﻿                         序列表

<110>  长春金赛药业有限责任公司

<120>  抗体融合蛋白、制备方法及其应用

<130>  OP191309

<150>  201811620872.2
<151>  2018-12-28

<160>  13

<170>  SIPOSequenceListing 1.0

<210>  1
<211>  205
<212>  PRT
<213>  结合人VEGF-A的Trap(Trap binding to human VEGF-A)

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

<210>  2
<211>  107
<212>  PRT
<213>  047 Ab-6的VL(VL of 047 Ab-6 )

<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 Ser Ala Ser Gln Asp Val Thr Thr Ala 
            20                  25                  30          
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
        35                  40                  45              
Tyr Ser Ala Ser Phe Pro Tyr Arg 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 Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Met Tyr His Pro Ser 
                85                  90                  95      
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105         

<210>  3
<211>  118
<212>  PRT
<213>  047 Ab-6的VH(VH of 047 Ab-6)

<400>  3
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 Tyr Phe Pro Phe Ser Asp Ser 
            20                  25                  30          
Trp Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ala Trp Ile Ser Pro Tyr Gly Gly Ser Ser Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Gln Asp Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala 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 Lys Arg His Trp Pro Gly Gly Phe Asp His Trp Gly Gln Gly Thr 
            100                 105                 110         
Leu Val Thr Val Ser Ser 
        115             

<210>  4
<211>  443
<212>  PRT
<213>  H1(H1)

<400>  4
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 Tyr Phe Pro Phe Ser Asp Ser 
            20                  25                  30          
Trp Ile His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ala Trp Ile Ser Pro Tyr Gly Gly Ser Ser Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Gln Asp Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala 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 Lys Arg His Trp Pro Gly Gly Phe Asp His Trp Gly Gln Gly Thr 
            100                 105                 110         
Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro 
        115                 120                 125             
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly 
    130                 135                 140                 
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 
145                 150                 155                 160 
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 
                165                 170                 175     
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser 
            180                 185                 190         
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser 
        195                 200                 205             
Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Gly 
    210                 215                 220                 
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ser Asp 
225                 230                 235                 240 
Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile 
                245                 250                 255     
His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser 
            260                 265                 270         
Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile 
        275                 280                 285             
Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile 
    290                 295                 300                 
Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr 
305                 310                 315                 320 
Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gln Thr 
                325                 330                 335     
Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu 
            340                 345                 350         
Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu 
        355                 360                 365             
Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gln 
    370                 375                 380                 
His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gln Ser Gly Ser Glu 
385                 390                 395                 400 
Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser 
                405                 410                 415     
Asp Gln Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys 
            420                 425                 430         
Lys Asn Ser Thr Phe Val Arg Val His Glu Lys 
        435                 440             

<210>  5
<211>  666
<212>  PRT
<213>  H2(H2)

<400>  5
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 Asn Tyr 
            20                  25                  30          
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met 
        35                  40                  45              
Gly Tyr Ile Asn Pro Tyr Asn Asp Gly Thr Lys Tyr Ser Glu Lys Phe 
    50                  55                  60                  
Lys Gly Arg Val Thr Ile Thr Arg Asp Thr Ser Ala 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 Leu Phe Thr Phe Asp Asn Trp Gly Gln Gly Thr Leu 
            100                 105                 110         
Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
        115                 120                 125             
Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
    130                 135                 140                 
Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
145                 150                 155                 160 
Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                165                 170                 175     
Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
            180                 185                 190         
Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
        195                 200                 205             
Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Gly Gly Gly Gly 
    210                 215                 220                 
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ser Asp Thr Gly Arg 
225                 230                 235                 240 
Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr 
                245                 250                 255     
Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile 
            260                 265                 270         
Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly 
        275                 280                 285             
Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala 
    290                 295                 300                 
Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly 
305                 310                 315                 320 
His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gln Thr Asn Thr Ile 
                325                 330                 335     
Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly 
            340                 345                 350         
Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly 
        355                 360                 365             
Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gln His Lys Lys 
    370                 375                 380                 
Leu Val Asn Arg Asp Leu Lys Thr Gln Ser Gly Ser Glu Met Lys Lys 
385                 390                 395                 400 
Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gln Gly 
                405                 410                 415     
Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser 
            420                 425                 430         
Thr Phe Val Arg Val His Glu Lys Asp Lys Thr His Thr Cys Pro Pro 
        435                 440                 445             
Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro 
    450                 455                 460                 
Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 
465                 470                 475                 480 
Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn 
                485                 490                 495     
Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 
            500                 505                 510         
Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 
        515                 520                 525             
Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 
    530                 535                 540                 
Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys 
545                 550                 555                 560 
Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp 
                565                 570                 575     
Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe 
            580                 585                 590         
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
        595                 600                 605             
Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 
    610                 615                 620                 
Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 
625                 630                 635                 640 
Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
                645                 650                 655     
Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
            660                 665     

