﻿                         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>  特异性结合RANKL和NGF的抗原结合分子及其医药用途

<140>  PCT/CN2022/
<141>  2022-05-12

<150>  202110515444.9
<151>  2021-05-12

<160>  111

<170>  PatentIn 3.5

<210>  1
<211>  5
<212>  PRT
<213>  人工序列

<220>
<223>  1-22H HCDR1


<400>  1
Asp Tyr Ala Met Ser 
1               5   

<210>  2
<211>  17
<212>  PRT
<213>  人工序列

<220>
<223>  1-22H HCDR2


<400>  2
Gly Ile Ser Ala Ser Gly Ser Ser Thr Tyr Tyr Ala Asp Ser Val Lys 
1               5                   10                  15      
Gly 
    

<210>  3
<211>  13
<212>  PRT
<213>  人工序列

<220>
<223>  1-22H HCDR3


<400>  3
Asp Pro Gly Thr Thr Val Ile Met Ser Trp Phe Asp Pro 
1               5                   10              

<210>  4
<211>  12
<212>  PRT
<213>  人工序列

<220>
<223>  1-22H LCDR1


<400>  4
Arg Ala Ser Gln Ser Val Arg Gly Arg Tyr Leu Ala 
1               5                   10          

<210>  5
<211>  7
<212>  PRT
<213>  人工序列

<220>
<223>  1-22H LCDR2


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

<210>  6
<211>  9
<212>  PRT
<213>  人工序列

<220>
<223>  1-22H LCDR3


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

<210>  7
<211>  5
<212>  PRT
<213>  人工序列

<220>
<223>  5-16H HCDR1


<400>  7
Ser Tyr Ala Met Ser 
1               5   

<210>  8
<211>  17
<212>  PRT
<213>  人工序列

<220>
<223>  5-16H HCDR2


<400>  8
Gly Ile Thr Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys 
1               5                   10                  15      
Gly 
    

<210>  9
<211>  13
<212>  PRT
<213>  人工序列

<220>
<223>  5-16H HCDR3


<400>  9
Asp Pro Ala Ser Ile Val Ile Met Ser Trp Phe Asp Pro 
1               5                   10              

<210>  10
<211>  13
<212>  PRT
<213>  人工序列

<220>
<223>  5-51H HCDR3


<400>  10
Asp Pro Cys Phe Ser Tyr Ile Met Ser Trp Phe Asp Pro 
1               5                   10              

<210>  11
<211>  13
<212>  PRT
<213>  人工序列

<220>
<223>  5-53H HCDR3


<400>  11
Asp Pro Cys Phe Thr Tyr Ile Met Ser Trp Phe Asp Pro 
1               5                   10              

<210>  12
<211>  13
<212>  PRT
<213>  人工序列

<220>
<223>  5-58H HCDR3


<400>  12
Asp Pro Gly Phe Thr Tyr Ile Met Ser Trp Phe Asp Pro 
1               5                   10              

<210>  13
<211>  5
<212>  PRT
<213>  人工序列

<220>
<223>  D35H HCDR1


<400>  13
Ala Tyr Pro Met Ser 
1               5   

<210>  14
<211>  13
<212>  PRT
<213>  人工序列

<220>
<223>  D75H HCDR3


<400>  14
Asp Pro Gly Thr Thr Ser Ile Met Ser Trp Phe Asp Pro 
1               5                   10              

<210>  15
<211>  13
<212>  PRT
<213>  人工序列

<220>
<223>  D80H HCDR3


<400>  15
Asp Pro Gly Ser Thr Ile Ile Met Ser Trp Phe Asp Pro 
1               5                   10              

<210>  16
<211>  7
<212>  PRT
<213>  人工序列

<220>
<223>  2-52L LCDR2


<400>  16
Gln Gly Ser Ser Arg Ala Thr 
1               5           

<210>  17
<211>  12
<212>  PRT
<213>  人工序列

<220>
<223>  2-72L LCDR1


<400>  17
Arg Ala Ser Gln Ser Leu Gly Ala Arg Gly Leu Ala 
1               5                   10          

<210>  18
<211>  7
<212>  PRT
<213>  人工序列

<220>
<223>  2-72L LCDR2


<400>  18
Gly Thr Ser Ser Arg Ala Thr 
1               5           

<210>  19
<211>  12
<212>  PRT
<213>  人工序列

<220>
<223>  2-76L LCDR1


<400>  19
Arg Ala Ser Gln Ala Ile Pro Tyr Asn Gln Leu Ala 
1               5                   10          

