                         SEQUENCE LISTING

<110>  SHANDONG BOAN BIOTECHNOLOGY CO., LTD.
 
<120>  CLDN18.2/CD3 bispecific antibodies for the therapy of 
       CLDN18.2-expressing solid tumors

<130>  BA15

<150>  US63/147,233
<151>  2021-02-08

<160>  52    

<170>  PatentIn version 3.5

<210>  1
<211>  125
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH

<400>  1

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


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


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


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


Gln Gly Arg Val Thr Val Thr Ala 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      


Ala Arg Glu Arg Asp Asn Trp Asp Pro Tyr Tyr Tyr Tyr Tyr Gly Met 
            100                 105                 110         


Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
        115                 120                 125 


<210>  2
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VL

<400>  2

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


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Asn Ser Trp 
            20                  25                  30          


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


Tyr Lys Ala Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


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


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


<210>  3
<211>  124
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH

<400>  3

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          


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


Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Leu Arg Phe Phe Asp Trp Leu Leu Gly Ser Ala Phe Asp 
            100                 105                 110         


Ile Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
        115                 120                 


<210>  4
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VL

<400>  4

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


Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Asn Asp 
            20                  25                  30          


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


Tyr Ala Ala Ser Ser Leu Gln 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 Phe Ala Thr Tyr Tyr Cys Leu Gln Asp Tyr Asn Tyr Pro Arg 
                85                  90                  95      


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


<210>  5
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH

<400>  5

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


Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr 
            20                  25                  30          


Gly Met Ser Trp Val Arg Gln Thr Pro Asp Lys Arg Leu Glu Leu Val 
        35                  40                  45              


Ala Thr Ile Asn Ser Asn Gly Gly Ser Thr Tyr Tyr Pro Asp Ser Val 
    50                  55                  60                  


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


Leu Gln Met Ser Ser Leu Lys Ser Glu Asp Thr Ala Met Tyr Tyr Cys 
                85                  90                  95      


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


Leu Val Thr Val Ser Ser 
        115             


<210>  6
<211>  113
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VL

<400>  6

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


Glu Lys Val Thr Met Ser Cys Gln Ser Ser Gln Ser Leu Leu Asn Ser 
            20                  25                  30          


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


Pro Pro Lys Leu Leu Met Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 
    50                  55                  60                  


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


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


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


Lys 
    


<210>  7
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH

<400>  7

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


Ser Val Lys Ile Ser Cys Lys Ala Ser Asp Tyr Ser Phe Thr Ser Tyr 
            20                  25                  30          


Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser Leu Glu Trp Ile 
        35                  40                  45              


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


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


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


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


Thr Leu Val Thr Val Ser Ser 
        115                 


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

<220>
<223>  VL

<400>  8

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


Glu Lys Val Thr Met 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 Asn Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 
    50                  55                  60                  


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


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


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


Lys 
    


<210>  9
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH

<400>  9

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


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


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


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


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


Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Asp Tyr Phe Cys 
                85                  90                  95      


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


Thr Leu Thr Val Ser Ser 
        115             


<210>  10
<211>  113
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VL

<400>  10

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


Glu Lys Val Thr Met Ser 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 Ser Thr Arg Asp Ser Gly Val 
    50                  55                  60                  


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


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


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


Lys 
    


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

<220>
<223>  CDR1

<400>  11

Gly Tyr Ala Phe Ser Asn Tyr Trp Met Asn 
1               5                   10  


<210>  12
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2

<400>  12

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


Gly 
    


<210>  13
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR3

<400>  13

Tyr Tyr Arg Gly Asn Cys Phe Asp Tyr 
1               5                   


<210>  14
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR1

<400>  14

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


Thr 
    


<210>  15
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2

<400>  15

Trp Ala Ser Thr Arg Asp Ser 
1               5           


<210>  16
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR3

<400>  16

Gln Asn Ala Tyr Thr Tyr Pro Leu Thr 
1               5                   


<210>  17
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH1

<400>  17

Gln 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 Ala Phe Ser Asn Tyr 
            20                  25                  30          


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


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


Lys Gly Arg Val Thr Ile Thr Arg Asp Thr Ser Ala 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      


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


Leu Val Thr Val Ser Ser 
        115             


<210>  18
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH2

<400>  18

Gln 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 Ala Phe Ser Asn Tyr 
            20                  25                  30          


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


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


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


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


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


Leu Val Thr Val Ser Ser 
        115             


<210>  19
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH3

<400>  19

Gln 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 Ala Phe Ser Asn Tyr 
            20                  25                  30          


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


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


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


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


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


Leu Val Thr Val Ser Ser 
        115             


<210>  20
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH4

<400>  20

Gln 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 Ala Phe Ser Asn Tyr 
            20                  25                  30          


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


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


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


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


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


Leu Val Thr Val Ser Ser 
        115             


<210>  21
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH5

<400>  21

Gln 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 Ala Phe Ser Asn Tyr 
            20                  25                  30          


