                         SEQUENCE LISTING

<110>  Direvo Biotech AG
 
<120>  Specific Protease for Inactivation of Human Tumour Necrosis 
       Factor-alpha

<130>  070880wo

<150>  EP 06112706.4
<151>  2006-04-18

<150>  US 60/792,715
<151>  2006-04-18

<160>  34    

<170>  PatentIn version 3.3

<210>  1
<211>  224
<212>  PRT
<213>  Homo sapiens

<400>  1

Ile Val Gly Gly Tyr Asn Cys Glu Glu Asn Ser Val Pro Tyr Gln Val 
1               5                   10                  15      

Ser Leu Asn Ser Gly Tyr His Phe Cys Gly Gly Ser Leu Ile Asn Glu 
            20                  25                  30          

Gln Trp Val Val Ser Ala Gly His Cys Tyr Lys Ser Arg Ile Gln Val 
        35                  40                  45              

Arg Leu Gly Glu His Asn Ile Glu Val Leu Glu Gly Asn Glu Gln Phe 
    50                  55                  60                  

Ile Asn Ala Ala Lys Ile Ile Arg His Pro Gln Tyr Asp Arg Lys Thr 
65                  70                  75                  80  

Leu Asn Asn Asp Ile Met Leu Ile Lys Leu Ser Ser Arg Ala Val Ile 
                85                  90                  95      

Asn Ala Arg Val Ser Thr Ile Ser Leu Pro Thr Ala Pro Pro Ala Thr 
            100                 105                 110         

Gly Thr Lys Cys Leu Ile Ser Gly Trp Gly Asn Thr Ala Ser Ser Gly 
        115                 120                 125             

Ala Asp Tyr Pro Asp Glu Leu Gln Cys Leu Asp Ala Pro Val Leu Ser 
    130                 135                 140                 

Gln Ala Lys Cys Glu Ala Ser Tyr Pro Gly Lys Ile Thr Ser Asn Met 
145                 150                 155                 160 

Phe Cys Val Gly Phe Leu Glu Gly Gly Lys Asp Ser Cys Gln Gly Asp 
                165                 170                 175     

Ser Gly Gly Pro Val Val Cys Asn Gly Gln Leu Gln Gly Val Val Ser 
            180                 185                 190         

Trp Gly Asp Gly Cys Ala Gln Lys Asn Lys Pro Gly Val Tyr Thr Lys 
        195                 200                 205             

Val Tyr Asn Tyr Val Lys Trp Ile Lys Asn Thr Ile Ala Ala Asn Ser 
    210                 215                 220                 


<210>  2
<211>  238
<212>  PRT
<213>  artificial

<220>
<223>  variant E

<400>  2

Ile Val Gly Gly Tyr Asp Cys Glu Glu Asn Ser Val Pro Tyr His Val 
1               5                   10                  15      

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

Ile Asn Glu Gln Trp Val Val Thr Ala Gly His Cys Tyr Ala Phe Phe 
        35                  40                  45              

Pro Ala Asp Lys Ser Arg Ile Gln Val Arg Leu Gly Val His Ser Thr 
    50                  55                  60                  

Gly Ala Leu Glu Gly Asn Glu Gln Ile Ile Asn Ala Ala Lys Ile Ile 
65                  70                  75                  80  

Arg His Pro Gln Tyr Asp Trp Lys Thr Leu Asn Asn Asp Ile Met Leu 
                85                  90                  95      

Ile Lys Leu Ser Ser Pro Ala Val Ile Asn Ala His Val Ser Thr Ile 
            100                 105                 110         

Ser Leu Pro Thr Ala Pro Pro Ala Thr Gly Thr Lys Cys Leu Ile Ser 
        115                 120                 125             

Gly Trp Gly Asn Ser Lys Asp Pro Tyr Lys Pro Ser Ser Arg Ala Asp 
    130                 135                 140                 

Tyr Pro Gly Glu Val Gln Cys Leu Asp Ala Pro Val Leu Ser Gln Thr 
145                 150                 155                 160 

Lys Cys Glu Ala Ser Tyr Pro Gly Lys Ile Thr Ser Asn Met Phe Cys 
                165                 170                 175     

Ala Gly Phe Leu Glu Gly Gly Lys Asp Ser Cys Gln Gly Asp Ser Gly 
            180                 185                 190         

