                               SEQUENCE LISTING

<110> THE BROAD INSTITUTE, INC.
      DANA-FARBER CANCER INSTITUTE, INC.
 
<120> ANTAGONISTIC BIPARATOPIC ANTIBODIES THAT SPECIFICALLY BIND 
      FIBROBLAST GROWTH FACTOR RECEPTOR 2 AND METHODS OF USING SAME

<130> 167741.022601/PCT

<140> PCT/US2021/035468
<141> 2021-06-02

<150> 63/033,975
<151> 2020-06-03

<160> 26    

<170> PatentIn version 3.5

<210> 1
<211> 122
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 1
Glu Val Gln Leu Leu 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 Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


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


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


<210> 2
<211> 110
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 2
Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 
1               5                   10                  15      


Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 
            20                  25                  30          


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


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


Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 
65                  70                  75                  80  


Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Trp Asp Asp Ser Leu 
                85                  90                  95      


Asn Tyr Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
            100                 105                 110 


<210> 3
<211> 452
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 3
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys 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 Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Gly Arg Ile Arg Ser Lys Ile Asp Gly Gly Thr Thr Asp Tyr Ala Ala 
    50                  55                  60                  


Pro Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 
65                  70                  75                  80  


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


Tyr Cys Ala Arg Asp Arg Ser Pro Ser Asp Ser Ser Ala Phe Ala Ile 
            100                 105                 110         


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly 
        115                 120                 125             


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


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


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


Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr 
            180                 185                 190         


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


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


Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
225                 230                 235                 240 


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
                245                 250                 255     


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
            260                 265                 270         


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


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


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
305                 310                 315                 320 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
                325                 330                 335     


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


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


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
    370                 375                 380                 


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
385                 390                 395                 400 


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


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
            420                 425                 430         


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
        435                 440                 445             


Ser Pro Gly Lys 
    450         


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

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 4
Asp Ile Glu Leu Thr Gln Pro Pro Ser Val Ser Val Ser Pro Gly Gln 
1               5                   10                  15      


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


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


Asp Asp Asn Asp 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 Asp Ser Leu Ser Val Val 
                85                  90                  95      


Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys Ala Ala 
            100                 105                 110         


Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn 
        115                 120                 125             


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


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


Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser 
                165                 170                 175     


Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Arg Ser Tyr Ser 
            180                 185                 190         


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


Thr Glu Cys Ser 
    210         


<210> 5
<211> 457
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 5
Glu 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 Pro Phe Thr Ser Thr 
            20                  25                  30          


Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


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


Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala 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 Thr Tyr Gly Ile Tyr Asp Thr Tyr Asp Met Tyr Thr Glu Tyr 
            100                 105                 110         


Val Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala 
        115                 120                 125             


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


Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe 
145                 150                 155                 160 


Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly 
                165                 170                 175     


Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu 
            180                 185                 190         


Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr 
        195                 200                 205             


Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys 
    210                 215                 220                 


Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
225                 230                 235                 240 


Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
                245                 250                 255     


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


Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
        275                 280                 285             


Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
    290                 295                 300                 


Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
305                 310                 315                 320 


Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                325                 330                 335     


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


Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met 
        355                 360                 365             


Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 
    370                 375                 380                 


Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
385                 390                 395                 400 


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


Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
            420                 425                 430         


Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
        435                 440                 445             


Lys Ser Leu Ser Leu Ser Pro Gly Lys 
    450                 455         


<210> 6
<211> 214
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 6
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


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


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


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


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


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


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


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


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


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


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


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


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


Phe Asn Arg Gly Glu Cys 
    210                 


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

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 7
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


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


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


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


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


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


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


<210> 8
<211> 114
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 8
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 
1               5                   10                  15      


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


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


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


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


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


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


Ser Ser 
        


<210> 9
<211> 5
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      peptide

<400> 9
Asn Tyr Tyr Ile His 
1               5   


<210> 10
<211> 17
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      peptide

<400> 10
Ala Ile Tyr Pro Asp Asn Ser Asp Thr Thr Tyr Ser Pro Ser Phe Gln 
1               5                   10                  15      


Gly 
    


<210> 11
<211> 4
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      peptide

<400> 11
Gly Ala Asp Ile 
1               


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

<220>
<223> Description of Artificial Sequence: Synthetic
      peptide

<400> 12
Arg Ala Ser Gln Asp Ile Asp Pro Tyr Leu Ser Asn 
1               5                   10          


<210> 13
<211> 7
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      peptide

