                         SEQUENCE LISTING

<110>  H. Lundbeck A/S
 
<120>  USE OF A pS396 ASSAY TO DIAGNOSE TAUOPHATIES

<130>  1154-WO-PCT

<160>  74    

<170>  PatentIn version 3.5

<210>  1
<211>  441
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Tau

<400>  1

Met Ala Glu Pro Arg Gln Glu Phe Glu Val Met Glu Asp His Ala Gly 
1               5                   10                  15      


Thr Tyr Gly Leu Gly Asp Arg Lys Asp Gln Gly Gly Tyr Thr Met His 
            20                  25                  30          


Gln Asp Gln Glu Gly Asp Thr Asp Ala Gly Leu Lys Glu Ser Pro Leu 
        35                  40                  45              


Gln Thr Pro Thr Glu Asp Gly Ser Glu Glu Pro Gly Ser Glu Thr Ser 
    50                  55                  60                  


Asp Ala Lys Ser Thr Pro Thr Ala Glu Asp Val Thr Ala Pro Leu Val 
65                  70                  75                  80  


Asp Glu Gly Ala Pro Gly Lys Gln Ala Ala Ala Gln Pro His Thr Glu 
                85                  90                  95      


Ile Pro Glu Gly Thr Thr Ala Glu Glu Ala Gly Ile Gly Asp Thr Pro 
            100                 105                 110         


Ser Leu Glu Asp Glu Ala Ala Gly His Val Thr Gln Ala Arg Met Val 
        115                 120                 125             


Ser Lys Ser Lys Asp Gly Thr Gly Ser Asp Asp Lys Lys Ala Lys Gly 
    130                 135                 140                 


Ala Asp Gly Lys Thr Lys Ile Ala Thr Pro Arg Gly Ala Ala Pro Pro 
145                 150                 155                 160 


Gly Gln Lys Gly Gln Ala Asn Ala Thr Arg Ile Pro Ala Lys Thr Pro 
                165                 170                 175     


Pro Ala Pro Lys Thr Pro Pro Ser Ser Gly Glu Pro Pro Lys Ser Gly 
            180                 185                 190         


Asp Arg Ser Gly Tyr Ser Ser Pro Gly Ser Pro Gly Thr Pro Gly Ser 
        195                 200                 205             


Arg Ser Arg Thr Pro Ser Leu Pro Thr Pro Pro Thr Arg Glu Pro Lys 
    210                 215                 220                 


Lys Val Ala Val Val Arg Thr Pro Pro Lys Ser Pro Ser Ser Ala Lys 
225                 230                 235                 240 


Ser Arg Leu Gln Thr Ala Pro Val Pro Met Pro Asp Leu Lys Asn Val 
                245                 250                 255     


Lys Ser Lys Ile Gly Ser Thr Glu Asn Leu Lys His Gln Pro Gly Gly 
            260                 265                 270         


Gly Lys Val Gln Ile Ile Asn Lys Lys Leu Asp Leu Ser Asn Val Gln 
        275                 280                 285             


Ser Lys Cys Gly Ser Lys Asp Asn Ile Lys His Val Pro Gly Gly Gly 
    290                 295                 300                 


Ser Val Gln Ile Val Tyr Lys Pro Val Asp Leu Ser Lys Val Thr Ser 
305                 310                 315                 320 


Lys Cys Gly Ser Leu Gly Asn Ile His His Lys Pro Gly Gly Gly Gln 
                325                 330                 335     


Val Glu Val Lys Ser Glu Lys Leu Asp Phe Lys Asp Arg Val Gln Ser 
            340                 345                 350         


Lys Ile Gly Ser Leu Asp Asn Ile Thr His Val Pro Gly Gly Gly Asn 
        355                 360                 365             


Lys Lys Ile Glu Thr His Lys Leu Thr Phe Arg Glu Asn Ala Lys Ala 
    370                 375                 380                 


Lys Thr Asp His Gly Ala Glu Ile Val Tyr Lys Ser Pro Val Val Ser 
385                 390                 395                 400 


Gly Asp Thr Ser Pro Arg His Leu Ser Asn Val Ser Ser Thr Gly Ser 
                405                 410                 415     


