                         SEQUENCE LISTING

<110>  ONCOMED PHARMACEUTICALS, INC.
       Gurney, Austin
 
<120>  RSPO1 BINDING AGENTS AND USES THEREOF

<130>  2293.125PC01

<140>  To Be Assigned
<141>  Herewith

<150>  62/037,880
<151>  2014-08-15

<160>  41    

<170>  PatentIn version 3.5

<210>  1
<211>  263
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human RSPO1 protein sequence


<220>
<221>  SIGNAL
<222>  (1)..(20)
<223>  predicted signal sequence

<400>  1

Met Arg Leu Gly Leu Cys Val Val Ala Leu Val Leu Ser Trp Thr His 
1               5                   10                  15      


Leu Thr Ile Ser Ser Arg Gly Ile Lys Gly Lys Arg Gln Arg Arg Ile 
            20                  25                  30          


Ser Ala Glu Gly Ser Gln Ala Cys Ala Lys Gly Cys Glu Leu Cys Ser 
        35                  40                  45              


Glu Val Asn Gly Cys Leu Lys Cys Ser Pro Lys Leu Phe Ile Leu Leu 
    50                  55                  60                  


Glu Arg Asn Asp Ile Arg Gln Val Gly Val Cys Leu Pro Ser Cys Pro 
65                  70                  75                  80  


Pro Gly Tyr Phe Asp Ala Arg Asn Pro Asp Met Asn Lys Cys Ile Lys 
                85                  90                  95      


Cys Lys Ile Glu His Cys Glu Ala Cys Phe Ser His Asn Phe Cys Thr 
            100                 105                 110         


Lys Cys Lys Glu Gly Leu Tyr Leu His Lys Gly Arg Cys Tyr Pro Ala 
        115                 120                 125             


Cys Pro Glu Gly Ser Ser Ala Ala Asn Gly Thr Met Glu Cys Ser Ser 
    130                 135                 140                 


Pro Ala Gln Cys Glu Met Ser Glu Trp Ser Pro Trp Gly Pro Cys Ser 
145                 150                 155                 160 


Lys Lys Gln Gln Leu Cys Gly Phe Arg Arg Gly Ser Glu Glu Arg Thr 
                165                 170                 175     


Arg Arg Val Leu His Ala Pro Val Gly Asp His Ala Ala Cys Ser Asp 
            180                 185                 190         


Thr Lys Glu Thr Arg Arg Cys Thr Val Arg Arg Val Pro Cys Pro Glu 
        195                 200                 205             


Gly Gln Lys Arg Arg Lys Gly Gly Gln Gly Arg Arg Glu Asn Ala Asn 
    210                 215                 220                 


Arg Asn Leu Ala Arg Lys Glu Ser Lys Glu Ala Gly Ala Gly Ser Arg 
225                 230                 235                 240 


Arg Arg Lys Gly Gln Gln Gln Gln Gln Gln Gln Gly Thr Val Gly Pro 
                245                 250                 255     


Leu Thr Ser Ala Gly Pro Ala 
            260             


<210>  2
<211>  52
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human RSPO1 furin-like domain 1

<400>  2

Ala Glu Gly Ser Gln Ala Cys Ala Lys Gly Cys Glu Leu Cys Ser Glu 
1               5                   10                  15      


Val Asn Gly Cys Leu Lys Cys Ser Pro Lys Leu Phe Ile Leu Leu Glu 
            20                  25                  30          


Arg Asn Asp Ile Arg Gln Val Gly Val Cys Leu Pro Ser Cys Pro Pro 
        35                  40                  45              


Gly Tyr Phe Asp 
    50          


<210>  3
<211>  45
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human RSPO1 furin-like domain 2

<400>  3

Met Asn Lys Cys Ile Lys Cys Lys Ile Glu His Cys Glu Ala Cys Phe 
1               5                   10                  15      


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


Gly Arg Cys Tyr Pro Ala Cys Pro Glu Gly Ser Ser Ala 
        35                  40                  45  


<210>  4
<211>  61
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human RSPO1 thrombospondin domain

<400>  4

Gln Cys Glu Met Ser Glu Trp Ser Pro Trp Gly Pro Cys Ser Lys Lys 
1               5                   10                  15      


Gln Gln Leu Cys Gly Phe Arg Arg Gly Ser Glu Glu Arg Thr Arg Arg 
            20                  25                  30          


Val Leu His Ala Pro Val Gly Asp His Ala Ala Cys Ser Asp Thr Lys 
        35                  40                  45              


Glu Thr Arg Arg Cys Thr Val Arg Arg Val Pro Cys Pro 
    50                  55                  60      


<210>  5
<211>  233
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human RSPO1 amino acids 31-263

