                         SEQUENCE LISTING

<110>  Dizal (Jiangsu) Pharmaceutical Co., Ltd.
 
<120>  NOVEL ANTI-FGFR2B ANTIBODIES

<130>  070542-8006WO03

<160>  19    

<170>  PatentIn version 3.5

<210>  1
<211>  5
<212>  PRT
<213>  Mus musculus


<220>
<221>  HCDR1
<222>  (1)..(5)

<400>  1

Asn Tyr Trp Met His 
1               5   


<210>  2
<211>  10
<212>  PRT
<213>  Mus musculus


<220>
<221>  LCDR1
<222>  (1)..(10)

<400>  2

Ser Ala Ser Ser Gly Leu Ser Tyr Met Ser 
1               5                   10  


<210>  3
<211>  17
<212>  PRT
<213>  Mus musculus


<220>
<221>  HCDR2
<222>  (1)..(17)

<400>  3

Ala Ile Tyr Pro Glu Asn Gly Asp Ile Asn Tyr Asn Gln Lys Phe Lys 
1               5                   10                  15      


Gly 
    


<210>  4
<211>  7
<212>  PRT
<213>  Mus musculus


<220>
<221>  LCDR2
<222>  (1)..(7)

<400>  4

Asp Thr Ser Asn Leu Ala Ser 
1               5           


<210>  5
<211>  4
<212>  PRT
<213>  Mus musculus


<220>
<221>  HCDR2
<222>  (1)..(4)

<400>  5

Arg Gly Asp Tyr 
1               


<210>  6
<211>  9
<212>  PRT
<213>  Mus musculus


<220>
<221>  LCDR3
<222>  (1)..(9)

<400>  6

Gln Gln Trp Ser Ser Tyr Pro Tyr Thr 
1               5                   


<210>  7
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  REMOVAL OF NG HOT SPOT


<220>
<221>  MODIFIED HCDR2
<222>  (1)..(17)

<400>  7

Ala Ile Tyr Pro Glu Asn Arg Asp Ile Asn Tyr Asn Gln Lys Phe Lys 
1               5                   10                  15      


Gly 
    


<210>  8
<211>  113
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  HUMANIZED 21-26 ANTIBODY HEAVY CHAIN VARIABLE REGION AMINO ACID 
       SEQUENCE


<220>
<221>  Hu21-26 VH
<222>  (1)..(113)

<400>  8

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
            20                  25                  30          


Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Ala Ile Tyr Pro Glu Asn Arg Asp Ile Asn Tyr Asn Gln Lys Phe 
    50                  55                  60                  


Lys Gly Arg Val Thr Leu Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Thr Ser Arg Gly Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser 
            100                 105                 110         


Ser 
    


<210>  9
<211>  339
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  HUMANIZED 21-26 ANTIBODY HEAVY CHAIN VARIABLE REGION CODING 
       SEQUENCE

<400>  9
gaggtgcagc tggtgcagag cggcgccgag gtgaagaagc ccggcgccag cgtgaaggtg       60

agctgcaagg ccagcggcta caccttcacc aactactgga tgcactgggt gaggcaggcc      120

cccggccagg gcctggagtg gatgggcgcc atctaccccg agaacaggga catcaactac      180

aaccagaagt tcaagggcag ggtgaccctg accagggaca ccagcatcag caccgcctac      240

atggagctga gcaggctgag gagcgacgac accgccgtgt actactgcac cagcaggggc      300

gactactggg gccagggcac caccgtgacc gtgagcagc                             339


<210>  10
<211>  106
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  HUMANIZED 21-26/21-21 ANTIBODIES LIGHT CHAIN VARIABLE REGION 
       AMINO ACID SEQUENCE

<400>  10

Ala Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Ser Ala Ser Ser Gly Leu Ser Tyr Met 
            20                  25                  30          


Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 
        35                  40                  45              


Asp Thr Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser 
    50                  55                  60                  


Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 
65                  70                  75                  80  


Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Tyr Pro Tyr Thr 
                85                  90                  95      


Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 
            100                 105     


<210>  11
<211>  318
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  HUMANIZED 21-26/21-21 ANTIBODIES LIGHT CHAIN VARIABLE REGION 
       CODING SEQUENCE

<400>  11
gccatccagc tgacccagag ccccagcagc ctgagcgcca gcgtgggcga cagggtgacc       60

atcacctgca gcgccagcag cggcctgagc tacatgagct ggtaccagca gaagcccggc      120

aaggccccca agctgctgat ctacgacacc agcaacctgg ccagcggcgt gcccagcagg      180

ttcagcggca gcggcagcgg caccgacttc accctgacca tcagcagcct gcagcccgag      240

gacttcgcca cctactactg ccagcagtgg agcagctacc cctacacctt cggccagggc      300

accaagctgg agatcaag                                                    318


<210>  12
<211>  113
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CHIMERIC 21 ANTIBODY HEAVY CHAIN VARIABLE REGION AMINO ACID 
       SEQUENCE

<400>  12

Glu Val Gln Leu His Gln Ser Gly Thr Val Leu Ala Arg Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Met Ser Cys Lys Thr Ser Gly Tyr Thr Phe Thr Asn Tyr 
            20                  25                  30          


Trp Met His Trp Ile Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile 
        35                  40                  45              


Gly Ala Ile Tyr Pro Glu Asn Gly Asp Ile Asn Tyr Asn Gln Lys Phe 
    50                  55                  60                  


Lys Gly Lys Ala Lys Leu Thr Ala Val Thr Ser Ala Ser Thr Ala Tyr 
65                  70                  75                  80  


Met Asp Leu Ser Ser Leu Thr Asn Glu Asp Ser Ala Val Tyr Tyr Cys 
                85                  90                  95      


Thr Ser Arg Gly Asp Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val Ser 
            100                 105                 110         


Ser 
    


<210>  13
<211>  339
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CHIMERIC 21 ANTIBODY HEAVY CHAIN VARIABLE REGION CODING SEQUENCE

<400>  13
gaggttcagc tccaccagtc tgggactgtg ctggcaaggc ctggggcttc agtgaagatg       60

tcctgcaaga cttctggcta cacatttacc aactactgga tgcactggat aaaacagagg      120

cctggacagg gtctggaatg gataggggct atttatcctg aaaatggtga tattaactac      180

aaccagaagt tcaagggcaa ggccaaactg actgcagtca catccgccag cactgcctac      240

atggacctca gcagcctgac aaatgaggac tctgcggtct attactgtac aagtcggggg      300

gactactggg gccaaggcac cactctcaca gtctcctca                             339


<210>  14
<211>  106
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CHIMERIC 21 ANTIBODY LIGHT CHAIN VARIABLE REGION AMINO ACID 
       SEQUENCE

<400>  14

Gln Ile Val Leu Thr Gln Ser Pro Ala Ile Met Ser Ala Ser Pro Gly 
1               5                   10                  15      


Glu Lys Val Thr Met Thr Cys Ser Ala Ser Ser Gly Leu Ser Tyr Met 
            20                  25                  30          


Ser Trp Tyr Gln Gln Lys Pro Gly Ser Ser Pro Arg Leu Leu Ile Tyr 
        35                  40                  45              


Asp Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser 
    50                  55                  60                  


Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Arg Met Glu Ala Glu 
65                  70                  75                  80  


Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Tyr Pro Tyr Thr 
                85                  90                  95      


Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
            100                 105     


<210>  15
<211>  318
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  CHIMERIC 21 ANTIBODY LIGHT CHAIN VARIABLE REGION CODING SEQUENCE

