﻿               SEQUENCE LISTING

<110> 神州细胞工程有限公司

<120> 人源化抗TNFα抗体及其用途

<130> CIE200075PCT

<160> 43

<170> BiSSAP 1.3.6

<210> 1
<211> 177
<212> PRT
<213> Artificial Sequence


<220> 
<223> 人TNFα蛋白(UniProtKB P01375)胞外区氨基酸序列Gly57-Leu233

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

<210> 2
<211> 54
<212> DNA
<213> Artificial Sequence


<220> 
<223> 构建噬菌体抗体库时所用兔抗体scFv的Linker核苷酸序列

<400> 2
tctagtggtg gcggtggttc gggcggtggt ggaggtggta gttctagatc ttcc           54


<210> 3
<211> 738
<212> DNA
<213> Artificial Sequence


<220> 
<223> 兔抗体TNFα-R511 scFv核苷酸序列

<400> 3
gagctcgatc tgacccagac tccatcctcc gtgtctgcac ctgtgggagg cacagtcacc      60

atcaattgcc aggccagtga ggatattagt aactatttag cctggtatca gcagaaacca     120

gggcagcctc ccaagctcct gatctatggt gcatccaggc tggcgtctgg ggtcccatcg     180

cggttcaaag gcagtagctc tgggacagag ttcactctca ccatcagtgg cgtgcagcgt     240

gaggatgctg ccacctacta ctgtctaggc agttatagtg ctactgatgc tgctttcggc     300

ggagggacca aggtggagat caaatctagt ggtggcggtg gttcgggcgg tggtggaggt     360

ggtagttcta gatcttccca gtcgctggag gagtccgggg gagacctggt caagcctggg     420

gcatccctga cactcacctg cacagcctct ggattctcct tcaatagcta ctacatgtgc     480

tgggtccgcc aggctccagg gaaggggctg gagtggatcg catgcattga cgctgctggt     540

agtggtagca cttactacgc gagctgggcg agaggccgat tcaccatctc cagtaccccg     600

tcgaccacgg tgactctgca aatgaccagt ctgacagccg cggacacggc cacctatttc     660

tgtgcgagag atgatcctgg ttggtataat tcagacttta cattgtgggg cccaggcacc     720

ctggtcaccg tctcttca                                                   738


<210> 4
<211> 360
<212> DNA
<213> Artificial Sequence


<220> 
<223> 兔抗体TNFα-R511 重链可变区核苷酸序列

<400> 4
cagtcgctgg aggagtccgg gggagacctg gtcaagcctg gggcatccct gacactcacc      60

tgcacagcct ctggattctc cttcaatagc tactacatgt gctgggtccg ccaggctcca     120

gggaaggggc tggagtggat cgcatgcatt gacgctgctg gtagtggtag cacttactac     180

gcgagctggg cgagaggccg attcaccatc tccagtaccc cgtcgaccac ggtgactctg     240

caaatgacca gtctgacagc cgcggacacg gccacctatt tctgtgcgag agatgatcct     300

ggttggtata attcagactt tacattgtgg ggcccaggca ccctggtcac cgtctcttca     360


<210> 5
<211> 324
<212> DNA
<213> Artificial Sequence


<220> 
<223> 兔抗体TNFα-R511 轻链可变区核苷酸序列

<400> 5
gagctcgatc tgacccagac tccatcctcc gtgtctgcac ctgtgggagg cacagtcacc      60

atcaattgcc aggccagtga ggatattagt aactatttag cctggtatca gcagaaacca     120

gggcagcctc ccaagctcct gatctatggt gcatccaggc tggcgtctgg ggtcccatcg     180

cggttcaaag gcagtagctc tgggacagag ttcactctca ccatcagtgg cgtgcagcgt     240

gaggatgctg ccacctacta ctgtctaggc agttatagtg ctactgatgc tgctttcggc     300

ggagggacca aggtggagat caaa                                            324


<210> 6
<211> 972
<212> DNA
<213> Artificial Sequence


<220> 
<223> 兔IgG重链恒定区核苷酸序列

<400> 6
ggtcaaccta aggctccgtc agtcttccca ctggccccct gctgcgggga cacacccagc      60

