                         SEQUENCE LISTING

<110>  Genmab B.V.
       Forssmann, Ulf
       Ahmadi, Tahamtan
       Overdijk, Marije
       Ellekilde-Pedersen, Merete
       Mortensen, Jens Thing
       Gupta, Manish
 
<120>  DOSAGE REGIMENS FOR A COMBINATION OF ANTI-DR5 ANTIBODIES FOR 
       USE IN TREATING CANCER

<130>  P/0143-WO-PCT

<150>  US 62/845,746
<151>  2019-05-09

<160>  48    

<170>  PatentIn version 3.5

<210>  1
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized VH region CDR1

<400>  1

Gly Phe Asn Ile Lys Asp Thr Phe 
1               5               


<210>  2
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized VH region CDR2

<400>  2

Ile Asp Pro Ala Asn Gly Asn Thr 
1               5               


<210>  3
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized VH region CDR3

<400>  3

Val Arg Gly Leu Tyr Thr Tyr Tyr Phe Asp Tyr 
1               5                   10      


<210>  4
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized VH region

<400>  4

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


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


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


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


Gln Gly Lys Ala Thr Ile Thr Thr Asp Thr Ser Ser Asn 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      


Val Arg Gly Leu Tyr Thr Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


Leu Val Thr Val Ser Ser 
        115             


<210>  5
<211>  6
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized VL region CDR1

<400>  5

Gln Ser Ile Ser Asn Asn 
1               5       


<210>  6
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized VL region CDR3

<400>  6

Gln Gln Gly Asn Ser Trp Pro Tyr Thr 
1               5                   


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

<220>
<223>  humanized VL region

<400>  7

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


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


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


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


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


Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Asn Ser Trp Pro Tyr 
                85                  90                  95      


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


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

<220>
<223>  humanized VH region CDR2

<400>  8

Ile Asp Pro Ala Asn Thr Asn Thr 
1               5               


<210>  9
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized VH region

<400>  9

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


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


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


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


Gln Gly Lys Ala Thr Ile Thr Thr Asp Thr Ser Ser Asn 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      


Val Arg Gly Leu Tyr Thr Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


Leu Val Thr Val Ser Ser 
        115             


<210>  10
<211>  8
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized VH region CDR1

<400>  10

Gly Phe Asn Ile Lys Asp Thr His 
1               5               


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

<220>
<223>  humanized VH region CDR3

<400>  11

Ala Arg Trp Gly Thr Asn Val Tyr Phe Ala Tyr 
1               5                   10      


<210>  12
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized VH region

<400>  12

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


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


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


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


Gln Gly Arg Val Thr Ile Thr Val Asp Thr Ser Ala 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 Trp Gly Thr Asn Val Tyr Phe Ala Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


Leu Val Thr Val Ser Ser 
        115             


<210>  13
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized VH region CDR1

<400>  13

Ser Ser Val Ser Tyr 
1               5   


<210>  14
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized VH region CDR3

<400>  14

Gln Gln Tyr His Ser Tyr Pro Pro Thr 
1               5                   


<210>  15
<211>  106
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized VL region

<400>  15

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 Ser Ala Ser Ser Ser Val Ser Tyr Met 
            20                  25                  30          


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


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


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


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


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


<210>  16
<211>  10
<212>  PRT
<213>  Artificial sequence

<220>
<223>  VH region CDR1

<400>  16

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


<210>  17
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH region CDR2

<400>  17

Ile His Asn Ser Gly Thr Thr 
1               5           


<210>  18
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH region CDR3

<400>  18

Ala Arg Asp Arg Gly Gly Asp Tyr Tyr Tyr Gly Met Asp Val 
1               5                   10                  


<210>  19
<211>  122
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH region

<400>  19

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 Gly Ser Ile Ser Ser Gly 
            20                  25                  30          


Asp Tyr Phe Trp Ser Trp Ile Arg Gln Leu Pro Gly Lys Gly Leu Glu 
        35                  40                  45              


Cys Ile Gly His Ile His Asn Ser Gly Thr Thr Tyr Tyr Asn Pro Ser 
    50                  55                  60                  


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


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


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


Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
        115                 120         


<210>  20
<211>  122
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH region

<400>  20

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 Gly Ser Ile Ser Ser Gly 
            20                  25                  30          


Asp Tyr Phe Trp Ser Trp Ile Arg Gln Leu Pro Gly Lys Gly Leu Glu 
        35                  40                  45              


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


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


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


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


Gly Gln Gly Thr Thr Val Thr Val Ser Ser 
        115                 120         


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

<220>
<223>  humanized VH region CDR1

<400>  21

Gln Gly Ile Ser Arg Ser Tyr 
1               5           


<210>  22
<211>  9
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized VH region CDR3

<400>  22

Gln Gln Phe Gly Ser Ser Pro Trp Thr 
1               5                   


<210>  23
<211>  108
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized VH region

<400>  23

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


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


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


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


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


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


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


<210>  24
<211>  440
<212>  PRT
<213>  Homo Sapiens

<400>  24

Met Glu Gln Arg Gly Gln Asn Ala Pro Ala Ala Ser Gly Ala Arg Lys 
1               5                   10                  15      


Arg His Gly Pro Gly Pro Arg Glu Ala Arg Gly Ala Arg Pro Gly Pro 
            20                  25                  30          


Arg Val Pro Lys Thr Leu Val Leu Val Val Ala Ala Val Leu Leu Leu 
        35                  40                  45              


Val Ser Ala Glu Ser Ala Leu Ile Thr Gln Gln Asp Leu Ala Pro Gln 
    50                  55                  60                  


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


Cys Pro Pro Gly His His Ile Ser Glu Asp Gly Arg Asp Cys Ile Ser 
                85                  90                  95      


Cys Lys Tyr Gly Gln Asp Tyr Ser Thr His Trp Asn Asp Leu Leu Phe 
            100                 105                 110         


