﻿                         序列表

<110>  北京东方百泰生物科技股份有限公司
       北京精益泰翔技术发展有限公司

<120>  一种抗LAG-3的单克隆抗体、其抗原结合片段及其应用

<150>  202011436581.5
<151>  2020-12-10

<160>  47

<170>  SIPOSequenceListing 1.0

<210>  1
<211>  5
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  1
Asp Thr Tyr Met His 
1               5   

<210>  2
<211>  17
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  2
Lys Ile Asp Pro Ala Asn Gly Asn Thr Lys Tyr Asp Pro Lys Phe Gln 
1               5                   10                  15      
Gly 
    

<210>  3
<211>  8
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  3
Asp Thr Thr Val Gly Leu Asp Tyr 
1               5               

<210>  4
<211>  10
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  4
Arg Ala Ser Ser Ser Val Asn Tyr Met Tyr 
1               5                   10  

<210>  5
<211>  7
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  5
Tyr Thr Ser Lys Leu Ala Ser 
1               5           

<210>  6
<211>  9
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  6
Gln Gln Trp Ser Ser Asn Pro His Thr 
1               5                   

<210>  7
<211>  7
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  7
Tyr Thr Ser Asn Leu Ala Pro 
1               5           

<210>  8
<211>  10
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  8
Gln Gln Phe Thr Ser Ser Pro Ser Met Thr 
1               5                   10  

<210>  9
<211>  7
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  9
Gly Tyr Ser Phe Thr Ser Tyr 
1               5           

<210>  10
<211>  17
<212>  PRT
<213>  SIPOSequenceListing 1.0

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

<210>  11
<211>  12
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  11
Ile Gly Gly Arg Leu Thr Gly Asp Ala Met Asp Tyr 
1               5                   10          

<210>  12
<211>  15
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  12
Arg Ala Ser Glu Ser Val Asp Ser Tyr Gly Asn Ser Phe Met His 
1               5                   10                  15  

<210>  13
<211>  7
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  13
Leu Ala Ser Asn Leu Glu Ser 
1               5           

<210>  14
<211>  9
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  14
Gln Gln Asn Asn Glu Asp Pro Trp Thr 
1               5                   

<210>  15
<211>  5
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  15
Thr Tyr Ala Val His 
1               5   

<210>  16
<211>  17
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  16
Val Ile Trp Ser Gly Gly Ser Thr Asp Tyr Asn Thr Ala Phe Ile Ser 
1               5                   10                  15      
Arg 
    

<210>  17
<211>  8
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  17
Leu Asp Gly Thr Phe Phe Asp Tyr 
1               5               

<210>  18
<211>  12
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  18
Thr Ala Ser Ser Ser Val Ser Ser Ser Tyr Leu His 
1               5                   10          

<210>  19
<211>  7
<212>  PRT
<213>  SIPOSequenceListing 1.0

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

<210>  20
<211>  9
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  20
His Gln Tyr His Arg Ser Pro Pro Thr 
1               5                   

<210>  21
<211>  117
<212>  PRT
<213>  SIPOSequenceListing 1.0

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

<210>  22
<211>  106
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  22
Asp Ile Val Ile Thr Gln Ser Thr Ala Ile Met Ser Ala Ser Leu Gly 
1               5                   10                  15      
Glu Lys Val Thr Met Ser Cys Arg Ala Ser Ser Ser Val Asn Tyr Met 
            20                  25                  30          
Tyr Trp Tyr Gln Gln Lys Ser Asp Ala Ser Pro Lys Leu Trp Ile Tyr 
        35                  40                  45              
Tyr Thr Ser Lys Leu Ala Ser Gly Val Pro Ala Arg Phe Ser Gly Ser 
    50                  55                  60                  
Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Ser Met Glu Ala Glu 
65                  70                  75                  80  
Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asn Pro His Thr 
                85                  90                  95      
Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105     