tccacggtga ccctgggctg cctggtcaaa ggctacctcc cggagccagt gaccgtgacc     120

tggaactcgg gcaccctcac caatggggta cgcaccttcc cgtccgtccg gcagtcctca     180

ggcctctact cgctgagcag cgtggtgagc gtgacctcaa gcagccagcc cgtcacctgc     240

aacgtggccc acccagccac caacaccaaa gtggacaaga ccgttgcgcc ctcgacatgc     300

agcaagccca cgtgcccacc ccctgaactc ctggggggac cgtctgtctt catcttcccc     360

ccaaaaccca aggacaccct catgatctca cgcacccccg aggtcacatg cgtggtggtg     420

gacgtgagcc aggatgaccc cgaggtgcag ttcacatggt acataaacaa cgagcaggtg     480

cgcaccgccc ggccgccgct acgggagcag cagttcaaca gcacgatccg cgtggtcagc     540

accctcccca tcgcgcacca ggactggctg aggggcaagg agttcaagtg caaagtccac     600

aacaaggcac tcccggcccc catcgagaaa accatctcca aagccagagg gcagcccctg     660

gagccgaagg tctacaccat gggccctccc cgggaggagc tgagcagcag gtcggtcagc     720

ctgacctgca tgatcaacgg cttctaccct tccgacatct cggtggagtg ggagaagaac     780

gggaaggcag aggacaacta caagaccacg ccggccgtgc tggacagcga cggctcctac     840

ttcctctaca gcaagctctc agtgcccacg agtgagtggc agcggggcga cgtcttcacc     900

tgctccgtga tgcacgaggc cttgcacaac cactacacgc agaagtccat ctcccgctct     960

ccgggtaaat aa                                                         972


<210> 7
<211> 321
<212> DNA
<213> Artificial Sequence


<220> 
<223> 兔kappa轻链恒定区核苷酸序列

<400> 7
agggatccag ttgcacctac tgtcctcctc ttcccaccat ctaaggagga gctgacaact      60

ggaacagcca ccatcgtgtg cgtggcgaat aaattctatc ccagtgacat caccgtcacc     120

tggaaggtgg atggcaccac ccaacagagc ggcatcgaga acagtaaaac accgcagagc     180

cccgaagaca atacctacag cctgagcagc actctgtcac tgaccagcgc acagtacaac     240

agccacagcg tgtacacctg cgaggtggtc caaggctcag cctcaccgat cgtccagagc     300

ttcaataggg gtgactgtta g                                               321


<210> 8
<211> 120
<212> PRT
<213> Artificial Sequence


<220> 
<223> 兔抗体TNFα-R511 重链可变区氨基酸序列

<400> 8
Gln Ser Leu Glu Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Ala Ser 
1               5                   10                  15      
Leu Thr Leu Thr Cys Thr Ala Ser Gly Phe Ser Phe Asn Ser Tyr Tyr 
            20                  25                  30          
Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala 
        35                  40                  45              
Cys Ile Asp Ala Ala Gly Ser Gly Ser Thr Tyr Tyr Ala Ser Trp Ala 
    50                  55                  60                  
Arg Gly Arg Phe Thr Ile Ser Ser Thr Pro Ser Thr Thr Val Thr Leu 
65                  70                  75                  80  
Gln Met Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala 
                85                  90                  95      
Arg Asp Asp Pro Gly Trp Tyr Asn Ser Asp Phe Thr Leu Trp Gly Pro 
            100                 105                 110         
Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 

<210> 9
<211> 108
<212> PRT
<213> Artificial Sequence


<220> 
<223> 兔抗体TNFα-R511 轻链可变区氨基酸序列

<400> 9
Glu Leu Asp Leu Thr Gln Thr Pro Ser Ser Val Ser Ala Pro Val Gly 
1               5                   10                  15      
Gly Thr Val Thr Ile Asn Cys Gln Ala Ser Glu Asp Ile Ser Asn Tyr 
            20                  25                  30          
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile 
        35                  40                  45              
Tyr Gly Ala Ser Arg Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly 
    50                  55                  60                  
Ser Ser Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Gly Val Gln Arg 
65                  70                  75                  80  
Glu Asp Ala Ala Thr Tyr Tyr Cys Leu Gly Ser Tyr Ser Ala Thr Asp 
                85                  90                  95      
Ala Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105             

