﻿                         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LAG-3抗体药物组合物及其用途

<160>  43

<170>  SIPOSequenceListing 1.0

<210>  1
<211>  442
<212>  PRT
<213>  人工序列

<220>
<221>  肽
<223>  带Flag标签的LAG-3胞外区：LAG-3-Flag


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

<210>  2
<211>  525
<212>  PRT
<213>  智人

<220>
<221>  肽
<223>  全长LAG3


<400>  2
Met Trp Glu Ala Gln Phe Leu Gly Leu Leu Phe Leu Gln Pro Leu Trp 
1               5                   10                  15      
Val Ala Pro Val Lys Pro Leu Gln Pro Gly Ala Glu Val Pro Val Val 
            20                  25                  30          
Trp Ala Gln Glu Gly Ala Pro Ala Gln Leu Pro Cys Ser Pro Thr Ile 
        35                  40                  45              
Pro Leu Gln Asp Leu Ser Leu Leu Arg Arg Ala Gly Val Thr Trp Gln 
    50                  55                  60                  
His Gln Pro Asp Ser Gly Pro Pro Ala Ala Ala Pro Gly His Pro Leu 
65                  70                  75                  80  
Ala Pro Gly Pro His Pro Ala Ala Pro Ser Ser Trp Gly Pro Arg Pro 
                85                  90                  95      
Arg Arg Tyr Thr Val Leu Ser Val Gly Pro Gly Gly Leu Arg Ser Gly 
            100                 105                 110         
Arg Leu Pro Leu Gln Pro Arg Val Gln Leu Asp Glu Arg Gly Arg Gln 
        115                 120                 125             
Arg Gly Asp Phe Ser Leu Trp Leu Arg Pro Ala Arg Arg Ala Asp Ala 
    130                 135                 140                 
Gly Glu Tyr Arg Ala Ala Val His Leu Arg Asp Arg Ala Leu Ser Cys 
145                 150                 155                 160 
Arg Leu Arg Leu Arg Leu Gly Gln Ala Ser Met Thr Ala Ser Pro Pro 
                165                 170                 175     
Gly Ser Leu Arg Ala Ser Asp Trp Val Ile Leu Asn Cys Ser Phe Ser 
            180                 185                 190         
Arg Pro Asp Arg Pro Ala Ser Val His Trp Phe Arg Asn Arg Gly Gln 
        195                 200                 205             
Gly Arg Val Pro Val Arg Glu Ser Pro His His His Leu Ala Glu Ser 
    210                 215                 220                 
Phe Leu Phe Leu Pro Gln Val Ser Pro Met Asp Ser Gly Pro Trp Gly 
225                 230                 235                 240 
Cys Ile Leu Thr Tyr Arg Asp Gly Phe Asn Val Ser Ile Met Tyr Asn 
                245                 250                 255     
Leu Thr Val Leu Gly Leu Glu Pro Pro Thr Pro Leu Thr Val Tyr Ala 
            260                 265                 270         
Gly Ala Gly Ser Arg Val Gly Leu Pro Cys Arg Leu Pro Ala Gly Val 
        275                 280                 285             
Gly Thr Arg Ser Phe Leu Thr Ala Lys Trp Thr Pro Pro Gly Gly Gly 
    290                 295                 300                 
Pro Asp Leu Leu Val Thr Gly Asp Asn Gly Asp Phe Thr Leu Arg Leu 
305                 310                 315                 320 
Glu Asp Val Ser Gln Ala Gln Ala Gly Thr Tyr Thr Cys His Ile His 
                325                 330                 335     
Leu Gln Glu Gln Gln Leu Asn Ala Thr Val Thr Leu Ala Ile Ile Thr 
            340                 345                 350         
Val Thr Pro Lys Ser Phe Gly Ser Pro Gly Ser Leu Gly Lys Leu Leu 
        355                 360                 365             
Cys Glu Val Thr Pro Val Ser Gly Gln Glu Arg Phe Val Trp Ser Ser 
    370                 375                 380                 
Leu Asp Thr Pro Ser Gln Arg Ser Phe Ser Gly Pro Trp Leu Glu Ala 
385                 390                 395                 400 
Gln Glu Ala Gln Leu Leu Ser Gln Pro Trp Gln Cys Gln Leu Tyr Gln 
                405                 410                 415     
Gly Glu Arg Leu Leu Gly Ala Ala Val Tyr Phe Thr Glu Leu Ser Ser 
            420                 425                 430         
Pro Gly Ala Gln Arg Ser Gly Arg Ala Pro Gly Ala Leu Pro Ala Gly 
        435                 440                 445             
His Leu Leu Leu Phe Leu Ile Leu Gly Val Leu Ser Leu Leu Leu Leu 
    450                 455                 460                 
Val Thr Gly Ala Phe Gly Phe His Leu Trp Arg Arg Gln Trp Arg Pro 
465                 470                 475                 480 
Arg Arg Phe Ser Ala Leu Glu Gln Gly Ile His Pro Pro Gln Ala Gln 
                485                 490                 495     
Ser Lys Ile Glu Glu Leu Glu Gln Glu Pro Glu Pro Glu Pro Glu Pro 
            500                 505                 510         
Glu Pro Glu Pro Glu Pro Glu Pro Glu Pro Glu Gln Leu 
        515                 520                 525 

