                         SEQUENCE LISTING

<110>  OncoMed Pharmaceuticals, Inc.
       Dupont, Jakob
 
<120>  Treatment of Gastric Cancer

<130>  2293.119PC01/PAC/MIG/BMB

<140>  PCT/US2015/024251
<141>  2015-04-03

<150>  US 61/975,302
<151>  2014-04-04

<160>  80    

<170>  PatentIn version 3.5

<210>  1
<211>  464
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  21M18 Heavy chain with signal sequence


<220>
<221>  SIGNAL
<222>  (1)..(19)

<400>  1

Met Lys His Leu Trp Phe Phe Leu Leu Leu Val Ala Ala Pro Arg Trp 
1               5                   10                  15      


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


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


Thr Ala Tyr Tyr Ile His Trp Val Lys Gln Ala Pro Gly Gln Gly Leu 
    50                  55                  60                  


Glu Trp Ile Gly Tyr Ile Ser Ser Tyr Asn Gly Ala Thr Asn Tyr Asn 
65                  70                  75                  80  


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


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


Tyr Tyr Cys Ala Arg Asp Tyr Asp Tyr Asp Val Gly Met Asp Tyr Trp 
        115                 120                 125             


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


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


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


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


Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
        195                 200                 205             


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  2
<211>  464
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  21R79 Heavy chain with signal sequence


<220>
<221>  SIGNAL
<222>  (1)..(19)

<400>  2

Met Lys His Leu Trp Phe Phe Leu Leu Leu Val Ala Ala Pro Arg Trp 
1               5                   10                  15      


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


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


Thr Ala Tyr Tyr Ile His Trp Val Lys Gln Ala Pro Gly Gln Gly Leu 
    50                  55                  60                  


Glu Trp Ile Gly Tyr Ile Ala Asn Tyr Asn Arg Ala Thr Asn Tyr Asn 
65                  70                  75                  80  


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


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


Tyr Tyr Cys Ala Arg Asp Tyr Asp Tyr Asp Val Gly Met Asp Tyr Trp 
        115                 120                 125             


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


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


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


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


Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
        195                 200                 205             


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  3
<211>  466
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  219R45 Heavy chain with signal sequence


<220>
<221>  SIGNAL
<222>  (1)..(19)

<400>  3

Met Lys His Leu Trp Phe Phe Leu Leu Leu Val Ala Ala Pro Arg Trp 
1               5                   10                  15      


Val Leu 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 Ala Ser Gly Tyr Thr Phe 
        35                  40                  45              


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


Glu Trp Met Gly Asp Ile Asn Pro Ser Asn Gly Arg Thr Ser Tyr Lys 
65                  70                  75                  80  


Glu Lys Phe Lys Arg Arg Val Thr Leu Ser Val Asp Lys Ser Ser Ser 
                85                  90                  95      


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


Tyr Phe Cys Thr Ile His Tyr Asp Asp Lys Tyr Tyr Pro Leu Met Asp 
        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 Lys 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 Lys 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>  4
<211>  238
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Light chain with signal sequence


<220>
<221>  SIGNAL
<222>  (1)..(20)

<400>  4

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 Ser Cys Arg Ala Ser Glu Ser 
        35                  40                  45              


Val Asp Asn Tyr Gly Ile Ser Phe Met Lys Trp Phe Gln Gln Lys Pro 
    50                  55                  60                  


Gly Gln Pro Pro Lys Leu Leu Ile Tyr Ala Ala Ser Asn Gln Gly Ser 
65                  70                  75                  80  


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


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


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


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


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


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


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


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


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


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


<210>  5
<211>  445
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  21M18 Heavy chain without predicted signal sequence

<400>  5

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


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


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


Gly Tyr Ile Ser Ser Tyr Asn Gly Ala Thr Asn Tyr Asn Gln Lys Phe 
    50                  55                  60                  


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


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


Ala Arg Asp Tyr Asp Tyr Asp Val Gly Met Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  6
<211>  445
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  21R79 Heavy chain without predicted signal sequence

<400>  6

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


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


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


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


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


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


Ala Arg Asp Tyr Asp Tyr Asp Val Gly Met Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  7
<211>  447
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  219R45 Heavy chain without predicted signal sequence

<400>  7

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


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


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


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


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


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


Thr Ile His Tyr Asp Asp Lys Tyr Tyr Pro Leu Met Asp 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 Lys 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 Lys 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>  8
<211>  217
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Light chain without predicted signal sequence

<400>  8

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 Ser Cys Arg Ala Ser Glu Ser Val Asp Asn Tyr 
            20                  25                  30          


Gly Ile Ser Phe Met Lys Trp Phe Gln Gln Lys Pro Gly Gln Pro Pro 
        35                  40                  45              


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


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


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


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


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


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


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


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


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


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


Thr Lys Ser Phe Asn Arg Gly Glu Cys 
    210                 215         


<210>  9
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  21M18 Heavy chain variable region

<400>  9

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


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


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


Gly Tyr Ile Ser Ser Tyr Asn Gly Ala Thr Asn Tyr Asn Gln Lys Phe 
    50                  55                  60                  


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


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


Ala Arg Asp Tyr Asp Tyr Asp Val Gly Met Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  10
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  21R79 Heavy chain variable region

<400>  10

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


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


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


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


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


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


Ala Arg Asp Tyr Asp Tyr Asp Val Gly Met Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  11
<211>  121
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  219R45 Heavy chain variable region

<400>  11

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


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


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


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


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


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


Thr Ile His Tyr Asp Asp Lys Tyr Tyr Pro Leu Met Asp Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


<210>  12
<211>  111
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Light chain variable region

<400>  12

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 Ser Cys Arg Ala Ser Glu Ser Val Asp Asn Tyr 
            20                  25                  30          


Gly Ile Ser Phe Met Lys Trp Phe Gln Gln Lys Pro Gly Gln Pro Pro 
        35                  40                  45              


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


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


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


Glu Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 
            100                 105                 110     


<210>  13
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  21R75, 21R79, 21R83, and 21M18 Heavy chain CDR1

<400>  13

Thr Ala Tyr Tyr Ile His 
1               5       


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

<220>
<223>  21R79 Heavy chain CDR2

<400>  14

Tyr Ile Ala Asn Tyr Asn Arg Ala Thr Asn Tyr Asn Gln Lys Phe Lys 
1               5                   10                  15      


Gly 
    


<210>  15
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  21M18 Heavy chain CDR2

<400>  15

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


Gly 
    


<210>  16
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  21R75, 21R79, 21R83, and 21M18 Heavy chain CDR3

<400>  16

Arg Asp Tyr Asp Tyr Asp Val Gly Met Asp Tyr 
1               5                   10      


<210>  17
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  219R45 Heavy chain CDR1

<400>  17

Asn Tyr Trp Met His 
1               5   


<210>  18
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  219R45 Heavy chain CDR2

<400>  18

Asp Ile Asn Pro Ser Asn Gly Arg Thr Ser Tyr Lys Glu Lys Phe Lys 
1               5                   10                  15      


Arg 
    


<210>  19
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  219R45 Heavy chain CDR3

<400>  19

His Tyr Asp Asp Lys Tyr Tyr Pro Leu Met Asp Tyr 
1               5                   10          


<210>  20
<211>  15
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Light chain CDR1

<400>  20

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


<210>  21
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Light chain CDR2

<400>  21

Ala Ala Ser Asn Gln Gly Ser 
1               5           


<210>  22
<211>  12
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Light chain CDR3

<400>  22

Gln Gln Ser Lys Glu Val Pro Trp Thr Phe Gly Gly 
1               5                   10          


<210>  23
<211>  522
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human DLL4 with signal sequence


<220>
<221>  SIGNAL
<222>  (1)..(26)

<400>  23

Met Ala Ala Ala Ser Arg Ser Ala Ser Gly Trp Ala Leu Leu Leu Leu 
1               5                   10                  15      


Val Ala Leu Trp Gln Gln Arg Ala Ala Gly Ser Gly Val Phe Gln Leu 
            20                  25                  30          


Gln Leu Gln Glu Phe Ile Asn Glu Arg Gly Val Leu Ala Ser Gly Arg 
        35                  40                  45              


Pro Cys Glu Pro Gly Cys Arg Thr Phe Phe Arg Val Cys Leu Lys His 
    50                  55                  60                  


Phe Gln Ala Val Val Ser Pro Gly Pro Cys Thr Phe Gly Thr Val Ser 
65                  70                  75                  80  


Thr Pro Val Leu Gly Thr Asn Ser Phe Ala Val Arg Asp Asp Ser Ser 
                85                  90                  95      


Gly Gly Gly Arg Asn Pro Leu Gln Leu Pro Phe Asn Phe Thr Trp Pro 
            100                 105                 110         


Gly Thr Phe Ser Leu Ile Ile Glu Ala Trp His Ala Pro Gly Asp Asp 
        115                 120                 125             


Leu Arg Pro Glu Ala Leu Pro Pro Asp Ala Leu Ile Ser Lys Ile Ala 
    130                 135                 140                 


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


Thr Ser Thr Leu Thr Arg Leu Arg Tyr Ser Tyr Arg Val Ile Cys Ser 
                165                 170                 175     


Asp Asn Tyr Tyr Gly Asp Asn Cys Ser Arg Leu Cys Lys Lys Arg Asn 
            180                 185                 190         


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


Leu Pro Gly Trp Thr Gly Glu Tyr Cys Gln Gln Pro Ile Cys Leu Ser 
    210                 215                 220                 


Gly Cys His Glu Gln Asn Gly Tyr Cys Ser Lys Pro Ala Glu Cys Leu 
225                 230                 235                 240 


Cys Arg Pro Gly Trp Gln Gly Arg Leu Cys Asn Glu Cys Ile Pro His 
                245                 250                 255     


Asn Gly Cys Arg His Gly Thr Cys Ser Thr Pro Trp Gln Cys Thr Cys 
            260                 265                 270         


Asp Glu Gly Trp Gly Gly Leu Phe Cys Asp Gln Asp Leu Asn Tyr Cys 
        275                 280                 285             


Thr His His Ser Pro Cys Lys Asn Gly Ala Thr Cys Ser Asn Ser Gly 
    290                 295                 300                 


Gln Arg Ser Tyr Thr Cys Thr Cys Arg Pro Gly Tyr Thr Gly Val Asp 
305                 310                 315                 320 


Cys Glu Leu Glu Leu Ser Glu Cys Asp Ser Asn Pro Cys Arg Asn Gly 
                325                 330                 335     


Gly Ser Cys Lys Asp Gln Glu Asp Gly Tyr His Cys Leu Cys Pro Pro 
            340                 345                 350         


Gly Tyr Tyr Gly Leu His Cys Glu His Ser Thr Leu Ser Cys Ala Asp 
        355                 360                 365             


Ser Pro Cys Phe Asn Gly Gly Ser Cys Arg Glu Arg Asn Gln Gly Ala 
    370                 375                 380                 