<210> 10
<211> 11
<212> PRT
<213> Artificial Sequence


<220> 
<223> 兔抗体TNFα-R511 /人源化抗体TNFα-H511轻链CDR1氨基酸序列

<400> 10
Gln Ala Ser Glu Asp Ile Ser Asn Tyr Leu Ala 
1               5                   10      

<210> 11
<211> 7
<212> PRT
<213> Artificial Sequence


<220> 
<223> 兔抗体TNFα-R511 /人源化抗体TNFα-H511轻链CDR2氨基酸序列

<400> 11
Gly Ala Ser Arg Leu Ala Ser 
1               5           

<210> 12
<211> 10
<212> PRT
<213> Artificial Sequence


<220> 
<223> 兔抗体TNFα-R511 /人源化抗体TNFα-H511轻链CDR3氨基酸序列

<400> 12
Leu Gly Ser Tyr Ser Ala Thr Asp Ala Ala 
1               5                   10  

<210> 13
<211> 10
<212> PRT
<213> Artificial Sequence


<220> 
<223> 兔抗体TNFα-R511重链CDR1氨基酸序列

<400> 13
Gly Phe Ser Phe Asn Ser Tyr Tyr Met Cys 
1               5                   10  

<210> 14
<211> 18
<212> PRT
<213> Artificial Sequence


<220> 
<223> 兔抗体TNFα-R511 /人源化抗体TNFα-H511重链CDR2氨基酸序列

<400> 14
Cys Ile Asp Ala Ala Gly Ser Gly Ser Thr Tyr Tyr Ala Ser Trp Ala 
1               5                   10                  15      
Arg Gly 
        

<210> 15
<211> 14
<212> PRT
<213> Artificial Sequence


<220> 
<223> 兔抗体TNFα-R511重链CDR3氨基酸序列

<400> 15
Ala Arg Asp Asp Pro Gly Trp Tyr Asn Ser Asp Phe Thr Leu 
1               5                   10                  

<210> 16
<211> 451
<212> PRT
<213> Artificial Sequence


<220> 
<223> 人源化抗体TNFα-H511重链氨基酸序列

<400> 16
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 Gly Phe Ser Phe Asn Gln Tyr 
            20                  25                  30          
Tyr Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile 
        35                  40                  45              
Ala Cys Ile Asp Ala Ala Gly Ser Gly Ser Thr Tyr Tyr Ala Ser Trp 
    50                  55                  60                  
Ala Arg Gly Arg Phe Thr Ile Ser Arg Gly Ser Ala Lys Asn Thr Val 
65                  70                  75                  80  
Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Phe 
                85                  90                  95      
Cys Ala Arg Asp Asp Pro Gly Trp Tyr Asn Thr Asp Phe Thr Leu Trp 
            100                 105                 110         
Gly Pro Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro 
        115                 120                 125             
Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr 
    130                 135                 140                 
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr 
145                 150                 155                 160 
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro 
                165                 170                 175     
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
            180                 185                 190         
Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn 
        195                 200                 205             
His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser 
    210                 215                 220                 
Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
225                 230                 235                 240 
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
                245                 250                 255     
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
            260                 265                 270         
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu 
        275                 280                 285             
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr 
    290                 295                 300                 
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
305                 310                 315                 320 
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
                325                 330                 335     
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
            340                 345                 350         
Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val 
        355                 360                 365             
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
    370                 375                 380                 
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
385                 390                 395                 400 
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr 
                405                 410                 415     
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
            420                 425                 430         
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
        435                 440                 445             
Ser Pro Gly 
    450     

<210> 17
<211> 215
<212> PRT
<213> Artificial Sequence


<220> 
<223> 人源化抗体TNFα-H511 轻链氨基酸序列

<400> 17
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 Asn Cys Gln Ala Ser Glu Asp Ile Ser Asn Tyr 
            20                  25                  30          
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Pro Pro Lys Leu Leu Ile 
        35                  40                  45              
Tyr Gly Ala Ser Arg Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  
Glu Asp Val Ala Thr Tyr Tyr Cys Leu Gly Ser Tyr Ser Ala Thr Asp 
                85                  90                  95      
Ala Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala 
            100                 105                 110         
Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser 
        115                 120                 125             
Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu 
    130                 135                 140                 
Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser 
145                 150                 155                 160 
Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu 
                165                 170                 175     
Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val 
            180                 185                 190         
Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys 
        195                 200                 205             
Ser Phe Asn Arg Gly Glu Cys 
    210                 215 

