﻿                         序列表

<110>  江苏恒瑞医药股份有限公司
       上海恒瑞医药有限公司

<120>  一种PD-L1抗体药物组合物及其用途

<130>  P184014191C

<150>  CN201710341680.7
<151>  2017-05-16

<160>  29

<170>  SIPOSequenceListing 1.0

<210>  1
<211>  5
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  DOMAIN
<223>  抗体1的HCDR1


<220>
<221>  UNSURE
<222>  (5)..(5)
<223>  Xaa选自N或T。


<220>
<221>  UNSURE
<222>  (5)..(5)
<223>  The 'Xaa' at location 5 stands for Asn or Thr.


<400>  1
Asn Asp Tyr Trp Xaa 
1               5   

<210>  2
<211>  16
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  DOMAIN
<223>  抗体1的HCDR2


<400>  2
Tyr Ile Ser Tyr Thr Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser 
1               5                   10                  15      

<210>  3
<211>  10
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  3
Ser Gly Gly Trp Leu Ala Pro Phe Asp Tyr 
1               5                   10  

<210>  4
<211>  17
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  DOMAIN
<223>  抗体1的LCDR1


<220>
<221>  UNSURE
<222>  (9)..(9)
<223>  Xaa选自R或H。


<220>
<221>  UNSURE
<222>  (14)..(14)
<223>  Xaa选自N或H。


<220>
<221>  UNSURE
<222>  (9)..(9)
<223>  The 'Xaa' at location 9 stands for  Arg or His.


<220>
<221>  UNSURE
<222>  (14)..(14)
<223>  The 'Xaa' at location 14 stands for  Asn or His.


<400>  4
Lys Ser Ser Gln Ser Leu Phe Tyr Xaa Ser Asn Gln Lys Xaa Ser Leu 
1               5                   10                  15      
Ala 
    

<210>  5
<211>  7
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  DOMAIN
<223>  抗体1的LCDR2


<400>  5
Gly Ala Ser Thr Arg Glu Ser 
1               5           

<210>  6
<211>  9
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  DOMAIN
<223>  抗体1的LCDR3


<400>  6
Gln Gln Tyr Tyr Gly Tyr Pro Tyr Thr 
1               5                   

<210>  7
<211>  5
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  DOMAIN
<223>  抗体2的HCDR1


<400>  7
Ser Tyr Trp Met His 
1               5   

<210>  8
<211>  17
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  DOMAIN
<223>  抗体2的HCDR2


<220>
<221>  UNSURE
<222>  (3)..(3)
<223>  Xaa选自H或G。


<220>
<221>  UNSURE
<222>  (8)..(8)
<223>  Xaa选自G或F。


<220>
<221>  UNSURE
<222>  (3)..(3)
<223>  The 'Xaa' at location 3 stands for His or Gly.


<220>
<221>  UNSURE
<222>  (8)..(8)
<223>  The 'Xaa' at location 8 stands for Gly or Phe.
.


<400>  8
Arg Ile Xaa Pro Asn Ser Gly Xaa Thr Ser Tyr Asn Glu Lys Phe Lys 
1               5                   10                  15      
Asn 
    

<210>  9
<211>  10
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  DOMAIN
<223>  抗体2的HCDR3


<400>  9
Gly Gly Ser Ser Tyr Asp Tyr Phe Asp Tyr 
1               5                   10  

<210>  10
<211>  15
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  DOMAIN
<223>  抗体2的LCDR1


<400>  10
Arg Ala Ser Glu Ser Val Ser Ile His Gly Thr His Leu Met His 
1               5                   10                  15  

<210>  11
<211>  7
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  DOMAIN
<223>  抗体2的LCDR2


<400>  11
Ala Ala Ser Asn Leu Glu Ser 
1               5           

<210>  12
<211>  9
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  DOMAIN
<223>  抗体2的LCDR3


<400>  12
Gln Gln Ser Phe Glu Asp Pro Leu Thr 
1               5                   

<210>  13
<211>  119
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  DOMAIN
<223>  亲和力成熟后的人源化抗体2的重链可变区序列


<400>  13
Gln Val Gln Leu Val Gln Ser Gly Ala 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 Ser Tyr 
            20                  25                  30          
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              
Gly Arg Ile Gly Pro Asn Ser Gly Phe Thr Ser Tyr Asn Glu Lys Phe 
    50                  55                  60                  
Lys Asn Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Ser Ser Tyr Asp Tyr Phe Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         
Thr Thr Val Thr Val Ser Ser 
        115                 

