                         SEQUENCE LISTING

<110>  Merck Sharp & Dohme Corp.
       Zhao, Jia
       Rios, Sandra
       Dukleska Schussler, Svetlana
 
<120>  Purification Process for Removal of Tyrosine Sulfation Antibody 
       Variants; Purified Compositions

<130>  24380

<150>  62/414,209
<151>  2016-10-28

<160>  65    

<170>  PatentIn version 3.5

<210>  1
<211>  408
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  1
atgaaatgca gctgggtcat cttcttcctg atggcagtgg ttataggaat caattcagag       60

gttcagctgc tccagtctgg ggcagaactt gtgaggtcag gggcctcagt caagttgtcc      120

tgcacagcct ctggcttcaa cattgaagac tactatatgc actggatgaa acagaggcct      180

gaacagggcc tggagtggat tggatggatt gatcctgtga atggtgatac tgaatatgcc      240

ccgaagttcc agggcaaggc cactatgact gcagacacat cctccaacac agcctaccta      300

cacctcaaca gcctgacatc tgaggacact gccgtctatt actgtaattt ctatgatggt      360

tacctctttg ctttctgggg ccaagggacc ctggtcactg tctctgca                   408


<210>  2
<211>  136
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  2

Met Lys Cys Ser Trp Val Ile Phe Phe Leu Met Ala Val Val Ile Gly 
1               5                   10                  15      


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


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


Glu Asp Tyr Tyr Met His Trp Met Lys Gln Arg Pro Glu Gln Gly Leu 
    50                  55                  60                  


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


Pro Lys Phe Gln Gly Lys Ala Thr Met Thr Ala Asp Thr Ser Ser Asn 
                85                  90                  95      


Thr Ala Tyr Leu His Leu Asn Ser Leu Thr Ser Glu Asp Thr Ala Val 
            100                 105                 110         


Tyr Tyr Cys Asn Phe Tyr Asp Gly Tyr Leu Phe Ala Phe Trp Gly Gln 
        115                 120                 125             


Gly Thr Leu Val Thr Val Ser Ala 
    130                 135     


<210>  3
<211>  10
<212>  PRT
<213>  Mus

<400>  3

Gly Phe Asn Ile Glu Asp Tyr Tyr Met His 
1               5                   10  


<210>  4
<211>  17
<212>  PRT
<213>  Mus

<400>  4

Trp Ile Asp Pro Val Asn Gly Asp Thr Glu Tyr Ala Pro Lys Phe Gln 
1               5                   10                  15      


Gly 
    


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

<400>  5

Tyr Asp Gly Tyr Leu Phe Ala Phe 
1               5               


<210>  6
<211>  396
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  6
atgaggtgcc tagctgagtt cctggggctg cttgtgctct ggatccctgg agccattggg       60

gatattgtgc tgactcaggc tgcaccctct gtacctgtca ctcctggaga gtcagtgtcc      120

atctcctgca ggtctagtaa gagtctcctg catagtgatg gcaacactta tctgtattgg      180

ctcctgcaga ggccaggcca gtctcctcag ctcctgatat atcggatgtc caaccttgcc      240

tcaggggtcc cagacaggtt cagcggcagt gggtcaggaa ctgttttcac actgagaatc      300

agcagactgg aggctgagga tgtgggtatt tattactgta tgcaacatct agaatatcct      360

ttcacgtttg gaggggggac caagctggaa ataaaa                                396


<210>  7
<211>  132
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  7

Met Arg Cys Leu Ala Glu Phe Leu Gly Leu Leu Val Leu Trp Ile Pro 
1               5                   10                  15      


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


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


Leu Leu His Ser Asp Gly Asn Thr Tyr Leu Tyr Trp Leu 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 Val Phe 
                85                  90                  95      


Thr Leu Arg Ile Ser Arg Leu Glu Ala Glu Asp Val Gly Ile 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 
    130         