Ile Asp Met Val Asp Ser Pro Gln Leu Ala Thr Leu Ala Asp Glu Val 
            420                 425                 430         


Ser Ala Ser Leu Ala Lys Gln Gly Leu 
        435                 440     


<210>  2
<211>  16
<212>  PRT
<213>  Artificial

<220>
<223>  D1.2 LC CDR1

<400>  2

Arg Ser Ser Gln Ser Leu Val His Ser Asn Gly Asn Thr Tyr Leu His 
1               5                   10                  15      


<210>  3
<211>  7
<212>  PRT
<213>  artificial

<220>
<223>  D1.2 LC CDR2

<400>  3

Lys Val Ser Asn Arg Phe Ser 
1               5           


<210>  4
<211>  7
<212>  PRT
<213>  artificial

<220>
<223>  D1.2 LC CDR3

<400>  4

Ser Gln Ser Thr His Val Pro 
1               5           


<210>  5
<211>  219
<212>  PRT
<213>  artificial

<220>
<223>  D1.2 VL

<400>  5

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


Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser 
            20                  25                  30          


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


Pro Lys Phe Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro 
    50                  55                  60                  


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


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


Thr His Val Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys 
            100                 105                 110         


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


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


Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg 
145                 150                 155                 160 


Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser 
                165                 170                 175     


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


Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser 
        195                 200                 205             


Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys 
    210                 215                 


<210>  6
<211>  13
<212>  PRT
<213>  artificial

<220>
<223>  D1.2 HC CDR1

<400>  6

Lys Ala Ser Gly Asn Thr Phe Thr Asp Tyr Glu Ile His 
1               5                   10              


<210>  7
<211>  17
<212>  PRT
<213>  artificial

<220>
<223>  D1.2 HC CDR2

<400>  7

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


Gly 
    


<210>  8
<211>  6
<212>  PRT
<213>  artificial

<220>
<223>  D1.2 HC CDR3

<400>  8

Ser Arg Gly Phe Asp Tyr 
1               5       


<210>  9
<211>  451
<212>  PRT
<213>  artificial

<220>
<223>  D1.2 VH

<400>  9

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


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


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


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


Lys Gly Lys Ala Arg Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr 
65                  70                  75                  80  


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


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


Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro 
        115                 120                 125             


Gly Cys Gly Asp Thr Thr Gly Ser Ser Val Thr Leu Gly Cys Leu Val 
    130                 135                 140                 


Lys Gly Tyr Phe Pro Glu Ser Val Thr Val Thr Trp Asn Ser Gly Ser 
145                 150                 155                 160 


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


Tyr Thr Met Ser Ser Ser Val Thr Val Pro Ser Ser Thr Trp Pro Ser 
            180                 185                 190         


Gln Thr Val Thr Cys Ser Val Ala His Pro Ala Ser Ser Thr Thr Val 
        195                 200                 205             


Asp Lys Lys Leu Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Cys 
    210                 215                 220                 


Pro Pro Cys Lys Glu Cys His Lys Cys Pro Ala Pro Asn Leu Glu Gly 
225                 230                 235                 240 


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


Ile Ser Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Val Ser Glu 
            260                 265                 270         


Asp Asp Pro Asp Val Arg Ile Ser Trp Phe Val Asn Asn Val Glu Val 
        275                 280                 285             


His Thr Ala Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Ile 
    290                 295                 300                 


Arg Val Val Ser Ala Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly 
305                 310                 315                 320 


Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Asp Leu Pro Ser Pro Ile 
                325                 330                 335     


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


Tyr Ile Leu Pro Pro Pro Ala Glu Gln Leu Ser Arg Lys Asp Val Ser 
        355                 360                 365             


Leu Thr Cys Leu Val Val Gly Phe Asn Pro Gly Asp Ile Ser Val Glu 
    370                 375                 380                 


Trp Thr Ser Asn Gly His Thr Glu Glu Asn Tyr Lys Asp Thr Ala Pro 
385                 390                 395                 400 


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


Lys Thr Ser Lys Trp Glu Lys Thr Asp Ser Phe Ser Cys Asn Val Arg 
            420                 425                 430         


His Glu Gly Leu Lys Asn Tyr Tyr Leu Lys Lys Thr Ile Ser Arg Ser 
        435                 440                 445             


