﻿                         序列表

<110>  江苏恒瑞医药股份有限公司
       上海恒瑞医药有限公司
 
<120>  抗体药物偶联物的制备方法

<130>  P184313590T

<150>  CN201710202043.1
<151>  2017-03-30

<150>  CN201710233373.7
<151>  2017-04-11

<150>  CN201710342257.9
<151>  2017-05-16

<160>  17

<170>  SIPOSequenceListing 1.0

<210>  1
<211>  219
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220> 
<223>  mAb001轻链氨基酸序列

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

<210>  2
<211>  453
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220> 
<223>  mAb001重链氨基酸序列

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

<210>  3
<211>  218
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220> 
<223>  mAb002轻链氨基酸序列

<400>  3
Asp Ile Val Leu Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly 
1               5                   10                  15      
Glu Arg Ala Thr Ile Asn Cys Arg Ala Asp Lys Ser Val Ser Thr Ser 
            20                  25                  30          
Thr Tyr Asn Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 
        35                  40                  45              
Lys Leu Leu Ile Tyr Leu Ala Ser Asn Leu Ala Ser Gly Val Pro Asp 
    50                  55                  60                  
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
65                  70                  75                  80  
Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln His Ser Arg 
                85                  90                  95      
Asp Leu Pro Pro Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg 
            100                 105                 110         
Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
        115                 120                 125             
Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
    130                 135                 140                 
Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
145                 150                 155                 160 
Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
                165                 170                 175     
Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
            180                 185                 190         
His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
        195                 200                 205             
Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
    210                 215             

<210>  4
<211>  446
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220> 
<223>  mAb002重链氨基酸序列

<400>  4
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg 
1               5                   10                  15      
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Ser Asn Tyr 
            20                  25                  30          
Gly Val His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Leu 
        35                  40                  45              
Ala Val Ile Trp Ser Gly Gly Ser Thr Asn Tyr Ala Ala Ala Phe Val 
    50                  55                  60                  
Ser Arg Leu Thr Ile Ser Lys Asp Asn Ser Lys Asn Thr Val Tyr Leu 
65                  70                  75                  80  
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 
                85                  90                  95      
Arg Asn His Asp Asn Pro Tyr Asn Tyr Ala Met Asp Tyr Trp Gly Gln 
            100                 105                 110         
Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val 
        115                 120                 125             
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala 
    130                 135                 140                 
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser 
145                 150                 155                 160 
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val 
                165                 170                 175     
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro 
            180                 185                 190         
Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys 
        195                 200                 205             
Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys Val 
    210                 215                 220                 
Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe 
225                 230                 235                 240 
Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro 
                245                 250                 255     
Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val 
            260                 265                 270         
Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr 
        275                 280                 285             
Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val 
    290                 295                 300                 
Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys 
305                 310                 315                 320 
Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser 
                325                 330                 335     
Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro 
            340                 345                 350         
Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val 
        355                 360                 365             
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly 
    370                 375                 380                 
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp 
385                 390                 395                 400 
Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp 
                405                 410                 415     
Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His 
            420                 425                 430         
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
        435                 440                 445     

<210>  5
<211>  16
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220> 
<223>  mAb001-LCDR1序列

<400>  5
Arg Ser Ser Gln Asn Ile Val His Ser Asn Gly Asn Thr Tyr Leu Asp 
1               5                   10                  15      

<210>  6
<211>  7
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220> 
<223>  mAb001-LCDR2序列

<400>  6
Lys Val Ser Asn Arg Phe Ser 
1               5           

<210>  7
<211>  9
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220> 
<223>  mAb001-LCDR3序列

<400>  7
Phe Gln Tyr Ser His Val Pro Trp Thr 
1               5                   

<210>  8
<211>  5
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220> 
<223>  mAb001-HCDR1序列

<400>  8
Asn Tyr Tyr Ile Tyr 
1               5   

<210>  9
<211>  17
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220> 
<223>  mAb001-HCDR1序列

<400>  9
Gly Ile Asn Pro Thr Ser Gly Gly Ser Asn Phe Asn Glu Lys Phe Lys 
1               5                   10                  15      
Thr 
    

<210>  10
<211>  14
<212>  PRT
<213>  人工序列(Artificial Sequence)

<220> 
<223>  mAb001-HCDR3序列

<400>  10
Gln Gly Leu Trp Phe Asp Ser Asp Gly Arg Gly Phe Asp Phe 
1               5                   10                  

<210>  11
<211>  15
<212>  PRT
<213>  鼠源 (Mus musculus)

<400>  11
Arg Ala Asn Lys Ser Val Ser Thr Ser Thr Tyr Asn Tyr Leu His 
1               5                   10                  15  

<210>  12
<211>  7
<212>  PRT
<213>  鼠源 (Mus musculus)

<400>  12
Leu Ala Ser Asn Leu Ala Ser 
1               5           

<210>  13
<211>  9
<212>  PRT
<213>  鼠源 (Mus musculus)

<400>  13
Gln His Ser Arg Asp Leu Pro Pro Thr 
1               5                   

<210>  14
<211>  5
<212>  PRT
<213>  鼠源 (Mus musculus)

<400>  14
Asn Tyr Gly Val His 
1               5   

<210>  15
<211>  16
<212>  PRT
<213>  鼠源 (Mus musculus)

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

<210>  16
<211>  12
<212>  PRT
<213>  鼠源 (Mus musculus)

<400>  16
Asn His Asp Asn Pro Tyr Asn Tyr Ala Met Asp Tyr 
1               5                   10          

<210>  17
<211>  15
<212>  PRT
<213>  人工序列 (Artificial Sequence)

<220> 
<223>  优化的mAb002-LCDR1序列

<400>  17
Arg Ala Asp Lys Ser Val Ser Thr Ser Thr Tyr Asn Tyr Leu His 
1               5                   10                  15  