<400>  15
caaattgttc tcacccagtc tccagcaatc atgtctgcat ctccagggga gaaggtcacc       60

atgacctgca gtgccagctc aggtttaagt tacatgtcct ggtaccagca gaagccagga      120

tcctccccca gactcctgat ttatgacaca tccaacctgg cttctggagt ccctgttcgc      180

ttcagtggca gtgggtctgg gacctcttac tctctcacaa tcagccgaat ggaggctgaa      240

gatgctgcca cttattactg ccagcagtgg agtagttacc cgtacacgtt cggagggggg      300

accaagctgg aaataaaa                                                    318


<210>  16
<211>  113
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  HUMANIZED 21-21 ANTIBODY HEAVY CHAIN VARIABLE REGION AMINO ACID 
       SEQUENCE

<400>  16

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
            20                  25                  30          


Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Ala Ile Tyr Pro Glu Asn Gly Asp Ile Asn Tyr Asn Gln Lys Phe 
    50                  55                  60                  


Lys Gly Arg Val Thr Leu Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Thr Ser Arg Gly Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser 
            100                 105                 110         


Ser 
    


<210>  17
<211>  339
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  HUMANIZED 21-21 ANTIBODY HEAVY CHAIN VARIABLE REGION CODING 
       SEQUENCE

<400>  17
gaggtgcagc tggtgcagag cggcgccgag gtgaagaagc ccggcgccag cgtgaaggtg       60

agctgcaagg ccagcggcta caccttcacc aactactgga tgcactgggt gaggcaggcc      120

cccggccagg gcctggagtg gatgggcgcc atctaccccg agaacggcga catcaactac      180

aaccagaagt tcaagggcag ggtgaccctg accagggaca ccagcatcag caccgcctac      240

atggagctga gcaggctgag gagcgacgac accgccgtgt actactgcac cagcaggggc      300

gactactggg gccagggcac caccgtgacc gtgagcagc                             339


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

<220>
<223>  HUMANIZED 21-26 ANTIBODY LIGHT CHAIN AMINO ACID SEQUENCE

<400>  18

Ala Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


Asp Arg Val Thr Ile Thr Cys Ser Ala Ser Ser Gly Leu Ser Tyr Met 
            20                  25                  30          


Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr 
        35                  40                  45              


Asp Thr Ser Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser 
    50                  55                  60                  


Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu 
65                  70                  75                  80  


Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Tyr Pro Tyr Thr 
                85                  90                  95      


Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala Pro 
            100                 105                 110         


Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr 
        115                 120                 125             


Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys 
    130                 135                 140                 


Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu 
145                 150                 155                 160 


Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser 
                165                 170                 175     


Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala 
            180                 185                 190         


Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe 
        195                 200                 205             


Asn Arg Gly Glu Cys 
    210             


<210>  19
<211>  443
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  HUMANIZED 21-26 ANTIBODY HEAVY CHAIN AMINO ACID SEQUENCE

<400>  19

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala 
1               5                   10                  15      


Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr 
            20                  25                  30          


Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 
        35                  40                  45              


Gly Ala Ile Tyr Pro Glu Asn Arg Asp Ile Asn Tyr Asn Gln Lys Phe 
    50                  55                  60                  


Lys Gly Arg Val Thr Leu Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr 
65                  70                  75                  80  


Met Glu Leu Ser Arg Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys 
                85                  90                  95      


Thr Ser Arg Gly Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser 
            100                 105                 110         


Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser 
        115                 120                 125             


Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp 
    130                 135                 140                 


Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr 
145                 150                 155                 160 


Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr 
                165                 170                 175     


Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln 
            180                 185                 190         


Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp 
        195                 200                 205             


Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro 
    210                 215                 220                 


Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro 
225                 230                 235                 240 


Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 
                245                 250                 255     


Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn 
            260                 265                 270         


Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg 
        275                 280                 285             


Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val 
    290                 295                 300                 


Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser 
305                 310                 315                 320 


Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys 
                325                 330                 335     


Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp 
            340                 345                 350         


Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe 
        355                 360                 365             


Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
    370                 375                 380                 


Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe 
385                 390                 395                 400 


Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 
                405                 410                 415     


Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
            420                 425                 430         


Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
        435                 440             