<210>  14
<211>  111
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  DOMAIN
<223>  亲和力成熟后的人源化抗体2的轻链可变区


<400>  14
Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala Val Ser Pro Gly 
1               5                   10                  15      
Gln Arg Ala Thr Ile Thr Cys Arg Ala Ser Glu Ser Val Ser Ile His 
            20                  25                  30          
Gly Thr His Leu Met His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 
        35                  40                  45              
Lys Leu Leu Ile Tyr Ala Ala Ser Asn 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 Asn 
65                  70                  75                  80  
Pro Val Glu Ala Glu Asp Thr Ala Asn Tyr Tyr Cys Gln Gln Ser Phe 
                85                  90                  95      
Glu Asp Pro Leu Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110     

<210>  15
<211>  446
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  CHAIN
<223>  HRP00052抗体重链序列


<400>  15
Gln Val Gln Leu Val Gln Ser Gly Ala 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 Ser Tyr 
            20                  25                  30          
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              
Gly Arg Ile Gly Pro Asn Ser Gly Phe Thr Ser Tyr Asn Glu Lys Phe 
    50                  55                  60                  
Lys Asn Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Ser Ser Tyr Asp Tyr Phe Asp Tyr 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 Cys Ser Arg Ser Thr Ser Glu Ser 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 Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro 
        195                 200                 205             
Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro 
    210                 215                 220                 
Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe 
225                 230                 235                 240 
Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
                245                 250                 255     
Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val 
            260                 265                 270         
Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
        275                 280                 285             
Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val 
    290                 295                 300                 
Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
305                 310                 315                 320 
Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser 
                325                 330                 335     
Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
            340                 345                 350         
Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 
        355                 360                 365             
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 
    370                 375                 380                 
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp 
385                 390                 395                 400 
Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp 
                405                 410                 415     
Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
            420                 425                 430         
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 
        435                 440                 445     

<210>  16
<211>  1341
<212>  DNA
<213>  人工序列(Artificial Sequence)

<220>
<221>  gene
<223>  HRP00052抗体重链序列编码基因序列


<400>  16
caggtgcaac tggtgcagag cggtgccgag gtgaagaagc ctggcgcaag cgtgaaagtg        60
agctgcaagg ccagcggcta caccttcacc agctactgga tgcactgggt gaggcaggcc       120
cctggacagg gcctggagtg gatgggcagg atcgggccca acagtggttt cactagctac       180
aatgaaaagt tcaagaacag ggtaaccatg accagggaca cctccaccag cacagtgtat       240
atggagctga gcagcctgag gagcgaggac accgccgtgt actactgtgc cagaggcggc       300
agcagctacg actacttcga ctattggggc cagggcacca ccgtgaccgt gagcagtgct       360
tccaccaagg gcccatcggt cttccccctg gcgccctgct ccaggagcac ctccgagagc       420
acagccgccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg       480
aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga       540
ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggcac gaagacctac       600
acctgcaacg tagatcacaa gcccagcaac accaaggtgg acaagagagt tgagtccaaa       660
tatggtcccc catgcccacc atgcccagca cctgaggctg ctgggggacc atcagtcttc       720
ctgttccccc caaaacccaa ggacactctc atgatctccc ggacccctga ggtcacgtgc       780
gtggtggtgg acgtgagcca ggaagacccc gaggtccagt tcaactggta cgtggatggc       840
gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agttcaacag cacgtaccgt       900
gtggtcagcg tcctcaccgt cctgcaccag gactggctga acggcaagga gtacaagtgc       960
aaggtctcca acaaaggcct cccgtcctcc atcgagaaaa ccatctccaa agccaaaggg      1020
cagccccgag agccacaggt gtacaccctg cccccatccc aggaggagat gaccaagaac      1080
caggtcagcc tgacctgcct ggtcaaaggc ttctacccca gcgacatcgc cgtggagtgg      1140
gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac      1200
ggctccttct tcctctacag caggctcacc gtggacaaga gcaggtggca ggaggggaat      1260
gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacaca gaagagcctc      1320
tccctgtctc tgggtaaatg a                                                1341

<210>  17
<211>  218
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  CHAIN
<223>  HRP00052抗体轻链序列


