                         б

<110>  麣鵥＼޹˾
       
<120>  һTIM-3ȫԴӡԭƬμҽҩ;

<130>  LC19210001P

<150>  CN201810197885.7
<151>  2018-03-15

<160>  43    

<170>  PatentIn version 3.5

<210>  1
<211>  498
<212>  DNA
<213>  Mus musculus

<400>  1
ttatgagtgt ggccactcag gtcctggggt tgctgctgct gtggcttaca ggtgccagat       60

gtgacatcca gatgactcag tctccagcct ccctatctgc atctgtggga gaaactgtca      120

ccatcacttg tcgagcaagt gagaatattt acagttattt aacatggtat cagcagaaac      180

agggaaaatc tcctcagctc ctggtctata atgcaaaaac cttagcagaa ggtgtgccat      240

caaggttcag tggcagtgga tcaggcacac agttttctct gaggatcaac agcctgcagc      300

ctgaagattt tgggaattat tactgtcaac agcattatgg tactccgctc acgttcggtg      360

ctgggaccaa gctggagctg aaacgggctg atgctgcacc aactgtatcc atcttcccac      420

catccagtga gcagttaaca tctggaggtg cctcagtcgt gtgcttctga acaactctac      480

cccagagaca tcaaagcc                                                    498


<210>  2
<211>  535
<212>  DNA
<213>  Mus musculus

<400>  2
atggactcca ggctcaattt agttttcctt gttcttattt taaaaggagt ccagtgtgaa       60

gtgaagctgg tggagtctga gggaggctta gtgcagcctg gaagttccat gaaactctcc      120

tgcacagcct ctggattcac tttcagtgac tattacatga cttgggtccg ccaggttcca      180

gaaaagggtc tagaatgggt tgcaagcatt aattatgatg gtcgtaatac ctactatctg      240

gactccttga agagccgttt catcatctcg agagacaatg caaagaacat tctatacctg      300

cagatgagca gtctgaagtc tgaggacaca gccacgtatt actgtgcaag aggatattat      360

tactacggta gtagccctaa ctactttgac tactggggcc aaggcaccac tctcacagtc      420

tcctcagcca aaacgacacc cccatctgtc tatccactgg cccctggatc tgctgcccaa      480

actaactcca tggtgaccct gggatgcctg gtcaagggct atactagcca gtatc           535


<210>  3
<211>  107
<212>  PRT
<213>  Mus musculus VL

<400>  3

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


Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Glu Asn Ile Tyr Ser Tyr 
            20                  25                  30          


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


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


Ser Gly Ser Gly Thr Gln Phe Ser Leu Arg Ile Asn Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Gly Asn Tyr Tyr Cys Gln Gln His Tyr Gly Thr Pro Leu 
                85                  90                  95      


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


<210>  4
<211>  123
<212>  PRT
<213>  Mus musculus VH

<400>  4

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


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


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


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


Lys Ser Arg Phe Ile Ile Ser Arg Asp Asn Ala Lys Asn Ile Leu Tyr 
65                  70                  75                  80  


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


Ala Arg Gly Tyr Tyr Tyr Tyr Gly Ser Ser Pro Asn Tyr Phe Asp Tyr 
            100                 105                 110         


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


<210>  5
<211>  11
<212>  PRT
<213>  Mus musculus CDR

<400>  5

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


<210>  6
<211>  7
<212>  PRT
<213>  Mus musculus CDR

<400>  6

Asn Ala Lys Thr Leu Ala Glu 
1               5           


<210>  7
<211>  9
<212>  PRT
<213>  Mus musculus CDR

<400>  7

Gln Gln His Tyr Gly Thr Pro Leu Thr 
1               5                   


<210>  8
<211>  5
<212>  PRT
<213>  Mus musculus CDR

<400>  8

Asp Tyr Tyr Met Thr 
1               5   


<210>  9
<211>  17
<212>  PRT
<213>  Mus musculus CDR

<400>  9

Ser Ile Asn Tyr Asp Gly Arg Asn Thr Tyr Tyr Leu Asp Ser Leu Lys 
1               5                   10                  15      


Ser 
    


<210>  10
<211>  14
<212>  PRT
<213>  Mus musculus CDR

<400>  10

Gly Tyr Tyr Tyr Tyr Gly Ser Ser Pro Asn Tyr Phe Asp Tyr 
1               5                   10                  


