﻿               SEQUENCE LISTING

<110> Université Pierre-et-Marie-Curie
      Centre National de la Recherche Scientifique
      Institut National de la Santé et de la Recherche Médicale
      SENNLAUB Florian
      HOUSSET Michael
      GUILLONEAU Xavier
      SAHEL José-Alain
      KAROYAN Philippe

<120> AGENTS THAT ACTIVATE CD47 AND THEIR USE IN THE TREATMENT OF INFLAMMATION

<130> CV - 582/PCT

<160> 14

<170> BiSSAP 1.3.6

<210> 1
<211> 10
<212> PRT
<213> Artificial Sequence


<220> 
<223> 4N1K peptide

<400> 1
Lys Arg Phe Tyr Val Val Met Trp Lys Lys 
1               5                   10  

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


<220> 
<223> Peptide linker

<400> 2
Gly Gly Gly Lys Gly Gly Gly Gly 
1               5               

<210> 3
<211> 8
<212> PRT
<213> Artificial Sequence


<220> 
<223> Peptide linker

<400> 3
Gly Gly Gly Asn Gly Ser Gly Gly 
1               5               

<210> 4
<211> 8
<212> PRT
<213> Artificial Sequence


<220> 
<223> Peptide linker

<400> 4
Gly Gly Gly Cys Gly Gly Gly Gly 
1               5               

<210> 5
<211> 4
<212> PRT
<213> Artificial Sequence


<220> 
<223> Peptide linker

<400> 5
Gly Pro Asn Gly 
1               

<210> 6
<211> 8
<212> PRT
<213> Artificial Sequence


<220> 
<223> Peptide linker

<400> 6
Gly Gly Gly Gly Gly Gly Gly Gly 
1               5               

<210> 7
<211> 28
<212> PRT
<213> Artificial Sequence


<220> 
<223> 4N1K dimer

<400> 7
Lys Arg Phe Tyr Val Val Met Trp Lys Lys Gly Gly Gly Gly Gly Gly 
1               5                   10                  15      
Gly Gly Lys Arg Phe Tyr Val Val Met Trp Lys Lys 
            20                  25              

<210> 8
<211> 369
<212> PRT
<213> Homo sapiens


<220> 
<223> TSP-1 C-terminal

<400> 8
Met Ala Cys Pro Gly Phe Leu Trp Ala Leu Val Ile Ser Thr Cys Leu 
1               5                   10                  15      
Glu Phe Ser Met Ala Asp Tyr Lys Asp Asp Asp Asp Lys Ala Leu Ala 
            20                  25                  30          
Asp Cys Cys Pro Leu Glu His Asn Pro Asp Gln Leu Asp Ser Asp Ser 
        35                  40                  45              
Asp Arg Ile Gly Asp Thr Cys Asp Asn Asn Gln Asp Ile Asp Glu Asp 
    50                  55                  60                  
Gly His Gln Asn Asn Leu Asp Asn Cys Pro Tyr Val Pro Asn Ala Asn 
65                  70                  75                  80  
Gln Ala Asp His Asp Lys Asp Gly Lys Gly Asp Ala Cys Asp His Asp 
                85                  90                  95      
Asp Asp Asn Asp Gly Ile Pro Asp Asp Lys Asp Asn Cys Arg Leu Val 
            100                 105                 110         
Pro Asn Pro Asp Gln Lys Asp Ser Asp Gly Asp Gly Arg Gly Asp Ala 
        115                 120                 125             
Cys Lys Asp Asp Phe Asp His Asp Ser Val Pro Asp Ile Asp Asp Ile 
    130                 135                 140                 
Cys Pro Glu Asn Val Asp Ile Ser Glu Thr Asp Phe Arg Arg Phe Gln 
145                 150                 155                 160 
Met Ile Pro Leu Asp Pro Lys Gly Thr Ser Gln Asn Asp Pro Asn Trp 
                165                 170                 175     
Val Val Arg His Gln Gly Lys Glu Leu Val Gln Thr Val Asn Cys Asp 
            180                 185                 190         
Pro Gly Leu Ala Val Gly Tyr Asp Glu Phe Asn Ala Val Asp Phe Ser 
        195                 200                 205             
Gly Thr Phe Phe Ile Asn Thr Glu Arg Asp Asp Asp Tyr Ala Gly Phe 
    210                 215                 220                 
Val Phe Gly Tyr Gln Ser Ser Ser Arg Phe Tyr Val Val Met Trp Lys 
225                 230                 235                 240 
Gln Val Thr Gln Ser Tyr Trp Asp Thr Asn Pro Thr Arg Ala Gln Gly 
                245                 250                 255     
Tyr Ser Gly Leu Ser Val Lys Val Val Asn Ser Thr Thr Gly Pro Gly 
            260                 265                 270         
Glu His Leu Arg Asn Ala Leu Trp His Thr Gly Asn Thr Pro Gly Gln 
        275                 280                 285             
Val Arg Thr Leu Trp His Asp Pro Arg His Ile Gly Trp Lys Asp Phe 
    290                 295                 300                 
Thr Ala Tyr Arg Trp Arg Leu Ser His Arg Pro Lys Thr Gly Phe Ile 
305                 310                 315                 320 
Arg Val Val Met Tyr Glu Gly Lys Lys Ile Met Ala Asp Ser Gly Pro 
                325                 330                 335     
Ile Tyr Asp Lys Thr Tyr Ala Gly Gly Arg Leu Gly Leu Phe Val Phe 
            340                 345                 350         
Ser Gln Glu Met Val Phe Phe Ser Asp Leu Lys Tyr Glu Cys Arg Asp 
        355                 360                 365             
Pro 
    

