                         SEQUENCE LISTING

<110>  CENTOCOR ORTHO BIOTECH INC.
       SWANSON, Ronald V.
       CHI, Ellen
       RAGHUNATHAN, Gopalan
       ZHAO, Shanrong
       FRANSSON, Johan
       CORDIER, Wendy
       ALMAGRO, Juan C.
       HYUN, Linus
       GILES-KOMAR, Jill
       O'NEIL, Karyn T.
       CARTON, Jill M.
       ZHOU, Hong Mimi
       TEPLYAKOV, Alexey V.
 
<120>  ENGINEERED ANTI- IL-13 ANTIBODIES, COMPOSITIONS, METHODS AND USES

<130>  CEN5229WOPCT

<140>  Unknown
<141>  Herewith

<150>  61/090,472
<151>  2008-08-20

<150>  61/097,232
<151>  2008-09-16

<160>  29    

<170>  PatentIn version 3.5

<210>  1
<211>  112
<212>  PRT
<213>  Homo sapiens


<220> 
<221> NAME/KEY: VARIANT        
<222> LOCATION: 110
<223> OTHER INFORMATION: Xaa = Any Amino Acid

<400>  1

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


Val Asn Ile Thr Gln Asn Gln Lys Ala Pro Leu Cys Asn Gly Ser Met 
            20                  25                  30          


Val Trp Ser Ile Asn Leu Thr Ala Gly Met Tyr Cys Ala Ala Leu Glu 
        35                  40                  45              


Ser Leu Ile Asn Val Ser Gly Cys Ser Ala Ile Glu Lys Thr Gln Arg 
    50                  55                  60                  


Met Leu Ser Gly Phe Cys Pro His Lys Val Ser Ala Gly Gln Phe Ser 
65                  70                  75                  80  


Ser Leu His Val Arg Asp Thr Lys Ile Glu Val Ala Gln Phe Val Lys 
                85                  90                  95      


Asp Leu Leu Leu His Leu Lys Lys Leu Phe Arg Glu Gly Xaa Phe Asn 
            100                 105                 110         


<210>  2
<211>  107
<212>  PRT
<213>  Mus musculus


<220>
<221>  BINDING
<222>  (24)..(34)
<223>  CDR1

<220>
<221>  BINDING
<222>  (50)..(56)
<223>  CDR2

<220>
<221>  BINDING
<222>  (89)..(97)
<223>  CDR3

<400>  2

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


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


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


Tyr Ser Gly Ser Thr Leu Gln Ser Gly Ile Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


Glu Asp Phe Ala Met Tyr Phe Cys Gln Gln His Asn Glu Tyr Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg
            100                 105         108


<210>  3
<211>  121
<212>  PRT
<213>  Mus musculus


<220>
<221>  BINDING
<222>  (26)..(37)
<223>  CDR1

<220>
<221>  BINDING
<222>  (52)..(67)
<223>  CDR2

<220>
<221>  BINDING
<222>  (100)..(110)
<223>  CDR3

<400>  3

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


Thr Leu Ser Leu Thr Cys Ser Phe Ser Gly Phe Ser Leu Ser Thr Tyr 
            20                  25                  30          


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


Trp Leu Ala His Ile Trp Trp Asp Asp Val Lys Arg Tyr Asn Pro Ala 
    50                  55                  60                  


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


Phe Leu Lys Ile Ala Ser Val Asp Thr Ser Asp Thr Ala Thr Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Met Gly Ser Asp Tyr Asp Val Trp Phe Asp Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ala 
        115                 120     


<210>  4
<211>  107
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized immunogobulin light chain variable region


<220>
<221>  BINDING
<222>  (24)..(34)
<223>  CDR1

<220>
<221>  BINDING
<222>  (50)..(56)
<223>  CDR2

<220>
<221>  BINDING
<222>  (89)..(97)
<223>  CDR3

<400>  4

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 Lys Ser Ile Ser Lys Tyr 
            20                  25                  30          


