﻿                         序列表

<110>  杭州九源基因工程有限公司

<120>  靶向PD-L1和TGFβ的双功能融合蛋白及其制备方法与应用

<160>  44

<170>  SIPOSequenceListing 1.0

<210>  1
<211>  10
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  1
Arg Thr Asp Ser Asn Ile Asn Gly Met His 
1               5                   10  

<210>  2
<211>  9
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  2
Thr Ile Phe Ile Asp Gly Asn Thr Ile 
1               5                   

<210>  3
<211>  8
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  3
Asp Val Ser Gly Tyr Gly Arg Ala 
1               5               

<210>  4
<211>  10
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  4
Arg Thr Asp Arg Asn Ile Asn Thr Met His 
1               5                   10  

<210>  5
<211>  9
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  5
Thr Ile Phe Ile Asp Leu Asn Thr Ile 
1               5                   

<210>  6
<211>  10
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  6
Gly Phe Thr Phe Ser Arg Arg Cys Lys Ala 
1               5                   10  

<210>  7
<211>  10
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  7
Lys Ile Leu Thr Thr Ser Gly Ser Thr Tyr 
1               5                   10  

<210>  8
<211>  19
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  8
Asp Ser Phe Glu Asp Pro Thr Cys Thr Leu Val Thr Ser Ser Gly Ala 
1               5                   10                  15      
Phe Gln Tyr 
            

<210>  9
<211>  128
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  9
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Arg Arg 
            20                  25                  30          
Cys Lys Ala Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Arg Val 
        35                  40                  45              
Ala Lys Ile Leu Thr Thr Ser Gly Ser Thr Tyr Leu Ala Asp Ser Val 
    50                  55                  60                  
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Val 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 Ala Asp Ser Phe Glu Asp Pro Thr Cys Thr Leu Val Thr Ser Ser 
            100                 105                 110         
Gly Ala Phe Gln Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125             

<210>  10
<211>  116
<212>  PRT
<213>  人工序列(Artificial Sequence)

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

<210>  11
<211>  116
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  11
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Arg Thr Asp Ser Asn Ile Asn 
            20                  25                  30          
Gly Met His Trp Tyr Arg Gln Ala Pro Gly Lys Gly Arg Glu Trp Val 
        35                  40                  45              
Gly Thr Ile Phe Ile Asp Gly Asn Thr Ile Val Thr Asp Ser Val Lys 
    50                  55                  60                  
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  
Gln Met Asn Thr Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      
Ala Asp Val Ser Gly Tyr Gly Arg Ala Trp Gly Gln Gly Thr Thr Val 
            100                 105                 110         
Thr Val Ser Ser 
        115     

<210>  12
<211>  116
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  12
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala His Ser Arg Thr Asp Ser Asn Ile Asn 
            20                  25                  30          
Gly Met His Trp Tyr Arg Gln Ala Pro Gly Lys Gly Arg Glu Trp Val 
        35                  40                  45              
Gly Thr Ile Phe Ile Asp Gly Asn Thr Ile Val Thr Asp Ser Val Lys 
    50                  55                  60                  
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  
Gln Met Asn Thr Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      
Ala Asp Val Ser Gly Tyr Gly Arg Ala Trp Gly Gln Gly Thr Thr Val 
            100                 105                 110         
Thr Val Ser Ser 
        115     

<210>  13
<211>  116
<212>  PRT
<213>  人工序列(Artificial Sequence)

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

<210>  14
<211>  25
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  14
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala His Ser 
            20                  25  

<210>  15
<211>  14
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  15
Trp Tyr Arg Gln Ala Pro Gly Lys Gly Arg Glu Trp Val Gly 
1               5                   10                  

<210>  16
<211>  39
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  16
Val Thr Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala 
1               5                   10                  15      
Lys Asn Thr Leu Tyr Leu Gln Met Asn Thr Leu Arg Ala Glu Asp Thr 
            20                  25                  30          
Ala Val Tyr Tyr Cys Ala Ala 
        35                  

<210>  17
<211>  11
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  17
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
1               5                   10      

<210>  18
<211>  25
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  18
Glu Val Gln Val Gln Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala His Ser 
            20                  25  

<210>  19
<211>  14
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  19
Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Asp Trp Val Gly 
1               5                   10                  