Gly Pro Val Val His Asn Gly Gln Leu Gln Gly Val Val Ser Trp Gly 
        195                 200                 205             

Glu Gly Cys Ala Gln Lys Asn Lys Pro Gly Val Tyr Thr Asn Val Tyr 
    210                 215                 220                 

Asn Tyr Val Glu Trp Ile Gln Asp Thr Ile Ala Ala Asn Ser 
225                 230                 235             


<210>  3
<211>  238
<212>  PRT
<213>  artificial

<220>
<223>  variant F

<400>  3

Ile Val Gly Gly Tyr Asp Cys Glu Glu Asn Ser Val Pro Tyr His Val 
1               5                   10                  15      

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

Ile Asn Glu Gln Trp Val Val Thr Ala Gly His Cys Tyr Ser Phe Leu 
        35                  40                  45              

Pro Leu Asp Lys Ser Arg Ile Gln Val Arg Leu Gly Val His Ser Thr 
    50                  55                  60                  

Gly Ala Leu Glu Gly Asn Glu Gln Ile Ile Asn Ala Ala Lys Ile Ile 
65                  70                  75                  80  

Arg His Pro Gln Tyr Asp Trp Lys Thr Leu Asn Asn Asp Ile Met Leu 
                85                  90                  95      

Ile Lys Leu Ser Ser Pro Ala Val Ile Asn Ala His Val Ser Thr Ile 
            100                 105                 110         

Ser Leu Pro Thr Ala Pro Pro Ala Thr Gly Thr Lys Cys Leu Ile Ser 
        115                 120                 125             

Gly Trp Gly Asn Ser Lys Asp Pro Tyr Lys Pro Ser Ser Arg Ala Asp 
    130                 135                 140                 

Tyr Pro Gly Glu Val Gln Cys Leu Asp Ala Pro Val Leu Ser Gln Thr 
145                 150                 155                 160 

Lys Cys Glu Ala Ser Tyr Pro Gly Lys Ile Thr Ser Asn Met Phe Cys 
                165                 170                 175     

Ala Gly Phe Leu Glu Gly Gly Lys Asp Ser Cys Gln Gly Asp Ser Gly 
            180                 185                 190         

Gly Pro Val Val His Asn Gly Gln Leu Gln Gly Val Val Ser Trp Gly 
        195                 200                 205             

Glu Gly Cys Ala Gln Lys Asn Lys Pro Gly Val Tyr Thr Asn Val Tyr 
    210                 215                 220                 

Asn Tyr Val Glu Trp Ile Gln Asp Thr Ile Ala Ala Asn Ser 
225                 230                 235             


<210>  4
<211>  241
<212>  PRT
<213>  artificial

<220>
<223>  variant G

<400>  4

Ile Val Gly Gly Tyr Asp Cys Glu Glu Asn Ser Val Pro Tyr His Val 
1               5                   10                  15      

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

Ile Asn Glu Gln Trp Val Val Thr Ala Gly His Cys Tyr Ser Phe Leu 
        35                  40                  45              

Pro Leu Asp Lys Ser Arg Ile Gln Val Arg Leu Gly Val His Ser Thr 
    50                  55                  60                  

Gly Ala Leu Glu Gly Asn Glu Gln Ile Ile Asn Ala Ala Lys Ile Ile 
65                  70                  75                  80  

Arg His Pro Gln Tyr Asp Trp Lys Thr Leu Asn Asn Asp Ile Met Leu 
                85                  90                  95      

Ile Lys Leu Ser Ser Pro Ala Val Ile Asn Ala His Val Ser Thr Ile 
            100                 105                 110         

Ser Leu Pro Thr Ala Pro Pro Ala Thr Gly Thr Lys Cys Leu Ile Ser 
        115                 120                 125             

Gly Trp Gly Asn Ser Lys Asp Pro Tyr Lys Pro Ser Ser Gly Pro Ser 
    130                 135                 140                 

Thr Ala Asp Tyr Pro Gly Glu Val Gln Cys Leu Asp Ala Pro Val Leu 
145                 150                 155                 160 

Ser Gln Thr Lys Cys Glu Ala Ser Tyr Pro Gly Lys Ile Thr Ser Asn 
                165                 170                 175     

Met Phe Cys Ala Gly Phe Leu Glu Gly Gly Lys Asp Ser Cys Gln Gly 
            180                 185                 190         

