                         SEQUENCE LISTING

<110>  Schering Corporation
       Presta, Leonard G.
       Ermakov, Grigori
 
<120>  Engineered Anti-IL-23R Antibodies

<130>  BP06866WO

<150>  US 61/223,971
<151>  2009-07-08

<150>  US 61/092,312
<151>  2008-08-27

<160>  28    

<170>  PatentIn version 3.5

<210>  1
<211>  119
<212>  PRT
<213>  Rattus norvegicus


<220>
<221>  CDRH1
<222>  (26)..(35)

<220>
<221>  CDRH2
<222>  (50)..(68)

<220>
<221>  CDRH3
<222>  (101)..(108)

<400>  1

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


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


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


Ala Asp Ile Asn Ser Lys Ser Tyr Asn Tyr Ala Thr Tyr Tyr Ala Asp 
    50                  55                  60                  


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


Val Tyr Leu Glu Met Asp Asn Leu Lys Thr Glu Asp Thr Ala Leu Tyr 
                85                  90                  95      


Tyr Cys Thr Val His His Ser Asp Tyr Phe Glu Tyr Trp Gly Gln Gly 
            100                 105                 110         


Val Met Val Thr Val Ser Ser 
        115                 


<210>  2
<211>  109
<212>  PRT
<213>  Rattus norvegicus


<220>
<221>  CDRL1
<222>  (24)..(34)

<220>
<221>  CDRL2
<222>  (50)..(56)

<220>
<221>  CDRL3
<222>  (89)..(97)

<400>  2

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


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


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


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


Ser Gly Ser Gly Thr Gln Tyr Ser Leu Lys Ile Asn Ser Leu Glu Ser 
65                  70                  75                  80  


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


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


<210>  3
<211>  10
<212>  PRT
<213>  Rattus norvegicus

<400>  3

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


<210>  4
<211>  19
<212>  PRT
<213>  Rattus norvegicus

<400>  4

Asp Ile Asn Ser Lys Ser Tyr Asn Tyr Ala Thr Tyr Tyr Ala Asp Ser 
1               5                   10                  15      


Val Lys Asp 
            


<210>  5
<211>  8
<212>  PRT
<213>  Rattus norvegicus

<400>  5

His His Ser Asp Tyr Phe Glu Tyr 
1               5               


<210>  6
<211>  11
<212>  PRT
<213>  Rattus norvegicus

<400>  6

Leu Ala Ser Glu Asp Ile Tyr Asn Asn Leu Ala 
1               5                   10      


<210>  7
<211>  7
<212>  PRT
<213>  Rattus norvegicus

<400>  7

His Ala Ser Ser Leu Gln Asp 
1               5           


<210>  8
<211>  9
<212>  PRT
<213>  Rattus norvegicus

<400>  8

Leu Gln Asp Ser Glu Tyr Pro Pro Thr 
1               5                   


<210>  9
<211>  629
<212>  PRT
<213>  Homo sapiens


<220>
<221>  SIGNAL
<222>  (1)..(23)

<400>  9

Met Asn Gln Val Thr Ile Gln Trp Asp Ala Val Ile Ala Leu Tyr Ile 
1               5                   10                  15      


Leu Phe Ser Trp Cys His Gly Gly Ile Thr Asn Ile Asn Cys Ser Gly 
            20                  25                  30          


His Ile Trp Val Glu Pro Ala Thr Ile Phe Lys Met Gly Met Asn Ile 
        35                  40                  45              


Ser Ile Tyr Cys Gln Ala Ala Ile Lys Asn Cys Gln Pro Arg Lys Leu 
    50                  55                  60                  


His Phe Tyr Lys Asn Gly Ile Lys Glu Arg Phe Gln Ile Thr Arg Ile 
65                  70                  75                  80  


Asn Lys Thr Thr Ala Arg Leu Trp Tyr Lys Asn Phe Leu Glu Pro His 
                85                  90                  95      


Ala Ser Met Tyr Cys Thr Ala Glu Cys Pro Lys His Phe Gln Glu Thr 
            100                 105                 110         


Leu Ile Cys Gly Lys Asp Ile Ser Ser Gly Tyr Pro Pro Asp Ile Pro 
        115                 120                 125             


Asp Glu Val Thr Cys Val Ile Tyr Glu Tyr Ser Gly Asn Met Thr Cys 
    130                 135                 140                 


