcagc tggtggagtc cggcggcgga gtggtgcagc ctggaaggtc cctgagactg       60

gactgtaagg ccagcggctt cacctttagc agctacggca tgagctgggt gagacaggcc      120

cctggcaagg gcctggagct ggtggctacc atcaatagca atggcggcag cacctactac      180

cccgacagcg tgaagggcag attcactatc agcagagaca actccaagaa taccctgttc      240

ctgcagatga atagcctgag agccgaggac accgccgtgt actactgcgc caggctgggc      300

accggcaccc tgggatttgc ctactggggc cagggtaccc tggttaccgt tagcagcgcg      360

agcaccaaag gcccgagcgt gtttccgctg gccccgagca gcaaaagcac cagcggtggc      420

accgcagcgc tgggttgcct ggtgaaagat tatttcccgg aaccggtgac ggtgtcgtgg      480

aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga      540

ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac ccagacctac      600

atctgcaacg tgaatcacaa gcccagcaac accaaggtgg acaagaaagt tgagcccaaa      660

tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg      720

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag      780

gtcacatgcg tggtggtgga cgtgagccac gaagaccctg aggtcaagtt caactggtac      840

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc      900

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag      960

tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa     1020

gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg     1080

accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc     1140

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg     1200

gactccgacg gctccttctt cctctacagc aagctcaccg tggacaagag caggtggcag     1260

caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag     1320

aagagcctct ccctgtctcc gggtaaatga                                      1350


<210>  47
<211>  645
<212>  DNA
<213>  ˹

<220>
<223>  h10D8OF

<400>  47
gagatcgtga tgacccagag ccccgccacc ctgtccctga gcccaggaga gagagccacc       60

ctgagctgca aggcctccca ggacgtgaag accgccgtga gctggtatca acagaagcct      120

ggccaggccc ccagactgct gatctactgg gcctccacca gggccaccgg catccctgct      180

agattcagcg gctccggctc cggcaccgat tacaccctga ccatcagcag cctggagcct      240

gaggatttcg ccgtgtacta ctgtcagcag cactactcca ccccttggac cttcggccag      300

ggcaccaagg tggagatcaa gcgtacggtg gctgcaccat ctgtcttcat cttcccgcca      360

tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat      420

cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag      480

gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg      540

ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc      600

ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttga                      645


<210>  48
<211>  423
<212>  DNA
<213>  ˹

<220>
<223>  TIGIT

<400>  48
atgcgctggt gtctgctgct gatttgggcc cagggactga gacaggctcc tctggcttca       60

ggaatgatga ccggcaccat cgagaccacc ggaaacatca gcgccgagaa gggaggaagc      120

atcatcctcc agtgccacct gagtagcaca accgcacagg tcacccaggt caattgggag      180

cagcaggacc agctgctggc catttgcaac gccgatctgg gttggcacat ctctcctagc      240

ttcaaggaca gagtggcccc aggaccagga ctgggactga cactgcagag tctgaccgtg      300

aacgacaccg gcgagtactt ctgcatctac cacacctacc cagacggcac ctacacagga      360

cggatcttcc tggaggtgct ggagtctagc gtggcagagc acggagccag attccagatc      420

cct                                                                    423


<210>  49
<211>  990
<212>  DNA
<213>  ˹

<220>
<223>  СIgG2a㶨

<400>  49
gccaagacca ccgcccctag cgtgtaccct ctggcccctg tgtgtggcga taccaccggc       60

tcctccgtga ccctgggctg tctggtgaag ggctacttcc ctgagcccgt gaccctgacc      120

tggaatagcg gcagcctgag cagcggcgtg cacaccttcc ccgccgtgct gcagtccgac      180

ctgtacaccc tgtcctccag cgtgaccgtg acctcctcca cctggcctag ccagagcatc      240

acctgcaacg tggctcaccc cgctagcagc accaaggtgg acaagaagat cgagcccagg      300

ggccctacca tcaagccttg ccctccctgc aagtgccccg ctcctaacct gctgggcggc      360

ccaagcgtgt tcatctttcc ccccaagatc aaggatgtgc tgatgatcag cctgagcccc      420

atcgtgacct gtgtggtggt ggacgtgtcc gaggatgatc ccgatgtgca gatcagctgg      480

ttcgtgaaca acgtggaggt gcacaccgct cagacccaga cccaccggga ggactataat      540

agcaccctga gggtggtgag cgctctgcct atccagcacc aggactggat gtccggcaag      600

gagtttaagt gtaaggtgaa caacaaggat ctgcccgccc ccatcgagcg gaccatcagc      660

aagcccaagg gcagcgtgcg ggcccctcag gtttatgtgc tgcccccccc tgaggaggag      720

atgaccaaga agcaggtgac cctgacatgc atggtgaccg actttatgcc cgaggatatc      780

tacgtggagt ggaccaacaa tggcaagacc gagctgaact acaagaacac cgagcccgtg      840

ctggattccg acggcagcta tttcatgtac tccaagctgc gggtggagaa gaagaactgg      900

gtggagcgga acagctatag ctgctccgtg gtgcacgagg gcctgcacaa ccaccacacc      960

accaagagct tttcccggac ccccggtaaa                                       990


<210>  50
<211>  321
<212>  DNA
<213>  ˹

<220>
<223>  СIgG2a㶨

<400>  50
cgtgctgacg ccgcccctac cgtgagcatc tttcctccct ccagcgagca gctgaccagc       60