Cys Leu Arg Cys Thr Arg Cys Asp Ser Gly Glu Val Glu Leu Ser Pro 
        115                 120                 125             


Cys Thr Thr Thr Arg Asn Thr Val Cys Gln Cys Glu Glu Gly Thr Phe 
    130                 135                 140                 


Arg Glu Glu Asp Ser Pro Glu Met Cys Arg Lys Cys Arg Thr Gly Cys 
145                 150                 155                 160 


Pro Arg Gly Met Val Lys Val Gly Asp Cys Thr Pro Trp Ser Asp Ile 
                165                 170                 175     


Glu Cys Val His Lys Glu Ser Gly Thr Lys His Ser Gly Glu Val Pro 
            180                 185                 190         


Ala Val Glu Glu Thr Val Thr Ser Ser Pro Gly Thr Pro Ala Ser Pro 
        195                 200                 205             


Cys Ser Leu Ser Gly Ile Ile Ile Gly Val Thr Val Ala Ala Val Val 
    210                 215                 220                 


Leu Ile Val Ala Val Phe Val Cys Lys Ser Leu Leu Trp Lys Lys Val 
225                 230                 235                 240 


Leu Pro Tyr Leu Lys Gly Ile Cys Ser Gly Gly Gly Gly Asp Pro Glu 
                245                 250                 255     


Arg Val Asp Arg Ser Ser Gln Arg Pro Gly Ala Glu Asp Asn Val Leu 
            260                 265                 270         


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


Met Glu Val Gln Glu Pro Ala Glu Pro Thr Gly Val Asn Met Leu Ser 
    290                 295                 300                 


Pro Gly Glu Ser Glu His Leu Leu Glu Pro Ala Glu Ala Glu Arg Ser 
305                 310                 315                 320 


Gln Arg Arg Arg Leu Leu Val Pro Ala Asn Glu Gly Asp Pro Thr Glu 
                325                 330                 335     


Thr Leu Arg Gln Cys Phe Asp Asp Phe Ala Asp Leu Val Pro Phe Asp 
            340                 345                 350         


Ser Trp Glu Pro Leu Met Arg Lys Leu Gly Leu Met Asp Asn Glu Ile 
        355                 360                 365             


Lys Val Ala Lys Ala Glu Ala Ala Gly His Arg Asp Thr Leu Tyr Thr 
    370                 375                 380                 


Met Leu Ile Lys Trp Val Asn Lys Thr Gly Arg Asp Ala Ser Val His 
385                 390                 395                 400 


Thr Leu Leu Asp Ala Leu Glu Thr Leu Gly Glu Arg Leu Ala Lys Gln 
                405                 410                 415     


Lys Ile Glu Asp His Leu Leu Ser Ser Gly Lys Phe Met Tyr Leu Glu 
            420                 425                 430         


Gly Asn Ala Asp Ser Ala Met Ser 
        435                 440 


<210>  25
<211>  448
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized heavy chain

<400>  25

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


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


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


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


Gln Gly Lys Ala Thr Ile Thr Thr Asp Thr Ser Ser Asn 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      


Val Arg Gly Leu Tyr Thr Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  26
<211>  448
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized heavy chain

<400>  26

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


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


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


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


Gln Gly Lys Ala Thr Ile Thr Thr Asp Thr Ser Ser Asn 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      


Val Arg Gly Leu Tyr Thr Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  27
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized light chain

<400>  27

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


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


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


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


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


Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Asn Ser Trp Pro Tyr 
                85                  90                  95      


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


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


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


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


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


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


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


Phe Asn Arg Gly Glu Cys 
    210                 


<210>  28
<211>  448
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized heavy chain

<400>  28

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


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


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


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


Gln Gly Lys Ala Thr Ile Thr Thr Asp Thr Ser Ser Asn 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      


Val Arg Gly Leu Tyr Thr Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  29
<211>  448
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized heavy chain

<400>  29

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


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


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


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


Gln Gly Lys Ala Thr Ile Thr Thr Asp Thr Ser Ser Asn 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      


Val Arg Gly Leu Tyr Thr Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  30
<211>  448
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized heavy chain

<400>  30

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


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


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


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


Gln Gly Lys Ala Thr Ile Thr Thr Asp Thr Ser Ser Asn 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      


Val Arg Gly Leu Tyr Thr Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  31
<211>  448
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized heavy chain

<400>  31

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


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


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


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


Gln Gly Arg Val Thr Ile Thr Val Asp Thr Ser Ala 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 Trp Gly Thr Asn Val Tyr Phe Ala Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  32
<211>  448
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized heavy chain

<400>  32

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


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


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


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


Gln Gly Arg Val Thr Ile Thr Val Asp Thr Ser Ala 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 Trp Gly Thr Asn Val Tyr Phe Ala Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  33
<211>  448
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized heavy chain

<400>  33

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


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


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


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


Gln Gly Arg Val Thr Ile Thr Val Asp Thr Ser Ala 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 Trp Gly Thr Asn Val Tyr Phe Ala Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  34
<211>  448
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized heavy chain

<400>  34

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


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


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


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


Gln Gly Arg Val Thr Ile Thr Val Asp Thr Ser Ala 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 Trp Gly Thr Asn Val Tyr Phe Ala Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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

<220>
<223>  humanized light chain

<400>  35

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 Ser Ala Ser Ser Ser Val Ser Tyr Met 
            20                  25                  30          


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


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


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


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


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


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


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


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


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


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


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


Asn Arg Gly Glu Cys 
    210             


<210>  36
<211>  411
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  modified human DR5

<400>  36

Met Glu Gln Arg Gly Gln Asn Ala Pro Ala Ala Ser Gly Ala Arg Lys 
1               5                   10                  15      


Arg His Gly Pro Gly Pro Arg Glu Ala Arg Gly Ala Arg Pro Gly Pro 
            20                  25                  30          


