                         SEQUENCE LISTING

<110>  WuXi Biologics (Shanghai) CO., LTD.
       Wuxi Biologics Ireland Limited
 
<120>  Novel Bispecific CTLA-4/PD-1 Polypeptide Complexes

<130>  IEC180018PCT WBP3245

<160>  31    

<170>  PatentIn version 3.5

<210>  1
<211>  10
<212>  PRT
<213>  artificial sequence

<220>
<223>  CDR1

<400>  1

Gly Phe Thr Phe Ser Ser Tyr Thr Met His 
1               5                   10  


<210>  2
<211>  17
<212>  PRT
<213>  artificial sequence

<220>
<223>  CDR2

<400>  2

Phe Ile Ser Tyr Asp Gly Asn Asn Lys Tyr Tyr Ala Asp Ser Val Lys 
1               5                   10                  15      


Gly 
    


<210>  3
<211>  9
<212>  PRT
<213>  artificial sequence

<220>
<223>  CDR3

<400>  3

Thr Gly Trp Leu Gly Pro Phe Asp Tyr 
1               5                   


<210>  4
<211>  12
<212>  PRT
<213>  artificial sequence

<220>
<223>  CDR1

<400>  4

Arg Ala Ser Gln Ser Val Gly Ser Ser Tyr Leu Ala 
1               5                   10          


<210>  5
<211>  7
<212>  PRT
<213>  artificial sequence

<220>
<223>  CDR2

<400>  5

Gly Ala Phe Ser Arg Ala Thr 
1               5           


<210>  6
<211>  9
<212>  PRT
<213>  artificial sequence

<220>
<223>  CDR3

<400>  6

Gln Gln Tyr Gly Ser Ser Pro Trp Thr 
1               5                   


<210>  7
<211>  10
<212>  PRT
<213>  artificial sequence

<220>
<223>  CDR1

<400>  7

Gly Phe Thr Phe Ser Ser His Ala Met Ser 
1               5                   10  


<210>  8
<211>  17
<212>  PRT
<213>  artificial sequence

<220>
<223>  CDR2

<400>  8

Thr Ile Thr Gly Gly Gly Gly Ser Ile Tyr Tyr Ala Asp Ser Val Lys 
1               5                   10                  15      


Gly 
    


<210>  9
<211>  10
<212>  PRT
<213>  artificial sequence

<220>
<223>  CDR3

<400>  9

Asn Arg Ala Gly Glu Gly Tyr Phe Asp Tyr 
1               5                   10  


<210>  10
<211>  11
<212>  PRT
<213>  artificial sequence

<220>
<223>  CDR1

<400>  10

Gly Gly Asp Asn Ile Gly Asn Lys Asp Val His 
1               5                   10      


<210>  11
<211>  7
<212>  PRT
<213>  artificial sequence

<220>
<223>  CDR2

<400>  11

Arg Asp Ser Asn Arg Pro Ser 
1               5           


<210>  12
<211>  8
<212>  PRT
<213>  artificial sequence

<220>
<223>  CDR3

<400>  12

Gln Val Trp Asp Ser Ile Trp Val 
1               5               


<210>  13
<211>  12
<212>  PRT
<213>  artificial sequence

<220>
<223>  CDR1

<400>  13

Ala Asp Ser Ile Ser Ser Thr Thr Tyr Tyr Trp Val 
1               5                   10          


<210>  14
<211>  16
<212>  PRT
<213>  artificial sequence

<220>
<223>  CDR2

<400>  14

Ser Ile Ser Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser Leu Lys Ser 
1               5                   10                  15      


<210>  15
<211>  13
<212>  PRT
<213>  artificial sequence

<220>
<223>  CDR3

<400>  15

His Leu Gly Tyr Asn Gly Arg Tyr Leu Pro Phe Asp Tyr 
1               5                   10              


<210>  16
<211>  14
<212>  PRT
<213>  artificial sequence

<220>
<223>  CDR1

<400>  16

Thr Gly Thr Ser Ser Asp Val Gly Phe Tyr Asn Tyr Val Ser 
1               5                   10                  


<210>  17
<211>  7
<212>  PRT
<213>  artificial sequence

<220>
<223>  CDR2

<400>  17

Asp Val Ser Asn Arg Pro Ser 
1               5           


<210>  18
<211>  10
<212>  PRT
<213>  artificial sequence

<220>
<223>  CDR3

<400>  18

Ser Ser Tyr Thr Ser Ile Ser Thr Trp Val 
1               5                   10  


<210>  19
<211>  118
<212>  PRT
<213>  artificial sequence

<220>
<223>  VH

<400>  19

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


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


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


Thr Phe Ile Ser Tyr Asp Gly Asn 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 Ile Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Thr Gly Trp Leu Gly Pro Phe Asp Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