ggcggagcct ccgtggtgtg ctttctgaac aacttttatc ctaaggacat caatgtgaag      120

tggaagatcg atggctccga gaggcagaat ggcgtgctga actcctggac cgatcaggac      180

tccaaggact ccacctactc catgtccagc accctgaccc tgaccaagga tgagtatgag      240

cggcacaatt cctatacctg tgaggctacc cacaagacca gcacctcccc tatcgtgaag      300

agcttcaata ggaacgagtg t                                                321


<210>  51
<211>  366
<212>  DNA
<213>  ˹

<220>
<223>  CD3ɱ

<400>  51
gtgctagccc aggtccagct gcagcagtct ggggctgaac tggcaagacc tggggcctca       60

gtgaagatgt cctgcaaggc ttctggctac acctttacta ggtacacgat gcactgggta      120

aaacagaggc ctggacaggg tctggaatgg attggataca ttaatcctag ccgtggttat      180

actaattaca atcagaagtt caaggacaag gccacattga ctacagacaa atcctccagc      240

acagcctaca tgcaactgag cagcctgaca tctgaggact ctgcagtcta ttactgtgca      300

agatattatg atgatcatta ctgccttgac tactggggcc aaggcaccac ggtgaccgtg      360

agcgcc                                                                 366


<210>  52
<211>  45
<212>  DNA
<213>  ˹

<220>
<223>  

<400>  52
gggggaggtg gcagcggggg aggtggcagc ggcggcggga gctcc                       45


<210>  53
<211>  381
<212>  DNA
<213>  ˹

<220>
<223>  CD3ɱ

<400>  53
gggggaggtg gcagcggggg aggtggcagc ggcggcggga gctcccaaat tgttctcacc       60

cagtctccag caatcatgtc tgcatctcca ggggagaagg tcaccatgac ctgcagtgcc      120

agctcaagtg taagttacat gaactggtac cagcagaagt caggcacctc ccccaaaaga      180

tggatttatg acacatccaa actggcttct ggagtccctg ctcacttcag gggcagtggg      240

tctgggacct cttactctct cacaatcagc ggcatggagg ctgaagatgc tgccacttat      300

tactgccagc agtggagtag taacccattc acgttcggct cggggacaaa gttggaaata      360

aaccggggcg gtggggatcc c                                                381


<210>  54
<211>  1254
<212>  DNA
<213>  ˹

<220>
<223>  ȫPVR

<400>  54
atggctagag ctatggctgc tgcttggcca ctgctgctgg tggccctgct ggtgctgtct       60