<210>  3
<211>  675
<212>  PRT
<213>  人工序列

<220>
<221>  肽
<223>  LAG-3胞外区和hIgG1 Fc的融合蛋白


<400>  3
Met Trp Glu Ala Gln Phe Leu Gly Leu Leu Phe Leu Gln Pro Leu Trp 
1               5                   10                  15      
Val Ala Pro Val Lys Pro Leu Gln Pro Gly Ala Glu Val Pro Val Val 
            20                  25                  30          
Trp Ala Gln Glu Gly Ala Pro Ala Gln Leu Pro Cys Ser Pro Thr Ile 
        35                  40                  45              
Pro Leu Gln Asp Leu Ser Leu Leu Arg Arg Ala Gly Val Thr Trp Gln 
    50                  55                  60                  
His Gln Pro Asp Ser Gly Pro Pro Ala Ala Ala Pro Gly His Pro Leu 
65                  70                  75                  80  
Ala Pro Gly Pro His Pro Ala Ala Pro Ser Ser Trp Gly Pro Arg Pro 
                85                  90                  95      
Arg Arg Tyr Thr Val Leu Ser Val Gly Pro Gly Gly Leu Arg Ser Gly 
            100                 105                 110         
Arg Leu Pro Leu Gln Pro Arg Val Gln Leu Asp Glu Arg Gly Arg Gln 
        115                 120                 125             
Arg Gly Asp Phe Ser Leu Trp Leu Arg Pro Ala Arg Arg Ala Asp Ala 
    130                 135                 140                 
Gly Glu Tyr Arg Ala Ala Val His Leu Arg Asp Arg Ala Leu Ser Cys 
145                 150                 155                 160 
Arg Leu Arg Leu Arg Leu Gly Gln Ala Ser Met Thr Ala Ser Pro Pro 
                165                 170                 175     
Gly Ser Leu Arg Ala Ser Asp Trp Val Ile Leu Asn Cys Ser Phe Ser 
            180                 185                 190         
Arg Pro Asp Arg Pro Ala Ser Val His Trp Phe Arg Asn Arg Gly Gln 
        195                 200                 205             
Gly Arg Val Pro Val Arg Glu Ser Pro His His His Leu Ala Glu Ser 
    210                 215                 220                 
Phe Leu Phe Leu Pro Gln Val Ser Pro Met Asp Ser Gly Pro Trp Gly 
225                 230                 235                 240 
Cys Ile Leu Thr Tyr Arg Asp Gly Phe Asn Val Ser Ile Met Tyr Asn 
                245                 250                 255     
Leu Thr Val Leu Gly Leu Glu Pro Pro Thr Pro Leu Thr Val Tyr Ala 
            260                 265                 270         
Gly Ala Gly Ser Arg Val Gly Leu Pro Cys Arg Leu Pro Ala Gly Val 
        275                 280                 285             
Gly Thr Arg Ser Phe Leu Thr Ala Lys Trp Thr Pro Pro Gly Gly Gly 
    290                 295                 300                 
Pro Asp Leu Leu Val Thr Gly Asp Asn Gly Asp Phe Thr Leu Arg Leu 
305                 310                 315                 320 
Glu Asp Val Ser Gln Ala Gln Ala Gly Thr Tyr Thr Cys His Ile His 
                325                 330                 335     
Leu Gln Glu Gln Gln Leu Asn Ala Thr Val Thr Leu Ala Ile Ile Thr 
            340                 345                 350         
Val Thr Pro Lys Ser Phe Gly Ser Pro Gly Ser Leu Gly Lys Leu Leu 
        355                 360                 365             
Cys Glu Val Thr Pro Val Ser Gly Gln Glu Arg Phe Val Trp Ser Ser 
    370                 375                 380                 
Leu Asp Thr Pro Ser Gln Arg Ser Phe Ser Gly Pro Trp Leu Glu Ala 
385                 390                 395                 400 
Gln Glu Ala Gln Leu Leu Ser Gln Pro Trp Gln Cys Gln Leu Tyr Gln 
                405                 410                 415     
Gly Glu Arg Leu Leu Gly Ala Ala Val Tyr Phe Thr Glu Leu Ser Ser 
            420                 425                 430         
Pro Gly Asp Asp Asp Asp Lys Gly Ser Gly Ser Gly Glu Pro Lys Ser 
        435                 440                 445             
Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
    450                 455                 460                 
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
465                 470                 475                 480 
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                485                 490                 495     
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
            500                 505                 510         
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
        515                 520                 525             
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    530                 535                 540                 
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
545                 550                 555                 560 
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                565                 570                 575     
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val 
            580                 585                 590         
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        595                 600                 605             
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    610                 615                 620                 
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
625                 630                 635                 640 
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
                645                 650                 655     
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            660                 665                 670         
Ser Pro Gly 
        675 