Thr Trp Asn Ala Gly Lys Leu Thr Tyr Ile Asp Thr Lys Tyr Val Val 
145                 150                 155                 160 


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


Ser Tyr Ile Asn Ile Ser Thr Asp Ser Leu Gln Gly Gly Lys Lys Tyr 
            180                 185                 190         


Leu Val Trp Val Gln Ala Ala Asn Ala Leu Gly Met Glu Glu Ser Lys 
        195                 200                 205             


Gln Leu Gln Ile His Leu Asp Asp Ile Val Ile Pro Ser Ala Ala Val 
    210                 215                 220                 


Ile Ser Arg Ala Glu Thr Ile Asn Ala Thr Val Pro Lys Thr Ile Ile 
225                 230                 235                 240 


Tyr Trp Asp Ser Gln Thr Thr Ile Glu Lys Val Ser Cys Glu Met Arg 
                245                 250                 255     


Tyr Lys Ala Thr Thr Asn Gln Thr Trp Asn Val Lys Glu Phe Asp Thr 
            260                 265                 270         


Asn Phe Thr Tyr Val Gln Gln Ser Glu Phe Tyr Leu Glu Pro Asn Ile 
        275                 280                 285             


Lys Tyr Val Phe Gln Val Arg Cys Gln Glu Thr Gly Lys Arg Tyr Trp 
    290                 295                 300                 


Gln Pro Trp Ser Ser Pro Phe Phe His Lys Thr Pro Glu Thr Val Pro 
305                 310                 315                 320 


Gln Val Thr Ser Lys Ala Phe Gln His Asp Thr Trp Asn Ser Gly Leu 
                325                 330                 335     


Thr Val Ala Ser Ile Ser Thr Gly His Leu Thr Ser Asp Asn Arg Gly 
            340                 345                 350         


Asp Ile Gly Leu Leu Leu Gly Met Ile Val Phe Ala Val Met Leu Ser 
        355                 360                 365             


Ile Leu Ser Leu Ile Gly Ile Phe Asn Arg Ser Phe Arg Thr Gly Ile 
    370                 375                 380                 


Lys Arg Arg Ile Leu Leu Leu Ile Pro Lys Trp Leu Tyr Glu Asp Ile 
385                 390                 395                 400 


Pro Asn Met Lys Asn Ser Asn Val Val Lys Met Leu Gln Glu Asn Ser 
                405                 410                 415     


Glu Leu Met Asn Asn Asn Ser Ser Glu Gln Val Leu Tyr Val Asp Pro 
            420                 425                 430         


Met Ile Thr Glu Ile Lys Glu Ile Phe Ile Pro Glu His Lys Pro Thr 
        435                 440                 445             


Asp Tyr Lys Lys Glu Asn Thr Gly Pro Leu Glu Thr Arg Asp Tyr Pro 
    450                 455                 460                 


Gln Asn Ser Leu Phe Asp Asn Thr Thr Val Val Tyr Ile Pro Asp Leu 
465                 470                 475                 480 


Asn Thr Gly Tyr Lys Pro Gln Ile Ser Asn Phe Leu Pro Glu Gly Ser 
                485                 490                 495     


His Leu Ser Asn Asn Asn Glu Ile Thr Ser Leu Thr Leu Lys Pro Pro 
            500                 505                 510         


Val Asp Ser Leu Asp Ser Gly Asn Asn Pro Arg Leu Gln Lys His Pro 
        515                 520                 525             


Asn Phe Ala Phe Ser Val Ser Ser Val Asn Ser Leu Ser Asn Thr Ile 
    530                 535                 540                 


Phe Leu Gly Glu Leu Ser Leu Ile Leu Asn Gln Gly Glu Cys Ser Ser 
545                 550                 555                 560 


Pro Asp Ile Gln Asn Ser Val Glu Glu Glu Thr Thr Met Leu Leu Glu 
                565                 570                 575     


Asn Asp Ser Pro Ser Glu Thr Ile Pro Glu Gln Thr Leu Leu Pro Asp 
            580                 585                 590         


Glu Phe Val Ser Cys Leu Gly Ile Val Asn Glu Glu Leu Pro Ser Ile 
        595                 600                 605             


Asn Thr Tyr Phe Pro Gln Asn Ile Leu Glu Ser His Phe Asn Arg Ile 
    610                 615                 620                 