<210>  6
<211>  666
<212>  PRT
<213>  H3(H3)

<400>  6
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 Asn Tyr 
            20                  25                  30          
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met 
        35                  40                  45              
Gly Tyr Ile Asn Pro Tyr Asn Asp Gly Thr Lys Tyr Ser Glu Lys Phe 
    50                  55                  60                  
Lys Gly Arg Val Thr Ile Thr Arg Asp Thr Ser Ala 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 Leu Phe Thr Phe Asp Asn Trp Gly Gln Gly Thr Leu 
            100                 105                 110         
Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu 
        115                 120                 125             
Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys 
    130                 135                 140                 
Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser 
145                 150                 155                 160 
Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser 
                165                 170                 175     
Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser 
            180                 185                 190         
Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn 
        195                 200                 205             
Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys 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 Asp Glu Leu 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 Gly Gly 
        435                 440                 445             
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ser Asp Thr 
    450                 455                 460                 
Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His 
465                 470                 475                 480 
Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro 
                485                 490                 495     
Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro 
            500                 505                 510         
Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser 
        515                 520                 525             
Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val 
    530                 535                 540                 
Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gln Thr Asn 
545                 550                 555                 560 
Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser 
                565                 570                 575     
Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn 
            580                 585                 590         
Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gln His 
        595                 600                 605             
Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gln Ser Gly Ser Glu Met 
    610                 615                 620                 
Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp 
625                 630                 635                 640 
Gln Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys 
                645                 650                 655     
Asn Ser Thr Phe Val Arg Val His Glu Lys 
            660                 665     

<210>  7
<211>  563
<212>  PRT
<213>  H4(H4)

<400>  7
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 Asn Tyr 
            20                  25                  30          
Val Met His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met 
        35                  40                  45              
Gly Tyr Ile Asn Pro Tyr Asn Asp Gly Thr Lys Tyr Ser Glu Lys Phe 
    50                  55                  60                  
Lys Gly Arg Val Thr Ile Thr Arg Asp Thr Ser Ala 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 Leu Phe Thr Phe Asp Asn Trp Gly Gln Gly Thr Leu 
            100                 105                 110         
Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
        115                 120                 125             
Gly Gly Gly Ser Ser Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser 
    130                 135                 140                 
Glu Ile Pro Glu Ile Ile His Met Thr Glu Gly Arg Glu Leu Val Ile 
145                 150                 155                 160 
Pro Cys Arg Val Thr Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe 
                165                 170                 175     
Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser 
            180                 185                 190         
Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu 
        195                 200                 205             
Leu Thr Cys Glu Ala Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr 
    210                 215                 220                 
Leu Thr His Arg Gln Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro 
225                 230                 235                 240 
Ser His Gly Ile Glu Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys 
                245                 250                 255     
Thr Ala Arg Thr Glu Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr 
            260                 265                 270         
Pro Ser Ser Lys His Gln His Lys Lys Leu Val Asn Arg Asp Leu Lys 
        275                 280                 285             
Thr Gln Ser Gly Ser Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile 
    290                 295                 300                 
Asp Gly Val Thr Arg Ser Asp Gln Gly Leu Tyr Thr Cys Ala Ala Ser 
305                 310                 315                 320 
Ser Gly Leu Met Thr Lys Lys Asn Ser Thr Phe Val Arg Val His Glu 
                325                 330                 335     
Lys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
            340                 345                 350         
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
        355                 360                 365             
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
    370                 375                 380                 
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
385                 390                 395                 400 
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
                405                 410                 415     
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
            420                 425                 430         
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
        435                 440                 445             
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
    450                 455                 460                 
Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val 
465                 470                 475                 480 
Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
                485                 490                 495     
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
            500                 505                 510         
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr 
        515                 520                 525             
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
    530                 535                 540                 
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
545                 550                 555                 560 
Ser Pro Gly 
            