<400> 13
Asp Ala Ser Asn Leu Gln Ser 
1               5           


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

<220>
<223> Description of Artificial Sequence: Synthetic
      peptide

<400> 14
Gln Gln Thr Thr Ser His Pro Tyr Thr 
1               5                   


<210> 15
<211> 821
<212> PRT
<213> Homo sapiens

<400> 15
Met Val Ser Trp Gly Arg Phe Ile Cys Leu Val Val Val Thr Met Ala 
1               5                   10                  15      


Thr Leu Ser Leu Ala Arg Pro Ser Phe Ser Leu Val Glu Asp Thr Thr 
            20                  25                  30          


Leu Glu Pro Glu Glu Pro Pro Thr Lys Tyr Gln Ile Ser Gln Pro Glu 
        35                  40                  45              


Val Tyr Val Ala Ala Pro Gly Glu Ser Leu Glu Val Arg Cys Leu Leu 
    50                  55                  60                  


Lys Asp Ala Ala Val Ile Ser Trp Thr Lys Asp Gly Val His Leu Gly 
65                  70                  75                  80  


Pro Asn Asn Arg Thr Val Leu Ile Gly Glu Tyr Leu Gln Ile Lys Gly 
                85                  90                  95      


Ala Thr Pro Arg Asp Ser Gly Leu Tyr Ala Cys Thr Ala Ser Arg Thr 
            100                 105                 110         


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


Ser Ser Gly Asp Asp Glu Asp Asp Thr Asp Gly Ala Glu Asp Phe Val 
    130                 135                 140                 


Ser Glu Asn Ser Asn Asn Lys Arg Ala Pro Tyr Trp Thr Asn Thr Glu 
145                 150                 155                 160 


Lys Met Glu Lys Arg Leu His Ala Val Pro Ala Ala Asn Thr Val Lys 
                165                 170                 175     


Phe Arg Cys Pro Ala Gly Gly Asn Pro Met Pro Thr Met Arg Trp Leu 
            180                 185                 190         


Lys Asn Gly Lys Glu Phe Lys Gln Glu His Arg Ile Gly Gly Tyr Lys 
        195                 200                 205             


Val Arg Asn Gln His Trp Ser Leu Ile Met Glu Ser Val Val Pro Ser 
    210                 215                 220                 


Asp Lys Gly Asn Tyr Thr Cys Val Val Glu Asn Glu Tyr Gly Ser Ile 
225                 230                 235                 240 


Asn His Thr Tyr His Leu Asp Val Val Glu Arg Ser Pro His Arg Pro 
                245                 250                 255     


Ile Leu Gln Ala Gly Leu Pro Ala Asn Ala Ser Thr Val Val Gly Gly 
            260                 265                 270         


Asp Val Glu Phe Val Cys Lys Val Tyr Ser Asp Ala Gln Pro His Ile 
        275                 280                 285             


Gln Trp Ile Lys His Val Glu Lys Asn Gly Ser Lys Tyr Gly Pro Asp 
    290                 295                 300                 


Gly Leu Pro Tyr Leu Lys Val Leu Lys Ala Ala Gly Val Asn Thr Thr 
305                 310                 315                 320 


Asp Lys Glu Ile Glu Val Leu Tyr Ile Arg Asn Val Thr Phe Glu Asp 
                325                 330                 335     


Ala Gly Glu Tyr Thr Cys Leu Ala Gly Asn Ser Ile Gly Ile Ser Phe 
            340                 345                 350         


His Ser Ala Trp Leu Thr Val Leu Pro Ala Pro Gly Arg Glu Lys Glu 
        355                 360                 365             


Ile Thr Ala Ser Pro Asp Tyr Leu Glu Ile Ala Ile Tyr Cys Ile Gly 
    370                 375                 380                 


Val Phe Leu Ile Ala Cys Met Val Val Thr Val Ile Leu Cys Arg Met 
385                 390                 395                 400 


Lys Asn Thr Thr Lys Lys Pro Asp Phe Ser Ser Gln Pro Ala Val His 
                405                 410                 415     


Lys Leu Thr Lys Arg Ile Pro Leu Arg Arg Gln Val Thr Val Ser Ala 
            420                 425                 430         


Glu Ser Ser Ser Ser Met Asn Ser Asn Thr Pro Leu Val Arg Ile Thr 
        435                 440                 445             


Thr Arg Leu Ser Ser Thr Ala Asp Thr Pro Met Leu Ala Gly Val Ser 
    450                 455                 460                 


Glu Tyr Glu Leu Pro Glu Asp Pro Lys Trp Glu Phe Pro Arg Asp Lys 
465                 470                 475                 480 