<400>  17
Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala Val Ser Pro Gly 
1               5                   10                  15      
Gln Arg Ala Thr Ile Thr Cys Arg Ala Ser Glu Ser Val Ser Ile His 
            20                  25                  30          
Gly Thr His Leu Met His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 
        35                  40                  45              
Lys Leu Leu Ile Tyr Ala Ala Ser Asn 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 Asn 
65                  70                  75                  80  
Pro Val Glu Ala Glu Asp Thr Ala Asn Tyr Tyr Cys Gln Gln Ser Phe 
                85                  90                  95      
Glu Asp Pro Leu Thr Phe Gly Gln Gly Thr Lys Leu 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>  18
<211>  657
<212>  DNA
<213>  人工序列(Artificial Sequence)

<220>
<221>  gene
<223>  HRP00052抗体轻链序列编码基因序列


<400>  18
gacatcgtgc tgacccagag tcccgcctca cttgccgtga gccccggtca gagggccacc        60
atcacctgta gggccagcga gagcgtgagc atccacggca cccacctgat gcactggtat       120
caacagaaac ccggccagcc ccccaaactg ctgatctacg ccgccagcaa cctggagagc       180
ggcgtgcccg ccaggttcag cggctccggc agcggcaccg acttcaccct cactatcaac       240
cccgtggagg ccgaggacac cgccaactac tactgccagc agagcttcga ggaccccctg       300
accttcggcc agggcaccaa gctggagatc aagcgtacgg tggctgcacc atctgtcttc       360
atcttcccgc catctgatga gcagttgaaa tctggaactg cctctgttgt gtgcctgctg       420
aataacttct atcccagaga ggccaaagta cagtggaagg tggataacgc cctccaatcg       480
ggtaactccc aggagagtgt cacagagcag gacagcaagg acagcaccta cagcctcagc       540
agcaccctga cgctgagcaa agcagactac gagaaacaca aagtctacgc ctgcgaagtc       600
acccatcagg gcctgagctc gcccgtcaca aagagcttca acaggggaga gtgttga          657

<210>  19
<211>  290
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  PEPTIDE
<223>  人PD-L1全长氨基酸序列


<400>  19
Met Arg Ile Phe Ala Val Phe Ile Phe Met Thr Tyr Trp His Leu Leu 
1               5                   10                  15      
Asn Ala Phe Thr Val Thr Val Pro Lys Asp Leu Tyr Val Val Glu Tyr 
            20                  25                  30          
Gly Ser Asn Met Thr Ile Glu Cys Lys Phe Pro Val Glu Lys Gln Leu 
        35                  40                  45              
Asp Leu Ala Ala Leu Ile Val Tyr Trp Glu Met Glu Asp Lys Asn Ile 
    50                  55                  60                  
Ile Gln Phe Val His Gly Glu Glu Asp Leu Lys Val Gln His Ser Ser 
65                  70                  75                  80  
Tyr Arg Gln Arg Ala Arg Leu Leu Lys Asp Gln Leu Ser Leu Gly Asn 
                85                  90                  95      
Ala Ala Leu Gln Ile Thr Asp Val Lys Leu Gln Asp Ala Gly Val Tyr 
            100                 105                 110         
Arg Cys Met Ile Ser Tyr Gly Gly Ala Asp Tyr Lys Arg Ile Thr Val 
        115                 120                 125             
Lys Val Asn Ala Pro Tyr Asn Lys Ile Asn Gln Arg Ile Leu Val Val 
    130                 135                 140                 
Asp Pro Val Thr Ser Glu His Glu Leu Thr Cys Gln Ala Glu Gly Tyr 
145                 150                 155                 160 
Pro Lys Ala Glu Val Ile Trp Thr Ser Ser Asp His Gln Val Leu Ser 
                165                 170                 175     
Gly Lys Thr Thr Thr Thr Asn Ser Lys Arg Glu Glu Lys Leu Phe Asn 
            180                 185                 190         
Val Thr Ser Thr Leu Arg Ile Asn Thr Thr Thr Asn Glu Ile Phe Tyr 
        195                 200                 205             
Cys Thr Phe Arg Arg Leu Asp Pro Glu Glu Asn His Thr Ala Glu Leu 
    210                 215                 220                 
Val Ile Pro Glu Leu Pro Leu Ala His Pro Pro Asn Glu Arg Thr His 
225                 230                 235                 240 
Leu Val Ile Leu Gly Ala Ile Leu Leu Cys Leu Gly Val Ala Leu Thr 
                245                 250                 255     
Phe Ile Phe Arg Leu Arg Lys Gly Arg Met Met Asp Val Lys Lys Cys 
            260                 265                 270         
Gly Ile Gln Asp Thr Asn Ser Lys Lys Gln Ser Asp Thr His Leu Glu 
        275                 280                 285             
Glu Thr 
    290 