<210>  8
<211>  439
<212>  PRT
<213>  L1(L1)

<400>  8
Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly 
1               5                   10                  15      
Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 
            20                  25                  30          
Lys Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              
Pro Gln Leu Leu Ile Tyr Arg Val Ser Lys Arg Phe Ser Gly Val Pro 
    50                  55                  60                  
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 
65                  70                  75                  80  
Ser Arg Val Glu Ala Gly Asp Val Gly Val Tyr Tyr Cys Ser Gln Ser 
                85                  90                  95      
Thr His Val Pro Phe Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105                 110         
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 
        115                 120                 125             
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 
    130                 135                 140                 
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 
145                 150                 155                 160 
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 
                165                 170                 175     
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 
            180                 185                 190         
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 
        195                 200                 205             
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser 
    210                 215                 220                 
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ser Asp Thr Gly Arg Pro 
225                 230                 235                 240 
Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile Ile His Met Thr Glu 
                245                 250                 255     
Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr Ser Pro Asn Ile Thr 
            260                 265                 270         
Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu Ile Pro Asp Gly Lys 
        275                 280                 285             
Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile Ile Ser Asn Ala Thr 
    290                 295                 300                 
Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala Thr Val Asn Gly His 
305                 310                 315                 320 
Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gln Thr Asn Thr Ile Ile 
                325                 330                 335     
Asp Val Val Leu Ser Pro Ser His Gly Ile Glu Leu Ser Val Gly Glu 
            340                 345                 350         
Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu Leu Asn Val Gly Ile 
        355                 360                 365             
Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His Gln His Lys Lys Leu 
    370                 375                 380                 
Val Asn Arg Asp Leu Lys Thr Gln Ser Gly Ser Glu Met Lys Lys Phe 
385                 390                 395                 400 
Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg Ser Asp Gln Gly Leu 
                405                 410                 415     
Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr Lys Lys Asn Ser Thr 
            420                 425                 430         
Phe Val Arg Val His Glu Lys 
        435                 

<210>  9
<211>  219
<212>  PRT
<213>  L2(L2)

<400>  9
Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly 
1               5                   10                  15      
Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 
            20                  25                  30          
Lys Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              
Pro Gln Leu Leu Ile Tyr Arg Val Ser Lys Arg Phe Ser Gly Val Pro 
    50                  55                  60                  
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 
65                  70                  75                  80  
Ser Arg Val Glu Ala Gly Asp Val Gly Val Tyr Tyr Cys Ser Gln Ser 
                85                  90                  95      
Thr His Val Pro Phe Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105                 110         
Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu 
        115                 120                 125             
Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe 
    130                 135                 140                 
Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 
145                 150                 155                 160 
Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 
                165                 170                 175     
Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 
            180                 185                 190         
Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 
        195                 200                 205             
Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
    210                 215                 

<210>  10
<211>  558
<212>  PRT
<213>  L3(L3)

