                         SEQUENCE LISTING

<110>  Boehringer Ingelheim International GmbH
       Litzenburger, Tobias
       Miller, Sandra
       Pracht, Catrin
       Boxhammer, Rainer
       Magram, Jeanne
       Giblin, Patricia
       Rajotte, Daniel
 
<120>  Effectors of PAR-2 Activation and Their Use in the Modulation of 
       Inflammation

<130>  09-0439

<150>  US 61/086,282
<151>  2008-08-05

<160>  44    

<170>  PatentIn version 3.4

<210>  1
<211>  397
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Arg Ser Pro Ser Ala Ala Trp Leu Leu Gly Ala Ala Ile Leu Leu 
1               5                   10                  15      


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


Ser Lys Gly Arg Ser Leu Ile Gly Lys Val Asp Gly Thr Ser His Val 
        35                  40                  45              


Thr Gly Lys Gly Val Thr Val Glu Thr Val Phe Ser Val Asp Glu Phe 
    50                  55                  60                  


Ser Ala Ser Val Leu Thr Gly Lys Leu Thr Thr Val Phe Leu Pro Ile 
65                  70                  75                  80  


Val Tyr Thr Ile Val Phe Val Val Gly Leu Pro Ser Asn Gly Met Ala 
                85                  90                  95      


Leu Trp Val Phe Leu Phe Arg Thr Lys Lys Lys His Pro Ala Val Ile 
            100                 105                 110         


Tyr Met Ala Asn Leu Ala Leu Ala Asp Leu Leu Ser Val Ile Trp Phe 
        115                 120                 125             


Pro Leu Lys Ile Ala Tyr His Ile His Gly Asn Asn Trp Ile Tyr Gly 
    130                 135                 140                 


Glu Ala Leu Cys Asn Val Leu Ile Gly Phe Phe Tyr Gly Asn Met Tyr 
145                 150                 155                 160 


Cys Ser Ile Leu Phe Met Thr Cys Leu Ser Val Gln Arg Tyr Trp Val 
                165                 170                 175     


Ile Val Asn Pro Met Gly His Ser Arg Lys Lys Ala Asn Ile Ala Ile 
            180                 185                 190         


Gly Ile Ser Leu Ala Ile Trp Leu Leu Ile Leu Leu Val Thr Ile Pro 
        195                 200                 205             


Leu Tyr Val Val Lys Gln Thr Ile Phe Ile Pro Ala Leu Asn Ile Thr 
    210                 215                 220                 


Thr Cys His Asp Val Leu Pro Glu Gln Leu Leu Val Gly Asp Met Phe 
225                 230                 235                 240 


Asn Tyr Phe Leu Ser Leu Ala Ile Gly Val Phe Leu Phe Pro Ala Phe 
                245                 250                 255     


Leu Thr Ala Ser Ala Tyr Val Leu Met Ile Arg Met Leu Arg Ser Ser 
            260                 265                 270         


Ala Met Asp Glu Asn Ser Glu Lys Lys Arg Lys Arg Ala Ile Lys Leu 
        275                 280                 285             


Ile Val Thr Val Leu Ala Met Tyr Leu Ile Cys Phe Thr Pro Ser Asn 
    290                 295                 300                 


Leu Leu Leu Val Val His Tyr Phe Leu Ile Lys Ser Gln Gly Gln Ser 
305                 310                 315                 320 


His Val Tyr Ala Leu Tyr Ile Val Ala Leu Cys Leu Ser Thr Leu Asn 
                325                 330                 335     


Ser Cys Ile Asp Pro Phe Val Tyr Tyr Phe Val Ser His Asp Phe Arg 
            340                 345                 350         


Asp His Ala Lys Asn Ala Leu Leu Cys Arg Ser Val Arg Thr Val Lys 
        355                 360                 365             


Gln Met Gln Val Ser Leu Thr Ser Lys Lys His Ser Arg Lys Ser Ser 
    370                 375                 380                 


Ser Tyr Ser Ser Ser Ser Thr Thr Val Lys Thr Ser Tyr 
385                 390                 395         


<210>  2
<211>  21
<212>  PRT
<213>  Mus musculus

<400>  2

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


Thr Gly Lys Gly Val 
            20      


<210>  3
<211>  21
<212>  PRT
<213>  Rattus norvegicus

<400>  3

Ser Lys Gly Arg Ser Leu Ile Gly Arg Leu Asp Thr Pro Pro Pro Ile 
1               5                   10                  15      