<400>  5

Arg Ile Ser Ala Glu Gly Ser Gln Ala Cys Ala Lys Gly Cys Glu Leu 
1               5                   10                  15      


Cys Ser Glu Val Asn Gly Cys Leu Lys Cys Ser Pro Lys Leu Phe Ile 
            20                  25                  30          


Leu Leu Glu Arg Asn Asp Ile Arg Gln Val Gly Val Cys Leu Pro Ser 
        35                  40                  45              


Cys Pro Pro Gly Tyr Phe Asp Ala Arg Asn Pro Asp Met Asn Lys Cys 
    50                  55                  60                  


Ile Lys Cys Lys Ile Glu His Cys Glu Ala Cys Phe Ser His Asn Phe 
65                  70                  75                  80  


Cys Thr Lys Cys Lys Glu Gly Leu Tyr Leu His Lys Gly Arg Cys Tyr 
                85                  90                  95      


Pro Ala Cys Pro Glu Gly Ser Ser Ala Ala Asn Gly Thr Met Glu Cys 
            100                 105                 110         


Ser Ser Pro Ala Gln Cys Glu Met Ser Glu Trp Ser Pro Trp Gly Pro 
        115                 120                 125             


Cys Ser Lys Lys Gln Gln Leu Cys Gly Phe Arg Arg Gly Ser Glu Glu 
    130                 135                 140                 


Arg Thr Arg Arg Val Leu His Ala Pro Val Gly Asp His Ala Ala Cys 
145                 150                 155                 160 


Ser Asp Thr Lys Glu Thr Arg Arg Cys Thr Val Arg Arg Val Pro Cys 
                165                 170                 175     


Pro Glu Gly Gln Lys Arg Arg Lys Gly Gly Gln Gly Arg Arg Glu Asn 
            180                 185                 190         


Ala Asn Arg Asn Leu Ala Arg Lys Glu Ser Lys Glu Ala Gly Ala Gly 
        195                 200                 205             


Ser Arg Arg Arg Lys Gly Gln Gln Gln Gln Gln Gln Gln Gly Thr Val 
    210                 215                 220                 


Gly Pro Leu Thr Ser Ala Gly Pro Ala 
225                 230             


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

<220>
<223>  89M5 Heavy chain CDR1

<400>  6

Thr Gly Tyr Thr Met His 
1               5       


<210>  7
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  89M5 Heavy chain CDR2

<400>  7

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


Gly 
    


<210>  8
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  89M5 Heavy chain CDR3

<400>  8

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


<210>  9
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  89M5 Light chain CDR1

<400>  9

Lys Ala Ser Gln Asp Val Ile Phe Ala Val Ala 
1               5                   10      


<210>  10
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  89M5 Light chain CDR2

<400>  10

Trp Ala Ser Thr Arg His Thr 
1               5           


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

<220>
<223>  89M5 Light chain CDR3

<400>  11

Gln Gln His Tyr Ser Thr Pro Trp 
1               5               


<210>  12
<211>  121
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  89M5 Heavy chain variable region

<400>  12

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


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


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


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


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


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


Ala Arg Lys Glu Phe Ser Asp Gly Tyr Tyr Phe Phe Ala Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ala 
        115                 120     


<210>  13
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  89M5 Light chain variable region

<400>  13

Asp Ile Val Met Thr Gln Ser His Lys Phe Met Ser Thr Ser Val Gly 
1               5                   10                  15      


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


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


Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Thr Gly 
    50                  55                  60                  


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


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


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


<210>  14
<211>  464
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  89M5 Heavy chain amino acid sequence


<220>
<221>  SIGNAL
<222>  (1)..(19)
<223>  predicted signal sequence

<400>  14

Met Gly Trp Ser Trp Ile Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly 
1               5                   10                  15      


Val Leu Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys 
            20                  25                  30          


Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Thr Ser Gly Tyr Thr Phe 
        35                  40                  45              


Thr Gly Tyr Thr Met His Trp Val Arg Gln Ser His Gly Lys Thr Leu 
    50                  55                  60                  


Glu Trp Ile Gly Gly Ile Asn Pro Asn Asn Gly Gly Thr Thr Tyr Asn 
65                  70                  75                  80  


Gln Asn Phe Lys Gly Lys Ala Thr Leu Thr Val Glu Lys Ser Ser Thr 
                85                  90                  95      


Thr Ala Tyr Leu Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala Leu 
            100                 105                 110         


Tyr Tyr Cys Ala Arg Lys Glu Phe Ser Asp Gly Tyr Tyr Phe Phe Ala 
        115                 120                 125             


Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Lys Thr Thr 
    130                 135                 140                 


Pro Pro Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn 
145                 150                 155                 160 


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


Val Thr Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr 
            180                 185                 190         


Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val 
        195                 200                 205             


Thr Val Pro Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val 
    210                 215                 220                 


Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg 
225                 230                 235                 240 


Asp Cys Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser 
                245                 250                 255     


Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu 
            260                 265                 270         


Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro 
        275                 280                 285             


Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala 
    290                 295                 300                 


Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val 
305                 310                 315                 320 


Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe 
                325                 330                 335     


Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr 
            340                 345                 350         


Ile Ser Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile 
        355                 360                 365             


Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys 
    370                 375                 380                 


Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp 
385                 390                 395                 400 


Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp 
                405                 410                 415     


Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser 
            420                 425                 430         


Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly 
        435                 440                 445             


Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys 
    450                 455                 460                 


<210>  15
<211>  445
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  89M5 Heavy chain amino acid sequence without predicted signal 
       sequence

<400>  15

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


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


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


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


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


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


Ala Arg Lys Glu Phe Ser Asp Gly Tyr Tyr Phe Phe Ala Tyr Trp Gly 
            100                 105                 110         


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


Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met Val 
    130                 135                 140                 


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


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


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


Ser Ser Thr Trp Pro Ser Glu Thr Val Thr Cys Asn Val Ala His Pro 
        195                 200                 205             


Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys Gly 
    210                 215                 220                 


Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe Ile 
225                 230                 235                 240 


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


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


Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr Gln 
        275                 280                 285             


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


Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg 
305                 310                 315                 320 


Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys 
                325                 330                 335     


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


Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile Thr 
        355                 360                 365             


Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly Gln 
    370                 375                 380                 


Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp Thr Asp Gly 
385                 390                 395                 400 


Ser Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp Glu 
                405                 410                 415     


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


His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys 
        435                 440                 445 


<210>  16
<211>  238
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  89M5 Light chain amino acid sequence


<220>
<221>  SIGNAL
<222>  (1)..(24)
<223>  predicted signal sequence

<400>  16

Met Gly Phe Lys Met Glu Ser Gln Ile Gln Ala Phe Val Phe Val Phe 
1               5                   10                  15      


Leu Trp Leu Ser Gly Val Asp Gly Asp Ile Val Met Thr Gln Ser His 
            20                  25                  30          


Lys Phe Met Ser Thr Ser Val Gly Asp Arg Val Asn Ile Thr Cys Lys 
        35                  40                  45              


Ala Ser Gln Asp Val Ile Phe Ala Val Ala Trp Tyr Gln Gln Lys Pro 
    50                  55                  60                  


Gly Gln Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg His Thr 
65                  70                  75                  80  


Gly Val Pro Asp Arg Phe Thr Gly Ser Val Ser Gly Thr Asp Tyr Thr 
                85                  90                  95      


Leu Thr Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Leu Tyr Tyr Cys 
            100                 105                 110         


Gln Gln His Tyr Ser Thr Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu 
        115                 120                 125             


Glu Ile Lys Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro 
    130                 135                 140                 


Ser Ser Glu Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu 
145                 150                 155                 160 


Asn Asn Phe Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly 
                165                 170                 175     


Ser Glu Arg Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser 
            180                 185                 190         


Lys Asp Ser Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp 
        195                 200                 205             


Glu Tyr Glu Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr 
    210                 215                 220                 


Ser Thr Ser Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys 
225                 230                 235             


<210>  17
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  89M5 Light chain amino acid sequence without predicted signal 
       sequence

<400>  17

Asp Ile Val Met Thr Gln Ser His Lys Phe Met Ser Thr Ser Val Gly 
1               5                   10                  15      


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


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


Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Thr Gly 
    50                  55                  60                  


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


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


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


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


Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile 
    130                 135                 140                 


Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu 
145                 150                 155                 160 


Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser 
                165                 170                 175     


Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr 
            180                 185                 190         


Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser 
        195                 200                 205             


Phe Asn Arg Asn Glu Cys 
    210                 


<210>  18
<211>  363
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  89M5 Heavy chain variable region nucleotide sequence

<400>  18
gaggtccagc tgcaacagtc tggacctgag ctggtgaagc ctggggcttc agtgaagata       60

tcctgcaaga cttctggata cacattcact ggatacacca tgcactgggt gaggcagagc      120

catggaaaga cccttgagtg gattggaggt attaatccta acaatggtgg tactacttac      180

aaccagaact tcaagggcaa ggccacattg actgtagaga agtcctccac cacagcctac      240

ttggagctcc gcagcctgac atctgaggat tctgcactct attactgtgc aagaaaggag      300

ttctctgatg gttactactt ttttgcttac tggggccaag ggactctggt cactgtctct      360

gca                                                                    363


<210>  19
<211>  321
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  89M5 Light chain variable region nucleotide sequence

