                         б

<110>  ҩ޹˾
            Ƽ޹˾
 
<120>  CLDN18.2弰;

<130>  C20W7116

<150>  CN 2019106280189
<151>  2019-07-12

<160>  64    

<170>  PatentIn version 3.5

<210>  1
<211>  118
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A1 VH

<400>  1

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 Ser Ser 
            20                  25                  30          


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


Gly Thr Ile Val Pro Ser Asp Ser Tyr Thr Asn Tyr Asn Gln Lys Phe 
    50                  55                  60                  


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


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


Thr Arg Phe Arg Thr Gly Asn Ser Phe Asp Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


Leu Val Thr Val Ser Ser 
        115             


<210>  2
<211>  354
<212>  DNA
<213>  ˹

<220>
<223>  18.2-A1 VH

<400>  2
gaggtccaac tcgttcaatc tggagcagag gtaaaaaagc ctggagccag cgtcaaggtt       60

agttgtaagg catctggtta cacctttacc agctcttggc tcatttgggt gcgccaggca      120

cctggtcagg gattggaatg gattggcact atcgtcccct ctgactctta caccaactac      180

aatcagaaat ttaaagatcg cgccactttg acagtcgata agtctacgag tacggcttat      240

atggagctca gttccctgcg cagcgaggac acagccgtct attactgcac ccgcttcagg      300

accggtaaca gctttgacta ctggggacaa ggtacattgg ttacggtcag ctct            354


<210>  3
<211>  5
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A1 CDR H1

<400>  3

Ser Ser Trp Leu Ile 
1               5   


<210>  4
<211>  17
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A1 CDR H2

<400>  4

Thr Ile Val Pro Ser Asp Ser Tyr Thr Asn Tyr Asn Gln Lys Phe Lys 
1               5                   10                  15      


Asp 
    


<210>  5
<211>  9
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A1 CDR H3

<400>  5

Phe Arg Thr Gly Asn Ser Phe Asp Tyr 
1               5                   


<210>  6
<211>  113
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A1 VL

<400>  6

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


Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Asn Ser 
            20                  25                  30          


Gly Asn Gln Lys Asn Tyr Leu Thr Trp Tyr Gln Gln Lys Pro Gly Gln 
        35                  40                  45              


Pro Pro Lys Leu Leu Ile Tyr Trp Ala Val Ala Arg Gln Ser Gly Val 
    50                  55                  60                  


Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
65                  70                  75                  80  


Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Asn 
                85                  90                  95      


Ser Ile Ala Tyr Pro Phe Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 
            100                 105                 110         


Lys 
    


<210>  7
<211>  339
<212>  DNA
<213>  ˹

<220>
<223>  18.2-A1 VL

<400>  7
gacatcgtta tgactcagtc tcccgactcc ctcagcgtcg gcttgggtga acgcgccact       60

atcaattgta agtccagtca gtccgtcctc aattccggga atcagaagaa ctaccttaca      120

tggtatcagc agaaacctgg tcagccacca aaattgctca tctattgggc cgtggccagg      180

cagagcggcg tgcccgaccg ctttagtggg agcggctctg gcacagattt tacacttact      240

attagtagtc ttcaggccga ggatgtcgcg gtatattact gtcagaatag catagcctat      300

ccctttacct tcggtcaggg aacgaaggtt gaaatcaag                             339


<210>  8
<211>  17
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A1 CDR L1

<400>  8

Lys Ser Ser Gln Ser Val Leu Asn Ser Gly Asn Gln Lys Asn Tyr Leu 
1               5                   10                  15      


Thr 
    


<210>  9
<211>  7
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A1 CDR L2

<400>  9

Trp Ala Val Ala Arg Gln Ser 
1               5           


<210>  10
<211>  9
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A1 CDR L3

<400>  10

Gln Asn Ser Ile Ala Tyr Pro Phe Thr 
1               5                   


<210>  11
<211>  118
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A2 VH

<400>  11

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 Ser Phe 
            20                  25                  30          


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


Gly Asn Val Ser Pro Ser Asp Ser Tyr Thr Asn Tyr Asn Gln Lys Phe 
    50                  55                  60                  


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


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


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


Leu Val Thr Val Ser Ser 
        115             


<210>  12
<211>  354
<212>  DNA
<213>  ˹

<220>
<223>  18.2-A2 VH

<400>  12
gaggtccaac tcgttcaatc tggagcagag gtaaaaaagc ctggagccag cgtcaaggtt       60

agttgtaagg catctggtta cacctttacc agcttttggg tcggttgggt gcgccaggca      120

cctggtcagg gattggaatg gattggcaat gtctccccct ctgactctta caccaactac      180

aatcagaaat ttaaagatcg cgccactttg acagtcgata agtctacgag tacggcttat      240

atggagctca gttccctgcg cagcgaggac acagccgtct attactgcac ccgcttatca      300

agcggtaaca gctttgacta ctggggacaa ggtacattgg ttacggtcag ctct            354


<210>  13
<211>  5
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A2 CDR H1

