                         SEQUENCE LISTING

<110>  ALETHIA BIOTHERAPEUTICS INC.
       NATIONAL RESEARCH COUNCIL OF CANADA
 
<120>  ANTI-SIGLEC-15 ANTIBODIES

<130>  11504-141

<140>  PCT/CA2013/000646
<141>  2013-07-17

<150>  US61/673,442
<151>  2012-07-19

<150>  US61/677,049
<151>  2013-03-12

<150>  US61/810,415
<151>  2013-04-10

<160>  92    

<170>  PatentIn version 3.5

<210>  1
<211>  987
<212>  DNA
<213>  Homo sapiens

<400>  1
atggaaaagt ccatctggct gctggcctgc ttggcgtggg ttctcccgac aggctcattt       60

gtgagaacta aaatagatac tacggagaac ttgctcaaca cagaggtgca cagctcgcca      120

gcgcagcgct ggtccatgca ggtgccaccc gaggtgagcg cggaggcagg cgacgcggca      180

gtgctgccct gcaccttcac gcacccgcac cgccactacg acgggccgct gacggccatc      240

tggcgcgcgg gcgagcccta tgcgggcccg caggtgttcc gctgcgctgc ggcgcggggc      300

agcgagctct gccagacggc gctgagcctg cacggccgct tccggctgct gggcaacccg      360

cgccgcaacg acctctcgct gcgcgtcgag cgcctcgccc tggctgacga ccgccgctac      420

ttctgccgcg tcgagttcgc cggcgacgtc catgaccgct acgagagccg ccacggcgtc      480

cggctgcacg tgacagccgc gccgcggatc gtcaacatct cggtgctgcc cagtccggct      540

cacgccttcc gcgcgctctg cactgccgaa ggggagccgc cgcccgccct cgcctggtcc      600

ggcccggccc tgggcaacag cttggcagcc gtgcggagcc cgcgtgaggg tcacggccac      660

ctagtgaccg ccgaactgcc cgcactgacc catgacggcc gctacacgtg tacggccgcc      720

aacagcctgg gccgctccga ggccagcgtc tacctgttcc gcttccatgg cgccagcggg      780

gcctcgacgg tcgccctcct gctcggcgct ctcggcttca aggcgctgct gctgctcggg      840

gtcctggccg cccgcgctgc ccgccgccgc ccagagcatc tggacacccc ggacacccca      900

ccacggtccc aggcccagga gtccaattat gaaaatttga gccagatgaa cccccggagc      960

ccaccagcca ccatgtgctc accgtga                                          987


<210>  2
<211>  328
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Glu Lys Ser Ile Trp Leu Leu Ala Cys Leu Ala Trp Val Leu Pro 
1               5                   10                  15      


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


Asn Thr Glu Val His Ser Ser Pro Ala Gln Arg Trp Ser Met Gln Val 
        35                  40                  45              


Pro Pro Glu Val Ser Ala Glu Ala Gly Asp Ala Ala Val Leu Pro Cys 
    50                  55                  60                  


Thr Phe Thr His Pro His Arg His Tyr Asp Gly Pro Leu Thr Ala Ile 
65                  70                  75                  80  


Trp Arg Ala Gly Glu Pro Tyr Ala Gly Pro Gln Val Phe Arg Cys Ala 
                85                  90                  95      


Ala Ala Arg Gly Ser Glu Leu Cys Gln Thr Ala Leu Ser Leu His Gly 
            100                 105                 110         


Arg Phe Arg Leu Leu Gly Asn Pro Arg Arg Asn Asp Leu Ser Leu Arg 
        115                 120                 125             


Val Glu Arg Leu Ala Leu Ala Asp Asp Arg Arg Tyr Phe Cys Arg Val 
    130                 135                 140                 


Glu Phe Ala Gly Asp Val His Asp Arg Tyr Glu Ser Arg His Gly Val 
145                 150                 155                 160 


Arg Leu His Val Thr Ala Ala Pro Arg Ile Val Asn Ile Ser Val Leu 
                165                 170                 175     


Pro Ser Pro Ala His Ala Phe Arg Ala Leu Cys Thr Ala Glu Gly Glu 
            180                 185                 190         


Pro Pro Pro Ala Leu Ala Trp Ser Gly Pro Ala Leu Gly Asn Ser Leu 
        195                 200                 205             


Ala Ala Val Arg Ser Pro Arg Glu Gly His Gly His Leu Val Thr Ala 
    210                 215                 220                 


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


Asn Ser Leu Gly Arg Ser Glu Ala Ser Val Tyr Leu Phe Arg Phe His 
                245                 250                 255     


Gly Ala Ser Gly Ala Ser Thr Val Ala Leu Leu Leu Gly Ala Leu Gly 
            260                 265                 270         


Phe Lys Ala Leu Leu Leu Leu Gly Val Leu Ala Ala Arg Ala Ala Arg 
        275                 280                 285             


Arg Arg Pro Glu His Leu Asp Thr Pro Asp Thr Pro Pro Arg Ser Gln 
    290                 295                 300                 


Ala Gln Glu Ser Asn Tyr Glu Asn Leu Ser Gln Met Asn Pro Arg Ser 
305                 310                 315                 320 


Pro Pro Ala Thr Met Cys Ser Pro 
                325             


<210>  3
<211>  1029
<212>  DNA
<213>  Mus musculus

<400>  3
atggaggggt ccctccaact cctggcctgc ttggcctgtg tgctccagat gggatccctt       60

gtgaaaacta gaagagacgc ttcgggggat ctgctcaaca cagaggcgca cagtgccccg      120

gcgcagcgct ggtccatgca ggtgcccgcg gaggtgaacg cggaggctgg cgacgcggcg      180

gtgctgccct gcaccttcac gcacccgcac cgccactacg acgggccgct gacggccatc      240

tggcgctcgg gcgagccgta cgcgggcccg caggtgttcc gctgcaccgc ggcgccgggc      300

agcgagctgt gccagacggc gctgagcctg cacggccgct tccgcctgct gggcaacccg      360

cgccgcaacg acctgtccct gcgcgtcgag cgcctcgccc tggcggacag cggccgctac      420

ttctgccgcg tggagttcac cggcgacgcc cacgatcgct atgagagtcg ccatggggtc      480

cgtctgcgcg tgactgcagc tgcgccgcgg atcgtcaaca tctcggtgct gccgggcccc      540

gcgcacgcct tccgcgcgct ctgcaccgcc gagggggagc ccccgcccgc cctcgcctgg      600

tcgggtcccg ccccaggcaa cagctccgct gccctgcagg gccagggtca cggctaccag      660

gtgaccgccg agttgcccgc gctgacccgc gacggccgct acacgtgcac ggcggccaat      720

agcctgggcc gcgccgaggc cagcgtctac ctgttccgct tccacggcgc ccccggaacc      780

tcgaccctag cgctcctgct gggcgcgctg ggcctcaagg ccttgctgct gcttggcatt      840

ctgggagcgc gtgccacccg acgccgacta gatcacctgg tcccccagga cacccctcca      900

cggtctcagg ctcaggagtc caattatgaa aatttgagcc agatgagtcc tccaggccac      960

cagctgccac gtgtttgctg tgaggaactc ctcagccatc accatctagt cattcaccat     1020

gagaaataa                                                             1029


<210>  4
<211>  342
<212>  PRT
<213>  Mus musculus

<400>  4

Met Glu Gly Ser Leu Gln Leu Leu Ala Cys Leu Ala Cys Val Leu Gln 
1               5                   10                  15      


Met Gly Ser Leu Val Lys Thr Arg Arg Asp Ala Ser Gly Asp Leu Leu 
            20                  25                  30          