Thr Gly Lys Gly Ala 
            20      


<210>  4
<211>  21
<212>  PRT
<213>  Macaca fascicularis

<400>  4

Ser Lys Gly Arg Ser Leu Ile Gly Arg Val Asp Gly Thr Phe His Val 
1               5                   10                  15      


Thr Gly Lys Gly Val 
            20      


<210>  5
<211>  21
<212>  PRT
<213>  Artificial

<220>
<223>  Consensus sequence of PAR-2 fragment

<400>  5

Ser Lys Gly Arg Ser Leu Ile Gly Arg Leu Asp Thr Thr Pro Pro Ile 
1               5                   10                  15      


Thr Gly Lys Gly Val 
            20      


<210>  6
<211>  110
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody identified via phage display

<400>  6

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


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


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


Asp Asp Ser Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser 
    50                  55                  60                  


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


Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Trp Asp Val Gly Ser Asp Gly 
                85                  90                  95      


Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln 
            100                 105                 110 


<210>  7
<211>  117
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody identified via phage display

<400>  7

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


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


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


Ser Thr Ile Ser Tyr Ser Ser Ser Ala Thr Ser Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Arg Ile Gln Asn Asp Pro Met Asp Val Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  8
<211>  108
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody identified via phage display

<400>  8

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


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


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


Asp Asp Asn Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser 
    50                  55                  60                  


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


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


Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln 
            100                 105             


<210>  9
<211>  119
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody identified via phage display

<400>  9

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn His 
            20                  25                  30          


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


Ser Gly Ile Ser Gly Gly Gly Ser Asn Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Arg His Gly Asp Gly Met Asp Tyr Phe Asp Phe Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser 
        115                 


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

<220>
<223>  Antibody identified via phage display

<400>  10

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


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

<220>
<223>  Antibody modified via affinity maturation

<400>  11

Ser Ala Ile Ser Thr Ser Gly His Leu Thr Gly Tyr Ala Asp Ser 
1               5                   10                  15  


<210>  12
<211>  15
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody modified via affinity maturation

<400>  12

Ser Ala Ile Ser Tyr Asn Gly Lys Leu Lys Gly Tyr Ala Asp Ser 
1               5                   10                  15  


<210>  13
<211>  15
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody modified via affinity maturation

<400>  13

Ser Ala Ile Ser Tyr Lys Gly His Leu Thr Gly Tyr Ala Asp Ser 
1               5                   10                  15  


<210>  14
<211>  15
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody modified via affinity maturation

<400>  14

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


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

<220>
<223>  Antibody modified via affinity maturation

<400>  15

Ser Ala Ile Ser Phe Ser Gly His Leu Thr Gly Tyr Ala Asp Ser 
1               5                   10                  15  


<210>  16
<211>  15
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody identified via phage display

<400>  16

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


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

<220>
<223>  Antibody modified via affinity maturation

<400>  17

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


<210>  18
<211>  10
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody identified via phage display

<400>  18

Ser Ser Trp Asp Val Gly Ser Asp Gly Trp 
1               5                   10  


<210>  19
<211>  13
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody modified via affinity maturation

<400>  19

Gln Thr Trp Asp Tyr Ser Ser Ile Arg Asp Glu Thr Asn 
1               5                   10              


<210>  20
<211>  12
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody modified via affinity maturation

<400>  20

Gln Ser Trp Ala Leu Val Gly Ser Ser Glu Ser Asn 
1               5                   10          


<210>  21
<211>  117
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody modified via affinity maturation

<400>  21

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


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


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


Ser Ala Ile Ser Tyr Ser Gly His Leu Thr Gly Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Arg Ile Gln Asn Asp Pro Met Asp Val Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


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

<220>
<223>  Antibody modified via affinity maturation

<400>  22

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn His 
            20                  25                  30          


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


Ser Ala Ile Ser His Pro Gly Lys Phe Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Arg His Gly Asp Gly Met Asp Tyr Phe Asp Phe Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  23
<211>  117
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody modified via affinity maturation

<400>  23

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


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


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


Ser Ala Ile Ser Tyr Asn Gly Lys Leu Lys Gly Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Arg Ile Gln Asn Asp Pro Met Asp Val Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  24
<211>  117
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody modified via affinity maturation