<210>  4
<211>  677
<212>  PRT
<213>  人工序列

<220>
<221>  肽
<223>  LAG-3胞外区和mIgG2a Fc的融合蛋白


<400>  4
Met Trp Glu Ala Gln Phe Leu Gly Leu Leu Phe Leu Gln Pro Leu Trp 
1               5                   10                  15      
Val Ala Pro Val Lys Pro Leu Gln Pro Gly Ala Glu Val Pro Val Val 
            20                  25                  30          
Trp Ala Gln Glu Gly Ala Pro Ala Gln Leu Pro Cys Ser Pro Thr Ile 
        35                  40                  45              
Pro Leu Gln Asp Leu Ser Leu Leu Arg Arg Ala Gly Val Thr Trp Gln 
    50                  55                  60                  
His Gln Pro Asp Ser Gly Pro Pro Ala Ala Ala Pro Gly His Pro Leu 
65                  70                  75                  80  
Ala Pro Gly Pro His Pro Ala Ala Pro Ser Ser Trp Gly Pro Arg Pro 
                85                  90                  95      
Arg Arg Tyr Thr Val Leu Ser Val Gly Pro Gly Gly Leu Arg Ser Gly 
            100                 105                 110         
Arg Leu Pro Leu Gln Pro Arg Val Gln Leu Asp Glu Arg Gly Arg Gln 
        115                 120                 125             
Arg Gly Asp Phe Ser Leu Trp Leu Arg Pro Ala Arg Arg Ala Asp Ala 
    130                 135                 140                 
Gly Glu Tyr Arg Ala Ala Val His Leu Arg Asp Arg Ala Leu Ser Cys 
145                 150                 155                 160 
Arg Leu Arg Leu Arg Leu Gly Gln Ala Ser Met Thr Ala Ser Pro Pro 
                165                 170                 175     
Gly Ser Leu Arg Ala Ser Asp Trp Val Ile Leu Asn Cys Ser Phe Ser 
            180                 185                 190         
Arg Pro Asp Arg Pro Ala Ser Val His Trp Phe Arg Asn Arg Gly Gln 
        195                 200                 205             
Gly Arg Val Pro Val Arg Glu Ser Pro His His His Leu Ala Glu Ser 
    210                 215                 220                 
Phe Leu Phe Leu Pro Gln Val Ser Pro Met Asp Ser Gly Pro Trp Gly 
225                 230                 235                 240 
Cys Ile Leu Thr Tyr Arg Asp Gly Phe Asn Val Ser Ile Met Tyr Asn 
                245                 250                 255     
Leu Thr Val Leu Gly Leu Glu Pro Pro Thr Pro Leu Thr Val Tyr Ala 
            260                 265                 270         
Gly Ala Gly Ser Arg Val Gly Leu Pro Cys Arg Leu Pro Ala Gly Val 
        275                 280                 285             
Gly Thr Arg Ser Phe Leu Thr Ala Lys Trp Thr Pro Pro Gly Gly Gly 
    290                 295                 300                 
Pro Asp Leu Leu Val Thr Gly Asp Asn Gly Asp Phe Thr Leu Arg Leu 
305                 310                 315                 320 
Glu Asp Val Ser Gln Ala Gln Ala Gly Thr Tyr Thr Cys His Ile His 
                325                 330                 335     
Leu Gln Glu Gln Gln Leu Asn Ala Thr Val Thr Leu Ala Ile Ile Thr 
            340                 345                 350         
Val Thr Pro Lys Ser Phe Gly Ser Pro Gly Ser Leu Gly Lys Leu Leu 
        355                 360                 365             
Cys Glu Val Thr Pro Val Ser Gly Gln Glu Arg Phe Val Trp Ser Ser 
    370                 375                 380                 
Leu Asp Thr Pro Ser Gln Arg Ser Phe Ser Gly Pro Trp Leu Glu Ala 
385                 390                 395                 400 