<210> 9
<211> 365
<212> PRT
<213> Artificial Sequence


<220> 
<223> Modified TSP-1 C-terminal

<400> 9
Met Ala Cys Pro Gly Phe Leu Trp Ala Leu Val Ile Ser Thr Cys Leu 
1               5                   10                  15      
Glu Phe Ser Met Ala Asp Tyr Lys Asp Asp Asp Asp Lys Ala Leu Cys 
            20                  25                  30          
Asp Asn Cys Pro Leu Glu His Asn Pro Asp Gln Leu Asp Ser Asp Ser 
        35                  40                  45              
Asp Arg Ile Gly Asp Thr Cys Asp Asn Asn Gln Asp Ile Asp Glu Asp 
    50                  55                  60                  
Gly His Gln Asn Asn Leu Asp Asn Cys Pro Tyr Val Pro Asn Ala Asn 
65                  70                  75                  80  
Gln Ala Asp His Asp Lys Asp Gly Lys Gly Asp Ala Cys Asp His Asp 
                85                  90                  95      
Asp Asp Asn Asp Gly Ile Pro Asp Asp Lys Asp Asn Cys Arg Leu Val 
            100                 105                 110         
Pro Asn Pro Asp Gln Lys Asp Ser Asp Gly Asp Gly Arg Gly Asp Ala 
        115                 120                 125             
Cys Lys Asp Asp Phe Asp His Asp Ser Val Pro Asp Ile Asp Asp Ile 
    130                 135                 140                 
Cys Pro Glu Asn Val Asp Ile Ser Glu Thr Asp Phe Arg Arg Phe Gln 
145                 150                 155                 160 
Met Ile Pro Leu Asp Pro Lys Gly Thr Ser Gln Asn Asp Pro Asn Trp 
                165                 170                 175     
Val Val Arg His Gln Gly Lys Glu Leu Val Gln Thr Val Asn Cys Asp 
            180                 185                 190         
Pro Gly Leu Ala Val Gly Tyr Asp Glu Phe Asn Ala Val Asp Phe Ser 
        195                 200                 205             
Gly Thr Phe Phe Ile Asn Thr Glu Arg Asp Asp Asp Tyr Ala Gly Phe 
    210                 215                 220                 
Val Phe Gly Tyr Gln Ser Ser Ser Arg Phe Tyr Val Val Met Trp Lys 
225                 230                 235                 240 
Gln Gln Ser Tyr Trp Asp Thr Asn Pro Thr Arg Ala Gln Gly Tyr Ser 
                245                 250                 255     
Gly Leu Ser Val Lys Val Val Asn Ser Thr Thr Gly Pro Gly Glu His 
            260                 265                 270         
Leu Arg Asn Ala Leu Trp His Thr Gly Asn Thr Pro Gly Arg Thr Leu 
        275                 280                 285             
Trp His Asp Pro Arg His Ile Gly Trp Lys Asp Phe Thr Ala Tyr Arg 
    290                 295                 300                 
Trp Arg Leu Ser His Arg Pro Lys Thr Gly Phe Ile Arg Val Val Met 
305                 310                 315                 320 
Tyr Glu Gly Lys Lys Ile Met Ala Asp Ser Gly Pro Ile Tyr Asp Lys 
                325                 330                 335     
Thr Tyr Ala Gly Gly Arg Leu Gly Leu Phe Val Phe Ser Gln Glu Met 
            340                 345                 350         
Val Phe Phe Ser Asp Leu Lys Tyr Glu Cys Arg Asp Pro 
        355                 360                 365 