<210>  20
<211>  7
<212>  PRT
<213>  人工序列

<220>
<223>  2-76L LCDR2


<400>  20
Gly Val Ser Ser Arg Ala Thr 
1               5           

<210>  21
<211>  7
<212>  PRT
<213>  人工序列

<220>
<223>  2-79L LCDR2


<400>  21
Gly Ser Ser Ser Arg Ala Thr 
1               5           

<210>  22
<211>  12
<212>  PRT
<213>  人工序列

<220>
<223>  2-87L LCDR1


<400>  22
Arg Ala Ser Gln Tyr Leu Pro Phe His Arg Leu Ala 
1               5                   10          

<210>  23
<211>  7
<212>  PRT
<213>  人工序列

<220>
<223>  2-87L LCDR2


<400>  23
Asp Thr Ser Ser Arg Ala Thr 
1               5           

<210>  24
<211>  12
<212>  PRT
<213>  人工序列

<220>
<223>  3-20L LCDR1


<400>  24
Arg Ala Ser Gln Ala Ile Arg Gly Pro Asn Leu Ala 
1               5                   10          

<210>  25
<211>  7
<212>  PRT
<213>  人工序列

<220>
<223>  3-20L LCDR2


<400>  25
Asp Thr Ser Ser Arg Ala Thr 
1               5           

<210>  26
<211>  12
<212>  PRT
<213>  人工序列

<220>
<223>  3-37L LCDR1


<400>  26
Arg Ala Ser Gln Ala Ile Arg Gly Arg Lys Leu Ala 
1               5                   10          

<210>  27
<211>  7
<212>  PRT
<213>  人工序列

<220>
<223>  3-37L LCDR2


<400>  27
Asp Thr Ser Ser Arg Ala Thr 
1               5           

<210>  28
<211>  12
<212>  PRT
<213>  人工序列

<220>
<223>  3-83L LCDR1


<400>  28
Arg Ala Ser Gln Ala Leu Gly Val Arg Gly Leu Ala 
1               5                   10          

<210>  29
<211>  12
<212>  PRT
<213>  人工序列

<220>
<223>  3-85L LCDR1


<400>  29
Arg Ala Ser Gln Ser Ile Pro Gly Pro Arg Leu Ala 
1               5                   10          

<210>  30
<211>  9
<212>  PRT
<213>  人工序列

<220>
<223>  4-64L LCDR3


<400>  30
Gln Gln Tyr Gly Ser Ser Pro Arg Ile 
1               5                   

<210>  31
<211>  122
<212>  PRT
<213>  人工序列

<220>
<223>  1-22H重链可变区


<400>  31
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ala Asp Tyr 
            20                  25                  30          
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ser Gly Ile Ser Ala Ser Gly Ser Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Lys Asp Pro Gly Thr Thr Val Ile Met Ser Trp Phe Asp Pro Trp 
            100                 105                 110         
Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120         

<210>  32
<211>  122
<212>  PRT
<213>  人工序列

<220>
<223>  5-16H重链可变区


<400>  32
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ser Gly Ile Thr Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Lys Asp Pro Ala Ser Ile Val Ile Met Ser Trp Phe Asp Pro Trp 
            100                 105                 110         
Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120         

<210>  33
<211>  122
<212>  PRT
<213>  人工序列

<220>
<223>  5-51H重链可变区


<400>  33
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ser Gly Ile Thr Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Lys Asp Pro Cys Phe Ser Tyr Ile Met Ser Trp Phe Asp Pro Trp 
            100                 105                 110         
Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120         

<210>  34
<211>  122
<212>  PRT
<213>  人工序列

<220>
<223>  5-53H重链可变区


<400>  34
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ser Gly Ile Thr Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Gln Asp Pro Cys Phe Thr Tyr Ile Met Ser Trp Phe Asp Pro Trp 
            100                 105                 110         
Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120         

<210>  35
<211>  122
<212>  PRT
<213>  人工序列

<220>
<223>  5-58H重链可变区


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

<210>  36
<211>  122
<212>  PRT
<213>  人工序列

<220>
<223>  D35H重链可变区


<400>  36
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ala Tyr 
            20                  25                  30          
Pro Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ser Gly Ile Thr Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Lys Asp Pro Gly Thr Thr Val Ile Met Ser Trp Phe Asp Pro Trp 
            100                 105                 110         
Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120         

<210>  37
<211>  122
<212>  PRT
<213>  人工序列

<220>
<223>  D75H重链可变区


<400>  37
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ser Gly Ile Thr Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Val Lys Asp Pro Gly Thr Thr Ser Ile Met Ser Trp Phe Asp Pro Trp 
            100                 105                 110         
Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120         

<210>  38
<211>  122
<212>  PRT
<213>  人工序列

<220>
<223>  D80H重链可变区


<400>  38
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ser Gly Ile Thr Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Val Lys Asp Pro Gly Ser Thr Ile Ile Met Ser Trp Phe Asp Pro Trp 
            100                 105                 110         
Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120         