Gln Glu Ala Gln Leu Leu Ser Gln Pro Trp Gln Cys Gln Leu Tyr Gln 
                405                 410                 415     
Gly Glu Arg Leu Leu Gly Ala Ala Val Tyr Phe Thr Glu Leu Ser Ser 
            420                 425                 430         
Pro Gly Asp Asp Asp Asp Lys Gly Ser Gly Ser Gly Glu Pro Arg Gly 
        435                 440                 445             
Pro Thr Ile Lys Pro Cys Pro Pro Cys Lys Cys Pro Ala Pro Asn Leu 
    450                 455                 460                 
Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Ile Lys Asp Val 
465                 470                 475                 480 
Leu Met Ile Ser Leu Ser Pro Ile Val Thr Cys Val Val Val Asp Val 
                485                 490                 495     
Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp Phe Val Asn Asn Val 
            500                 505                 510         
Glu Val His Thr Ala Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser 
        515                 520                 525             
Thr Leu Arg Val Val Ser Ala Leu Pro Ile Gln His Gln Asp Trp Met 
    530                 535                 540                 
Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Asp Leu Pro Ala 
545                 550                 555                 560 
Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly Ser Val Arg Ala Pro 
                565                 570                 575     
Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu Met Thr Lys Lys Gln 
            580                 585                 590         
Val Thr Leu Thr Cys Met Val Thr Asp Phe Met Pro Glu Asp Ile Tyr 
        595                 600                 605             
Val Glu Trp Thr Asn Asn Gly Lys Thr Glu Leu Asn Tyr Lys Asn Thr 
    610                 615                 620                 
Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe Met Tyr Ser Lys Leu 
625                 630                 635                 640 
Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn Ser Tyr Ser Cys Ser 
                645                 650                 655     
Val Val His Glu Gly Leu His Asn His His Thr Thr Lys Ser Phe Ser 
            660                 665                 670         
Arg Thr Pro Gly Lys 
        675         

<210>  5
<211>  124
<212>  PRT
<213>  鼠

<220>
<221>  结构域
<223>  mAb229-VH


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

<210>  6
<211>  107
<212>  PRT
<213>  鼠

<220>
<221>  结构域
<223>  mAb229-VL


<400>  6
Asp Ile Gln Met Thr Gln Ser Pro Ala Ser Leu Ser Val Ser Val Gly 
1               5                   10                  15      
Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Glu Asn Ile Tyr Ser Asn 
            20                  25                  30          
Leu Ala Trp Tyr Gln Gln Lys Gln Gly Lys Ser Pro Gln Leu Leu Val 
        35                  40                  45              
Tyr Ala Ala Thr Asn Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Gln Tyr Ser Leu Lys Ile Asn Ser Leu Gln Ser 
65                  70                  75                  80  
Glu Asp Phe Gly Ser Tyr Tyr Cys Gln His Phe Trp Ile Thr Pro Trp 
                85                  90                  95      
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105         