<210> 18
<211> 470
<212> PRT
<213> Artificial Sequence


<220> 
<223> 含有信号肽的人源化抗体TNFα-H511重链氨基酸序列

<400> 18
Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg 
1               5                   10                  15      
Val Leu Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln 
            20                  25                  30          
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe 
        35                  40                  45              
Asn Gln Tyr Tyr Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu 
    50                  55                  60                  
Glu Trp Ile Ala Cys Ile Asp Ala Ala Gly Ser Gly Ser Thr Tyr Tyr 
65                  70                  75                  80  
Ala Ser Trp Ala Arg Gly Arg Phe Thr Ile Ser Arg Gly Ser Ala Lys 
                85                  90                  95      
Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala 
            100                 105                 110         
Val Tyr Phe Cys Ala Arg Asp Asp Pro Gly Trp Tyr Asn Thr Asp Phe 
        115                 120                 125             
Thr Leu Trp Gly Pro Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr 
    130                 135                 140                 
Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser 
145                 150                 155                 160 
Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu 
                165                 170                 175     
Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His 
            180                 185                 190         
Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser 
        195                 200                 205             
Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys 
    210                 215                 220                 
Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu 
225                 230                 235                 240 
Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro 
                245                 250                 255     
Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys 
            260                 265                 270         
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val 
        275                 280                 285             
Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp 
    290                 295                 300                 
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr 
305                 310                 315                 320 
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
                325                 330                 335     
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu 
            340                 345                 350         
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg 
        355                 360                 365             
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys 
    370                 375                 380                 
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp 
385                 390                 395                 400 
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys 
                405                 410                 415     
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser 
            420                 425                 430         
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser 
        435                 440                 445             
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser 
    450                 455                 460                 
Leu Ser Leu Ser Pro Gly 
465                 470 

<210> 19
<211> 234
<212> PRT
<213> Artificial Sequence


<220> 
<223> 含有信号肽的人源化抗体TNFα-H511轻链氨基酸序列

<400> 19
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 
1               5                   10                  15      
Val His Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala 
            20                  25                  30          
Ser Val Gly Asp Arg Val Thr Ile Asn Cys Gln Ala Ser Glu Asp Ile 
        35                  40                  45              
Ser Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Pro Pro Lys 
    50                  55                  60                  
Leu Leu Ile Tyr Gly Ala Ser Arg Leu Ala Ser Gly Val Pro Ser Arg 
65                  70                  75                  80  
Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser 
                85                  90                  95      
Leu Gln Pro Glu Asp Val Ala Thr Tyr Tyr Cys Leu Gly Ser Tyr Ser 
            100                 105                 110         
Ala Thr Asp Ala Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 
        115                 120                 125             
Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
    130                 135                 140                 
Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
145                 150                 155                 160 
Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
                165                 170                 175     
Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
            180                 185                 190         
Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
        195                 200                 205             
His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
    210                 215                 220                 
Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
225                 230                 

<210> 20
<211> 19
<212> PRT
<213> Artificial Sequence


<220> 
<223> 人源化抗体TNFα-H511重链信号肽氨基酸序列

<400> 20
Met Gly Trp Ser Leu Ile Leu Leu Phe Leu Val Ala Val Ala Thr Arg 
1               5                   10                  15      
Val Leu Ser 
            

<210> 21
<211> 19
<212> PRT
<213> Artificial Sequence


<220> 
<223> 人源化抗体TNFα-H511轻链信号肽氨基酸序列

<400> 21
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 
1               5                   10                  15      
Val His Ser 
            

<210> 22
<211> 122
<212> PRT
<213> Artificial Sequence


<220> 
<223> 人源化抗体TNFα-H511重链可变区氨基酸序列

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

<210> 23
<211> 108
<212> PRT
<213> Artificial Sequence


<220> 
<223> 人源化抗体TNFα-H511轻链可变区氨基酸序列

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

<210> 24
<211> 329
<212> PRT
<213> Artificial Sequence


<220> 
<223> 人源化抗体TNFα-H511重链恒定区氨基酸序列

<400> 24
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      
Lys 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 Asp Glu 
225                 230                 235                 240 
Leu 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 
                325                 

<210> 25
<211> 107
<212> PRT
<213> Artificial Sequence


<220> 
<223> 人源化抗体TNFα-H511轻链恒定区氨基酸序列

<400> 25
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> 26
<211> 1420
<212> DNA
<213> Artificial Sequence