<400>  24

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


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


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


Ser Ala Ile Ser Tyr Lys Gly His Leu Thr Gly Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Arg Ile Gln Asn Asp Pro Met Asp Val Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  25
<211>  117
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody modified via affinity maturation

<400>  25

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


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


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


Gly Ala Ile Ser Phe Asp Gly Met Leu Thr Gly Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Arg Ile Gln Asn Asp Pro Met Asp Val Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  26
<211>  117
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody modified via affinity maturation

<400>  26

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


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


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


Ser Ala Ile Ser Phe Ser Gly His Leu Thr Gly Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Arg Ile Gln Asn Asp Pro Met Asp Val Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  27
<211>  113
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody modified via affinity maturation

<400>  27

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


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


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


Asp Asp Ser Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser 
    50                  55                  60                  


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


Asp Glu Ala Asp Tyr Tyr Cys Gln Thr Trp Asp Tyr Ser Ser Ile Arg 
                85                  90                  95      


Asp Glu Thr Asn Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 
            100                 105                 110         


Gln 
    


<210>  28
<211>  112
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody modified via affinity maturation

<400>  28

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


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


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


Asp Asp Ser Asn Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser 
    50                  55                  60                  


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


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


Glu Ser Asn Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln 
            100                 105                 110         


<210>  29
<211>  117
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody identified via phage display

<400>  29

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


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


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


Ser Thr Ile Ser Tyr Ser Ser Ser Ala Thr Ser Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Arg Ile Gln Asn Asp Pro Met Asp Val Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  30
<211>  119
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody identified via phage display

<400>  30

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn His 
            20                  25                  30          


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


Ser Gly Ile Ser Gly Gly Gly Ser Asn Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Arg His Gly Asp Gly Met Asp Tyr Phe Asp Phe Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  31
<211>  117
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody modified via affinity maturation

<400>  31

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


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


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


Ser Ala Ile Ser Tyr Ser Gly His Leu Thr Gly Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Arg Ile Gln Asn Asp Pro Met Asp Val Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  32
<211>  119
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody modified via affinity maturation

<400>  32

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn His 
            20                  25                  30          


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


Ser Ala Ile Ser His Pro Gly Lys Phe Thr Tyr Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Arg His Gly Asp Gly Met Asp Tyr Phe Asp Phe Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser 
        115                 


<210>  33
<211>  117
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody modified via affinity maturation

<400>  33

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


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


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


Ser Ala Ile Ser Tyr Asn Gly Lys Leu Lys Gly Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Arg Ile Gln Asn Asp Pro Met Asp Val Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  34
<211>  117
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody modified via affinity maturation

<400>  34

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


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


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


Ser Ala Ile Ser Tyr Lys Gly His Leu Thr Gly Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Arg Ile Gln Asn Asp Pro Met Asp Val Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  35
<211>  117
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody modified via affinity maturation

<400>  35

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


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


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


Gly Ala Ile Ser Phe Asp Gly Met Leu Thr Gly Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Arg Ile Gln Asn Asp Pro Met Asp Val Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  36
<211>  117
<212>  PRT
<213>  Artificial

<220>
<223>  Antibody modified via affinity maturation

<400>  36

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


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


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


Ser Ala Ile Ser Phe Ser Gly His Leu Thr Gly Tyr Ala Asp Ser Val 
    50                  55                  60                  


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


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


Ala Arg Ile Gln Asn Asp Pro Met Asp Val Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ser 
        115         


<210>  37
<211>  339
<212>  DNA
<213>  Artificial

<220>
<223>  Optimized cDNA sequence of variable region of Ab4999 light chain

<400>  37
gatatcgagc tgacccagcc ccccagcgtg agcgtggccc caggccagac cgccaggatc     60

agctgcagcg gcgacaacct gggcaagaaa tacgtgcagt ggtatcagca gaagcccggc    120

caggcccccg tgctggtgat ctacgacgac agcaacaggc ccagcggcat ccccgagagg    180

ttcagcggca gcaacagcgg caacaccgcc accctgacca tcagcggcac ccaggccgag    240

gacgaggccg actactactg ccagacctgg gactacagca gcatcaggga cgagaccaac    300

gtgttcggcg gagggaccaa gttaaccgtc ctaggtcag                           339


<210>  38
<211>  351
<212>  DNA
<213>  Artificial

<220>
<223>  Optimized cDNA sequence of variable region of Ab4999 heavy chain

<400>  38
caggtggagc tggtcgagag cggcggaggg ctggtgcagc caggcggcag cctgaggctg     60