<210>  20
<211>  242
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  PEPTIDE
<223>  带His、PADRE标签的PD-L1


<400>  20
Phe Thr Val Thr Val Pro Lys Asp Leu Tyr Val Val Glu Tyr Gly Ser 
1               5                   10                  15      
Asn Met Thr Ile Glu Cys Lys Phe Pro Val Glu Lys Gln Leu Asp Leu 
            20                  25                  30          
Ala Ala Leu Ile Val Tyr Trp Glu Met Glu Asp Lys Asn Ile Ile Gln 
        35                  40                  45              
Phe Val His Gly Glu Glu Asp Leu Lys Val Gln His Ser Ser Tyr Arg 
    50                  55                  60                  
Gln Arg Ala Arg Leu Leu Lys Asp Gln Leu Ser Leu Gly Asn Ala Ala 
65                  70                  75                  80  
Leu Gln Ile Thr Asp Val Lys Leu Gln Asp Ala Gly Val Tyr Arg Cys 
                85                  90                  95      
Met Ile Ser Tyr Gly Gly Ala Asp Tyr Lys Arg Ile Thr Val Lys Val 
            100                 105                 110         
Asn Ala Pro Tyr Asn Lys Ile Asn Gln Arg Ile Leu Val Val Asp Pro 
        115                 120                 125             
Val Thr Ser Glu His Glu Leu Thr Cys Gln Ala Glu Gly Tyr Pro Lys 
    130                 135                 140                 
Ala Glu Val Ile Trp Thr Ser Ser Asp His Gln Val Leu Ser Gly Lys 
145                 150                 155                 160 
Thr Thr Thr Thr Asn Ser Lys Arg Glu Glu Lys Leu Phe Asn Val Thr 
                165                 170                 175     
Ser Thr Leu Arg Ile Asn Thr Thr Thr Asn Glu Ile Phe Tyr Cys Thr 
            180                 185                 190         
Phe Arg Arg Leu Asp Pro Glu Glu Asn His Thr Ala Glu Leu Val Ile 
        195                 200                 205             
Pro Glu Leu Pro Leu Ala His Pro Pro Asn Glu Arg Gly Ser Gly Ala 
    210                 215                 220                 
Lys Phe Val Ala Ala Trp Thr Leu Lys Ala Ala Ala His His His His 
225                 230                 235                 240 
His His 
        

<210>  21
<211>  234
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  PEPTIDE
<223>  带FLAG、HIS标签的PD-L1：PD-L1(ECD)-Flag-His6


<400>  21
Phe Thr Val Thr Val Pro Lys Asp Leu Tyr Val Val Glu Tyr Gly Ser 
1               5                   10                  15      
Asn Met Thr Ile Glu Cys Lys Phe Pro Val Glu Lys Gln Leu Asp Leu 
            20                  25                  30          
Ala Ala Leu Ile Val Tyr Trp Glu Met Glu Asp Lys Asn Ile Ile Gln 
        35                  40                  45              
Phe Val His Gly Glu Glu Asp Leu Lys Val Gln His Ser Ser Tyr Arg 
    50                  55                  60                  
Gln Arg Ala Arg Leu Leu Lys Asp Gln Leu Ser Leu Gly Asn Ala Ala 
65                  70                  75                  80  
Leu Gln Ile Thr Asp Val Lys Leu Gln Asp Ala Gly Val Tyr Arg Cys 
                85                  90                  95      
Met Ile Ser Tyr Gly Gly Ala Asp Tyr Lys Arg Ile Thr Val Lys Val 
            100                 105                 110         
Asn Ala Pro Tyr Asn Lys Ile Asn Gln Arg Ile Leu Val Val Asp Pro 
        115                 120                 125             
Val Thr Ser Glu His Glu Leu Thr Cys Gln Ala Glu Gly Tyr Pro Lys 
    130                 135                 140                 
Ala Glu Val Ile Trp Thr Ser Ser Asp His Gln Val Leu Ser Gly Lys 
145                 150                 155                 160 
Thr Thr Thr Thr Asn Ser Lys Arg Glu Glu Lys Leu Phe Asn Val Thr 
                165                 170                 175     
Ser Thr Leu Arg Ile Asn Thr Thr Thr Asn Glu Ile Phe Tyr Cys Thr 
            180                 185                 190         
Phe Arg Arg Leu Asp Pro Glu Glu Asn His Thr Ala Glu Leu Val Ile 
        195                 200                 205             
Pro Glu Leu Pro Leu Ala His Pro Pro Asn Glu Arg Asp Tyr Lys Asp 
    210                 215                 220                 
Asp Asp Asp Lys His His His His His His 
225                 230                 