Pro Gly Lys 
    450     


<210>  10
<211>  11
<212>  PRT
<213>  Artificial

<220>
<223>  C10.2 LC CDR1

<400>  10

Gln Ala Ser Gln Gly Thr Ser Ile Asn Leu Asn 
1               5                   10      


<210>  11
<211>  7
<212>  PRT
<213>  artificial

<220>
<223>  C10.2 LC CDR2

<400>  11

Gly Ala Ser Asn Leu Glu Asp 
1               5           


<210>  12
<211>  7
<212>  PRT
<213>  artificial

<220>
<223>  C10.2 LC CDR3

<400>  12

Leu Gln His Thr Tyr Leu Pro 
1               5           


<210>  13
<211>  214
<212>  PRT
<213>  artificial

<220>
<223>  C10.2 VL

<400>  13

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


Asp Ile Val Thr Met Thr Cys Gln Ala Ser Gln Gly Thr Ser Ile Asn 
            20                  25                  30          


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


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


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


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


Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg Ala Asp Ala Ala 
            100                 105                 110         


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


Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile 
    130                 135                 140                 


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


Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser 
                165                 170                 175     


Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr 
            180                 185                 190         


Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser 
        195                 200                 205             


Phe Asn Arg Asn Glu Cys 
    210                 


<210>  14
<211>  13
<212>  PRT
<213>  artificial

<220>
<223>  C10.2 HC CDR1

<400>  14

Lys Ala Ser Gly Tyr Thr Phe Thr Asp Arg Thr Ile His 
1               5                   10              


<210>  15
<211>  17
<212>  PRT
<213>  artificial

<220>
<223>  C10.2 HC CDR2

<400>  15

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


Gly 
    


<210>  16
<211>  6
<212>  PRT
<213>  artificial

<220>
<223>  C10.2 HC CDR3

<400>  16

Arg Gly Ala Met Asp Tyr 
1               5       


<210>  17
<211>  439
<212>  PRT
<213>  artificial

<220>
<223>  C10.2 VH

<400>  17

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


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


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


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


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


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


Ala Arg Arg Gly Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr 
            100                 105                 110         


Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro 
        115                 120                 125             


Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val 
    130                 135                 140                 


Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser 
145                 150                 155                 160 


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


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


Glu Thr Val Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys Val 
        195                 200                 205             


Asp Lys Lys Ile Val Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys 
    210                 215                 220                 


Thr Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys 
225                 230                 235                 240 


Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val Val 
                245                 250                 255     


Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp 
            260                 265                 270         


Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe 
        275                 280                 285             


Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp 
    290                 295                 300                 


Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe 
305                 310                 315                 320 


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


Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys 
            340                 345                 350         


Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp 
        355                 360                 365             


Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys 
    370                 375                 380                 


Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser 
385                 390                 395                 400 


Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr 
                405                 410                 415     


Cys Ser Val Leu His Glu Gly Leu His Asn His His Thr Glu Lys Ser 
            420                 425                 430         


Leu Ser His Ser Pro Gly Lys 
        435                 


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

<220>
<223>  C5.2 LC CDR1

<400>  18

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


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

<220>
<223>  C5.2 LC CDR2

<400>  19

Gly Ala Ser Asn Leu Glu Asp 
1               5           


<210>  20
<211>  7
<212>  PRT
<213>  artificial

<220>
<223>  C5.2 LC CDR3

<400>  20

Leu Gln His Thr Tyr Leu Pro 
1               5           


<210>  21
<211>  214
<212>  PRT
<213>  artificial

<220>
<223>  C5.2 VL

<400>  21

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


Asp Ile Val Thr Met Thr Cys Gln Ala Ser Gln Asp Thr Ser Ile Asn 
            20                  25                  30          


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


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


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


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


Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg Ala Asp Ala Ala 
            100                 105                 110         


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


Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile 
    130                 135                 140                 


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


Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser 
                165                 170                 175     


Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr 
            180                 185                 190         


Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser 
        195                 200                 205             


Phe Asn Arg Asn Glu Cys 
    210                 


<210>  22
<211>  13
<212>  PRT
<213>  artificial

<220>
<223>  C5.2 HC CDR1

<400>  22

Lys Ala Ser Gly Tyr Thr Phe Thr Asp Arg Thr Ile His 
1               5                   10              