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


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


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


<210>  5
<211>  107
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Humanized immunoglobulin variable region


<220>
<221>  BINDING
<222>  (24)..(34)
<223>  CDR1

<220>
<221>  BINDING
<222>  (50)..(56)
<223>  CDR2

<220>
<221>  BINDING
<222>  (89)..(97)
<223>  CDR3

<400>  5

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 Lys Ser Ile Ser Lys Tyr 
            20                  25                  30          


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


Tyr Ser Gly Ser Thr Leu Gln Ser 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 Asn Glu Tyr Pro Tyr 
                85                  90                  95      


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


<210>  6
<211>  107
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Humanized immunoglobulin variable domain


<220>
<221>  BINDING
<222>  (24)..(34)
<223>  CDR1

<220>
<221>  BINDING
<222>  (50)..(56)
<223>  CDR2

<220>
<221>  BINDING
<222>  (89)..(97)
<223>  CDR3

<400>  6

Ala Ile Gln Leu 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 Lys Ser Ile Ser Lys Tyr 
            20                  25                  30          


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


Tyr Ser Gly Ser Thr Leu Gln Ser 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 Asn Glu Tyr Pro Tyr 
                85                  90                  95      


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


<210>  7
<211>  107
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized immunoglobulin variable domain


<220>
<221>  BINDING
<222>  (24)..(34)
<223>  CDR1

<220>
<221>  BINDING
<222>  (50)..(56)
<223>  CDR2

<220>
<221>  BINDING
<222>  (89)..(97)
<223>  CDR3

<400>  7

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 Lys Ser Ile Ser Lys Tyr 
            20                  25                  30          


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


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


Ser Gly Ser Gly Thr Glu 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 Asn Glu Tyr Pro Tyr 
                85                  90                  95      


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


<210>  8
<211>  107
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized immunoglobulin variable domain


<220>
<221>  BINDING
<222>  (24)..(34)
<223>  CDR1

<220>
<221>  BINDING
<222>  (50)..(56)
<223>  CDR2

<220>
<221>  BINDING
<222>  (89)..(97)
<223>  CDR3

<400>  8

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


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


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


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


Ser Gly Ser Gly Thr Glu 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 Asn Glu Tyr Pro Tyr 
                85                  90                  95      


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


<210>  9
<211>  107
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized immunoglobulin variable domain


<220>
<221>  BINDING
<222>  (24)..(34)
<223>  CDR1

<220>
<221>  BINDING
<222>  (50)..(56)
<223>  CDR2

<220>
<221>  BINDING
<222>  (89)..(97)
<223>  CDR3

<400>  9

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


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


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


Tyr Ser Gly Ser Thr Leu Gln Ser Gly Ile Pro Ala Arg Phe Ser Gly 
    50                  55                  60                  


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


Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln His Asn Glu Tyr Pro Tyr 
                85                  90                  95      


Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg
            100                 105         108


<210>  10
<211>  107
<212>  PRT
<213>  Artificial

<220>
<223>  Humanized immunoglobulin variable domain


<220>
<221>  BINDING
<222>  (24)..(34)
<223>  CDR1

<220>
<221>  BINDING
<222>  (50)..(56)
<223>  CDR2

<220>
<221>  BINDING
<222>  (89)..(97)
<223>  CDR3

<400>  10

Asp Ile Gln Leu 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 Lys Ser Ile Ser Lys Tyr 
            20                  25                  30          


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


Tyr Ser Gly Ser Thr Leu Gln Ser 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 Val Ala Thr Tyr Tyr Gly Gln Gln His Asn Glu Tyr Pro Tyr 
                85                  90                  95      


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


<210>  11
<211>  107
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Humanized immunoglobulin variable region