<400>  13

Ser Phe Trp Val Gly 
1               5   


<210>  14
<211>  17
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A2 CDR H2

<400>  14

Asn Val Ser Pro Ser Asp Ser Tyr Thr Asn Tyr Asn Gln Lys Phe Lys 
1               5                   10                  15      


Asp 
    


<210>  15
<211>  9
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A2 CDR H3

<400>  15

Leu Ser Ser Gly Asn Ser Phe Asp Tyr 
1               5                   


<210>  16
<211>  113
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A2 VL

<400>  16

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


Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Asn Ser 
            20                  25                  30          


Gly Asn Gln Lys Asn Tyr Leu Thr Trp Tyr Gln Gln Lys Pro Gly Gln 
        35                  40                  45              


Pro Pro Lys Leu Leu Ile Tyr Trp Ser Ser Thr Lys Gln Ser Gly Val 
    50                  55                  60                  


Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
65                  70                  75                  80  


Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Asn 
                85                  90                  95      


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


Lys 
    


<210>  17
<211>  339
<212>  DNA
<213>  ˹

<220>
<223>  18.2-A2 VL

<400>  17
gacatcgtta tgactcagtc tcccgactcc ctcagcgtca gcttgggtga acgcgccact       60

atcaattgta agtccagtca gtccgtcctc aattccggga atcagaagaa ctaccttaca      120

tggtatcagc agaaacctgg tcagccacca aaattgctca tctattggag ctcgaccaag      180

cagagcggcg tgcccgaccg ctttagtggg agcggctctg gcacagattt tacacttact      240

attagtagtc ttcaggccga ggatgtcgcg gtatattact gtcagaatgc cttttcgttc      300

ccctttacct tcggtcaggg aacgaaggtt gaaatcaag                             339


<210>  18
<211>  17
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A2 CDR L1

<400>  18

Lys Ser Ser Gln Ser Val Leu Asn Ser Gly Asn Gln Lys Asn Tyr Leu 
1               5                   10                  15      


Thr 
    


<210>  19
<211>  7
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A2 CDR L2

<400>  19

Trp Ser Ser Thr Lys Gln Ser 
1               5           


<210>  20
<211>  9
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A2 CDR L3

<400>  20

Gln Asn Ala Phe Ser Phe Pro Phe Thr 
1               5                   


<210>  21
<211>  118
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A3 VH

<400>  21

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 Ser Tyr 
            20                  25                  30          


Trp Leu Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 
        35                  40                  45              


Gly Ser Met Tyr Pro Ser Asp Ser Tyr Thr Asn Tyr Asn Gln Lys Phe 
    50                  55                  60                  


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


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


Thr Arg Phe Ser Arg Gly Asn Ser Phe Asp Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


Leu Val Thr Val Ser Ser 
        115             


<210>  22
<211>  354
<212>  DNA
<213>  ˹

<220>
<223>  18.2-A3 VH

<400>  22
gaggtccaac tcgttcaatc tggagcagag gtaaaaaagc ctggagccag cgtcaaggtt       60

agttgtaagg catctggtta cacctttacc agctattggc tcaattgggt gcgccaggca      120

cctggtcagg gattggaatg gattggcagt atgtatccct ctgactctta caccaactac      180

aatcagaaat ttaaagatcg cgccactttg acagtcgata agtctacgag tacggcttat      240

atggagctca gttccctgcg cagcgaggac acagccgtct attactgcac ccgcttcagc      300

cgcggcaaca gctttgacta ctggggacaa ggtacattgg ttacggtcag ctct            354


<210>  23
<211>  5
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A3 CDR H1

<400>  23

Ser Tyr Trp Leu Asn 
1               5   


<210>  24
<211>  17
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A3 CDR H2

<400>  24

Ser Met Tyr Pro Ser Asp Ser Tyr Thr Asn Tyr Asn Gln Lys Phe Lys 
1               5                   10                  15      


Asp 
    


<210>  25
<211>  9
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A3 CDR H3

<400>  25

Phe Ser Arg Gly Asn Ser Phe Asp Tyr 
1               5                   


<210>  26
<211>  113
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A3 VL

<400>  26

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


Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Leu Leu Glu Ser 
            20                  25                  30          