<220> 
<223> 含有信号肽的人源化抗体TNFα-H511重链核苷酸序列

<400> 26
atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagcgag      60

gtccaacttg tggagtctgg aggaggactg gtccaacctg gaggctccct gagactgtcc     120

tgtgctgcct ctggcttctc cttcaaccaa tactatatgt gttgggtgag acaggctcct     180

ggcaagggat tggagtggat tgcctgtatt gatgctgctg gctctggcag cacctactat     240

gcctcctggg caaggggcag gttcaccatc agcaggggct ctgccaagaa cacagtctac     300

ctccaaatga actccctgag ggctgaggac acagcagtct acttctgtgc cagggatgac     360

cctggctggt acaacacaga cttcaccctg tggggacctg gcaccctggt gacagtgtcc     420

tctgcaagca ccaagggccc atcggtcttc cccctggcac cctcctccaa gagcacctct     480

gggggcacag cggccctggg ctgcctggtc aaggactact tccccgaacc ggtgacggtg     540

tcgtggaact caggcgccct gaccagcggc gtgcacacct tcccggctgt cctacagtcc     600

tcaggactct actccctcag cagcgtggtg accgtgccct ccagcagctt gggcacccag     660

acctacatct gcaacgtgaa tcacaagccc agcaacacca aggtggacaa gaaagttgag     720

cccaaatctt gtgacaaaac tcacacatgc ccaccgtgcc cagcacctga actcctgggg     780

ggaccgtcag tcttcctctt ccccccaaaa cccaaggaca ccctcatgat ctcccggacc     840

cctgaggtca cgtgcgtggt ggtggacgtg agccacgaag accccgaggt caagttcaac     900

tggtacgtgg acggcgtgga ggtgcataat gccaagacaa agccgcggga ggagcagtac     960

aacagcacgt accgtgtggt cagcgtcctc accgtcctgc accaggactg gctgaatggc    1020

aaggagtaca agtgcaaggt ctccaacaaa gccctcccag cccccatcga gaaaaccatc    1080

tccaaagcca aagggcagcc ccgagaacca caggtgtaca ccctgccccc atcccgggat    1140

gagctgacca agaaccaggt cagcctgacc tgcctggtca aaggcttcta tcccagcgac    1200

atcgccgtgg agtgggagag caatgggcag ccggagaaca actacaagac cacgcctccc    1260

gtgctggact ccgacggctc cttcttcctc tacagcaagc tcaccgtgga caagagcagg    1320

tggcagcagg ggaacgtctt ctcatgctcc gtgatgcatg aggctctgca caaccactac    1380

acccagaagt ccctgtctct gagccctggc taatagtgaa                          1420


<210> 27
<211> 705
<212> DNA
<213> Artificial Sequence


<220> 
<223> 含有信号肽的人源化抗体TNFα-H511轻链核苷酸序列

<400> 27
atgggctggt cctgtatcat cctgttcctg gtggctacag ccacaggagt gcatagtgac      60

atccagatga cccagagccc atcctccctg tctgcctctg tgggagacag ggtgaccatc     120

aactgtcagg catctgagga catcagcaac tacctggctt ggtatcaaca gaagcctggc     180

aagcctccaa aactgctgat ttatggagcc agcagactgg catctggagt gccaagcagg     240

ttctctggct ctggctctgg cacagacttc accctgacca tctcctccct ccaacctgag     300

gatgtggcta cctactactg tctgggctcc tactctgcca cagatgctgc ctttggagga     360

ggcaccaagg tggagattaa gcgtacggtg gctgcaccat ctgtcttcat cttcccgcca     420

tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat     480

cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag     540

gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg     600

ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc     660

ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttaa                     705


<210> 28
<211> 57
<212> DNA
<213> Artificial Sequence


<220> 
<223> 兔抗体TNFα-R511 /人源化抗体TNFα-H511重链信号肽核苷酸序列

<400> 28
atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagc        57


<210> 29
<211> 57
<212> DNA
<213> Artificial Sequence


<220> 
<223> 兔抗体TNFα-R511 /人源化抗体TNFα-H511轻链信号肽核苷酸序列

<400> 29
atgggctggt cctgtatcat cctgttcctg gtggctacag ccacaggagt gcatagt        57