<220>
<221>  BINDING
<222>  (24)..(34)
<223>  CDR1

<220>
<221>  BINDING
<222>  (50)..(56)
<223>  CDR2

<220>
<221>  BINDING
<222>  (89)..(97)
<223>  CDR3

<400>  11

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


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


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


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


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


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


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


<210>  12
<211>  107
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Humanized immunoglobulin variable region


<220>
<221>  BINDING
<222>  (24)..(34)
<223>  CDR1

<220>
<221>  BINDING
<222>  (50)..(56)
<223>  CDR2

<220>
<221>  BINDING
<222>  (89)..(97)
<223>  CDR3

<400>  12

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 Lys Ser Ile Ser Lys Tyr 
            20                  25                  30          


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


Tyr Ser Gly Ser Thr Leu Gln Ser 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 Asn Glu Tyr Pro Tyr 
                85                  90                  95      


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


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

<220>
<223>  Humanized immunoglobulin variable region


<220>
<221>  BINDING
<222>  (24)..(34)
<223>  CDR1

<220>
<221>  BINDING
<222>  (50)..(56)
<223>  CDR2

<220>
<221>  BINDING
<222>  (89)..(97)
<223>  CDR3

<400>  13

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


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


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


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


Ser Gly Ser Gly Thr Glu 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 Asn Glu Tyr Pro Tyr 
                85                  90                  95      


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


<210>  14
<211>  107
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Humanized immunoglobulin variable region


<220>
<221>  BINDING
<222>  (24)..(34)
<223>  CDR1

<220>
<221>  BINDING
<222>  (50)..(56)
<223>  CDR2

<220>
<221>  BINDING
<222>  (89)..(97)
<223>  CDR3

<400>  14

Ala Ile Arg Met Thr Gln Ser Pro Ser Ser Phe Ser Ala Ser Thr Gly 
1               5                   10                  15      


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


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


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


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


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


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


<210>  15
<211>  107
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Humanized immunoglobulin variable domain


<220>
<221>  BINDING
<222>  (24)..(34)
<223>  CDR1

<220>
<221>  BINDING
<222>  (50)..(56)
<223>  CDR2

<220>
<221>  BINDING
<222>  (89)..(97)
<223>  CDR3

<400>  15

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 Lys Ser Ile Ser Lys Tyr 
            20                  25                  30          


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


Tyr Ser Gly Ser Thr Leu Gln Ser 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 Asn Glu Tyr Pro Tyr 
                85                  90                  95      


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


<210>  16
<211>  107
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Humanized immunoglobulin variable region


<220>
<221>  BINDING
<222>  (24)..(34)
<223>  CDR1

<220>
<221>  BINDING
<222>  (50)..(56)
<223>  CDR2

<220>
<221>  BINDING
<222>  (89)..(97)
<223>  CDR3

<400>  16

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


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


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


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


Ser Gly Ser Gly Thr Glu 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 Asn Glu Tyr Pro Tyr 
                85                  90                  95      


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


<210>  17
<211>  107
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Humanized immunoglobulin variable region


<220>
<221>  BINDING
<222>  (24)..(34)
<223>  CDR1

<220>
<221>  BINDING
<222>  (50)..(56)
<223>  CDR2

<220>
<221>  BINDING
<222>  (89)..(97)
<223>  CDR3

<400>  17

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


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


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


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


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


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


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


<210>  18
<211>  107
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Humanized immunoglobulin variable region


<220>
<221>  BINDING
<222>  (24)..(34)
<223>  CDR1

<220>
<221>  BINDING
<222>  (50)..(56)
<223>  CDR2

<220>
<221>  BINDING
<222>  (89)..(97)
<223>  CDR3

<400>  18

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


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


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


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


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


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


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


<210>  19
<211>  121
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Humanized immunoglobulin variable domain