Gly Asn Gln Lys Asn Tyr Leu Thr Trp Tyr Gln Gln Lys Pro Gly Gln 
        35                  40                  45              


Pro Pro Lys Leu Leu Ile Tyr Trp Ser Trp Ala Lys Asn Ser Gly Val 
    50                  55                  60                  


Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
65                  70                  75                  80  


Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Asn 
                85                  90                  95      


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


Lys 
    


<210>  27
<211>  339
<212>  DNA
<213>  ˹

<220>
<223>  18.2-A3 VL

<400>  27
gacatcgtta tgactcagtc tcccgactcc ctcaccgtcg ccttgggtga acgcgccact       60

atcaattgta agtccagtca gtccctcctc gagtccggga atcagaagaa ctaccttaca      120

tggtatcagc agaaacctgg tcagccacca aaattgctca tctattggag ctgggccaag      180

aatagcggcg tgcccgaccg ctttagtggg agcggctctg gcacagattt tacacttact      240

attagtagtc ttcaggccga ggatgtcgcg gtatattact gtcagaatgc ttatgcattt      300

ccctttacct tcggtcaggg aacgaaggtt gaaatcaag                             339


<210>  28
<211>  17
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A3 CDR L1

<400>  28

Lys Ser Ser Gln Ser Leu Leu Glu Ser Gly Asn Gln Lys Asn Tyr Leu 
1               5                   10                  15      


Thr 
    


<210>  29
<211>  7
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A3 CDR L2

<400>  29

Trp Ser Trp Ala Lys Asn Ser 
1               5           


<210>  30
<211>  9
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A3 CDR L3

<400>  30

Gln Asn Ala Tyr Ala Phe Pro Phe Thr 
1               5                   


<210>  31
<211>  118
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A4 VH

<400>  31

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 Ser Phe 
            20                  25                  30          


Trp Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile 
        35                  40                  45              


Gly Asn Ile Leu Pro Ser Asp Ser Tyr Thr Asn Tyr Asn Gln Lys Phe 
    50                  55                  60                  


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


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


Thr Arg Tyr Trp Arg Gly Asn Ser Phe Asp Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


Leu Val Thr Val Ser Ser 
        115             


<210>  32
<211>  354
<212>  DNA
<213>  ˹

<220>
<223>  18.2-A4 VH

<400>  32
gaggtccaac tcgttcaatc tggagcagag gtaaaaaagc ctggagccag cgtcaaggtt       60

agttgtaagg catctggtta cacctttacc agcttttgga tcagttgggt gcgccaggca      120

cctggtcagg gattggaatg gattggcaac attctcccct ctgactctta caccaactac      180

aatcagaaat ttaaagatcg cgccactttg acagtcgata agtctacgag tacggcttat      240

atggagctca gttccctgcg cagcgaggac acagccgtct attactgcac ccgctactgg      300

cgcggcaaca gctttgacta ctggggacaa ggtacattgg ttacggtcag ctct            354


<210>  33
<211>  5
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A4 CDR H1

<400>  33

Ser Phe Trp Ile Ser 
1               5   


<210>  34
<211>  17
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A4 CDR H2

<400>  34

Asn Ile Leu Pro Ser Asp Ser Tyr Thr Asn Tyr Asn Gln Lys Phe Lys 
1               5                   10                  15      


Asp 
    


<210>  35
<211>  9
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A4 CDR H3

<400>  35

Tyr Trp Arg Gly Asn Ser Phe Asp Tyr 
1               5                   


<210>  36
<211>  113
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A4 VL

<400>  36

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


Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Ile Ile Asn Ser 
            20                  25                  30          


Gly Asn Gln Lys Asn Tyr Leu Thr Trp Tyr Gln Gln Lys Pro Gly Gln 
        35                  40                  45              


Pro Pro Lys Leu Leu Ile Tyr Trp Gly Gly Thr Arg His Ser Gly Val 
    50                  55                  60                  


Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
65                  70                  75                  80  


Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Asn 
                85                  90                  95      


Gly Tyr Tyr Ser Pro Phe Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 
            100                 105                 110         


Lys 
    


<210>  37
<211>  339
<212>  DNA
<213>  ˹

<220>
<223>  18.2-A4 VL

<400>  37
gacatcgtta tgactcagtc tcccgactcc ctcgccctcg ccttgggtga acgcgccact       60

atcaattgta agtccagtca gtccatcatc aattccggga atcagaagaa ctaccttaca      120

tggtatcagc agaaacctgg tcagccacca aaattgctca tctattgggg cgggaccagg      180

catagcggcg tgcccgaccg ctttagtggg agcggctctg gcacagattt tacacttact      240

attagtagtc ttcaggccga ggatgtcgcg gtatattact gtcagaatgg ctattactct      300

ccctttacct tcggtcaggg aacgaaggtt gaaatcaag                             339


<210>  38
<211>  17
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A4 CDR L1