Ser Leu Leu Glu Lys 
625                 


<210>  10
<211>  662
<212>  PRT
<213>  Homo sapiens


<220>
<221>  SIGNAL
<222>  (1)..(24)

<400>  10

Met Glu Pro Leu Val Thr Trp Val Val Pro Leu Leu Phe Leu Phe Leu 
1               5                   10                  15      


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


Asp Pro Pro Tyr Pro Asp Ala Asp Ser Gly Ser Ala Ser Gly Pro Arg 
        35                  40                  45              


Asp Leu Arg Cys Tyr Arg Ile Ser Ser Asp Arg Tyr Glu Cys Ser Trp 
    50                  55                  60                  


Gln Tyr Glu Gly Pro Thr Ala Gly Val Ser His Phe Leu Arg Cys Cys 
65                  70                  75                  80  


Leu Ser Ser Gly Arg Cys Cys Tyr Phe Ala Ala Gly Ser Ala Thr Arg 
                85                  90                  95      


Leu Gln Phe Ser Asp Gln Ala Gly Val Ser Val Leu Tyr Thr Val Thr 
            100                 105                 110         


Leu Trp Val Glu Ser Trp Ala Arg Asn Gln Thr Glu Lys Ser Pro Glu 
        115                 120                 125             


Val Thr Leu Gln Leu Tyr Asn Ser Val Lys Tyr Glu Pro Pro Leu Gly 
    130                 135                 140                 


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


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


Pro Ser Ser Pro Trp Lys Leu Gly Asp Cys Gly Pro Gln Asp Asp Asp 
            180                 185                 190         


Thr Glu Ser Cys Leu Cys Pro Leu Glu Met Asn Val Ala Gln Glu Phe 
        195                 200                 205             


Gln Leu Arg Arg Arg Gln Leu Gly Ser Gln Gly Ser Ser Trp Ser Lys 
    210                 215                 220                 


Trp Ser Ser Pro Val Cys Val Pro Pro Glu Asn Pro Pro Gln Pro Gln 
225                 230                 235                 240 


Val Arg Phe Ser Val Glu Gln Leu Gly Gln Asp Gly Arg Arg Arg Leu 
                245                 250                 255     


Thr Leu Lys Glu Gln Pro Thr Gln Leu Glu Leu Pro Glu Gly Cys Gln 
            260                 265                 270         


Gly Leu Ala Pro Gly Thr Glu Val Thr Tyr Arg Leu Gln Leu His Met 
        275                 280                 285             


Leu Ser Cys Pro Cys Lys Ala Lys Ala Thr Arg Thr Leu His Leu Gly 
    290                 295                 300                 


Lys Met Pro Tyr Leu Ser Gly Ala Ala Tyr Asn Val Ala Val Ile Ser 
305                 310                 315                 320 


Ser Asn Gln Phe Gly Pro Gly Leu Asn Gln Thr Trp His Ile Pro Ala 
                325                 330                 335     


Asp Thr His Thr Glu Pro Val Ala Leu Asn Ile Ser Val Gly Thr Asn 
            340                 345                 350         


Gly Thr Thr Met Tyr Trp Pro Ala Arg Ala Gln Ser Met Thr Tyr Cys 
        355                 360                 365             


Ile Glu Trp Gln Pro Val Gly Gln Asp Gly Gly Leu Ala Thr Cys Ser 
    370                 375                 380                 


Leu Thr Ala Pro Gln Asp Pro Asp Pro Ala Gly Met Ala Thr Tyr Ser 
385                 390                 395                 400 


Trp Ser Arg Glu Ser Gly Ala Met Gly Gln Glu Lys Cys Tyr Tyr Ile 
                405                 410                 415     


Thr Ile Phe Ala Ser Ala His Pro Glu Lys Leu Thr Leu Trp Ser Thr 
            420                 425                 430         


Val Leu Ser Thr Tyr His Phe Gly Gly Asn Ala Ser Ala Ala Gly Thr 
        435                 440                 445             


Pro His His Val Ser Val Lys Asn His Ser Leu Asp Ser Val Ser Val 
    450                 455                 460                 


Asp Trp Ala Pro Ser Leu Leu Ser Thr Cys Pro Gly Val Leu Lys Glu 
465                 470                 475                 480 