Arg Val Pro Lys Thr Leu Val Leu Val Val Ala Ala Val Leu Leu Leu 
        35                  40                  45              


Val Ser Ala Glu Ser Ala Leu Ile Thr Gln Gln Asp Leu Ala Pro Gln 
    50                  55                  60                  


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


Cys Pro Pro Gly His His Ile Ser Glu Asp Gly Arg Asp Cys Ile Ser 
                85                  90                  95      


Cys Lys Tyr Gly Gln Asp Tyr Ser Thr His Trp Asn Asp Leu Leu Phe 
            100                 105                 110         


Cys Leu Arg Cys Thr Arg Cys Asp Ser Gly Glu Val Glu Leu Ser Pro 
        115                 120                 125             


Cys Thr Thr Thr Arg Asn Thr Val Cys Gln Cys Glu Glu Gly Thr Phe 
    130                 135                 140                 


Arg Glu Glu Asp Ser Pro Glu Met Cys Arg Lys Cys Arg Thr Gly Cys 
145                 150                 155                 160 


Pro Arg Gly Met Val Lys Val Gly Asp Cys Thr Pro Trp Ser Asp Ile 
                165                 170                 175     


Glu Cys Val His Lys Glu Ser Gly Ile Ile Ile Gly Val Thr Val Ala 
            180                 185                 190         


Ala Val Val Leu Ile Val Ala Val Phe Val Cys Lys Ser Leu Leu Trp 
        195                 200                 205             


Lys Lys Val Leu Pro Tyr Leu Lys Gly Ile Cys Ser Gly Gly Gly Gly 
    210                 215                 220                 


Asp Pro Glu Arg Val Asp Arg Ser Ser Gln Arg Pro Gly Ala Glu Asp 
225                 230                 235                 240 


Asn Val Leu Asn Glu Ile Val Ser Ile Leu Gln Pro Thr Gln Val Pro 
                245                 250                 255     


Glu Gln Glu Met Glu Val Gln Glu Pro Ala Glu Pro Thr Gly Val Asn 
            260                 265                 270         


Met Leu Ser Pro Gly Glu Ser Glu His Leu Leu Glu Pro Ala Glu Ala 
        275                 280                 285             


Glu Arg Ser Gln Arg Arg Arg Leu Leu Val Pro Ala Asn Glu Gly Asp 
    290                 295                 300                 


Pro Thr Glu Thr Leu Arg Gln Cys Phe Asp Asp Phe Ala Asp Leu Val 
305                 310                 315                 320 


Pro Phe Asp Ser Trp Glu Pro Leu Met Arg Lys Leu Gly Leu Met Asp 
                325                 330                 335     


Asn Glu Ile Lys Val Ala Lys Ala Glu Ala Ala Gly His Arg Asp Thr 
            340                 345                 350         


Leu Tyr Thr Met Leu Ile Lys Trp Val Asn Lys Thr Gly Arg Asp Ala 
        355                 360                 365             


Ser Val His Thr Leu Leu Asp Ala Leu Glu Thr Leu Gly Glu Arg Leu 
    370                 375                 380                 


Ala Asn Gln Lys Ile Glu Asp His Leu Leu Ser Ser Gly Lys Phe Met 
385                 390                 395                 400 


Tyr Leu Glu Gly Asn Ala Asp Ser Ala Met Ser 
                405                 410     


<210>  37
<211>  411
<212>  PRT
<213>  Homo Sapiens

<400>  37

Met Glu Gln Arg Gly Gln Asn Ala Pro Ala Ala Ser Gly Ala Arg Lys 
1               5                   10                  15      


Arg His Gly Pro Gly Pro Arg Glu Ala Arg Gly Ala Arg Pro Gly Pro 
            20                  25                  30          


Arg Val Pro Lys Thr Leu Val Leu Val Val Ala Ala Val Leu Leu Leu 
        35                  40                  45              


Val Ser Ala Glu Ser Ala Leu Ile Thr Gln Gln Asp Leu Ala Pro Gln 
    50                  55                  60                  


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


Cys Pro Pro Gly His His Ile Ser Glu Asp Gly Arg Asp Cys Ile Ser 
                85                  90                  95      


Cys Lys Tyr Gly Gln Asp Tyr Ser Thr His Trp Asn Asp Leu Leu Phe 
            100                 105                 110         


Cys Leu Arg Cys Thr Arg Cys Asp Ser Gly Glu Val Glu Leu Ser Pro 
        115                 120                 125             


Cys Thr Thr Thr Arg Asn Thr Val Cys Gln Cys Glu Glu Gly Thr Phe 
    130                 135                 140                 


Arg Glu Glu Asp Ser Pro Glu Met Cys Arg Lys Cys Arg Thr Gly Cys 
145                 150                 155                 160 


Pro Arg Gly Met Val Lys Val Gly Asp Cys Thr Pro Trp Ser Asp Ile 
                165                 170                 175     


Glu Cys Val His Lys Glu Ser Gly Ile Ile Ile Gly Val Thr Val Ala 
            180                 185                 190         


Ala Val Val Leu Ile Val Ala Val Phe Val Cys Lys Ser Leu Leu Trp 
        195                 200                 205             


Lys Lys Val Leu Pro Tyr Leu Lys Gly Ile Cys Ser Gly Gly Gly Gly 
    210                 215                 220                 


Asp Pro Glu Arg Val Asp Arg Ser Ser Gln Arg Pro Gly Ala Glu Asp 
225                 230                 235                 240 


Asn Val Leu Asn Glu Ile Val Ser Ile Leu Gln Pro Thr Gln Val Pro 
                245                 250                 255     


Glu Gln Glu Met Glu Val Gln Glu Pro Ala Glu Pro Thr Gly Val Asn 
            260                 265                 270         


Met Leu Ser Pro Gly Glu Ser Glu His Leu Leu Glu Pro Ala Glu Ala 
        275                 280                 285             


