  б

<110>  Ǽݣ޹˾, Ϻ޹˾

<120>  ѪصĿԭϵ׼;

<130>  0193-PA-009

<160>  46

<170>  PatentIn version 3.5

<210>  1
<211>  15
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  HCDR3

<400>  1

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


<210>  2
<211>  10
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  HCDR2

<400>  2

Ile Arg Leu Lys Ser Asn Asn Tyr Ala Thr 
1               5                   10  


<210>  3
<211>  8
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  HCDR1

<400>  3

Gly Tyr Thr Phe Gly Asp Asn Trp 
1               5               


<210>  4
<211>  9
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  LCDR3

<400>  4

Gln Gln Tyr Tyr Arg Tyr Pro Leu Thr 
1               5                   


<210>  5
<211>  2
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  LCDR2

<400>  5

Trp Ala 
1       


<210>  6
<211>  12
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  LCDR1

<400>  6

Gln Ser Leu Leu Tyr Ser Arg Asn Gln Lys Asn Tyr 
1               5                   10          


<210>  7
<211>  25
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  m2E5 H-FR1

<400>  7

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


Ser Met Lys Leu Ser Cys Val Ala Ser 
            20                  25  


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

<220>
<223>  m2E5 H-FR2

<400>  8

Met Asn Trp Val Arg Gln Ser Pro Glu Lys Gly Leu Glu Trp Val Ala 
1               5                   10                  15      


Glu 
    


<210>  9
<211>  38
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  m2E5 H-FR3

<400>  9

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


Ser Lys Ser Ser Val Tyr Leu Gln Met Asn Asn Leu Arg Thr Glu Asp 
            20                  25                  30          


Thr Gly Ile Tyr Tyr Cys 
        35              


<210>  10
<211>  11
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  m2E5 H-FR4

<400>  10

Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser 
1               5                   10      


<210>  11
<211>  26
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  m2E5 L-FR1

<400>  11

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


Glu Lys Ile Thr Met Ser Cys Lys Ser Ser 
            20                  25      


<210>  12
<211>  17
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  m2E5 L-FR2

<400>  12

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile 
1               5                   10                  15      


Tyr 
    


<210>  13
<211>  37
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  m2E5 L-FR3

<400>  13

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


Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Val Lys Ala Glu Asp Leu 
            20                  25                  30          


Ala Val Tyr Tyr Cys 
        35          


<210>  14
<211>  10
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  m2E5 L-FR4hu2E5 L-FR4

<400>  14

Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
1               5                   10  


<210>  15
<211>  25
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  hu2E5 H-FR1

<400>  15

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 
            20                  25  


<210>  16
<211>  17
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  hu2E5 H-FR2

<400>  16

Met Asn Trp Val Arg Gln Ala Ser Gly Lys Gly Leu Glu Trp Val Gly 
1               5                   10                  15      


Glu 
    


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

<220>
<223>  hu2E5 H-FR3

<400>  17

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


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


Thr Ala Val Tyr Tyr Cys 
        35              


<210>  18
<211>  11
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  hu2E5 H-FR4

<400>  18

Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
1               5                   10      


<210>  19
<211>  26
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  hu2E5 L-FR1

<400>  19

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 
            20                  25      


<210>  20
<211>  17
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  hu2E5 L-FR2

<400>  20

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro Lys Leu Leu Ile 
1               5                   10                  15      


Tyr 
    


<210>  21
<211>  37
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  hu2E5 L-FR3

<400>  21

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


Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala Glu Asp Val 
            20                  25                  30          


Ala Val Tyr Tyr Cys 
        35          


<210>  22
<211>  124
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  m2E5 VH

<400>  22

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


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


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


Ala Glu Ile Arg Leu Lys Ser Asn Asn Tyr Ala Thr Arg Tyr Ala Glu 
    50                  55                  60                  


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


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


Tyr Cys Thr Arg Thr Gln Phe Ile Thr Ser Val Val Ala Pro Phe Asp 
            100                 105                 110         


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


<210>  23
<211>  113
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  m2E5 VL

<400>  23

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


Glu Lys Ile Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser 
            20                  25                  30          


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


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


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


Lys 
    


<210>  24
<211>  124
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  hu2E5 VH3