<210>  20
<211>  39
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  20
Val Thr Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala 
1               5                   10                  15      
Lys Asn Thr Leu Tyr Leu Gln Met Asn Thr Leu Lys Pro Glu Asp Thr 
            20                  25                  30          
Ala Val Tyr Phe Cys Ala Ala 
        35                  

<210>  21
<211>  11
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  21
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser 
1               5                   10      

<210>  22
<211>  25
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  22
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser 
            20                  25  

<210>  23
<211>  25
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  23
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser 
            20                  25  

<210>  24
<211>  14
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  24
Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Arg Val Ala 
1               5                   10                  

<210>  25
<211>  39
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  25
Leu Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser 
1               5                   10                  15      
Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr 
            20                  25                  30          
Ala Val Tyr Tyr Cys Ala Ala 
        35                  

<210>  26
<211>  11
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  26
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
1               5                   10      

<210>  27
<211>  21
<212>  PRT
<213>  人工序列(Artificial Sequence)

<400>  27
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
1               5                   10                  15      
Gly Gly Gly Ser Gly 
            20      

<210>  28
<211>  232
<212>  PRT
<213>  Human IgG1 Fc序列(Artificial Sequence)

<400>  28
Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 
1               5                   10                  15      
Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
            20                  25                  30          
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
        35                  40                  45              
Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
    50                  55                  60                  
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
65                  70                  75                  80  
Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
                85                  90                  95      
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
            100                 105                 110         
Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
        115                 120                 125             
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr 
    130                 135                 140                 
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
145                 150                 155                 160 
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
                165                 170                 175     
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
            180                 185                 190         
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
        195                 200                 205             
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
    210                 215                 220                 
Ser Leu Ser Leu Ser Pro Gly Lys 
225                 230         

<210>  29
<211>  232
<212>  PRT
<213>  mut IgG1 Fc蛋白序列(Artificial Sequence)

<400>  29
Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 
1               5                   10                  15      
Pro Glu Phe Glu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
            20                  25                  30          
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
        35                  40                  45              
Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
    50                  55                  60                  
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
65                  70                  75                  80  
Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
                85                  90                  95      
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
            100                 105                 110         
Leu Pro Ala Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
        115                 120                 125             
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr 
    130                 135                 140                 
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser 
145                 150                 155                 160 
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
                165                 170                 175     
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
            180                 185                 190         
Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
        195                 200                 205             
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
    210                 215                 220                 
Ser Leu Ser Leu Ser Pro Gly Lys 
225                 230         

<210>  30
<211>  229
<212>  PRT
<213>  Human IgG4 Fc蛋白序列(Artificial Sequence)

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

<210>  31
<211>  136
<212>  PRT
<213>  TGFβ RII ECD(1-136)序列(Artificial Sequence)

<400>  31
Ile Pro Pro His Val Gln Lys Ser Val Asn Asn Asp Met Ile Val Thr 
1               5                   10                  15      
Asp Asn Asn Gly Ala Val Lys Phe Pro Gln Leu Cys Lys Phe Cys Asp 
            20                  25                  30          
Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys 
        35                  40                  45              
Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val 
    50                  55                  60                  
Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp 
65                  70                  75                  80  
Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro 
                85                  90                  95      
Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met 
            100                 105                 110         
Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu 
        115                 120                 125             
Glu Tyr Asn Thr Ser Asn Pro Asp 
    130                 135     

<210>  32
<211>  122
<212>  PRT
<213>  TGFβ RII ECD(15-136)序列(Artificial Sequence)

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

<210>  33
<211>  117
<212>  PRT
<213>  TGFβ RII ECD(19-136)序列(Artificial Sequence)

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

<210>  34
<211>  115
<212>  PRT
<213>  TGFβ RII ECD(22-136)序列(Artificial Sequence)

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

<210>  35
<211>  505
<212>  PRT
<213>  双功能融合蛋白D21-4-T蛋白序列(Artificial Sequence)

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

<210>  36
<211>  502
<212>  PRT
<213>  双功能融合蛋白D21-4-T-G4蛋白序列(Artificial Sequence)