Asn Tyr Ala Cys Glu Cys Pro Pro Asn Phe Thr Gly Ser Asn Cys Glu 
385                 390                 395                 400 


Lys Lys Val Asp Arg Cys Thr Ser Asn Pro Cys Ala Asn Gly Gly Gln 
                405                 410                 415     


Cys Leu Asn Arg Gly Pro Ser Arg Met Cys Arg Cys Arg Pro Gly Phe 
            420                 425                 430         


Thr Gly Thr Tyr Cys Glu Leu His Val Ser Asp Cys Ala Arg Asn Pro 
        435                 440                 445             


Cys Ala His Gly Gly Thr Cys His Asp Leu Glu Asn Gly Leu Met Cys 
    450                 455                 460                 


Thr Cys Pro Ala Gly Phe Ser Gly Arg Arg Cys Glu Val Arg Thr Ser 
465                 470                 475                 480 


Ile Asp Ala Cys Ala Ser Ser Pro Cys Phe Asn Arg Ala Thr Cys Tyr 
                485                 490                 495     


Thr Asp Leu Ser Thr Asp Thr Phe Val Cys Asn Cys Pro Tyr Gly Phe 
            500                 505                 510         


Val Gly Ser Arg Cys Glu Phe Pro Val Gly 
        515                 520         


<210>  24
<211>  496
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human DLL4 without predicted signal sequence

<400>  24

Ser Gly Val Phe Gln Leu Gln Leu Gln Glu Phe Ile Asn Glu Arg Gly 
1               5                   10                  15      


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


Arg Val Cys Leu Lys His Phe Gln Ala Val Val Ser Pro Gly Pro Cys 
        35                  40                  45              


Thr Phe Gly Thr Val Ser Thr Pro Val Leu Gly Thr Asn Ser Phe Ala 
    50                  55                  60                  


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


Phe Asn Phe Thr Trp Pro Gly Thr Phe Ser Leu Ile Ile Glu Ala Trp 
                85                  90                  95      


His Ala Pro Gly Asp Asp Leu Arg Pro Glu Ala Leu Pro Pro Asp Ala 
            100                 105                 110         


Leu Ile Ser Lys Ile Ala Ile Gln Gly Ser Leu Ala Val Gly Gln Asn 
        115                 120                 125             


Trp Leu Leu Asp Glu Gln Thr Ser Thr Leu Thr Arg Leu Arg Tyr Ser 
    130                 135                 140                 


Tyr Arg Val Ile Cys Ser Asp Asn Tyr Tyr Gly Asp Asn Cys Ser Arg 
145                 150                 155                 160 


Leu Cys Lys Lys Arg Asn Asp His Phe Gly His Tyr Val Cys Gln Pro 
                165                 170                 175     


Asp Gly Asn Leu Ser Cys Leu Pro Gly Trp Thr Gly Glu Tyr Cys Gln 
            180                 185                 190         


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


Lys Pro Ala Glu Cys Leu Cys Arg Pro Gly Trp Gln Gly Arg Leu Cys 
    210                 215                 220                 


Asn Glu Cys Ile Pro His Asn Gly Cys Arg His Gly Thr Cys Ser Thr 
225                 230                 235                 240 


Pro Trp Gln Cys Thr Cys Asp Glu Gly Trp Gly Gly Leu Phe Cys Asp 
                245                 250                 255     


Gln Asp Leu Asn Tyr Cys Thr His His Ser Pro Cys Lys Asn Gly Ala 
            260                 265                 270         


Thr Cys Ser Asn Ser Gly Gln Arg Ser Tyr Thr Cys Thr Cys Arg Pro 
        275                 280                 285             


Gly Tyr Thr Gly Val Asp Cys Glu Leu Glu Leu Ser Glu Cys Asp Ser 
    290                 295                 300                 


Asn Pro Cys Arg Asn Gly Gly Ser Cys Lys Asp Gln Glu Asp Gly Tyr 
305                 310                 315                 320 


His Cys Leu Cys Pro Pro Gly Tyr Tyr Gly Leu His Cys Glu His Ser 
                325                 330                 335     


Thr Leu Ser Cys Ala Asp Ser Pro Cys Phe Asn Gly Gly Ser Cys Arg 
            340                 345                 350         


Glu Arg Asn Gln Gly Ala Asn Tyr Ala Cys Glu Cys Pro Pro Asn Phe 
        355                 360                 365             


Thr Gly Ser Asn Cys Glu Lys Lys Val Asp Arg Cys Thr Ser Asn Pro 
    370                 375                 380                 


Cys Ala Asn Gly Gly Gln Cys Leu Asn Arg Gly Pro Ser Arg Met Cys 
385                 390                 395                 400 


Arg Cys Arg Pro Gly Phe Thr Gly Thr Tyr Cys Glu Leu His Val Ser 
                405                 410                 415     


Asp Cys Ala Arg Asn Pro Cys Ala His Gly Gly Thr Cys His Asp Leu 
            420                 425                 430         


Glu Asn Gly Leu Met Cys Thr Cys Pro Ala Gly Phe Ser Gly Arg Arg 
        435                 440                 445             


Cys Glu Val Arg Thr Ser Ile Asp Ala Cys Ala Ser Ser Pro Cys Phe 
    450                 455                 460                 


Asn Arg Ala Thr Cys Tyr Thr Asp Leu Ser Thr Asp Thr Phe Val Cys 
465                 470                 475                 480 


Asn Cys Pro Tyr Gly Phe Val Gly Ser Arg Cys Glu Phe Pro Val Gly 
                485                 490                 495     


<210>  25
<211>  128
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human DLL4 N-Terminal Region

<400>  25

Ser Gly Val Phe Gln Leu Gln Leu Gln Glu Phe Ile Asn Glu Arg Gly 
1               5                   10                  15      


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


Arg Val Cys Leu Lys His Phe Gln Ala Val Val Ser Pro Gly Pro Cys 
        35                  40                  45              


Thr Phe Gly Thr Val Ser Thr Pro Val Leu Gly Thr Asn Ser Phe Ala 
    50                  55                  60                  


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


Phe Asn Phe Thr Trp Pro Gly Thr Phe Ser Leu Ile Ile Glu Ala Trp 
                85                  90                  95      


His Ala Pro Gly Asp Asp Leu Arg Pro Glu Ala Leu Pro Pro Asp Ala 
            100                 105                 110         


Leu Ile Ser Lys Ile Ala Ile Gln Gly Ser Leu Ala Val Gly Gln Asn 
        115                 120                 125             


<210>  26
<211>  63
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human DLL4 DSL Domain

<400>  26

Trp Leu Leu Asp Glu Gln Thr Ser Thr Leu Thr Arg Leu Arg Tyr Ser 
1               5                   10                  15      


Tyr Arg Val Ile Cys Ser Asp Asn Tyr Tyr Gly Asp Asn Cys Ser Arg 
            20                  25                  30          


Leu Cys Lys Lys Arg Asn Asp His Phe Gly His Tyr Val Cys Gln Pro 
        35                  40                  45              


Asp Gly Asn Leu Ser Cys Leu Pro Gly Trp Thr Gly Glu Tyr Cys 
    50                  55                  60              


<210>  27
<211>  232
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human VEGF-A with signal sequence


<220>
<221>  SIGNAL
<222>  (1)..(26)

<400>  27

Met Asn Phe Leu Leu Ser Trp Val His Trp Ser Leu Ala Leu Leu Leu 
1               5                   10                  15      


Tyr Leu His His Ala Lys Trp Ser Gln Ala Ala Pro Met Ala Glu Gly 
            20                  25                  30          


Gly Gly Gln Asn His His Glu Val Val Lys Phe Met Asp Val Tyr Gln 
        35                  40                  45              


Arg Ser Tyr Cys His Pro Ile Glu Thr Leu Val Asp Ile Phe Gln Glu 
    50                  55                  60                  


Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys Pro Ser Cys Val Pro Leu 
65                  70                  75                  80  


Met Arg Cys Gly Gly Cys Cys Asn Asp Glu Gly Leu Glu Cys Val Pro 
                85                  90                  95      


Thr Glu Glu Ser Asn Ile Thr Met Gln Ile Met Arg Ile Lys Pro His 
            100                 105                 110         


Gln Gly Gln His Ile Gly Glu Met Ser Phe Leu Gln His Asn Lys Cys 
        115                 120                 125             


Glu Cys Arg Pro Lys Lys Asp Arg Ala Arg Gln Glu Lys Lys Ser Val 
    130                 135                 140                 


Arg Gly Lys Gly Lys Gly Gln Lys Arg Lys Arg Lys Lys Ser Arg Tyr 
145                 150                 155                 160 


Lys Ser Trp Ser Val Tyr Val Gly Ala Arg Cys Cys Leu Met Pro Trp 
                165                 170                 175     


Ser Leu Pro Gly Pro His Pro Cys Gly Pro Cys Ser Glu Arg Arg Lys 
            180                 185                 190         


His Leu Phe Val Gln Asp Pro Gln Thr Cys Lys Cys Ser Cys Lys Asn 
        195                 200                 205             


Thr Asp Ser Arg Cys Lys Ala Arg Gln Leu Glu Leu Asn Glu Arg Thr 
    210                 215                 220                 


Cys Arg Cys Asp Lys Pro Arg Arg 
225                 230         


<210>  28
<211>  206
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human VEGF-A without predicted signal sequence

<400>  28

Ala Pro Met Ala Glu Gly Gly Gly Gln Asn His His Glu Val Val Lys 
1               5                   10                  15      


Phe Met Asp Val Tyr Gln Arg Ser Tyr Cys His Pro Ile Glu Thr Leu 
            20                  25                  30          


Val Asp Ile Phe Gln Glu Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys 
        35                  40                  45              


Pro Ser Cys Val Pro Leu Met Arg Cys Gly Gly Cys Cys Asn Asp Glu 
    50                  55                  60                  


Gly Leu Glu Cys Val Pro Thr Glu Glu Ser Asn Ile Thr Met Gln Ile 
65                  70                  75                  80  


Met Arg Ile Lys Pro His Gln Gly Gln His Ile Gly Glu Met Ser Phe 
                85                  90                  95      


Leu Gln His Asn Lys Cys Glu Cys Arg Pro Lys Lys Asp Arg Ala Arg 
            100                 105                 110         


Gln Glu Lys Lys Ser Val Arg Gly Lys Gly Lys Gly Gln Lys Arg Lys 
        115                 120                 125             


Arg Lys Lys Ser Arg Tyr Lys Ser Trp Ser Val Tyr Val Gly Ala Arg 
    130                 135                 140                 


Cys Cys Leu Met Pro Trp Ser Leu Pro Gly Pro His Pro Cys Gly Pro 
145                 150                 155                 160 