tcctgcgccg cctccggatt caccttcagc agctacgcca tgaactgggt gcggcaggcc    120

ccaggcaagg gcctggagtg ggtgtccacc atcagctaca gcagcagcgc cacctcctac    180

gccgacagcg tgaagggcag gttcaccatc agcagggaca acagcaagaa caccctgtac    240

ctgcagatga acagcctgag ggccgaggac accgccgtgt actactgcgc caggatccag    300

aacgacccca tggatgtgtg gggccagggc accctggtga cagtgagctc a             351


<210>  39
<211>  351
<212>  DNA
<213>  Artificial

<220>
<223>  Optimized cDNA sequence of variable region of Ab5007 or Ab5151 
       heavy chain

<400>  39
caggtggagc tggtcgagag cggcggaggg ctggtgcagc caggcggcag cctgaggctg     60

tcctgcgccg cctccggatt caccttcagc agctacgcca tgaactgggt gcggcaggcc    120

ccaggcaagg gcctggagtg ggtgtccgcc atcagcttca gcggccacct gaccggctac    180

gccgacagcg tgaagggcag gttcaccatc agcagggaca acagcaagaa caccctgtac    240

ctgcagatga acagcctgag ggccgaggac accgccgtgt actactgcgc caggatccag    300

aacgacccca tggatgtgtg gggccagggc accctggtga cagtgagctc a             351


<210>  40
<211>  324
<212>  DNA
<213>  Artificial

<220>
<223>  Optimized cDNA sequence of variable region of Ab4996 light chain

<400>  40
gatatcgagc tgacccagcc ccccagcgtg agcgtggccc caggccagac cgccaggatc     60

agctgcagcg gcgacaacat cggcaccaag tacgtgtact ggtatcagca gaagcccggc    120

caggcccccg tgctggtgat ctacgacgac aacaacaggc ccagcggcat ccccgagagg    180

ttcagcggca gcaacagcgg caacaccgcc accctgacca tcagcggcac ccaggccgag    240

gacgaggccg actactactg ccagagctac gacagccaga ccatggtgtt cggcggaggg    300

accaagttaa ccgtgctggg acag                                           324


<210>  41
<211>  357
<212>  DNA
<213>  Artificial

<220>
<223>  Optimized cDNA sequence of variable region of Ab4996 heavy chain

<400>  41
caggtggagc tggtcgagag cggcggaggg ctggtgcagc caggcggcag cctgaggctg     60

tcctgcgccg cctccggatt caccttcagc aaccacgcca tgcactgggt gcggcaggcc    120

ccaggcaagg gcctggagtg ggtgtccgcc atcagccacc ccggcaagtt cacctactac    180

gccgacagcg tgaagggcag gttcaccatc agcagggaca acagcaagaa caccctgtac    240

ctgcagatga acagcctgag ggccgaggac accgccgtgt actactgcgc caggcacggc    300

gacggcatgg actacttcga cttttggggc cagggcaccc tggtgacagt gagctca       357


<210>  42
<211>  21
<212>  PRT
<213>  Homo sapiens

<400>  42

Ser Lys Gly Arg Ser Leu Ile Gly Lys Val Asp Gly Thr Ser His Val 
1               5                   10                  15      


Thr Gly Lys Gly Val 
            20      


<210>  43
<211>  29
<212>  PRT
<213>  Homo sapiens

<400>  43

Leu Asp Pro Arg Ser Phe Leu Leu Arg Asn Pro Asn Asp Lys Tyr Glu 
1               5                   10                  15      


Pro Phe Trp Glu Asp Glu Glu Lys Asn Glu Ser Gly Leu 
            20                  25                  


<210>  44
<211>  28
<212>  PRT
<213>  Homo sapiens

<400>  44

Pro Ala Pro Arg Gly Tyr Pro Gly Gln Val Ser Ala Asn Asp Ser Asp 
1               5                   10                  15      


Thr Leu Glu Leu Pro Asp Ser Ser Arg Ala Leu Leu 
            20                  25              