<210>  39
<211>  122
<212>  PRT
<213>  人工序列

<220>
<223>  2-52L重链可变区


<400>  39
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ser Gly Ile Thr Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Lys Asp Pro Gly Thr Thr Val Ile Met Ser Trp Phe Asp Pro Trp 
            100                 105                 110         
Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120         

<210>  40
<211>  108
<212>  PRT
<213>  人工序列

<220>
<223>  轻链可变区


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

<210>  41
<211>  108
<212>  PRT
<213>  人工序列

<220>
<223>  2-52L轻链可变区


<400>  41
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 
1               5                   10                  15      
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Gly Arg 
            20                  25                  30          
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 
        35                  40                  45              
Ile Tyr Gln Gly Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 
    50                  55                  60                  
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 
65                  70                  75                  80  
Pro Glu Asp Phe Ala Val Phe Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 
                85                  90                  95      
Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105             

<210>  42
<211>  108
<212>  PRT
<213>  人工序列

<220>
<223>  2-72L轻链可变区


<400>  42
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 
1               5                   10                  15      
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Leu Gly Ala Arg 
            20                  25                  30          
Gly Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 
        35                  40                  45              
Ile Tyr Gly Thr Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 
    50                  55                  60                  
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 
65                  70                  75                  80  
Pro Glu Asp Phe Ala Val Phe Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 
                85                  90                  95      
Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105             

<210>  43
<211>  108
<212>  PRT
<213>  人工序列

<220>
<223>  2-76L轻链可变区


<400>  43
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 
1               5                   10                  15      
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ala Ile Pro Tyr Asn 
            20                  25                  30          
Gln Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 
        35                  40                  45              
Ile Tyr Gly Val Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 
    50                  55                  60                  
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 
65                  70                  75                  80  
Pro Glu Asp Phe Ala Val Phe Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 
                85                  90                  95      
Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105             

<210>  44
<211>  108
<212>  PRT
<213>  人工序列

<220>
<223>  2-79L轻链可变区


<400>  44
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 
1               5                   10                  15      
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Gly Arg 
            20                  25                  30          
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 
        35                  40                  45              
Ile Tyr Gly Ser Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 
    50                  55                  60                  
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 
65                  70                  75                  80  
Pro Glu Asp Phe Ala Val Phe Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 
                85                  90                  95      
Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105             

<210>  45
<211>  108
<212>  PRT
<213>  人工序列

<220>
<223>  2-87L轻链可变区


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

<210>  46
<211>  108
<212>  PRT
<213>  人工序列

<220>
<223>  3-20L轻链可变区


<400>  46
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 
1               5                   10                  15      
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ala Ile Arg Gly Pro 
            20                  25                  30          
Asn Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 
        35                  40                  45              
Ile Tyr Asp Thr Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 
    50                  55                  60                  
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 
65                  70                  75                  80  
Pro Glu Asp Phe Ala Val Phe Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 
                85                  90                  95      
Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105             

<210>  47
<211>  108
<212>  PRT
<213>  人工序列

<220>
<223>  3-37L轻链可变区


<400>  47
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 
1               5                   10                  15      
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ala Ile Arg Gly Arg 
            20                  25                  30          
Lys Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 
        35                  40                  45              
Ile Tyr Asp Thr Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 
    50                  55                  60                  
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 
65                  70                  75                  80  
Pro Glu Asp Phe Ala Val Phe Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 
                85                  90                  95      
Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105             

<210>  48
<211>  108
<212>  PRT
<213>  人工序列

<220>
<223>  3-83L轻链可变区


<400>  48
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 
1               5                   10                  15      
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ala Leu Gly Val Arg 
            20                  25                  30          
Gly Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 
        35                  40                  45              
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 
    50                  55                  60                  
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 
65                  70                  75                  80  
Pro Glu Asp Phe Ala Val Phe Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 
                85                  90                  95      
Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105             

<210>  49
<211>  108
<212>  PRT
<213>  人工序列

<220>
<223>  3-85L轻链可变区


<400>  49
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 
1               5                   10                  15      
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Ile Pro Gly Pro 
            20                  25                  30          
Arg Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 
        35                  40                  45              
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 
    50                  55                  60                  
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 
65                  70                  75                  80  
Pro Glu Asp Phe Ala Val Phe Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 
                85                  90                  95      
Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
            100                 105             

<210>  50
<211>  108
<212>  PRT
<213>  人工序列

<220>
<223>  4-64L轻链可变区


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

<210>  51
<211>  327
<212>  PRT
<213>  homo sapiens



<400>  51
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>  52
<211>  107
<212>  PRT
<213>  homo sapiens