<210> 30
<211> 366
<212> DNA
<213> Artificial Sequence


<220> 
<223> 人源化抗体TNFα-H511重链可变区核苷酸序列

<400> 30
gaggtccaac ttgtggagtc tggaggagga ctggtccaac ctggaggctc cctgagactg      60

tcctgtgctg cctctggctt ctccttcaac caatactata tgtgttgggt gagacaggct     120

cctggcaagg gattggagtg gattgcctgt attgatgctg ctggctctgg cagcacctac     180

tatgcctcct gggcaagggg caggttcacc atcagcaggg gctctgccaa gaacacagtc     240

tacctccaaa tgaactccct gagggctgag gacacagcag tctacttctg tgccagggat     300

gaccctggct ggtacaacac agacttcacc ctgtggggac ctggcaccct ggtgacagtg     360

tcctct                                                                366


<210> 31
<211> 324
<212> DNA
<213> Artificial Sequence


<220> 
<223> 人源化抗体TNFα-H511轻链可变区核苷酸序列

<400> 31
gacatccaga tgacccagag cccatcctcc ctgtctgcct ctgtgggaga cagggtgacc      60

atcaactgtc aggcatctga ggacatcagc aactacctgg cttggtatca acagaagcct     120

ggcaagcctc caaaactgct gatttatgga gccagcagac tggcatctgg agtgccaagc     180

aggttctctg gctctggctc tggcacagac ttcaccctga ccatctcctc cctccaacct     240

gaggatgtgg ctacctacta ctgtctgggc tcctactctg ccacagatgc tgcctttgga     300

ggaggcacca aggtggagat taag                                            324


<210> 32
<211> 997
<212> DNA
<213> Artificial Sequence


<220> 
<223> 人源化抗体TNFα-H511重链恒定区核苷酸序列

<400> 32
gcaagcacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg      60

ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg     120

tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca     180

ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc     240

tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgagccc     300

aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga     360

ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct     420

gaggtcacgt gcgtggtggt ggacgtgagc cacgaagacc ccgaggtcaa gttcaactgg     480

tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac     540

agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag     600

gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc     660

aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggatgag     720

ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc     780

gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg     840

ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg     900

cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacc     960

cagaagtccc tgtctctgag ccctggctaa tagtgaa                              997


<210> 33
<211> 324
<212> DNA
<213> Artificial Sequence


<220> 
<223> 人源化抗体TNFα-H511轻链恒定区核苷酸序列

<400> 33
cgtacggtgg ctgcaccatc tgtcttcatc ttcccgccat ctgatgagca gttgaaatct      60

ggaactgcct ctgttgtgtg cctgctgaat aacttctatc ccagagaggc caaagtacag     120

tggaaggtgg ataacgccct ccaatcgggt aactcccagg agagtgtcac agagcaggac     180

agcaaggaca gcacctacag cctcagcagc accctgacgc tgagcaaagc agactacgag     240

aaacacaaag tctacgcctg cgaagtcacc catcagggcc tgagctcgcc cgtcacaaag     300

agcttcaaca ggggagagtg ttaa                                            324


<210> 34
<211> 246
<212> PRT
<213> Artificial Sequence


<220> 
<223> 兔抗体TNFα-R511 Scfv氨基酸序列

<400> 34
Glu Leu Asp Leu Thr Gln Thr Pro Ser Ser Val Ser Ala Pro Val Gly 
1               5                   10                  15      
Gly Thr Val Thr Ile Asn Cys Gln Ala Ser Glu Asp Ile Ser Asn Tyr 
            20                  25                  30          
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile 
        35                  40                  45              
Tyr Gly Ala Ser Arg Leu Ala Ser Gly Val Pro Ser Arg Phe Lys Gly 
    50                  55                  60                  
Ser Ser Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Gly Val Gln Arg 
65                  70                  75                  80  
Glu Asp Ala Ala Thr Tyr Tyr Cys Leu Gly Ser Tyr Ser Ala Thr Asp 
                85                  90                  95      
Ala Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Ser Ser Gly Gly 
            100                 105                 110         
Gly Gly Ser Gly Gly Gly Gly Gly Gly Ser Ser Arg Ser Ser Gln Ser 
        115                 120                 125             
Leu Glu Glu Ser Gly Gly Asp Leu Val Lys Pro Gly Ala Ser Leu Thr 
    130                 135                 140                 
Leu Thr Cys Thr Ala Ser Gly Phe Ser Phe Asn Ser Tyr Tyr Met Cys 
145                 150                 155                 160 
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile Ala Cys Ile 
                165                 170                 175     
Asp Ala Ala Gly Ser Gly Ser Thr Tyr Tyr Ala Ser Trp Ala Arg Gly 
            180                 185                 190         
Arg Phe Thr Ile Ser Ser Thr Pro Ser Thr Thr Val Thr Leu Gln Met 
        195                 200                 205             
Thr Ser Leu Thr Ala Ala Asp Thr Ala Thr Tyr Phe Cys Ala Arg Asp 
    210                 215                 220                 
Asp Pro Gly Trp Tyr Asn Ser Asp Phe Thr Leu Trp Gly Pro Gly Thr 
225                 230                 235                 240 
Leu Val Thr Val Ser Ser 
                245     