<400>  36
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Arg Thr Asp Arg Asn Ile Asn 
            20                  25                  30          
Thr Met His Trp Tyr Arg Gln Ala Pro Gly Lys Gly Arg Glu Trp Val 
        35                  40                  45              
Gly Thr Ile Phe Ile Asp Leu Asn Thr Ile Val Thr Asp Ser Val Lys 
    50                  55                  60                  
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  
Gln Met Asn Thr Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      
Ala Asp Val Ser Gly Tyr Gly Arg Ala Trp Gly Gln Gly Thr Thr Val 
            100                 105                 110         
Thr Val Ser Ser Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro 
        115                 120                 125             
Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
    130                 135                 140                 
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
145                 150                 155                 160 
Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr 
                165                 170                 175     
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
            180                 185                 190         
Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
        195                 200                 205             
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
    210                 215                 220                 
Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
225                 230                 235                 240 
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met 
                245                 250                 255     
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 
            260                 265                 270         
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
        275                 280                 285             
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
    290                 295                 300                 
Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val 
305                 310                 315                 320 
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
                325                 330                 335     
Lys Ser Leu Ser Leu Ser Leu Gly Ala Gly Gly Gly Gly Ser Gly Gly 
            340                 345                 350         
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Ile Pro 
        355                 360                 365             
Pro His Val Gln Lys Ser Val Asn Asn Asp Met Ile Val Thr Asp Asn 
    370                 375                 380                 
Asn Gly Ala Val Lys Phe Pro Gln Leu Cys Lys Phe Cys Asp Val Arg 
385                 390                 395                 400 
Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile 
                405                 410                 415     
Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg 
            420                 425                 430         
Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys 
        435                 440                 445             
Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys 
    450                 455                 460                 
Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser 
465                 470                 475                 480 
Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr 
                485                 490                 495     
Asn Thr Ser Asn Pro Asp 
            500         

<210>  37
<211>  505
<212>  PRT
<213>  双功能融合蛋白D21-4-T-mG1蛋白序列(Artificial Sequence)

<400>  37
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Arg Thr Asp Arg Asn Ile Asn 
            20                  25                  30          
Thr Met His Trp Tyr Arg Gln Ala Pro Gly Lys Gly Arg Glu Trp Val 
        35                  40                  45              
Gly Thr Ile Phe Ile Asp Leu Asn Thr Ile Val Thr Asp Ser Val Lys 
    50                  55                  60                  
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  
Gln Met Asn Thr Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      
Ala Asp Val Ser Gly Tyr Gly Arg Ala Trp Gly Gln Gly Thr Thr Val 
            100                 105                 110         
Thr Val Ser Ser Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 
        115                 120                 125             
Pro Cys Pro Ala Pro Glu Phe Glu Gly Gly Pro Ser Val Phe Leu Phe 
    130                 135                 140                 
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 
145                 150                 155                 160 
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 
                165                 170                 175     
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 
            180                 185                 190         
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 
        195                 200                 205             
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 
    210                 215                 220                 
Ser Asn Lys Ala Leu Pro Ala Ser Ile Glu Lys Thr Ile Ser Lys Ala 
225                 230                 235                 240 
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 
                245                 250                 255     
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 
            260                 265                 270         
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 
        275                 280                 285             
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 
    290                 295                 300                 
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 
305                 310                 315                 320 
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 
                325                 330                 335     
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly 
            340                 345                 350         
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
        355                 360                 365             
Gly Ile Pro Pro His Val Gln Lys Ser Val Asn Asn Asp Met Ile Val 
    370                 375                 380                 
Thr Asp Asn Asn Gly Ala Val Lys Phe Pro Gln Leu Cys Lys Phe Cys 
385                 390                 395                 400 
Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn 
                405                 410                 415     
Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala 
            420                 425                 430         
Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His 
        435                 440                 445             
Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser 
    450                 455                 460                 
Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe 
465                 470                 475                 480 
Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser 
                485                 490                 495     
Glu Glu Tyr Asn Thr Ser Asn Pro Asp 
            500                 505 

<210>  38
<211>  505
<212>  PRT
<213>  双功能融合蛋白D21-huVH1-T蛋白序列(Artificial Sequence)