<400>  24

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 Tyr Thr Phe Gly Asp Asn 
            20                  25                  30          


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


Gly Glu Ile Arg Leu Lys Ser Asn Asn Tyr Ala Thr Arg Tyr Ala Glu 
    50                  55                  60                  


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


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


Tyr Cys Thr Arg Thr Gln Phe Ile Thr Ser Val Val Ala Pro Phe Asp 
            100                 105                 110         


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


<210>  25
<211>  113
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  hu2E5VL0

<400>  25

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 Tyr Ser 
            20                  25                  30          


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


Pro Pro Lys Leu Leu Ile 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 Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln 
                85                  90                  95      


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


Lys 
    


<210>  26
<211>  330
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  IgG1㶨

<400>  26

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      


Arg 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 Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys 
    130                 135                 140                 


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


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


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


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


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


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


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


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


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


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


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


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


<210>  27
<211>  107
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  Ig㶨

<400>  27

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>  28
<211>  454
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  c2E5VHCH

<400>  28

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


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


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


Ala Glu Ile Arg Leu Lys Ser Asn Asn Tyr Ala Thr Arg Tyr Ala Glu 
    50                  55                  60                  


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


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


Tyr Cys Thr Arg Thr Gln Phe Ile Thr Ser Val Val Ala Pro Phe Asp 
            100                 105                 110         


Phe Trp Gly Gln Gly Thr Thr Leu Thr Val Ser Ser Ala Ser Thr Lys 
        115                 120                 125             


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Ser Leu Ser Pro Gly Lys 
    450                 


<210>  29
<211>  220
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  c2E5VLCL

<400>  29

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


Glu Lys Ile Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser 
            20                  25                  30          


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


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


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


Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 
        115                 120                 125             


Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 
    130                 135                 140                 


Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 
145                 150                 155                 160 


Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 
                165                 170                 175     


Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 
            180                 185                 190         


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


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


<210>  30
<211>  454
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  hu2E5VH3CH

<400>  30

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 Tyr Thr Phe Gly Asp Asn 
            20                  25                  30          


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


Gly Glu Ile Arg Leu Lys Ser Asn Asn Tyr Ala Thr Arg Tyr Ala Glu 
    50                  55                  60                  


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


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


Tyr Cys Thr Arg Thr Gln Phe Ile Thr Ser Val Val Ala Pro Phe Asp 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Ser Leu Ser Pro Gly Lys 
    450                 


<210>  31
<211>  220
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  hu2E5VL0CL

<400>  31

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 Tyr Ser 
            20                  25                  30          


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


Pro Pro Lys Leu Leu Ile 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 Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln 
                85                  90                  95      


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


Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 
        115                 120                 125             


Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 
    130                 135                 140                 


Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 
145                 150                 155                 160 


Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 
                165                 170                 175     


Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr 
            180                 185                 190         


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


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


<210>  32
<211>  25
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  m2E5 H-FR1; hu2E5 H-FR1

<220>
<221>  misc_feature
<222>  (3)..(3)
<223>  Xaa = LysGln

<220>
<221>  misc_feature
<222>  (4)..(4)
<223>  Xaa = LeuVal

<220>
<221>  misc_feature
<222>  (5)..(5)
<223>  Xaa = GluVal

<220>
<221>  misc_feature
<222>  (11)..(11)
<223>  Xaa = LeuSer

<220>
<221>  misc_feature
<222>  (18)..(18)
<223>  Xaa = LeuMet

<220>
<221>  misc_feature
<222>  (23)..(23)
<223>  Xaa = AlaVal

<400>  32

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


Ser Xaa Lys Leu Ser Cys Xaa Ala Ser 
            20                  25  


<210>  33
<211>  17
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  m2E5 H-FR2; hu2E5 H-FR2

<220>
<221>  misc_feature
<222>  (7)..(7)
<223>  Xaa = AlaSer

<220>
<221>  misc_feature
<222>  (8)..(8)
<223>  Xaa = ProSer

<220>
<221>  misc_feature
<222>  (9)..(9)
<223>  Xaa = GluGly

<220>
<221>  misc_feature
<222>  (16)..(16)
<223>  Xaa = AlaGly

<400>  33

Met Asn Trp Val Arg Gln Xaa Xaa Xaa Lys Gly Leu Glu Trp Val Xaa 
1               5                   10                  15      