Glu Arg Ser Gln Arg Arg Arg Leu Leu Val Pro Ala Asn Glu Gly Asp 
    290                 295                 300                 


Pro Thr Glu Thr Leu Arg Gln Cys Phe Asp Asp Phe Ala Asp Leu Val 
305                 310                 315                 320 


Pro Phe Asp Ser Trp Glu Pro Leu Met Arg Lys Leu Gly Leu Met Asp 
                325                 330                 335     


Asn Glu Ile Lys Val Ala Lys Ala Glu Ala Ala Gly His Arg Asp Thr 
            340                 345                 350         


Leu Tyr Thr Met Leu Ile Lys Trp Val Asn Lys Thr Gly Arg Asp Ala 
        355                 360                 365             


Ser Val His Thr Leu Leu Asp Ala Leu Glu Thr Leu Gly Glu Arg Leu 
    370                 375                 380                 


Ala Lys Gln Lys Ile Glu Asp His Leu Leu Ser Ser Gly Lys Phe Met 
385                 390                 395                 400 


Tyr Leu Glu Gly Asn Ala Asp Ser Ala Met Ser 
                405                 410     


<210>  38
<211>  440
<212>  PRT
<213>  Homo Sapiens

<400>  38

Met Glu Gln Arg Gly Gln Asn Ala Pro Ala Ala Ser Gly Ala Arg Lys 
1               5                   10                  15      


Arg His Gly Pro Gly Pro Arg Glu Ala Arg Gly Ala Arg Pro Gly Leu 
            20                  25                  30          


Arg Val Pro Lys Thr Leu Val Leu Val Val Ala Ala Val Leu Leu Leu 
        35                  40                  45              


Val Ser Ala Glu Ser Ala Leu Ile Thr Gln Gln Asp Leu Ala Pro Gln 
    50                  55                  60                  


Gln Arg Val Ala Pro Gln Gln Lys Arg Ser Ser Pro Ser Glu Gly Leu 
65                  70                  75                  80  


Cys Pro Pro Gly His His Ile Ser Glu Asp Gly Arg Asp Cys Ile Ser 
                85                  90                  95      


Cys Lys Tyr Gly Gln Asp Tyr Ser Thr His Trp Asn Asp Leu Leu Phe 
            100                 105                 110         


Cys Leu Arg Cys Thr Arg Cys Asp Ser Gly Glu Val Glu Leu Ser Pro 
        115                 120                 125             


Cys Thr Thr Thr Arg Asn Thr Val Cys Gln Cys Glu Glu Gly Thr Phe 
    130                 135                 140                 


Arg Glu Glu Asp Ser Pro Glu Met Cys Arg Lys Cys Arg Thr Gly Cys 
145                 150                 155                 160 


Pro Arg Gly Met Val Lys Val Gly Asp Cys Thr Pro Trp Ser Asp Ile 
                165                 170                 175     


Glu Cys Val His Lys Glu Ser Gly Thr Lys His Ser Gly Glu Ala Pro 
            180                 185                 190         


Ala Val Glu Glu Thr Val Thr Ser Ser Pro Gly Thr Pro Ala Ser Pro 
        195                 200                 205             


Cys Ser Leu Ser Gly Ile Ile Ile Gly Val Thr Val Ala Ala Val Val 
    210                 215                 220                 


Leu Ile Val Ala Val Phe Val Cys Lys Ser Leu Leu Trp Lys Lys Val 
225                 230                 235                 240 


Leu Pro Tyr Leu Lys Gly Ile Cys Ser Gly Gly Gly Gly Asp Pro Glu 
                245                 250                 255     


Arg Val Asp Arg Ser Ser Gln Arg Pro Gly Ala Glu Asp Asn Val Leu 
            260                 265                 270         


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


Met Glu Val Gln Glu Pro Ala Glu Pro Thr Gly Val Asn Met Leu Ser 
    290                 295                 300                 


Pro Gly Glu Ser Glu His Leu Leu Glu Pro Ala Glu Ala Glu Arg Ser 
305                 310                 315                 320 


Gln Arg Arg Arg Leu Leu Val Pro Ala Asn Glu Gly Asp Pro Thr Glu 
                325                 330                 335     


Thr Leu Arg Gln Cys Phe Asp Asp Phe Ala Asp Leu Val Pro Phe Asp 
            340                 345                 350         


Ser Trp Glu Pro Leu Met Arg Lys Leu Gly Leu Met Asp Asn Glu Ile 
        355                 360                 365             


Lys Val Ala Lys Ala Glu Ala Ala Gly His Arg Asp Thr Leu Tyr Thr 
    370                 375                 380                 


Met Leu Ile Lys Trp Val Asn Lys Thr Gly Arg Asp Ala Ser Val His 
385                 390                 395                 400 


Thr Leu Leu Asp Ala Leu Glu Thr Leu Gly Glu Arg Leu Ala Lys Gln 
                405                 410                 415     


Lys Ile Glu Asp His Leu Leu Ser Ser Gly Lys Phe Met Tyr Leu Glu 
            420                 425                 430         


Gly Asn Ala Asp Ser Ala Met Ser 
        435                 440 


<210>  39
<211>  445
<212>  PRT
<213>  Macaca fascicularis

<400>  39

Met Gly Gln Leu Arg Gln Ser Ala Pro Ala Ala Ser Gly Ala Arg Lys 
1               5                   10                  15      


Gly Arg Gly Pro Gly Pro Arg Glu Ala Arg Gly Ala Arg Pro Gly Leu 
            20                  25                  30          


Arg Val Leu Lys Thr Leu Val Leu Val Val Ala Ala Ala Arg Val Leu 
        35                  40                  45              


Leu Ser Val Ser Ala Asp Cys Ala Pro Ile Thr Arg Gln Ser Leu Asp 
    50                  55                  60                  


Pro Gln Arg Arg Ala Ala Pro Gln Gln Lys Arg Ser Ser Pro Thr Glu 
65                  70                  75                  80  