tggccccctc caggaaccgg cgacgtggtg gtgcaggctc caacccaggt gcctggcttc      120

ctgggcgatt ccgtgacact gccttgctac ctgcaggtgc caaacatgga ggtgacacac      180

gtgagccagc tgacatgggc tagacatgga gagtctggct ccatggccgt gttccaccag      240

acccagggcc ctagctactc tgagtccaag cgcctggagt ttgtggctgc tagactggga      300

gctgagctga ggaatgcttc cctgcggatg tttggcctga gagtggagga cgagggcaat      360

tatacatgcc tgttcgtgac ctttccacag ggcagccggt ctgtggatat ctggctgaga      420

gtgctggcca agccccagaa cacagctgag gtgcagaagg tgcagctgac aggagagcct      480

gtgccaatgg ctagatgcgt gtccacaggc ggcaggcccc ctgctcagat cacctggcac      540

tctgacctgg gcggcatgcc caatacatct caggtcccag gcttcctgtc cggcaccgtg      600

acagtgacca gcctgtggat tctggtgcct tccagccagg tggatggcaa gaacgtgacc      660

tgcaaggtgg agcatgagag ctttgagaag ccacagctgc tgacagtgaa tctgaccgtg      720

tactatccac ccgaggtgtc catcagcggc tacgacaaca attggtatct gggccagaat      780

gaggccacac tgacctgtga tgctaggtct aaccctgagc caaccggcta taattggtcc      840

accacaatgg gcccactgcc tccattcgct gtggctcagg gagctcagct gctgatcaga      900

ccagtggaca agcccatcaa caccacactg atctgtaacg tgacaaatgc tctgggcgcc      960

agacaggctg agctgaccgt gcaggtgaag gagggccctc catctgagca ttccggcatc     1020

agccgcaatg ccattatctt cctggtgctg ggcatcctgg tgttcctgat cctgctggga     1080

atcggcatct acttctactg gtccaagtgc tccagggagg tgctgtggca ttgccatctg     1140

tgcccttcct ccaccgagca tgcttctgct tccgctaacg gccacgtgtc ttactccgct     1200

gtgtccagag agaactcctc ctcccaggac cctcagacag agggcaccag gtga           1254


<210>  55
<211>  735
<212>  DNA
<213>  ˹

<220>
<223>  ȫTIGIT

<400>  55
atgcgctggt gtctgctgct gatttgggcc cagggactga gacaggctcc tctggcttca       60

ggaatgatga ccggcaccat cgagaccacc ggaaacatca gcgccgagaa gggaggaagc      120

atcatcctcc agtgccacct gagtagcaca accgcacagg tcacccaggt caattgggag      180

cagcaggacc agctgctggc catttgcaac gccgatctgg gttggcacat ctctcctagc      240

ttcaaggaca gagtggcccc aggaccagga ctgggactga cactgcagag tctgaccgtg      300

aacgacaccg gcgagtactt ctgcatctac cacacctacc cagacggcac ctacacagga      360

cggatcttcc tggaggtgct ggagtctagc gtggcagagc acggagccag attccagatc      420

cctctgctgg gagctatggc agctacactg gtcgtgatct gcaccgcagt gatcgtggtc      480

gtggctctga cacggaagaa gaaggccctg agaatccaca gcgtggaggg agacctgaga      540

agaaagagcg ccggacagga ggagtggtct cctagcgctc cttctcctcc aggctcttgt      600

gtgcaggcag aagcagctcc agcaggtctc tgcggagaac agagaggaga ggattgcgcc      660

gagctgcacg actacttcaa cgtgctgagc taccggagcc tgggcaattg cagcttcttc      720

accgagaccg gatga                                                       735


<210>  56
<211>  1011
<212>  DNA
<213>  ˹

<220>
<223>  ȫCD226

<400>  56
atggactacc ccaccctgct gctggccctg ctgcacgtgt acagggccct gtgcgaggag       60

gtgctgtggc acacaagcgt gcctttcgcc gagaacatga gcctggagtg cgtgtaccct      120

agcatgggca tcctgaccca ggtggagtgg ttcaagatcg gcacccagca ggattccatc      180

gccatcttta gccccacaca cggcatggtg atcaggaagc cttacgccga gagagtgtac      240

ttcctgaata gcaccatggc cagcaataat atgaccctgt tctttagaaa cgcctccgag      300

gatgacgtgg gctactactc ctgttccctg tacacctacc ctcagggcac ctggcagaag      360

gtgatccagg tggtgcagtc cgatagcttt gaggccgccg tgccttccaa ctcccacatc      420

gtgagcgagc ccggcaagaa tgtgacactg acatgccagc cccagatgac ctggcccgtg      480

caggccgtga ggtgggagaa gatccagcct aggcagatcg atctgctgac ctactgtaat      540

ctggtgcacg gcagaaactt caccagcaag ttccccagac agatcgtgtc caattgttcc      600

cacggcaggt ggagcgtgat cgtgatccct gatgtgacag tgtccgactc cggcctgtac      660

agatgctacc tgcaggccag cgccggcgag aacgagacct tcgtgatgag actgaccgtg      720

gccgagggca agaccgacaa tcagtacaca ctgtttgtgg ccggcggcac agtgctgctg      780

ctgctgttcg tgatcagcat caccacaatc atcgtgatct ttctgaatag aagaaggaga      840

agagagagga gagatctgtt cacagagagc tgggataccc agaaggcccc taataactac      900

aggtccccta tctccacatc ccagcctacc aatcagtcca tggatgatac aagggaggac      960

atctacgtga attaccctac attcagcaga agacctaaga ccagagtgtg a              1011


<210>  57
<211>  384
<212>  DNA
<213>  ˹

<220>
<223>  IL-2ӦԪ

<400>  57
ggtaccattt tctgagttac ttttgtatcc ccaccccctt aaagaaagga ggaaaaactg       60

tttcatacag aaggcgttaa ttgcatgaat tagagctatc acctaagtgt gggctaatgt      120

aacaaagagg gatttcacct acatccattc agtcagtctt tgggggttta aagaaattcc      180

aaagagtcat cagaagagga aaaatgaagg taatgttttt tcagacaggt aaagtctttg      240

aaaatatgtg taatatgtaa aacattttga cacccccata atatttttcc agaattaaca      300

gtataaattg catctcttgt tcaagagttc cctatcactc tctttaatca ctactcacag      360

taacctcaac tcctgccaaa gctt                                             384