<210>  23
<211>  107
<212>  PRT
<213>  SIPOSequenceListing 1.0

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

<210>  24
<211>  121
<212>  PRT
<213>  SIPOSequenceListing 1.0

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

<210>  25
<211>  111
<212>  PRT
<213>  SIPOSequenceListing 1.0

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

<210>  26
<211>  116
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  26
Gln Val Lys Leu Glu Glu Ser Gly Pro Gly Leu Val Gln Pro Ser Gln 
1               5                   10                  15      
Ser Leu Ser Ile Thr Cys Thr Val Ser Ala Phe Ser Leu Thr Thr Tyr 
            20                  25                  30          
Ala Val His Trp Val Arg Gln Ser Pro Gly Lys Gly Leu Glu Trp Leu 
        35                  40                  45              
Gly Val Ile Trp Ser Gly Gly Ser Thr Asp Tyr Asn Thr Ala Phe Ile 
    50                  55                  60                  
Ser Arg Leu Asn Ile Thr Lys Asp Asn Ser Lys Ser Gln Val Phe Phe 
65                  70                  75                  80  
Lys Met Asn Ser Leu Gln Ala Asn Asp Thr Ala Ile Tyr Tyr Cys Ala 
                85                  90                  95      
Arg Leu Asp Gly Thr Phe Phe Asp Tyr Trp Gly Gln Gly Thr Thr Leu 
            100                 105                 110         
Thr Val Ser Ser 
        115     

<210>  27
<211>  108
<212>  PRT
<213>  SIPOSequenceListing 1.0

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

<210>  28
<211>  106
<212>  PRT
<213>  SIPOSequenceListing 1.0

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

<210>  29
<211>  323
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  29
Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala 
1               5                   10                  15      
Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val Lys Gly Tyr 
            20                  25                  30          
Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser 
        35                  40                  45              
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu 
    50                  55                  60                  
Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val 
65                  70                  75                  80  
Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys 
                85                  90                  95      
Ile Val Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro 
            100                 105                 110         
Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu 
        115                 120                 125             
Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser 
    130                 135                 140                 
Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu 
145                 150                 155                 160 
Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr 
                165                 170                 175     
Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn 
            180                 185                 190         
Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro 
        195                 200                 205             
Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln 
    210                 215                 220                 
Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val 
225                 230                 235                 240 
Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val 
                245                 250                 255     
Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln 
            260                 265                 270         
Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn 
        275                 280                 285             
Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val 
    290                 295                 300                 
Leu His Glu Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His 
305                 310                 315                 320 
Ser Pro Gly 
            