Gly Leu Cys Pro Pro Gly His His Ile Ser Glu Asp Ser Arg Glu Cys 
                85                  90                  95      


Ile Ser Cys Lys Tyr Gly Gln Asp Tyr Ser Thr His Trp Asn Asp Phe 
            100                 105                 110         


Leu Phe Cys Leu Arg Cys Thr Lys Cys Asp Ser Gly Glu Val Glu Val 
        115                 120                 125             


Asn Ser Cys Thr Thr Thr Arg Asn Thr Val Cys Gln Cys Glu Glu Gly 
    130                 135                 140                 


Thr Phe Arg Glu Glu Asp Ser Pro Glu Ile Cys Arg Lys Cys Arg Thr 
145                 150                 155                 160 


Gly Cys Pro Arg Gly Met Val Lys Val Lys Asp Cys Thr Pro Trp Ser 
                165                 170                 175     


Asp Ile Glu Cys Val His Lys Glu Ser Gly Thr Lys His Thr Gly Glu 
            180                 185                 190         


Val Pro Ala Val Glu Lys Thr Val Thr Thr Ser Pro Gly Thr Pro Ala 
        195                 200                 205             


Ser Pro Cys Ser Leu Ser Gly Ile Ile Ile Gly Val Ile Val Leu Val 
    210                 215                 220                 


Val Ile Val Val Val Ala Val Ile Val Trp Lys Thr Ser Leu Trp Lys 
225                 230                 235                 240 


Lys Val Leu Pro Tyr Leu Lys Gly Val Cys Ser Gly Gly Gly Gly Asp 
                245                 250                 255     


Pro Glu Arg Val Asp Ser Ser Ser His Ser Pro Gln Arg Pro Gly Ala 
            260                 265                 270         


Glu Asp Asn Ala Leu Asn Glu Ile Val Ser Ile Val Gln Pro Ser Gln 
        275                 280                 285             


Val Pro Glu Gln Glu Met Glu Val Gln Glu Pro Ala Glu Gln Thr Asp 
    290                 295                 300                 


Val Asn Thr Leu Ser Pro Gly Glu Ser Glu His Leu Leu Glu Pro Ala 
305                 310                 315                 320 


Lys Ala Glu Gly Pro Gln Arg Arg Gly Gln Leu Val Pro Val Asn Glu 
                325                 330                 335     


Asn Asp Pro Thr Glu Thr Leu Arg Gln Cys Phe Asp Asp Phe Ala Ala 
            340                 345                 350         


Ile Val Pro Phe Asp Ala Trp Glu Pro Leu Val Arg Gln Leu Gly Leu 
        355                 360                 365             


Thr Asn Asn Glu Ile Lys Val Ala Lys Ala Glu Ala Ala Ser Ser Arg 
    370                 375                 380                 


Asp Thr Leu Tyr Val Met Leu Ile Lys Trp Val Asn Lys Thr Gly Arg 
385                 390                 395                 400 


Ala Ala Ser Val Asn Thr Leu Leu Asp Ala Leu Glu Thr Leu Glu Glu 
                405                 410                 415     


Arg Leu Ala Lys Gln Lys Ile Gln Asp Arg Leu Leu Ser Ser Gly Lys 
            420                 425                 430         


Phe Met Tyr Leu Glu Asp Asn Ala Asp Ser Ala Thr Ser 
        435                 440                 445 


<210>  40
<211>  416
<212>  PRT
<213>  Artificial sequence

<220>
<223>  modified Macaca fascicularis

<400>  40

Met Gly Gln Leu Arg Gln Ser Ala Pro Ala Ala Ser Gly Ala Arg Lys 
1               5                   10                  15      


Gly Arg Gly Pro Gly Pro Arg Glu Ala Arg Gly Ala Arg Pro Gly Leu 
            20                  25                  30          


Arg Val Leu Lys Thr Leu Val Leu Val Val Ala Ala Ala Arg Val Leu 
        35                  40                  45              


Leu Ser Val Ser Ala Asp Cys Ala Pro Ile Thr Arg Gln Ser Leu Asp 
    50                  55                  60                  


Pro Gln Arg Arg Ala Ala Pro Gln Gln Lys Arg Ser Ser Pro Thr Glu 
65                  70                  75                  80  


Gly Leu Cys Pro Pro Gly His His Ile Ser Glu Asp Ser Arg Glu Cys 
                85                  90                  95      


Ile Ser Cys Lys Tyr Gly Gln Asp Tyr Ser Thr His Trp Asn Asp Phe 
            100                 105                 110         


Leu Phe Cys Leu Arg Cys Thr Lys Cys Asp Ser Gly Glu Val Glu Val 
        115                 120                 125             


Asn Ser Cys Thr Thr Thr Arg Asn Thr Val Cys Gln Cys Glu Glu Gly 
    130                 135                 140                 


Thr Phe Arg Glu Glu Asp Ser Pro Glu Ile Cys Arg Lys Cys Arg Thr 
145                 150                 155                 160 


Gly Cys Pro Arg Gly Met Val Lys Val Lys Asp Cys Thr Pro Trp Ser 
                165                 170                 175     


Asp Ile Glu Cys Val His Lys Glu Ser Gly Ile Ile Ile Gly Val Ile 
            180                 185                 190         


Val Leu Val Val Ile Val Val Val Ala Val Ile Val Trp Lys Thr Ser 
        195                 200                 205             


Leu Trp Lys Lys Val Leu Pro Tyr Leu Lys Gly Val Cys Ser Gly Gly 
    210                 215                 220                 


Gly Gly Asp Pro Glu Arg Val Asp Ser Ser Ser His Ser Pro Gln Arg 
225                 230                 235                 240 


Pro Gly Ala Glu Asp Asn Ala Leu Asn Glu Ile Val Ser Ile Val Gln 
                245                 250                 255     