Leu Val Thr Val Ser Ser 
        115             


<210>  20
<211>  108
<212>  PRT
<213>  artificial sequence

<220>
<223>  VL

<400>  20

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


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser 
            20                  25                  30          


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


Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 
    50                  55                  60                  


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


Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 
                85                  90                  95      


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


<210>  21
<211>  118
<212>  PRT
<213>  artificial sequence

<220>
<223>  VH

<400>  21

Glu Val Gln Leu Leu 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 His 
            20                  25                  30          


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


Ser Thr Ile Thr Gly Gly Gly Gly Ser Ile 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 Lys Asn Arg Ala Gly Glu Gly Tyr Phe Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser 
        115             


<210>  22
<211>  105
<212>  PRT
<213>  artificial sequence

<220>
<223>  VL

<400>  22

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


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


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


Arg Asp Ser Asn Arg Pro Ser Gly Ile Pro Glu Gly Phe Ser Gly Ser 
    50                  55                  60                  


Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Arg Ala Gln Ala Gly 
65                  70                  75                  80  


Asp Glu Ala Asp Tyr Tyr Cys Gln Val Trp Asp Ser Ile Trp Val Phe 
                85                  90                  95      


Gly Gly Gly Thr Lys Leu Thr Val Leu 
            100                 105 


<210>  23
<211>  122
<212>  PRT
<213>  artificial sequence

<220>
<223>  VH

<400>  23

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


Thr Leu Thr Leu Thr Cys Thr Val Ser Ala Asp Ser Ile Ser Ser Thr 
            20                  25                  30          


Thr Tyr Tyr Trp Val Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu 
        35                  40                  45              


Trp Ile Gly Ser Ile Ser Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro Ser 
    50                  55                  60                  


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


Ser Leu Lys Leu Asn Ser Val Ala Ala Thr Asp Thr Ala Leu Tyr Tyr 
                85                  90                  95      


Cys Ala Arg His Leu Gly Tyr Asn Gly Arg Tyr Leu Pro Phe Asp Tyr 
            100                 105                 110         


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


<210>  24
<211>  110
<212>  PRT
<213>  artificial sequence

<220>
<223>  VL

<400>  24

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


Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Phe Tyr 
            20                  25                  30          


Asn Tyr Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Glu Leu 
        35                  40                  45              


Met Ile Tyr Asp Val Ser Asn Arg Pro Ser Gly Val Ser Asp Arg Phe 
    50                  55                  60                  


Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu 
65                  70                  75                  80  


Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Thr Ser Ile 
                85                  90                  95      


Ser Thr Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
            100                 105                 110 


<210>  25
<211>  688
<212>  PRT
<213>  artificial sequence

<220>
<223>  heavy chain

<400>  25

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


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


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


Thr Phe Ile Ser Tyr Asp Gly Asn 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 Ile Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Thr Gly Trp Leu Gly Pro Phe Asp Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


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


Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly 
    130                 135                 140                 


Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 
145                 150                 155                 160 


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


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


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


Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys 
    210                 215                 220                 


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


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


Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln 
            260                 265                 270         


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


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


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


Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys 
                325                 330                 335     


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


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


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


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


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


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


His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly Gly Gly Gly 
        435                 440                 445             


Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
    450                 455                 460                 


Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser 
465                 470                 475                 480 


His Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                485                 490                 495     


Val Ser Thr Ile Thr Gly Gly Gly Gly Ser Ile Tyr Tyr Ala Asp Ser 
            500                 505                 510         


Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu 
        515                 520                 525             


Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr 
    530                 535                 540                 


Cys Ala Lys Asn Arg Ala Gly Glu Gly Tyr Phe Asp Tyr Trp Gly Gln 
545                 550                 555                 560 


Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly 
                565                 570                 575     


Gly Ser Gly Gly Gly Gly Ser Ser Tyr Glu Leu Thr Gln Pro Leu Ser 
            580                 585                 590         


Val Ser Val Ala Leu Gly Gln Thr Ala Arg Ile Thr Cys Gly Gly Asp 
        595                 600                 605             


Asn Ile Gly Asn Lys Asp Val His Trp Tyr Gln Gln Lys Pro Gly Gln 
    610                 615                 620                 


Ala Pro Val Leu Val Ile Tyr Arg Asp Ser Asn Arg Pro Ser Gly Ile 
625                 630                 635                 640 


Pro Glu Gly Phe Ser Gly Ser Asn Ser Gly Asn Thr Ala Thr Leu Thr 
                645                 650                 655     


Ile Ser Arg Ala Gln Ala Gly Asp Glu Ala Asp Tyr Tyr Cys Gln Val 
            660                 665                 670         