Asn Thr Glu Ala His Ser Ala Pro Ala Gln Arg Trp Ser Met Gln Val 
        35                  40                  45              


Pro Ala Glu Val Asn Ala Glu Ala Gly Asp Ala Ala Val Leu Pro Cys 
    50                  55                  60                  


Thr Phe Thr His Pro His Arg His Tyr Asp Gly Pro Leu Thr Ala Ile 
65                  70                  75                  80  


Trp Arg Ser Gly Glu Pro Tyr Ala Gly Pro Gln Val Phe Arg Cys Thr 
                85                  90                  95      


Ala Ala Pro Gly Ser Glu Leu Cys Gln Thr Ala Leu Ser Leu His Gly 
            100                 105                 110         


Arg Phe Arg Leu Leu Gly Asn Pro Arg Arg Asn Asp Leu Ser Leu Arg 
        115                 120                 125             


Val Glu Arg Leu Ala Leu Ala Asp Ser Gly Arg Tyr Phe Cys Arg Val 
    130                 135                 140                 


Glu Phe Thr Gly Asp Ala His Asp Arg Tyr Glu Ser Arg His Gly Val 
145                 150                 155                 160 


Arg Leu Arg Val Thr Ala Ala Ala Pro Arg Ile Val Asn Ile Ser Val 
                165                 170                 175     


Leu Pro Gly Pro Ala His Ala Phe Arg Ala Leu Cys Thr Ala Glu Gly 
            180                 185                 190         


Glu Pro Pro Pro Ala Leu Ala Trp Ser Gly Pro Ala Pro Gly Asn Ser 
        195                 200                 205             


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


Leu Pro Ala Leu Thr Arg Asp Gly Arg Tyr Thr Cys Thr Ala Ala Asn 
225                 230                 235                 240 


Ser Leu Gly Arg Ala Glu Ala Ser Val Tyr Leu Phe Arg Phe His Gly 
                245                 250                 255     


Ala Pro Gly Thr Ser Thr Leu Ala Leu Leu Leu Gly Ala Leu Gly Leu 
            260                 265                 270         


Lys Ala Leu Leu Leu Leu Gly Ile Leu Gly Ala Arg Ala Thr Arg Arg 
        275                 280                 285             


Arg Leu Asp His Leu Val Pro Gln Asp Thr Pro Pro Arg Ser Gln Ala 
    290                 295                 300                 


Gln Glu Ser Asn Tyr Glu Asn Leu Ser Gln Met Ser Pro Pro Gly His 
305                 310                 315                 320 


Gln Leu Pro Arg Val Cys Cys Glu Glu Leu Leu Ser His His His Leu 
                325                 330                 335     


Val Ile His His Glu Lys 
            340         


<210>  5
<211>  239
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  25E9 light chain (kappa) chimeric

<400>  5

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 Ala Ala Pro Ser Val Pro 
            20                  25                  30          


Val Thr Pro Gly Glu Ser Val Ser Ile Ser Cys Arg Ser Thr Lys Ser 
        35                  40                  45              


Leu Leu His Ser Asn Gly Asn Thr Tyr Leu Tyr Trp Phe Leu Gln Arg 
    50                  55                  60                  


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


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


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


Cys Met Gln His Leu Glu Tyr Pro Phe Thr Phe Gly Gly Gly Thr Lys 
        115                 120                 125             


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


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


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


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


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


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


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


<210>  6
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  25E9 light chain mouse variable domain

<400>  6

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


Glu Ser Val Ser Ile Ser Cys Arg Ser Thr Lys Ser Leu Leu His Ser 
            20                  25                  30          


Asn Gly Asn Thr Tyr Leu Tyr Trp Phe Leu Gln Arg Pro Gly Gln Ser 
        35                  40                  45              


Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro 
    50                  55                  60                  


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His 
                85                  90                  95      


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


<210>  7
<211>  239
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  25E9 light chain (kappa) humanized variant 1

<400>  7

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 Leu Ser Leu Pro 
            20                  25                  30          


Val Thr Pro Gly Glu Pro Ala Ser Ile Ser Cys Arg Ser Thr Lys Ser 
        35                  40                  45              


Leu Leu His Ser Asn Gly Asn Thr Tyr Leu Tyr Trp Tyr Leu Gln Lys 
    50                  55                  60                  


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


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


Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr 
            100                 105                 110         


Cys Met Gln His Leu Glu Tyr Pro Phe Thr Phe Gly Gly Gly Thr Lys 
        115                 120                 125             


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


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


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


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


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


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


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


<210>  8
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  25E9 light chain humanized variant 1 variable domain

<400>  8

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


Glu Pro Ala Ser Ile Ser Cys Arg Ser Thr Lys Ser Leu Leu His Ser 
            20                  25                  30          


Asn Gly Asn Thr Tyr Leu Tyr Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro 
    50                  55                  60                  


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His 
                85                  90                  95      


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


<210>  9
<211>  239
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  25E9 light chain (kappa) humanized variant 2

<400>  9

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 Leu Ser Leu Pro 
            20                  25                  30          


Val Thr Pro Gly Glu Pro Ala Ser Ile Ser Cys Arg Ser Thr Lys Ser 
        35                  40                  45              


Leu Leu His Ser Asn Gly Asn Thr Tyr Leu Tyr Trp Phe Leu Gln Lys 
    50                  55                  60                  


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


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


Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr 
            100                 105                 110         


Cys Met Gln His Leu Glu Tyr Pro Phe Thr Phe Gly Gly Gly Thr Lys 
        115                 120                 125             


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


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


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


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


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


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


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


<210>  10
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  25E9 light chain humanized variant 2 variable domain

<400>  10

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


Glu Pro Ala Ser Ile Ser Cys Arg Ser Thr Lys Ser Leu Leu His Ser 
            20                  25                  30          


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


Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro 
    50                  55                  60                  


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His 
                85                  90                  95      


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


<210>  11
<211>  472
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  25E9 heavy chain (IgG1) chimeric

<400>  11

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


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


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


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


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


Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Ala Asp Arg Ser Ser Thr 
                85                  90                  95      


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


Tyr Tyr Cys Thr Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly 
        115                 120                 125             


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


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


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


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


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


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


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


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


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


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


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


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


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
                325                 330                 335     


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


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


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr 
    370                 375                 380                 


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


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
                405                 410                 415     


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


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


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


Ser Leu Ser Leu Ser Pro Gly Lys 
465                 470         


<210>  12
<211>  123
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  25E9 heavy chain mouse variable domain

<400>  12

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


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


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


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


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


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


Thr Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly Phe Ala Tyr 
            100                 105                 110         


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


<210>  13
<211>  472
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  25E9 heavy chain (IgG1) humanized variant 1

<400>  13

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


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


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


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


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


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


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


Tyr Tyr Cys Thr Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly 
        115                 120                 125             


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


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


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


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


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


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


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


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


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


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


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


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


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
                325                 330                 335     


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


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


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr 
    370                 375                 380                 


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


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
                405                 410                 415     


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


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


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


Ser Leu Ser Leu Ser Pro Gly Lys 
465                 470         


<210>  14
<211>  123
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  25E9 heavy chain humanized variant 1 variable domain

<400>  14

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


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


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


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


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


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


Thr Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly Phe Ala Tyr 
            100                 105                 110         


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


<210>  15
<211>  472
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  25E9 heavy chain (IgG1) humanized variant 2

<400>  15

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


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


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


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


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


Gln Lys Phe Lys Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Ser 
                85                  90                  95      


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


Tyr Tyr Cys Thr Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly 
        115                 120                 125             


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


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


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


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


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


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


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


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


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


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


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


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


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
                325                 330                 335     


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


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


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr 
    370                 375                 380                 


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


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
                405                 410                 415     