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


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


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


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


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


Leu Val Thr Val Ser Ser 
        115             


<210>  22
<211>  113
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VL1

<400>  22

Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser 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 Ser Thr Arg Asp 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 Thr Tyr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile 
            100                 105                 110         


Lys 
    


<210>  23
<211>  113
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VL2

<400>  23

Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser 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 Ser Thr Arg Asp 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 Val Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Asn 
                85                  90                  95      


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


Lys 
    


<210>  24
<211>  113
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VL3

<400>  24

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


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


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


Lys 
    


<210>  25
<211>  125
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH

<400>  25

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


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


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


Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 
    50                  55                  60                  


Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 
65                  70                  75                  80  


Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr 
                85                  90                  95      


Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp 
            100                 105                 110         


Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125 


<210>  26
<211>  109
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VL

<400>  26

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


Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly 
            20                  25                  30          


Tyr Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly 
        35                  40                  45              


Leu Ile Gly Gly Thr Lys Phe Leu Ala Pro Gly Thr Pro Ala Arg Phe 
    50                  55                  60                  


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


Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Ala Leu Trp Tyr Ser Asn 
                85                  90                  95      


Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
            100                 105                 


<210>  27
<211>  125
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH

<400>  27

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


Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 
            20                  25                  30          


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


Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp 
    50                  55                  60                  


Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 
65                  70                  75                  80  


Ala Tyr Leu Gln Met Asn Asn Leu Arg Thr Glu Asp Thr Ala Val Tyr 
                85                  90                  95      


Tyr Cys Val Arg His Gly Asn Trp Gly Asn Ser Tyr Ile Ser Tyr Trp 
            100                 105                 110         


Ala Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
        115                 120                 125 


<210>  28
<211>  125
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH

<400>  28

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


Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Thr Tyr 
            20                  25                  30          


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


Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Thr Tyr Ala Asp 
    50                  55                  60                  


Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 
65                  70                  75                  80  


Ala Tyr Leu Gln Met Asn Asn Leu Arg Thr Glu Asp Thr Ala Val Tyr 
                85                  90                  95      


Tyr Cys Val Arg His Gly Asn Trp Gly Asn Ser Tyr Ile Ser Tyr Trp 
            100                 105                 110         


Ala Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
        115                 120                 125 


<210>  29
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH

<400>  29

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 Thr Phe Ser Ser Tyr 
            20                  25                  30          


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


Ala Thr Ile Asn Ser Asn Gly Gly Ser Thr Tyr Tyr Pro Asp Ser Val 
    50                  55                  60                  


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


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


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


Thr Val Thr Val Ser Ser 
        115             


<210>  30
<211>  113
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VL

<400>  30

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


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


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


Ala Pro Arg Leu Leu Met Tyr Trp Ala Ser Thr Arg 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 Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Asn 
                85                  90                  95      


Thr Tyr Tyr Tyr Pro Phe Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile 
            100                 105                 110         


Lys 
    


<210>  31
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR1

<400>  31

Lys Tyr Ala Met Asn 
1               5   


<210>  32
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2

<400>  32

Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser 
1               5                   10                  15      


Val Lys Asp 
            


<210>  33
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR3

<400>  33

His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr 
1               5                   10                  


<210>  34
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR1

<400>  34

Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Tyr Tyr Pro Asn 
1               5                   10                  


<210>  35
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2

<400>  35

Gly Thr Lys Phe Leu Ala Pro 
1               5           


<210>  36
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR3

<400>  36

Ala Leu Trp Tyr Ser Asn Arg Trp Val 
1               5                   


<210>  37
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR1

<400>  37

Thr Tyr Ala Met Asn 
1               5   


<210>  38
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2

<400>  38

Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser 
1               5                   10                  15      


Val Lys Asp 
            


<210>  39
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR3

<400>  39

His Gly Asn Trp Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr 
1               5                   10                  


<210>  40
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2

<400>  40

Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Thr Tyr Ala Asp Ser 
1               5                   10                  15      


Val Lys Asp 
            


<210>  41
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker-1

<400>  41

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10                  15  


<210>  42
<211>  30
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Linker-2

<400>  42

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
1               5                   10                  15      


Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
            20                  25                  30  


<210>  43
<211>  109
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CL (constant region of human kappa light chain)

<400>  43

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 Thr Ser 
            100                 105                 


<210>  44
<211>  98
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CH1 of human IgGl heavy chain

<400>  44

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 
        


<210>  45
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Hinge

<400>  45

Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
1               5                   10                  15  


<210>  46
<211>  110
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CH2 of human IgGl heavy chain

<400>  46

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


Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
            20                  25                  30          


Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
        35                  40                  45              


Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
    50                  55                  60                  


Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
65                  70                  75                  80  


Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                85                  90                  95      


Ala Leu Ala Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys 
            100                 105                 110 


<210>  47
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CH3 of human IgGl heavy chain