<210>  23
<211>  17
<212>  PRT
<213>  artificial

<220>
<223>  C5.2 HC CDR2

<400>  23

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


Gly 
    


<210>  24
<211>  6
<212>  PRT
<213>  artificial

<220>
<223>  C5.2 HC CDR3

<400>  24

Arg Gly Thr Met Asp Tyr 
1               5       


<210>  25
<211>  439
<212>  PRT
<213>  artificial

<220>
<223>  C5.2 VH

<400>  25

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


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


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


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


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


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


Ala Arg Arg Gly Thr Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr 
            100                 105                 110         


Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro 
        115                 120                 125             


Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val 
    130                 135                 140                 


Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser 
145                 150                 155                 160 


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


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


Glu Thr Val Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys Val 
        195                 200                 205             


Asp Lys Lys Ile Val Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys 
    210                 215                 220                 


Thr Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys 
225                 230                 235                 240 


Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val Val 
                245                 250                 255     


Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp 
            260                 265                 270         


Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe 
        275                 280                 285             


Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp 
    290                 295                 300                 


Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe 
305                 310                 315                 320 


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


Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys 
            340                 345                 350         


Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp 
        355                 360                 365             


Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys 
    370                 375                 380                 


Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser 
385                 390                 395                 400 


Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr 
                405                 410                 415     


Cys Ser Val Leu His Glu Gly Leu His Asn His His Thr Glu Lys Ser 
            420                 425                 430         


Leu Ser His Ser Pro Gly Lys 
        435                 


<210>  26
<211>  11
<212>  PRT
<213>  artificial

<220>
<223>  C8.3 LC CDR1

<400>  26

Gln Ala Ser Gln Gly Thr Ser Ile Asn Leu Asn 
1               5                   10      


<210>  27
<211>  7
<212>  PRT
<213>  artificial

<220>
<223>  C8.3 LC CDR2

<400>  27

Gly Ser Ser Asn Leu Glu Asp 
1               5           


<210>  28
<211>  7
<212>  PRT
<213>  artificial

<220>
<223>  C8.3 LC CDR3

<400>  28

Leu Gln His Ser Tyr Leu Pro 
1               5           


<210>  29
<211>  214
<212>  PRT
<213>  artificial

<220>
<223>  C8.3 VL

<400>  29

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


Asp Ile Val Thr Met Thr Cys Gln Ala Ser Gln Gly Thr Ser Ile Asn 
            20                  25                  30          


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


Tyr Gly Ser Ser Asn Leu Glu Asp Gly Val Pro Ser Arg Phe Ser Gly 
    50                  55                  60                  


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


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


Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg Ala Asp Ala Ala 
            100                 105                 110         


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


Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile 
    130                 135                 140                 


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


Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser 
                165                 170                 175     


Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr 
            180                 185                 190         


Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser 
        195                 200                 205             


Phe Asn Arg Asn Glu Cys 
    210                 


<210>  30
<211>  13
<212>  PRT
<213>  artificial

<220>
<223>  C8.3 HC CDR1

<400>  30

Lys Ala Ser Gly Tyr Thr Phe Thr Asp Arg Thr Ile His 
1               5                   10              


<210>  31
<211>  17
<212>  PRT
<213>  artificial

<220>
<223>  C8.3 HC CDR2

<400>  31

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


Gly 
    


<210>  32
<211>  6
<212>  PRT
<213>  artificial

<220>
<223>  C8.3 HC CDR3

<400>  32

Arg Gly Ala Met Asp Tyr 
1               5       


<210>  33
<211>  439
<212>  PRT
<213>  artificial

<220>
<223>  C8.3 VH

<400>  33

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


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


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


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


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


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


Ala Arg Arg Gly Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr 
            100                 105                 110         


Val Ser Ser Ala Lys Thr Thr Pro Pro Ser Val Tyr Pro Leu Ala Pro 
        115                 120                 125             


Gly Ser Ala Ala Gln Thr Asn Ser Met Val Thr Leu Gly Cys Leu Val 
    130                 135                 140                 


Lys Gly Tyr Phe Pro Glu Pro Val Thr Val Thr Trp Asn Ser Gly Ser 
145                 150                 155                 160 