<210>  7
<211>  120
<212>  PRT
<213>  鼠

<220>
<221>  结构域
<223>  mAb303-VH


<400>  7
Glu Val Gln Leu Gln Gln Ser Gly Pro Val Leu Val Lys Pro Gly Ala 
1               5                   10                  15      
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Leu Thr Asp Tyr 
            20                  25                  30          
Tyr Met Asn Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile 
        35                  40                  45              
Gly Val Ile Asn Pro Tyr Asn Gly Asp Thr Ala Tyr Asn Gln Lys Phe 
    50                  55                  60                  
Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Asn Thr Ala Tyr 
65                  70                  75                  80  
Met Glu Ile Asn Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys 
                85                  90                  95      
Thr Arg Asp Asp Gly Tyr Tyr Asp Tyr Tyr Phe Asp Val Trp Gly Thr 
            100                 105                 110         
Gly Thr Thr Val Thr Val Ser Ser 
        115                 120 

<210>  8
<211>  107
<212>  PRT
<213>  鼠

<220>
<221>  结构域
<223>  mAb303-VL


<400>  8
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Leu Gly 
1               5                   10                  15      
Glu Arg Val Ile Leu Thr Cys Arg Ala Ser Gln Asp Ile Gly Ser Arg 
            20                  25                  30          
Leu Asn Trp Leu Gln Gln Gly Pro Asp Gly Thr Phe Lys Arg Leu Ile 
        35                  40                  45              
Tyr Ala Thr Ser Thr Leu Asp Ser Gly Val Pro Lys Arg Phe Ser Gly 
    50                  55                  60                  
Ser Arg Ser Gly Ser Asp Phe Ser Leu Thr Ile Ser Ser Leu Glu Ser 
65                  70                  75                  80  
Glu Asp Phe Val Asp Tyr Tyr Cys Leu Gln Leu Ala Ser Ser Pro Pro 
                85                  90                  95      
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105         

<210>  9
<211>  5
<212>  PRT
<213>  鼠

<220>
<221>  结构域
<223>  mAb229 HCDR1


<400>  9
Thr Ser Gly Met Ser 
1               5   

<210>  10
<211>  17
<212>  PRT
<213>  鼠

<220>
<221>  结构域
<223>  mAb229 HCDR2


<400>  10
Trp Ile Asn Thr Tyr Ser Gly Val Pro Thr Tyr Ala Asp Asp Phe Lys 
1               5                   10                  15      
Gly 
    

<210>  11
<211>  15
<212>  PRT
<213>  鼠

<220>
<221>  结构域
<223>  mAb229 HCDR3


<400>  11
Asp Asn Tyr Asp Ala Arg Asp Val Tyr Tyr Tyr Ala Met Asp Tyr 
1               5                   10                  15  

<210>  12
<211>  5
<212>  PRT
<213>  鼠

<220>
<221>  结构域
<223>  mAb303 HCDR1


<400>  12
Asp Tyr Tyr Met Asn 
1               5   

<210>  13
<211>  17
<212>  PRT
<213>  鼠

<220>
<221>  结构域
<223>  mAb303 HCDR2


<400>  13
Val Ile Asn Pro Tyr Asn Gly Asp Thr Ala Tyr Asn Gln Lys Phe Lys 
1               5                   10                  15      
Gly 
    

<210>  14
<211>  11
<212>  PRT
<213>  鼠

<220>
<221>  结构域
<223>  mAb303 HCD3


<400>  14
Asp Asp Gly Tyr Tyr Asp Tyr Tyr Phe Asp Val 
1               5                   10      

<210>  15
<211>  11
<212>  PRT
<213>  鼠

<220>
<221>  结构域
<223>  mAb229 LCDR1


<400>  15
Arg Ala Ser Glu Asn Ile Tyr Ser Asn Leu Ala 
1               5                   10      

<210>  16
<211>  7
<212>  PRT
<213>  鼠

<220>
<221>  结构域
<223>  mAb229 LCDR2


<400>  16
Ala Ala Thr Asn Leu Ala Asp 
1               5           

<210>  17
<211>  9
<212>  PRT
<213>  鼠

<220>
<221>  结构域
<223>  mAb229 LCDR3


<400>  17
Gln His Phe Trp Ile Thr Pro Trp Thr 
1               5                   

<210>  18
<211>  11
<212>  PRT
<213>  鼠

<220>
<221>  结构域
<223>  mAb303 LCDR1


<400>  18
Arg Ala Ser Gln Asp Ile Gly Ser Arg Leu Asn 
1               5                   10      