<210> 10
<211> 365
<212> PRT
<213> Artificial Sequence


<220> 
<223> Modified TSP-1 C-terminal

<400> 10
Met Ala Cys Pro Gly Phe Leu Trp Ala Leu Val Ile Ser Thr Cys Leu 
1               5                   10                  15      
Glu Phe Ser Met Ala Asp Tyr Lys Asp Asp Asp Asp Lys Ala Leu Ala 
            20                  25                  30          
Asp Asn Cys Pro Leu Glu His Asn Pro Asp Gln Leu Asp Ser Asp Ser 
        35                  40                  45              
Asp Arg Ile Gly Asp Thr Cys Asp Asn Asn Gln Asp Ile Asp Glu Asp 
    50                  55                  60                  
Gly His Gln Asn Asn Leu Asp Asn Cys Pro Tyr Val Pro Asn Ala Asn 
65                  70                  75                  80  
Gln Ala Asp His Asp Lys Asp Gly Lys Gly Asp Ala Cys Asp His Asp 
                85                  90                  95      
Asp Asp Asn Asp Gly Ile Pro Asp Asp Lys Asp Asn Cys Arg Leu Val 
            100                 105                 110         
Pro Asn Pro Asp Gln Lys Asp Ser Asp Gly Asp Gly Arg Gly Asp Ala 
        115                 120                 125             
Cys Lys Asp Asp Phe Asp His Asp Ser Val Pro Asp Ile Asp Asp Ile 
    130                 135                 140                 
Cys Pro Glu Asn Val Asp Ile Ser Glu Thr Asp Phe Arg Arg Phe Gln 
145                 150                 155                 160 
Met Ile Pro Leu Asp Pro Lys Gly Thr Ser Gln Asn Asp Pro Asn Trp 
                165                 170                 175     
Val Val Arg His Gln Gly Lys Glu Leu Val Gln Thr Val Asn Ser Asp 
            180                 185                 190         
Pro Gly Leu Ala Val Gly Tyr Asp Glu Phe Asn Ala Val Asp Phe Ser 
        195                 200                 205             
Gly Thr Phe Phe Ile Asn Thr Glu Arg Asp Asp Asp Tyr Ala Gly Phe 
    210                 215                 220                 
Val Phe Gly Tyr Gln Ser Ser Ser Arg Phe Tyr Val Val Met Trp Lys 
225                 230                 235                 240 
Gln Gln Ser Tyr Trp Asp Thr Asn Pro Thr Arg Ala Gln Gly Tyr Ser 
                245                 250                 255     
Gly Leu Ser Val Lys Val Val Lys Ser Thr Thr Gly Pro Gly Glu His 
            260                 265                 270         
Leu Arg Asn Ala Leu Trp His Thr Gly Asn Thr Pro Gly Arg Thr Leu 
        275                 280                 285             
Trp His Asp Pro Arg His Ile Gly Trp Lys Asp Phe Thr Ala Tyr Arg 
    290                 295                 300                 
Trp Arg Leu Ser His Arg Pro Lys Thr Gly Phe Ile Arg Val Val Met 
305                 310                 315                 320 
Tyr Glu Gly Lys Lys Ile Met Ala Asp Ser Gly Pro Ile Tyr Asp Lys 
                325                 330                 335     
Thr Tyr Ala Gly Gly Arg Leu Gly Leu Phe Val Phe Ser Gln Glu Met 
            340                 345                 350         
Val Phe Phe Ser Asp Leu Lys Tyr Glu Cys Arg Asp Pro 
        355                 360                 365 

<210> 11
<211> 369
<212> PRT
<213> Artificial Sequence


<220> 
<223> Modified TSP-1 C-terminal

<400> 11
Met Ala Cys Pro Gly Phe Leu Trp Ala Leu Val Ile Ser Thr Cys Leu 
1               5                   10                  15      
Glu Phe Ser Met Ala Asp Tyr Lys Asp Asp Asp Asp Lys Ala Leu Cys 
            20                  25                  30          
Asp Asn Cys Pro Leu Glu His Asn Pro Asp Gln Leu Asp Ser Asp Ser 
        35                  40                  45              
Asp Arg Ile Gly Asp Thr Cys Asp Asn Asn Gln Asp Ile Asp Glu Asp 
    50                  55                  60                  
Gly His Gln Asn Asn Leu Asp Asn Cys Pro Tyr Val Pro Asn Ala Asn 
65                  70                  75                  80  
Gln Ala Asp His Asp Lys Asp Gly Lys Gly Asp Ala Cys Asp His Asp 
                85                  90                  95      
Asp Asp Asn Asp Gly Ile Pro Asp Asp Lys Asp Asn Cys Arg Leu Val 
            100                 105                 110         
Pro Asn Pro Asp Gln Lys Asp Ser Asp Gly Asp Gly Arg Gly Asp Ala 
        115                 120                 125             
Cys Lys Asp Asp Phe Asp His Asp Ser Val Pro Asp Ile Asp Asp Ile 
    130                 135                 140                 
Cys Pro Glu Asn Val Asp Ile Ser Glu Thr Asp Phe Arg Arg Phe Gln 
145                 150                 155                 160 
Met Ile Pro Leu Asp Pro Lys Gly Thr Ser Gln Asn Asp Pro Asn Trp 
                165                 170                 175     
Val Val Arg His Gln Gly Lys Glu Leu Val Gln Thr Val Asn Cys Asp 
            180                 185                 190         
Pro Gly Leu Ala Val Gly Tyr Asp Glu Phe Asn Ala Val Asp Phe Ser 
        195                 200                 205             
Gly Thr Phe Phe Ile Asn Thr Glu Arg Asp Asp Asp Tyr Ala Gly Phe 
    210                 215                 220                 
Val Phe Gly Tyr Gln Ser Ser Ser Arg Phe Tyr Val Val Met Trp Lys 
225                 230                 235                 240 
Gln Asn Thr Gln Ser Tyr Trp Asp Thr Asn Pro Thr Arg Ala Gln Gly 
                245                 250                 255     
Tyr Ser Gly Leu Ser Val Lys Val Val Asn Ser Thr Thr Gly Pro Gly 
            260                 265                 270         
Glu His Leu Arg Asn Ala Leu Trp His Thr Gly Asn Thr Pro Gly Gln 
        275                 280                 285             
Asn Arg Thr Leu Trp His Asp Pro Arg His Ile Gly Trp Lys Asp Phe 
    290                 295                 300                 
Thr Ala Tyr Arg Trp Arg Leu Ser His Arg Pro Lys Thr Gly Phe Ile 
305                 310                 315                 320 
Arg Val Val Met Tyr Glu Gly Lys Lys Ile Met Ala Asp Ser Gly Pro 
                325                 330                 335     
Ile Tyr Asp Lys Thr Tyr Ala Gly Gly Arg Leu Gly Leu Phe Val Phe 
            340                 345                 350         
Ser Gln Glu Met Val Phe Phe Ser Asp Leu Lys Tyr Glu Cys Arg Asp 
        355                 360                 365             
Pro 
    