Tyr Val Val Arg Cys Arg Asp Glu Asp Ser Lys Gln Val Ser Glu His 
                485                 490                 495     


Pro Val Gln Pro Thr Glu Thr Gln Val Thr Leu Ser Gly Leu Arg Ala 
            500                 505                 510         


Gly Val Ala Tyr Thr Val Gln Val Arg Ala Asp Thr Ala Trp Leu Arg 
        515                 520                 525             


Gly Val Trp Ser Gln Pro Gln Arg Phe Ser Ile Glu Val Gln Val Ser 
    530                 535                 540                 


Asp Trp Leu Ile Phe Phe Ala Ser Leu Gly Ser Phe Leu Ser Ile Leu 
545                 550                 555                 560 


Leu Val Gly Val Leu Gly Tyr Leu Gly Leu Asn Arg Ala Ala Arg His 
                565                 570                 575     


Leu Cys Pro Pro Leu Pro Thr Pro Cys Ala Ser Ser Ala Ile Glu Phe 
            580                 585                 590         


Pro Gly Gly Lys Glu Thr Trp Gln Trp Ile Asn Pro Val Asp Phe Gln 
        595                 600                 605             


Glu Glu Ala Ser Leu Gln Glu Ala Leu Val Val Glu Met Ser Trp Asp 
    610                 615                 620                 


Lys Gly Glu Arg Thr Glu Pro Leu Glu Lys Thr Glu Leu Pro Glu Gly 
625                 630                 635                 640 


Ala Pro Glu Leu Ala Leu Asp Thr Glu Leu Ser Leu Glu Asp Gly Asp 
                645                 650                 655     


Arg Cys Lys Ala Lys Met 
            660         


<210>  11
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Rat CDRs and human frameworks


<220>
<221>  CDRH1
<222>  (26)..(35)

<220>
<221>  CDRH2
<222>  (50)..(68)

<220>
<221>  CDRH3
<222>  (101)..(108)

<400>  11

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 Asp Phe Asn Ser Tyr 
            20                  25                  30          


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


Ala Asp Ile Asn Ser Lys Ser Tyr Asn Tyr Ala Thr Tyr Tyr Ala Asp 
    50                  55                  60                  


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


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


Tyr Cys Ala Arg His His Ser Asp Tyr Phe Glu Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  12
<211>  109
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Rat CDRs and human frameworks


<220>
<221>  CDRL1
<222>  (24)..(34)

<220>
<221>  CDRL2
<222>  (50)..(56)

<220>
<221>  CDRL3
<222>  (89)..(97)

<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 Leu Ala Ser Glu Asp Ile Tyr Asn Asn 
            20                  25                  30          


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


Tyr His Ala Ser Ser Leu Gln Asp 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 Leu Gln Asp Ser Glu Tyr Pro Pro 
                85                  90                  95      


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


<210>  13
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Rat CDRs and modified human frameworks


<220>
<221>  CDRH1
<222>  (26)..(35)

<220>
<221>  CDRH2
<222>  (50)..(68)

<220>
<221>  CDRH3
<222>  (101)..(108)

<400>  13

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 Asp Phe Asn Ser Tyr 
            20                  25                  30          


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


Ala Asp Ile Asn Ser Lys Ser Tyr Asn Tyr Ala Thr Tyr Tyr Ala Asp 
    50                  55                  60                  


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


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


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


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  14
<211>  109
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Modified rat CDRs and modified human frameworks


<220>
<221>  CDRL1
<222>  (24)..(34)

<220>
<221>  CDRL2
<222>  (50)..(56)

<220>
<221>  CDRL3
<222>  (89)..(97)

<400>  14

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 Gln Asp Ile Tyr Thr Asn 
            20                  25                  30          


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


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


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


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


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


<210>  15
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Modified rat sequence

<400>  15

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


<210>  16
<211>  449
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Rat CDRs, modified human frameworks, and human IgG1 constant 
       domain


<220>
<221>  Variable
<222>  (1)..(119)

<220>
<221>  CDRH1
<222>  (26)..(35)

<220>
<221>  CDRH2
<222>  (50)..(68)

<220>
<221>  CDRH3
<222>  (101)..(108)

<220>
<221>  Constant
<222>  (120)..(449)

<400>  16

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 Asp Phe Asn Ser Tyr 
            20                  25                  30          