Pro Ser Gln Val Pro Glu Gln Glu Met Glu Val Gln Glu Pro Ala Glu 
            260                 265                 270         


Gln Thr Asp Val Asn Thr Leu Ser Pro Gly Glu Ser Glu His Leu Leu 
        275                 280                 285             


Glu Pro Ala Lys Ala Glu Gly Pro Gln Arg Arg Gly Gln Leu Val Pro 
    290                 295                 300                 


Val Asn Glu Asn Asp Pro Thr Glu Thr Leu Arg Gln Cys Phe Asp Asp 
305                 310                 315                 320 


Phe Ala Ala Ile Val Pro Phe Asp Ala Trp Glu Pro Leu Val Arg Gln 
                325                 330                 335     


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


Ser Ser Arg Asp Thr Leu Tyr Val Met Leu Ile Lys Trp Val Asn Lys 
        355                 360                 365             


Thr Gly Arg Ala Ala Ser Val Asn Thr Leu Leu Asp Ala Leu Glu Thr 
    370                 375                 380                 


Leu Glu Glu Arg Leu Ala Asn Gln Lys Ile Gln Asp Arg Leu Leu Ser 
385                 390                 395                 400 


Ser Gly Lys Phe Met Tyr Leu Glu Asp Asn Ala Asp Ser Ala Thr Ser 
                405                 410                 415     


<210>  41
<211>  381
<212>  PRT
<213>  Mus Musculus

<400>  41

Met Glu Pro Pro Gly Pro Ser Thr Pro Thr Ala Ser Ala Ala Ala Arg 
1               5                   10                  15      


Ala Asp His Tyr Thr Pro Gly Leu Arg Pro Leu Pro Lys Arg Arg Leu 
            20                  25                  30          


Leu Tyr Ser Phe Ala Leu Leu Leu Ala Val Leu Gln Ala Val Phe Val 
        35                  40                  45              


Pro Val Thr Ala Asn Pro Ala His Asn Arg Pro Ala Gly Leu Gln Arg 
    50                  55                  60                  


Pro Glu Glu Ser Pro Ser Arg Gly Pro Cys Leu Ala Gly Gln Tyr Leu 
65                  70                  75                  80  


Ser Glu Gly Asn Cys Lys Pro Cys Arg Glu Gly Ile Asp Tyr Thr Ser 
                85                  90                  95      


His Ser Asn His Ser Leu Asp Ser Cys Ile Leu Cys Thr Val Cys Lys 
            100                 105                 110         


Glu Asp Lys Val Val Glu Thr Arg Cys Asn Ile Thr Thr Asn Thr Val 
        115                 120                 125             


Cys Arg Cys Lys Pro Gly Thr Phe Glu Asp Lys Asp Ser Pro Glu Ile 
    130                 135                 140                 


Cys Gln Ser Cys Ser Asn Cys Thr Asp Gly Glu Glu Glu Leu Thr Ser 
145                 150                 155                 160 


Cys Thr Pro Arg Glu Asn Arg Lys Cys Val Ser Lys Thr Ala Trp Ala 
                165                 170                 175     


Ser Trp His Lys Leu Gly Leu Trp Ile Gly Leu Leu Val Pro Val Val 
            180                 185                 190         


Leu Leu Ile Gly Ala Leu Leu Val Trp Lys Thr Gly Ala Trp Arg Gln 
        195                 200                 205             


Trp Leu Leu Cys Ile Lys Arg Gly Cys Glu Arg Asp Pro Glu Ser Ala 
    210                 215                 220                 


Asn Ser Val His Ser Ser Leu Leu Asp Arg Gln Thr Ser Ser Thr Thr 
225                 230                 235                 240 


Asn Asp Ser Asn His Asn Thr Glu Pro Gly Lys Thr Gln Lys Thr Gly 
                245                 250                 255     


Lys Lys Leu Leu Val Pro Val Asn Gly Asn Asp Ser Ala Asp Asp Leu 
            260                 265                 270         


Lys Phe Ile Phe Glu Tyr Cys Ser Asp Ile Val Pro Phe Asp Ser Trp 
        275                 280                 285             


Asn Arg Leu Met Arg Gln Leu Gly Leu Thr Asp Asn Gln Ile Gln Met 
    290                 295                 300                 


Val Lys Ala Glu Thr Leu Val Thr Arg Glu Ala Leu Tyr Gln Met Leu 
305                 310                 315                 320 


Leu Lys Trp Arg His Gln Thr Gly Arg Ser Ala Ser Ile Asn His Leu 
                325                 330                 335     


Leu Asp Ala Leu Glu Ala Val Glu Glu Arg Asp Ala Met Glu Lys Ile 
            340                 345                 350         


Glu Asp Tyr Ala Val Lys Ser Gly Arg Phe Thr Tyr Gln Asn Ala Ala 
        355                 360                 365             


Ala Gln Pro Glu Thr Gly Pro Gly Gly Ser Gln Cys Val 
    370                 375                 380     


<210>  42
<211>  450
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  modified human DR5

<400>  42

Met Glu Gln Arg Gly Gln Asn Ala Pro Ala Ala Ser Gly Ala Arg Lys 
1               5                   10                  15      


Arg His Gly Pro Gly Pro Arg Glu Ala Arg Gly Ala Arg Pro Gly Leu 
            20                  25                  30          


Arg Val Pro Lys Thr Leu Val Leu Val Val Ala Ala Val Leu Leu Leu 
        35                  40                  45              


Val Ser Ala Glu Ser Ala Leu Ile Thr Gln Gln Asp Leu Ala Pro Gln 
    50                  55                  60                  


Gln Arg Val Ala Pro Gln Gln Lys Arg Ser Ser Pro Ser Glu Gly Leu 
65                  70                  75                  80  


Cys Pro Pro Gly His His Ile Ser Glu Asp Gly Arg Asp Cys Ile Ser 
                85                  90                  95      