<400>  10
Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly 
1               5                   10                  15      
Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 
            20                  25                  30          
Lys Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              
Pro Gln Leu Leu Ile Tyr Arg Val Ser Lys Arg Phe Ser Gly Val Pro 
    50                  55                  60                  
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile 
65                  70                  75                  80  
Ser Arg Val Glu Ala Gly Asp Val Gly Val Tyr Tyr Cys Ser Gln Ser 
                85                  90                  95      
Thr His Val Pro Phe Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105                 110         
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ser 
        115                 120                 125             
Asp Thr Gly Arg Pro Phe Val Glu Met Tyr Ser Glu Ile Pro Glu Ile 
    130                 135                 140                 
Ile His Met Thr Glu Gly Arg Glu Leu Val Ile Pro Cys Arg Val Thr 
145                 150                 155                 160 
Ser Pro Asn Ile Thr Val Thr Leu Lys Lys Phe Pro Leu Asp Thr Leu 
                165                 170                 175     
Ile Pro Asp Gly Lys Arg Ile Ile Trp Asp Ser Arg Lys Gly Phe Ile 
            180                 185                 190         
Ile Ser Asn Ala Thr Tyr Lys Glu Ile Gly Leu Leu Thr Cys Glu Ala 
        195                 200                 205             
Thr Val Asn Gly His Leu Tyr Lys Thr Asn Tyr Leu Thr His Arg Gln 
    210                 215                 220                 
Thr Asn Thr Ile Ile Asp Val Val Leu Ser Pro Ser His Gly Ile Glu 
225                 230                 235                 240 
Leu Ser Val Gly Glu Lys Leu Val Leu Asn Cys Thr Ala Arg Thr Glu 
                245                 250                 255     
Leu Asn Val Gly Ile Asp Phe Asn Trp Glu Tyr Pro Ser Ser Lys His 
            260                 265                 270         
Gln His Lys Lys Leu Val Asn Arg Asp Leu Lys Thr Gln Ser Gly Ser 
        275                 280                 285             
Glu Met Lys Lys Phe Leu Ser Thr Leu Thr Ile Asp Gly Val Thr Arg 
    290                 295                 300                 
Ser Asp Gln Gly Leu Tyr Thr Cys Ala Ala Ser Ser Gly Leu Met Thr 
305                 310                 315                 320 
Lys Lys Asn Ser Thr Phe Val Arg Val His Glu Lys Asp Lys Thr His 
                325                 330                 335     
Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val 
            340                 345                 350         
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
        355                 360                 365             
Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
    370                 375                 380                 
Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
385                 390                 395                 400 
Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
                405                 410                 415     
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
            420                 425                 430         
Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
        435                 440                 445             
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
    450                 455                 460                 
Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Trp Cys Leu 
465                 470                 475                 480 
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
                485                 490                 495     
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
            500                 505                 510         
Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
        515                 520                 525             
Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
    530                 535                 540                 
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
545                 550                 555             

<210>  11
<211>  234
<212>  PRT
<213>  人PD-L1-His(Human PD-L1-His)

<400>  11
Phe Thr Val Thr Val Pro Lys Asp Leu Tyr Val Val Glu Tyr Gly Ser 
1               5                   10                  15      
Asn Met Thr Ile Glu Cys Lys Phe Pro Val Glu Lys Gln Leu Asp Leu 
            20                  25                  30          
Ala Ala Leu Ile Val Tyr Trp Glu Met Glu Asp Lys Asn Ile Ile Gln 
        35                  40                  45              
Phe Val His Gly Glu Glu Asp Leu Lys Val Gln His Ser Ser Tyr Arg 
    50                  55                  60                  
Gln Arg Ala Arg Leu Leu Lys Asp Gln Leu Ser Leu Gly Asn Ala Ala 
65                  70                  75                  80  
Leu Gln Ile Thr Asp Val Lys Leu Gln Asp Ala Gly Val Tyr Arg Cys 
                85                  90                  95      
Met Ile Ser Tyr Gly Gly Ala Asp Tyr Lys Arg Ile Thr Val Lys Val 
            100                 105                 110         
Asn Ala Pro Tyr Asn Lys Ile Asn Gln Arg Ile Leu Val Val Asp Pro 
        115                 120                 125             
Val Thr Ser Glu His Glu Leu Thr Cys Gln Ala Glu Gly Tyr Pro Lys 
    130                 135                 140                 
Ala Glu Val Ile Trp Thr Ser Ser Asp His Gln Val Leu Ser Gly Lys 
145                 150                 155                 160 
Thr Thr Thr Thr Asn Ser Lys Arg Glu Glu Lys Leu Phe Asn Val Thr 
                165                 170                 175     
Ser Thr Leu Arg Ile Asn Thr Thr Thr Asn Glu Ile Phe Tyr Cys Thr 
            180                 185                 190         
Phe Arg Arg Leu Asp Pro Glu Glu Asn His Thr Ala Glu Leu Val Ile 
        195                 200                 205             
Pro Glu Leu Pro Leu Ala His Pro Pro Asn Glu Arg Thr Ser Gly Gly 
    210                 215                 220                 
Gly Gly Ser His His His His His His His 
225                 230                 