Cys Ser Glu Arg Arg Lys His Leu Phe Val Gln Asp Pro Gln Thr Cys 
                165                 170                 175     


Lys Cys Ser Cys Lys Asn Thr Asp Ser Arg Cys Lys Ala Arg Gln Leu 
            180                 185                 190         


Glu Leu Asn Glu Arg Thr Cys Arg Cys Asp Lys Pro Arg Arg 
        195                 200                 205     


<210>  29
<211>  1395
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  21M18 Heavy chain nucleotide sequence (13B Version 1)

<400>  29
atgaagcacc tgtggttctt tctgctgctg gtggccgctc ccagatgggt gctgtcccag       60

gtgcagctgg tgcagtctgg cgccgaagtg aagaaacctg gcgcctccgt gaagatctcc      120

tgcaaggcct ccggctactc cttcaccgct tactacatcc actgggtcaa gcaggcccct      180

gggcagggcc tggaatggat cggctacatc tcctcctaca acggcgccac caactacaac      240

cagaaattca agggccgcgt gaccttcacc accgacacct ccacctccac cgcctacatg      300

gaactgcggt ccctgcggag cgacgacacc gccgtgtact actgcgccag agactacgac      360

tacgacgtgg gcatggacta ctggggccag ggcaccctgg tcaccgtgtc ctctgcctcc      420

accaagggcc catccgtgtt ccctctggcc ccttgctccc ggtccacctc tgagtctacc      480

gccgctctgg gctgcctggt gaaggactac ttccctgagc ctgtgaccgt gtcctggaac      540

tctggcgccc tgacctctgg cgtgcacacc ttccctgccg tgctgcagtc ctccggcctg      600

tactccctgt ctagcgtggt gaccgtgcct tcctccaact tcggcaccca gacctacacc      660

tgtaacgtgg accacaagcc ttccaacacc aaggtggaca agaccgtgga gcggaagtgc      720

tgcgtggagt gccctccttg tcctgctcct cctgtggctg gcccttctgt gttcctgttc      780

cctccaaagc ctaaggacac cctgatgatc tcccggaccc ctgaagtgac ctgcgtggtg      840

gtggacgtgt cccacgagga ccctgaggtg cagttcaatt ggtacgtgga cggcgtggag      900

gtgcacaacg ccaagaccaa gcctcgggag gaacagttca actccacctt ccgggtggtg      960

tctgtgctga ccgtggtgca ccaggactgg ctgaacggca aagaatacaa gtgcaaggtg     1020

tccaacaagg gcctgcctgc ccctatcgaa aagaccatca gcaagaccaa gggccagcct     1080

cgcgagcctc aggtgtacac cctgcctccc agccgggaag aaatgaccaa gaaccaggtg     1140

tccctgacct gtctggtgga gggcttctac ccttccgata tcgccgtgga gtgggagtct     1200

aacggccagc ctgagaacaa ctacaagacc acccctccta tgctggactc cgacggctcc     1260

ttcttcctgt actccgaact gaccgtggac aagtcccggt ggcagcaggg caacgtgttc     1320

tcctgctccg tgatgcacga ggccctgcac aaccactaca cccagaagtc cctgtccctg     1380

tctcctggca agtag                                                      1395


<210>  30
<211>  1395
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  21R79 Heavy chain nucleotide sequence (13B Version 1)

<400>  30
atgaagcacc tgtggttctt tctgctgctg gtggccgctc ccagatgggt gctgtcccag       60

gtgcagctgg tgcagtctgg cgccgaagtg aagaaacctg gcgcctccgt gaagatctcc      120

tgcaaggcct ccggctactc cttcaccgcc tactacatcc actgggtgaa acaggcacca      180

ggccagggac tggaatggat cggctatatc gccaactaca accgggccac caactacaac      240

cagaaattca agggccgcgt gaccttcacc accgacacct ccacctccac agcctacatg      300

gaactgcggt ccctgcggag cgacgacacc gccgtgtact actgcgccag agactacgac      360

tacgacgtgg gcatggacta ctggggccag ggcaccctgg tgacagtgtc ctccgcctcc      420

accaagggcc cctccgtgtt ccctctggcc ccttgctccc ggtccacctc tgagtctacc      480

gccgctctgg gctgcctggt gaaggactac ttccctgagc ctgtgaccgt gtcctggaac      540

tctggcgccc tgacctctgg cgtgcacacc ttccctgccg tgctgcagtc ctccggcctg      600

tactccctgt ctagcgtggt gaccgtgcct tcctccaact tcggcaccca gacctacacc      660

tgtaacgtgg accacaagcc ttccaacacc aaggtggaca agaccgtgga gcggaagtgc      720

tgcgtggagt gccctccttg tcctgctcct cctgtggctg gcccttctgt gttcctgttc      780

cctccaaagc ctaaggacac cctgatgatc tcccggaccc ctgaagtgac ctgcgtggtg      840

gtggacgtgt cccacgagga ccctgaggtg cagttcaatt ggtacgtgga cggcgtggag      900

gtgcacaacg ccaagaccaa gcctcgggag gaacagttca actccacctt ccgggtggtg      960

tctgtgctga ccgtggtgca ccaggactgg ctgaacggca aagaatacaa gtgcaaggtg     1020

tccaacaagg gcctgcctgc ccctatcgaa aagaccatca gcaagaccaa gggccagcct     1080

cgcgagcctc aggtgtacac cctgcctccc agccgggaag aaatgaccaa gaaccaggtg     1140

tccctgacct gtctggtgga gggcttctac ccttccgata tcgccgtgga gtgggagtct     1200

aacggccagc ctgagaacaa ctacaagacc acccctccta tgctggactc cgacggctcc     1260

ttcttcctgt actccgaact gaccgtggac aagtcccggt ggcagcaggg caacgtgttc     1320

tcctgctccg tgatgcacga ggccctgcac aaccactaca cccagaagtc cctgtccctg     1380

tctcctggca agtag                                                      1395


<210>  31
<211>  1395
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  21R79 Heavy chain nucleotide sequence (13B Version 2)

<400>  31
atgaagcacc tatggttctt tctattatta gtggccgctc cccgttgggt gttatcgcag       60

gttcagctag ttcagtctgg agcggaagtt aagaaacctg gagcatccgt gaaaataagt      120

tgcaaggcat ccggttactc gttcaccgca tactatatcc actgggttaa acaggcacca      180

ggacagggac ttgaatggat cggatatatc gctaattata atagagctac aaactataac      240

caaaaattca aaggacgcgt gactttcaca actgacacct caacctcgac agcatacatg      300

gaattacggt ccctacggtc tgacgacact gccgtttact attgcgctag agattatgat      360

tatgatgttg gaatggacta ttggggccag ggaacactgg tgacagtgtc ttctgcatcc      420

actaagggac catccgtgtt ccctttggcc ccttgctctc gttcgacctc tgaatcgact      480

gccgctctgg gatgcctcgt gaaagattac ttccctgagc ctgtgaccgt ttcctggaac      540

tcgggcgccc taacctctgg cgtgcacaca ttccctgccg tgctacagtc ttctggccta      600

tactctttat cttcggttgt taccgtacct tcttctaact tcggaaccca aacttacacc      660

tgtaacgtag accacaagcc ttcgaacacc aaggtggaca agactgttga gcgaaagtgc      720

tgcgttgagt gccctccatg tcctgcacct cctgtggctg gcccttctgt gttcctgttc      780

cctccaaaac ctaaggacac tctaatgatc tctcggactc ctgaggtgac ttgcgtggtt      840

gtggacgtgt cccacgagga ccctgaggtg cagttcaatt ggtacgtgga cggagtcgag      900

gtgcacaatg caaagaccaa gcctcgggag gaacagttca actccacctt ccgggtggtt      960

tctgtgttga ccgttgtgca ccaagactgg ctgaacggca aagaatacaa gtgcaaggtg     1020

tccaacaagg gcctgcctgc ccctatcgaa aagaccatca gcaagaccaa gggccagcct     1080

cgcgagcctc aggtgtacac cctgcctccc agccgggaag aaatgaccaa gaaccaggtg     1140

tccctgacct gtctggtgga gggcttctac ccttccgaca tcgccgttga gtgggagtct     1200

aacggacagc cggagaacaa ctacaagact acgcctccaa tgctggactc cgacggctcc     1260

ttcttcctgt actccgaact gaccgtggac aagtcccggt ggcagcaggg caacgtgttc     1320

tcatgctccg taatgcacga agccttgcac aatcactaca ctcaaaagtc cctatcctta     1380

tctcctggca agtag                                                      1395


<210>  32
<211>  1401
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  219R45 Heavy chain nucleotide sequence (13A Version 1)

<400>  32
atgaagcatc tgtggttttt cctgttgctc gtggcggcac ccagatgggt gttgtcccaa       60

gtgcagctgg tccagagcgg ggctgaggtg aagaaacccg gagcaagcgt aaaagtatcg      120

tgtaaggcct cggggtacac gtttacaaac tactggatgc attgggtgcg gcaggctccg      180

ggacaggggt tggaatggat gggtgacatt aacccctcaa atggcagaac atcatataag      240

gaaaagttca aacgccgcgt cacactctcc gtggacaagt caagctcgac tgcgtacatg      300

gaactttcgt cgctgaggtc ggaggacacg gcagtgtact tttgcaccat ccattatgat      360

gacaagtatt accctctgat ggattattgg ggtcagggta cgttggtcac cgtctccagc      420

gcgtcgacga aaggtccctc ggtatttccc ctcgccccct gctcgaggtc gacatccgaa      480

tcaacagctg ccctcggctg cctggtcaaa gactacttcc cagagccggt aacggtgtcg      540

tggaactcgg gagcgcttac gtccggagtc cacacatttc cggcggtact gcaatcctcg      600

ggactgtatt cgttgtcgtc agtggtgact gtcccgtcct ccaatttcgg gactcagacc      660

tatacgtgca acgtcgacca caaaccctca aacaccaagg tggataagac agtggagcgc      720

aagtgctgcg tggagtgtcc cccgtgtccg gcaccccctg tcgccggacc ctcagtcttt      780

ttgtttccgc cgaagcccaa agatacactc atgatctcaa gaacgcccga ggtaacatgc      840

gtggtggtcg atgtaagcca cgaggatcca gaagtacaat tcaattggta tgtagacggg      900

gtcgaggtcc ataacgcaaa gacgaaaccg agggaagagc agttcaattc gactttccgg      960

gtggtgtcgg tgcttacagt cgtacatcag gactggttga acgggaagga gtacaagtgt     1020

aaagtatcga ataagggcct tccagcgccg attgaaaaga ccatctccaa gaccaaagga     1080

cagccacgag agccgcaagt ctatacgctt cctcccagcc gagaaaagat gactaaaaac     1140

caggtatcgc ttacgtgtct cgtcaagggt ttctaccctt cggacatcgc ggtggaatgg     1200

gagagcaatg gacaaccgga aaacaactac aagacgacac cgcctatgtt gaaaagcgat     1260

ggatcgtttt tcctctattc gaaactcacg gtcgataagt cacggtggca gcaggggaat     1320

gtgttctcct gttcagtgat gcacgaggcg ctccacaatc actataccca gaaaagcctg     1380

tcactttccc cgggaaaatg a                                               1401


<210>  33
<211>  1401
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  219R45 Heavy chain nucleotide sequence (13A Version 2)