Cys Lys Tyr Gly Gln Asp Tyr Ser Thr His Trp Asn Asp Leu Leu Phe 
            100                 105                 110         


Cys Leu Arg Cys Thr Arg Cys Asp Ser Gly Glu Val Glu Leu Ser Pro 
        115                 120                 125             


Cys Thr Thr Thr Arg Asn Thr Val Cys Gln Cys Glu Glu Gly Thr Phe 
    130                 135                 140                 


Arg Glu Glu Asp Ser Pro Glu Met Cys Arg Lys Cys Arg Thr Gly Cys 
145                 150                 155                 160 


Pro Arg Gly Met Val Lys Val Gly Asp Cys Thr Pro Trp Ser Asp Ile 
                165                 170                 175     


Glu Cys Val His Lys Glu Ser Gly Thr Lys His Ser Gly Glu Ala Pro 
            180                 185                 190         


Ala Val Glu Glu Thr Val Thr Ser Ser Pro Gly Thr Pro Ala Ser Pro 
        195                 200                 205             


Cys Ser Ala Pro Ser Thr Cys Ser Lys Pro Thr Cys Pro Pro Pro Glu 
    210                 215                 220                 


Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Pro Lys Asp 
225                 230                 235                 240 


Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp 
                245                 250                 255     


Val Ser Gln Asp Asp Pro Glu Val Gln Phe Thr Trp Tyr Ile Asn Asn 
            260                 265                 270         


Glu Gln Val Arg Thr Ala Arg Pro Pro Leu Arg Glu Gln Gln Phe Asn 
        275                 280                 285             


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


Leu Arg Gly Lys Glu Phe Lys Cys Lys Val His Asn Lys Ala Leu Pro 
305                 310                 315                 320 


Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Arg Gly Gln Pro Leu Glu 
                325                 330                 335     


Pro Lys Val Tyr Thr Met Gly Pro Pro Arg Glu Glu Leu Ser Ser Arg 
            340                 345                 350         


Ser Val Ser Leu Thr Cys Met Ile Asn Gly Phe Tyr Pro Ser Asp Ile 
        355                 360                 365             


Ser Val Glu Trp Glu Lys Asn Gly Lys Ala Glu Asp Asn Tyr Lys Thr 
    370                 375                 380                 


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


Leu Ser Val Pro Thr Ser Glu Trp Gln Arg Gly Asp Val Phe Thr Cys 
                405                 410                 415     


Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Ile 
            420                 425                 430         


Ser Arg Ser Pro Gly Lys His His His His His His His His Glu Pro 
        435                 440                 445             


Glu Ala 
    450 


<210>  43
<211>  423
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  modified human DR5

<400>  43

Met Glu Gln Arg Gly Gln Asn Ala Pro Ala Ala Ser Gly Ala Arg Lys 
1               5                   10                  15      


Arg His Gly Pro Gly Pro Arg Glu Ala Arg Gly Ala Arg Pro Gly Pro 
            20                  25                  30          


Arg Val Pro Lys Thr Leu Val Leu Val Val Ala Ala Val Leu Leu Leu 
        35                  40                  45              


Val Ser Ala Glu Ser Ala Leu Ile Thr Gln Gln Asp Leu Ala Pro Gln 
    50                  55                  60                  


Gln Arg Ala Ala Pro Gln Gln Lys Arg Ser Ser Pro Ser Glu Gly Pro 
65                  70                  75                  80  


Cys Leu Ala Gly Gln Tyr Leu Ser Glu Gly Asn Cys Lys Pro Cys Arg 
                85                  90                  95      


Glu Gly Ile Asp Tyr Thr Ser His Ser Asn His Ser Leu Asp Ser Cys 
            100                 105                 110         


Ile Leu Cys Thr Arg Cys Asp Ser Gly Glu Val Glu Leu Ser Pro Cys 
        115                 120                 125             


Thr Thr Thr Arg Asn Thr Val Cys Gln Cys Glu Glu Gly Thr Phe Arg 
    130                 135                 140                 


Glu Glu Asp Ser Pro Glu Met Cys Arg Lys Cys Arg Thr Gly Cys Pro 
145                 150                 155                 160 


Arg Gly Met Val Lys Val Gly Asp Cys Thr Pro Trp Ser Asp Ile Glu 
                165                 170                 175     


Cys Val His Lys Glu Ser Gly Ala Pro Ser Thr Cys Ser Lys Pro Thr 
            180                 185                 190         


Cys Pro Pro Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro 
        195                 200                 205             


Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 
    210                 215                 220                 


Cys Val Val Val Asp Val Ser Gln Asp Asp Pro Glu Val Gln Phe Thr 
225                 230                 235                 240 


Trp Tyr Ile Asn Asn Glu Gln Val Arg Thr Ala Arg Pro Pro Leu Arg 
                245                 250                 255     


Glu Gln Gln Phe Asn Ser Thr Ile Arg Val Val Ser Thr Leu Pro Ile 
            260                 265                 270         


Ala His Gln Asp Trp Leu Arg Gly Lys Glu Phe Lys Cys Lys Val His 
        275                 280                 285             


Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Arg 
    290                 295                 300                 


Gly Gln Pro Leu Glu Pro Lys Val Tyr Thr Met Gly Pro Pro Arg Glu 
305                 310                 315                 320 


Glu Leu Ser Ser Arg Ser Val Ser Leu Thr Cys Met Ile Asn Gly Phe 
                325                 330                 335     


Tyr Pro Ser Asp Ile Ser Val Glu Trp Glu Lys Asn Gly Lys Ala Glu 
            340                 345                 350         


Asp Asn Tyr Lys Thr Thr Pro Ala Val Leu Asp Ser Asp Gly Ser Tyr 
        355                 360                 365             


Phe Leu Tyr Ser Lys Leu Ser Val Pro Thr Ser Glu Trp Gln Arg Gly 
    370                 375                 380                 