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


Ala Asp Ile Asn Ser Lys Ser Tyr Asn Tyr Ala Thr Tyr Tyr Ala Asp 
    50                  55                  60                  


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


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


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


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


Pro Leu Ala Pro 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>  17
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Modified rat CDRs, modified human frameworks, and human kappa 
       constant domain


<220>
<221>  Variable
<222>  (1)..(109)

<220>
<221>  CDRL1
<222>  (24)..(34)

<220>
<221>  CDRL2
<222>  (50)..(56)

<220>
<221>  CDRL3
<222>  (89)..(97)

<220>
<221>  Constant
<222>  (110)..(214)

<400>  17

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 Gln Asp Ile Tyr Thr Asn 
            20                  25                  30          


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


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


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


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


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


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


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


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


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


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


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


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  18
<211>  19
<212>  PRT
<213>  Mus musculus

<400>  18

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


Val Leu Ser 
            


<210>  19
<211>  19
<212>  PRT
<213>  Rattus norvegicus

<400>  19

Met Ala Pro Val Gln Leu Leu Gly Leu Leu Val Leu Phe Leu Pro Ala 
1               5                   10                  15      


Met Arg Cys 
            


<210>  20
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Modified rat sequence

<400>  20

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


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

<220>
<223>  Modified rat sequence

<400>  21

His Ala Ser Ser Leu Gln Ser 
1               5           


<210>  22
<211>  119
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Modified rat CDRs and modified human frameworks


<220>
<221>  CDRH1
<222>  (26)..(35)

<220>
<221>  CDRH2
<222>  (50)..(68)

<220>
<221>  CDRH3
<222>  (101)..(108)

<400>  22

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 Asp Phe Ser Ser Tyr 
            20                  25                  30          


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


Ala Asp Ile Asn Ser Lys Ser Tyr Asn Tyr Ala Thr Tyr Tyr Ala Asp 
    50                  55                  60                  


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


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


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


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  23
<211>  109
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Modified rat CDRs and modified human frameworks


<220>
<221>  CDRL1
<222>  (24)..(34)

<220>
<221>  CDRL2
<222>  (50)..(56)

<220>
<221>  CDRL3
<222>  (89)..(97)

<400>  23

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 Gln Asp Ile Tyr Thr Asn 
            20                  25                  30          


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


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


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


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


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


<210>  24
<211>  449
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Modified rat CDRs, modified human frameworks, and human IgG1 
       constant domain


<220>
<221>  Variable
<222>  (1)..(119)

<220>
<221>  CDRH1
<222>  (26)..(35)

<220>
<221>  CDRH2
<222>  (50)..(68)

<220>
<221>  CDRH3
<222>  (101)..(108)

<220>
<221>  Constant
<222>  (120)..(449)

<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 Asp Phe Ser Ser Tyr 
            20                  25                  30          


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


Ala Asp Ile Asn Ser Lys Ser Tyr Asn Tyr Ala Thr Tyr Tyr Ala Asp 
    50                  55                  60                  


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


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


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


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


Pro Leu Ala Pro 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>  25
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Modified rat CDRs, modified human frameworks, and human kappa 
       constant domain


<220>
<221>  Variable
<222>  (1)..(109)

<220>
<221>  CDRL1
<222>  (24)..(34)

<220>
<221>  CDRL2
<222>  (50)..(56)

<220>
<221>  CDRL3
<222>  (89)..(97)

<220>
<221>  Constant
<222>  (110)..(214)

<400>  25

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 Gln Asp Ile Tyr Thr Asn 
            20                  25                  30          


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


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


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


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


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


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


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


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


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


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


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


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  26
<211>  446
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Modified rat CDRs, modified human frameworks, and modified human 
       IgG4 constant domain


<220>
<221>  Variable
<222>  (1)..(119)

<220>
<221>  CDRH1
<222>  (26)..(35)

<220>
<221>  CDRH2
<222>  (50)..(68)

<220>
<221>  CDRH3
<222>  (101)..(108)

<220>
<221>  Constant
<222>  (120)..(446)

<400>  26

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 Asp Phe Ser Ser Tyr 
            20                  25                  30          


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


Ala Asp Ile Asn Ser Lys Ser Tyr Asn Tyr Ala Thr Tyr Tyr Ala Asp 
    50                  55                  60                  