<210> 35
<211> 18
<212> PRT
<213> Artificial Sequence


<220> 
<223> 构建噬菌体抗体库时所用兔抗体scFv的Linker氨基酸序列

<400> 35
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Gly Gly Ser Ser Arg 
1               5                   10                  15      
Ser Ser 
        

<210> 36
<211> 1389
<212> DNA
<213> Artificial Sequence


<220> 
<223> 含有信号肽的兔抗体TNFα-R511重链核苷酸序列

<400> 36
atgggctggt ccctgattct gctgttcctg gtggctgtgg ctaccagggt gctgagccag      60

tcgctggagg agtccggggg agacctggtc aagcctgggg catccctgac actcacctgc     120

acagcctctg gattctcctt caatagctac tacatgtgct gggtccgcca ggctccaggg     180

aaggggctgg agtggatcgc atgcattgac gctgctggta gtggtagcac ttactacgcg     240

agctgggcga gaggccgatt caccatctcc agtaccccgt cgaccacggt gactctgcaa     300

atgaccagtc tgacagccgc ggacacggcc acctatttct gtgcgagaga tgatcctggt     360

tggtataatt cagactttac attgtggggc ccaggcaccc tggtcaccgt ctcttcaggt     420

caacctaagg ctccgtcagt cttcccactg gccccctgct gcggggacac acccagctcc     480

acggtgaccc tgggctgcct ggtcaaaggc tacctcccgg agccagtgac cgtgacctgg     540

aactcgggca ccctcaccaa tggggtacgc accttcccgt ccgtccggca gtcctcaggc     600

ctctactcgc tgagcagcgt ggtgagcgtg acctcaagca gccagcccgt cacctgcaac     660

gtggcccacc cagccaccaa caccaaagtg gacaagaccg ttgcgccctc gacatgcagc     720

aagcccacgt gcccaccccc tgaactcctg gggggaccgt ctgtcttcat cttcccccca     780

aaacccaagg acaccctcat gatctcacgc acccccgagg tcacatgcgt ggtggtggac     840

gtgagccagg atgaccccga ggtgcagttc acatggtaca taaacaacga gcaggtgcgc     900

accgcccggc cgccgctacg ggagcagcag ttcaacagca cgatccgcgt ggtcagcacc     960

ctccccatcg cgcaccagga ctggctgagg ggcaaggagt tcaagtgcaa agtccacaac    1020

aaggcactcc cggcccccat cgagaaaacc atctccaaag ccagagggca gcccctggag    1080

ccgaaggtct acaccatggg ccctccccgg gaggagctga gcagcaggtc ggtcagcctg    1140

acctgcatga tcaacggctt ctacccttcc gacatctcgg tggagtggga gaagaacggg    1200

aaggcagagg acaactacaa gaccacgccg gccgtgctgg acagcgacgg ctcctacttc    1260

ctctacagca agctctcagt gcccacgagt gagtggcagc ggggcgacgt cttcacctgc    1320

tccgtgatgc acgaggcctt gcacaaccac tacacgcaga agtccatctc ccgctctccg    1380

ggtaaataa                                                            1389


<210> 37
<211> 702
<212> DNA
<213> Artificial Sequence


<220> 
<223> 含有信号肽的兔抗体TNFα-R511轻链核苷酸序列

<400> 37
atgggctggt cctgtatcat cctgttcctg gtggctacag ccacaggagt gcatagcgag      60