Asp Ser Gly Gly Pro Val Val His Asn Gly Gln Leu Gln Gly Val Val 
        195                 200                 205             

Ser Trp Gly Glu Gly Cys Ala Gln Lys Asn Lys Pro Gly Val Tyr Thr 
    210                 215                 220                 

Asn Val Tyr Asn Tyr Val Glu Trp Ile Gln Asp Thr Ile Ala Ala Asn 
225                 230                 235                 240 

Ser 


<210>  5
<211>  241
<212>  PRT
<213>  artificial

<220>
<223>  variant H

<400>  5

Ile Val Gly Gly Tyr Asp Cys Glu Glu Asn Ser Val Pro Tyr His Val 
1               5                   10                  15      

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

Ile Asn Glu Gln Trp Val Val Thr Ala Gly His Cys Tyr Ser Phe Leu 
        35                  40                  45              

Pro Leu Asp Lys Ser Arg Ile Gln Val Arg Leu Gly Val His Ser Thr 
    50                  55                  60                  

Gly Ala Leu Glu Gly Asn Glu Gln Ile Ile Asn Ala Ala Lys Ile Ile 
65                  70                  75                  80  

Arg His Pro Gln Tyr Asp Trp Lys Thr Leu Asn Asn Asp Ile Met Leu 
                85                  90                  95      

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

Ser Leu Pro Thr Ala Pro Pro Ala Pro Gly Thr Lys Cys Leu Ile Ser 
        115                 120                 125             

Gly Trp Gly Asn Ser Lys Asp Pro Tyr Lys Pro Ser Ser Gly Pro Ser 
    130                 135                 140                 

Thr Ala Asp Tyr Pro Gly Glu Val Gln Cys Leu Asp Ala Pro Val Leu 
145                 150                 155                 160 

Ser Gln Thr Lys Cys Glu Ala Ser Tyr Pro Gly Lys Ile Thr Ser Asn 
                165                 170                 175     

Met Phe Cys Ala Gly Phe Leu Glu Gly Gly Lys Asp Ser Cys Gln Gly 
            180                 185                 190         

Asp Ser Gly Gly Pro Val Val Gln Asn Gly Gln Leu Gln Gly Val Val 
        195                 200                 205             

Ser Trp Gly Glu Gly Cys Ala Gln Lys Asn Lys Pro Gly Val Tyr Thr 
    210                 215                 220                 

Asn Val Tyr Asn Tyr Val Glu Trp Ile Gln Asp Thr Ile Ala Ala Asn 
225                 230                 235                 240 

Ser 
    

<210>  6
<211>  241
<212>  PRT
<213>  artificial

<220>
<223>  variant I

<400>  6

Ile Val Gly Gly Tyr Asp Cys Glu Glu Asn Ser Val Pro Tyr His Val 
1               5                   10                  15      


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


Ile Asn Glu Gln Trp Val Val Thr Ala Gly His Cys Tyr Ser Phe Leu 
        35                  40                  45              

Pro Leu Asp Lys Ser Arg Ile Gln Val Arg Leu Gly Met His Ser Thr 
    50                  55                  60                  

Arg Ala Leu Glu Gly Asn Glu Gln Ile Ile Asn Ala Ala Lys Ile Ile 
65                  70                  75                  80  

Arg His Pro Gln Tyr Asp Trp Lys Thr Leu Asn Asn Asp Ile Met Leu 
                85                  90                  95      

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

Ser Leu Pro Thr Ala Pro Pro Ala Ala Gly Thr Lys Cys Leu Ile Ser 
        115                 120                 125             

Gly Trp Gly Asn Ser Lys Asp Pro Tyr Lys Pro Ser Ser Gly Pro Ser 
    130                 135                 140                 

Thr Ala Asp Tyr Pro Gly Glu Val Gln Cys Leu Asp Ala Pro Val Leu 
145                 150                 155                 160 

Ser Gln Thr Lys Cys Glu Ala Ser Tyr Pro Gly Lys Ile Thr Ser Asn 
                165                 170                 175     

Met Phe Cys Ala Gly Phe Leu Glu Gly Gly Lys Asp Thr Cys Gln Gly 
            180                 185                 190         

Asp Ser Gly Gly Pro Val Val Gln Asn Gly Gln Leu Gln Gly Val Val 
        195                 200                 205             