<210>  22
<211>  447
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  PEPTIDE
<223>  PD-L1的Fc融合蛋白：PD-L1(ECD)-Fc


<400>  22
Phe Thr Val Thr Val Pro Lys Asp Leu Tyr Val Val Glu Tyr Gly Ser 
1               5                   10                  15      
Asn Met Thr Ile Glu Cys Lys Phe Pro Val Glu Lys Gln Leu Asp Leu 
            20                  25                  30          
Ala Ala Leu Ile Val Tyr Trp Glu Met Glu Asp Lys Asn Ile Ile Gln 
        35                  40                  45              
Phe Val His Gly Glu Glu Asp Leu Lys Val Gln His Ser Ser Tyr Arg 
    50                  55                  60                  
Gln Arg Ala Arg Leu Leu Lys Asp Gln Leu Ser Leu Gly Asn Ala Ala 
65                  70                  75                  80  
Leu Gln Ile Thr Asp Val Lys Leu Gln Asp Ala Gly Val Tyr Arg Cys 
                85                  90                  95      
Met Ile Ser Tyr Gly Gly Ala Asp Tyr Lys Arg Ile Thr Val Lys Val 
            100                 105                 110         
Asn Ala Pro Tyr Asn Lys Ile Asn Gln Arg Ile Leu Val Val Asp Pro 
        115                 120                 125             
Val Thr Ser Glu His Glu Leu Thr Cys Gln Ala Glu Gly Tyr Pro Lys 
    130                 135                 140                 
Ala Glu Val Ile Trp Thr Ser Ser Asp His Gln Val Leu Ser Gly Lys 
145                 150                 155                 160 
Thr Thr Thr Thr Asn Ser Lys Arg Glu Glu Lys Leu Phe Asn Val Thr 
                165                 170                 175     
Ser Thr Leu Arg Ile Asn Thr Thr Thr Asn Glu Ile Phe Tyr Cys Thr 
            180                 185                 190         
Phe Arg Arg Leu Asp Pro Glu Glu Asn His Thr Ala Glu Leu Val Ile 
        195                 200                 205             
Pro Glu Leu Pro Leu Ala His Pro Pro Asn Glu Arg Asp Lys Thr His 
    210                 215                 220                 
Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu 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 His Glu Asp Pro Glu 
            260                 265                 270         
Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
        275                 280                 285             
Thr Lys Pro Arg Glu Glu Gln Tyr 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 Ala Leu Pro Ala Pro 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 Arg 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 Lys Leu Thr Val Asp Lys Ser Arg 
                405                 410                 415     
Trp Gln Gln 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 Pro Gly Lys 
        435                 440                 445         

<210>  23
<211>  382
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  PEPTIDE
<223>  PD-1的Fc融合蛋白：PD-1(ECD)-Fc


<400>  23
Pro Gly Trp Phe Leu Asp Ser Pro Asp Arg Pro Trp Asn Pro Pro Thr 
1               5                   10                  15      
Phe Ser Pro Ala Leu Leu Val Val Thr Glu Gly Asp Asn Ala Thr Phe 
            20                  25                  30          
Thr Cys Ser Phe Ser Asn Thr Ser Glu Ser Phe Val Leu Asn Trp Tyr 
        35                  40                  45              
Arg Met Ser Pro Ser Asn Gln Thr Asp Lys Leu Ala Ala Phe Pro Glu 
    50                  55                  60                  
Asp Arg Ser Gln Pro Gly Gln Asp Cys Arg Phe Arg Val Thr Gln Leu 
65                  70                  75                  80  
Pro Asn Gly Arg Asp Phe His Met Ser Val Val Arg Ala Arg Arg Asn 
                85                  90                  95      
Asp Ser Gly Thr Tyr Leu Cys Gly Ala Ile Ser Leu Ala Pro Lys Ala 
            100                 105                 110         
Gln Ile Lys Glu Ser Leu Arg Ala Glu Leu Arg Val Thr Glu Arg Arg 
        115                 120                 125             
Ala Glu Val Pro Thr Ala His Pro Ser Pro Ser Pro Arg Pro Ala Gly 
    130                 135                 140                 
Gln Phe Gln Thr Leu Val Glu Pro Lys Ser Ser Asp Lys Thr His Thr 
145                 150                 155                 160 
Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe 
                165                 170                 175     
Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
            180                 185                 190         
Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
        195                 200                 205             
Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
    210                 215                 220                 
Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val 
225                 230                 235                 240 
Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
                245                 250                 255     
Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 
            260                 265                 270         
Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
        275                 280                 285             
Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 
    290                 295                 300                 
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 
305                 310                 315                 320 
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp 
                325                 330                 335     
Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 
            340                 345                 350         
Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
        355                 360                 365             
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    370                 375                 380         