<210> 12
<211> 369
<212> PRT
<213> Artificial Sequence


<220> 
<223> Modified TSP-1 C-terminal

<400> 12
Met Ala Cys Pro Gly Phe Leu Trp Ala Leu Val Ile Ser Thr Cys Leu 
1               5                   10                  15      
Glu Phe Ser Met Ala Asp Tyr Lys Asp Asp Asp Asp Lys Ala Leu Ala 
            20                  25                  30          
Asp Asn Cys Pro Leu Glu His Asn Pro Asp Gln Leu Asp Ser Asp Ser 
        35                  40                  45              
Asp Arg Ile Gly Asp Thr Cys Asp Asn Asn Gln Asp Ile Asp Glu Asp 
    50                  55                  60                  
Gly His Gln Asn Asn Leu Asp Asn Cys Pro Tyr Val Pro Asn Ala Asn 
65                  70                  75                  80  
Gln Ala Asp His Asp Lys Asp Gly Lys Gly Asp Ala Cys Asp His Asp 
                85                  90                  95      
Asp Asp Asn Asp Gly Ile Pro Asp Asp Lys Asp Asn Cys Arg Leu Val 
            100                 105                 110         
Pro Asn Pro Asp Gln Lys Asp Ser Asp Gly Asp Gly Arg Gly Asp Ala 
        115                 120                 125             
Cys Lys Asp Asp Phe Asp His Asp Ser Val Pro Asp Ile Asp Asp Ile 
    130                 135                 140                 
Cys Pro Glu Asn Val Asp Ile Ser Glu Thr Asp Phe Arg Arg Phe Gln 
145                 150                 155                 160 
Met Ile Pro Leu Asp Pro Lys Gly Thr Ser Gln Asn Asp Pro Asn Trp 
                165                 170                 175     
Val Val Arg His Gln Gly Lys Glu Leu Val Gln Thr Val Asn Ser Asp 
            180                 185                 190         
Pro Gly Leu Ala Val Gly Tyr Asp Glu Phe Asn Ala Val Asp Phe Ser 
        195                 200                 205             
Gly Thr Phe Phe Ile Asn Thr Glu Arg Asp Asp Asp Tyr Ala Gly Phe 
    210                 215                 220                 
Val Phe Gly Tyr Gln Ser Ser Ser Arg Phe Tyr Val Val Met Trp Lys 
225                 230                 235                 240 
Gln Asn Thr Gln Ser Tyr Trp Asp Thr Asn Pro Thr Arg Ala Gln Gly 
                245                 250                 255     
Tyr Ser Gly Leu Ser Val Lys Val Val Lys Ser Thr Thr Gly Pro Gly 
            260                 265                 270         
Glu His Leu Arg Asn Ala Leu Trp His Thr Gly Asn Thr Pro Gly Gln 
        275                 280                 285             
Asn Arg Thr Leu Trp His Asp Pro Arg His Ile Gly Trp Lys Asp Phe 
    290                 295                 300                 
Thr Ala Tyr Arg Trp Arg Leu Ser His Arg Pro Lys Thr Gly Phe Ile 
305                 310                 315                 320 
Arg Val Val Met Tyr Glu Gly Lys Lys Ile Met Ala Asp Ser Gly Pro 
                325                 330                 335     
Ile Tyr Asp Lys Thr Tyr Ala Gly Gly Arg Leu Gly Leu Phe Val Phe 
            340                 345                 350         
Ser Gln Glu Met Val Phe Phe Ser Asp Leu Lys Tyr Glu Cys Arg Asp 
        355                 360                 365             
Pro 
    