Ser Trp Gly Glu Gly Cys Ala Gln Lys Asn Lys Pro Gly Val Tyr Thr 
    210                 215                 220                 

Asn Val Tyr Asn Tyr Val Glu Trp Ile Gln Asp Thr Ile Ala Ala Asn 
225                 230                 235                 240 

Ser 
    

<210>  7
<211>  244
<212>  PRT
<213>  artificial

<220>
<223>  variant J

<400>  7

Ile Val Gly Gly Tyr Asp Cys Glu Glu Asn Ser Val Pro Tyr His Val 
1               5                   10                  15      

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

Ile Asn Glu Gln Trp Val Val Thr Ala Gly His Cys Tyr Ser Phe Leu 
        35                  40                  45              

Pro Leu Asp Lys Ser Arg Ile Gln Val Arg Leu Gly Val His Ser Thr 
    50                  55                  60                  

Gly Ala Leu Glu Gly Asn Glu Gln Ile Ile Asn Ala Ala Lys Ile Ile 
65                  70                  75                  80  

Arg His Pro Gln Tyr Asp Trp Lys Thr Leu Asn Asn Asp Ile Met Leu 
                85                  90                  95      

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

Ser Leu Pro Thr Ala Pro Pro Ala Pro Gly Thr Lys Cys Leu Ile Ser 
        115                 120                 125             

Gly Trp Gly Asn Ser Lys Gly Pro Arg Asp Pro Tyr Lys Pro Ser Ser 
    130                 135                 140                 

Gly Pro Ser Thr Ala Asp Tyr Pro Gly Glu Val Gln Cys Leu Asp Ala 
145                 150                 155                 160 

Pro Val Leu Ser Gln Thr Lys Cys Glu Ala Ser Tyr Pro Gly Lys Ile 
                165                 170                 175     

Thr Ser Asn Met Phe Cys Ala Gly Phe Leu Glu Gly Gly Lys Asp Ser 
            180                 185                 190         

Cys Gln Gly Asp Ser Gly Gly Pro Val Val Gln Asn Gly Gln Leu Gln 
        195                 200                 205             

Gly Val Val Ser Trp Gly Glu Gly Cys Ala Gln Lys Asn Lys Pro Gly 
    210                 215                 220                 

Val Tyr Thr Asn Val Tyr Asn Tyr Val Glu Trp Ile Gln Asp Thr Ile 
225                 230                 235                 240 

Ala Ala Asn Ser


<210>  8
<211>  244
<212>  PRT
<213>  artificial

<220>
<223>  variant K

<400>  8

Ile Val Gly Gly Tyr Asp Cys Glu Glu Asn Ser Val Pro Tyr His Val 
1               5                   10                  15      

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

Ile Asn Glu Gln Trp Val Val Thr Ala Gly His Cys Tyr Ser Phe Leu 
        35                  40                  45              

Pro Leu Asp Lys Ser Arg Ile Gln Val Arg Leu Gly Val His Ser Thr 
    50                  55                  60                  

Gly Ala Leu Glu Gly Asn Glu Gln Ile Ile Asn Ala Ala Lys Ile Ile 
65                  70                  75                  80  

Arg His Pro Gln Tyr Asp Trp Lys Thr Leu Asn Asn Asp Ile Met Leu 
                85                  90                  95      

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

Ser Leu Pro Thr Ala Pro Pro Ala Pro Gly Thr Lys Cys Leu Ile Ser 
        115                 120                 125             

Gly Trp Gly Asn Ser Lys Asn Pro Gly Ala Leu Tyr Lys Pro Ser Ser 
    130                 135                 140                 

Gly Pro Ser Thr Ala Asp Tyr Pro Gly Glu Val Gln Cys Leu Asp Ala 
145                 150                 155                 160 

Pro Val Leu Ser Gln Thr Lys Cys Glu Ala Ser Tyr Pro Gly Lys Ile 
                165                 170                 175     

Thr Ser Asn Met Phe Cys Ala Gly Phe Leu Glu Gly Gly Lys Asp Ser 
            180                 185                 190         

Cys Gln Gly Asp Ser Gly Gly Pro Val Val Gln Asn Gly Gln Leu Gln 
        195                 200                 205             

Gly Val Val Ser Trp Gly Glu Gly Cys Ala Gln Lys Asn Lys Pro Gly 
    210                 215                 220                 