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


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


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


Ser Leu Ser Leu Ser Pro Gly Lys 
465                 470         


<210>  16
<211>  123
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  25E9 heavy chain humanized variant 2 variable domain

<400>  16

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


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


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


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


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


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


Thr Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly Phe Ala Tyr 
            100                 105                 110         


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


<210>  17
<211>  472
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  25E9 heavy chain (IgG1) humanized variant 3

<400>  17

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


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


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


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


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


Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Ala Asp Arg Ser Thr Ser 
                85                  90                  95      


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


Tyr Tyr Cys Thr Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly 
        115                 120                 125             


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


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


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


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


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


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


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


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


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


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


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


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


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
                325                 330                 335     


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


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


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr 
    370                 375                 380                 


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


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
                405                 410                 415     


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


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


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


Ser Leu Ser Leu Ser Pro Gly Lys 
465                 470         


<210>  18
<211>  123
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  25E9 heavy chain humanized variant 3 variable domain

<400>  18

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


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


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


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


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


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


Thr Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly Phe Ala Tyr 
            100                 105                 110         


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


<210>  19
<211>  472
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  25E9 heavy chain (IgG1) humanized variant 4

<400>  19

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


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


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


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


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


Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Ala Asp Arg Ser Thr Ser 
                85                  90                  95      


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


Tyr Tyr Cys Thr Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly 
        115                 120                 125             


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


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


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


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


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


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


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


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


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


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


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


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


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
                325                 330                 335     


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


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


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr 
    370                 375                 380                 


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


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
                405                 410                 415     


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


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


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


Ser Leu Ser Leu Ser Pro Gly Lys 
465                 470         


<210>  20
<211>  123
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  25E9 heavy chain humanized variant 4 variable domain

<400>  20

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


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


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


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


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


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


Thr Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly Phe Ala Tyr 
            100                 105                 110         


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


<210>  21
<211>  239
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  chimeric 25D8 light chain (kappa)

<400>  21

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 Ala Ala Phe Ser Asn Pro 
            20                  25                  30          


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


Leu Leu His Ser Asn Gly Ile Thr Tyr Leu Tyr Trp Tyr Leu Gln Lys 
    50                  55                  60                  


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


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


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


Cys Ala Gln Asn Leu Glu Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys 
        115                 120                 125             


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


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


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


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


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


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


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


<210>  22
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  25D8 light chain mouse variable domain

<400>  22

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


Thr Ser Ala Ser Ile Ser Cys Arg Ser Ser Lys Ser Leu Leu His Ser 
            20                  25                  30          


Asn Gly Ile Thr Tyr Leu Tyr Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


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


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ala Gln Asn 
                85                  90                  95      


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


<210>  23
<211>  239
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized 25D8 light chain (kappa)

<400>  23

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 Thr Pro Leu Ser Leu Pro 
            20                  25                  30          


Val Thr Pro Gly Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Lys Ser 
        35                  40                  45              


Leu Leu His Ser Asn Gly Ile Thr Tyr Leu Tyr Trp Tyr Leu Gln Lys 
    50                  55                  60                  


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


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


Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr 
            100                 105                 110         


Cys Ala Gln Asn Leu Glu Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys 
        115                 120                 125             


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


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


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


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


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


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


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


<210>  24
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized 25D8 light chain variable domain

<400>  24

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


Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Lys Ser Leu Leu His Ser 
            20                  25                  30          


Asn Gly Ile Thr Tyr Leu Tyr Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


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


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ala Gln Asn 
                85                  90                  95      


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


<210>  25
<211>  463
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Chimeric 25D8 heavy chain (IgG2)

<400>  25

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


Thr His Ala Gln Val Gln Val Gln Gln Pro Gly Ala Glu Leu Val Lys 
            20                  25                  30          


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


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


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


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


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


Tyr Tyr Cys Ala Arg Gly Gly Asp Gly Asp Tyr Phe Asp Tyr Trp Gly 
        115                 120                 125             


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  26
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  25D8 heavy chain mouse variable domain

<400>  26

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


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


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


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


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


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


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


Thr Leu Thr Val Ser Ser 
        115             


<210>  27
<211>  463
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized 25D8 heavy chain (IgG2)

<400>  27

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


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


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


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


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


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


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


Tyr Tyr Cys Ala Arg Gly Gly Asp Gly Asp Tyr Phe Asp Tyr Trp Gly 
        115                 120                 125             


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  28
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized 25D8 heavy chain variable domain

<400>  28

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


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


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


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


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


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


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


Thr Val Thr Val Ser Ser 
        115             


<210>  29
<211>  468
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  25E9 heavy chain (Igg2) humanized variant 1

<400>  29

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


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


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


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


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


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


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


Tyr Tyr Cys Thr Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly 
        115                 120                 125             


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Ser Pro Gly Lys 
465             


<210>  30
<211>  468
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  25E9 heavy chain (IgG2) chimeric

<400>  30

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


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


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


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


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


Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Ala Asp Arg Ser Ser Thr 
                85                  90                  95      


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


Tyr Tyr Cys Thr Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly 
        115                 120                 125             


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Ser Pro Gly Lys 
465             


<210>  31
<211>  330
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human IgG1 constant region

<400>  31

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>  32
<211>  326
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Human IgG2 constant region

<400>  32

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>  33
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Generic 25E9 light chain variable domain (consensus 1)


<220>
<221>  MISC_FEATURE
<222>  (7)..(7)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:6

<220>
<221>  MISC_FEATURE
<222>  (8)..(8)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:6

<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:6

<220>
<221>  MISC_FEATURE
<222>  (11)..(11)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:6

<220>
<221>  MISC_FEATURE
<222>  (18)..(18)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:6

<220>
<221>  MISC_FEATURE
<222>  (19)..(19)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:6

<220>
<221>  MISC_FEATURE
<222>  (41)..(41)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:6

<220>
<221>  MISC_FEATURE
<222>  (44)..(44)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:6

<220>
<221>  MISC_FEATURE
<222>  (75)..(75)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:6

<220>
<221>  MISC_FEATURE
<222>  (79)..(79)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:6

<220>
<221>  MISC_FEATURE
<222>  (109)..(109)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:6

<400>  33

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


Glu Xaa Xaa Ser Ile Ser Cys Arg Ser Thr Lys Ser Leu Leu His Ser 
            20                  25                  30          


Asn Gly Asn Thr Tyr Leu Tyr Trp Xaa Leu Gln Xaa Pro Gly Gln Ser 
        35                  40                  45              


Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro 
    50                  55                  60                  


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His 
                85                  90                  95      


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


<210>  34
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Generic 25E9 light chain variable domain (consensus 2)


<220>
<221>  MISC_FEATURE
<222>  (7)..(7)
<223>  Xaa may be a conservative amino acid substitution in comparison 
       with SEQ ID NO.:6

<220>
<221>  MISC_FEATURE
<222>  (8)..(8)
<223>  Xaa may be a semi-conservative amino acid substitution in 
       comparison with SEQ ID NO.:6

<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  Xaa may be P or L

<220>
<221>  MISC_FEATURE
<222>  (11)..(11)
<223>  Xaa may be a conservative amino acid substitution in comparison 
       with SEQ ID NO.:6

<220>
<221>  MISC_FEATURE
<222>  (18)..(18)
<223>  Xaa may be a semi-conservative amino acid substitution in 
       comparison with SEQ ID NO.:6

<220>
<221>  MISC_FEATURE
<222>  (19)..(19)
<223>  Xaa may be a semi-conservative amino acid substitution in 
       comparison with SEQ ID NO.:6

<220>
<221>  MISC_FEATURE
<222>  (41)..(41)
<223>  Xaa may be a conservative amino acid substitution in comparison 
       with SEQ ID NO.:6