<400>  19
gacattgtga tgacccagtc tcacaaattc atgtccacat cagtgggaga cagggtcaac       60

atcacctgca aggccagtca ggatgtgatt tttgctgtag cctggtatca acagaaacca      120

ggacaatctc ctaaactact gatttactgg gcatccaccc ggcacactgg agtccctgat      180

cgcttcacag gcagtgtatc tgggacagat tatactctca ccatcagcag tgtgcaggct      240

gaagacctgg cactttatta ctgtcagcaa cattatagca ctccgtggac gttcggtgga      300

ggcaccaagc tggaaatcaa a                                                321


<210>  20
<211>  1398
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  89M5 Heavy chain nucleotide sequence

<400>  20
atgggatgga gctggatctt tctctttctc ctgtcaggaa ctgcaggtgt cctctctgag       60

gtccagctgc aacagtctgg acctgagctg gtgaagcctg gggcttcagt gaagatatcc      120

tgcaagactt ctggatacac attcactgga tacaccatgc actgggtgag gcagagccat      180

ggaaagaccc ttgagtggat tggaggtatt aatcctaaca atggtggtac tacttacaac      240

cagaacttca agggcaaggc cacattgact gtagagaagt cctccaccac agcctacttg      300

gagctccgca gcctgacatc tgaggattct gcactctatt actgtgcaag aaaggagttc      360

tctgatggtt actacttttt tgcttactgg ggccaaggga ctctggtcac tgtctcttca      420

gccaaaacga cacccccatc tgtctatcca ctggcccctg gatctgctgc ccaaactaac      480

tccatggtga ccctgggatg cctggtcaag ggctatttcc ctgagccagt gacagtgacc      540

tggaactctg gatccctgtc cagcggtgtg cacaccttcc cagctgtcct gcagtctgac      600

ctctacactc tgagcagctc agtgactgtc ccctccagca cctggcccag cgagaccgtc      660

acctgcaacg ttgcccaccc ggccagcagc accaaggtgg acaagaaaat tgtgcccagg      720

gattgtggtt gtaagccttg catatgtaca gtcccagaag tatcatctgt cttcatcttc      780

cccccaaagc ccaaggatgt gctcaccatt actctgactc ctaaggtcac gtgtgttgtg      840

gtagacatca gcaaggatga tcccgaggtc cagttcagct ggtttgtaga tgatgtggag      900

gtgcacacag ctcagacgca accccgggag gagcagttca acagcacttt ccgctcagtc      960

agtgaacttc ccatcatgca ccaggactgg ctcaatggca aggagttcaa atgcagggtc     1020

aacagtgcag ctttccctgc ccccatcgag aaaaccatct ccaaaaccaa aggcagaccg     1080

aaggctccac aggtgtacac cattccacct cccaaggagc agatggccaa ggataaagtc     1140

agtctgacct gcatgataac agacttcttc cctgaagaca ttactgtgga gtggcagtgg     1200

aatgggcagc cagcggagaa ctacaagaac actcagccca tcatggacac agatggctct     1260

tacttcgtct acagcaagct caatgtgcag aagagcaact gggaggcagg aaatactttc     1320

acctgctctg tgttacatga gggcctgcac aaccaccata ctgagaagag cctctcccac     1380

tctcctggta aatgataa                                                   1398


<210>  21
<211>  720
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  89M5 Light chain nucleotide sequence

<400>  21
atgggcttca agatggagtc acagattcag gcatttgtat tcgtgtttct ctggttgtct       60

ggtgttgacg gagacattgt gatgacccag tctcacaaat tcatgtccac atcagtggga      120

gacagggtca acatcacctg caaggccagt caggatgtga tttttgctgt agcctggtat      180

caacagaaac caggacaatc tcctaaacta ctgatttact gggcatccac ccggcacact      240

ggagtccctg atcgcttcac aggcagtgta tctgggacag attatactct caccatcagc      300

agtgtgcagg ctgaagacct ggcactttat tactgtcagc aacattatag cactccgtgg      360

acgttcggtg gaggcaccaa gctggaaatc aaacgggctg atgctgcacc aactgtatcc      420

atcttcccac catccagtga gcagttaaca tctggaggtg cctcagtcgt gtgcttcttg      480

aacaacttct accccaaaga catcaatgtc aagtggaaga ttgatggcag tgaacgacaa      540

aatggcgtcc tgaacagttg gactgatcag gacagcaaag acagcaccta cagcatgagc      600

agcaccctca cgttgaccaa ggacgagtat gaacgacata acagctatac ctgtgaggcc      660

actcacaaga catcaacttc acccattgtc aagagcttca acaggaatga gtgttagtga      720


<210>  22
<211>  121
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized h89M5-H2L2  Heavy chain variable region amino acid 
       sequence

<400>  22

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


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


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


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


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


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


Ala Arg Lys Glu Phe Ser Asp Gly Tyr Tyr Phe Phe Ala Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