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


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


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


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


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


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


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


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


Ser 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>  27
<211>  1395
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Mouse signal sequence, modified rat CDRs, modified human 
       frameworks, modified human IgG4 constant domain


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

<400>  27
atggccgtgc tgggcctgct gttctgcctg gtgaccttcc cttcctgcgt gctgtcccag       60

gtgcagctgg tcgagtctgg cggcggtgtg gtgcagcctg gccggtccct gagactgtcc      120

tgcgccgcct ccggcttcga cttctcctcc tacggcatgt cctgggtgcg ccaggctcct      180

ggcaagggcc tcgacctggt ggccgacatc aactccaagt cctacaacta cgccacctac      240

tacgccgact ccgtgaagga ccggttcacc atctcccggg acaactccaa gaacaccctg      300

tacctgcaga tgaactccct gcgggccgag gacaccgccg tgtactactg cgccgtgcac      360

cactccgact acttcgagta ctggggccag ggcaccctgg tgaccgtgtc ctccgctagc      420

accaagggcc cttccgtgtt ccctctggcc ccttgctccc ggtccacctc cgagtccacc      480

gccgctctgg gctgtctggt gaaggactac ttccctgagc ctgtgacagt gtcctggaac      540

tctggcgccc tgacctccgg cgtgcacacc ttccctgccg tgctgcagtc ctccggcctg      600

tactccctgt cctccgtggt gacagtgcct tcctcctccc tgggcaccaa gacctacacc      660

tgcaacgtgg accacaagcc ttccaacacc aaggtggaca agcgggtgga gtccaagtac      720

ggccctcctt gccctccctg ccctgcccct gagttcctgg gcggaccctc cgtgttcctg      780

ttccctccta agcctaagga caccctgatg atctcccgga cccctgaagt gacctgcgtg      840

gtggtggatg tgtcccagga agatcctgag gtccagttca attggtacgt ggacggcgtg      900

gaggtgcaca acgccaagac caagcctcgg gaggaacagt tcaactccac ctaccgggtg      960

gtgtccgtgc tgaccgtgct gcaccaggac tggctgaacg gcaaagaata caagtgcaag     1020

gtgtccaaca agggcctgcc ctcctccatc gaaaagacca tctccaaggc caagggccag     1080

cctcgcgagc ctcaggtgta caccctgcct ccctctcaag aagagatgac caagaaccag     1140

gtgtccctga catgcctggt gaagggcttc tacccttccg atatcgccgt ggagtgggag     1200

tccaacggcc agcctgagaa caactacaag accacccctc ctgtgctgga ctccgacggc     1260

tccttcttcc tgtactccag gctgaccgtg gacaagtccc ggtggcagga aggcaacgtc     1320

ttttcctgct ccgtgatgca cgaggccctg cacaaccact acacccagaa gtccctgtcc     1380

ctgtctctgg gcaag                                                      1395


<210>  28
<211>  699
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  Rat signal sequence, modified rat CDRs, modified human 
       frameworks, human kappa constant domain


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

<400>  28
atggcccctg tgcagctgct gggcctgctg gtgctgttcc tgcctgccat gagatgcgac       60

atccagatga cccagtcccc ctcctctctg tccgcctccg tgggcgacag agtgaccatc      120

acctgccggg cctcccagga catctacacc aacctggcct ggtatcagca gaagcctggc      180

aaggccccta agctgctgat ctaccacgcc tccagcctgc agtccggcgt gccttcccgg      240

ttctccggct ccggctctgg caccgactac accctgacca tctcttccct gcagcctgag      300

gacttcgcca cctactactg cctgcaggac tccgagtacc ctcctacctt cggccagggc      360

accaaggtgg agatcaagcg tacggtggcc gctccttccg tgttcatctt ccctccctcc      420

gacgagcagc tgaagtccgg caccgcctct gtggtgtgcc tgctgaacaa cttctaccct      480

cgggaggcca aggtgcagtg gaaggtggac aacgccctgc agtctggcaa ctcccaggaa      540

tccgtcaccg agcaggactc caaggactct acctactccc tgtcctccac cctgaccctg      600

tccaaggccg actacgagaa gcacaaggtg tacgcctgcg aagtgaccca ccagggcctg      660

tcctctcccg tgaccaagtc cttcaaccgg ggcgagtgc                             699