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


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


Glu Thr Val Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys Val 
        195                 200                 205             


Asp Lys Lys Ile Val Pro Arg Asp Cys Gly Cys Lys Pro Cys Ile Cys 
    210                 215                 220                 


Thr Val Pro Glu Val Ser Ser Val Phe Ile Phe Pro Pro Lys Pro Lys 
225                 230                 235                 240 


Asp Val Leu Thr Ile Thr Leu Thr Pro Lys Val Thr Cys Val Val Val 
                245                 250                 255     


Asp Ile Ser Lys Asp Asp Pro Glu Val Gln Phe Ser Trp Phe Val Asp 
            260                 265                 270         


Asp Val Glu Val His Thr Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe 
        275                 280                 285             


Asn Ser Thr Phe Arg Ser Val Ser Glu Leu Pro Ile Met His Gln Asp 
    290                 295                 300                 


Trp Leu Asn Gly Lys Glu Phe Lys Cys Arg Val Asn Ser Ala Ala Phe 
305                 310                 315                 320 


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


Ala Pro Gln Val Tyr Thr Ile Pro Pro Pro Lys Glu Gln Met Ala Lys 
            340                 345                 350         


Asp Lys Val Ser Leu Thr Cys Met Ile Thr Asp Phe Phe Pro Glu Asp 
        355                 360                 365             


Ile Thr Val Glu Trp Gln Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys 
    370                 375                 380                 


Asn Thr Gln Pro Ile Met Asp Thr Asp Gly Ser Tyr Phe Val Tyr Ser 
385                 390                 395                 400 


Lys Leu Asn Val Gln Lys Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr 
                405                 410                 415     


Cys Ser Val Leu His Glu Gly Leu His Asn His His Thr Glu Lys Ser 
            420                 425                 430         


Leu Ser His Ser Pro Gly Lys 
        435                 


<210>  34
<211>  11
<212>  PRT
<213>  artificial

<220>
<223>  C10-2 Humanized LC CDR1

<400>  34

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


<210>  35
<211>  7
<212>  PRT
<213>  artificial

<220>
<223>  C10-2 Humanized LC CDR2

<400>  35

Gly Ala Ser Asn Leu Glu Thr 
1               5           


<210>  36
<211>  9
<212>  PRT
<213>  artificial

<220>
<223>  C10-2 Humanized LC CDR3

<400>  36

Leu Gln His Thr Tyr Leu Pro Phe Thr 
1               5                   


<210>  37
<211>  214
<212>  PRT
<213>  Artificial

<220>
<223>  C10-2 Humanized VL

<400>  37

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


Asp Arg Val Thr Met Thr Cys Gln Ala Ser Gln Asp Thr Ser Ile Asn 
            20                  25                  30          


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


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


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


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


Thr Phe Gly Ser 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>  38
<211>  5
<212>  PRT
<213>  artificial

<220>
<223>  C10-2 Humanized HC CDR1

<400>  38

Asp Arg Thr Ile His 
1               5   


<210>  39
<211>  17
<212>  PRT
<213>  artificial

<220>
<223>  C10-2 Humanized HC CDR2

<400>  39

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


Gly 
    


<210>  40
<211>  6
<212>  PRT
<213>  artificial

<220>
<223>  C10-2 Humanized HC CDR3

<400>  40

Arg Gly Ala Met Asp Tyr 
1               5       


<210>  41
<211>  445
<212>  PRT
<213>  artificial

<220>
<223>  C10-2 Humanized VH

<400>  41

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


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


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


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


Gln Gly Arg Ala Thr Leu Thr Ala 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 Arg Gly Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr 
            100                 105                 110         


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


Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val 
    130                 135                 140                 


Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala 
145                 150                 155                 160 


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  42
<211>  18
<212>  PRT
<213>  artificial

<220>
<223>  D55E HC CDR2

<400>  42

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


Gly Arg 
        


<210>  43
<211>  444
<212>  PRT
<213>  artificial

<220>
<223>  D55E VH

<400>  43

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


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


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


Gly Tyr Ile Tyr Pro Gly Glu Gly Ser Thr Lys Tyr Ser Gln Lys Phe 
    50                  55                  60                  