<210>  23
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  h89M5-H2L2  Light chain variable region amino acid sequence

<400>  23

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


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


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


Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


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


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


<210>  24
<211>  466
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  h89M5-H2L2  Heavy chain amino acid sequence


<220>
<221>  SIGNAL
<222>  (1)..(19)
<223>  predicted signal sequence

<400>  24

Met Asp Trp Thr Trp Arg Ile Leu Phe Leu Val Ala Ala Ala Thr Gly 
1               5                   10                  15      


Ala His Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys 
            20                  25                  30          


Pro Gly Ala Ser Val Lys Val Ser Cys Lys Thr Ser Gly Tyr Thr Phe 
        35                  40                  45              


Thr Gly Tyr Thr Met His Trp Val Arg Gln Ala Pro Gly Gln Arg Leu 
    50                  55                  60                  


Glu Trp Met Gly Gly Ile Asn Pro Asn Asn Gly Gly Thr Thr Tyr Asn 
65                  70                  75                  80  


Gln Asn Phe Lys Gly Arg Val Thr Ile Thr Arg Asp Thr Ser Ala Ser 
                85                  90                  95      


Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val 
            100                 105                 110         


Tyr Tyr Cys Ala Arg Lys Glu Phe Ser Asp Gly Tyr Tyr Phe Phe Ala 
        115                 120                 125             


Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys 
    130                 135                 140                 


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


Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro 
                165                 170                 175     


Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr 
            180                 185                 190         


Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val 
        195                 200                 205             


Val Thr Val Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn 
    210                 215                 220                 


Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg 
225                 230                 235                 240 


Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly 
                245                 250                 255     


Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile 
            260                 265                 270         


Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu 
        275                 280                 285             


Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His 
    290                 295                 300                 


Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg 
305                 310                 315                 320 


Val Val Ser Val Leu Thr Val Val His Gln Asp Trp Leu Asn Gly Lys 
                325                 330                 335     


Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu 
            340                 345                 350         


Lys Thr Ile Ser Lys Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr 
        355                 360                 365             


Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu 
    370                 375                 380                 


Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp 
385                 390                 395                 400 


Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met 
                405                 410                 415     


Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp 
            420                 425                 430         


Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His 
        435                 440                 445             


Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro 
    450                 455                 460                 


Gly Lys 
465     


<210>  25
<211>  447
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  h89M5-H2L2  Heavy chain amino acid sequence without predicted 
       signal sequence

<400>  25

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


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


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


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


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


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


Ala Arg Lys Glu Phe Ser Asp Gly Tyr Tyr Phe Phe Ala Tyr Trp Gly 
            100                 105                 110         


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


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


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


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


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


Pro Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His 
        195                 200                 205             


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  26
<211>  236
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  h89M5-H2L2  Light chain amino acid sequence


<220>
<221>  SIGNAL
<222>  (1)..(22)
<223>  predicted signal sequence

<400>  26

Met Asp Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Trp 
1               5                   10                  15      


Leu Arg Gly Ala Arg Cys Asp Ile Gln Met Thr Gln Ser Pro Ser Ser 
            20                  25                  30          


Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser 
        35                  40                  45              


Gln Asp Val Ile Phe Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys 
    50                  55                  60                  


Ala Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val 
65                  70                  75                  80  


Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr 
                85                  90                  95      


Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln 
            100                 105                 110         


His Tyr Ser Thr Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile 
        115                 120                 125             


Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp 
    130                 135                 140                 


Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn 
145                 150                 155                 160 


Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu 
                165                 170                 175     


Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp 
            180                 185                 190         


Ser Thr Tyr Ser Leu Ser Asn Thr Leu Thr Leu Ser Lys Ala Asp Tyr 
        195                 200                 205             


Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser 
    210                 215                 220                 


Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
225                 230                 235     


<210>  27
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  h89M5-H2L2  Light chain amino acid sequence without predicted 
       signal sequence

<400>  27

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


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


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


Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Tyr Ser Thr Pro Trp 
                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     


Asn 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>  28
<211>  363
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  h89M5-H2L2  Heavy chain variable region nucleotide sequence

<400>  28
caggtccagc tcgtgcagtc tggggctgag gtgaagaagc ctggggcctc tgtgaaggtt       60

tcctgcaaga cttctggata caccttcact ggatacacca tgcactgggt tagacaggcc      120

cccggacaaa ggctggagtg gatgggaggt attaatccta acaatggtgg tactacttac      180

aaccagaact tcaagggcag agtcaccatt accagggaca catccgcaag cacagcctac      240

atggagctgt ccagcctgag atctgaagac acagctgtgt attactgtgc aagaaaggag      300

ttctctgatg gatactactt ttttgcttac tggggccaag ggaccctggt caccgtcagc      360

tca                                                                    363


<210>  29
<211>  321
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  h89M5-H2L2  Light chain variable region nucleotide sequence