Trp Asp Ser Ile Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
        675                 680                 685             


<210>  26
<211>  697
<212>  PRT
<213>  artificial sequence

<220>
<223>  heavy chain

<400>  26

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


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


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


Thr Phe Ile Ser Tyr Asp Gly Asn 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 Ile Tyr Tyr Cys 
                85                  90                  95      


Ala Arg Thr Gly Trp Leu Gly Pro Phe Asp Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


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


Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly 
    130                 135                 140                 


Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 
145                 150                 155                 160 


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


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


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


Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys 
    210                 215                 220                 


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


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


Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln 
            260                 265                 270         


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


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


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


Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys 
                325                 330                 335     


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


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


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


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


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


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


His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Gly Gly Gly Gly 
        435                 440                 445             


Ser Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser 
    450                 455                 460                 


Glu Thr Leu Thr Leu Thr Cys Thr Val Ser Ala Asp Ser Ile Ser Ser 
465                 470                 475                 480 


Thr Thr Tyr Tyr Trp Val Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu 
                485                 490                 495     


Glu Trp Ile Gly Ser Ile Ser Tyr Ser Gly Ser Thr Tyr Tyr Asn Pro 
            500                 505                 510         


Ser Leu Lys Ser Arg Val Thr Val Ser Val Asp Thr Ser Lys Asn Gln 
        515                 520                 525             


Phe Ser Leu Lys Leu Asn Ser Val Ala Ala Thr Asp Thr Ala Leu Tyr 
    530                 535                 540                 


Tyr Cys Ala Arg His Leu Gly Tyr Asn Gly Arg Tyr Leu Pro Phe Asp 
545                 550                 555                 560 


Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly 
                565                 570                 575     


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala Leu Thr 
            580                 585                 590         


Gln Pro Ala Ser Val Ser Gly Ser Pro Gly Gln Ser Ile Thr Ile Ser 
        595                 600                 605             


Cys Thr Gly Thr Ser Ser Asp Val Gly Phe Tyr Asn Tyr Val Ser Trp 
    610                 615                 620                 


Tyr Gln Gln His Pro Gly Lys Ala Pro Glu Leu Met Ile Tyr Asp Val 
625                 630                 635                 640 


Ser Asn Arg Pro Ser Gly Val Ser Asp Arg Phe Ser Gly Ser Lys Ser 
                645                 650                 655     


Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu Gln Ala Glu Asp Glu 
            660                 665                 670         


Ala Asp Tyr Tyr Cys Ser Ser Tyr Thr Ser Ile Ser Thr Trp Val Phe 
        675                 680                 685             


Gly Gly Gly Thr Lys Leu Thr Val Leu 
    690                 695         


<210>  27
<211>  215
<212>  PRT
<213>  artificial sequence

<220>
<223>  light chain

<400>  27

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


Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Gly Ser Ser 
            20                  25                  30          


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


Ile Tyr Gly Ala Phe Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 
    50                  55                  60                  


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


Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 
                85                  90                  95      


Trp Thr Phe Gly Gln 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>  28
<211>  2068
<212>  DNA
<213>  artificial sequence

<220>
<223>  heavy chain

<400>  28
caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc       60

tcctgtgcag cctctggatt caccttcagt agctatacta tgcactgggt ccgccaggct      120

ccaggcaagg ggctggagtg ggtgacattt atatcatatg atggaaacaa taaatactac      180

gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat      240

ctgcaaatga acagcctgag agctgaggac acggctatat attactgtgc gaggaccggc      300

tggctggggc cctttgacta ctggggccag ggaaccctgg tcaccgtctc ctcagcgtcg      360

accaagggcc catccgtctt ccccctggcg ccctgctcca ggagcacctc cgagagcaca      420

gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac      480

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc      540

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcacgaa gacctacacc      600

tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga gtccaaatat      660

ggtcccccat gcccaccatg cccagcacct gagttcctgg ggggaccatc agtcttcctg      720

ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg      780

gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgtg      840

gaggtgcata atgccaagac aaagccgcgg gaggagcagt tcaacagcac gtaccgtgtg      900

gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaaggagta caagtgcaag      960

gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag     1020

ccccgagagc cacaggtgta caccctgccc ccatcccagg aggagatgac caagaaccag     1080

gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggag     1140

agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc     1200

tccttcttcc tctacagcag gctaaccgtg gacaagagca ggtggcagga ggggaatgtc     1260

ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gagcctctcc     1320

ctgtctctgg gtaaaggtgg cggtggctcg gaggtgcagc tgttggagtc tgggggaggc     1380

ttggtacagc ctggggggtc cctgagactg tcctgcgcag cctctggatt cacctttagc     1440

agccatgcca tgagctgggt ccgccaggct ccagggaagg ggctggagtg ggtctcaact     1500

attactggtg gtggtggtag catatactac gcagactccg tgaagggccg gttcaccatc     1560

tccagagaca attccaagaa cacgctgtat ctgcaaatga acagcctgag agccgaggac     1620

acggccgtat attattgtgc gaaaaaccgc gctggggagg gttactttga ctactggggc     1680

cagggaaccc tggtcaccgt ctcctcaggt ggtggcggtt caggcggagg tggctctggc     1740

ggtggcggat cgtcctatga gctgactcag ccactctcag tgtcagtggc cctgggacag     1800

acggccagga ttacctgtgg gggagacaac attggaaata aagatgtgca ctggtaccag     1860

cagaagccag gccaggcccc tgtgctggtc atctataggg atagcaaccg gccctctggg     1920

atccctgagg gattctctgg ctccaactcg gggaacacgg ccaccctgac catcagcaga     1980

gcccaagccg gggatgaggc tgactattac tgtcaggtgt gggacagcat ttgggtgttc     2040

ggcggaggga ccaagctgac cgtcctat                                        2068


<210>  29
<211>  2094
<212>  DNA
<213>  artificial sequence

<220>
<223>  heavy chain

<400>  29
caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc       60

tcctgtgcag cctctggatt caccttcagt agctatacta tgcactgggt ccgccaggct      120

ccaggcaagg ggctggagtg ggtgacattt atatcatatg atggaaacaa taaatactac      180

gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat      240

ctgcaaatga acagcctgag agctgaggac acggctatat attactgtgc gaggaccggc      300

tggctggggc cctttgacta ctggggccag ggaaccctgg tcaccgtctc ctcagcgtcg      360

accaagggcc catccgtctt ccccctggcg ccctgctcca ggagcacctc cgagagcaca      420

gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac      480

tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc      540

tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcacgaa gacctacacc      600

tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agagagttga gtccaaatat      660

ggtcccccat gcccaccatg cccagcacct gagttcctgg ggggaccatc agtcttcctg      720

ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg      780

gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgtg      840

gaggtgcata atgccaagac aaagccgcgg gaggagcagt tcaacagcac gtaccgtgtg      900

gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaaggagta caagtgcaag      960

gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag     1020

ccccgagagc cacaggtgta caccctgccc ccatcccagg aggagatgac caagaaccag     1080

gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtgggag     1140

agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc     1200

tccttcttcc tctacagcag gctaaccgtg gacaagagca ggtggcagga ggggaatgtc     1260

ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gagcctctcc     1320

ctgtctctgg gtaaaggtgg cggtggctcg cagctgcagc tgcaggagtc gggcccagga     1380

ctggtgaagc cttcggagac cctgaccctc acctgcactg tctctgctga ctccatcagc     1440

agtactactt actactgggt ctggatccgc cagcccccag ggaagggact ggagtggatt     1500

gggagtatct cttatagtgg gagcacctac tacaatccgt ccctcaagag tcgagtcacc     1560

gtatccgtag acacgtccaa gaaccagttc tccctgaagc tgaactctgt ggccgccaca     1620

gacacggctc tatattactg tgcgagacat ctagggtata atgggaggta cctccccttt     1680

gactactggg gccagggaac cctggtcacc gtctcctccg gtggtggcgg ttcaggcgga     1740

ggtggctctg gcggtggcgg atcgcagtct gccctgactc agcctgcctc cgtgtctggg     1800

tctcctggac agtcgatcac catctcctgc actggaacca gcagtgacgt tggtttttat     1860

aactatgtct cctggtacca acagcaccca ggcaaagccc ccgaactcat gatttatgat     1920

gtcagtaatc ggccctcagg ggtttctgat cgcttctctg gctccaagtc tggcaacacg     1980

gcctccctga ccatctctgg gctccaggct gaggacgagg ctgattatta ctgcagctca     2040

tatacaagca tcagcacttg ggtgttcggc ggagggacca agctgaccgt ccta           2094


<210>  30
<211>  645
<212>  DNA
<213>  artificial sequence

<220>
<223>  light chain

<400>  30
gaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc       60

ctctcctgca gggccagtca gagtgttggc agcagctact tagcctggta ccagcagaaa      120

cctggccagg ctcccaggct cctcatctat ggtgcattca gcagggccac tggcatccca      180

gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag      240

cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcaccgtg gacgttcggc      300

caagggacca aggtggaaat caaacgtacg gtggctgcac catctgtctt catcttcccg      360

ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc      420

tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc      480

caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg      540

acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag      600

ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgt                      645


<210>  31
<211>  15
<212>  PRT
<213>  artificial sequence

<220>
<223>  Linker

<400>  31

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