Gln Gly Arg Ala Thr Leu Thr Ala 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 Arg Gly Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr 
            100                 105                 110         


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


Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val 
    130                 135                 140                 


Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala 
145                 150                 155                 160 


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  44
<211>  18
<212>  PRT
<213>  artificial

<220>
<223>  D55Q HC CDR2

<400>  44

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


Gly Arg 
        


<210>  45
<211>  444
<212>  PRT
<213>  artificial

<220>
<223>  D55Q VH

<400>  45

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


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


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


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


Gln Gly Arg Ala Thr Leu Thr Ala 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 Arg Gly Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr 
            100                 105                 110         


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


Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val 
    130                 135                 140                 


Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala 
145                 150                 155                 160 


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  46
<211>  18
<212>  PRT
<213>  artificial

<220>
<223>  D55S HC CDR2

<400>  46

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


Gly Arg 
        


<210>  47
<211>  444
<212>  PRT
<213>  Artificial

<220>
<223>  D55S VH

<400>  47

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


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


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


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


Gln Gly Arg Ala Thr Leu Thr Ala 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 Arg Gly Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr 
            100                 105                 110         


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


Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val 
    130                 135                 140                 


Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala 
145                 150                 155                 160 


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  48
<211>  11
<212>  PRT
<213>  artificial

<220>
<223>  N32S LC CDR1

<400>  48

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


<210>  49
<211>  214
<212>  PRT
<213>  artificial

<220>
<223>  N32S VL

<400>  49

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


Asp Arg Val Thr Met Thr Cys Gln Ala Ser Gln Asp Thr Ser Ile Ser 
            20                  25                  30          


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


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


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


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


Thr Phe Gly Ser 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>  50
<211>  11
<212>  PRT
<213>  artificial

<220>
<223>  N32Q LC CDR1

<400>  50

Gln Ala Ser Gln Asp Thr Ser Ile Gln Leu Gln 
1               5                   10      


<210>  51
<211>  214
<212>  PRT
<213>  artificial

<220>
<223>  N32Q VH

<400>  51

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


Asp Arg Val Thr Met Thr Cys Gln Ala Ser Gln Asp Thr Ser Ile Gln 
            20                  25                  30          


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


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


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


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


Thr Phe Gly Ser 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>  52
<211>  11
<212>  PRT
<213>  artificial

<220>
<223>  N34S LC CDR1

<400>  52

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


<210>  53
<211>  214
<212>  PRT
<213>  Artificial

<220>
<223>  N34S VL

<400>  53

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


Asp Arg Val Thr Met Thr Cys Gln Ala Ser Gln Asp Thr Ser Ile Asn 
            20                  25                  30          


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


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


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


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


Thr Phe Gly Ser 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>  54
<211>  11
<212>  PRT
<213>  artificial

<220>
<223>  N34Q LC CDR1

<400>  54

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


<210>  55
<211>  214
<212>  PRT
<213>  artificial

<220>
<223>  N34Q VL

<400>  55

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


Asp Arg Val Thr Met Thr Cys Gln Ala Ser Gln Asp Thr Ser Ile Asn 
            20                  25                  30          


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


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


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


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


Thr Phe Gly Ser 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>  56
<211>  11
<212>  PRT
<213>  artificial

<220>
<223>  N32S,N34S LC CDR1

<400>  56

Gln Ala Ser Gln Asp Thr Ser Ile Ser Leu Ser 
1               5                   10      


<210>  57
<211>  214
<212>  PRT
<213>  artificial

<220>
<223>  N32S,N34S VL

<400>  57

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


Asp Arg Val Thr Met Thr Cys Gln Ala Ser Gln Asp Thr Ser Ile Ser 
            20                  25                  30          


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


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


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


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


Thr Phe Gly Ser 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>  58
<211>  11
<212>  PRT
<213>  Artificial

<220>
<223>  N32Q, N34S LC CDR1

<400>  58

Gln Ala Ser Gln Asp Thr Ser Ile Gln Leu Ser 
1               5                   10      


<210>  59
<211>  214
<212>  PRT
<213>  artificial

<220>
<223>  N32Q, N34S VL

<400>  59

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


Asp Arg Val Thr Met Thr Cys Gln Ala Ser Gln Asp Thr Ser Ile Gln 
            20                  25                  30          


