                         SEQUENCE LISTING

<110>  ҽҩ޹˾
 
<120>  żＰƱ;

<130>  P21403867C

<150>  2021101781361
<151>  2021-02-09

<150>  2021103408065
<151>  2021-03-30

<150>  202110825932X
<151>  2021-07-21

<150>  2021108259067
<151>  2021-07-21

<150>  2021108259226
<151>  2021-07-21

<160>  60    

<170>  PatentIn version 3.5

<210>  1
<211>  246
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  scFv 1D1

<400>  1

Glu Gly 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 Ile Ser Ser Tyr 
            20                  25                  30          


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


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


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


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


Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Leu Thr Gln 
    130                 135                 140                 


Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser 
145                 150                 155                 160 


Cys Arg Ala Ser Gln Ser Val Ser Ser Ile Tyr Leu Ala Trp Asn Gln 
                165                 170                 175     


Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Thr Phe Lys 
            180                 185                 190         


Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr 
        195                 200                 205             


Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro Glu Asp Phe Ala Val 
    210                 215                 220                 


Tyr Tyr Cys Gln Gln Tyr Asp Thr Ser Ser Ile Thr Phe Gly Gln Gly 
225                 230                 235                 240 


Thr Arg Leu Glu Ile Lys 
                245     


<210>  2
<211>  243
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  scFv 2E3

<400>  2

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 Tyr 
            20                  25                  30          


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


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


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


Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly 
        115                 120                 125             


Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly 
    130                 135                 140                 


Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala 
145                 150                 155                 160 


Ser Gln Arg Ile Ser Ser Ser Phe Leu Ala Trp Tyr Gln Gln Lys Pro 
                165                 170                 175     


Gly Gln Ala Pro Ser Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr 
            180                 185                 190         


Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr 
        195                 200                 205             


Leu Thr Ile Ser Ser Leu Glu Pro Glu Asp Phe Ala Val Phe Tyr Cys 
    210                 215                 220                 


Gln Gln Tyr Ser Asn Ser Pro Leu Thr Phe Gly Gly Gly Thr Lys Val 
225                 230                 235                 240 


Glu Ile Lys 
            


<210>  3
<211>  123
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  1D1-01 VH

<400>  3

Glu Gly 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 Ile Ser Ser Tyr 
            20                  25                  30          


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


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


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


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


<210>  4
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  1D1-01 chothia HCDR1

<400>  4

Gly Phe Thr Ile Ser Ser Tyr 
1               5           


<210>  5
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  1D1-01 chothia HCDR2

<400>  5

Lys Gln Asp Gly Ser Glu 
1               5       


<210>  6
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  1D1-01 chothia HCDR3

<400>  6

Arg Met Tyr Ser Ser Gly Trp Tyr Trp Gly Ala Phe Asp Met 
1               5                   10                  


<210>  7
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  1D1-01 kabat HCDR1

<400>  7

Ser Tyr Trp Met Asn 
1               5   


<210>  8
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  1D1-01 kabat HCDR2

<400>  8

Asn Ile Lys Gln Asp Gly Ser Glu Lys Tyr Tyr Val Asp Ser Val Gln 
1               5                   10                  15      


Gly 
    


<210>  9
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  1D1-01 kabat HCDR3

<400>  9

Arg Met Tyr Ser Ser Gly Trp Tyr Trp Gly Ala Phe Asp Met 
1               5                   10                  


<210>  10
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  1D1-01 IMGT HCDR1

<400>  10

Gly Phe Thr Ile Ser Ser Tyr Trp 
1               5               


<210>  11
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  1D1-01 IMGT HCDR2

<400>  11

Ile Lys Gln Asp Gly Ser Glu Lys 
1               5               


<210>  12
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  1D1-01 IMGT HCDR3

<400>  12

Ala Arg Arg Met Tyr Ser Ser Gly Trp Tyr Trp Gly Ala Phe Asp Met 
1               5                   10                  15      


<210>  13
<211>  108
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  1D1-01 VL

<400>  13

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 Ser Ser Ile 
            20                  25                  30          


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


Ile Tyr Gly Thr Phe Lys 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 Ser Leu Glu 
65                  70                  75                  80  


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


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


<210>  14
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  1D1-01 chothia LCDR1

<400>  14

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


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

<220>
<223>  1D1-01 chothia LCDR2

<400>  15

Gly Thr Phe Lys Arg Ala Thr 
1               5           


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

<220>
<223>  1D1-01 chothia LCDR3

<400>  16

Gln Gln Tyr Asp Thr Ser Ser Ile Thr 
1               5                   


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

<220>
<223>  1D1-01 kabat LCDR1

<400>  17

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


<210>  18
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  1D1-01 kabat LCDR2