<400>  52
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>  53
<211>  449
<212>  PRT
<213>  人工序列

<220>
<223>  D35H重链


<400>  53
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ala Tyr 
            20                  25                  30          
Pro Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ser Gly Ile Thr Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Lys Asp Pro Gly Thr Thr Val Ile Met Ser Trp Phe Asp Pro Trp 
            100                 105                 110         
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro 
        115                 120                 125             
Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr 
    130                 135                 140                 
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 
145                 150                 155                 160 
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 
                165                 170                 175     
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
            180                 185                 190         
Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp 
        195                 200                 205             
His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr 
    210                 215                 220                 
Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro 
225                 230                 235                 240 
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
                245                 250                 255     
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp 
            260                 265                 270         
Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
        275                 280                 285             
Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val 
    290                 295                 300                 
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 
305                 310                 315                 320 
Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys 
                325                 330                 335     
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
            340                 345                 350         
Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr 
        355                 360                 365             
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
    370                 375                 380                 
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
385                 390                 395                 400 
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys 
                405                 410                 415     
Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
            420                 425                 430         
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 
        435                 440                 445             
Lys 
    

<210>  54
<211>  215
<212>  PRT
<213>  人工序列

<220>
<223>  D35H轻链


<400>  54
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 
1               5                   10                  15      
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Gly Arg 
            20                  25                  30          
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 
        35                  40                  45              
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 
    50                  55                  60                  
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 
65                  70                  75                  80  
Pro Glu Asp Phe Ala Val Phe Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 
                85                  90                  95      
Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala 
            100                 105                 110         
Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser 
        115                 120                 125             
Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu 
    130                 135                 140                 
Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser 
145                 150                 155                 160 
Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu 
                165                 170                 175     
Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val 
            180                 185                 190         
Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys 
        195                 200                 205             
Ser Phe Asn Arg Gly Glu Cys 
    210                 215 

<210>  55
<211>  509
<212>  PRT
<213>  人工序列

<220>
<223>  D75H重链


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

<210>  56
<211>  449
<212>  PRT
<213>  人工序列

<220>
<223>  D80H重链


<400>  56
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ser Gly Ile Thr Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Val Lys Asp Pro Gly Ser Thr Ile Ile Met Ser Trp Phe Asp Pro Trp 
            100                 105                 110         
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro 
        115                 120                 125             
Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr 
    130                 135                 140                 
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 
145                 150                 155                 160 
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 
                165                 170                 175     
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
            180                 185                 190         
Val Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp 
        195                 200                 205             
His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr 
    210                 215                 220                 
Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro 
225                 230                 235                 240 
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
                245                 250                 255     
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp 
            260                 265                 270         
Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
        275                 280                 285             
Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val 
    290                 295                 300                 
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 
305                 310                 315                 320 
Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys 
                325                 330                 335     
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
            340                 345                 350         
Leu Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr 
        355                 360                 365             
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
    370                 375                 380                 
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
385                 390                 395                 400 
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys 
                405                 410                 415     
Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
            420                 425                 430         
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly 
        435                 440                 445             
Lys 
    

<210>  57
<211>  448
<212>  PRT
<213>  人工序列

<220>
<223>  Denosumab重链


<400>  57
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ser Gly Ile Thr Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Lys Asp Pro Gly Thr Thr Val Ile Met Ser Trp Phe Asp Pro Trp 
            100                 105                 110         
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro 
        115                 120                 125             
Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr 
    130                 135                 140                 
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 
145                 150                 155                 160 
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 
                165                 170                 175     
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
            180                 185                 190         
Val Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp 
        195                 200                 205             
His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys 
    210                 215                 220                 
Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser 
225                 230                 235                 240 
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
                245                 250                 255     
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro 
            260                 265                 270         
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
        275                 280                 285             
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val 
    290                 295                 300                 
Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
305                 310                 315                 320 
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr 
                325                 330                 335     
Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
            340                 345                 350         
Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys 
        355                 360                 365             
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
    370                 375                 380                 
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp 
385                 390                 395                 400 
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser 
                405                 410                 415     
Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
            420                 425                 430         
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
        435                 440                 445             

<210>  58
<211>  5
<212>  PRT
<213>  人工序列

<220>
<223>  Tanezumab HCDR1


<400>  58
Gly Tyr Asp Leu Asn 
1               5   

<210>  59
<211>  16
<212>  PRT
<213>  人工序列

<220>
<223>  Tanezumab HCDR2


<400>  59
Ile Ile Trp Gly Asp Gly Thr Thr Asp Tyr Asn Ser Ala Val Lys Ser 
1               5                   10                  15      