<210>  19
<211>  7
<212>  PRT
<213>  鼠

<220>
<221>  结构域
<223>  mAb303 LCDR2


<400>  19
Ala Thr Ser Thr Leu Asp Ser 
1               5           

<210>  20
<211>  9
<212>  PRT
<213>  鼠

<220>
<221>  结构域
<223>  mAb303 LCDR3


<400>  20
Leu Gln Leu Ala Ser Ser Pro Pro Thr 
1               5                   

<210>  21
<211>  124
<212>  PRT
<213>  人工序列

<220>
<221>  结构域
<223>  Hu229VH.1


<400>  21
Gln Val Gln Leu Val Gln Ser Gly Ser Glu Leu Lys Lys Pro Gly Ala 
1               5                   10                  15      
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Thr Ser 
            20                  25                  30          
Gly Met Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              
Gly Trp Ile Asn Thr Tyr Ser Gly Val Pro Thr Tyr Ala Asp Asp Phe 
    50                  55                  60                  
Lys Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  
Leu Gln Ile Ser Ser Leu Lys Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Arg Asp Asn Tyr Asp Ala Arg Asp Val Tyr Tyr Tyr Ala Met Asp 
            100                 105                 110         
Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
        115                 120                 

<210>  22
<211>  107
<212>  PRT
<213>  人工序列

<220>
<221>  结构域
<223>  Hu229VL.1


<400>  22
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Asn Ile Tyr Ser Asn 
            20                  25                  30          
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
        35                  40                  45              
Tyr Ala Ala Thr Asn Leu Ala Asp 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 His Phe Trp Ile Thr Pro Trp 
                85                  90                  95      
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105         

<210>  23
<211>  124
<212>  PRT
<213>  人工序列

<220>
<221>  结构域
<223>  Hu229VH.1A


<400>  23
Gln Val Gln Leu Val Gln Ser Gly Ser Glu Leu Lys Lys Pro Gly Ala 
1               5                   10                  15      
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Thr Ser 
            20                  25                  30          
Gly Met Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Lys Trp Met 
        35                  40                  45              
Gly Trp Ile Asn Thr Tyr Ser Gly Val Pro Thr Tyr Ala Asp Asp Phe 
    50                  55                  60                  
Lys Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  
Leu Gln Ile Ser Ser Leu Lys Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Arg Asp Asn Tyr Asp Ala Arg Asp Val Tyr Tyr Tyr Ala Met Asp 
            100                 105                 110         
Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
        115                 120                 

<210>  24
<211>  124
<212>  PRT
<213>  人工序列

<220>
<221>  结构域
<223>  Hu229VH.1B


<400>  24
Gln Val Gln Leu Val Gln Ser Gly Ser Glu Leu Lys Lys Pro Gly Ala 
1               5                   10                  15      
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Thr Ser 
            20                  25                  30          
Gly Met Ser Trp Val Lys Gln Ala Pro Gly Gln Gly Leu Lys Trp Met 
        35                  40                  45              
Gly Trp Ile Asn Thr Tyr Ser Gly Val Pro Thr Tyr Ala Asp Asp Phe 
    50                  55                  60                  
Lys Gly Arg Phe Val Phe Ser Leu Asp Thr Ser Val Ser Thr Ala Tyr 
65                  70                  75                  80  
Leu Gln Ile Ser Ser Leu Lys Ala Glu Asp Thr Ala Thr Tyr Tyr Cys 
                85                  90                  95      
Ala Arg Asp Asn Tyr Asp Ala Arg Asp Val Tyr Tyr Tyr Ala Met Asp 
            100                 105                 110         
Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
        115                 120                 

<210>  25
<211>  124
<212>  PRT
<213>  人工序列

<220>
<221>  结构域
<223>  Hu229VH.1C


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

<210>  26
<211>  107
<212>  PRT
<213>  人工序列

<220>
<221>  结构域
<223>  Hu229VL.1A


<400>  26
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Asn Ile Tyr Ser Asn 
            20                  25                  30          
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Val 
        35                  40                  45              
Tyr Ala Ala Thr Asn Leu Ala Asp 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 His Phe Trp Ile Thr Pro Trp 
                85                  90                  95      
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105         

<210>  27
<211>  107
<212>  PRT
<213>  人工序列

<220>
<221>  结构域
<223>  Hu229VL.1B


<400>  27
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Asn Ile Tyr Ser Asn 
            20                  25                  30          
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Val 
        35                  40                  45              
Tyr Ala Ala Thr Asn Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Gln Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln His Phe Trp Ile Thr Pro Trp 
                85                  90                  95      
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105         