<210> 13
<211> 1168
<212> PRT
<213> Artificial Sequence


<220> 
<223> HTRA1-resistant modified TSP1

<400> 13
Leu Ala Trp Gly Leu Gly Val Leu Phe Leu Met His Val Cys Gly Thr 
1               5                   10                  15      
Asn Arg Ile Pro Glu Ser Gly Gly Asp Asn Ser Val Phe Asp Ile Phe 
            20                  25                  30          
Glu Leu Thr Gly Ala Ala Arg Lys Gly Ser Gly Arg Arg Leu Val Lys 
        35                  40                  45              
Gly Pro Asp Pro Ser Ser Pro Ala Phe Arg Ile Glu Asp Ala Asn Leu 
    50                  55                  60                  
Ile Pro Pro Val Pro Asp Asp Lys Phe Gln Asp Leu Val Asp Ala Val 
65                  70                  75                  80  
Arg Ala Glu Lys Gly Phe Leu Leu Leu Ala Ser Leu Arg Gln Met Lys 
                85                  90                  95      
Lys Thr Arg Gly Thr Leu Leu Ala Leu Glu Arg Lys Asp His Ser Gly 
            100                 105                 110         
Gln Val Phe Ser Val Val Ser Asn Gly Lys Ala Gly Thr Leu Asp Leu 
        115                 120                 125             
Ser Leu Thr Val Gln Gly Lys Gln His Val Val Ser Val Glu Glu Ala 
    130                 135                 140                 
Leu Leu Ala Thr Gly Gln Trp Lys Ser Ile Thr Leu Phe Val Gln Glu 
145                 150                 155                 160 
Asp Arg Ala Gln Leu Tyr Ile Asp Cys Glu Lys Met Glu Asn Ala Glu 
                165                 170                 175     
Leu Asp Val Pro Ile Gln Ser Val Phe Thr Arg Asp Leu Ala Ser Lys 
            180                 185                 190         
Ser Arg Met Tyr Val Ala Lys Gly Ser Ala Arg Glu Ser His Phe Arg 
        195                 200                 205             
Gly Leu Leu Gln Asn Val His Leu Val Phe Glu Asn Ser Val Glu Asp 
    210                 215                 220                 
Ile Leu Ser Lys Lys Gly Cys Gln Gln Gly Thr Ser Val Leu Leu Thr 
225                 230                 235                 240 
Leu Asp Asn Asn Val Val Asn Gly Ser Ser Pro Ala Ile Arg Thr Asn 
                245                 250                 255     
Tyr Ile Gly His Lys Thr Lys Asp Leu Gln Ala Ile Cys Gly Ile Ser 
            260                 265                 270         
Cys Asp Glu Leu Ser Ser Met Val Leu Glu Leu Arg Gly Leu Arg Thr 
        275                 280                 285             
Ile Val Thr Thr Leu Gln Asp Ser Ile Arg Lys Val Thr Glu Glu Asn 
    290                 295                 300                 
Lys Glu Leu Ala Asn Glu Leu Arg Arg Pro Pro Leu Cys Tyr His Asn 
305                 310                 315                 320 
Gly Val Gln Tyr Arg Asn Asn Glu Glu Trp Thr Val Asp Ser Cys Thr 
                325                 330                 335     
Glu Cys His Cys Gln Asn Ser Val Thr Ile Cys Lys Lys Val Ser Cys 
            340                 345                 350         
Pro Ile Met Pro Cys Ser Asn Ala Thr Val Pro Asp Gly Glu Cys Cys 
        355                 360                 365             
Pro Arg Cys Trp Pro Ser Asp Ser Ala Asp Asp Gly Trp Ser Pro Trp 
    370                 375                 380                 
Ser Glu Trp Thr Ser Cys Ser Thr Ser Cys Gly Asn Gly Ile Gln Gln 
385                 390                 395                 400 
Arg Gly Arg Ser Cys Asp Ser Leu Asn Asn Arg Cys Leu Gly Pro Ser 
                405                 410                 415     
Ile Gln Thr Arg Ala Cys Ser Leu Ser Lys Cys Asp Thr Arg Ile Arg 
            420                 425                 430         
Gln Asp Gly Gly Trp Ser His Trp Ser Pro Trp Ser Ser Cys Ser Val 
        435                 440                 445             
Thr Cys Gly Asp Gly Val Ile Thr Arg Ile Arg Leu Cys Asn Ser Pro 
    450                 455                 460                 
Ser Pro Gln Met Asn Gly Lys Pro Cys Glu Gly Glu Ala Arg Glu Thr 
465                 470                 475                 480 
Lys Ala Cys Lys Lys Asp Ala Cys Pro Ile Asn Gly Gly Trp Gly Pro 
                485                 490                 495     
Trp Ser Pro Trp Asp Ile Cys Ser Val Thr Cys Gly Gly Gly Val Gln 
            500                 505                 510         
Lys Arg Ser Arg Leu Cys Asn Asn Pro Thr Pro Gln Phe Gly Gly Lys 
        515                 520                 525             
Asp Cys Val Gly Asp Val Thr Glu Asn Gln Ile Cys Asn Lys Gln Asp 
    530                 535                 540                 
Cys Pro Ile Asp Gly Cys Leu Ser Asn Pro Cys Phe Ala Gly Val Lys 
545                 550                 555                 560 
Cys Thr Ser Tyr Pro Asp Gly Ser Trp Lys Cys Gly Ala Cys Pro Pro 
                565                 570                 575     