<400>  29
gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtcggaga cagagtcacc       60

atcacttgca aggcctccca ggatgtgatt tttgctgttg cctggtatca gcagaaacca      120

gggaaagccc ctaagctcct gatctattgg gcatccaccc ggcacactgg ggtcccatca      180

aggttcagtg gcagtggatc tgggacagat tacactctca ccatcagcag tctgcaacct      240

gaagattttg caacttacta ctgtcagcaa cattatagca ctccttggac tttcggcgga      300

gggaccaagg tggagatcaa a                                                321


<210>  30
<211>  1401
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  h89M5-H2L2  Heavy chain nucleotide sequence

<400>  30
atggactgga cctggaggat actctttctc gtggcagcag ccacaggagc ccactcccag       60

gtccagctcg tgcagtctgg ggctgaggtg aagaagcctg gggcctctgt gaaggtttcc      120

tgcaagactt ctggatacac cttcactgga tacaccatgc actgggttag acaggccccc      180

ggacaaaggc tggagtggat gggaggtatt aatcctaaca atggtggtac tacttacaac      240

cagaacttca agggcagagt caccattacc agggacacat ccgcaagcac agcctacatg      300

gagctgtcca gcctgagatc tgaagacaca gctgtgtatt actgtgcaag aaaggagttc      360

tctgatggat actacttttt tgcttactgg ggccaaggga ccctggtcac cgtcagctca      420

gccagcacaa agggccctag cgtcttccct ctggctccct gcagcaggag caccagcgag      480

agcacagccg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg      540

tggaactcag gcgctctgac cagcggcgtg cacaccttcc cagctgtcct acagtcctca      600

ggactctact ccctcagcag cgtggtgacc gtgccctcca gcaacttcgg cacccagacc      660

tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagac agttgagcgc      720

aaatgttgtg tcgagtgccc accgtgccca gcaccacctg tggcaggacc gtcagtcttc      780

ctcttccccc caaaacccaa ggacaccctc atgatctccc ggacccctga ggtcacgtgc      840

gtggtggtgg acgtgagcca cgaagacccc gaggtccagt tcaactggta cgtggacggc      900

gtggaggtgc ataatgccaa gacaaagcca cgggaggagc agttcaacag cacgttccgt      960

gtggtcagcg tcctcaccgt tgtgcaccag gactggctga acggcaagga gtacaagtgc     1020

aaggtctcca acaaaggcct cccagccccc atcgagaaaa ccatctccaa aaccaaaggg     1080

cagccccgag aaccacaggt gtacaccctg cccccatccc gggaggagat gaccaagaac     1140

caggtcagcc tgacctgcct ggtcaaaggc ttctacccca gcgacatcgc cgtggagtgg     1200

gagagcaatg ggcagccgga gaacaactac aagaccacac ctcccatgct ggactccgac     1260

ggctccttct tcctctacag caagctcacc gtggacaaga gcaggtggca gcaggggaac     1320

gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacgca gaagagcctc     1380

tccctgtctc cgggtaaatg a                                               1401


<210>  31
<211>  711
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  h89M5-H2L2  Light chain nucleotide sequence

<400>  31
atggacatga gggtccccgc acagctcctg gggctcctgc tcctctggct ccggggtgcc       60

agatgtgaca tccagatgac ccagtctcca tcctccctgt ctgcatctgt cggagacaga      120

gtcaccatca cttgcaaggc ctcccaggat gtgatttttg ctgttgcctg gtatcagcag      180

aaaccaggga aagcccctaa gctcctgatc tattgggcat ccacccggca cactggggtc      240

ccatcaaggt tcagtggcag tggatctggg acagattaca ctctcaccat cagcagtctg      300

caacctgaag attttgcaac ttactactgt cagcaacatt atagcactcc ttggactttc      360

ggcggaggga ccaaggtgga gatcaaacgg actgtggctg caccatctgt cttcatcttc      420

cctccatctg atgagcagtt gaaatctgga actgcctctg ttgtgtgcct gctgaataac      480

ttctatccca gagaggccaa agtccagtgg aaggtggata acgccctcca atccggtaac      540

tcccaggaga gtgtcacaga gcaggacagc aaggacagca cctacagcct cagcaacacc      600

ctgacactga gcaaagcaga ctacgagaaa cacaaagtct acgcctgcga agtcacccat      660

cagggcctga gctcccccgt cacaaagagc ttcaacaggg gagagtgcta a               711


<210>  32
<211>  121
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  h89M5-H8L5  Heavy chain variable region amino acid sequence

<400>  32

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


Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Gly Tyr 
            20                  25                  30          


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


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


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


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


Ala Arg Lys Glu Phe Ser Asp Gly Tyr Tyr Phe Phe Ala Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