<400>  33
atgaagcacc tctggttctt cctgctcctc gtggctgctc ctcggtgggt cctctcccaa       60

gtgcagctgg tccagagcgg ggctgaggtg aagaaacccg gagcttccgt caaagtctcc      120

tgtaaggctt ccggatacac ctttaccaac tattggatgc actgggtgcg gcaggctcct      180

ggacaagggc tggaatggat gggagacatc aatccttcca atggcagaac ctcctacaag      240

gaaaaattca aacggcgggt cacactctcc gtggacaagt ctagctccac agcttacatg      300

gaactctcct ccctgcggtc cgaagacaca gctgtctact tctgcaccat ccactacgac      360

gacaagtact accctctgat ggactactgg ggccagggaa ccctggtcac cgtgtccagc      420

gcttccacaa aaggaccctc cgtctttccc ctcgccccct gctcccggtc cacatccgaa      480

tcaacagctg ccctcggctg cctggtcaaa gactacttcc cagagcctgt cacagtgtcc      540

tggaactccg gagctctcac atccggagtc cacacatttc ctgctgtgct ccaatcctcc      600

ggactgtatt ccctctcctc cgtggtgaca gtgccttcct ccaatttcgg gacacagacc      660

tatacatgca acgtggacca caaaccctcc aacaccaaag tcgataagac agtggagcgc      720

aagtgctgcg tggagtgtcc cccttgtcct gctccccctg tggctggacc ttccgtcttt      780

ctgtttcctc ctaaacctaa agacaccctc atgatctccc ggacccccga ggtcacatgc      840

gtggtcgtcg atgtgagcca cgaggacccc gaagtccaat ttaattggta tgtggacggg      900

gtggaggtcc ataacgctaa gaccaaacct agggaagagc agttcaattc cactttccgg      960

gtggtgtccg tgctgaccgt cgttcatcag gactggctca acgggaaaga atacaaatgc     1020

aaagtctcta ataagggcct ccctgctcct attgaaaaaa caatttccaa aacaaaagga     1080

caacctcggg agcctcaagt ctacacactg ccaccttccc gggaaaaaat gacaaaaaat     1140

caagtctccc tcacatgtct cgtcaaggga ttctaccctt ccgacattgc tgtggaatgg     1200

gaatccaatg gacaacctga aaacaactac aagacaacac ctcctatgct caaaagcgat     1260

gggtcctttt tcctctattc caaactcaca gtcgataagt ctcggtggca gcaggggaat     1320

gtgttctcct gttccgtgat gcacgaggct ctccacaatc actataccca gaaaagcctg     1380

tccctctccc ctggaaaatg a                                               1401


<210>  34
<211>  717
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Light chain nucleotide sequence

<400>  34
atggtgctgc agacccaggt gttcatctcc ctgctgctgt ggatctccgg cgcctacggc       60

gacatcgtga tgacccagtc cccagactcc ctggctgtgt ctctgggaga gcgggccacc      120

atctcttgca gagcctccga gtccgtggac aactacggca tctccttcat gaagtggttc      180

cagcagaagc ccggccagcc cccaaagctg ctgatctacg ccgcctccaa ccagggatct      240

ggcgtgcccg accggttctc tggatccggc tctggcaccg actttaccct gaccatcagc      300

tccctgcagg ccgaggacgt ggccgtgtac tactgccagc agtccaaaga ggtgccctgg      360

accttcggcg gaggcaccaa ggtggaaatc aagcggaccg tggccgctcc ctccgtgttc      420

atcttcccac cctccgacga gcagctgaag tccggaaccg cctccgtcgt gtgcctgctg      480

aacaacttct acccccgcga ggccaaggtg cagtggaagg tggacaacgc cctgcagtcc      540

ggcaactccc aggaatccgt caccgagcag gactccaagg acagcaccta ctccctgtcc      600

tccaccctga ccctgtccaa ggccgactac gagaagcaca aggtgtacgc ctgcgaagtg      660

acccaccagg gcctgtccag ccccgtgacc aagtccttca accggggcga gtgttag         717


<210>  35
<211>  357
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  21M18 Heavy chain variable region nucleotide sequence

<400>  35
caggtgcagc tggtgcagtc tggcgccgaa gtgaagaaac ctggcgcctc cgtgaagatc       60

tcctgcaagg cctccggcta ctccttcacc gcttactaca tccactgggt caagcaggcc      120

cctgggcagg gcctggaatg gatcggctac atctcctcct acaacggcgc caccaactac      180

aaccagaaat tcaagggccg cgtgaccttc accaccgaca cctccacctc caccgcctac      240

atggaactgc ggtccctgcg gagcgacgac accgccgtgt actactgcgc cagagactac      300

gactacgacg tgggcatgga ctactggggc cagggcaccc tggtcaccgt gtcctct         357


<210>  36
<211>  357
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  21R79 Heavy chain variable region nucleotide sequence (13B)

<400>  36
caggtgcagc tggtgcagtc tggcgccgaa gtgaagaaac ctggcgcctc cgtgaagatc       60

tcctgcaagg cctccggcta ctccttcacc gcctactaca tccactgggt gaaacaggca      120

ccaggccagg gactggaatg gatcggctat atcgccaact acaaccgggc caccaactac      180

aaccagaaat tcaagggccg cgtgaccttc accaccgaca cctccacctc cacagcctac      240

atggaactgc ggtccctgcg gagcgacgac accgccgtgt actactgcgc cagagactac      300

gactacgacg tgggcatgga ctactggggc cagggcaccc tggtgacagt gtcctcc         357


<210>  37
<211>  357
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  21R79 Heavy chain variable region nucleotide sequence (13B 
       Version 2 )

<400>  37
caggttcagc tagttcagtc tggagcggaa gttaagaaac ctggagcatc cgtgaaaata       60

agttgcaagg catccggtta ctcgttcacc gcatactata tccactgggt taaacaggca      120

ccaggacagg gacttgaatg gatcggatat atcgctaatt ataatagagc tacaaactat      180

aaccaaaaat tcaaaggacg cgtgactttc acaactgaca cctcaacctc gacagcatac      240

atggaattac ggtccctacg gtctgacgac actgccgttt actattgcgc tagagattat      300

gattatgatg ttggaatgga ctattggggc cagggaacac tggtgacagt gtcttct         357


<210>  38
<211>  363
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  219R45 Heavy chain variable region nucleotide sequence (13A 
       version 1)

<400>  38
caagtgcagc tggtccagag cggggctgag gtgaagaaac ccggagcaag cgtaaaagta       60

tcgtgtaagg cctcggggta cacgtttaca aactactgga tgcattgggt gcggcaggct      120

ccgggacagg ggttggaatg gatgggtgac attaacccct caaatggcag aacatcatat      180

aaggaaaagt tcaaacgccg cgtcacactc tccgtggaca agtcaagctc gactgcgtac      240

atggaacttt cgtcgctgag gtcggaggac acggcagtgt acttttgcac catccattat      300

gatgacaagt attaccctct gatggattat tggggtcagg gtacgttggt caccgtctcc      360

agc                                                                    363


<210>  39
<211>  363
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  219R45 Heavy chain variable region nucleotide sequence (13A 
       Version 2)

<400>  39
caagtgcagc tggtccagag cggggctgag gtgaagaaac ccggagcttc cgtcaaagtc       60

tcctgtaagg cttccggata cacctttacc aactattgga tgcactgggt gcggcaggct      120

cctggacaag ggctggaatg gatgggagac atcaatcctt ccaatggcag aacctcctac      180

aaggaaaaat tcaaacggcg ggtcacactc tccgtggaca agtctagctc cacagcttac      240

atggaactct cctccctgcg gtccgaagac acagctgtct acttctgcac catccactac      300

gacgacaagt actaccctct gatggactac tggggccagg gaaccctggt caccgtgtcc      360

agc                                                                    363


<210>  40
<211>  333
<212>  DNA
<213>  Artificial Sequence

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

<400>  40
gacatcgtga tgacccagtc cccagactcc ctggctgtgt ctctgggaga gcgggccacc       60

atctcttgca gagcctccga gtccgtggac aactacggca tctccttcat gaagtggttc      120

cagcagaagc ccggccagcc cccaaagctg ctgatctacg ccgcctccaa ccagggatct      180

ggcgtgcccg accggttctc tggatccggc tctggcaccg actttaccct gaccatcagc      240

tccctgcagg ccgaggacgt ggccgtgtac tactgccagc agtccaaaga ggtgccctgg      300

accttcggcg gaggcaccaa ggtggaaatc aag                                   333


<210>  41
<211>  330
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human IgG1 Heavy chain constant region

<400>  41

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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  42
<211>  326
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human IgG2 Heavy chain constant region

<400>  42

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


Ser Thr Ser Glu Ser 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 Asn Phe Gly Thr Gln Thr 
65                  70                  75                  80  


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


Thr Val Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro 
            100                 105                 110         


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


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


Val Ser His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp Gly 
145                 150                 155                 160 


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


Ser Thr Phe Arg Val Val Ser Val Leu Thr Val Val His Gln Asp Trp 
            180                 185                 190         


Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu Pro 
        195                 200                 205             


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


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


Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile 
                245                 250                 255     


Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr 
            260                 265                 270         


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


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


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu 
305                 310                 315                 320 


Ser Leu Ser Pro Gly Lys 
                325     


<210>  43
<211>  377
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human IgG3 Heavy chain constant region

<400>  43

Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg 
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 Thr Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys 
                85                  90                  95      


Arg Val Glu Leu Lys Thr Pro Leu Gly Asp Thr Thr His Thr Cys Pro 
            100                 105                 110         


Arg Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg 
        115                 120                 125             


Cys Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys 
    130                 135                 140                 


Pro Glu Pro Lys Ser Cys Asp Thr Pro Pro Pro Cys Pro Arg Cys Pro 
145                 150                 155                 160 


Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
                165                 170                 175     


Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
            180                 185                 190         


Val Val Asp Val Ser His Glu Asp Pro Glu Val Gln Phe Lys Trp Tyr 
        195                 200                 205             


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


Gln Tyr Asn Ser Thr Phe Arg Val Val Ser Val Leu Thr Val Leu His 
225                 230                 235                 240 


Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                245                 250                 255     


Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Thr Lys Gly Gln 
            260                 265                 270         


Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 
        275                 280                 285             


Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 
    290                 295                 300                 