Val Tyr Thr Asn Val Tyr Asn Tyr Val Glu Trp Ile Gln Asp Thr Ile 
225                 230                 235                 240 

Ala Ala Asn Ser 
                


<210>  9
<211>  241
<212>  PRT
<213>  artificial

<220>
<223>  variant L

<400>  9

Ile Val Gly Gly Tyr Asp Cys Glu Glu Asn Thr Val Pro Tyr His Val 
1               5                   10                  15      

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

Ile Asn Glu Gln Trp Val Val Thr Ala Ser His Cys Tyr Ser Phe Leu 
        35                  40                  45              

Pro Leu Asp Lys Ser Arg Ile Gln Val Arg Leu Gly Met His Ser Thr 
    50                  55                  60                  

Arg Ala Leu Glu Gly Asn Glu Gln Ile Ile Asn Ala Ala Lys Ile Ile 
65                  70                  75                  80  

Arg His Pro Gln Tyr Asp Trp Lys Thr Leu Asn Asn Asp Ile Met Leu 
                85                  90                  95      

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

Ser Leu Pro Thr Ala Pro Pro Ala Ala Gly Thr Met Cys Leu Ile Ser 
        115                 120                 125             

Gly Trp Gly Asn Ser Lys Asp Pro Tyr Lys Pro Ser Ser Gly Pro Ser 
    130                 135                 140                 

Thr Ala Asp Tyr Pro Gly Glu Val Gln Cys Leu Asp Ala Pro Val Leu 
145                 150                 155                 160 

Ser Gln Thr Lys Cys Glu Ala Ser Tyr Pro Gly Lys Ile Thr Ser Asn 
                165                 170                 175     

Met Phe Cys Ala Gly Phe Leu Glu Gly Gly Lys Asp Thr Cys Gln Gly 
            180                 185                 190         

Asp Ser Gly Gly Pro Ala Val Gln Asn Gly Gln Leu Gln Gly Val Val 
        195                 200                 205             

Ser Trp Gly Glu Gly Cys Ala Gln Lys Asn Lys Pro Gly Val Tyr Thr 
    210                 215                 220                 

Asn Val Tyr Asn Tyr Val Glu Trp Ile Gln Asp Thr Ile Ala Ala Asn 
225                 230                 235                 240 

Ser


<210>  10
<211>  241
<212>  PRT
<213>  artificial

<220>
<223>  variant M

<400>  10

Ile Val Gly Gly Tyr Asp Cys Glu Glu Asn Ser Val Pro Tyr His Val 
1               5                   10                  15      

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

Ile Asn Glu Gln Trp Val Val Thr Ala Ser His Cys Tyr Ser Phe Leu 
        35                  40                  45              

Pro Leu Asp Lys Ser Arg Thr Gln Val Arg Leu Gly Met His Ser Thr 
    50                  55                  60                  

Gly Ala Leu Glu Gly Asn Glu Gln Ile Ile Asp Val Ala Lys Ile Ile 
65                  70                  75                  80  

Arg His Pro Gln Tyr Asp Trp Lys Thr Leu Asn Asn Asp Ile Met Leu 
                85                  90                  95      

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

Ser Leu Pro Thr Ala Pro Pro Ala Ala Gly Thr Met Cys Leu Val Ser 
        115                 120                 125             

Gly Trp Gly Asn Ser Lys Asp Pro Tyr Lys Pro Ser Ser Gly Pro Pro 
    130                 135                 140                 

Thr Ala Asp Tyr Pro Gly Glu Val Gln Cys Leu Asp Ala Pro Val Leu 
145                 150                 155                 160 

Ser Gln Thr Lys Cys Glu Ala Ser Tyr Pro Gly Lys Ile Thr Ser Asn 
                165                 170                 175     

Met Phe Cys Ala Gly Phe Leu Glu Gly Gly Lys Asp Thr Cys Gln Gly 
            180                 185                 190         

Asp Ser Gly Gly Pro Ala Val Gln Asp Gly Gln Leu Gln Gly Val Val 
        195                 200                 205             

Ser Trp Gly Glu Gly Cys Ala Gln Lys Asn Lys Pro Gly Val Tyr Thr 
    210                 215                 220                 

Asn Val Tyr Asn Tyr Val Glu Trp Ile Arg Asp Thr Ile Ala Ala Asn 
225                 230                 235                 240 