<220>
<221>  MISC_FEATURE
<222>  (44)..(44)
<223>  Xaa may be a conservative amino acid substitution in comparison 
       with SEQ ID NO.:6

<220>
<221>  MISC_FEATURE
<222>  (75)..(75)
<223>  Xaa may be A or D

<220>
<221>  MISC_FEATURE
<222>  (79)..(79)
<223>  Xaa may be a conservative amino acid substitution in comparison 
       with SEQ ID NO.:6

<220>
<221>  MISC_FEATURE
<222>  (109)..(109)
<223>  Xaa may be a conservative amino acid substitution in comparison 
       with SEQ ID NO.:6

<400>  34

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


Glu Xaa Xaa Ser Ile Ser Cys Arg Ser Thr Lys Ser Leu Leu His Ser 
            20                  25                  30          


Asn Gly Asn Thr Tyr Leu Tyr Trp Xaa Leu Gln Xaa Pro Gly Gln Ser 
        35                  40                  45              


Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro 
    50                  55                  60                  


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His 
                85                  90                  95      


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


<210>  35
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Generic 25E9 light chain variable domain (consensus 3)


<220>
<221>  MISC_FEATURE
<222>  (7)..(7)
<223>  Xaa may be A or S

<220>
<221>  MISC_FEATURE
<222>  (8)..(8)
<223>  Xaa may be A or P

<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  Xaa may be P or L

<220>
<221>  MISC_FEATURE
<222>  (11)..(11)
<223>  Xaa may be a hydrophobic amino acid

<220>
<221>  MISC_FEATURE
<222>  (18)..(18)
<223>  Xaa may be S or P

<220>
<221>  MISC_FEATURE
<222>  (19)..(19)
<223>  Xaa may be a hydrophobic amino acid

<220>
<221>  MISC_FEATURE
<222>  (41)..(41)
<223>  Xaa may be an aromatic amino acid

<220>
<221>  MISC_FEATURE
<222>  (44)..(44)
<223>  Xaa may be a basic amino acid

<220>
<221>  MISC_FEATURE
<222>  (75)..(75)
<223>  Xaa may be A or D

<220>
<221>  MISC_FEATURE
<222>  (79)..(79)
<223>  Xaa may be a basic amino acid

<220>
<221>  MISC_FEATURE
<222>  (109)..(109)
<223>  Xaa may be a hydrophobic amino acid

<400>  35

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


Glu Xaa Xaa Ser Ile Ser Cys Arg Ser Thr Lys Ser Leu Leu His Ser 
            20                  25                  30          


Asn Gly Asn Thr Tyr Leu Tyr Trp Xaa Leu Gln Xaa Pro Gly Gln Ser 
        35                  40                  45              


Pro Gln Leu Leu Ile Tyr Arg Met Ser Asn Leu Ala Ser Gly Val Pro 
    50                  55                  60                  


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln His 
                85                  90                  95      


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


<210>  36
<211>  123
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Generic 25E9 heavy chain variable domain (consensus 1)


<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:12

<220>
<221>  MISC_FEATURE
<222>  (11)..(11)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:12

<220>
<221>  MISC_FEATURE
<222>  (12)..(12)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:12

<220>
<221>  MISC_FEATURE
<222>  (13)..(13)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:12

<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:12

<220>
<221>  MISC_FEATURE
<222>  (19)..(19)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:12

<220>
<221>  MISC_FEATURE
<222>  (20)..(20)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:12

<220>
<221>  MISC_FEATURE
<222>  (38)..(38)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:12

<220>
<221>  MISC_FEATURE
<222>  (40)..(40)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:12

<220>
<221>  MISC_FEATURE
<222>  (42)..(42)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:12

<220>
<221>  MISC_FEATURE
<222>  (43)..(43)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:12

<220>
<221>  MISC_FEATURE
<222>  (48)..(48)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:12

<220>
<221>  MISC_FEATURE
<222>  (67)..(67)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:12

<220>
<221>  MISC_FEATURE
<222>  (68)..(68)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:12

<220>
<221>  MISC_FEATURE
<222>  (70)..(70)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:12

<220>
<221>  MISC_FEATURE
<222>  (74)..(74)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:12

<220>
<221>  MISC_FEATURE
<222>  (76)..(76)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:12

<220>
<221>  MISC_FEATURE
<222>  (77)..(77)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:12

<220>
<221>  MISC_FEATURE
<222>  (87)..(87)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:12

<220>
<221>  MISC_FEATURE
<222>  (91)..(91)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:12

<220>
<221>  MISC_FEATURE
<222>  (123)..(123)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:12

<400>  36

Glu Ile Gln Leu Gln Gln Ser Gly Xaa Glu Xaa Xaa Xaa Pro Gly Xaa 
1               5                   10                  15      


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


Asp Met His Trp Val Xaa Gln Xaa Pro Xaa Xaa Gly Leu Glu Trp Xaa 
        35                  40                  45              


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


Lys Gly Xaa Xaa Thr Xaa Thr Ala Asp Xaa Ser Xaa Xaa Thr Ala Tyr 
65                  70                  75                  80  


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


Thr Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly Phe Ala Tyr 
            100                 105                 110         


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


<210>  37
<211>  123
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Generic 25E9 heavy chain variable domain (consensus 2)


<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  Xaa may be a semi-conservative amino acid substitution in 
       comparison with SEQ ID NO.:12

<220>
<221>  MISC_FEATURE
<222>  (11)..(11)
<223>  Xaa may be a conservative amino acid substitution in comparison 
       with SEQ ID NO.:12

<220>
<221>  MISC_FEATURE
<222>  (12)..(12)
<223>  Xaa may be V or K

<220>
<221>  MISC_FEATURE
<222>  (13)..(13)
<223>  Xaa may be a conservative amino acid substitution in comparison 
       with SEQ ID NO.:12

<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  Xaa may be a conservative amino acid substitution in comparison 
       with SEQ ID NO.:12

<220>
<221>  MISC_FEATURE
<222>  (19)..(19)
<223>  Xaa may be a semi-conservative amino acid substitution in 
       comparison with SEQ ID NO.:12

<220>
<221>  MISC_FEATURE
<222>  (20)..(20)
<223>  Xaa may be a conservative amino acid substitution in comparison 
       with SEQ ID NO.:12

<220>
<221>  MISC_FEATURE
<222>  (38)..(38)
<223>  Xaa may be a conservative amino acid substitution in comparison 
       with SEQ ID NO.:12

<220>
<221>  MISC_FEATURE
<222>  (40)..(40)
<223>  Xaa may be a conservative amino acid substitution in comparison 
       with SEQ ID NO.:12

<220>
<221>  MISC_FEATURE
<222>  (42)..(42)
<223>  Xaa may be V or G

<220>
<221>  MISC_FEATURE
<222>  (43)..(43)
<223>  Xaa may be a conservative amino acid substitution in comparison 
       with SEQ ID NO.:12

<220>
<221>  MISC_FEATURE
<222>  (48)..(48)
<223>  Xaa may be a conservative amino acid substitution in comparison 
       with SEQ ID NO.:12

<220>
<221>  MISC_FEATURE
<222>  (67)..(67)
<223>  Xaa may be a conservative amino acid substitution in comparison 
       with SEQ ID NO.:12

<220>
<221>  MISC_FEATURE
<222>  (68)..(68)
<223>  Xaa may be a semi-conservative amino acid substitution in 
       comparison with SEQ ID NO.:12

<220>
<221>  MISC_FEATURE
<222>  (70)..(70)
<223>  Xaa may be a conservative amino acid substitution in comparison 
       with SEQ ID NO.:12

<220>
<221>  MISC_FEATURE
<222>  (74)..(74)
<223>  Xaa may be a conservative amino acid substitution in comparison 
       with SEQ ID NO.:12