<400>  38
Glu Val Gln Val Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala His Ser Arg Thr Asp Ser Asn Ile Asn 
            20                  25                  30          
Gly Met His Trp Tyr Arg Gln Ala Pro Gly Lys Gly Arg Glu Trp Val 
        35                  40                  45              
Gly Thr Ile Phe Ile Asp Gly Asn Thr Ile Val Thr Asp Ser Val Lys 
    50                  55                  60                  
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  
Gln Met Asn Thr Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      
Ala Asp Val Ser Gly Tyr Gly Arg Ala Trp Gly Gln Gly Thr Thr Val 
            100                 105                 110         
Thr Val Ser Ser Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 
        115                 120                 125             
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe 
    130                 135                 140                 
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 
145                 150                 155                 160 
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 
                165                 170                 175     
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 
            180                 185                 190         
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 
        195                 200                 205             
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 
    210                 215                 220                 
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 
225                 230                 235                 240 
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 
                245                 250                 255     
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 
            260                 265                 270         
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 
        275                 280                 285             
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 
    290                 295                 300                 
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 
305                 310                 315                 320 
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 
                325                 330                 335     
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly 
            340                 345                 350         
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
        355                 360                 365             
Gly Ile Pro Pro His Val Gln Lys Ser Val Asn Asn Asp Met Ile Val 
    370                 375                 380                 
Thr Asp Asn Asn Gly Ala Val Lys Phe Pro Gln Leu Cys Lys Phe Cys 
385                 390                 395                 400 
Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn 
                405                 410                 415     
Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala 
            420                 425                 430         
Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His 
        435                 440                 445             
Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser 
    450                 455                 460                 
Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe 
465                 470                 475                 480 
Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser 
                485                 490                 495     
Glu Glu Tyr Asn Thr Ser Asn Pro Asp 
            500                 505 

<210>  39
<211>  505
<212>  PRT
<213>  双功能融合蛋白D21-huVH2-T蛋白序列(Artificial Sequence)

<400>  39
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Arg Thr Asp Ser Asn Ile Asn 
            20                  25                  30          
Gly Met His Trp Tyr Arg Gln Ala Pro Gly Lys Gly Arg Glu Trp Val 
        35                  40                  45              
Gly Thr Ile Phe Ile Asp Gly Asn Thr Ile Val Thr Asp Ser Val Lys 
    50                  55                  60                  
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  
Gln Met Asn Thr Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      
Ala Asp Val Ser Gly Tyr Gly Arg Ala Trp Gly Gln Gly Thr Thr Val 
            100                 105                 110         
Thr Val Ser Ser Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 
        115                 120                 125             
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe 
    130                 135                 140                 
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 
145                 150                 155                 160 
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 
                165                 170                 175     
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 
            180                 185                 190         
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 
        195                 200                 205             
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 
    210                 215                 220                 
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 
225                 230                 235                 240 
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 
                245                 250                 255     
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 
            260                 265                 270         
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 
        275                 280                 285             
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 
    290                 295                 300                 
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 
305                 310                 315                 320 
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 
                325                 330                 335     
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly 
            340                 345                 350         
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
        355                 360                 365             
Gly Ile Pro Pro His Val Gln Lys Ser Val Asn Asn Asp Met Ile Val 
    370                 375                 380                 
Thr Asp Asn Asn Gly Ala Val Lys Phe Pro Gln Leu Cys Lys Phe Cys 
385                 390                 395                 400 
Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn 
                405                 410                 415     
Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala 
            420                 425                 430         
Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His 
        435                 440                 445             
Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser 
    450                 455                 460                 
Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe 
465                 470                 475                 480 
Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser 
                485                 490                 495     
Glu Glu Tyr Asn Thr Ser Asn Pro Asp 
            500                 505 

<210>  40
<211>  348
<212>  PRT
<213>  纳米抗体D21-4蛋白序列(Artificial Sequence)

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

<210>  41
<211>  1044
<212>  DNA
<213>  纳米抗体D21-4 DNA序列(Artificial Sequence)

<400>  41
gaggtgcagc tggtggaatc cggaggcgga ctcgtgcaac ccggcggctc tctgagactg        60
agctgtgccg cttctcggac cgacagaaac atcaacacca tgcactggta tagacaggct       120
cctggcaagg gccgcgagtg ggtcggcaca atcttcatcg acctgaacac catcgtgaca       180
gattccgtga aaggcagatt caccatctcc cgggacaacg ccaagaatac actgtacctg       240
cagatgaaca ccctgcgggc cgaggacacc gccgtgtact actgcgctgc tgatgtgtct       300
ggctacggca gagcctgggg ccagggcacc accgtgaccg tgtccagcga gcctaagtcc       360
tgcgacaaga cccacacatg ccccccttgt cctgctccag agctgctggg aggaccaagc       420
gtgttcctgt ttccacccaa gcctaaggat accctgatga tctccaggac cccagaggtg       480
acatgcgtgg tggtggacgt gagccacgag gatcctgagg tgaagttcaa ctggtacgtg       540
gacggcgtgg aggtgcataa tgctaagaca aagccaaggg aggagcagta caactctacc       600
tatcgggtgg tgtccgtgct gacagtgctg catcaggatt ggctgaacgg caaggagtat       660
aagtgcaagg tgtctaataa ggccctgccc gctcctatcg agaagaccat ctccaaggcc       720
aagggccagc caagagagcc ccaggtgtac acactgcctc caagccgcga ggagatgacc       780
aagaaccagg tgtctctgac atgtctggtg aagggcttct atccttctga catcgctgtg       840
gagtgggagt ccaatggcca gccagaaaac aactataaaa caacaccccc tgtgctggat       900
tctgatggct ccttcttcct gtattcaaaa ctgaccgtgg acaaaagtcg ctggcagcag       960
ggcaacgtgt tctcctgcag cgtgatgcac gaagccctgc acaaccatta cactcagaaa      1020
tcactgtcac tgtctcctgg caag                                             1078