<210>  28
<211>  107
<212>  PRT
<213>  人工序列

<220>
<221>  结构域
<223>  Hu229VL.1C


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

<210>  29
<211>  120
<212>  PRT
<213>  人工序列

<220>
<221>  结构域
<223>  Hu303_VH.1


<400>  29
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 Asp Tyr 
            20                  25                  30          
Tyr Met Asn Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met 
        35                  40                  45              
Gly Val Ile Asn Pro Tyr Asn Gly Asp Thr Ala Tyr Asn Gln 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 Asp Asp Gly Tyr Tyr Asp Tyr Tyr Phe Asp Val Trp Gly Gln 
            100                 105                 110         
Gly Thr Thr Val Thr Val Ser Ser 
        115                 120 

<210>  30
<211>  107
<212>  PRT
<213>  人工序列

<220>
<221>  结构域
<223>  Hu303_VL.1


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

<210>  31
<211>  120
<212>  PRT
<213>  人工序列

<220>
<221>  结构域
<223>  Hu303_VH.1A


<400>  31
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 Asp Tyr 
            20                  25                  30          
Tyr Met Asn Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met 
        35                  40                  45              
Gly Val Ile Asn Pro Tyr Asn Gly Asp Thr Ala Tyr Asn Gln Lys Phe 
    50                  55                  60                  
Lys Gly Arg Val Thr Ile Thr Val Asp Lys 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      
Thr Arg Asp Asp Gly Tyr Tyr Asp Tyr Tyr Phe Asp Val Trp Gly Gln 
            100                 105                 110         
Gly Thr Thr Val Thr Val Ser Ser 
        115                 120 

<210>  32
<211>  120
<212>  PRT
<213>  人工序列

<220>
<221>  结构域
<223>  Hu303_VH.1B


<400>  32
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 Leu Thr Asp Tyr 
            20                  25                  30          
Tyr Met Asn Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met 
        35                  40                  45              
Gly Val Ile Asn Pro Tyr Asn Gly Asp Thr Ala Tyr Asn Gln Lys Phe 
    50                  55                  60                  
Lys Gly Arg Val Thr Ile Thr Val Asp Lys 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      
Thr Arg Asp Asp Gly Tyr Tyr Asp Tyr Tyr Phe Asp Val Trp Gly Gln 
            100                 105                 110         
Gly Thr Thr Val Thr Val Ser Ser 
        115                 120 

<210>  33
<211>  120
<212>  PRT
<213>  人工序列

<220>
<221>  结构域
<223>  Hu303_VH.1C


<400>  33
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 Leu Thr Asp Tyr 
            20                  25                  30          
Tyr Met Asn Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Ile 
        35                  40                  45              
Gly Val Ile Asn Pro Tyr Asn Gly Asp Thr Ala Tyr Asn Gln Lys Phe 
    50                  55                  60                  
Lys Gly Arg Ala Thr Leu Thr Val Asp Lys 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      
Thr Arg Asp Asp Gly Tyr Tyr Asp Tyr Tyr Phe Asp Val Trp Gly Gln 
            100                 105                 110         
Gly Thr Thr Val Thr Val Ser Ser 
        115                 120 

<210>  34
<211>  107
<212>  PRT
<213>  人工序列

<220>
<221>  结构域
<223>  Hu303_VL.1A


<400>  34
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Gly Ser Arg 
            20                  25                  30          
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Arg Leu Ile 
        35                  40                  45              
Tyr Ala Thr Ser Thr Leu Asp Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  
Ser Arg 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 Leu Gln Leu Ala Ser Ser Pro Pro 
                85                  90                  95      
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105         

<210>  35
<211>  107
<212>  PRT
<213>  人工序列

<220>
<221>  结构域
<223>  Hu303_VL.1B


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

<210>  36
<211>  107
<212>  PRT
<213>  人工序列

<220>
<221>  结构域
<223>  Hu303_VL.1C


<400>  36
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Gly Ser Arg 
            20                  25                  30          
Leu Asn Trp Leu Gln Gln Lys Pro Gly Lys Ala Phe Lys Arg Leu Ile 
        35                  40                  45              
Tyr Ala Thr Ser Thr Leu Asp Ser Gly Val Pro Lys Arg Phe Ser Gly 
    50                  55                  60                  
Ser Arg 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 Leu Gln Leu Ala Ser Ser Pro Pro 
                85                  90                  95      
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105         