Ser Asp Ile Ala Val Glu Trp Glu Ser Ser Gly Gln Pro Glu Asn Asn 
305                 310                 315                 320 


Tyr Asn Thr Thr Pro Pro Met Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                325                 330                 335     


Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Ile 
            340                 345                 350         


Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn Arg Phe Thr Gln 
        355                 360                 365             


Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    370                 375         


<210>  44
<211>  327
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human IgG4 Heavy chain constant region

<400>  44

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


Ser Thr Ser Glu Ser 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 Lys Thr 
65                  70                  75                  80  


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


Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Ser Cys Pro Ala Pro 
            100                 105                 110         


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


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


Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp 
145                 150                 155                 160 


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


Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp 
            180                 185                 190         


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


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


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


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


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


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


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


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


Leu Ser Leu Ser Leu Gly Lys 
                325         


<210>  45
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  FLAG peptide

<400>  45

Asp Tyr Lys Asp Asp Asp Asp Lys 
1               5               


<210>  46
<211>  464
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Parental 21R79 Heavy chain with signal sequence


<220>
<221>  SIGNAL
<222>  (1)..(19)
<223>  unmodified chain

<400>  46

Met Lys His Leu Trp Phe Phe Leu Leu Leu Val Ala Ala Pro Arg Trp 
1               5                   10                  15      


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


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


Thr Ala Tyr Tyr Ile His Trp Val Lys Gln Ala Pro Gly Gln Gly Leu 
    50                  55                  60                  


Glu Trp Ile Gly Tyr Ile Ala Asn Tyr Asn Arg Ala Thr Asn Tyr Asn 
65                  70                  75                  80  


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


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


Tyr Tyr Cys Ala Arg Asp Tyr Asp Tyr Asp Val Gly Met Asp Tyr Trp 
        115                 120                 125             


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


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


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


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


Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
        195                 200                 205             


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  47
<211>  466
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Parental 219R45 Heavy chain with signal sequence


<220>
<221>  SIGNAL
<222>  (1)..(19)

<400>  47

Met Lys His Leu Trp Phe Phe Leu Leu Leu Val Ala Ala Pro Arg Trp 
1               5                   10                  15      


Val Leu 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 Ala Ser Gly Tyr Thr Phe 
        35                  40                  45              


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


Glu Trp Met Gly Asp Ile Asn Pro Ser Asn Gly Arg Thr Ser Tyr Lys 
65                  70                  75                  80  


Glu Lys Phe Lys Arg Arg Val Thr Leu Ser Val Asp Lys Ser Ser Ser 
                85                  90                  95      


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


Tyr Phe Cys Thr Ile His Tyr Asp Asp Lys Tyr Tyr Pro Leu Met Asp 
        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>  48
<211>  445
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Parental 21R79 Heavy chain without predicted signal sequence

<400>  48

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


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


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


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


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


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


Ala Arg Asp Tyr Asp Tyr Asp Val Gly Met Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  49
<211>  447
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Parental 219R45 Heavy chain without signal sequence

<400>  49

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


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


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


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


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


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


Thr Ile His Tyr Asp Asp Lys Tyr Tyr Pro Leu Met Asp 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>  50
<211>  357
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Parental 21R79 Heavy chain variable region nucleotide sequence

<400>  50
caagtgcagc tcgtgcagtc aggggcggag gtcaagaagc cgggagcatc ggtcaaaatc       60

tcgtgtaagg cctcggggta ctcctttact gcgtattaca tccattgggt aaagcaggcg      120

ccagggcagg gattggagtg gattgggtat atcgccaatt acaatcgcgc gacgaactat      180

aaccagaaat tcaagggaag ggtgaccttc acaacggata catcgacatc gacggcctac      240

atggaacttc gcagcctgcg atcagatgac acggcggtat actattgcgc aagagattac      300

gactatgatg tgggaatgga ctattggggt caaggtactc tggtcacagt ctcctcc         357


<210>  51
<211>  363
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Parental 219R45 Heavy chain variable region nucleotide sequence

<400>  51
caggtacagc tcgtgcaatc gggggcagag gtcaaaaagc ccggtgcgtc ggtaaaggtc       60

agctgcaaag cgtcaggtta tacattcacg aattactgga tgcattgggt cagacaggcc      120

cctggacaag ggcttgaatg gatgggagat atcaatccgt cgaacggacg gactagctat      180

aaggagaagt ttaagaggcg cgtaacactg tcggtggaca aatcgtcctc aacggcctac      240

atggagttgt catccctgcg gtcggaagat acggcggtct acttctgtac tatccactat      300

gacgataagt actacccgct tatggactac tggggtcagg gaacattggt aaccgtgagc      360

agc                                                                    363


<210>  52
<211>  1392
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Parental 21R79 Heavy chain nucleotide sequence with signal 
       sequence

<400>  52
atgaaacact tgtggttttt cctcttgctc gtggcagctc ctcggtgggt actttcacaa       60

gtgcagctcg tgcagtcagg ggcggaggtc aagaagccgg gagcatcggt caaaatctcg      120

tgtaaggcct cggggtactc ctttactgcg tattacatcc attgggtaaa gcaggcgcca      180

gggcagggat tggagtggat tgggtatatc gccaattaca atcgcgcgac gaactataac      240

cagaaattca agggaagggt gaccttcaca acggatacat cgacatcgac ggcctacatg      300

gaacttcgca gcctgcgatc agatgacacg gcggtatact attgcgcaag agattacgac      360

tatgatgtgg gaatggacta ttggggtcaa ggtactctgg tcacagtctc ctccgccagc      420

accaagggcc ctagcgtctt ccctctggct ccctgcagca ggagcaccag cgagagcaca      480

gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac      540

tcaggcgctc tgaccagcgg cgtgcacacc ttcccagctg tcctacagtc ctcaggactc      600

tactccctca gcagcgtggt gaccgtgccc tccagcaact tcggcaccca gacctacacc      660

tgcaacgtag atcacaagcc cagcaacacc aaggtggaca agacagttga gcgcaaatgt      720

tgtgtcgagt gcccaccgtg cccagcacca cctgtggcag gaccgtcagt cttcctcttc      780

cccccaaaac ccaaggacac cctcatgatc tcccggaccc ctgaggtcac gtgcgtggtg      840

gtggacgtga gccacgaaga ccccgaggtc cagttcaact ggtacgtgga cggcgtggag      900

gtgcataatg ccaagacaaa gccacgggag gagcagttca acagcacgtt ccgtgtggtc      960

agcgtcctca ccgttgtgca ccaggactgg ctgaacggca aggagtacaa gtgcaaggtc     1020

tccaacaaag gcctcccagc ccccatcgag aaaaccatct ccaaaaccaa agggcagccc     1080

cgagaaccac aggtgtacac cctgccccca tcccgggagg agatgaccaa gaaccaggtc     1140

agcctgacct gcctggtcaa aggcttctac cccagcgaca tcgccgtgga gtgggagagc     1200

aatgggcagc cggagaacaa ctacaagacc acacctccca tgctggactc cgacggctcc     1260

ttcttcctct acagcaagct caccgtggac aagagcaggt ggcagcaggg gaacgtcttc     1320

tcatgctccg tgatgcatga ggctctgcac aaccactaca cgcagaagag cctctccctg     1380

tctccgggta aa                                                         1392


<210>  53
<211>  1398
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Parental 219R45 Heavy chain nucleotide sequence with signal 
       sequence

<400>  53
atgaaacacc tctggttctt tttgctcctg gtggcagctc cccgatgggt gcttagccag       60

gtacagctcg tgcaatcggg ggcagaggtc aaaaagcccg gtgcgtcggt aaaggtcagc      120

tgcaaagcgt caggttatac attcacgaat tactggatgc attgggtcag acaggcccct      180

ggacaagggc ttgaatggat gggagatatc aatccgtcga acggacggac tagctataag      240

gagaagttta agaggcgcgt aacactgtcg gtggacaaat cgtcctcaac ggcctacatg      300

gagttgtcat ccctgcggtc ggaagatacg gcggtctact tctgtactat ccactatgac      360

gataagtact acccgcttat ggactactgg ggtcagggaa cattggtaac cgtgagcagc      420

gcgtccacaa 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 cgggtaaa                                                   1398


<210>  54
<211>  333
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Parental 21R79 and 219R45 light chain variable region nucleotide 
       sequence

<400>  54
gacatcgtga tgacccagtc ccctgactcc ctggctgtgt ccctgggcga gagggccacc       60

atctcctgca gagccagcga atccgtcgat aattatggca tttcctttat gaagtggttc      120

cagcagaaac caggacagcc tcctaagctg ctcatttacg ctgcatccaa ccaagggtcc      180

ggggtccctg acaggttctc cggcagcggg tccggaacag atttcactct caccatcagc      240

agcctgcagg ctgaagatgt ggctgtctat tactgtcagc aaagcaagga ggtgccttgg      300

acattcggag gagggaccaa ggtggaaatc aaa                                   333


<210>  55
<211>  717
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Parental 21R79 and 219R45 light chain nucleotide sequence

<400>  55
atggtgctcc agacccaggt cttcatttcc ctgctgctct ggatcagcgg agcctacggg       60

gacatcgtga tgacccagtc ccctgactcc ctggctgtgt ccctgggcga gagggccacc      120

atctcctgca gagccagcga atccgtcgat aattatggca tttcctttat gaagtggttc      180

cagcagaaac caggacagcc tcctaagctg ctcatttacg ctgcatccaa ccaagggtcc      240

ggggtccctg acaggttctc cggcagcggg tccggaacag atttcactct caccatcagc      300

agcctgcagg ctgaagatgt ggctgtctat tactgtcagc aaagcaagga ggtgccttgg      360

acattcggag gagggaccaa ggtggaaatc aaacgtacgg tggctgcccc ctccgtcttc      420

atcttccccc ccagcgatga gcagctgaaa agcggcactg ccagcgtggt gtgcctgctg      480

aataacttct atccccggga ggccaaagtg cagtggaagg tggataacgc cctccaaagc      540

ggcaactccc aggagagcgt cacagagcag gacagcaagg acagcaccta cagcctcagc      600

agcaccctga ccctgagcaa agccgactac gagaaacaca aagtctacgc ctgcgaagtc      660

acccatcagg gcctgagcag ccccgtcaca aagagcttca acaggggcga gtgttga         717


<210>  56
<211>  445
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  21R75 Heavy chain without predicted signal sequence

<400>  56

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


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


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


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


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


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


Ala Arg Asp Tyr Asp Tyr Asp Val Gly Met Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  57
<211>  464
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  21R75 Heavy chain with predicted signal sequence


<220>
<221>  SIGNAL
<222>  (1)..(19)

<400>  57

Met Lys His Leu Trp Phe Phe Leu Leu Leu Val Ala Ala Pro Arg Trp 
1               5                   10                  15      


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


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


Thr Ala Tyr Tyr Ile His Trp Val Lys Gln Ala Pro Gly Gln Gly Leu 
    50                  55                  60                  