<210>  42
<211>  1515
<212>  DNA
<213>  PD-L1/TGFβ trap双功能抗体双功能融合蛋白D21-4-T DNA序列(Artificial Sequence)

<400>  42
gaagtgcagc tggtggaatc cggcggcgga ctcgtccaac ccggaggctc tctgagactg        60
tcctgcgccg ctagcagaac cgatcggaac atcaacacca tgcactggta cagacaggct       120
cctggcaaag gcagagagtg ggtgggcacc atcttcatcg acctgaatac catcgtgacc       180
gattctgtga agggccggtt caccatctcc cgggacaacg ccaagaacac cctgtacctg       240
cagatgaaca cactgcgcgc cgaggacaca gctgtgtact attgtgctgc cgacgtgtct       300
ggctacggca gagcctgggg ccagggcacc accgtgacag tgtccagcga gcctaagtcc       360
tgcgacaaga cccacacatg ccccccttgt cctgctccag agctgctggg aggaccaagc       420
gtgttcctgt ttccacccaa gcctaaggat accctgatga tctccaggac cccagaggtg       480
acatgcgtgg tggtggacgt gagccacgag gatcctgagg tgaagttcaa ctggtacgtg       540
gacggcgtgg aggtgcataa tgctaagaca aagccaaggg aggagcagta caactctacc       600
tatcgggtgg tgtccgtgct gacagtgctg catcaggatt ggctgaacgg caaggagtat       660
aagtgcaagg tgtctaataa ggccctgccc gctcctatcg agaagaccat ctccaaggcc       720
aagggccagc caagagagcc ccaggtgtac acactgcctc caagccgcga ggagatgacc       780
aagaaccagg tgtctctgac atgtctggtg aagggcttct atccttctga catcgctgtg       840
gagtgggagt ccaatggcca gccagagaac aattacaaga ccacaccccc tgtgctggac       900
agcgatggct ctttctttct gtattccaag ctgaccgtgg ataagagcag gtggcagcag       960
ggcaacgtgt tttcttgctc cgtgatgcac gaggccctgc acaatcatta cacacagaag      1020
agcctgtctc tgtccccagg agctggagga ggaggaagcg gaggcggcgg ctctggcggc      1080
ggcggctcag gcggcggcgg cagcggcatc ccaccccatg tgcagaagtc tgtgaacaat      1140
gacatgatcg tgaccgataa caatggcgcc gtgaagtttc cacagctgtg caagttctgt      1200
gacgtgaggt tttccacctg tgataaccag aagtcctgca tgagcaattg ttctatcaca      1260
tccatctgcg agaagccaca ggaggtgtgc gtggccgtgt ggcggaagaa cgacgagaat      1320
atcaccctgg agacagtgtg ccacgatcct aagctgccat accatgactt catcctggag      1380
gatgccgcta gcccaaagtg tatcatgaag gagaagaaga agcccggcga gaccttcttt      1440
atgtgctctt gttccagcga cgagtgcaac gataatatca tctttagcga ggagtataac      1500
acatctaatc ctgac                                                       1565

<210>  43
<211>  491
<212>  PRT
<213>  双功能融合蛋白D21-4-T-14蛋白序列(Artificial Sequence)