Ser 


<210>  11

<211>  157
<212>  PRT
<213>  homo sapiens

<400>  11

Val Arg Ser Ser Ser Arg Thr Pro Ser Asp Lys Pro Val Ala His Val 
1               5                   10                  15      

Val Ala Asn Pro Gln Ala Glu Gly Gln Leu Gln Trp Leu Asn Arg Arg 
            20                  25                  30          

Ala Asn Ala Leu Leu Ala Asn Gly Val Glu Leu Arg Asp Asn Gln Leu 
        35                  40                  45              

Val Val Pro Ser Glu Gly Leu Tyr Leu Ile Tyr Ser Gln Val Leu Phe 
    50                  55                  60                  

Lys Gly Gln Gly Cys Pro Ser Thr His Val Leu Leu Thr His Thr Ile 
65                  70                  75                  80  

Ser Arg Ile Ala Val Ser Tyr Gln Thr Lys Val Asn Leu Leu Ser Ala 
                85                  90                  95      

Ile Lys Ser Pro Cys Gln Arg Glu Thr Pro Glu Gly Ala Glu Ala Lys 
            100                 105                 110         

Pro Trp Tyr Glu Pro Ile Tyr Leu Gly Gly Val Phe Gln Leu Glu Lys 
        115                 120                 125             

Gly Asp Arg Leu Ser Ala Glu Ile Asn Arg Pro Asp Tyr Leu Asp Phe 
    130                 135                 140                 

Ala Glu Ser Gly Gln Val Tyr Phe Gly Ile Ile Ala Leu 
145                 150                 155         


<210>  12
<211>  159
<212>  PRT
<213>  artificial

<220>
<223>  cloned human TNF-alpha

<400>  12

Met Ala His His His His Val Cys Thr Pro Ser Asp Lys Pro Val Ala 
1               5                   10                  15      

His Val Val Ala Asn Pro Gln Ala Glu Gly Gln Leu Gln Trp Leu Asn 
            20                  25                  30          

Arg Arg Ala Asn Ala Leu Leu Ala Asn Gly Val Glu Leu Arg Asp Asn 
        35                  40                  45              

Gln Leu Val Val Pro Ser Glu Gly Leu Tyr Leu Ile Tyr Ser Gln Val 
    50                  55                  60                  

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

Thr Ile Ser Arg Ile Ala Val Ser Tyr Gln Thr Lys Val Asn Leu Leu 
                85                  90                  95      

Ser Ala Ile Lys Ser Pro Cys Gln Arg Glu Thr Pro Glu Gly Ala Glu 
            100                 105                 110         

Ala Lys Pro Trp Tyr Glu Pro Ile Tyr Leu Gly Gly Val Phe Gln Leu 
        115                 120                 125             

Glu Lys Gly Asp Arg Leu Ser Ala Glu Ile Asn Arg Pro Asp Tyr Leu 
    130                 135                 140                 

Leu Phe Ala Glu Ser Gly Gln Val Tyr Phe Gly Ile Ile Ala Leu 
145                 150                 155                 


<210>  13
<211>  16
<212>  PRT
<213>  artificial

<220>
<223>  assay peptide

<400>  13

Gly Gln Leu Gln Trp Leu Asn Arg Arg Ala Asn Ala Leu Leu Ala Cys 
1               5                   10                  15      


<210>  14
<211>  29
<212>  DNA
<213>  artificial

<220>
<223>  primer A

<400>  14
tggcaggagg ggccactcag gcctttgca                                       29


<210>  15
<211>  26
<212>  DNA
<213>  artificial

<220>
<223>  primer B

<400>  15
cacctagtgg cctagtcggc cttagc                                          26


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

<220>
<223>  general SDR2 sequence


<220>
<221>  MISC_FEATURE
<222>  (1)..()
<223>  Xaa= small or charged amino acid

<220>
<221>  MISC_FEATURE
<222>  (2)..()
<223>  Xaa= P, N or hydrophobic amino acid

<220>
<221>  MISC_FEATURE
<222>  (3)..()
<223>  Xaa= hydrophobic amino acid

<220>
<221>  MISC_FEATURE
<222>  (4)..()
<223>  Xaa= P, D, N or hydrophobic amino acid

<220>
<221>  MISC_FEATURE
<222>  (5)..()
<223>  Xaa= P, T, R or hydrophobic amino acid