<220>
<221>  MISC_FEATURE
<222>  (76)..(76)
<223>  Xaa may be a conservative amino acid substitution in comparison 
       with SEQ ID NO.:12

<220>
<221>  MISC_FEATURE
<222>  (77)..(77)
<223>  Xaa may be a conservative amino acid substitution in comparison 
       with SEQ ID NO.:12

<220>
<221>  MISC_FEATURE
<222>  (87)..(87)
<223>  Xaa may be T or R

<220>
<221>  MISC_FEATURE
<222>  (91)..(91)
<223>  Xaa may be a conservative amino acid substitution in comparison 
       with SEQ ID NO.:12

<220>
<221>  MISC_FEATURE
<222>  (123)..(123)
<223>  Xaa may be a conservative amino acid substitution in comparison 
       with SEQ ID NO.:12

<400>  37

Glu Ile Gln Leu Gln Gln Ser Gly Xaa Glu Xaa Xaa Xaa Pro Gly Xaa 
1               5                   10                  15      


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


Asp Met His Trp Val Xaa Gln Xaa Pro Xaa Xaa Gly Leu Glu Trp Xaa 
        35                  40                  45              


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


Lys Gly Xaa Xaa Thr Xaa Thr Ala Asp Xaa Ser Xaa Xaa Thr Ala Tyr 
65                  70                  75                  80  


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


Thr Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly Phe Ala Tyr 
            100                 105                 110         


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


<210>  38
<211>  123
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Generic 25E9 heavy chain variable domain (consensus 3)


<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  Xaa may be a hydrophobic amino acid

<220>
<221>  MISC_FEATURE
<222>  (11)..(11)
<223>  Xaa may be a hydrophobic amino acid

<220>
<221>  MISC_FEATURE
<222>  (12)..(12)
<223>  Xaa may be V or K

<220>
<221>  MISC_FEATURE
<222>  (13)..(13)
<223>  Xaa may be a basic amino acid

<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  Xaa may be A or S

<220>
<221>  MISC_FEATURE
<222>  (19)..(19)
<223>  Xaa may be T or K

<220>
<221>  MISC_FEATURE
<222>  (20)..(20)
<223>  Xaa may be a hydrophobic amino acid

<220>
<221>  MISC_FEATURE
<222>  (38)..(38)
<223>  Xaa may be a basic amino acid

<220>
<221>  MISC_FEATURE
<222>  (40)..(40)
<223>  Xaa may be T or A

<220>
<221>  MISC_FEATURE
<222>  (42)..(42)
<223>  Xaa may be V or G

<220>
<221>  MISC_FEATURE
<222>  (43)..(43)
<223>  Xaa may be a basic amino acid

<220>
<221>  MISC_FEATURE
<222>  (48)..(48)
<223>  Xaa may be a hydrophobic amino acid

<220>
<221>  MISC_FEATURE
<222>  (67)..(67)
<223>  Xaa may be a basic amino acid

<220>
<221>  MISC_FEATURE
<222>  (68)..(68)
<223>  Xaa may be a hydrophobic amino acid

<220>
<221>  MISC_FEATURE
<222>  (70)..(70)
<223>  Xaa may be a hydrophobic amino acid

<220>
<221>  MISC_FEATURE
<222>  (74)..(74)
<223>  Xaa may be a basic amino acid

<220>
<221>  MISC_FEATURE
<222>  (76)..(76)
<223>  Xaa may be a neutral hydrophilic amino acid

<220>
<221>  MISC_FEATURE
<222>  (77)..(77)
<223>  Xaa may be a neutral hydrophilic amino acid

<220>
<221>  MISC_FEATURE
<222>  (87)..(87)
<223>  Xaa may be T or R

<220>
<221>  MISC_FEATURE
<222>  (91)..(91)
<223>  Xaa may be a neutral hydrophilic amino acid

<220>
<221>  MISC_FEATURE
<222>  (123)..(123)
<223>  Xaa may be A or S

<400>  38

Glu Ile Gln Leu Gln Gln Ser Gly Xaa Glu Xaa Xaa Xaa Pro Gly Xaa 
1               5                   10                  15      


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


Asp Met His Trp Val Xaa Gln Xaa Pro Xaa Xaa Gly Leu Glu Trp Xaa 
        35                  40                  45              


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


Lys Gly Xaa Xaa Thr Xaa Thr Ala Asp Xaa Ser Xaa Xaa Thr Ala Tyr 
65                  70                  75                  80  


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


Thr Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly Phe Ala Tyr 
            100                 105                 110         


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


<210>  39
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Generic 25D8 light chain variable domain (consensus 1)


<220>
<221>  MISC_FEATURE
<222>  (7)..(7)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:22

<220>
<221>  MISC_FEATURE
<222>  (8)..(8)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:22

<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:22

<220>
<221>  MISC_FEATURE
<222>  (11)..(11)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:22

<220>
<221>  MISC_FEATURE
<222>  (15)..(15)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:22

<220>
<221>  MISC_FEATURE
<222>  (17)..(17)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:22

<220>
<221>  MISC_FEATURE
<222>  (18)..(18)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:22

<220>
<221>  MISC_FEATURE
<222>  (69)..(69)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:22

<220>
<221>  MISC_FEATURE
<222>  (79)..(79)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:22

<220>
<221>  MISC_FEATURE
<222>  (109)..(109)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:22

<400>  39

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


Xaa Xaa Ala Ser Ile Ser Cys Arg Ser Ser Lys Ser Leu Leu His Ser 
            20                  25                  30          


Asn Gly Ile Thr Tyr Leu Tyr Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


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


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ala Gln Asn 
                85                  90                  95      


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


<210>  40
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Generic 25D8 light chain variable domain (consensus 2)


<220>
<221>  MISC_FEATURE
<222>  (7)..(7)
<223>  Xaa may be a conservartive amino acid substitution in comparison 
       with SEQ ID NO.:22

<220>
<221>  MISC_FEATURE
<222>  (8)..(8)
<223>  Xaa may be a semi-conservartive amino acid substitution in 
       comparison with SEQ ID NO.:22

<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  Xaa may be a conservartive amino acid substitution in comparison 
       with SEQ ID NO.:22

<220>
<221>  MISC_FEATURE
<222>  (11)..(11)
<223>  Xaa may be N or L

<220>
<221>  MISC_FEATURE
<222>  (15)..(15)
<223>  Xaa may be L or P

<220>
<221>  MISC_FEATURE
<222>  (17)..(17)
<223>  Xaa may be T or E

<220>
<221>  MISC_FEATURE
<222>  (18)..(18)
<223>  Xaa may be a semi-conservartive amino acid substitution in 
       comparison with SEQ ID NO.:22

<220>
<221>  MISC_FEATURE
<222>  (69)..(69)
<223>  Xaa may be a semi-conservartive amino acid substitution in 
       comparison with SEQ ID NO.:22

<220>
<221>  MISC_FEATURE
<222>  (79)..(79)
<223>  Xaa may be a conservartive amino acid substitution in comparison 
       with SEQ ID NO.:22

<220>
<221>  MISC_FEATURE
<222>  (109)..(109)
<223>  Xaa may be a conservartive amino acid substitution in comparison 
       with SEQ ID NO.:22

<400>  40

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


Xaa Xaa Ala Ser Ile Ser Cys Arg Ser Ser Lys Ser Leu Leu His Ser 
            20                  25                  30          


Asn Gly Ile Thr Tyr Leu Tyr Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


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


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ala Gln Asn 
                85                  90                  95      


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


<210>  41
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Generic 25D8 light chain variable domain (consensus 3)