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


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


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


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


Thr Phe Gly Ser 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>  60
<211>  11
<212>  PRT
<213>  artificial

<220>
<223>  N32Q, N34Q LC CDR1

<400>  60

Gln Ala Ser Gln Asp Thr Ser Ile Gln Leu Gln 
1               5                   10      


<210>  61
<211>  214
<212>  PRT
<213>  artificial

<220>
<223>  N32Q, N34Q VL

<400>  61

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


Asp Arg Val Thr Met Thr Cys Gln Ala Ser Gln Asp Thr Ser Ile Gln 
            20                  25                  30          


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


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


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


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


Thr Phe Gly Ser 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>  62
<211>  11
<212>  PRT
<213>  artificial

<220>
<223>  N32S, N34Q LC CDR1

<400>  62

Gln Ala Ser Gln Asp Thr Ser Ile Ser Leu Gln 
1               5                   10      


<210>  63
<211>  214
<212>  PRT
<213>  artificial

<220>
<223>  N32S, N34Q LC

<400>  63

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


Asp Arg Val Thr Met Thr Cys Gln Ala Ser Gln Asp Thr Ser Ile Ser 
            20                  25                  30          


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


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


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


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


Thr Phe Gly Ser 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>  64
<211>  6
<212>  PRT
<213>  artificial

<220>
<223>  A101 HC CDR3

<400>  64

Arg Gly Thr Met Asp Tyr 
1               5       


<210>  65
<211>  444
<212>  PRT
<213>  artificial

<220>
<223>  A101 VH

<400>  65

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


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


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


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


Gln Gly Arg Ala Thr Leu Thr Ala 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 Arg Gly Thr Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr 
            100                 105                 110         


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


Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val 
    130                 135                 140                 


Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala 
145                 150                 155                 160 


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  66
<211>  18
<212>  PRT
<213>  artificial

<220>
<223>  D55E, A101T HC CDR2

<400>  66

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


Gly Arg 
        


<210>  67
<211>  6
<212>  PRT
<213>  artificial

<220>
<223>  D55E, A101T HC CDR3

<400>  67

Arg Gly Thr Met Asp Tyr 
1               5       


<210>  68
<211>  444
<212>  PRT
<213>  artificial

<220>
<223>  D55E, A101T VH

<400>  68

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


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


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


Gly Tyr Ile Tyr Pro Gly Glu Gly Ser Thr Lys Tyr Ser Gln Lys Phe 
    50                  55                  60                  


Gln Gly Arg Ala Thr Leu Thr Ala 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 Arg Gly Thr Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr 
            100                 105                 110         


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


Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val 
    130                 135                 140                 


Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala 
145                 150                 155                 160 


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  69
<211>  18
<212>  PRT
<213>  artificial

<220>
<223>  D55Q, A101T HC CDR2

<400>  69

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


Gly Arg 
        


<210>  70
<211>  6
<212>  PRT
<213>  artificial

<220>
<223>  D55Q, A101T HC CDR3

<400>  70

Arg Gly Thr Met Asp Tyr 
1               5       


<210>  71
<211>  444
<212>  PRT
<213>  artificial

<220>
<223>  D55Q, A101T VH

<400>  71

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


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


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


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


Gln Gly Arg Ala Thr Leu Thr Ala 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 Arg Gly Thr Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr 
            100                 105                 110         


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


Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val 
    130                 135                 140                 


Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala 
145                 150                 155                 160 


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  72
<211>  18
<212>  PRT
<213>  artificial

<220>
<223>  D55S, A101T HC CDR2

<400>  72

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


Gly Arg 
        


<210>  73
<211>  6
<212>  PRT
<213>  artificial

<220>
<223>  D55S, A101T HC CDR3

<400>  73

Arg Gly Thr Met Asp Tyr 
1               5       


<210>  74
<211>  444
<212>  PRT
<213>  artificial

<220>
<223>  D55S, A101T VH

<400>  74

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


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


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


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


Gln Gly Arg Ala Thr Leu Thr Ala 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 Arg Gly Thr Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr 
            100                 105                 110         


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


Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val 
    130                 135                 140                 


Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala 
145                 150                 155                 160 


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


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