<210>  60
<211>  13
<212>  PRT
<213>  人工序列

<220>
<223>  Tanezumab HCDR3


<400>  60
Gly Gly Tyr Trp Tyr Ala Thr Ser Tyr Tyr Phe Asp Tyr 
1               5                   10              

<210>  61
<211>  11
<212>  PRT
<213>  人工序列

<220>
<223>  Tanezumab LCDR1


<400>  61
Arg Ala Ser Gln Ser Ile Ser Asn Asn Leu Asn 
1               5                   10      

<210>  62
<211>  7
<212>  PRT
<213>  人工序列

<220>
<223>  Tanezumab LCDR2


<400>  62
Tyr Thr Ser Arg Phe His Ser 
1               5           

<210>  63
<211>  13
<212>  PRT
<213>  人工序列

<220>
<223>  Tanezumab LCDR3


<400>  63
Gly Gly Tyr Trp Tyr Ala Thr Ser Tyr Tyr Phe Asp Tyr 
1               5                   10              

<210>  64
<211>  121
<212>  PRT
<213>  人工序列

<220>
<223>  Tanezumab重链可变区


<400>  64
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu 
1               5                   10                  15      
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ile Gly Tyr 
            20                  25                  30          
Asp Leu Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile 
        35                  40                  45              
Gly Ile Ile Trp Gly Asp Gly Thr Thr Asp Tyr Asn Ser Ala Val Lys 
    50                  55                  60                  
Ser Arg Val Thr Ile Ser Lys Asp Thr Ser Lys Asn Gln Phe Ser Leu 
65                  70                  75                  80  
Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      
Arg Gly Gly Tyr Trp Tyr Ala Thr Ser Tyr Tyr Phe Asp Tyr Trp Gly 
            100                 105                 110 
Gln Gly Thr Leu Val Thr Val Ser Ser
        115                 120                

<210>  65
<211>  107
<212>  PRT
<213>  人工序列

<220>
<223>  Tanezumab轻链可变区


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

<210>  66
<211>  326
<212>  PRT
<213>  人工序列

<220>
<223>  重链恒定区


<400>  66
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 Asn Phe Gly Thr Gln Thr 
65                  70                  75                  80  
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys 
                85                  90                  95      
Thr Val Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro 
            100                 105                 110         
Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
        115                 120                 125             
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
    130                 135                 140                 
Val Ser His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly 
145                 150                 155                 160 
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn 
                165                 170                 175     
Ser Thr Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp 
            180                 185                 190         
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro 
        195                 200                 205             
Ser Ser Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu 
    210                 215                 220                 
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
225                 230                 235                 240 
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
                245                 250                 255     
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
            260                 265                 270         
Thr Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
        275                 280                 285             
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
    290                 295                 300                 
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
305                 310                 315                 320 
Ser Leu Ser Pro Gly Lys 
                325     

<210>  67
<211>  448
<212>  PRT
<213>  人工序列

<220>
<223>  N-mAb重链


<400>  67
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu 
1               5                   10                  15      
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ile Gly Tyr 
            20                  25                  30          
Asp Leu Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile 
        35                  40                  45              
Gly Ile Ile Trp Gly Asp Gly Thr Thr Asp Tyr Asn Ser Ala Val Lys 
    50                  55                  60                  
Ser Arg Val Thr Ile Ser Lys Asp Thr Ser Lys Asn Gln Phe Ser Leu 
65                  70                  75                  80  
Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      
Arg Gly Gly Tyr Trp Tyr Ala Thr Ser Tyr Tyr Phe Asp Tyr Trp Gly 
            100                 105                 110         
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 
        115                 120                 125             
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala 
    130                 135                 140                 
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 
145                 150                 155                 160 
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 
                165                 170                 175     
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 
            180                 185                 190         
Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His 
        195                 200                 205             
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly 
    210                 215                 220                 
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser 
225                 230                 235                 240 
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
                245                 250                 255     
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro 
            260                 265                 270         
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
        275                 280                 285             
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val 
    290                 295                 300                 
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
305                 310                 315                 320 
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr 
                325                 330                 335     
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
            340                 345                 350         
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys 
        355                 360                 365             
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
    370                 375                 380                 
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
385                 390                 395                 400 
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser 
                405                 410                 415     
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
            420                 425                 430         
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 
        435                 440                 445             

<210>  68
<211>  214
<212>  PRT
<213>  人工序列

<220>
<223>  N-mAb轻链


<400>  68
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 Ser Ile Ser Asn Asn 
            20                  25                  30          
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 
        35                  40                  45              
Tyr Tyr Thr Ser Arg Phe His Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  
Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Glu His Thr Leu Pro Tyr 
                85                  90                  95      
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala 
            100                 105                 110         
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly 
        115                 120                 125             
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala 
    130                 135                 140                 
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln 
145                 150                 155                 160 
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser 
                165                 170                 175     
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr 
            180                 185                 190         
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser 
        195                 200                 205             
Phe Asn Arg Gly Glu Cys 
    210                 