<210>  30
<211>  330
<212>  PRT
<213>  SIPOSequenceListing 1.0

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

<210>  31
<211>  336
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  31
Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Cys Gly 
1               5                   10                  15      
Asp Thr Thr Gly Ser Ser Val Thr Leu Gly Cys Leu Val Lys Gly Tyr 
            20                  25                  30          
Phe Pro Glu Ser Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser 
        35                  40                  45              
Ser Val His Thr Phe Pro Ala Leu Leu Gln Ser Gly Leu Tyr Thr Met 
    50                  55                  60                  
Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser Gln Thr Val 
65                  70                  75                  80  
Thr Cys Ser Val Ala His Pro Ala Ser Ser Thr Thr Val Asp Lys Lys 
                85                  90                  95      
Leu Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Cys Pro Pro Cys 
            100                 105                 110         
Lys Glu Cys His Lys Cys Pro Ala Pro Asn Leu Glu Gly Gly Pro Ser 
        115                 120                 125             
Val Phe Ile Phe Pro Pro Asn Ile Lys Asp Val Leu Met Ile Ser Leu 
    130                 135                 140                 
Thr Pro Lys Val Thr Cys Val Val Val Asp Val Ser Glu Asp Asp Pro 
145                 150                 155                 160 
Asp Val Gln Ile Ser Trp Phe Val Asn Asn Val Glu Val His Thr Ala 
                165                 170                 175     
Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Ile Arg Val Val 
            180                 185                 190         
Ser Thr Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys Glu Phe 
        195                 200                 205             
Lys Cys Lys Val Asn Asn Lys Asp Leu Pro Ser Pro Ile Glu Arg Thr 
    210                 215                 220                 
Ile Ser Lys Ile Lys Gly Leu Val Arg Ala Pro Gln Val Tyr Ile Leu 
225                 230                 235                 240 
Pro Pro Pro Ala Glu Gln Leu Ser Arg Lys Asp Val Ser Leu Thr Cys 
                245                 250                 255     
Leu Val Val Gly Phe Asn Pro Gly Asp Ile Ser Val Glu Trp Thr Ser 
            260                 265                 270         
Asn Gly His Thr Glu Glu Asn Tyr Lys Asp Thr Ala Pro Val Leu Asp 
        275                 280                 285             
Ser Asp Gly Ser Tyr Phe Ile Tyr Ser Lys Leu Asn Met Lys Thr Ser 
    290                 295                 300                 
Lys Trp Glu Lys Thr Asp Ser Phe Ser Cys Asn Val Arg His Glu Gly 
305                 310                 315                 320 
Leu Lys Asn Tyr Tyr Leu Lys Lys Thr Ile Ser Arg Ser Pro Gly Lys 
                325                 330                 335     

<210>  32
<211>  399
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  32
Ala Thr Thr Thr Ala Pro Ser Val Tyr Pro Leu Val Pro Gly Cys Ser 
1               5                   10                  15      
Asp Thr Ser Gly Ser Ser Val Thr Leu Gly Cys Leu Val Lys Gly Tyr 
            20                  25                  30          
Phe Pro Glu Pro Val Thr Val Lys Trp Asn Tyr Gly Ala Leu Ser Ser 
        35                  40                  45              
Gly Val Arg Thr Val Ser Ser Val Leu Gln Ser Gly Phe Tyr Ser Leu 
    50                  55                  60                  
Ser Ser Leu Val Thr Val Pro Ser Ser Thr Trp Pro Ser Gln Thr Val 
65                  70                  75                  80  
Ile Cys Asn Val Ala His Pro Ala Ser Lys Thr Glu Leu Ile Lys Arg 
                85                  90                  95      
Ile Glu Pro Arg Ile Pro Lys Pro Ser Thr Pro Pro Gly Ser Ser Cys 
            100                 105                 110         
Pro Pro Gly Asn Ile Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro 
        115                 120                 125             
Lys Pro Lys Asp Ala Leu Met Ile Ser Leu Thr Pro Lys Val Thr Cys 
    130                 135                 140                 
Val Val Val Asp Val Ser Glu Asp Asp Pro Asp Val His Val Ser Trp 
145                 150                 155                 160 
Phe Val Asp Asn Lys Glu Val His Thr Ala Trp Thr Gln Pro Arg Glu 
                165                 170                 175     
Ala Gln Tyr Asn Ser Thr Phe Arg Val Val Ser Ala Leu Pro Ile Gln 
            180                 185                 190         
His Gln Asp Trp Met Arg Gly Lys Glu Phe Lys Cys Lys Val Asn Asn 
        195                 200                 205             
Lys Ala Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly 
    210                 215                 220                 
Arg Ala Gln Thr Pro Gln Val Tyr Thr Ile Pro Pro Pro Arg Glu Gln 
225                 230                 235                 240 
Met Ser Lys Lys Lys Val Ser Leu Thr Cys Leu Val Thr Asn Phe Phe 
                245                 250                 255     
Ser Glu Ala Ile Ser Val Glu Trp Glu Arg Asn Gly Glu Leu Glu Gln 
            260                 265                 270         
Asp Tyr Lys Asn Thr Pro Pro Ile Leu Asp Ser Asp Gly Thr Tyr Phe 
        275                 280                 285             
Leu Tyr Ser Lys Leu Thr Val Asp Thr Asp Ser Trp Leu Gln Gly Glu 
    290                 295                 300                 
Ile Phe Thr Cys Ser Val Val His Glu Ala Leu His Asn His His Thr 
305                 310                 315                 320 
Gln Lys Asn Leu Ser Arg Ser Pro Glu Leu Glu Leu Asn Glu Thr Cys 
                325                 330                 335     
Ala Glu Ala Gln Asp Gly Glu Leu Asp Gly Leu Trp Thr Thr Ile Thr 
            340                 345                 350         
Ile Phe Ile Ser Leu Phe Leu Leu Ser Val Cys Tyr Ser Ala Ser Val 
        355                 360                 365             
Thr Leu Phe Lys Val Lys Trp Ile Phe Ser Ser Val Val Gln Val Lys 
    370                 375                 380                 
Gln Thr Ala Ile Pro Asp Tyr Arg Asn Met Ile Gly Gln Gly Ala 
385                 390                 395                 