<210>  8
<211>  16
<212>  PRT
<213>  Mus

<400>  8

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


<210>  9
<211>  8
<212>  PRT
<213>  Mus

<400>  9

Tyr Arg Met Ser Asn Leu Ala Ser 
1               5               


<210>  10
<211>  9
<212>  PRT
<213>  Mus

<400>  10

Met Gln His Leu Glu Tyr Pro Phe Thr 
1               5                   


<210>  11
<211>  414
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  11
atgggatgga gctggatctt tcttttcctc ctgtcaggaa ctgcaggtgt ccgttgccag       60

atccgactgc agcagtctgg acctgagctg gtgaagcctg gggcttcagt gaagatatcc      120

tgcaaggctt ctgggtcctc cttcactgac tactatataa actgggtgaa gcagaagcct      180

ggacagggac ttgagtggat tggatggatt tatcctggaa gcggtaattc tatctacaat      240

gagaacttca aggccaaggc cacattgact gtagacacat cctccagcac agcctacatg      300

catctcagca gcctgacatc tgaggacact gctgtctatt tctgtgcaag agaggctgat      360

tacgacgatg ctttggacta ctggggtcaa ggaacctcgg tcaccgtctc ctca            414


<210>  12
<211>  138
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  12

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


Val Arg Cys Gln Ile Arg Leu Gln Gln Ser Gly Pro Glu Leu Val Lys 
            20                  25                  30          


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


Thr Asp Tyr Tyr Ile Asn Trp Val Lys Gln Lys Pro Gly Gln Gly Leu 
    50                  55                  60                  


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


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


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


Tyr Phe Cys Ala Arg Glu Ala Asp Tyr Asp Asp Ala Leu Asp Tyr Trp 
        115                 120                 125             


Gly Gln Gly Thr Ser Val Thr Val Ser Ser 
    130                 135             


<210>  13
<211>  10
<212>  PRT
<213>  Mus

<400>  13

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


<210>  14
<211>  17
<212>  PRT
<213>  Mus

<400>  14

Trp Ile Tyr Pro Gly Ser Gly Asn Ser Ile Tyr Asn Glu Asn Phe Lys 
1               5                   10                  15      


Ala 
    


<210>  15
<211>  10
<212>  PRT
<213>  Mus

<400>  15

Glu Ala Asp Tyr Asp Asp Ala Leu Asp Tyr 
1               5                   10  


<210>  16
<211>  384
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  16
atggtatcca cacctcagtt ccttgtattt ttgcttttct ggattccagc ctccagaggt       60

cacatcttgc tgactcagtc tccagccatt ctgtctgtga gtccaggaga aagagtcagt      120

ttctcctgca gggccagtca gagcattggc acaagcatac actggtatca gcaaagaaca      180

aatggttctc caaggcttct cataaagtat gcttctgagt ctatctctgg gatcccttcc      240

aggtttagtg gcagtggatc agggacagat tttactctta gcatcaacag tgtggagtca      300

gaagatattg cagattatta ctgtcaacaa agtaatagct ggccaacgta cacgttcgga      360

ggggggacca agctggaaat aaaa                                             384


<210>  17
<211>  128
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  17

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


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


Val Ser Pro Gly Glu Arg Val Ser Phe Ser Cys Arg Ala Ser Gln Ser 
        35                  40                  45              


Ile Gly Thr Ser Ile His Trp Tyr Gln Gln Arg Thr Asn Gly Ser Pro 
    50                  55                  60                  


Arg Leu Leu Ile Lys Tyr Ala Ser Glu Ser Ile Ser Gly Ile Pro Ser 
65                  70                  75                  80  


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


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


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


<210>  18
<211>  11
<212>  PRT
<213>  Mus

<400>  18

Arg Ala Ser Gln Ser Ile Gly Thr Ser Ile His 
1               5                   10      


<210>  19
<211>  7
<212>  PRT
<213>  Mus

<400>  19

Tyr Ala Ser Glu Ser Ile Ser 
1               5           


<210>  20
<211>  10
<212>  PRT
<213>  Mus

<400>  20

Gln Gln Ser Asn Ser Trp Pro Thr Tyr Thr 
1               5                   10  


<210>  21
<211>  426
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  21
atgagatgga gctgtatcat cctcttcttg gtagcaacag ctacaggtgt caactcccag       60

gtccaactgc agcagcctgg ggctgagctt gtgatgcctg gggcttcagc gaagatgtcc      120

tgcaaggctt ctggctacac actcactgac tactggatgc actgggtgaa gcagaggcct      180

ggacaaggcc ttgagtggat cggagcgatt gatatttctg atagttattc tagctacaat      240

caaaagttca agggcaaggc cacattgact gtagacgaat cctccagcac agcctacatg      300

cagctcacca gcctgacatc tgaggactct gcggtctatt actgtgcaag atcccctttc      360

tacaatagta gaggggggaa ctactttgac tactggggcc aaggcaccac tctcacagtc      420

tcctca                                                                 426


<210>  22
<211>  142
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  22

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


Val Asn Ser Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Met 
            20                  25                  30          