<220>
<221>  MISC_FEATURE
<222>  (7)..(7)
<223>  Xaa may be A or T

<220>
<221>  MISC_FEATURE
<222>  (8)..(8)
<223>  Xaa may be A or P

<220>
<221>  MISC_FEATURE
<222>  (9)..(9)
<223>  Xaa may be F or L

<220>
<221>  MISC_FEATURE
<222>  (11)..(11)
<223>  Xaa may be N or L

<220>
<221>  MISC_FEATURE
<222>  (15)..(15)
<223>  Xaa may be L or P

<220>
<221>  MISC_FEATURE
<222>  (17)..(17)
<223>  Xaa may be T or E

<220>
<221>  MISC_FEATURE
<222>  (18)..(18)
<223>  Xaa may be S or P

<220>
<221>  MISC_FEATURE
<222>  (69)..(69)
<223>  Xaa may be S or G

<220>
<221>  MISC_FEATURE
<222>  (79)..(79)
<223>  Xaa may be a basic amino acid

<220>
<221>  MISC_FEATURE
<222>  (109)..(109)
<223>  Xaa may be a hydrophobic amino acid

<400>  41

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


Xaa Xaa Ala Ser Ile Ser Cys Arg Ser Ser Lys Ser Leu Leu His Ser 
            20                  25                  30          


Asn Gly Ile Thr Tyr Leu Tyr Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


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


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ala Gln Asn 
                85                  90                  95      


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


<210>  42
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Generic 25D8 heavy chain variable domain (consensus 1)


<220>
<221>  MISC_FEATURE
<222>  (4)..(4)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:26

<220>
<221>  MISC_FEATURE
<222>  (7)..(7)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:26

<220>
<221>  MISC_FEATURE
<222>  (11)..(11)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:26

<220>
<221>  MISC_FEATURE
<222>  (12)..(12)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:26

<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:26

<220>
<221>  MISC_FEATURE
<222>  (20)..(20)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:26

<220>
<221>  MISC_FEATURE
<222>  (38)..(38)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:26

<220>
<221>  MISC_FEATURE
<222>  (40)..(40)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:26

<220>
<221>  MISC_FEATURE
<222>  (48)..(48)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:26

<220>
<221>  MISC_FEATURE
<222>  (67)..(67)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:26

<220>
<221>  MISC_FEATURE
<222>  (68)..(68)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:26

<220>
<221>  MISC_FEATURE
<222>  (70)..(70)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:26

<220>
<221>  MISC_FEATURE
<222>  (72)..(72)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:26

<220>
<221>  MISC_FEATURE
<222>  (76)..(76)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:26

<220>
<221>  MISC_FEATURE
<222>  (82)..(82)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:26

<220>
<221>  MISC_FEATURE
<222>  (87)..(87)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:26

<220>
<221>  MISC_FEATURE
<222>  (91)..(91)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:26

<220>
<221>  MISC_FEATURE
<222>  (114)..(114)
<223>  Xaa may be an amino acid substitution in comparison with SEQ ID 
       NO.:26

<400>  42

Gln Val Gln Xaa Gln Gln Xaa Gly Ala Glu Xaa Xaa Lys Pro Gly Xaa 
1               5                   10                  15      


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


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


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


Asn Thr Xaa Xaa Thr Xaa Thr Xaa Asp Lys Ser Xaa Ser Thr Ala Tyr 
65                  70                  75                  80  


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


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


Thr Xaa Thr Val Ser Ser 
        115             


<210>  43
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Generic 25D8 heavy chain variable domain (consensus 2)


<220>
<221>  MISC_FEATURE
<222>  (4)..(4)
<223>  Xaa may be a conservartive amino acid substitution in comparison 
       with SEQ ID NO.:26

<220>
<221>  MISC_FEATURE
<222>  (7)..(7)
<223>  Xaa may be a semi-conservartive amino acid substitution in 
       comparison with SEQ ID NO.:26

<220>
<221>  MISC_FEATURE
<222>  (11)..(11)
<223>  Xaa may be a conservartive amino acid substitution in comparison 
       with SEQ ID NO.:26

<220>
<221>  MISC_FEATURE
<222>  (12)..(12)
<223>  Xaa may be V or K

<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  Xaa may be a conservartive amino acid substitution in comparison 
       with SEQ ID NO.:26

<220>
<221>  MISC_FEATURE
<222>  (20)..(20)
<223>  Xaa may be a conservartive amino acid substitution in comparison 
       with SEQ ID NO.:26

<220>
<221>  MISC_FEATURE
<222>  (38)..(38)
<223>  Xaa may be a conservartive amino acid substitution in comparison 
       with SEQ ID NO.:26

<220>
<221>  MISC_FEATURE
<222>  (40)..(40)
<223>  Xaa may be R or A

<220>
<221>  MISC_FEATURE
<222>  (48)..(48)
<223>  Xaa may be a conservartive amino acid substitution in comparison 
       with SEQ ID NO.:26

<220>
<221>  MISC_FEATURE
<222>  (67)..(67)
<223>  Xaa may be a conservartive amino acid substitution in comparison 
       with SEQ ID NO.:26

<220>
<221>  MISC_FEATURE
<222>  (68)..(68)
<223>  Xaa may be a semi-conservartive amino acid substitution in 
       comparison with SEQ ID NO.:26

<220>
<221>  MISC_FEATURE
<222>  (70)..(70)
<223>  Xaa may be a conservartive amino acid substitution in comparison 
       with SEQ ID NO.:26

<220>
<221>  MISC_FEATURE
<222>  (72)..(72)
<223>  Xaa may be a semi-conservartive amino acid substitution in 
       comparison with SEQ ID NO.:26

<220>
<221>  MISC_FEATURE
<222>  (76)..(76)
<223>  Xaa may be a conservartive amino acid substitution in comparison 
       with SEQ ID NO.:26

<220>
<221>  MISC_FEATURE
<222>  (82)..(82)
<223>  Xaa may be a conservartive amino acid substitution in comparison 
       with SEQ ID NO.:26

<220>
<221>  MISC_FEATURE
<222>  (87)..(87)
<223>  Xaa may be T or R

<220>
<221>  MISC_FEATURE
<222>  (91)..(91)
<223>  Xaa may be a conservartive amino acid substitution in comparison 
       with SEQ ID NO.:26

<220>
<221>  MISC_FEATURE
<222>  (114)..(114)
<223>  Xaa may be a conservartive amino acid substitution in comparison 
       with SEQ ID NO.:26

<400>  43

Gln Val Gln Xaa Gln Gln Xaa Gly Ala Glu Xaa Xaa Lys Pro Gly Xaa 
1               5                   10                  15      


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


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


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


Asn Thr Xaa Xaa Thr Xaa Thr Xaa Asp Lys Ser Xaa Ser Thr Ala Tyr 
65                  70                  75                  80  


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


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


Thr Xaa Thr Val Ser Ser 
        115             


<210>  44
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Generic 25D8 heavy chain variable domain (consensus 3)


<220>
<221>  MISC_FEATURE
<222>  (4)..(4)
<223>  Xaa may be a hydrophobic amino acid

<220>
<221>  MISC_FEATURE
<222>  (7)..(7)
<223>  Xaa may be P or S

<220>
<221>  MISC_FEATURE
<222>  (11)..(11)
<223>  Xaa may be a hydrophobic amino acid

<220>
<221>  MISC_FEATURE
<222>  (12)..(12)
<223>  Xaa may be V or K

<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  Xaa may be A or S

<220>
<221>  MISC_FEATURE
<222>  (20)..(20)
<223>  Xaa may be a hydrophobic amino acid

<220>
<221>  MISC_FEATURE
<222>  (38)..(38)
<223>  Xaa may be a basic amino acid

<220>
<221>  MISC_FEATURE
<222>  (40)..(40)
<223>  Xaa may be R or A

<220>
<221>  MISC_FEATURE
<222>  (48)..(48)
<223>  Xaa may be a hydrophobic amino acid