<400>  47

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


Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe 
            20                  25                  30          


Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu 
        35                  40                  45              


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


Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly 
65                  70                  75                  80  


Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
                85                  90                  95      


Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
            100                 105         


<210>  48
<211>  330
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  constant region of mouse IgG2a heavy chain

<400>  48

Ala Lys Thr Thr Ala Pro Ser Val Tyr Pro Leu Ala Pro Val Cys Gly 
1               5                   10                  15      


Asp Thr Thr Gly Ser Ser Val Thr Leu Gly Cys Leu Val Lys Gly Tyr 
            20                  25                  30          


Phe Pro Glu Pro Val Thr Leu Thr Trp Asn Ser Gly Ser Leu Ser Ser 
        35                  40                  45              


Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu 
    50                  55                  60                  


Ser Ser Ser Val Thr Val Thr Ser Ser Thr Trp Pro Ser Gln Ser Ile 
65                  70                  75                  80  


Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys 
                85                  90                  95      


Ile Glu Pro Arg Gly Pro Thr Ile Lys Pro Cys Pro Pro Cys Lys Cys 
            100                 105                 110         


Pro Ala Pro Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro 
        115                 120                 125             


Lys Ile Lys Asp Val Leu Met Ile Ser Leu Ser Pro Ile Val Thr Cys 
    130                 135                 140                 


Val Val Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp 
145                 150                 155                 160 


Phe Val Asn Asn Val Glu Val His Thr Ala Gln Thr Gln Thr His Arg 
                165                 170                 175     


Glu Asp Tyr Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro Ile Gln 
            180                 185                 190         


His Gln Asp Trp Met Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn 
        195                 200                 205             


Lys Asp Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly 
    210                 215                 220                 


Ser Val Arg Ala Pro Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu 
225                 230                 235                 240 


Met Thr Lys Lys Gln Val Thr Leu Thr Cys Met Val Thr Asp Phe Met 
                245                 250                 255     


Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr Glu Leu 
            260                 265                 270         


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


Met Tyr Ser Lys Leu Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn 
    290                 295                 300                 


Ser Tyr Ser Cys Ser Val Val His Glu Gly Leu His Asn His His Thr 
305                 310                 315                 320 


Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys 
                325                 330 


<210>  49
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  hinge area of constant region of mouse IgG2a heavy chain

<400>  49

Glu Pro Arg Gly Pro Thr Ile Lys Pro Cys Pro Pro Cys Lys Cys Pro 
1               5                   10                  15      


<210>  50
<211>  97
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CH1 of constant region of mouse IgG2a heavy chain

<400>  50

Ala Lys Thr Thr Ala Pro Ser Val Tyr Pro Leu Ala Pro Val Cys Gly 
1               5                   10                  15      


Asp Thr Thr Gly Ser Ser Val Thr Leu Gly Cys Leu Val Lys Gly Tyr 
            20                  25                  30          


Phe Pro Glu Pro Val Thr Leu Thr Trp Asn Ser Gly Ser Leu Ser Ser 
        35                  40                  45              


Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu 
    50                  55                  60                  


Ser Ser Ser Val Thr Val Thr Ser Ser Thr Trp Pro Ser Gln Ser Ile 
65                  70                  75                  80  


Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys 
                85                  90                  95      


Ile 
    


<210>  51
<211>  217
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CH2+CH3 of constant region of mouse IgG2a heavy chain

<400>  51

Ala Pro Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys 
1               5                   10                  15      


Ile Lys Asp Val Leu Met Ile Ser Leu Ser Pro Ile Val Thr Cys Val 
            20                  25                  30          


Val Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp Phe 
        35                  40                  45              


Val Asn Asn Val Glu Val His Thr Ala Gln Thr Gln Thr His Arg Glu 
    50                  55                  60                  


Asp Tyr Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro Ile Gln His 
65                  70                  75                  80  


Gln Asp Trp Met Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Lys 
                85                  90                  95      


Asp Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly Ser 
            100                 105                 110         


Val Arg Ala Pro Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu Met 
        115                 120                 125             


Thr Lys Lys Gln Val Thr Leu Thr Cys Met Val Thr Asp Phe Met Pro 
    130                 135                 140                 


Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr Glu Leu Asn 
145                 150                 155                 160 


Tyr Lys Asn Thr Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe Met 
                165                 170                 175     


Tyr Ser Lys Leu Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn Ser 
            180                 185                 190         


Tyr Ser Cys Ser Val Val His Glu Gly Leu His Asn His His Thr Thr 
        195                 200                 205             


Lys Ser Phe Ser Arg Thr Pro Gly Lys 
    210                 215         


<210>  52
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CL (constant region of mouse kappa light chain)

<400>  52

Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu 
1               5                   10                  15      


Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe 
            20                  25                  30          


Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg 
        35                  40                  45              


Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser 
    50                  55                  60                  


Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu 
65                  70                  75                  80  


Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser 
                85                  90                  95      


Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys 
            100                 105         