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


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


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


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


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


Tyr Tyr Cys Ala Arg Ser Pro Phe Tyr Asn Ser Arg Gly Gly Asn Tyr 
        115                 120                 125             


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


<210>  23
<211>  10
<212>  PRT
<213>  Mus

<400>  23

Gly Tyr Thr Leu Thr Asp Tyr Trp Met His 
1               5                   10  


<210>  24
<211>  17
<212>  PRT
<213>  Mus

<400>  24

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


Gly 
    


<210>  25
<211>  14
<212>  PRT
<213>  Mus

<400>  25

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


<210>  26
<211>  384
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  26
atgatgtcct ctgctcagtt ccttggtctc ctgttgctct gttttcaagg taccagatgt       60

gatatccaga tgacacagac tacatcctcc ctgtctgcct ctctgggaga cagagtcacc      120

atcagttgca gggcaagtca ggacattagc aattatttaa actggtatca gcagaaacca      180

gatggaactg ttaaactcct gatctactac acatcaagat tacactcagg agtcccatca      240

aggttcagtg gcagtgggtc tggaacagat tattctctca ccattagcaa cctggagcaa      300

gaagatattg ccacttactt ttgccaacag ggtgatacgc ttcctccgtg gacgttcggt      360

ggaggcacca agctggaaat caaa                                             384


<210>  27
<211>  128
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  27

Met Met Ser Ser Ala Gln Phe Leu Gly Leu Leu Leu Leu Cys Phe Gln 
1               5                   10                  15      


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


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


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


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


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


Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asp 
            100                 105                 110         


Thr Leu Pro Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 
        115                 120                 125             


<210>  28
<211>  11
<212>  PRT
<213>  Mus

<400>  28

Arg Ala Ser Gln Asp Ile Ser Asn Tyr Leu Asn 
1               5                   10      


<210>  29
<211>  7
<212>  PRT
<213>  Mus

<400>  29

Tyr Thr Ser Arg Leu His Ser 
1               5           


<210>  30
<211>  10
<212>  PRT
<213>  Mus

<400>  30

Gln Gln Gly Asp Thr Leu Pro Pro Trp Thr 
1               5                   10  


<210>  31
<211>  447
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  31
atgggatgga cctggatctt tctcttcttc ctgtcaggaa ctgcaggtgt cctctctgag       60

gtcctgctgc tacagtctgg acctgaactg gtgaagcctg ggacttcagt gaaaatcccc      120

tgcaaggctt ctggatacac attcactgac tacaacgtgg actgggtgaa gcagcgccat      180

ggaaagggcc ttgagtggat tggagatatt aatccaaaca atggtggtac tatctacagt      240

cagaaattca agggcaaggc cacattgact gttgacaagt cctccagcac agccttcatg      300

gagctccgca gcctgacatc tgaggacact gcagtctatt tctgtgcaag gaactatagg      360

tggtttggtg ctatggacca ctggggtcaa ggaacctcag tcaccgtctc ctcagccaaa      420

acaacagccc catcggtcta tccactg                                          447


<210>  32
<211>  138
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  32

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


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


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


Thr Asp Tyr Asn Val Asp Trp Val Lys Gln Arg His Gly Lys Gly Leu 
    50                  55                  60                  


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


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


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


Tyr Phe Cys Ala Arg Asn Tyr Arg Trp Phe Gly Ala Met Asp His Trp 
        115                 120                 125             


Gly Gln Gly Thr Ser Val Thr Val Ser Ser 
    130                 135             


<210>  33
<211>  5
<212>  PRT
<213>  Mus

<400>  33

Asp Tyr Asn Val Asp 
1               5   


<210>  34
<211>  17
<212>  PRT
<213>  Mus

<400>  34

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


Gly 
    


<210>  35
<211>  10
<212>  PRT
<213>  Mus

<400>  35

Asn Tyr Arg Trp Phe Gly Ala Met Asp His 
1               5                   10  


<210>  36
<211>  547
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  36
atggagacag acacaatcct gctatgggtg ctgctgctct gggttccagg ttccactggt       60