<210>  33
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  h89M5-H8L5  Light chain variable region amino acid sequence

<400>  33

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 Ala Ser Gln Asp Val Ile Phe Ala 
            20                  25                  30          


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


Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala 
65                  70                  75                  80  


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


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


<210>  34
<211>  470
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  h89M5-H8L5  Heavy chain amino acid sequence


<220>
<221>  SIGNAL
<222>  (1)..(19)
<223>  predicted signal sequence

<400>  34

Met Asp Trp Thr Trp Arg Ile Leu Phe Leu Val Ala Ala Ala Thr Gly 
1               5                   10                  15      


Ala His Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys 
            20                  25                  30          


Pro Gly Glu Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe 
        35                  40                  45              


Thr Gly Tyr Thr Met His Trp Val Arg Gln Met Pro Gly Lys Gly Leu 
    50                  55                  60                  


Glu Trp Met Gly Gly Ile Asn Pro Asn Asn Gly Gly Thr Thr Tyr Asn 
65                  70                  75                  80  


Gln Asn Phe Lys Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser 
                85                  90                  95      


Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met 
            100                 105                 110         


Tyr Tyr Cys Ala Arg Lys Glu Phe Ser Asp Gly Tyr Tyr Phe Phe Ala 
        115                 120                 125             


Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys 
    130                 135                 140                 


Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly 
145                 150                 155                 160 


Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro 
                165                 170                 175     


Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr 
            180                 185                 190         


Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val 
        195                 200                 205             


Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn 
    210                 215                 220                 


Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro 
225                 230                 235                 240 


Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu 
                245                 250                 255     


Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp 
            260                 265                 270         


Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
        275                 280                 285             


Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly 
    290                 295                 300                 


Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn 
305                 310                 315                 320 


Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp 
                325                 330                 335     


Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro 
            340                 345                 350         


Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu 
        355                 360                 365             


Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn 
    370                 375                 380                 


Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
385                 390                 395                 400 


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
                405                 410                 415     


Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys 
            420                 425                 430         


Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys 
        435                 440                 445             


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
    450                 455                 460                 


Ser Leu Ser Pro Gly Lys 
465                 470 


<210>  35
<211>  451
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  h89M5-H8L5  Heavy chain amino acid sequence without predicted 
       signal sequence

<400>  35

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


Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Gly Tyr 
            20                  25                  30          


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


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


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


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


Ala Arg Lys Glu Phe Ser Asp Gly Tyr Tyr Phe Phe Ala Tyr Trp Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Pro Gly Lys 
    450     


<210>  36
<211>  234
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  h89M5-H8L5  Light chain amino acid sequence


<220>
<221>  SIGNAL
<222>  (1)..(20)
<223>  predicted signal sequence

<400>  36

Met Val Leu Gln Thr Gln Val Phe Ile Ser Leu Leu Leu Trp Ile Ser 
1               5                   10                  15      


Gly Ala Tyr Gly Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala 
            20                  25                  30          


Val Ser Leu Gly Glu Arg Ala Thr Ile Asn Cys Lys Ala Ser Gln Asp 
        35                  40                  45              


Val Ile Phe Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro 
    50                  55                  60                  


Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp 
65                  70                  75                  80  


Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser 
                85                  90                  95      


Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln His Tyr 
            100                 105                 110         


Ser Thr Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg 
        115                 120                 125             


Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 
    130                 135                 140                 


Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 
145                 150                 155                 160 


Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 
                165                 170                 175     


Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 
            180                 185                 190         


Tyr Ser Leu Ser Asn Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 
        195                 200                 205             


His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 
    210                 215                 220                 


Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
225                 230                 


<210>  37
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  h89M5-H8L5  Light chain amino acid sequence without predicted 
       signal sequence

<400>  37

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 Ala Ser Gln Asp Val Ile Phe Ala 
            20                  25                  30          


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


Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Ser Gly 
    50                  55                  60                  


Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Ala 
65                  70                  75                  80  


Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln His Tyr Ser Thr Pro Trp 
                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     


Asn 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>  38
<211>  363
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  h89M5-H8L5  Heavy chain variable region nucleotide sequence

<400>  38
gaagtgcagc tggtgcagtc tggagcagag gtcaaaaagc ccggggagtc tctgaggatc       60

tcctgcaagg gttctggata cagctttact ggatacacca tgcactgggt gcgccagatg      120

cccgggaaag gactggagtg gatggggggt attaatccta acaatggtgg tactacttac      180

aaccagaact tcaagggcca cgtcaccatc tcagctgaca agtccatcag cactgcctac      240

ctgcaatgga gcagcctgaa ggcttctgac accgccatgt attactgtgc aagaaaggag      300

ttctctgatg gatactactt ttttgcttac tggggccaag ggaccctggt gaccgtcagc      360

tca                                                                    363


<210>  39
<211>  321
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  h89M5-H8L5  Light chain variable region nucleotide sequence