<210>  11
<211>  10
<212>  PRT
<213>  Mus musculus CDR

<400>  11

Gly Phe Thr Phe Ser Asp Tyr Tyr Met Thr 
1               5                   10  


<210>  12
<211>  10
<212>  PRT
<213>  Mus musculus CDR

<400>  12

Ser Ile Asn Tyr Asp Gly Arg Asn Thr Tyr 
1               5                   10  


<210>  13
<211>  7
<212>  PRT
<213>  Mus musculus CDR

<400>  13

Gly Phe Thr Phe Ser Asp Tyr 
1               5           


<210>  14
<211>  6
<212>  PRT
<213>  Mus musculus CDR

<400>  14

Asn Tyr Asp Gly Arg Asn 
1               5       


<210>  15
<211>  7
<212>  PRT
<213>  Mus musculus CDR

<400>  15

Tyr Ser Tyr Leu Thr Trp Tyr 
1               5           


<210>  16
<211>  10
<212>  PRT
<213>  Mus musculus CDR

<400>  16

Leu Leu Val Tyr Asn Ala Lys Thr Leu Ala 
1               5                   10  


<210>  17
<211>  8
<212>  PRT
<213>  Mus musculus CDR

<400>  17

Gln Gln His Tyr Gly Thr Pro Leu 
1               5               


<210>  18
<211>  6
<212>  PRT
<213>  Mus musculus CDR

<400>  18

Ser Asp Tyr Tyr Met Thr 
1               5       


<210>  19
<211>  13
<212>  PRT
<213>  Mus musculus CDR

<400>  19

Trp Val Ala Ser Ile Asn Tyr Asp Gly Arg Asn Thr Tyr 
1               5                   10              


<210>  20
<211>  15
<212>  PRT
<213>  Mus musculus CDR

<400>  20

Ala Arg Gly Tyr Tyr Tyr Tyr Gly Ser Ser Pro Asn Tyr Phe Asp 
1               5                   10                  15  


<210>  21
<211>  107
<212>  PRT
<213>  Homo sapiens

<400>  21

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


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


Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln 
        35                  40                  45              


Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser 
    50                  55                  60                  


Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu 
65                  70                  75                  80  


Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser 
                85                  90                  95      


Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys 
            100                 105         


<210>  22
<211>  327
<212>  PRT
<213>  Homo sapiens

<400>  22

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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Leu Ser Leu Ser Leu Gly Lys 
                325         


<210>  23
<211>  330
<212>  PRT
<213>  Homo sapiens

<400>  23

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 Glu Glu 
225                 230                 235                 240 


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


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


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


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


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


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


<210>  24
<211>  326
<212>  PRT
<213>  Homo sapiens

<400>  24

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>  25
<211>  214
<212>  PRT
<213>  Mus musculus and  Homo sapiens chimera

<400>  25

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


Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Glu Asn Ile Tyr Ser Tyr 
            20                  25                  30          


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


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


Ser Gly Ser Gly Thr Gln Phe Ser Leu Arg Ile Asn Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Gly Asn Tyr Tyr Cys Gln Gln His Tyr Gly Thr Pro Leu 
                85                  90                  95      


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


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


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


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


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


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


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


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  26
<211>  450
<212>  PRT
<213>  Mus musculus and  Homo sapiens chimera

<400>  26

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


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


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


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


Lys Ser Arg Phe Ile Ile Ser Arg Asp Asn Ala Lys Asn Ile Leu Tyr 
65                  70                  75                  80  


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


Ala Arg Gly Tyr Tyr Tyr Tyr Gly Ser Ser Pro Asn Tyr Phe Asp Tyr 
            100                 105                 110         


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


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


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


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


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


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


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


Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly 
225                 230                 235                 240 


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


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


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


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


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


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


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


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


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


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


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


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


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


Gly Lys 
    450 


<210>  27
<211>  107
<212>  PRT
<213>  humanized

<400>  27

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


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


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


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


Ser Gly Ser Gly Thr Gln Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


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


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


<210>  28
<211>  107
<212>  PRT
<213>  humanized

<400>  28

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


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


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


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


Ser Gly Ser Gly Thr Gln Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Tyr Gly Thr Pro Leu 
                85                  90                  95      


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


<210>  29
<211>  107
<212>  PRT
<213>  humanized

<400>  29

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


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


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


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


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


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Tyr Gly Thr Pro Leu 
                85                  90                  95      