gacattgtgt tgacccaatc tccagcttct ttggctgtgt ctccagggca gagggccacc      120

atttcctgca aggccagtca aagtcttgat tatgaaggtg atagtgatat gaattggtac      180

caacagaaac caggacagcc acccagactc ctcatctctg gtgcatccaa tctagagtct      240

gggatcccag ccaggttcag tggcagtggg tctgggacag acttcactgt taacatccat      300

cctgtggagg aggaggatgc tgcaacctat tactgtcagc aaagtactga ggatcctcgg      360

acgttcggtg gaggcaccaa gctggaaatc aaacgggctg atgctgcacc aactgtatcc      420

atcttcccac catccagtga gcagttaaca tctggaggtg cctcagtcgt gtgcttcttg      480

aacaacttct accccaaaga catcaatgtc aagtggaaga ttgatggcag tgaacgacaa      540

aatggcg                                                                547


<210>  37
<211>  131
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  37

Met Glu Thr Asp Thr Ile Leu Leu Trp Val Leu Leu Leu Trp Val Pro 
1               5                   10                  15      


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


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


Leu Asp Tyr Glu Gly Asp Ser Asp Met Asn Trp Tyr Gln Gln Lys Pro 
    50                  55                  60                  


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


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


Val Asn Ile His Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr Cys 
            100                 105                 110         


Gln Gln Ser Thr Glu Asp Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu 
        115                 120                 125             


Glu Ile Lys 
    130     


<210>  38
<211>  15
<212>  PRT
<213>  Mus

<400>  38

Lys Ala Ser Gln Ser Leu Asp Tyr Glu Gly Asp Ser Asp Met Asn 
1               5                   10                  15  


<210>  39
<211>  7
<212>  PRT
<213>  Mus

<400>  39

Gly Ala Ser Asn Leu Glu Ser 
1               5           


<210>  40
<211>  9
<212>  PRT
<213>  Mus

<400>  40

Gln Gln Ser Thr Glu Asp Pro Arg Thr 
1               5                   


<210>  41
<211>  218
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  41

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 Ala Ser Gln Ser Leu Asp Tyr Glu 
            20                  25                  30          


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


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


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


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


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


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


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


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


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


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


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


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


<210>  42
<211>  449
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  42

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


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


Asn Val Asp Trp Val Arg Gln Ala Arg Gly Gln Arg Leu Glu Trp Ile 
        35                  40                  45              


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


Gln Glu Arg Val Thr Ile Thr Val 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 Asn Tyr Arg Trp Phe Gly Ala Met Asp His Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Lys 
    


<210>  43
<211>  218
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  43

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 Ala Ser Gln Ser Leu Asp Tyr Glu 
            20                  25                  30          


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


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


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


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


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


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


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


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


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


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


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


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


<210>  44
<211>  449
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  44

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


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


Asn Val Asp Trp Val Arg Gln Ala Arg Gly Gln Arg Leu Glu Trp Ile 
        35                  40                  45              


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


Gln Glu Arg Val Thr Ile Thr Val 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 Asn Tyr Arg Trp Phe Gly Ala Met Asp His Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Lys 
    


<210>  45
<211>  218
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  45

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 Ala Ser Gln Ser Leu Asp Tyr Glu 
            20                  25                  30          


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


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


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


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


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


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


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


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


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


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


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


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


<210>  46
<211>  449
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  46

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


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


Asn Val Asp Trp Val Arg Gln Ala Arg Gly Gln Arg Leu Glu Trp Ile 
        35                  40                  45              


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


Gln Glu Arg Val Thr Ile Thr Val 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 Asn Tyr Arg Trp Phe Gly Ala Met Asp His Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Lys 
    


<210>  47
<211>  218
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  47

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 Ala Ser Gln Ser Leu Asp Tyr Glu 
            20                  25                  30          


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


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


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


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


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


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


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


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


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


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


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


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


<210>  48
<211>  449
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  48

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


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


Asn Val Asp Trp Val Arg Gln Ala Arg Gly Gln Arg Leu Glu Trp Ile 
        35                  40                  45              


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


Gln Glu Arg Val Thr Ile Thr Val 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 Asn Tyr Arg Trp Phe Gly Ala Met Asp His Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


Lys 
    


<210>  49
<211>  218
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  49

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 Ala Ser Gln Ser Leu Asp Tyr Glu 
            20                  25                  30          