<220>
<221>  BINDING
<222>  (26)..(37)
<223>  CDR1

<220>
<221>  BINDING
<222>  (52)..(67)
<223>  CDR2

<220>
<221>  BINDING
<222>  (100)..(110)
<223>  CDR3

<400>  19

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


Thr Leu Thr Leu Thr Cys Thr Phe Ser Gly Phe Ser Leu Ser Thr Tyr 
            20                  25                  30          


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


Trp Leu Ala His Ile Trp Trp Asp Asp Val Lys Arg Tyr Asn Pro Ala 
    50                  55                  60                  


Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Lys Asn Gln Val 
65                  70                  75                  80  


Val Leu Thr Met Thr Asn Met Asp Pro Val Asp Thr Ala Thr Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Met Gly Ser Asp Tyr Asp Val Trp Phe Asp Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


<210>  20
<211>  121
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Humanized immunoglobulin variable domain


<220>
<221>  BINDING
<222>  (26)..(37)
<223>  CDR1

<220>
<221>  BINDING
<222>  (52)..(67)
<223>  CDR2

<220>
<221>  BINDING
<222>  (100)..(110)
<223>  CDR3

<400>  20

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


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


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


Trp Leu Ala His Ile Trp Trp Asp Asp Val Lys Arg Tyr Asn Pro Ala 
    50                  55                  60                  


Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Lys Ser Gln Val 
65                  70                  75                  80  


Val Leu Thr Met Thr Asn Met Asp Pro Val Asp Thr Ala Thr Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Met Gly Ser Asp Tyr Asp Val Trp Phe Asp Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


<210>  21
<211>  121
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Humanized immunoglobulin variable region


<220>
<221>  BINDING
<222>  (26)..(37)
<223>  CDR1

<220>
<221>  BINDING
<222>  (52)..(67)
<223>  CDR2

<220>
<221>  BINDING
<222>  (100)..(110)
<223>  CDR3

<400>  21

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


Thr Leu Thr Leu Thr Cys Thr Phe Ser Gly Phe Ser Leu Ser Thr Tyr 
            20                  25                  30          


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


Trp Leu Ala His Ile Trp Trp Asp Asp Val Lys Arg Tyr Asn Pro Ala 
    50                  55                  60                  


Leu Lys Ser Arg Leu Thr Ile Thr Lys Asp Thr Ser Lys Asn Gln Val 
65                  70                  75                  80  


Val Leu Thr Met Thr Asn Met Asp Pro Val Asp Thr Ala Thr Tyr Tyr 
                85                  90                  95      


Cys Ala His Met Gly Ser Asp Tyr Asp Val Trp Phe Asp Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


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

<220>
<223>  Humanized immunglobulin variable region


<220>
<221>  BINDING
<222>  (26)..(37)
<223>  CDR1

<220>
<221>  BINDING
<222>  (52)..(67)
<223>  CDR2

<220>
<221>  BINDING
<222>  (100)..(110)
<223>  CDR3

<400>  22

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


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


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


Trp Ile Gly His Ile Trp Trp Asp Asp Val Lys Arg Tyr Asn Pro Ala 
    50                  55                  60                  


Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe 
65                  70                  75                  80  


Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Met Gly Ser Asp Tyr Asp Val Trp Phe Asp Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


<210>  23
<211>  121
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Humanized immunoglobulin variable region


<220>
<221>  BINDING
<222>  (26)..(37)
<223>  CDR1

<220>
<221>  BINDING
<222>  (52)..(67)
<223>  CDR2

<220>
<221>  BINDING
<222>  (100)..(110)
<223>  CDR3

<400>  23

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


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


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


Trp Ile Gly His Ile Trp Trp Asp Asp Val Lys Arg Tyr Asn Pro Ala 
    50                  55                  60                  


Leu Lys Ser Arg Val Thr Met Ser Val Asp Thr Ser Lys Asn Gln Phe 
65                  70                  75                  80  


Ser Leu Lys Leu Ser Ser Val Thr Ala Val Asp Thr Ala Val Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Met Gly Ser Asp Tyr Asp Val Trp Phe Asp Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