Gly Tyr Ser Gly Asn Gly Ile Gln Cys Thr Asp Val Asp Glu Cys Lys 
            580                 585                 590         
Glu Val Pro Asp Ala Cys Phe Asn His Asn Gly Glu His Arg Cys Glu 
        595                 600                 605             
Asn Thr Asp Pro Gly Tyr Asn Cys Leu Pro Cys Pro Pro Arg Tyr Arg 
    610                 615                 620                 
Gly Asn Gln Pro Val Gly Val Gly Leu Glu Ala Ala Lys Thr Glu Lys 
625                 630                 635                 640 
Gln Val Cys Glu Pro Glu Asn Pro Cys Lys Asp Gly Thr His Asp Cys 
                645                 650                 655     
Asn Lys Asn Ala Lys Cys Asn Tyr Leu Gly His Tyr Ser Asp Pro Met 
            660                 665                 670         
Tyr Arg Cys Glu Cys Lys Pro Gly Tyr Ala Gly Asn Gly Ile Ile Cys 
        675                 680                 685             
Gly Glu Asp Thr Asp Leu Asp Gly Trp Pro Asn Glu Asn Leu Val Cys 
    690                 695                 700                 
Val Ala Asn Ala Thr Tyr His Cys Lys Lys Asp Asn Cys Pro Asn Leu 
705                 710                 715                 720 
Pro Asn Ser Gly Gln Glu Asp Tyr Asp Lys Asp Gly Ile Gly Asp Ala 
                725                 730                 735     
Cys Asp Asp Asp Asp Asp Asn Asp Lys Ile Pro Asp Asp Arg Asp Asn 
            740                 745                 750         
Cys Pro Phe His Tyr Asn Pro Ala Gln Tyr Asp Tyr Asp Arg Asp Asp 
        755                 760                 765             
Val Gly Asp Arg Cys Asp Asn Cys Pro Tyr Asn His Asn Pro Asp Gln 
    770                 775                 780                 
Ala Asp Thr Asp Asn Asn Gly Glu Gly Asp Ala Cys Ala Ala Asp Ile 
785                 790                 795                 800 
Asp Gly Asp Gly Ile Leu Asn Glu Arg Asp Asn Cys Gln Tyr Val Tyr 
                805                 810                 815     
Asn Val Asp Gln Arg Asp Thr Asp Met Asp Gly Val Gly Asp Gln Cys 
            820                 825                 830         
Asp Asn Cys Pro Leu Glu His Asn Pro Asp Gln Leu Asp Ser Asp Ser 
        835                 840                 845             
Asp Arg Ile Gly Asp Thr Cys Asp Asn Asn Gln Asp Ile Asp Glu Asp 
    850                 855                 860                 
Gly His Gln Asn Asn Leu Asp Asn Cys Pro Tyr Val Pro Asn Ala Asn 
865                 870                 875                 880 
Gln Ala Asp His Asp Lys Asp Gly Lys Gly Asp Ala Cys Asp His Asp 
                885                 890                 895     
Asp Asp Asn Asp Gly Ile Pro Asp Asp Lys Asp Asn Cys Arg Leu Val 
            900                 905                 910         
Pro Asn Pro Asp Gln Lys Asp Ser Asp Gly Asp Gly Arg Gly Asp Ala 
        915                 920                 925             
Cys Lys Asp Asp Phe Asp His Asp Ser Val Pro Asp Ile Asp Asp Ile 
    930                 935                 940                 
Cys Pro Glu Asn Val Asp Ile Ser Glu Thr Asp Phe Arg Arg Phe Gln 
945                 950                 955                 960 
Met Ile Pro Leu Asp Pro Lys Gly Thr Ser Gln Asn Asp Pro Asn Trp 
                965                 970                 975     
Val Val Arg His Gln Gly Lys Glu Leu Val Gln Thr Val Asn Cys Asp 
            980                 985                 990         
Pro Gly Leu Ala Val Gly Tyr Asp Glu Phe Asn Ala Val Asp Phe Ser 
        995                 1000                1005            
Gly Thr Phe Phe Ile Asn Thr Glu Arg Asp Asp Asp Tyr Ala Gly Phe 
    1010                1015                1020                
Val Phe Gly Tyr Gln Ser Ser Ser Arg Phe Tyr Val Val Met Trp Lys 
1025                1030                1035                1040
Gln Val Thr Gln Thr Tyr Trp Glu Asp Gln Pro Thr Arg Ala Tyr Gly 
                1045                1050                1055    
Tyr Ser Gly Val Ser Leu Lys Val Val Asn Ser Thr Thr Gly Thr Gly 
            1060                1065                1070        
Glu His Leu Arg Asn Ala Leu Trp His Thr Gly Asn Thr Pro Gly Gln 
        1075                1080                1085            
Val Arg Thr Leu Trp His Asp Pro Arg Asn Ile Gly Trp Lys Asp Tyr 
    1090                1095                1100                
Thr Ala Tyr Arg Trp His Leu Thr His Arg Pro Lys Thr Gly Tyr Ile 
1105                1110                1115                1120
Arg Val Val Met Tyr Glu Gly Lys Lys Ile Met Ala Asp Ser Gly Pro 
                1125                1130                1135    
Ile Tyr Asp Lys Thr Tyr Ala Gly Gly Arg Leu Gly Leu Phe Val Phe 
            1140                1145                1150        
Ser Gln Glu Met Val Phe Phe Ser Asp Leu Lys Tyr Glu Cys Arg Asp 
        1155                1160                1165            