<400>  43
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Arg Thr Asp Arg Asn Ile Asn 
            20                  25                  30          
Thr Met His Trp Tyr Arg Gln Ala Pro Gly Lys Gly Arg Glu Trp Val 
        35                  40                  45              
Gly Thr Ile Phe Ile Asp Leu Asn Thr Ile Val Thr Asp Ser Val Lys 
    50                  55                  60                  
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  
Gln Met Asn Thr Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      
Ala Asp Val Ser Gly Tyr Gly Arg Ala Trp Gly Gln Gly Thr Thr Val 
            100                 105                 110         
Thr Val Ser Ser Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 
        115                 120                 125             
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe 
    130                 135                 140                 
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 
145                 150                 155                 160 
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 
                165                 170                 175     
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 
            180                 185                 190         
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 
        195                 200                 205             
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 
    210                 215                 220                 
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 
225                 230                 235                 240 
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 
                245                 250                 255     
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 
            260                 265                 270         
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 
        275                 280                 285             
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 
    290                 295                 300                 
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 
305                 310                 315                 320 
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 
                325                 330                 335     
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly 
            340                 345                 350         
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
        355                 360                 365             
Gly Val Thr Asp Asn Asn Gly Ala Val Lys Phe Pro Gln Leu Cys Lys 
    370                 375                 380                 
Phe Cys Asp Val Arg Phe Ser Thr Cys Asp Asn Gln Lys Ser Cys Met 
385                 390                 395                 400 
Ser Asn Cys Ser Ile Thr Ser Ile Cys Glu Lys Pro Gln Glu Val Cys 
                405                 410                 415     
Val Ala Val Trp Arg Lys Asn Asp Glu Asn Ile Thr Leu Glu Thr Val 
            420                 425                 430         
Cys His Asp Pro Lys Leu Pro Tyr His Asp Phe Ile Leu Glu Asp Ala 
        435                 440                 445             
Ala Ser Pro Lys Cys Ile Met Lys Glu Lys Lys Lys Pro Gly Glu Thr 
    450                 455                 460                 
Phe Phe Met Cys Ser Cys Ser Ser Asp Glu Cys Asn Asp Asn Ile Ile 
465                 470                 475                 480 
Phe Ser Glu Glu Tyr Asn Thr Ser Asn Pro Asp 
                485                 490     

<210>  44
<211>  484
<212>  PRT
<213>  双功能融合蛋白D21-4-T-21蛋白序列(Artificial Sequence)

<400>  44
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Arg Thr Asp Arg Asn Ile Asn 
            20                  25                  30          
Thr Met His Trp Tyr Arg Gln Ala Pro Gly Lys Gly Arg Glu Trp Val 
        35                  40                  45              
Gly Thr Ile Phe Ile Asp Leu Asn Thr Ile Val Thr Asp Ser Val Lys 
    50                  55                  60                  
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu 
65                  70                  75                  80  
Gln Met Asn Thr Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      
Ala Asp Val Ser Gly Tyr Gly Arg Ala Trp Gly Gln Gly Thr Thr Val 
            100                 105                 110         
Thr Val Ser Ser Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro 
        115                 120                 125             
Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe 
    130                 135                 140                 
Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 
145                 150                 155                 160 
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 
                165                 170                 175     
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 
            180                 185                 190         
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 
        195                 200                 205             
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 
    210                 215                 220                 
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 
225                 230                 235                 240 
Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg 
                245                 250                 255     
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly 
            260                 265                 270         
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 
        275                 280                 285             
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 
    290                 295                 300                 
Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 
305                 310                 315                 320 
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 
                325                 330                 335     
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Ala Gly Gly Gly Gly 
            340                 345                 350         
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
        355                 360                 365             
Gly Val Lys Phe Pro Gln Leu Cys Lys Phe Cys Asp Val Arg Phe Ser 
    370                 375                 380                 
Thr Cys Asp Asn Gln Lys Ser Cys Met Ser Asn Cys Ser Ile Thr Ser 
385                 390                 395                 400 
Ile Cys Glu Lys Pro Gln Glu Val Cys Val Ala Val Trp Arg Lys Asn 
                405                 410                 415     
Asp Glu Asn Ile Thr Leu Glu Thr Val Cys His Asp Pro Lys Leu Pro 
            420                 425                 430         
Tyr His Asp Phe Ile Leu Glu Asp Ala Ala Ser Pro Lys Cys Ile Met 
        435                 440                 445             
Lys Glu Lys Lys Lys Pro Gly Glu Thr Phe Phe Met Cys Ser Cys Ser 
    450                 455                 460                 
Ser Asp Glu Cys Asn Asp Asn Ile Ile Phe Ser Glu Glu Tyr Asn Thr 
465                 470                 475                 480 
Ser Asn Pro Asp 
                