<210>  37
<211>  107
<212>  PRT
<213>  人工序列

<220>
<221>  结构域
<223>  Hu303_VL.1D


<400>  37
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      
Asp Arg Val Thr Leu Thr Cys Arg Ala Ser Gln Asp Ile Gly Ser Arg 
            20                  25                  30          
Leu Asn Trp Leu Gln Gln Lys Pro Gly Gly Ala Phe Lys Arg Leu Ile 
        35                  40                  45              
Tyr Ala Thr Ser Thr Leu Asp Ser Gly Val Pro Lys Arg Phe Ser Gly 
    50                  55                  60                  
Ser Arg Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  
Glu Asp Phe Ala Asp Tyr Tyr Cys Leu Gln Leu Ala Ser Ser Pro Pro 
                85                  90                  95      
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105         

<210>  38
<211>  327
<212>  PRT
<213>  人工序列

<220>
<221>  结构域
<223>  重链恒定区，S228P突变.


<400>  38
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg 
1               5                   10                  15      
Ser Thr Ser Glu Ser 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 Lys Thr 
65                  70                  75                  80  
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys 
                85                  90                  95      
Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro 
            100                 105                 110         
Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
        115                 120                 125             
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
    130                 135                 140                 
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp 
145                 150                 155                 160 
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe 
                165                 170                 175     
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
            180                 185                 190         
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu 
        195                 200                 205             
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
    210                 215                 220                 
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys 
225                 230                 235                 240 
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
                245                 250                 255     
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
            260                 265                 270         
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
        275                 280                 285             
Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser 
    290                 295                 300                 
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
305                 310                 315                 320 
Leu Ser Leu Ser Leu Gly Lys 
                325         

<210>  39
<211>  107
<212>  PRT
<213>  人工序列

<220>
<221>  结构域
<223>  kappa轻链恒定区


<400>  39
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>  40
<211>  451
<212>  PRT
<213>  人工序列

<220>
<221>  CHAIN
<223>  Hu229-013的重链氨基酸序列


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

<210>  41
<211>  214
<212>  PRT
<213>  人工序列

<220>
<221>  CHAIN
<223>  Hu229-013的轻链氨基酸序列


<400>  41
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Asn Ile Tyr Ser Asn 
            20                  25                  30          
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Val 
        35                  40                  45              
Tyr Ala Ala Thr Asn Leu Ala Asp 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 His Phe Trp Ile Thr Pro Trp 
                85                  90                  95      
Thr Phe Gly Gly 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>  42
<211>  447
<212>  PRT
<213>  人工序列

<220>
<221>  CHAIN
<223>  Hu303-005的重链氨基酸序列


<400>  42
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 Asp Tyr 
            20                  25                  30          
Tyr Met Asn Trp Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Met 
        35                  40                  45              
Gly Val Ile Asn Pro Tyr Asn Gly Asp Thr Ala Tyr Asn Gln 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 Asp Asp Gly Tyr Tyr Asp Tyr Tyr Phe Asp Val Trp Gly Gln 
            100                 105                 110         
Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 
        115                 120                 125             
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala 
    130                 135                 140                 
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 
145                 150                 155                 160 
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 
                165                 170                 175     
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 
            180                 185                 190         
Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys 
        195                 200                 205             
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro 
    210                 215                 220                 
Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val 
225                 230                 235                 240 
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
                245                 250                 255     
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu 
            260                 265                 270         
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
        275                 280                 285             
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser 
    290                 295                 300                 
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
305                 310                 315                 320 
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile 
                325                 330                 335     
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
            340                 345                 350         
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
        355                 360                 365             
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
    370                 375                 380                 
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
385                 390                 395                 400 
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg 
                405                 410                 415     
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
            420                 425                 430         
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 
        435                 440                 445         

<210>  43
<211>  214
<212>  PRT
<213>  人工序列

<220>
<221>  CHAIN
<223>  Hu303-005的轻链氨基酸序列


<400>  43
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Gly Ser Arg 
            20                  25                  30          
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Arg Leu Ile 
        35                  40                  45              
Tyr Ala Thr Ser Thr Leu Asp Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  
Ser Arg 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 Leu Gln Leu Ala Ser Ser Pro Pro 
                85                  90                  95      
Thr Phe Gly Gly 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                 