<210> 14
<211> 1171
<212> PRT
<213> Artificial Sequence


<220> 
<223> HTRA1-resistant derived TSP2

<400> 14
Met Val Trp Arg Leu Val Leu Leu Ala Leu Trp Val Trp Pro Ser Thr 
1               5                   10                  15      
Gln Ala Gly His Gln Asp Lys Asp Thr Thr Phe Asp Leu Phe Ser Ile 
            20                  25                  30          
Ser Asn Ile Asn Arg Lys Thr Ile Gly Ala Lys Gln Phe Arg Gly Pro 
        35                  40                  45              
Asp Pro Gly Val Pro Ala Tyr Arg Phe Val Arg Phe Asp Tyr Ile Pro 
    50                  55                  60                  
Pro Val Asn Ala Asp Asp Leu Ser Lys Ile Thr Lys Ile Met Arg Gln 
65                  70                  75                  80  
Lys Glu Gly Phe Phe Leu Thr Ala Gln Leu Lys Gln Asp Gly Lys Ser 
                85                  90                  95      
Arg Gly Thr Leu Leu Ala Leu Glu Gly Pro Gly Leu Ser Gln Arg Gln 
            100                 105                 110         
Phe Glu Ile Val Ser Asn Gly Pro Ala Asp Thr Leu Asp Leu Thr Tyr 
        115                 120                 125             
Trp Ile Asp Gly Thr Arg His Val Val Ser Leu Glu Asp Val Gly Leu 
    130                 135                 140                 
Ala Asp Ser Gln Trp Lys Asn Val Thr Val Gln Val Ala Gly Glu Thr 
145                 150                 155                 160 
Tyr Ser Leu His Val Gly Cys Asp Leu Ile Asp Ser Phe Ala Leu Asp 
                165                 170                 175     
Glu Pro Phe Tyr Glu His Leu Gln Ala Glu Lys Ser Arg Met Tyr Val 
            180                 185                 190         
Ala Lys Gly Ser Ala Arg Glu Ser His Phe Arg Gly Leu Leu Gln Asn 
        195                 200                 205             
Val His Leu Val Phe Glu Asn Ser Val Glu Asp Ile Leu Ser Lys Lys 
    210                 215                 220                 
Gly Cys Gln Gln Gly Gln Gly Ala Glu Ile Asn Ala Ile Ser Glu Asn 
225                 230                 235                 240 
Thr Glu Thr Leu Arg Leu Gly Pro His Val Thr Thr Glu Tyr Val Gly 
                245                 250                 255     
Pro Ser Ser Glu Arg Arg Pro Glu Val Cys Glu Arg Ser Cys Glu Glu 
            260                 265                 270         
Leu Gly Asn Met Val Gln Glu Leu Ser Gly Leu His Val Leu Val Asn 
        275                 280                 285             
Gln Leu Ser Glu Asn Leu Lys Arg Val Ser Asn Asp Asn Gln Phe Leu 
    290                 295                 300                 
Trp Glu Leu Ile Gly Gly Pro Pro Lys Thr Arg Asn Met Ser Ala Cys 
305                 310                 315                 320 
Trp Gln Asp Gly Arg Phe Phe Ala Glu Asn Glu Thr Trp Val Val Asp 
                325                 330                 335     
Ser Cys Thr Thr Cys Thr Cys Lys Lys Phe Lys Thr Ile Cys His Gln 
            340                 345                 350         
Ile Thr Cys Pro Pro Ala Thr Cys Ala Ser Pro Ser Phe Val Glu Gly 
        355                 360                 365             
Glu Cys Cys Pro Ser Cys Leu His Ser Val Asp Gly Glu Glu Gly Trp 
    370                 375                 380                 
Ser Pro Trp Ala Glu Trp Thr Gln Cys Ser Val Thr Cys Gly Ser Gly 
385                 390                 395                 400 
Thr Gln Gln Arg Gly Arg Ser Cys Asp Val Thr Ser Asn Thr Cys Leu 
                405                 410                 415     
Gly Pro Ser Ile Gln Thr Arg Ala Cys Ser Leu Ser Lys Cys Asp Thr 
            420                 425                 430         
Arg Ile Arg Gln Asp Gly Gly Trp Ser His Trp Ser Pro Trp Ser Ser 
        435                 440                 445             
Cys Ser Val Thr Cys Gly Val Gly Asn Ile Thr Arg Ile Arg Leu Cys 
    450                 455                 460                 
Asn Ser Pro Val Pro Gln Met Gly Gly Lys Asn Cys Lys Gly Ser Gly 
465                 470                 475                 480 
Arg Glu Thr Lys Ala Cys Gln Gly Ala Pro Cys Pro Ile Asp Gly Arg 
                485                 490                 495     
Trp Ser Pro Trp Ser Pro Trp Ser Ala Cys Thr Val Thr Cys Ala Gly 
            500                 505                 510         
Gly Ile Arg Glu Arg Thr Arg Val Cys Asn Ser Pro Glu Pro Gln Tyr 
        515                 520                 525             
Gly Gly Lys Ala Cys Val Gly Asp Val Gln Glu Arg Gln Met Cys Asn 
    530                 535                 540                 
Lys Arg Ser Cys Pro Val Asp Gly Cys Leu Ser Asn Pro Cys Phe Pro 
545                 550                 555                 560 
Gly Ala Gln Cys Ser Ser Phe Pro Asp Gly Ser Trp Ser Cys Gly Ser 
                565                 570                 575     