<400>  38

Lys Ser Ser Gln Ser Ile Ile Asn Ser Gly Asn Gln Lys Asn Tyr Leu 
1               5                   10                  15      


Thr 
    


<210>  39
<211>  7
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A4 CDR L2

<400>  39

Trp Gly Gly Thr Arg His Ser 
1               5           


<210>  40
<211>  9
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A4 CDR L3

<400>  40

Gln Asn Gly Tyr Tyr Ser Pro Phe Thr 
1               5                   


<210>  41
<211>  118
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A5 VH

<400>  41

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 Ser Ser 
            20                  25                  30          


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


Gly Asn Ser Tyr Pro Ser Asp Ser Tyr Thr Asn Tyr Asn Gln Lys Phe 
    50                  55                  60                  


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


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


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


Leu Val Thr Val Ser Ser 
        115             


<210>  42
<211>  354
<212>  DNA
<213>  ˹

<220>
<223>  18.2-A5 VH

<400>  42
gaggtccaac tcgttcaatc tggagcagag gtaaaaaagc ctggagccag cgtcaaggtt       60

agttgtaagg catctggtta cacctttacc agctcttggg tcggttgggt gcgccaggca      120

cctggtcagg gattggaatg gattggcaat agctacccct ctgactctta caccaactac      180

aatcagaaat ttaaagatcg cgccactttg acagtcgata agtctacgag tacggcttat      240

atggagctca gttccctgcg cagcgaggac acagccgtct attactgcac ccgcttgggg      300

cgcggcaaca gctttgacta ctggggacaa ggtacattgg ttacggtcag ctct            354


<210>  43
<211>  5
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A5 CDR H1

<400>  43

Ser Ser Trp Val Gly 
1               5   


<210>  44
<211>  17
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A5 CDR H2

<400>  44

Asn Ser Tyr Pro Ser Asp Ser Tyr Thr Asn Tyr Asn Gln Lys Phe Lys 
1               5                   10                  15      


Asp 
    


<210>  45
<211>  9
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A5 CDR H3

<400>  45

Leu Gly Arg Gly Asn Ser Phe Asp Tyr 
1               5                   


<210>  46
<211>  113
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A5 VL

<400>  46

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


Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Leu Ile His Ser 
            20                  25                  30          


Gly Asn Gln Lys Asn Tyr Leu Thr Trp Tyr Gln Gln Lys Pro Gly Gln 
        35                  40                  45              


Pro Pro Lys Leu Leu Ile Tyr Trp Gly Leu Ser Lys Asn Ser Gly Val 
    50                  55                  60                  


Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
65                  70                  75                  80  


Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Asn 
                85                  90                  95      


Ser Ile Tyr Tyr Pro Phe Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 
            100                 105                 110         


Lys 
    


<210>  47
<211>  339
<212>  DNA
<213>  ˹

<220>
<223>  18.2-A5 VL

<400>  47
gacatcgtta tgactcagtc tcccgactcc ctcaccgtcg ccttgggtga acgcgccact       60

atcaattgta agtccagtca gtccctcatc cattccggga atcagaagaa ctaccttaca      120

tggtatcagc agaaacctgg tcagccacca aaattgctca tctattgggg cttgagcaag      180

aatagcggcg tgcccgaccg ctttagtggg agcggctctg gcacagattt tacacttact      240

attagtagtc ttcaggccga ggatgtcgcg gtatattact gtcagaatag catttactat      300

ccctttacct tcggtcaggg aacgaaggtt gaaatcaag                             339


<210>  48
<211>  17
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A5 CDR L1

<400>  48

Lys Ser Ser Gln Ser Leu Ile His Ser Gly Asn Gln Lys Asn Tyr Leu 
1               5                   10                  15      


Thr 
    


<210>  49
<211>  7
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A5 CDR L2

<400>  49

Trp Gly Leu Ser Lys Asn Ser 
1               5           


<210>  50
<211>  9
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A5 CDR L3

<400>  50

Gln Asn Ser Ile Tyr Tyr Pro Phe Thr 
1               5                   


<210>  51
<211>  330
<212>  PRT
<213>  ˹

<220>
<223>  㶨

<400>  51

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 Glu Glu 
225                 230                 235                 240 


Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr 
                245                 250                 255     


Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn 
            260                 265                 270         


Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe 
        275                 280                 285             


Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn 
    290                 295                 300                 


Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr 
305                 310                 315                 320 


Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
                325                 330 


<210>  52
<211>  993
<212>  DNA
<213>  ˹

<220>
<223>  㶨

<400>  52
gcgagcacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg       60

ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg      120

tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca      180

ggactctact ccctcagcag cgtggtgact gtgccctcta gcagcttggg cacccagacc      240

tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgagccc      300

aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga      360

ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct      420

gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa 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 ccgggaagag      720

atgaccaaga 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 ccactacacg      960

cagaagagcc tctccctgtc tccgggtaaa tga                                   993


<210>  53
<211>  107
<212>  PRT
<213>  ˹

<220>
<223>  㶨

<400>  53

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>  54
<211>  324
<212>  DNA
<213>  ˹

<220>
<223>  㶨

<400>  54
cggaccgtgg cagcaccaag tgtcttcatc ttcccgccat ctgatgagca gttgaaatct       60

ggaactgctt 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>  55
<211>  118
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A6 VH

<400>  55

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 Ser Tyr 
            20                  25                  30          


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


Gly Ile Ile Tyr Pro Ser Asp Ser Tyr Thr Asn Tyr Asn Gln Lys Phe 
    50                  55                  60                  


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


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


Thr Arg Phe Trp Arg Gly Asn Ser Phe Asp Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


Leu Val Thr Val Ser Ser 
        115             


<210>  56
<211>  354
<212>  DNA
<213>  ˹

<220>
<223>  18.2-A6 VH

<400>  56
gaggtccaac tcgttcaatc tggagcagag gtaaaaaagc ctggagccag cgtcaaggtt       60

agttgtaagg catctggtta cacctttacc agctattggc tcggttgggt gcgccaggca      120

cctggtcagg gattggaatg gattggcatt atatacccct ctgactctta caccaactac      180

aatcagaaat ttaaagatcg cgccactttg acagtcgata agtctacgag tacggcttat      240

atggagctca gttccctgcg cagcgaggac acagccgtct attactgcac ccgcttctgg      300

cgcggtaaca gctttgacta ctggggacaa ggtacattgg ttacggtcag ctct            354


<210>  57
<211>  5
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A6 CDR H1

<400>  57

Ser Tyr Trp Leu Gly 
1               5   


<210>  58
<211>  17
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A6 CDR H2

<400>  58

Ile Ile Tyr Pro Ser Asp Ser Tyr Thr Asn Tyr Asn Gln Lys Phe Lys 
1               5                   10                  15      


Asp 
    


<210>  59
<211>  9
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A6 CDR H3

<400>  59

Phe Trp Arg Gly Asn Ser Phe Asp Tyr 
1               5                   


<210>  60
<211>  113
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A6 VL

<400>  60

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


Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Leu Leu Asn Ser 
            20                  25                  30          


Gly Asn Gln Lys Asn Tyr Leu Thr Trp Tyr Gln Gln Lys Pro Gly Gln 
        35                  40                  45              


Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ala Gly Lys Glu Ser Gly Val 
    50                  55                  60                  


Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 
65                  70                  75                  80  


Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Asn 
                85                  90                  95      


Gly Tyr Ser His Pro Phe Thr Phe Gly Gln Gly Thr Lys Val Glu Ile 
            100                 105                 110         


Lys 
    


<210>  61
<211>  339
<212>  DNA
<213>  ˹

<220>
<223>  18.2-A6 VL

<400>  61
gacatcgtta tgactcagtc tcccgactcc ctcaccatcg gcttgggtga acgcgccact       60

atcaattgta agtccagtca gtccctcctc aattccggga atcagaagaa ctaccttaca      120

tggtatcagc agaaacctgg tcagccacca aaattgctca tctattgggc cgcgggcaag      180

gagagcggcg tgcccgaccg ctttagtggg agcggctctg gcacagattt tacacttact      240

attagtagtc ttcaggccga ggatgtcgcg gtatattact gtcagaacgg gtattcccat      300

ccctttacct tcggtcaggg aacgaaggtt gaaatcaag                             339


<210>  62
<211>  17
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A6 CDR L1

<400>  62

Lys Ser Ser Gln Ser Leu Leu Glu Ser Gly Asn Gln Lys Asn Tyr Leu 
1               5                   10                  15      


Thr 
    


<210>  63
<211>  7
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A6 CDR L2

<400>  63

Trp Ala Ala Gly Lys Glu Ser 
1               5           


<210>  64
<211>  9
<212>  PRT
<213>  ˹

<220>
<223>  18.2-A6 CDR L3

<400>  64

Gln Asn Gly Tyr Ser His Pro Phe Thr 
1               5                   