<220>
<221>  MISC_FEATURE
<222>  (67)..(67)
<223>  Xaa may be a basic amino acid

<220>
<221>  MISC_FEATURE
<222>  (68)..(68)
<223>  Xaa may be a hydrophobic amino acid

<220>
<221>  MISC_FEATURE
<222>  (70)..(70)
<223>  Xaa may be a hydrophobic amino acid

<220>
<221>  MISC_FEATURE
<222>  (72)..(72)
<223>  Xaa may be a hydrophobic amino acid

<220>
<221>  MISC_FEATURE
<222>  (76)..(76)
<223>  Xaa may be a neutral hydrophilic amino acid

<220>
<221>  MISC_FEATURE
<222>  (82)..(82)
<223>  Xaa may be Q or E

<220>
<221>  MISC_FEATURE
<222>  (87)..(87)
<223>  Xaa may be T or R

<220>
<221>  MISC_FEATURE
<222>  (91)..(91)
<223>  Xaa may be a neutral hydrophilic amino acid

<220>
<221>  MISC_FEATURE
<222>  (114)..(114)
<223>  Xaa may be a hydrophobic amino acid

<400>  44

Gln Val Gln Xaa Gln Gln Xaa Gly Ala Glu Xaa Xaa Lys Pro Gly Xaa 
1               5                   10                  15      


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


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


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


Asn Thr Xaa Xaa Thr Xaa Thr Xaa Asp Lys Ser Xaa Ser Thr Ala Tyr 
65                  70                  75                  80  


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


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


Thr Xaa Thr Val Ser Ser 
        115             


<210>  45
<211>  467
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Chimeric 25D8 heavy chain (IgG1)

<400>  45

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


Thr His Ala Gln Val Gln Val Gln Gln Pro Gly Ala Glu Leu Val Lys 
            20                  25                  30          


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


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


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


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


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


Tyr Tyr Cys Ala Arg Gly Gly Asp Gly Asp Tyr Phe Asp Tyr Trp Gly 
        115                 120                 125             


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


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


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


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


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


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


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


Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
                245                 250                 255     


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


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


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


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


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


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


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


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


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


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


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


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


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


Pro Gly Lys 
465         


<210>  46
<211>  467
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized 25D8 heavy chain (IgG1)

<400>  46

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


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


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


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


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


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


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


Tyr Tyr Cys Ala Arg Gly Gly Asp Gly Asp Tyr Phe Asp Tyr Trp Gly 
        115                 120                 125             


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


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


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


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


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


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


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


Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly 
                245                 250                 255     


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


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


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


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


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


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


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


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


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


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


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


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


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


Pro Gly Lys 
465         


<210>  47
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR1 of the 25E9 light chain mouse variable domain

<400>  47

Arg Ser Thr Lys Ser Leu Leu His Ser Asn Gly Asn Thr Tyr Leu Tyr 
1               5                   10                  15      


<210>  48
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2 of the 25E9 light chain mouse variable domain

<400>  48

Arg Met Ser Asn Leu Ala Ser 
1               5           


<210>  49
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR3 of the 25E9 light chain mouse variable domain

<400>  49

Met Gln His Leu Glu Tyr Pro Phe Thr 
1               5                   


<210>  50
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR1 of the 25E9 heavy chain mouse variable domain

<400>  50

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


<210>  51
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2 of the 25E9 heavy chain mouse variable domain

<400>  51

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


Gly 
    


<210>  52
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR3 of the 25E9 heavy chain mouse variable domain

<400>  52

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


<210>  53
<211>  16
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR1 of the 25D8 light chain mouse variable domain

<400>  53

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


<210>  54
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2 of the 25D8 light chain mouse variable domain

<400>  54

Gln Met Ser Asn Leu Ala Ser Gly 
1               5               


<210>  55
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR3 of the 25D8 light chain mouse variable domain

<400>  55

Ala Gln Asn Leu Glu Leu Pro Tyr Thr 
1               5                   


<210>  56
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR1 of the 25D8 heavy chain mouse variable domain

<400>  56

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


<210>  57
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR2 of the 25D8 heavy chain mouse variable domain

<400>  57

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


Thr 
    


<210>  58
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  CDR3 of the 25D8 heavy chain mouse variable domain

<400>  58

Gly Gly Asp Gly Asp Tyr Phe Asp Tyr 
1               5                   


<210>  59
<211>  468
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  25E9 heavy chain (IgG2) humanized variant 2

<400>  59

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


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


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


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


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


Gln Lys Phe Lys Gly Arg Ala Thr Leu Thr Ala Asp Arg Ser Thr Ser 
                85                  90                  95      


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


Tyr Tyr Cys Thr Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly 
        115                 120                 125             


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Ser Pro Gly Lys 
465             


<210>  60
<211>  468
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  25E9 heavy chain (IgG2) humanized variant 3

<400>  60

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


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


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


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


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


Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Ala Asp Arg Ser Thr Ser 
                85                  90                  95      


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


Tyr Tyr Cys Thr Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly 
        115                 120                 125             


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Ser Pro Gly Lys 
465             


<210>  61
<211>  468
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  25E9 heavy chain (IgG2) humanized variant 4

<400>  61

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


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


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


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


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


Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Ala Asp Arg Ser Thr Ser 
                85                  90                  95      


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


Tyr Tyr Cys Thr Ser Phe Tyr Tyr Thr Tyr Ser Asn Tyr Asp Val Gly 
        115                 120                 125             


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Ser Pro Gly Lys 
465             


<210>  62
<211>  336
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  25E9 light chain mouse variable domain

<400>  62
gatattgtga tgacccaggc tgcaccctct gtacctgtca ctcctggaga gtcagtatcc       60

atctcctgca ggtctactaa gagtctcctg catagtaatg gcaacactta cttgtattgg      120

ttcctgcaga ggccaggcca gtctcctcag ctcctgatat atcggatgtc caaccttgcc      180

tcaggagtcc cagacaggtt cagtggcagt gggtcaggaa ctgctttcac actgagaatc      240

agtagagtgg aggctgagga tgtgggtgtt tattactgta tgcaacatct agaatatcct      300

ttcacgttcg gaggggggac caagctggaa ataaaa                                336


<210>  63
<211>  369
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  25E9 heavy chain mouse variable domain

<400>  63
gagatccagc tgcagcagtc tggagttgag ctggtgaggc ctggggcttc agtgacgctg       60

tcctgcaagg cttcgggcta cacatttact gactatgaca tgcactgggt gaagcagaca      120

cctgttcatg gcctggaatg gattggaact attgatcctg aaactggtgg tactgcctac      180

aatcagaagt tcaagggcaa ggccacactg actgcggaca gatcctccac cacagcctac      240

atggagctca gcagcctgac atctgaggac tctgccgtct attactgtac aagtttctac      300

tatacttact ctaattacga cgtggggttt gcttactggg gccaagggac tctggtcact      360

gtctctgca                                                              369


<210>  64
<211>  336
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  humanized 25E9 light chain variable domain variant 1

<400>  64
gacatcgtga tgacccagtc ccccctgtcc ctgcctgtga cacctggcga gcccgcctcc       60

atctcctgcc ggtccaccaa gtccctgctg cactccaacg gcaacaccta cctgtactgg      120

tatctgcaga agcccggcca gtcccctcag ctgctgatct accggatgtc caacctggcc      180

tccggcgtgc ccgacagatt ctccggctct ggctccggca ccgacttcac cctgaagatc      240

tcccgggtgg aagccgagga cgtgggcgtg tactactgca tgcagcacct ggaatacccc      300

ttcaccttcg gcggaggcac caaggtggaa atcaag                                336


<210>  65
<211>  369
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  humanized 25E9 heavy chain variable domain variant 1