Glu Trp Ile Gly Tyr Ile Ala Gly Tyr Lys Asp Ala Thr Asn Tyr Asn 
65                  70                  75                  80  


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


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


Tyr Tyr Cys Ala Arg Asp Tyr Asp Tyr Asp Val Gly Met Asp Tyr Trp 
        115                 120                 125             


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


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


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


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


Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
        195                 200                 205             


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  58
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  21R75 Heavy chain variable region

<400>  58

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


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


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


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


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


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


Ala Arg Asp Tyr Asp Tyr Asp Val Gly Met Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  59
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  21R75 Heavy chain CDR2

<400>  59

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


Gly 
    


<210>  60
<211>  1392
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  21R75 Heavy chain nucleotide sequence with signal sequence (13B 
       Version 1)


<220>
<221>  SIGNAL
<222>  (1)..(57)

<400>  60
atgaagcacc tgtggttctt tctgctgctg gtggccgctc ccagatgggt gctgtcccag       60

gtgcagctgg tgcagtctgg cgccgaagtg aagaaacctg gcgcctccgt gaagatctcc      120

tgcaaggcct ccggctactc cttcaccgcc tactacatcc actgggtcaa gcaggcccct      180

ggacagggcc tggaatggat cggctatatc gccggctaca aggacgccac caactacaac      240

cagaaattca agggcagagt gaccttcacc accgacacct ccacctctac cgcctacatg      300

gaactgcggt ccctgcggag cgacgacacc gccgtgtact actgcgccag agactacgac      360

tacgacgtgg gcatggacta ctggggccag ggcacactcg tgaccgtgtc ctctgcttcc      420

accaagggcc cctccgtgtt tcctctggcc ccttgctcca gatccacctc cgagtctacc      480

gccgctctgg gctgcctcgt gaaggactac ttccccgagc ccgtgacagt gtcttggaac      540

tctggcgccc tgacctccgg cgtgcacacc tttccagctg tgctgcagtc ctccggcctg      600

tactccctgt cctccgtcgt gactgtgccc tcctccaact tcggcaccca gacctacacc      660

tgtaacgtgg accacaagcc ctccaacacc aaggtggaca agaccgtgga acggaagtgc      720

tgcgtggaat gccccccttg tcctgcccct cctgtggctg gccctagcgt gttcctgttc      780

cccccaaagc ccaaggacac cctgatgatc tcccggaccc ccgaagtgac ctgcgtggtg      840

gtggatgtgt cccacgagga ccccgaggtg cagttcaatt ggtacgtgga cggcgtggaa      900

gtgcacaacg ccaagaccaa gcccagagag gaacagttca actccacctt ccgggtggtg      960

tccgtgctga ccgtggtgca tcaggactgg ctgaacggca aagagtacaa gtgcaaggtg     1020

tccaacaagg gcctgcctgc ccccatcgaa aagaccatct ctaagaccaa gggacagccc     1080

cgcgagcccc aggtgtacac actgcctcca tcccgggaag agatgaccaa gaaccaggtg     1140

tccctgacct gtctggtgga aggcttctac ccctccgata tcgccgtgga atgggagtcc     1200

aacggccagc ccgagaacaa ctacaagacc acccccccca tgctggactc cgacggctca     1260

ttcttcctgt acagcgagct gacagtggac aagtcccggt ggcagcaggg caacgtgttc     1320

tcctgctccg tgatgcacga ggccctgcac aaccactaca cccagaagtc cctgtccctg     1380

agccccggca ag                                                         1392


<210>  61
<211>  1392
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  21R75 Heavy chain nucleotide sequence with signal sequence (13B 
       Version S1-2)


<220>
<221>  SIGNAL
<222>  (1)..(57)

<400>  61
atgaagcacc tgtggttctt tctgctgctg gtggccgctc ccagatgggt gctgtcccag       60

gttcagctag ttcagtctgg agcggaagtt aagaaacctg gagcatccgt gaaaataagt      120

tgcaaggcat ccggttactc gttcaccgca tactatatcc actgggttaa acaggcacca      180

ggacagggac ttgaatggat cggatatatc gctggatata aagatgctac aaactataac      240

caaaaattca aaggacgcgt gactttcaca actgacacct caacctcgac agcatacatg      300

gaattacggt ccctacggtc tgacgacact gccgtttact attgcgctag agattatgat      360

tatgatgttg gaatggacta ttggggccag ggaacactgg tgacagtgtc ttctgcatcc      420

actaagggac catccgtgtt ccctttggcc ccttgctctc gttcgacctc tgaatcgact      480

gccgctctgg gatgcctcgt gaaagattac ttccctgagc ctgtgaccgt ttcctggaac      540

tcgggcgccc taacctctgg cgtgcacaca ttccctgccg tgctacagtc ttctggccta      600

tactctttat cttcggttgt taccgtacct tcttctaact tcggaaccca aacttacacc      660

tgtaacgtag accacaagcc ttcgaacacc aaggtggaca agactgttga gcgaaagtgc      720

tgcgttgagt gccctccatg tcctgcacct cctgtggctg gcccttctgt gttcctgttc      780

cctccaaaac ctaaggacac tctaatgatc tctcggactc ctgaggtgac ttgcgtggtt      840

gtggacgtgt cccacgagga ccctgaggtg cagttcaatt ggtacgtgga cggagtcgag      900

gtgcacaatg caaagaccaa gcctcgggag gaacagttca actccacctt ccgggtggtt      960

tctgtgttga ccgttgtgca ccaagactgg ctgaacggca aagaatacaa gtgcaaggtg     1020

tccaacaagg gcctgcctgc ccctatcgaa aagaccatca gcaagaccaa gggccagcct     1080

cgcgagcctc aggtgtacac cctgcctccc agccgggaag aaatgaccaa gaaccaggtg     1140

tccctgacct gtctggtgga gggcttctac ccttccgaca tcgccgttga gtgggagtct     1200

aacggacagc cggagaacaa ctacaagact acgcctccaa tgctggactc cgacggctcc     1260

ttcttcctgt actccgaact gaccgtggac aagtcccggt ggcagcaggg caacgtgttc     1320

tcatgctccg taatgcacga agccttgcac aatcactaca ctcaaaagtc cctatcctta     1380

tctcctggca ag                                                         1392


<210>  62
<211>  445
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  21R83 Heavy chain without predicted signal sequence

<400>  62

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


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


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


Gly Tyr Ile Ser Asn Tyr Asn Arg Ala Thr Asn Tyr Asn Gln Lys Phe 
    50                  55                  60                  


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


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


Ala Arg Asp Tyr Asp Tyr Asp Val Gly Met Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  63
<211>  464
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  21R83 Heavy chain with predicted signal sequence


<220>
<221>  SIGNAL
<222>  (1)..(19)

<400>  63

Met Lys His Leu Trp Phe Phe Leu Leu Leu Val Ala Ala Pro Arg Trp 
1               5                   10                  15      


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


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


Thr Ala Tyr Tyr Ile His Trp Val Lys Gln Ala Pro Gly Gln Gly Leu 
    50                  55                  60                  


Glu Trp Ile Gly Tyr Ile Ser Asn Tyr Asn Arg Ala Thr Asn Tyr Asn 
65                  70                  75                  80  


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


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


Tyr Tyr Cys Ala Arg Asp Tyr Asp Tyr Asp Val Gly Met Asp Tyr Trp 
        115                 120                 125             


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


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


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


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


Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
        195                 200                 205             


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  64
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  21R83 Heavy chain variable region

<400>  64

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


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


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


Gly Tyr Ile Ser Asn Tyr Asn Arg Ala Thr Asn Tyr Asn Gln Lys Phe 
    50                  55                  60                  


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


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


Ala Arg Asp Tyr Asp Tyr Asp Val Gly Met Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  65
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  21R83 Heavy chain CDR2

<400>  65

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


Gly 
    


<210>  66
<211>  1392
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  21R83 Heavy chain nucleotide sequence with signal sequence (13B 
       Version 1)


<220>
<221>  SIGNAL
<222>  (1)..(57)

<400>  66
atgaagcacc tgtggttctt tctgctgctg gtggccgctc ccagatgggt gctgtcccag       60

gtgcagctgg tgcagtctgg cgccgaagtg aagaaacctg gcgcctccgt gaagatctcc      120

tgcaaggcct ccggctactc cttcaccgcc tactacatcc actgggtcaa gcaggcccct      180

ggacagggcc tggaatggat cggctacatc tccaactaca accgggccac caattacaac      240

cagaaattca agggccgcgt gaccttcacc accgacacct ctacctctac cgcctacatg      300

gaactgcggt ccctgcggag cgacgacacc gccgtgtact actgcgccag agactacgac      360

tacgacgtgg gcatggacta ctggggccag ggcacactcg tgaccgtgtc tagcgcttcc      420

accaagggcc cctccgtgtt tcctctggcc ccttgctcca gatccacctc cgagtctacc      480

gccgctctgg gctgcctcgt gaaggactac ttccccgagc ccgtgacagt gtcctggaac      540

tctggcgctc tgacctccgg cgtgcacacc tttccagctg tgctgcagtc ctccggcctg      600

tactccctgt cctccgtcgt gactgtgccc tcctccaact tcggcaccca gacctacacc      660

tgtaacgtgg accacaagcc ctccaacacc aaggtggaca agaccgtgga acggaagtgc      720

tgcgtggaat gccccccttg tcctgcccct cctgtggctg gccctagcgt gttcctgttc      780

cccccaaagc ccaaggacac cctgatgatc tcccggaccc ccgaagtgac ctgcgtggtg      840

gtggatgtgt cccacgagga ccccgaggtg cagttcaatt ggtacgtgga cggcgtggaa      900

gtgcacaacg ccaagaccaa gcccagagag gaacagttca actccacctt ccgggtggtg      960

tccgtgctga ccgtggtgca tcaggactgg ctgaacggca aagagtacaa gtgcaaggtg     1020

tccaacaagg gcctgcctgc ccccatcgaa aagaccatct ctaagaccaa gggacagccc     1080

cgcgagcccc aggtgtacac actgcctcca tcccgggaag agatgaccaa gaaccaggtg     1140

tccctgacct gtctggtgga aggcttctac ccctccgata tcgccgtgga atgggagtcc     1200

aacggccagc ccgagaacaa ctacaagacc acccccccca tgctggactc cgacggctca     1260

ttcttcctgt acagcgagct gacagtggac aagtcccggt ggcagcaggg caacgtgttc     1320

tcctgctccg tgatgcacga ggccctgcac aaccactaca cccagaagtc cctgtccctg     1380

agccccggca ag                                                         1392


<210>  67
<211>  1392
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  21R75 Heavy chain nucleotide sequence with signal sequence (13B 
       Version S1-2)


<220>
<221>  SIGNAL
<222>  (1)..(57)