<210>  69
<211>  447
<212>  PRT
<213>  人工序列

<220>
<223>  Tanezumab重链


<400>  69
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu 
1               5                   10                  15      
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ile Gly Tyr 
            20                  25                  30          
Asp Leu Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile 
        35                  40                  45              
Gly Ile Ile Trp Gly Asp Gly Thr Thr Asp Tyr Asn Ser Ala Val Lys 
    50                  55                  60                  
Ser Arg Val Thr Ile Ser Lys Asp Thr Ser Lys Asn Gln Phe Ser Leu 
65                  70                  75                  80  
Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      
Arg Gly Gly Tyr Trp Tyr Ala Thr Ser Tyr Tyr Phe Asp Tyr Trp Gly 
            100                 105                 110         
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 
        115                 120                 125             
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala 
    130                 135                 140                 
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 
145                 150                 155                 160 
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 
                165                 170                 175     
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 
            180                 185                 190         
Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His 
        195                 200                 205             
Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys 
    210                 215                 220                 
Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala 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 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 Phe Arg Val Val Ser 
    290                 295                 300                 
Val Leu Thr Val Val 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 Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
            340                 345                 350         
Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu 
        355                 360                 365             
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
    370                 375                 380                 
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser 
385                 390                 395                 400 
Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg 
                405                 410                 415     
Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
            420                 425                 430         
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
        435                 440                 445         

<210>  70
<211>  6
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  70
Ala Ser Thr Lys Gly Pro 
1               5       

<210>  71
<211>  6
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  71
Thr Val Ala Ala Pro Ser 
1               5       

<210>  72
<211>  13
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  72
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro 
1               5                   10              

<210>  73
<211>  12
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  73
Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro 
1               5                   10          

<210>  74
<211>  16
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  74
Ala Lys Thr Thr Pro Lys Leu Glu Glu Gly Glu Phe Ser Glu Ala Arg 
1               5                   10                  15      

<210>  75
<211>  17
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  75
Ala Lys Thr Thr Pro Lys Leu Glu Glu Gly Glu Phe Ser Glu Ala Arg 
1               5                   10                  15      
Val 
    

<210>  76
<211>  9
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  76
Ala Lys Thr Thr Pro Lys Leu Gly Gly 
1               5                   

<210>  77
<211>  10
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  77
Ser Ala Lys Thr Thr Pro Lys Leu Gly Gly 
1               5                   10  

<210>  78
<211>  6
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  78
Ser Ala Lys Thr Thr Pro 
1               5       

<210>  79
<211>  6
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  79
Arg Ala Asp Ala Ala Pro 
1               5       

<210>  80
<211>  9
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  80
Arg Ala Asp Ala Ala Pro Thr Val Ser 
1               5                   

<210>  81
<211>  12
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  81
Arg Ala Asp Ala Ala Ala Ala Gly Gly Pro Gly Ser 
1               5                   10          

<210>  82
<211>  18
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  82
Ser Ala Lys Thr Thr Pro Lys Leu Glu Glu Gly Glu Phe Ser Glu Ala 
1               5                   10                  15      
Arg Val 
        

<210>  83
<211>  5
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  83
Ala Asp Ala Ala Pro 
1               5   

<210>  84
<211>  12
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  84
Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro 
1               5                   10          

<210>  85
<211>  5
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  85
Thr Val Ala Ala Pro 
1               5   

<210>  86
<211>  12
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  86
Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro 
1               5                   10          

<210>  87
<211>  6
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  87
Gln Pro Lys Ala Ala Pro 
1               5       

<210>  88
<211>  13
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  88
Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro 
1               5                   10              

<210>  89
<211>  6
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  89
Ala Lys Thr Thr Pro Pro 
1               5       

<210>  90
<211>  13
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  90
Ala Lys Thr Thr Pro Pro Ser Val Thr Pro Leu Ala Pro 
1               5                   10              

<210>  91
<211>  6
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  91
Ala Lys Thr Thr Ala Pro 
1               5       

<210>  92
<211>  13
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  92
Ala Lys Thr Thr Ala Pro Ser Val Tyr Pro Leu Ala Pro 
1               5                   10              

<210>  93
<211>  13
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  93
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro 
1               5                   10              

<210>  94
<211>  15
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  94
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10                  15  

<210>  95
<211>  15
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  95
Gly Glu Asn Lys Val Glu Tyr Ala Pro Ala Leu Met Ala Leu Ser 
1               5                   10                  15  