<400>  65
gagattcagc tgcagcagtc aggagccgaa gtgaagaaac ccggctccag cgtcaaggtg       60

agttgcaagg cctccggata cactttcacc gactatgata tgcactgggt gagacaggca      120

cctgggcagg gtctggagtg gatggggacc atcgatccag aaaccggcgg aacagcctac      180

aaccagaagt ttaaaggtcg agtgacaatt actgctgaca agtccaccag cacagcatat      240

atggagctgt ctagtctgcg ttctgaagat acagccgtct actattgcac ttctttctac      300

tacacctaca gtaactacga cgtggggttt gcttactggg gccagggaac tctggtcacc      360

gtgtcatcc                                                              369


<210>  66
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25D8 light chain variable domain

<400>  66

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


Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser 
            20                  25                  30          


Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


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


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Gly 
                85                  90                  95      


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


<210>  67
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25D8 light chain variable domain

<400>  67

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


Glu Pro Ala Ser Ile Ser Cys Arg Ala Ser Gln Ser Leu Leu His Ser 
            20                  25                  30          


Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


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


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Gly 
                85                  90                  95      


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


<210>  68
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25D8 light chain variable domain

<400>  68

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


Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Leu His Ser 
            20                  25                  30          


Asp Gly Lys Thr Tyr Leu Tyr Trp Tyr Leu Gln Lys Pro Gly Gln Pro 
        35                  40                  45              


Pro Gln Leu Leu Ile Tyr Glu Val Ser Asn Arg Phe Ser Gly Val Pro 
    50                  55                  60                  


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ser 
                85                  90                  95      


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


<210>  69
<211>  98
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25D8 light chain variable domain

<400>  69

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


Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser 
            20                  25                  30          


Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


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


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala 
                85                  90                  95      


Leu Gln 
        


<210>  70
<211>  98
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25D8 light chain variable domain

<400>  70

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


Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser 
            20                  25                  30          


Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


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


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala 
                85                  90                  95      


Leu Gln 
        


<210>  71
<211>  99
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25D8 light chain variable domain

<400>  71

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


Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Leu His Ser 
            20                  25                  30          


Asp Gly Lys Thr Tyr Leu Tyr Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


Pro Gln Leu Leu Ile Tyr Glu Val Ser Asn Arg Phe Ser Gly Val Pro 
    50                  55                  60                  


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ser 
                85                  90                  95      


Ile Gln Leu 
            


<210>  72
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25D8 light chain variable domain


<220>
<221>  misc_feature
<222>  (101)..(101)
<223>  Xaa can be any naturally occurring amino acid

<400>  72

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


Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser 
            20                  25                  30          


Asp Gly Asn Asn Tyr Leu Asn Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


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


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala 
                85                  90                  95      


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


<210>  73
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25D8 heavy chain variable domain

<400>  73

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


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


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


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


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


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


Ala Arg Gly Lys Gly Glu Phe Glu Gly Met Asp Val Trp Gly Gln Gly 
            100                 105                 110         


Thr Thr Val Thr Val Ser Ser 
        115                 


<210>  74
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25D8 heavy chain variable domain

<400>  74

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


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


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


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


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


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


Ala Arg Asp Thr His Ser Trp Phe Ala Phe Asp Ile Trp Gly Gln Gly 
            100                 105                 110         


Thr Met Val Thr Val Ser Ser 
        115                 


<210>  75
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25D8 heavy chain variable domain

<400>  75

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


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


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


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


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


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


Ala Arg Asp Pro Asn Phe Gly Asp Phe Asp Ser Trp Gly Gln Gly Thr 
            100                 105                 110         


Leu Val Thr Val Ser Ser 
        115             


<210>  76
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25D8 heavy chain variable domain

<400>  76

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


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


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


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


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


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


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


Leu Val Thr Val Ser Ser 
        115             


<210>  77
<211>  120
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25D8 heavy chain variable domain

<400>  77

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 Ser Tyr 
            20                  25                  30          


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


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


Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 
65                  70                  75                  80  


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


Ala Arg Glu Gly Asp Gly Tyr Ile Gln Ala Phe Asp Tyr Trp Gly Gln 
            100                 105                 110         


Gly Thr Leu Val Thr Val Ser Ser 
        115                 120 


<210>  78
<211>  98
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25D8 heavy chain variable domain

<400>  78

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


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


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


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


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


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


Ala Arg 
        


<210>  79
<211>  98
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25D8 heavy chain variable domain

<400>  79

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 Ser Tyr 
            20                  25                  30          


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


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


Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 
65                  70                  75                  80  


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


Ala Arg 
        


<210>  80
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25D8 heavy chain variable domain

<400>  80

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 Ser Tyr 
            20                  25                  30          


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


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


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


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


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


Leu Val Thr Val Ser Ser 
        115             


<210>  81
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25E9 light chain variable domain

<400>  81

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


Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser 
            20                  25                  30          


Thr Gly Asn Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


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


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


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


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


<210>  82
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25E9 light chain variable domain

<400>  82

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


Glu Pro Ala Ser Ile Ser Cys Arg Ala Ser Gln Ser Leu Leu His Ser 
            20                  25                  30          


Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


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


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Gly 
                85                  90                  95      


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


<210>  83
<211>  98
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25E9 light chain variable domain

<400>  83

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


Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser 
            20                  25                  30          


Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


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


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala 
                85                  90                  95      


Leu Gln 
        


<210>  84
<211>  98
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25E9 light chain variable domain

<400>  84

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


Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser 
            20                  25                  30          


Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


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


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala 
                85                  90                  95      


Leu Gln 
        


<210>  85
<211>  112
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25E9 light chain variable domain


<220>
<221>  misc_feature
<222>  (101)..(101)
<223>  Xaa can be any naturally occurring amino acid

<400>  85

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


Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser 
            20                  25                  30          


Asp Gly Asn Asn Tyr Leu Asn Trp Tyr Leu Gln Lys Pro Gly Gln Ser 
        35                  40                  45              


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


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


Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala 
                85                  90                  95      


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


<210>  86
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25E9 heavy chain variable domain

<400>  86

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


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


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


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


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


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


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


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  87
<211>  123
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25E9 heavy chain variable domain

<400>  87

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


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


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


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


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


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


Ala Arg Gly Asn Tyr Asp Ser Ser Gly Tyr Asp Asp Ala Phe Asp Ile 
            100                 105                 110         


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


<210>  88
<211>  123
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25E9 heavy chain variable domain

<400>  88

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


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


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


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


Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Met Thr Thr Ala Tyr 
65                  70                  75                  80  


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


Ala Thr Thr Arg Met Lys Ile Thr Val Phe Ala Ser Thr Phe Asp Tyr 
            100                 105                 110         


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


<210>  89
<211>  96
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25E9 heavy chain variable domain

<400>  89

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


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


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


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


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


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


<210>  90
<211>  96
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25E9 heavy chain variable domain

<400>  90

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 Ser Tyr 
            20                  25                  30          


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


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


Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr 
65                  70                  75                  80  


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


<210>  91
<211>  98
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25E9 heavy chain variable domain

<400>  91

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


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


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


Gly Leu Val Asp Pro Glu Asp Gly Glu Thr Ile Tyr Ala Glu Lys Phe 
    50                  55                  60                  


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


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


Ala Thr 
        


<210>  92
<211>  123
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  candidate human model for the 25E9 heavy chain variable domain


<220>
<221>  misc_feature
<222>  (109)..(109)
<223>  Xaa can be any naturally occurring amino acid

<400>  92

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 Ser Tyr 
            20                  25                  30          


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


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


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


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


Ala Arg Ala Pro Gly Tyr Gly Ser Arg Gly Asp Tyr Xaa Phe Asp Tyr 
            100                 105                 110         


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