<400>  67
atgaagcacc tgtggttctt tctgctgctg gtggccgctc ccagatgggt gctgtcccag       60

gttcagctag ttcagtctgg agcggaagtt aagaaacctg gagcatccgt gaaaataagt      120

tgcaaggcat ccggttactc gttcaccgca tactatatcc actgggttaa acaggcacca      180

ggacagggac ttgaatggat cggatatatc gctggatata aagatgctac aaactataac      240

caaaaattca aaggacgcgt gactttcaca actgacacct caacctcgac agcatacatg      300

gaattacggt ccctacggtc tgacgacact gccgtttact attgcgctag agattatgat      360

tatgatgttg gaatggacta ttggggccag ggaacactgg tgacagtgtc ttctgcatcc      420

actaagggac catccgtgtt ccctttggcc ccttgctctc gttcgacctc tgaatcgact      480

gccgctctgg gatgcctcgt gaaagattac ttccctgagc ctgtgaccgt ttcctggaac      540

tcgggcgccc taacctctgg cgtgcacaca ttccctgccg tgctacagtc ttctggccta      600

tactctttat cttcggttgt taccgtacct tcttctaact tcggaaccca aacttacacc      660

tgtaacgtag accacaagcc ttcgaacacc aaggtggaca agactgttga gcgaaagtgc      720

tgcgttgagt gccctccatg tcctgcacct cctgtggctg gcccttctgt gttcctgttc      780

cctccaaaac ctaaggacac tctaatgatc tctcggactc ctgaggtgac ttgcgtggtt      840

gtggacgtgt cccacgagga ccctgaggtg cagttcaatt ggtacgtgga cggagtcgag      900

gtgcacaatg caaagaccaa gcctcgggag gaacagttca actccacctt ccgggtggtt      960

tctgtgttga ccgttgtgca ccaagactgg ctgaacggca aagaatacaa gtgcaaggtg     1020

tccaacaagg gcctgcctgc ccctatcgaa aagaccatca gcaagaccaa gggccagcct     1080

cgcgagcctc aggtgtacac cctgcctccc agccgggaag aaatgaccaa gaaccaggtg     1140

tccctgacct gtctggtgga gggcttctac ccttccgaca tcgccgttga gtgggagtct     1200

aacggacagc cggagaacaa ctacaagact acgcctccaa tgctggactc cgacggctcc     1260

ttcttcctgt actccgaact gaccgtggac aagtcccggt ggcagcaggg caacgtgttc     1320

tcatgctccg taatgcacga agccttgcac aatcactaca ctcaaaagtc cctatcctta     1380

tctcctggca ag                                                         1392


<210>  68
<211>  357
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  21R75 Heavy chain variable region nucleotide sequence (13B 
       Version 1)

<400>  68
caggtgcagc tggtgcagtc tggcgccgaa gtgaagaaac ctggcgcctc cgtgaagatc       60

tcctgcaagg cctccggcta ctccttcacc gcctactaca tccactgggt caagcaggcc      120

cctggacagg gcctggaatg gatcggctat atcgccggct acaaggacgc caccaactac      180

aaccagaaat tcaagggcag agtgaccttc accaccgaca cctccacctc taccgcctac      240

atggaactgc ggtccctgcg gagcgacgac accgccgtgt actactgcgc cagagactac      300

gactacgacg tgggcatgga ctactggggc cagggcacac tcgtgaccgt gtcctct         357


<210>  69
<211>  357
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  21R75 Heavy chain variable region nucleotide sequence (13B 
       Version 2)

<400>  69
caggttcagc tagttcagtc tggagcggaa gttaagaaac ctggagcatc cgtgaaaata       60

agttgcaagg catccggtta ctcgttcacc gcatactata tccactgggt taaacaggca      120

ccaggacagg gacttgaatg gatcggatat atcgctggat ataaagatgc tacaaactat      180

aaccaaaaat tcaaaggacg cgtgactttc acaactgaca cctcaacctc gacagcatac      240

atggaattac ggtccctacg gtctgacgac actgccgttt actattgcgc tagagattat      300

gattatgatg ttggaatgga ctattggggc cagggaacac tggtgacagt gtcttct         357


<210>  70
<211>  357
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  21R83 Heavy chain variable region nucleotide sequence (13B 
       Version 1)

<400>  70
caggtgcagc tggtgcagtc tggcgccgaa gtgaagaaac ctggcgcctc cgtgaagatc       60

tcctgcaagg cctccggcta ctccttcacc gcctactaca tccactgggt caagcaggcc      120

cctggacagg gcctggaatg gatcggctac atctccaact acaaccgggc caccaattac      180

aaccagaaat tcaagggccg cgtgaccttc accaccgaca cctctacctc taccgcctac      240

atggaactgc ggtccctgcg gagcgacgac accgccgtgt actactgcgc cagagactac      300

gactacgacg tgggcatgga ctactggggc cagggcacac tcgtgaccgt gtctagc         357


<210>  71
<211>  357
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  21R75 Heavy chain variable region nucleotide sequence (13B 
       Version 2)

<400>  71
caggttcagc tagttcagtc tggagcggaa gttaagaaac ctggagcatc cgtgaaaata       60

agttgcaagg catccggtta ctcgttcacc gcatactata tccactgggt taaacaggca      120

ccaggacagg gacttgaatg gatcggatat atcgctggat ataaagatgc tacaaactat      180

aaccaaaaat tcaaaggacg cgtgactttc acaactgaca cctcaacctc gacagcatac      240

atggaattac ggtccctacg gtctgacgac actgccgttt actattgcgc tagagattat      300

gattatgatg ttggaatgga ctattggggc cagggaacac tggtgacagt gtcttct         357


<210>  72
<211>  1395
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  21R83 Heavy chain nucleotide sequence with signal sequence


<220>
<221>  SIGNAL
<222>  (1)..(57)

<400>  72
atgaagcacc tatggttctt tctattatta gtggccgctc cccgttgggt gttatcgcag       60

gttcagctag ttcagtctgg agcggaagtt aagaaacctg gagcatccgt gaaaataagt      120

tgcaaggcat ccggttactc gttcaccgca tactatatcc actgggttaa acaggcacca      180

ggacagggac ttgaatggat cggatatatc tccaattata atagagctac aaactataac      240

caaaaattca aaggacgcgt gactttcaca actgacacct caacctcgac agcatacatg      300

gaattacggt ccctacggtc tgacgacact gccgtttact attgcgctag agattatgat      360

tatgatgttg gaatggacta ttggggccag ggaacactgg tgacagtgtc ttctgcatcc      420

actaagggac catccgtgtt ccctttggcc ccttgctctc gttcgacctc tgaatcgact      480

gccgctctgg gatgcctcgt gaaagattac ttccctgagc ctgtgaccgt ttcctggaac      540

tcgggcgccc taacctctgg cgtgcacaca ttccctgccg tgctacagtc ttctggccta      600

tactctttat cttcggttgt taccgtacct tcttctaact tcggaaccca aacttacacc      660

tgtaacgtag accacaagcc ttcgaacacc aaggtggaca agactgttga gcgaaagtgc      720

tgcgttgagt gccctccatg tcctgcacct cctgtggctg gcccttctgt gttcctgttc      780

cctccaaaac ctaaggacac tctaatgatc tctcggactc ctgaggtgac ttgcgtggtt      840

gtggacgtgt cccacgagga ccctgaggtg cagttcaatt ggtacgtgga cggagtcgag      900

gtgcacaatg caaagaccaa gcctcgggag gaacagttca actccacctt ccgggtggtt      960

tctgtgttga ccgttgtgca ccaagactgg ctgaacggca aagaatacaa gtgcaaggtg     1020

tccaacaagg gcctgcctgc ccctatcgaa aagaccatca gcaagaccaa gggccagcct     1080

cgcgagcctc aggtgtacac cctgcctccc agccgggaag aaatgaccaa gaaccaggtg     1140

tccctgacct gtctggtgga gggcttctac ccttccgaca tcgccgttga gtgggagtct     1200

aacggacagc cggagaacaa ctacaagact acgcctccaa tgctggactc cgacggctcc     1260

ttcttcctgt actccgaact gaccgtggac aagtcccggt ggcagcaggg caacgtgttc     1320

tcatgctccg taatgcacga agccttgcac aatcactaca ctcaaaagtc cctatcctta     1380

tctcctggca agtag                                                      1395


<210>  73
<211>  357
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  21R83 Heavy chain variable region nucleotide sequence (13B 
       Version 2)

<400>  73
caggttcagc tagttcagtc tggagcggaa gttaagaaac ctggagcatc cgtgaaaata       60

agttgcaagg catccggtta ctcgttcacc gcatactata tccactgggt taaacaggca      120

ccaggacagg gacttgaatg gatcggatat atctccaatt ataatagagc tacaaactat      180

aaccaaaaat tcaaaggacg cgtgactttc acaactgaca cctcaacctc gacagcatac      240

atggaattac ggtccctacg gtctgacgac actgccgttt actattgcgc tagagattat      300

gattatgatg ttggaatgga ctattggggc cagggaacac tggtgacagt gtcttct         357


<210>  74
<211>  1395
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  21R75 Heavy chain nucleotide sequence with signal sequence (13B 
       Version 2)


<220>
<221>  SIGNAL
<222>  (1)..(57)

<400>  74
atgaagcacc tatggttctt tctattatta gtggccgctc cccgttgggt gttatcgcag       60

gttcagctag ttcagtctgg agcggaagtt aagaaacctg gagcatccgt gaaaataagt      120

tgcaaggcat ccggttactc gttcaccgca tactatatcc actgggttaa acaggcacca      180

ggacagggac ttgaatggat cggatatatc gctggatata aagatgctac aaactataac      240

caaaaattca aaggacgcgt gactttcaca actgacacct caacctcgac agcatacatg      300

gaattacggt ccctacggtc tgacgacact gccgtttact attgcgctag agattatgat      360

tatgatgttg gaatggacta ttggggccag ggaacactgg tgacagtgtc ttctgcatcc      420

actaagggac catccgtgtt ccctttggcc ccttgctctc gttcgacctc tgaatcgact      480

gccgctctgg gatgcctcgt gaaagattac ttccctgagc ctgtgaccgt ttcctggaac      540

tcgggcgccc taacctctgg cgtgcacaca ttccctgccg tgctacagtc ttctggccta      600

tactctttat cttcggttgt taccgtacct tcttctaact tcggaaccca aacttacacc      660

tgtaacgtag accacaagcc ttcgaacacc aaggtggaca agactgttga gcgaaagtgc      720

tgcgttgagt gccctccatg tcctgcacct cctgtggctg gcccttctgt gttcctgttc      780

cctccaaaac ctaaggacac tctaatgatc tctcggactc ctgaggtgac ttgcgtggtt      840

gtggacgtgt cccacgagga ccctgaggtg cagttcaatt ggtacgtgga cggagtcgag      900

gtgcacaatg caaagaccaa gcctcgggag gaacagttca actccacctt ccgggtggtt      960

tctgtgttga ccgttgtgca ccaagactgg ctgaacggca aagaatacaa gtgcaaggtg     1020

tccaacaagg gcctgcctgc ccctatcgaa aagaccatca gcaagaccaa gggccagcct     1080

cgcgagcctc aggtgtacac cctgcctccc agccgggaag aaatgaccaa gaaccaggtg     1140

tccctgacct gtctggtgga gggcttctac ccttccgaca tcgccgttga gtgggagtct     1200

aacggacagc cggagaacaa ctacaagact acgcctccaa tgctggactc cgacggctcc     1260

ttcttcctgt actccgaact gaccgtggac aagtcccggt ggcagcaggg caacgtgttc     1320

tcatgctccg taatgcacga agccttgcac aatcactaca ctcaaaagtc cctatcctta     1380

tctcctggca agtag                                                      1395


<210>  75
<211>  1395
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  21M18 Heavy chain nucleotide sequence (version 2)