Asp Val Phe Thr Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
385                 390                 395                 400 


Thr Gln Lys Ser Ile Ser Arg Ser Pro Gly Lys His His His His His 
                405                 410                 415     


His His His Glu Pro Glu Ala 
            420             


<210>  44
<211>  423
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  modified human DR5

<400>  44

Met Glu Gln Arg Gly Gln Asn Ala Pro Ala Ala Ser Gly Ala Arg Lys 
1               5                   10                  15      


Arg His Gly Pro Gly Pro Arg Glu Ala Arg Gly Ala Arg Pro Gly Pro 
            20                  25                  30          


Arg Val Pro Lys Thr Leu Val Leu Val Val Ala Ala Val Leu Leu Leu 
        35                  40                  45              


Val Ser Ala Glu Ser Ala Leu Ile Thr Gln Gln Asp Leu Ala Pro Gln 
    50                  55                  60                  


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


Cys Pro Pro Gly His His Ile Ser Glu Asp Gly Arg Asp Cys Ile Ser 
                85                  90                  95      


Cys Lys Tyr Gly Gln Asp Tyr Ser Thr His Trp Asn Asp Leu Leu Phe 
            100                 105                 110         


Cys Leu Arg Cys Thr Arg Cys Asp Ser Gly Glu Val Glu Leu Ser Pro 
        115                 120                 125             


Cys Thr Thr Thr Arg Asn Thr Val Cys Gln Cys Lys Pro Gly Thr Phe 
    130                 135                 140                 


Glu Asp Lys Asp Ser Pro Glu Ile Cys Gln Ser Cys Ser Asn Cys Thr 
145                 150                 155                 160 


Asp Gly Glu Glu Glu Val Gly Asp Cys Thr Pro Trp Ser Asp Ile Glu 
                165                 170                 175     


Cys Val His Lys Glu Ser Gly Ala Pro Ser Thr Cys Ser Lys Pro Thr 
            180                 185                 190         


Cys Pro Pro Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro 
        195                 200                 205             


Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr 
    210                 215                 220                 


Cys Val Val Val Asp Val Ser Gln Asp Asp Pro Glu Val Gln Phe Thr 
225                 230                 235                 240 


Trp Tyr Ile Asn Asn Glu Gln Val Arg Thr Ala Arg Pro Pro Leu Arg 
                245                 250                 255     


Glu Gln Gln Phe Asn Ser Thr Ile Arg Val Val Ser Thr Leu Pro Ile 
            260                 265                 270         


Ala His Gln Asp Trp Leu Arg Gly Lys Glu Phe Lys Cys Lys Val His 
        275                 280                 285             


Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Arg 
    290                 295                 300                 


Gly Gln Pro Leu Glu Pro Lys Val Tyr Thr Met Gly Pro Pro Arg Glu 
305                 310                 315                 320 


Glu Leu Ser Ser Arg Ser Val Ser Leu Thr Cys Met Ile Asn Gly Phe 
                325                 330                 335     


Tyr Pro Ser Asp Ile Ser Val Glu Trp Glu Lys Asn Gly Lys Ala Glu 
            340                 345                 350         


Asp Asn Tyr Lys Thr Thr Pro Ala Val Leu Asp Ser Asp Gly Ser Tyr 
        355                 360                 365             


Phe Leu Tyr Ser Lys Leu Ser Val Pro Thr Ser Glu Trp Gln Arg Gly 
    370                 375                 380                 


Asp Val Phe Thr Cys Ser Val Met His Glu Ala Leu His Asn His Tyr 
385                 390                 395                 400 


Thr Gln Lys Ser Ile Ser Arg Ser Pro Gly Lys His His His His His 
                405                 410                 415     


His His His Glu Pro Glu Ala 
            420             


<210>  45
<211>  154
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  modified human DR5

<400>  45

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


Val His Ser Gln Gln Asp Leu Ala Pro Gln Gln Arg Ala Ala Pro Gln 
            20                  25                  30          


Gln Lys Arg Ser Ser Pro Ser Glu Gly Leu Cys Pro Pro Gly His His 
        35                  40                  45              


Ile Ser Glu Asp Gly Arg Asp Cys Ile Ser Cys Lys Tyr Gly Gln Asp 
    50                  55                  60                  


Tyr Ser Thr His Trp Asn Asp Leu Leu Phe Cys Leu Arg Cys Thr Arg 
65                  70                  75                  80  


Cys Asp Ser Gly Glu Val Glu Leu Ser Pro Cys Thr Thr Thr Arg Asn 
                85                  90                  95      


Thr Val Cys Gln Cys Glu Glu Gly Thr Phe Arg Glu Glu Asp Ser Pro 
            100                 105                 110         


Glu Met Cys Arg Lys Cys Arg Thr Gly Cys Pro Arg Gly Met Val Lys 
        115                 120                 125             


Val Gly Asp Cys Thr Pro Trp Ser Asp Ile Glu Cys Val His Lys Glu 
    130                 135                 140                 


Ser Gly His His His His His His His His 
145                 150                 


<210>  46
<211>  330
<212>  PRT
<213>  Homo Sapiens

<400>  46

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


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


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


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


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


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


Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys 
            100                 105                 110         


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


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


Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp 
145                 150                 155                 160 


Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu 
                165                 170                 175     


Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu 
            180                 185                 190         


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


Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly 
    210                 215                 220                 


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


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


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


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


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


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


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


<210>  47
<211>  447
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized heavy chain

<400>  47

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


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


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


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


Gln Gly Lys Ala Thr Ile Thr Thr Asp Thr Ser Ser Asn 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      


Val Arg Gly Leu Tyr Thr Tyr Tyr Phe Asp Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  48
<211>  447
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  humanized heavy chain

<400>  48

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


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


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


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


Gln Gly Arg Val Thr Ile Thr Val Asp Thr Ser Ala 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 Trp Gly Thr Asn Val Tyr Phe Ala Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