<400>  18

Gly Thr Phe Lys Arg Ala Thr 
1               5           


<210>  19
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  1D1-01 kabat LCDR3

<400>  19

Gln Gln Tyr Asp Thr Ser Ser Ile Thr 
1               5                   


<210>  20
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  1D1-01 IMGT LCDR1

<400>  20

Gln Ser Val Ser Ser Ile Tyr 
1               5           


<210>  21
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  202-2-1 Kabat/IMGT LCDR3

<400>  21

Gln Gln Leu Asn Ser Tyr Pro Leu Thr 
1               5                   


<210>  22
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  1D1-01 IMGT LCDR3

<400>  22

Gln Gln Tyr Asp Thr Ser Ser Ile Thr 
1               5                   


<210>  23
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  2E3-02 VH

<400>  23

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 Tyr 
            20                  25                  30          


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


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


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


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  24
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  2E3-02 chothia HCDR1

<400>  24

Gly Phe Thr Phe Ser Ser Tyr 
1               5           


<210>  25
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  2E3-02 chothia HCDR2

<400>  25

Ser Gly Ser Gly Gly Ser 
1               5       


<210>  26
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  2E3-02 chothia HCDR3

<400>  26

Ala Arg Ser Gly Tyr Asp Tyr Phe Phe Asp Tyr 
1               5                   10      


<210>  27
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  2E3-02 kabat HCDR1

<400>  27

Ser Tyr Ala Met Asn 
1               5   


<210>  28
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  2E3-02 kabat HCDR2

<400>  28

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


Gly 
    


<210>  29
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  2E3-02 kabat HCDR3

<400>  29

Ala Arg Ser Gly Tyr Asp Tyr Phe Phe Asp Tyr 
1               5                   10      


<210>  30
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  2E3-02 IMGT HCDR1

<400>  30

Gly Phe Thr Phe Ser Ser Tyr Ala 
1               5               


<210>  31
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  2E3-02 IMGT HCDR2

<400>  31

Ile Ser Gly Ser Gly Gly Ser Thr 
1               5               


<210>  32
<211>  13
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  2E3-02 IMGT HCDR3

<400>  32

Ala Lys Ala Arg Ser Gly Tyr Asp Tyr Phe Phe Asp Tyr 
1               5                   10              


<210>  33
<211>  108
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  2E3-02 VL

<400>  33

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 Arg Ile Ser Ser Ser 
            20                  25                  30          


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


Ile Tyr Gly Ala Ser 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 Ser Leu Glu 
65                  70                  75                  80  


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


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


<210>  34
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  2E3-02 chothia LCDR1

<400>  34

Arg Ala Ser Gln Arg Ile Ser Ser Ser Phe Leu Ala 
1               5                   10          


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

<220>
<223>  2E3-02 chothia LCDR2

<400>  35

Gly Ala Ser Ser Arg Ala Thr 
1               5           


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

<220>
<223>  2E3-02 chothia LCDR3

<400>  36

Gln Gln Tyr Ser Asn Ser Pro Leu Thr 
1               5                   


<210>  37
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  2E3-02 kabat LCDR1

<400>  37

Arg Ala Ser Gln Arg Ile Ser Ser Ser Phe Leu Ala 
1               5                   10          


<210>  38
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  2E3-02 kabat LCDR2

<400>  38

Gly Ala Ser Ser Arg Ala Thr 
1               5           


<210>  39
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  2E3-02 kabat LCDR3

<400>  39

Gln Gln Tyr Ser Asn Ser Pro Leu Thr 
1               5                   


<210>  40
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  2E3-02  IMGT LCDR1

<400>  40

Gln Arg Ile Ser Ser Ser Phe 
1               5           


<210>  41
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  202-2-1 IMGT LCDR1

<400>  41

Gln Gly Ile Ser Ser Tyr 
1               5       


<210>  42
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  2E3-02 IMGT LCDR3

<400>  42

Gln Gln Tyr Ser Asn Ser Pro Leu Thr 
1               5                   


<210>  43
<211>  330
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  IgG1 CH

<400>  43

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


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


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


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


Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr 
65                  70                  75                  80  


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


Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys 
            100                 105                 110         


Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro 
        115                 120                 125             


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


Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
145                 150                 155                 160 


Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
                165                 170                 175     


Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
            180                 185                 190         


His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn 
        195                 200                 205             


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


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


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


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


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


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


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


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


<210>  44
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Kappa CL

<400>  44

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>  45
<211>  453
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  1D1-01 HC

<400>  45

Glu Gly 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 Ile Ser Ser Tyr 
            20                  25                  30          


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


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


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


Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ser Thr Lys Gly 
        115                 120                 125             


Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly 
    130                 135                 140                 


Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val 
145                 150                 155                 160 


Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe 
                165                 170                 175     


Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val 
            180                 185                 190         


Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val 
        195                 200                 205             


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


Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu 
225                 230                 235                 240 


Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
                245                 250                 255     


Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
            260                 265                 270         


Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 
        275                 280                 285             


Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 
    290                 295                 300                 


Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
305                 310                 315                 320 


Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 
                325                 330                 335     


Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
            340                 345                 350         


Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 
        355                 360                 365             


Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
    370                 375                 380                 


Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
385                 390                 395                 400 


Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 
                405                 410                 415     


Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 
            420                 425                 430         


Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
        435                 440                 445             


Leu Ser Pro Gly Lys 
    450             


<210>  46
<211>  215
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  1D1-01 LC

<400>  46

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 Ser Ser Ile 
            20                  25                  30          


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


Ile Tyr Gly Thr Phe Lys 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 Ser Leu Glu 
65                  70                  75                  80  


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


Ile Thr Phe Gly Gln Gly Thr Arg Leu 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>  47
<211>  450
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  2E3-02 HC

<400>  47

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 Tyr 
            20                  25                  30          


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


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


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


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


Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala 
    130                 135                 140                 


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


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


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


Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys 
        195                 200                 205             


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


Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly 
225                 230                 235                 240 


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


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
            260                 265                 270         


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


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg 
    290                 295                 300                 


Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys 
305                 310                 315                 320 


Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu 
                325                 330                 335     


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


Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu 
        355                 360                 365             


Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
    370                 375                 380                 


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


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


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
            420                 425                 430         


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
        435                 440                 445             


Gly Lys 
    450 


<210>  48
<211>  215
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  2E3-02 LC

<400>  48

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 Arg Ile Ser Ser Ser 
            20                  25                  30          


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


Ile Tyr Gly Ala Ser 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 Ser Leu Glu 
65                  70                  75                  80  


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


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


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


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


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


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


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


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


Ser Phe Asn Arg Gly Glu Cys 
    210                 215 


<210>  49
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  202-2-1 VH

<400>  49

Glu 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 Thr Tyr 
            20                  25                  30          


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


Ala Val Ile Trp Tyr Asp Val Ser His 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 Ser 
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 Asp Trp Gly Asp Pro Asp Ala Phe Asp Ile Trp Gly Gln Gly 
            100                 105                 110         


Thr Met Val Thr Val Ser Ser 
        115                 


<210>  50
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  202-2-1 VL

<400>  50

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


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


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


Tyr Ala Ala Ser Thr Leu Gln 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  


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


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


<210>  51
<211>  449
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  202-2-1 HC

<400>  51

Glu 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 Thr Tyr 
            20                  25                  30          


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


Ala Val Ile Trp Tyr Asp Val Ser His 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 Ser 
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 Asp Trp Gly Asp Pro Asp Ala Phe Asp Ile Trp Gly Gln Gly 
            100                 105                 110         


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


Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu 
    130                 135                 140                 


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


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


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


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


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


Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro 
225                 230                 235                 240 


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


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
            260                 265                 270         


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


Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 
    290                 295                 300                 


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


Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys 
                325                 330                 335     


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


Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr 
        355                 360                 365             


Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
    370                 375                 380                 


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


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


Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
            420                 425                 430         


Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
        435                 440                 445             


Lys 
    


<210>  52
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  202-2-1 LC

<400>  52

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


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


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


Tyr Ala Ala Ser Thr Leu Gln 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  


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


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


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


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


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


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


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


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


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  53
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  202-2-1 Kabat HCDR1

<400>  53

Thr Tyr Gly Met His 
1               5   


<210>  54
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  202-2-1 Kabat HCDR2

<400>  54

Val Ile Trp Tyr Asp Val Ser His Lys Tyr Tyr Ala Asp Ser Val Lys 
1               5                   10                  15      


Gly 
    


<210>  55
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  202-2-1 Kabat HCDR3

<400>  55

Asp Trp Gly Asp Pro Asp Ala Phe Asp Ile 
1               5                   10  


<210>  56
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  202-2-1 IMGT HCDR1

<400>  56

Gly Phe Thr Phe Ser Thr Tyr Gly 
1               5               


<210>  57
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  202-2-1 IMGT HCDR2

<400>  57

Ile Trp Tyr Asp Val Ser His Lys 
1               5               


<210>  58
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  202-2-1 IMGT HCDR3

<400>  58

Ala Arg Asp Trp Gly Asp Pro Asp Ala Phe Asp Ile 
1               5                   10          


<210>  59
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  202-2-1 Kabat LCDR1

<400>  59

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


<210>  60
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  202-2-1 Kabat LCDR2

<400>  60

Ala Ala Ser Thr Leu Gln Ser 
1               5           