<210>  24
<211>  121
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Humanized immunoglobulin variable region


<220>
<221>  BINDING
<222>  (26)..(37)
<223>  CDR1

<220>
<221>  BINDING
<222>  (52)..(67)
<223>  CDR2

<220>
<221>  BINDING
<222>  (100)..(110)
<223>  CDR3

<400>  24

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


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


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


Trp Val Ala His Ile Trp Trp Asp Asp Val Lys Arg Tyr Asn Pro Ala 
    50                  55                  60                  


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


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


Cys Ala Arg Met Gly Ser Asp Tyr Asp Val Trp Phe Asp Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


<210>  25
<211>  106
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Humanized antibody light chain


<220>
<221>  BINDING
<222>  (24)..(34)
<223>  CDR1

<220>
<221>  BINDING
<222>  (50)..(56)
<223>  CDR2

<220>
<221>  BINDING
<222>  (89)..(97)
<223>  CDR3

<400>  25

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


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


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


Tyr Ser Gly Ser Thr Leu Gln Ser Gly Ile Pro Ala Arg Phe Ser Gly 
    50                  55                  60                  


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


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


Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg
            100                 105     108


<210>  26
<211>  121
<212>  PRT
<213>  Artificial sequence

<220>
<223>  Humanized antibody heavy chain


<220>
<221>  BINDING
<222>  (26)..(37)
<223>  CDR1

<220>
<221>  BINDING
<222>  (52)..(67)
<223>  CDR2

<220>
<221>  BINDING
<222>  (100)..(110)
<223>  CDR3

<400>  26

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


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


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


Trp Leu Ala His Ile Trp Trp Asp Asp Val Lys Arg Tyr Asn Pro Ala 
    50                  55                  60                  


Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Lys Ser Gln Val 
65                  70                  75                  80  


Val Leu Thr Met Thr Asn Met Asp Pro Val Asp Thr Ala Thr Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Leu Gly Ser Asp Tyr Asp Val Trp Phe Asp Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


<210>  27
<211>  107
<212>  PRT
<213>  Artificial sequence

<220> 
<221> NAME/KEY: VARIANT        
<222> LOCATION: 38, 54, 91, 92, 93, 94
<223> OTHER INFORMATION: Xaa = Any Amino Acid

<400>  27

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


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


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


Tyr Ser Gly Ser Thr Xaa Gln Ser Gly Ile Pro Ala Arg Phe Ser Gly 
    50                  55                  60                  


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


Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Xaa Xaa Xaa Xaa Pro Tyr 
                85                  90                  95      


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


<210>  28
<211>  121
<212>  PRT
<213>  Artificial sequence

<220> 
<221> NAME/KEY: VARIANT        
<222> LOCATION: 31, 34, 100, 106
<223> OTHER INFORMATION: Xaa = Any Amino Acid

<400>  28

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


Thr Leu Thr Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Ser Xaa Tyr 
            20                  25                  30          


Gly Xaa Gly Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Ala Leu Glu 
        35                  40                  45              


Trp Leu Ala His Ile Trp Trp Asp Asp Val Lys Arg Tyr Asn Pro Ala 
    50                  55                  60                  


Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser Lys Ser Gln Val 
65                  70                  75                  80  


Val Leu Thr Met Thr Asn Met Asp Pro Val Asp Thr Ala Thr Tyr Tyr 
                85                  90                  95      


Cys Ala Arg Xaa Gly Ser Asp Tyr Asp Xaa Trp Phe Asp Tyr Trp Gly 
            100                 105                 110         


Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120     


<210>  29
<211>  9
<212>  PRT
<213>  Artificial sequence

<220> 
<221> NAME/KEY: VARIANT        
<222> LOCATION: 3, 4, 5, 6
<223> OTHER INFORMATION: Xaa = Any Amino Acid

<400>  29

Gln Gln Xaa Xaa Xaa Xaa Pro Tyr Thr 
1               5                   