<220>
<221>  MISC_FEATURE
<222>  (6)..()
<223>  Xaa= A, L or polar amino acid

<400>  16

Xaa Xaa Xaa Xaa Xaa Xaa 
1               5       


<210>  17
<211>  5
<212>  PRT
<213>  artificial

<220>
<223>  general SDR3 sequence


<220>
<221>  MISC_FEATURE
<222>  (1)..()
<223>  Xaa= L, R or small amino acid

<220>
<221>  MISC_FEATURE
<222>  (2)..()
<223>  Xaa= V, T, S, A, M, G or positive amino acid

<220>
<221>  MISC_FEATURE
<222>  (3)..()
<223>  Xaa= D, A, P, T, N, G, E, L, Q, V, S, R

<220>
<221>  MISC_FEATURE
<222>  (4)..()
<223>  Xaa= F, P, S, D, V, Q, T, R, L, I, Y

<220>
<221>  MISC_FEATURE
<222>  (5)..()
<223>  Xaa= peptidic moiety having 1 to 4 arbitrary amino acids

<400>  17

Xaa Xaa Xaa Xaa Xaa 
1               5   


<210>  18
<211>  4
<212>  PRT
<213>  artificial

<220>
<223>  SDR3 fragment

<400>  18

Arg Asp Pro Tyr 
1               


<210>  19
<211>  4
<212>  PRT
<213>  artificial

<220>
<223>  SDR3 fragment

<400>  19

Gly Ala Leu Tyr 
1               


<210>  20
<211>  6
<212>  PRT
<213>  artificial

<220>
<223>  SDR2a

<400>  20

Ala Phe Phe Pro Ala Asp 
1               5       


<210>  21
<211>  6
<212>  PRT
<213>  artificial

<220>
<223>  SDR2b

<400>  21

Ser Phe Leu Pro Leu Asp 
1               5       


<210>  22
<211>  5
<212>  PRT
<213>  artificial

<220>
<223>  SDR3a

<400>  22

Ser Lys Asp Pro Tyr 
1               5   


<210>  23
<211>  8
<212>  PRT
<213>  artificial

<220>
<223>  SDR3b

<400>  23

Ser Lys Gly Pro Arg Asp Pro Tyr 
1               5               


<210>  24
<211>  8
<212>  PRT
<213>  artificial

<220>
<223>  SDR3c

<400>  24

Ser Lys Asn Pro Gly Ala Leu Tyr 
1               5               


<210>  25
<211>  224
<212>  PRT
<213>  Homo sapiens

<400>  25

Ile Val Gly Gly Tyr Ile Cys Glu Glu Asn Ser Val Pro Tyr Gln Val 
1               5                   10                  15      

Ser Leu Asn Ser Gly Tyr His Phe Cys Gly Gly Ser Leu Ile Ser Glu 
            20                  25                  30          

Gln Trp Val Val Ser Ala Gly His Cys Tyr Lys Ser Arg Ile Gln Val 
        35                  40                  45              

Arg Leu Gly Glu His Asn Ile Glu Val Leu Glu Gly Asn Glu Gln Phe 
    50                  55                  60                  

Ile Asn Ala Ala Lys Ile Ile Arg His Pro Lys Tyr Asn Ser Arg Thr 
65                  70                  75                  80  

Leu Asp Asn Asp Ile Leu Leu Ile Lys Leu Ser Ser Pro Ala Val Ile 
                85                  90                  95      

Asn Ser Arg Val Ser Ala Ile Ser Leu Pro Thr Ala Pro Pro Ala Ala 
            100                 105                 110         

Gly Thr Glu Ser Leu Ile Ser Gly Trp Gly Asn Thr Leu Ser Ser Gly 
        115                 120                 125             

Ala Asp Tyr Pro Asp Glu Leu Gln Cys Leu Asp Ala Pro Val Leu Ser 
    130                 135                 140                 

Gln Ala Glu Cys Glu Ala Ser Tyr Pro Gly Lys Ile Thr Asn Asn Met 
145                 150                 155                 160 

Phe Cys Val Gly Phe Leu Glu Gly Gly Lys Asp Ser Cys Gln Gly Asp 
                165                 170                 175     

Ser Gly Gly Pro Val Val Ser Asn Gly Glu Leu Gln Gly Ile Val Ser 
            180                 185                 190         