ctcgatctga cccagactcc atcctccgtg tctgcacctg tgggaggcac agtcaccatc     120

aattgccagg ccagtgagga tattagtaac tatttagcct ggtatcagca gaaaccaggg     180

cagcctccca agctcctgat ctatggtgca tccaggctgg cgtctggggt cccatcgcgg     240

ttcaaaggca gtagctctgg gacagagttc actctcacca tcagtggcgt gcagcgtgag     300

gatgctgcca cctactactg tctaggcagt tatagtgcta ctgatgctgc tttcggcgga     360

gggaccaagg tggagatcaa aagggatcca gttgcaccta ctgtcctcct cttcccacca     420

tctaaggagg agctgacaac tggaacagcc accatcgtgt gcgtggcgaa taaattctat     480

cccagtgaca tcaccgtcac ctggaaggtg gatggcacca cccaacagag cggcatcgag     540

aacagtaaaa caccgcagag ccccgaagac aatacctaca gcctgagcag cactctgtca     600

ctgaccagcg cacagtacaa cagccacagc gtgtacacct gcgaggtggt ccaaggctca     660

gcctcaccga tcgtccagag cttcaatagg ggtgactgtt ag                        702


<210> 38
<211> 462
<212> PRT
<213> Artificial Sequence


<220> 
<223> 含有信号肽的兔抗体TNFα-R511重链氨基酸序列

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

<210> 39
<211> 233
<212> PRT
<213> Artificial Sequence


<220> 
<223> 含有信号肽的兔抗体TNFα-R511轻链氨基酸序列

<400> 39
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly 
1               5                   10                  15      
Val His Ser Glu Leu Asp Leu Thr Gln Thr Pro Ser Ser Val Ser Ala 
            20                  25                  30          
Pro Val Gly Gly Thr Val Thr Ile Asn Cys Gln Ala Ser Glu Asp Ile 
        35                  40                  45              
Ser Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys 
    50                  55                  60                  
Leu Leu Ile Tyr Gly Ala Ser Arg Leu Ala Ser Gly Val Pro Ser Arg 
65                  70                  75                  80  
Phe Lys Gly Ser Ser Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Gly 
                85                  90                  95      
Val Gln Arg Glu Asp Ala Ala Thr Tyr Tyr Cys Leu Gly Ser Tyr Ser 
            100                 105                 110         
Ala Thr Asp Ala Ala Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 
        115                 120                 125             
Asp Pro Val Ala Pro Thr Val Leu Leu Phe Pro Pro Ser Lys Glu Glu 
    130                 135                 140                 
Leu Thr Thr Gly Thr Ala Thr Ile Val Cys Val Ala Asn Lys Phe Tyr 
145                 150                 155                 160 
Pro Ser Asp Ile Thr Val Thr Trp Lys Val Asp Gly Thr Thr Gln Gln 
                165                 170                 175     
Ser Gly Ile Glu Asn Ser Lys Thr Pro Gln Ser Pro Glu Asp Asn Thr 
            180                 185                 190         
Tyr Ser Leu Ser Ser Thr Leu Ser Leu Thr Ser Ala Gln Tyr Asn Ser 
        195                 200                 205             
His Ser Val Tyr Thr Cys Glu Val Val Gln Gly Ser Ala Ser Pro Ile 
    210                 215                 220                 
Val Gln Ser Phe Asn Arg Gly Asp Cys 
225                 230             

<210> 40
<211> 323
<212> PRT
<213> Artificial Sequence


<220> 
<223> 兔抗体TNFα-R511重链恒定区氨基酸序列

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

<210> 41
<211> 106
<212> PRT
<213> Artificial Sequence


<220> 
<223> 兔抗体TNFα-R511轻链恒定区氨基酸序列

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

<210> 42
<211> 10
<212> PRT
<213> Artificial Sequence


<220> 
<223> 人源化抗体TNFα-H511重链CDR1氨基酸序列

<400> 42
Gly Phe Ser Phe Asn Gln Tyr Tyr Met Cys 
1               5                   10  

<210> 43
<211> 14
<212> PRT
<213> Artificial Sequence


<220> 
<223> 人源化抗体TNFα-H511重链CDR3氨基酸序列

<400> 43
Ala Arg Asp Asp Pro Gly Trp Tyr Asn Thr Asp Phe Thr Leu 
1               5                   10                  