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


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


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


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


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


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


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


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


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


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


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


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


<210>  50
<211>  446
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  50

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


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


Asn Val Asp Trp Val Arg Gln Ala Arg Gly Gln Arg Leu Glu Trp Ile 
        35                  40                  45              


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


Gln Glu Arg Val Thr Ile Thr Val 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 Asn Tyr Arg Trp Phe Gly Ala Met Asp His Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  51
<211>  218
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  51

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 Ala Ser Gln Ser Leu Asp Tyr Glu 
            20                  25                  30          


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


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


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


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


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


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


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


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


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


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


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


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


<210>  52
<211>  446
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  52

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


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


Asn Val Asp Trp Val Arg Gln Ala Arg Gly Gln Arg Leu Glu Trp Ile 
        35                  40                  45              


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


Gln Glu Arg Val Thr Ile Thr Val 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 Asn Tyr Arg Trp Phe Gly Ala Met Asp His Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  53
<211>  218
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  53

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 Ala Ser Gln Ser Leu Asp Tyr Glu 
            20                  25                  30          


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


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


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


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


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


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


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


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


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


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


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


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


<210>  54
<211>  446
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  54

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


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


Asn Val Asp Trp Val Arg Gln Ala Arg Gly Gln Arg Leu Glu Trp Ile 
        35                  40                  45              


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


Gln Glu Arg Val Thr Ile Thr Val 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 Asn Tyr Arg Trp Phe Gly Ala Met Asp His Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  55
<211>  218
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  55

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 Ala Ser Gln Ser Leu Asp Tyr Glu 
            20                  25                  30          


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


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


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


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


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


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


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


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


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


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


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


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


<210>  56
<211>  446
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  56

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


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


Asn Val Asp Trp Val Arg Gln Ala Arg Gly Gln Arg Leu Glu Trp Ile 
        35                  40                  45              


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


Gln Glu Arg Val Thr Ile Thr Val 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 Asn Tyr Arg Trp Phe Gly Ala Met Asp His Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  57
<211>  218
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  57

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 Ala Ser Gln Ser Leu Asp Tyr Glu 
            20                  25                  30          


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


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


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


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


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


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


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


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


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


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


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


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


<210>  58
<211>  446
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized mouse

<400>  58

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


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


Asn Val Asp Trp Val Arg Gln Ala Arg Gly Gln Arg Leu Glu Trp Ile 
        35                  40                  45              


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


Gln Glu Arg Val Thr Ile Thr Val 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 Asn Tyr Arg Trp Phe Gly Ala Met Asp His Trp Gly Gln Gly 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  59
<211>  17
<212>  PRT
<213>  Mus

<400>  59

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


Glu 
    


<210>  60
<211>  17
<212>  PRT
<213>  Mus

<400>  60

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


Glu 
    


<210>  61
<211>  17
<212>  PRT
<213>  Mus

<400>  61

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


Glu 
    


<210>  62
<211>  17
<212>  PRT
<213>  Mus

<400>  62

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


Glu 
    


<210>  63
<211>  17
<212>  PRT
<213>  Mus

<400>  63

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


Glu 
    


<210>  64
<211>  17
<212>  PRT
<213>  Mus


<220>
<221>  MISC_FEATURE
<222>  (6)..(6)
<223>  X is D,N,S or Q

<220>
<221>  MISC_FEATURE
<222>  (12)..(12)
<223>  X is A or S

<220>
<221>  MISC_FEATURE
<222>  (16)..(16)
<223>  X is Q or K

<220>
<221>  MISC_FEATURE
<222>  (17)..(17)
<223>  X is E or G

<400>  64

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


Xaa 
    


<210>  65
<211>  19
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic peptide


<220>
<221>  misc_feature
<222>  (1)..(1)
<223>  Xaa can be any naturally occurring amino acid

<220>
<221>  misc_feature
<222>  (3)..(3)
<223>  Xaa can be any naturally occurring amino acid

<220>
<221>  misc_feature
<222>  (5)..(5)
<223>  Xaa can be any naturally occurring amino acid

<220>
<221>  misc_feature
<222>  (13)..(19)
<223>  Xaa can be any naturally occurring amino acid

<400>  65

Xaa Ser Xaa Ser Xaa Asp Tyr Glu Gly Asp Ser Asp Xaa Xaa Xaa Xaa 
1               5                   10                  15      


Xaa Xaa Xaa 
            