Trp Gly Tyr Gly Cys Ala Gln Lys Asn Arg Pro Gly Val Tyr Thr Lys 
        195                 200                 205             

Val Tyr Asn Tyr Val Asp Trp Ile Lys Asp Thr Ile Ala Ala Asn Ser 
    210                 215                 220                 


<210>  26
<211>  224
<212>  PRT
<213>  Homo sapiens

<400>  26

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

Ser Leu Asn Ser Gly Ser His Phe Cys Gly Gly Ser Leu Ile Ser Glu 
            20                  25                  30          

Gln Trp Val Val Ser Ala Ala His Cys Tyr Lys Thr Arg Ile Gln Val 
        35                  40                  45              

Arg Leu Gly Glu His Asn Ile Lys Val Leu Glu Gly Asn Glu Gln Phe 
    50                  55                  60                  

Ile Asn Ala Ala Lys Ile Ile Arg His Pro Lys Tyr Asn Arg Asp Thr 
65                  70                  75                  80  

Leu Asp Asn Asp Ile Met Leu Ile Lys Leu Ser Ser Pro Ala Val Ile 
                85                  90                  95      

Asn Ala Arg Val Ser Thr Ile Ser Leu Pro Thr Ala Pro Pro Ala Ala 
            100                 105                 110         

Gly Thr Glu Cys Leu Ile Ser Gly Trp Gly Asn Thr Leu Ser Phe Gly 
        115                 120                 125             

Ala Asp Tyr Pro Asp Glu Leu Lys Cys Leu Asp Ala Pro Val Leu Thr 
    130                 135                 140                 

Gln Ala Glu Cys Lys Ala Ser Tyr Pro Gly Lys Ile Thr Asn Ser Met 
145                 150                 155                 160 

Phe Cys Val Gly Phe Leu Glu Gly Gly Lys Asp Ser Cys Gln Arg Asp 
                165                 170                 175     

Ser Gly Gly Pro Val Val Cys Asn Gly Gln Leu Gln Gly Val Val Ser 
            180                 185                 190         

Trp Gly His Gly Cys Ala Trp Lys Asn Arg Pro Gly Val Tyr Thr Lys 
        195                 200                 205             

Val Tyr Asn Tyr Val Asp Trp Ile Lys Asp Thr Ile Ala Ala Asn Ser 
    210                 215                 220                 


<210>  27
<211>  50
<212>  DNA
<213>  artificial

<220>
<223>  primer AF

<400>  27
ctggcaggag gggccactca ggcctttgca atcgttgggg gctacaactg                50


<210>  28
<211>  23
<212>  DNA
<213>  artificial

<220>
<223>  primer AR

<400>  28
gtagcagtgg cccgcggata cca                                             23


<210>  29
<211>  18
<212>  DNA
<213>  artificial

<220>
<223>  primer BF

<400>  29
aagtcccgga tccaggtg                                                   18


<210>  30
<211>  19
<212>  DNA
<213>  artificial

<220>
<223>  primer BR

<400>  30
gttgccccag ccagagatg                                                  19


<210>  31
<211>  21
<212>  DNA
<213>  artificial

<220>
<223>  primer CF

<400>  31
gtcggcgcca gagctagcag t                                               21


<210>  32
<211>  44
<212>  DNA
<213>  artificial

<220>
<223>  primer CR

<400>  32
acacctagtg gcctagtcgg ccttagctat tggcagctat ggtg                      44


<210>  33
<211>  59
<212>  DNA
<213>  artificial

<220>
<223>  primer DF


<220>
<221>  misc_feature
<222>  (24)..(40)
<223>  n= a, t, c, g

<220>
<221>  misc_feature
<222>  (26)..(41)
<223>  b= t, c, g

<400>  33
tggtatccgc gggccactgc tacnnbnnbn nbnnbnnbnn baagtcccgg atccaggtg      59


<210>  34
<211>  52
<212>  DNA
<213>  artificial

<220>
<223>  primer DR


<220>
<221>  misc_feature
<222>  (19)..(31)
<223>  v= g, c, a

<220>
<221>  misc_feature
<222>  (20)..(33)
<223>  n= a, t, c, g

<400>  34
ggcgccagag ctagcagtvn nvnnvnnvnn vnngttgccc cagccagaga tg             52





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