<210>  33
<211>  117
<212>  PRT
<213>  SIPOSequenceListing 1.0

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

<210>  34
<211>  106
<212>  PRT
<213>  SIPOSequenceListing 1.0

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

<210>  35
<211>  106
<212>  PRT
<213>  SIPOSequenceListing 1.0

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

<210>  36
<211>  117
<212>  PRT
<213>  SIPOSequenceListing 1.0

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

<210>  37
<211>  117
<212>  PRT
<213>  SIPOSequenceListing 1.0

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

<210>  38
<211>  106
<212>  PRT
<213>  SIPOSequenceListing 1.0

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

<210>  39
<211>  330
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  39
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys 
1               5                   10                  15      
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr 
            20                  25                  30          
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser 
        35                  40                  45              
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser 
    50                  55                  60                  
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr 
65                  70                  75                  80  
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys 
                85                  90                  95      
Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys 
            100                 105                 110         
Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
        115                 120                 125             
Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys 
    130                 135                 140                 
Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
145                 150                 155                 160 
Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
                165                 170                 175     
Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
            180                 185                 190         
His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
        195                 200                 205             
Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
    210                 215                 220                 
Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu 
225                 230                 235                 240 
Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr 
                245                 250                 255     
Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
            260                 265                 270         
Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
        275                 280                 285             
Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
    290                 295                 300                 
Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
305                 310                 315                 320 
Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                325                 330 

<210>  40
<211>  326
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  40
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             
Ala Pro 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>  41
<211>  327
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  41
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>  42
<211>  107
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  42
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>  43
<211>  113
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  43
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg 
1               5                   10                  15      
Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Tyr 
            20                  25                  30          
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ala Val Ile Trp Tyr Asp Ser Ser Arg Lys Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Phe 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Thr Asn Asn Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser 
            100                 105                 110         
Ser 
    

<210>  44
<211>  107
<212>  PRT
<213>  SIPOSequenceListing 1.0

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

<210>  45
<211>  107
<212>  PRT
<213>  SIPOSequenceListing 1.0

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

<210>  46
<211>  113
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  46
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg 
1               5                   10                  15      
Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Asn 
            20                  25                  30          
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ala Val Ile Trp Tyr Asp Ser Ser Arg Lys Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Phe 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Thr Asn Asn Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser 
            100                 105                 110         
Ser 
    

<210>  47
<211>  113
<212>  PRT
<213>  SIPOSequenceListing 1.0

<400>  47
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg 
1               5                   10                  15      
Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Tyr 
            20                  25                  30          
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              
Ala Val Ile Trp Tyr Asp Gly Ser Lys Lys Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Phe 
65                  70                  75                  80  
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      
Ala Thr Asn Asn Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser 
            100                 105                 110         
Ser 
    