<210>  12
<211>  354
<212>  PRT
<213>  人VEGF-A-mFc(human VEGF-A-mFc)

<400>  12
Ala Pro Met Ala Glu Gly Gly Gly Gln Asn His His Glu Val Val Lys 
1               5                   10                  15      
Phe Met Asp Val Tyr Gln Arg Ser Tyr Cys His Pro Ile Glu Thr Leu 
            20                  25                  30          
Val Asp Ile Phe Gln Glu Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys 
        35                  40                  45              
Pro Ser Cys Val Pro Leu Met Arg Cys Gly Gly Cys Cys Asn Asp Glu 
    50                  55                  60                  
Gly Leu Glu Cys Val Pro Thr Glu Glu Ser Asn Ile Thr Met Gln Ile 
65                  70                  75                  80  
Met Arg Ile Lys Pro His Gln Gly Gln His Ile Gly Glu Met Ser Phe 
                85                  90                  95      
Leu Gln His Asn Lys Cys Glu Cys Arg Pro Lys Lys Asp Arg Ala Arg 
            100                 105                 110         
Gln Glu Lys Cys Asp Lys Pro Arg Arg Ser Gly Gly Gly Gly Ser Val 
        115                 120                 125             
Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val 
    130                 135                 140                 
Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile 
145                 150                 155                 160 
Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp 
                165                 170                 175     
Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His 
            180                 185                 190         
Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg 
        195                 200                 205             
Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys 
    210                 215                 220                 
Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu 
225                 230                 235                 240 
Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr 
                245                 250                 255     
Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu 
            260                 265                 270         
Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp 
        275                 280                 285             
Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile 
    290                 295                 300                 
Met Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln 
305                 310                 315                 320 
Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His 
                325                 330                 335     
Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro 
            340                 345                 350         
Gly Lys 
        

<210>  13
<211>  134
<212>  PRT
<213>  人VEGF-A-His(human VEGF-A-His)

<400>  13
Ala Pro Met Ala Glu Gly Gly Gly Gln Asn His His Glu Val Val Lys 
1               5                   10                  15      
Phe Met Asp Val Tyr Gln Arg Ser Tyr Cys His Pro Ile Glu Thr Leu 
            20                  25                  30          
Val Asp Ile Phe Gln Glu Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys 
        35                  40                  45              
Pro Ser Cys Val Pro Leu Met Arg Cys Gly Gly Cys Cys Asn Asp Glu 
    50                  55                  60                  
Gly Leu Glu Cys Val Pro Thr Glu Glu Ser Asn Ile Thr Met Gln Ile 
65                  70                  75                  80  
Met Arg Ile Lys Pro His Gln Gly Gln His Ile Gly Glu Met Ser Phe 
                85                  90                  95      
Leu Gln His Asn Lys Cys Glu Cys Arg Pro Lys Lys Asp Arg Ala Arg 
            100                 105                 110         
Gln Glu Lys Cys Asp Lys Pro Arg Arg Ser Gly Gly Gly Gly Ser His 
        115                 120                 125             
His His His His His His 
    130                 