Glu 
    


<210>  34
<211>  38
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  m2E5 H-FR3; hu2E5 H-FR3

<220>
<221>  misc_feature
<222>  (19)..(19)
<223>  Xaa = AsnSer

<220>
<221>  misc_feature
<222>  (20)..(20)
<223>  Xaa = SerThr

<220>
<221>  misc_feature
<222>  (27)..(27)
<223>  Xaa = AsnSer

<220>
<221>  misc_feature
<222>  (29)..(29)
<223>  Xaa = LysArg

<220>
<221>  misc_feature
<222>  (34)..(34)
<223>  Xaa = AlaGly

<220>
<221>  misc_feature
<222>  (35)..(35)
<223>  Xaa = IleVal

<400>  34

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


Ser Lys Xaa Xaa Val Tyr Leu Gln Met Asn Xaa Leu Xaa Thr Glu Asp 
            20                  25                  30          


Thr Xaa Xaa Tyr Tyr Cys 
        35              


<210>  35
<211>  11
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  m2E5 H-FR4; hu2E5 H-FR4

<220>
<221>  misc_feature
<222>  (7)..(7)
<223>  Xaa = LeuVal

<400>  35

Trp Gly Gln Gly Thr Thr Xaa Thr Val Ser Ser 
1               5                   10      


<210>  36
<211>  26
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  m2E5 L-FR1; hu2E5 L-FR1

<220>
<221>  misc_feature
<222>  (5)..(5)
<223>  Xaa = SerThr

<220>
<221>  misc_feature
<222>  (9)..(9)
<223>  Xaa = AspSer

<220>
<221>  misc_feature
<222>  (12)..(12)
<223>  Xaa = AlaGly

<220>
<221>  misc_feature
<222>  (15)..(15)
<223>  Xaa = LeuVal

<220>
<221>  misc_feature
<222>  (18)..(18)
<223>  Xaa = LysArg

<220>
<221>  misc_feature
<222>  (19)..(19)
<223>  Xaa = AlaIle

<220>
<221>  misc_feature
<222>  (21)..(21)
<223>  Xaa = IleMet

<220>
<221>  misc_feature
<222>  (22)..(22)
<223>  Xaa = AsnSer

<400>  36

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


Glu Xaa Xaa Thr Xaa Xaa Cys Lys Ser Ser 
            20                  25      


<210>  37
<211>  17
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  m2E5 L-FR2; hu2E5 L-FR2

<220>
<221>  misc_feature
<222>  (11)..(11)
<223>  Xaa = ProSer

<400>  37

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Xaa Pro Lys Leu Leu Ile 
1               5                   10                  15      


Tyr 
    


<210>  38
<211>  37
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  hu2E5 L-FR3; m2E5 L-FR3

<220>
<221>  misc_feature
<222>  (12)..(12)
<223>  Xaa = SerThr

<220>
<221>  misc_feature
<222>  (27)..(27)
<223>  Xaa = LeuVal

<220>
<221>  misc_feature
<222>  (28)..(28)
<223>  Xaa = LysGln

<220>
<221>  misc_feature
<222>  (32)..(32)
<223>  Xaa = LeuVal

<400>  38

Ser Thr Arg Glu Ser Gly Val Pro Asp Arg Phe Xaa Gly Ser Gly Ser 
1               5                   10                  15      


Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Xaa Xaa Ala Glu Asp Xaa 
            20                  25                  30          


Ala Val Tyr Tyr Cys 
        35          


<210>  39
<211>  124
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  m2E5 VH; hu2E5 VH3