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


<210>  30
<211>  107
<212>  PRT
<213>  humanized

<400>  30

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


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


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


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


Ser Gly Ser Gly Thr Gln Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Tyr Gly Thr Pro Leu 
                85                  90                  95      


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


<210>  31
<211>  107
<212>  PRT
<213>  humanized

<400>  31

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


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


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


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


Ser Gly Ser Gly Thr Gln Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Tyr Gly Thr Pro Leu 
                85                  90                  95      


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


<210>  32
<211>  107
<212>  PRT
<213>  humanized

<400>  32

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


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


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


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


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


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


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


<210>  33
<211>  107
<212>  PRT
<213>  humanized

<400>  33

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


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


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


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


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


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Tyr Gly Thr Pro Leu 
                85                  90                  95      


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


<210>  34
<211>  123
<212>  PRT
<213>  humanized

<400>  34

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


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


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


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


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


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


Ala Arg Gly Tyr Tyr Tyr Tyr Gly Ser Ser Pro Asn Tyr Phe Asp Tyr 
            100                 105                 110         


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


<210>  35
<211>  123
<212>  PRT
<213>  humanized

<400>  35

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


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


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


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


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


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


Ala Arg Gly Tyr Tyr Tyr Tyr Gly Ser Ser Pro Asn Tyr Phe Asp Tyr 
            100                 105                 110         


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


<210>  36
<211>  123
<212>  PRT
<213>  humanized

<400>  36

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


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


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


Ser Ser Ile Asn Tyr Asp Gly Arg Asn Thr Tyr Tyr Leu Asp Ser Leu 
    50                  55                  60                  


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


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


Ala Arg Gly Tyr Tyr Tyr Tyr Gly Ser Ser Pro Asn Tyr Phe Asp Tyr 
            100                 105                 110         


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


<210>  37
<211>  123
<212>  PRT
<213>  humanized

<400>  37

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


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


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


Ser Ser Ile Asn Tyr Asp Gly Arg Asn Thr Tyr Tyr Leu Asp Ser Leu 
    50                  55                  60                  


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


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


Ala Arg Gly Tyr Tyr Tyr Tyr Gly Ser Ser Pro Asn Tyr Phe Asp Tyr 
            100                 105                 110         


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


<210>  38
<211>  214
<212>  PRT
<213>  humanized

<400>  38

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


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


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


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


Ser Gly Ser Gly Thr Gln Phe Ser Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


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


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


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


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


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


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


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


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


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  39
<211>  450
<212>  PRT
<213>  humanized

<400>  39

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


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


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


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


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


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


Ala Arg Gly Tyr Tyr Tyr Tyr Gly Ser Ser Pro Asn Tyr Phe Asp Tyr 
            100                 105                 110         


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


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


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


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


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


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


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


Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly 
225                 230                 235                 240 


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


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


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


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


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


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


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


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


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


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


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


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


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


Gly Lys 
    450 


<210>  40
<211>  214
<212>  PRT
<213>  humanized

<400>  40

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


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


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


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


Ser Gly Ser Gly Thr Gln Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 
65                  70                  75                  80  


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Tyr Gly Thr Pro Leu 
                85                  90                  95      


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


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


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


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


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


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


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


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  41
<211>  450
<212>  PRT
<213>  humanized

<400>  41

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


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


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


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


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


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


Ala Arg Gly Tyr Tyr Tyr Tyr Gly Ser Ser Pro Asn Tyr Phe Asp Tyr 
            100                 105                 110         


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


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


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


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


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


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


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


Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly 
225                 230                 235                 240 


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


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


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


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


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


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


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


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


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


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


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


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


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


Gly Lys 
    450 


<210>  42
<211>  450
<212>  PRT
<213>  humanized

<400>  42

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


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


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


Ser Ser Ile Asn Tyr Asp Gly Arg Asn Thr Tyr Tyr Leu Asp Ser Leu 
    50                  55                  60                  


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


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


Ala Arg Gly Tyr Tyr Tyr Tyr Gly Ser Ser Pro Asn Tyr Phe Asp Tyr 
            100                 105                 110         


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


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


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


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


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


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


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


Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly 
225                 230                 235                 240 


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


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


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


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


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


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


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


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


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


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


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


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


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


Gly Lys 
    450 


<210>  43
<211>  214
<212>  PRT
<213>  humanized

<400>  43

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


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


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


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


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


Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln His Tyr Gly Thr Pro Leu 
                85                  90                  95      


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


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


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


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


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


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


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


Phe Asn Arg Gly Glu Cys 
    210                 