Cys Pro Val Gly Phe Leu Gly Asn Gly Thr His Cys Glu Asp Leu Asp 
            580                 585                 590         
Glu Cys Ala Leu Val Pro Asp Ile Cys Phe Ser Thr Ser Lys Val Pro 
        595                 600                 605             
Arg Cys Val Asn Thr Gln Pro Gly Phe His Cys Leu Pro Cys Pro Pro 
    610                 615                 620                 
Arg Tyr Arg Gly Asn Gln Pro Val Gly Val Gly Leu Glu Ala Ala Lys 
625                 630                 635                 640 
Thr Glu Lys Gln Val Cys Glu Pro Glu Asn Pro Cys Lys Asp Lys Thr 
                645                 650                 655     
His Asn Cys His Lys His Ala Glu Cys Ile Tyr Leu Gly His Phe Ser 
            660                 665                 670         
Asp Pro Met Tyr Lys Cys Glu Cys Gln Thr Gly Tyr Ala Gly Asp Gly 
        675                 680                 685             
Leu Ile Cys Gly Glu Asp Ser Asp Leu Asp Gly Trp Pro Asn Leu Asn 
    690                 695                 700                 
Leu Val Cys Ala Thr Asn Ala Thr Tyr His Cys Ile Lys Asp Asn Cys 
705                 710                 715                 720 
Pro His Leu Pro Asn Ser Gly Gln Glu Asp Phe Asp Lys Asp Gly Ile 
                725                 730                 735     
Gly Asp Ala Cys Asp Asp Asp Asp Asp Asn Asp Gly Val Thr Asp Glu 
            740                 745                 750         
Lys Asp Asn Cys Gln Leu Leu Phe Asn Pro Arg Gln Ala Asp Tyr Asp 
        755                 760                 765             
Lys Asp Glu Val Gly Asp Arg Cys Asp Asn Cys Pro Tyr Val His Asn 
    770                 775                 780                 
Pro Ala Gln Ile Asp Thr Asp Asn Asn Gly Glu Gly Asp Ala Cys Ser 
785                 790                 795                 800 
Val Asp Ile Asp Gly Asp Asp Val Phe Asn Glu Arg Asp Asn Cys Pro 
                805                 810                 815     
Tyr Val Tyr Asn Thr Asp Gln Arg Asp Thr Asp Gly Asp Gly Val Gly 
            820                 825                 830         
Asp His Cys Asp Asn Cys Pro Leu Val His Asn Pro Asp Gln Thr Asp 
        835                 840                 845             
Val Asp Asn Asp Leu Val Gly Asp Gln Cys Asp Asn Asn Glu Asp Ile 
    850                 855                 860                 
Asp Asp Asp Gly His Gln Asn Asn Gln Asp Asn Cys Pro Tyr Ile Ser 
865                 870                 875                 880 
Asn Ala Asn Gln Ala Asp His Asp Arg Asp Gly Gln Gly Asp Ala Cys 
                885                 890                 895     
Asp Pro Asp Asp Asp Asn Asp Gly Val Pro Asp Asp Arg Asp Asn Cys 
            900                 905                 910         
Arg Leu Val Phe Asn Pro Asp Gln Glu Asp Leu Asp Gly Asp Gly Arg 
        915                 920                 925             
Gly Asp Ile Cys Lys Asp Asp Phe Asp Asn Asp Asn Ile Pro Asp Ile 
    930                 935                 940                 
Asp Asp Val Cys Pro Glu Asn Asn Ala Ile Ser Glu Thr Asp Phe Arg 
945                 950                 955                 960 
Asn Phe Gln Met Val Pro Leu Asp Pro Lys Gly Thr Thr Gln Ile Asp 
                965                 970                 975     
Pro Asn Trp Val Ile Arg His Gln Gly Lys Glu Leu Val Gln Thr Ala 
            980                 985                 990         
Asn Ser Asp Pro Gly Ile Ala Val Gly Phe Asp Glu Phe Gly Ser Val 
        995                 1000                1005            
Asp Phe Ser Gly Thr Phe Tyr Val Asn Thr Asp Arg Asp Asp Asp Tyr 
    1010                1015                1020                
Ala Gly Phe Val Phe Gly Tyr Gln Ser Ser Ser Arg Phe Tyr Val Val 
1025                1030                1035                1040
Met Trp Lys Gln Val Thr Gln Thr Tyr Trp Glu Asp Gln Pro Thr Arg 
                1045                1050                1055    
Ala Tyr Gly Tyr Ser Gly Val Ser Leu Lys Val Val Asn Ser Thr Thr 
            1060                1065                1070        
Gly Thr Gly Glu His Leu Arg Asn Ala Leu Trp His Thr Gly Asn Thr 
        1075                1080                1085            
Pro Gly Gln Val Arg Thr Leu Trp His Asp Pro Arg Asn Ile Gly Trp 
    1090                1095                1100                
Lys Asp Tyr Thr Ala Tyr Arg Trp His Leu Thr His Arg Pro Lys Thr 
1105                1110                1115                1120
Gly Phe Ile Arg Val Val Met Tyr Glu Gly Lys Lys Ile Met Ala Asp 
                1125                1130                1135    
Ser Gly Pro Ile Tyr Asp Lys Thr Tyr Ala Gly Gly Arg Leu Gly Leu 
            1140                1145                1150        
Phe Val Phe Ser Gln Glu Met Val Phe Phe Ser Asp Leu Lys Tyr Glu 
        1155                1160                1165            
Cys Arg Asp 
    1170    