<220>
<221>  misc_feature
<222>  (3)..(3)
<223>  Xaa = LysGln

<220>
<221>  misc_feature
<222>  (4)..(4)
<223>  Xaa = LeuVal

<220>
<221>  misc_feature
<222>  (5)..(5)
<223>  Xaa = GluVal

<220>
<221>  misc_feature
<222>  (11)..(11)
<223>  Xaa = LeuSer

<220>
<221>  misc_feature
<222>  (18)..(18)
<223>  Xaa = LeuMet

<220>
<221>  misc_feature
<222>  (23)..(23)
<223>  Xaa = AlaVal

<220>
<221>  misc_feature
<222>  (40)..(40)
<223>  Xaa = AlaSer

<220>
<221>  misc_feature
<222>  (41)..(41)
<223>  Xaa = ProSer

<220>
<221>  misc_feature
<222>  (42)..(42)
<223>  Xaa = GluGly

<220>
<221>  misc_feature
<222>  (49)..(49)
<223>  Xaa = AlaGly

<220>
<221>  misc_feature
<222>  (79)..(79)
<223>  Xaa = AsnSer

<220>
<221>  misc_feature
<222>  (80)..(80)
<223>  Xaa = SerThr

<220>
<221>  misc_feature
<222>  (87)..(87)
<223>  Xaa = AsnSer

<220>
<221>  misc_feature
<222>  (89)..(89)
<223>  Xaa = LysArg

<220>
<221>  misc_feature
<222>  (94)..(94)
<223>  Xaa = AlaGly

<220>
<221>  misc_feature
<222>  (95)..(95)
<223>  Xaa = IleVal

<220>
<221>  misc_feature
<222>  (120)..(120)
<223>  Xaa = LeuVal

<400>  39

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


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


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


Xaa Glu Ile Arg Leu Lys Ser Asn Asn Tyr Ala Thr Arg Tyr Ala Glu 
    50                  55                  60                  


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


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


Tyr Cys Thr Arg Thr Gln Phe Ile Thr Ser Val Val Ala Pro Phe Asp 
            100                 105                 110         


Phe Trp Gly Gln Gly Thr Thr Xaa Thr Val Ser Ser 
        115                 120                 


<210>  40
<211>  113
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  m2E5 VL; hu2E5VL0

<220>
<221>  misc_feature
<222>  (5)..(5)
<223>  Xaa = SerThr

<220>
<221>  misc_feature
<222>  (9)..(9)
<223>  Xaa = AspSer

<220>
<221>  misc_feature
<222>  (12)..(12)
<223>  Xaa = AlaGly

<220>
<221>  misc_feature
<222>  (15)..(15)
<223>  Xaa = LeuVal

<220>
<221>  misc_feature
<222>  (18)..(18)
<223>  Xaa = LysArg

<220>
<221>  misc_feature
<222>  (19)..(19)
<223>  Xaa = AlaIle

<220>
<221>  misc_feature
<222>  (21)..(21)
<223>  Xaa = IleMet

<220>
<221>  misc_feature
<222>  (22)..(22)
<223>  Xaa = AsnSer

<220>
<221>  misc_feature
<222>  (49)..(49)
<223>  Xaa = ProSer

<220>
<221>  misc_feature
<222>  (69)..(69)
<223>  Xaa = SerThr

<220>
<221>  misc_feature
<222>  (84)..(84)
<223>  Xaa = LeuVal

<220>
<221>  misc_feature
<222>  (85)..(85)
<223>  Xaa = LysGln

<220>
<221>  misc_feature
<222>  (89)..(89)
<223>  Xaa = LeuVal

<400>  40

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


Glu Xaa Xaa Thr Xaa Xaa Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser 
            20                  25                  30          


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


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


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


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


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


Lys 
    


<210>  41
<211>  5
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  HCDR1 (Kabat)

<400>  41

Asp Asn Trp Met Asn 
1               5   


<210>  42
<211>  19
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  HCDR2 (Kabat)

<400>  42

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


Val Lys Gly 
            


<210>  43
<211>  6
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  HCDR3 (Kabat)

<400>  43

Thr Gln Phe Ile Thr Ser 
1               5       


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

<220>
<223>  LCDR1 (Kabat)

<400>  44

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


Ala 
    


<210>  45
<211>  7
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  LCDR2 (Kabat)

<400>  45

Trp Ala Ser Thr Arg Glu Ser 
1               5           


<210>  46
<211>  10
<212>  PRT
<213>  ˹УArtificial Sequence

<220>
<223>  HCDR1 ()

<400>  46

Gly Tyr Thr Phe Gly Asp Asn Trp Met Asn 
1               5                   10  