<210> 24
<211>  118
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  DOMAIN
<223>  1 hVH- CDR graft


<400>  24
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
1               5                   10                  15      
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Asn Asp 
            20                  25                  30          
Tyr Trp Asn Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu Trp Ile 
        35                  40                  45              
Gly Tyr Ile Ser Tyr Thr Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys 
    50                  55                  60                  
Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu 
65                  70                  75                  80  
Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      
Arg Ser Gly Gly Trp Leu Ala Pro Phe Asp Tyr Trp Gly Arg Gly Thr 
            100                 105                 110         
Leu Val Thr Val Ser Ser 
        115             

<210>  25
<211>  113
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  DOMAIN
<223>  1 hVL CDR graft


<400>  25
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 Ser Leu Phe Tyr Arg 
            20                  25                  30          
Ser Asn Gln Lys Asn Ser Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
        35                  40                  45              
Pro Pro Lys Leu Leu Ile Tyr Gly 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 Gly Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Val Glu Ile 
            100                 105                 110         
Lys 
    

<210>  26
<211>  119
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  DOMAIN
<223>  2- hVH.1


<400>  26
Gln Val Gln Leu Val Gln Ser Gly Ala 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 Ser Tyr 
            20                  25                  30          
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              
Gly Arg Ile His Pro Asn Ser Gly Gly Thr Ser Tyr Asn Glu Lys Phe 
    50                  55                  60                  
Lys Asn Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Ser Ser Tyr Asp Tyr Phe Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         
Thr Thr Val Thr Val Ser Ser 
        115                 

<210>  27
<211>  111
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<223>  2-hVL.1


<400>  27
Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala Val Ser Pro Gly 
1               5                   10                  15      
Gln Arg Ala Thr Ile Thr Cys Arg Ala Ser Glu Ser Val Ser Ile His 
            20                  25                  30          
Gly Thr His Leu Met His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 
        35                  40                  45              
Lys Leu Leu Ile Tyr Ala Ala Ser Asn 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 Asn 
65                  70                  75                  80  
Pro Val Glu Ala Asn Asp Thr Ala Asn Tyr Tyr Cys Gln Gln Ser Phe 
                85                  90                  95      
Glu Asp Pro Leu Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110     

<210>  28
<211>  118
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  DOMAIN
<223>  亲和力成熟后的人源化抗体1重链可变区


<400>  28
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln 
1               5                   10                  15      
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Asn Asp 
            20                  25                  30          
Tyr Trp Thr Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu Tyr Ile 
        35                  40                  45              
Gly Tyr Ile Ser Tyr Thr Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys 
    50                  55                  60                  
Ser Arg Val Thr Ile Ser Arg Asp Thr Ser Lys Asn Gln Phe Ser Leu 
65                  70                  75                  80  
Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      
Arg Ser Gly Gly Trp Leu Ala Pro Phe Asp Tyr Trp Gly Arg Gly Thr 
            100                 105                 110         
Leu Val Thr Val Ser Ser 
        115             

<210>  29
<211>  113
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220>
<221>  DOMAIN
<223>  亲和力成熟后的人源化抗体1的轻链可变区


<400>  29
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 Ser Leu Phe Tyr His 
            20                  25                  30          
Ser Asn Gln Lys His Ser Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 
        35                  40                  45              
Pro Pro Lys Leu Leu Ile Tyr Gly 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 Gly Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Val Glu Ile 
            100                 105                 110         
Lys 
    