<400>  39
gacatcgtga tgacccagtc tccagactcc ctggctgtgt ctctgggcga gagggccacc       60

atcaactgca aggcttccca ggacgtgatt tttgctgttg cctggtatca gcagaaacca      120

ggacagcctc ctaagctgct catttactgg gcatctaccc gccacactgg ggtccctgac      180

cgcttcagtg gcagcgggtc tgggacagat ttcactctca ccatcagcag cctccaggct      240

gaagatgtgg cagtttatta ctgtcagcaa cattatagca ctccttggac tttcggcgga      300

gggaccaagg tggagatcaa a                                                321


<210>  40
<211>  1413
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  h89M5-H8L5  Heavy chain nucleotide sequence

<400>  40
atggactgga cctggaggat actctttctc gtggcggcag ccacaggagc ccactccgaa       60

gtgcagctgg tgcagtctgg agcagaggtc aaaaagcccg gggagtctct gaggatctcc      120

tgcaagggtt ctggatacag ctttactgga tacaccatgc actgggtgcg ccagatgccc      180

gggaaaggac tggagtggat ggggggtatt aatcctaaca atggtggtac tacttacaac      240

cagaacttca agggccacgt caccatctca gctgacaagt ccatcagcac tgcctacctg      300

caatggagca gcctgaaggc ttctgacacc gccatgtatt actgtgcaag aaaggagttc      360

tctgatggat actacttttt tgcttactgg ggccaaggga ccctggtgac cgtcagctca      420

gccagcacaa agggcccctc cgtgttccct ctggcccctt cctccaagtc cacctccggc      480

ggcaccgccg ctctgggctg cctggtgaag gactacttcc ctgagcctgt gaccgtgtcc      540

tggaactctg gcgcactgac ctctggcgtg cacaccttcc cagccgtgct ccagtcctcc      600

ggcctgtact ccctgtcctc cgtcgtcacc gtgccttcct cctccctggg cacccagacc      660

tacatctgca acgtgaacca caagccttcc aacacaaagg tggacaagcg ggtggagcct      720

aagtcctgcg acaagaccca cacctgccct ccctgccctg cccctgagct gctgggcgga      780

ccttccgtgt tcctgttccc tcctaagcct aaggacaccc tgatgatctc ccggacccct      840

gaagtgacat gcgtggtggt ggacgtgtcc cacgaggacc ctgaggtgaa gttcaactgg      900

tatgtggacg gcgtggaggt gcacaacgct aagaccaagc cgagggagga gcagtacaac      960

tccacctacc gggtggtgtc tgtgctgacc gtgctgcacc aggactggct gaacggcaaa     1020

gaatacaagt gcaaggtctc caacaaggcc ctgcccgctc ccatcgagaa aaccatcagc     1080

aaggcaaagg gccagcctcg cgagcctcag gtgtacaccc tgccacccag ccgggaggag     1140

atgaccaaga accaggtgtc cctgacctgt ctggtgaagg gcttttaccc ttccgatatt     1200

gccgtggagt gggagtctaa cggccagccc gagaacaact acaagaccac ccctcctgtg     1260

ctggactccg acggctcctt cttcctgtac tccaagctga ccgtggacaa gtcccggtgg     1320

cagcagggca acgtgttctc ctgctccgtg atgcacgagg ccctgcacaa ccactacacc     1380

cagaagagcc tgtctctgtc tcctggcaag tga                                  1413


<210>  41
<211>  705
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  h89M5-H8L5  Light chain nucleotide sequence

<400>  41
atggtgctcc agacccaggt cttcatttct ctgctcctct ggatctctgg tgcctacggg       60

gacatcgtga tgacccagtc tccagactcc ctggctgtgt ctctgggcga gagggccacc      120

atcaactgca aggcttccca ggacgtgatt tttgctgttg cctggtatca gcagaaacca      180

ggacagcctc ctaagctgct catttactgg gcatctaccc gccacactgg ggtccctgac      240

cgcttcagtg gcagcgggtc tgggacagat ttcactctca ccatcagcag cctccaggct      300

gaagatgtgg cagtttatta ctgtcagcaa cattatagca ctccttggac tttcggcgga      360

gggaccaagg tggagatcaa acggactgtg gctgcaccat ctgtcttcat cttccctcca      420

tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat      480

cccagagagg ccaaagtcca gtggaaggtg gataacgccc tccaatccgg taactcccag      540

gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcaa caccctgaca      600

ctgagcaaag cagactacga gaaacacaaa gtctatgcct gcgaagtcac ccatcagggc      660

ctgtcttccc ccgtcacaaa gagcttcaac aggggagagt gctaa                      705