<210>  96
<211>  15
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  96
Gly Pro Ala Lys Glu Leu Thr Pro Leu Lys Glu Ala Lys Val Ser 
1               5                   10                  15  

<210>  97
<211>  15
<212>  PRT
<213>  人工序列

<220>
<223>  连接子


<400>  97
Gly His Glu Ala Ala Ala Val Met Gln Val Gln Tyr Pro Ala Ser 
1               5                   10                  15  

<210>  98
<211>  576
<212>  PRT
<213>  人工序列

<220>
<223>  双特异性抗体1的第一链


<400>  98
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ser Gly Ile Thr Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Val Lys Asp Pro Gly Thr Thr Ser Ile Met Ser Trp Phe Asp Pro Trp 
            100                 105                 110         
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro 
        115                 120                 125             
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu 
    130                 135                 140                 
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ile Gly Tyr 
145                 150                 155                 160 
Asp Leu Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile 
                165                 170                 175     
Gly Ile Ile Trp Gly Asp Gly Thr Thr Asp Tyr Asn Ser Ala Val Lys 
            180                 185                 190         
Ser Arg Val Thr Ile Ser Lys Asp Thr Ser Lys Asn Gln Phe Ser Leu 
        195                 200                 205             
Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala 
    210                 215                 220                 
Arg Gly Gly Tyr Trp Tyr Ala Thr Ser Tyr Tyr Phe Asp Tyr Trp Gly 
225                 230                 235                 240 
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 
                245                 250                 255     
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala 
            260                 265                 270         
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 
        275                 280                 285             
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 
    290                 295                 300                 
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 
305                 310                 315                 320 
Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His 
                325                 330                 335     
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly 
            340                 345                 350         
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser 
        355                 360                 365             
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
    370                 375                 380                 
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro 
385                 390                 395                 400 
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
                405                 410                 415     
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val 
            420                 425                 430         
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
        435                 440                 445             
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr 
    450                 455                 460                 
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
465                 470                 475                 480 
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys 
                485                 490                 495     
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
            500                 505                 510         
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
        515                 520                 525             
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser 
    530                 535                 540                 
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
545                 550                 555                 560 
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 
                565                 570                 575     

<210>  99
<211>  327
<212>  PRT
<213>  人工序列

<220>
<223>  双特异性抗体1的第二链


<400>  99
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly 
1               5                   10                  15      
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Arg Gly Arg 
            20                  25                  30          
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu 
        35                  40                  45              
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 
    50                  55                  60                  
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 
65                  70                  75                  80  
Pro Glu Asp Phe Ala Val Phe Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 
                85                  90                  95      
Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Thr Val Ala Ala 
            100                 105                 110         
Pro Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val 
        115                 120                 125             
Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Asn 
    130                 135                 140                 
Asn Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu 
145                 150                 155                 160 
Ile Tyr Tyr Thr Ser Arg Phe His Ser Gly Val Pro Ser Arg Phe Ser 
                165                 170                 175     
Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln 
            180                 185                 190         
Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Glu His Thr Leu Pro 
        195                 200                 205             
Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala 
    210                 215                 220                 
Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser 
225                 230                 235                 240 
Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu 
                245                 250                 255     
Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser 
            260                 265                 270         
Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu 
        275                 280                 285             
Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val 
    290                 295                 300                 
Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys 
305                 310                 315                 320 
Ser Phe Asn Arg Gly Glu Cys 
                325         

<210>  100
<211>  576
<212>  PRT
<213>  人工序列

<220>
<223>  双特异性抗体2的第一链


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

<210>  101
<211>  576
<212>  PRT
<213>  人工序列

<220>
<223>  双特异性抗体3的第一链


<400>  101
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ser Gly Ile Thr Gly Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Val Lys Asp Pro Gly Ser Thr Ile Ile Met Ser Trp Phe Asp Pro Trp 
            100                 105                 110         
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro 
        115                 120                 125             
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu 
    130                 135                 140                 
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ile Gly Tyr 
145                 150                 155                 160 
Asp Leu Asn Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile 
                165                 170                 175     
Gly Ile Ile Trp Gly Asp Gly Thr Thr Asp Tyr Asn Ser Ala Val Lys 
            180                 185                 190         
Ser Arg Val Thr Ile Ser Lys Asp Thr Ser Lys Asn Gln Phe Ser Leu 
        195                 200                 205             
Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala 
    210                 215                 220                 
Arg Gly Gly Tyr Trp Tyr Ala Thr Ser Tyr Tyr Phe Asp Tyr Trp Gly 
225                 230                 235                 240 
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser 
                245                 250                 255     
Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala 
            260                 265                 270         
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val 
        275                 280                 285             
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala 
    290                 295                 300                 
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val 
305                 310                 315                 320 
Pro Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His 
                325                 330                 335     
Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly 
            340                 345                 350         
Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser 
        355                 360                 365             
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg 
    370                 375                 380                 
Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro 
385                 390                 395                 400 
Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala 
                405                 410                 415     
Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val 
            420                 425                 430         
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr 
        435                 440                 445             
Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr 
    450                 455                 460                 
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu 
465                 470                 475                 480 
Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys 
                485                 490                 495     
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser 
            500                 505                 510         
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp 
        515                 520                 525             
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser 
    530                 535                 540                 
Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala 
545                 550                 555                 560 
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 
                565                 570                 575     