<400>  75
atgaagcacc tatggttctt tctattatta gtggccgctc cccgttgggt gttatcgcag       60

gttcagctag ttcagtctgg agcggaagtt aagaaacctg gagcatccgt gaaaataagt      120

tgcaaggcat ccggttactc gttcaccgca tactatatcc actgggttaa acaggcacca      180

ggacagggac ttgaatggat cggatatatc tcctcttata atggagctac aaactataac      240

caaaaattca aaggacgcgt gactttcaca actgacacct caacctcgac agcatacatg      300

gaattacggt ccctacggtc tgacgacact gccgtttact attgcgctag agattatgat      360

tatgatgttg gaatggacta ttggggccag ggaacactgg tgacagtgtc ttctgcatcc      420

actaagggac catccgtgtt ccctttggcc ccttgctctc gttcgacctc tgaatcgact      480

gccgctctgg gatgcctcgt gaaagattac ttccctgagc ctgtgaccgt ttcctggaac      540

tcgggcgccc taacctctgg cgtgcacaca ttccctgccg tgctacagtc ttctggccta      600

tactctttat cttcggttgt taccgtacct tcttctaact tcggaaccca aacttacacc      660

tgtaacgtag accacaagcc ttcgaacacc aaggtggaca agactgttga gcgaaagtgc      720

tgcgttgagt gccctccatg tcctgcacct cctgtggctg gcccttctgt gttcctgttc      780

cctccaaaac ctaaggacac tctaatgatc tctcggactc ctgaggtgac ttgcgtggtt      840

gtggacgtgt cccacgagga ccctgaggtg cagttcaatt ggtacgtgga cggagtcgag      900

gtgcacaatg caaagaccaa gcctcgggag gaacagttca actccacctt ccgggtggtt      960

tctgtgttga ccgttgtgca ccaagactgg ctgaacggca aagaatacaa gtgcaaggtg     1020

tccaacaagg gcctgcctgc ccctatcgaa aagaccatca gcaagaccaa gggccagcct     1080

cgcgagcctc aggtgtacac cctgcctccc agccgggaag aaatgaccaa gaaccaggtg     1140

tccctgacct gtctggtgga gggcttctac ccttccgaca tcgccgttga gtgggagtct     1200

aacggacagc cggagaacaa ctacaagact acgcctccaa tgctggactc cgacggctcc     1260

ttcttcctgt actccgaact gaccgtggac aagtcccggt ggcagcaggg caacgtgttc     1320

tcatgctccg taatgcacga agccttgcac aatcactaca ctcaaaagtc cctatcctta     1380

tctcctggca agtag                                                      1395


<210>  76
<211>  351
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  21M18 Heavy chain variable region (version 2)

<400>  76
cagctagttc agtctggagc ggaagttaag aaacctggag catccgtgaa aataagttgc       60

aaggcatccg gttactcgtt caccgcatac tatatccact gggttaaaca ggcaccagga      120

cagggacttg aatggatcgg atatatctcc tcttataatg gagctacaaa ctataaccaa      180

aaattcaaag gacgcgtgac tttcacaact gacacctcaa cctcgacagc atacatggaa      240

ttacggtccc tacggtctga cgacactgcc gtttactatt gcgctagaga ttatgattat      300

gatgttggaa tggactattg gggccaggga acactggtga cagtgtcttc t               351


<210>  77
<211>  1392
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  21R75 Heavy chain nucleotide sequence with signal sequence (13B 
       Version 1T)


<220>
<221>  SIGNAL
<222>  (1)..(57)

<400>  77
atgaagcacc tgtggttctt tctgctgctg gtggccgctc ccagatgggt gctgtctcag       60

gtgcagctgg tgcagtctgg cgccgaagtg aagaaacctg gcgcctccgt gaagatctcc      120

tgcaaggcct ccggctactc cttcaccgcc tactacatcc actgggtcaa gcaggcccct      180

ggacagggcc tggaatggat cggctatatc gccggctaca aggacgccac caactacaac      240

cagaaattca agggcagagt gaccttcacc accgacacct ccacctctac cgcctacatg      300

gaactgcggt ccctgcggag cgacgacacc gccgtgtact actgcgccag agactacgac      360

tacgacgtgg gcatggacta ctggggccag ggcacactcg tgaccgtgtc ctctgcttcc      420

accaagggcc cctccgtgtt tcctctggcc ccttgctcca gatccacctc cgagtctacc      480

gccgctctgg gctgcctcgt gaaggactac ttccccgagc ccgtgacagt gtcttggaac      540

tctggcgccc tgacctccgg cgtgcacacc tttccagctg tgctgcagtc ctccggcctg      600

tactccctgt cctccgtcgt gactgtgccc tcctccaact tcggcaccca gacctacacc      660

tgtaacgtgg accacaagcc ctccaacacc aaggtggaca agaccgtgga acggaagtgc      720

tgcgtggaat gccccccttg tcctgcccct cctgtggctg gccctagcgt gttcctgttc      780

cccccaaagc ccaaggacac cctgatgatc tcccggaccc ccgaagtgac ctgcgtggtg      840

gtggatgtgt cccacgagga ccccgaggtg cagttcaatt ggtacgtgga cggcgtggaa      900

gtgcacaacg ccaagaccaa gcccagagag gaacagttca actccacctt ccgggtggtg      960

tccgtgctga ccgtggtgca tcaggactgg ctgaacggca aagagtacaa gtgcaaggtg     1020

tccaacaagg gcctgcctgc ccccatcgaa aagaccatct ctaagaccaa gggacagccc     1080

cgcgagcccc aggtgtacac actgcctcca tcccgggaag agatgaccaa gaaccaggtg     1140

tccctgacct gtctggtgga aggcttctac ccctccgata tcgccgtgga atgggagtcc     1200

aacggccagc ccgagaacaa ctacaagacc acccccccca tgctggactc cgacggctca     1260

ttcttcctgt acagcgagct gacagtggac aagtcccggt ggcagcaggg caacgtgttc     1320

tcctgctccg tgatgcacga ggccctgcac aaccactaca cccagaagtc cctgtccctg     1380

agccccggca ag                                                         1392


<210>  78
<211>  1392
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  21R83 Heavy chain nucleotide sequence with signal sequence


<220>
<221>  SIGNAL
<222>  (1)..(57)

<400>  78
atgaagcacc tgtggttctt tctgctgctg gtggccgctc ccagatgggt gctgtctcag       60

gtgcagctgg tgcagtctgg cgccgaagtg aagaaacctg gcgcctccgt gaagatctcc      120

tgcaaggcct ccggctactc cttcaccgcc tactacatcc actgggtcaa gcaggcccct      180

ggacagggcc tggaatggat cggctacatc tccaactaca accgggccac caattacaac      240

cagaaattca agggccgcgt gaccttcacc accgacacct ctacctctac cgcctacatg      300

gaactgcggt ccctgcggag cgacgacacc gccgtgtact actgcgccag agactacgac      360

tacgacgtgg gcatggacta ctggggccag ggcacactcg tgaccgtgtc tagcgcttcc      420

accaagggcc cctccgtgtt tcctctggcc ccttgctcca gatccacctc cgagtctacc      480

gccgctctgg gctgcctcgt gaaggactac ttccccgagc ccgtgacagt gtcctggaac      540

tctggcgctc tgacctccgg cgtgcacacc tttccagctg tgctgcagtc ctccggcctg      600

tactccctgt cctccgtcgt gactgtgccc tcctccaact tcggcaccca gacctacacc      660

tgtaacgtgg accacaagcc ctccaacacc aaggtggaca agaccgtgga acggaagtgc      720

tgcgtggaat gccccccttg tcctgcccct cctgtggctg gccctagcgt gttcctgttc      780

cccccaaagc ccaaggacac cctgatgatc tcccggaccc ccgaagtgac ctgcgtggtg      840

gtggatgtgt cccacgagga ccccgaggtg cagttcaatt ggtacgtgga cggcgtggaa      900

gtgcacaacg ccaagaccaa gcccagagag gaacagttca actccacctt ccgggtggtg      960

tccgtgctga ccgtggtgca tcaggactgg ctgaacggca aagagtacaa gtgcaaggtg     1020

tccaacaagg gcctgcctgc ccccatcgaa aagaccatct ctaagaccaa gggacagccc     1080

cgcgagcccc aggtgtacac actgcctcca tcccgggaag agatgaccaa gaaccaggtg     1140

tccctgacct gtctggtgga aggcttctac ccctccgata tcgccgtgga atgggagtcc     1200

aacggccagc ccgagaacaa ctacaagacc acccccccca tgctggactc cgacggctca     1260

ttcttcctgt acagcgagct gacagtggac aagtcccggt ggcagcaggg caacgtgttc     1320

tcctgctccg tgatgcacga ggccctgcac aaccactaca cccagaagtc cctgtccctg     1380

agccccggca ag                                                         1392


<210>  79
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Alternative 21R75, 21R79, 21R83, and 21M18 Heavy chain CDR1

<400>  79

Ala Tyr Tyr Ile His 
1               5   


<210>  80
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Anti-DLL4 heavy chain CDR2 consensus sequence


<220>
<221>  MISC_FEATURE
<222>  (3)..(3)
<223>  can be serine or alanine

<220>
<221>  MISC_FEATURE
<222>  (4)..(4)
<223>  can be serine, asparagine, or glycine

<220>
<221>  MISC_FEATURE
<222>  (6)..(6)
<223>  can be asparagine or lysine

<220>
<221>  MISC_FEATURE
<222>  (7)..(7)
<223>  can be glycine, arginine, or aspartic acid

<400>  80

Tyr Ile Xaa Xaa Tyr Xaa Xaa Ala Thr Asn Tyr Asn Gln Lys Phe Lys 
1               5                   10                  15      


Gly 
    