<210>  102
<211>  5
<212>  PRT
<213>  人工序列

<220>
<223>  AMR2 HCDR1


<400>  102
Asp Tyr Asp Met Ser 
1               5   

<210>  103
<211>  17
<212>  PRT
<213>  人工序列

<220>
<223>  AMR2 HCDR2


<400>  103
Trp Ile Tyr Pro Ser Gly Gly Ser Ile Tyr Tyr Ala Asp Ser Val Lys 
1               5                   10                  15      
Gly 
    

<210>  104
<211>  18
<212>  PRT
<213>  人工序列

<220>
<223>  AMR2 HCDR3


<400>  104
Ser Gly Leu Thr Arg Thr Arg Trp Pro Ile Tyr Tyr Ala Asp Gly Met 
1               5                   10                  15      
Asp Val 
        

<210>  105
<211>  13
<212>  PRT
<213>  人工序列

<220>
<223>  AMR2 LCDR1


<400>  105
Thr Gly Ser Ser Ser Asn Ile Gly Asn Asn Ala Val Ser 
1               5                   10              

<210>  106
<211>  7
<212>  PRT
<213>  人工序列

<220>
<223>  AMR2 LCDR2


<400>  106
Ser Asp Arg His Arg Pro Ser 
1               5           

<210>  107
<211>  11
<212>  PRT
<213>  人工序列

<220>
<223>  AMR2 LCDR3


<400>  107
Gly Ser Trp Asp Ala Ser Leu Ser Gly Tyr Val 
1               5                   10      

<210>  108
<211>  126
<212>  PRT
<213>  人工序列

<220>
<223>  AMR2重链可变区


<400>  108
Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser 
1               5                   10                  15      
Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr Asp 
            20                  25                  30          
Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser 
        35                  40                  45              
Trp Ile Tyr Pro Ser Gly Gly Ser Ile Tyr Tyr Ala Asp Ser Val Lys 
    50                  55                  60                  
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      
Arg Ser Gly Leu Thr Arg Thr Arg Trp Pro Ile Tyr Tyr Ala Asp Gly 
            100                 105                 110         
Met Asp Val Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125     

<210>  109
<211>  110
<212>  PRT
<213>  人工序列

<220>
<223>  AMR2轻链可变区


<400>  109
Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 
1               5                   10                  15      
Arg Val Thr Ile Ser Cys Thr Gly Ser Ser Ser Asn Ile Gly Asn Asn 
            20                  25                  30          
Ala Val Ser Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 
        35                  40                  45              
Ile Tyr Ser Asp Arg His Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 
    50                  55                  60                  
Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 
65                  70                  75                  80  
Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ser Trp Asp Ala Ser Leu 
                85                  90                  95      
Ser Gly Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
            100                 105                 110 

<210>  110
<211>  454
<212>  PRT
<213>  人工序列

<220>
<223>  AMR2重链


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

<210>  111
<211>  216
<212>  PRT
<213>  人工序列

<220>
<223>  AMR2轻链


<400>  111
Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 
1               5                   10                  15      
Arg Val Thr Ile Ser Cys Thr Gly Ser Ser Ser Asn Ile Gly Asn Asn 
            20                  25                  30          
Ala Val Ser Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 
        35                  40                  45              
Ile Tyr Ser Asp Arg His Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 
    50                  55                  60                  
Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 
65                  70                  75                  80  
Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gly Ser Trp Asp Ala Ser Leu 
                85                  90                  95      
Ser Gly Tyr Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln 
            100                 105                 110         
Pro Lys Ala Asn Pro Thr Val Thr Leu Phe Pro Pro Ser Ser Glu Glu 
        115                 120                 125             
Leu Gln Ala Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr 
    130                 135                 140                 
Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro Val Lys 
145                 150                 155                 160 
Ala Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn Asn Lys Tyr 
                165                 170                 175     
Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His 
            180                 185                 190         
Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys 
        195                 200                 205             
Thr Val Ala Pro Thr Glu Cys Ser 
    210                 215     
 