Leu Thr Leu Gly Lys Pro Leu Gly Glu Gly Cys Phe Gly Gln Val Val 
                485                 490                 495     


Met Ala Glu Ala Val Gly Ile Asp Lys Asp Lys Pro Lys Glu Ala Val 
            500                 505                 510         


Thr Val Ala Val Lys Met Leu Lys Asp Asp Ala Thr Glu Lys Asp Leu 
        515                 520                 525             


Ser Asp Leu Val Ser Glu Met Glu Met Met Lys Met Ile Gly Lys His 
    530                 535                 540                 


Lys Asn Ile Ile Asn Leu Leu Gly Ala Cys Thr Gln Asp Gly Pro Leu 
545                 550                 555                 560 


Tyr Val Ile Val Glu Tyr Ala Ser Lys Gly Asn Leu Arg Glu Tyr Leu 
                565                 570                 575     


Arg Ala Arg Arg Pro Pro Gly Met Glu Tyr Ser Tyr Asp Ile Asn Arg 
            580                 585                 590         


Val Pro Glu Glu Gln Met Thr Phe Lys Asp Leu Val Ser Cys Thr Tyr 
        595                 600                 605             


Gln Leu Ala Arg Gly Met Glu Tyr Leu Ala Ser Gln Lys Cys Ile His 
    610                 615                 620                 


Arg Asp Leu Ala Ala Arg Asn Val Leu Val Thr Glu Asn Asn Val Met 
625                 630                 635                 640 


Lys Ile Ala Asp Phe Gly Leu Ala Arg Asp Ile Asn Asn Ile Asp Tyr 
                645                 650                 655     


Tyr Lys Lys Thr Thr Asn Gly Arg Leu Pro Val Lys Trp Met Ala Pro 
            660                 665                 670         


Glu Ala Leu Phe Asp Arg Val Tyr Thr His Gln Ser Asp Val Trp Ser 
        675                 680                 685             


Phe Gly Val Leu Met Trp Glu Ile Phe Thr Leu Gly Gly Ser Pro Tyr 
    690                 695                 700                 


Pro Gly Ile Pro Val Glu Glu Leu Phe Lys Leu Leu Lys Glu Gly His 
705                 710                 715                 720 


Arg Met Asp Lys Pro Ala Asn Cys Thr Asn Glu Leu Tyr Met Met Met 
                725                 730                 735     


Arg Asp Cys Trp His Ala Val Pro Ser Gln Arg Pro Thr Phe Lys Gln 
            740                 745                 750         


Leu Val Glu Asp Leu Asp Arg Ile Leu Thr Leu Thr Thr Asn Glu Glu 
        755                 760                 765             


Tyr Leu Asp Leu Ser Gln Pro Leu Glu Gln Tyr Ser Pro Ser Tyr Pro 
    770                 775                 780                 


Asp Thr Arg Ser Ser Cys Ser Ser Gly Asp Asp Ser Val Phe Ser Pro 
785                 790                 795                 800 


Asp Pro Met Pro Tyr Glu Pro Cys Leu Pro Gln Tyr Pro His Ile Asn 
                805                 810                 815     


Gly Ser Val Lys Thr 
            820     


<210> 16
<211> 111
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 16
Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 
1               5                   10                  15      


Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 
            20                  25                  30          


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


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


Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 
65                  70                  75                  80  


Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Trp Asp Asp Ser Leu 
                85                  90                  95      


Asn Tyr Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly 
            100                 105                 110     


<210> 17
<211> 114
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 17
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 
1               5                   10                  15      


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


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


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


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


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


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


Ser Ser 
        


<210> 18
<211> 107
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 18
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


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


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


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


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


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


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


<210> 19
<211> 119
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 19
Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro Gly Glu 
1               5                   10                  15      


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


Gly Met Asn Trp Met Lys Gln Ala Pro Gly Lys Gly Phe Lys Trp Met 
        35                  40                  45              


Gly Trp Ile Asn Thr Ser Thr Gly Glu Ser Thr Tyr Ala Asp Asp Phe 
    50                  55                  60                  


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


Leu Gln Ile Asn Asn Leu Lys Asn Glu Asp Met Ala Thr Tyr Phe Cys 
                85                  90                  95      


Ala Arg Asn Ser Tyr Tyr Gly Gly Ser Tyr Gly Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Thr Leu Thr Val Ser Ser 
        115                 


<210> 20
<211> 113
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 20
Asp Ile Val Met Ser Gln Ser Pro Ser Ser Leu Ala Val Ser Val Gly 
1               5                   10                  15      


Glu Lys Val Thr Met Lys Cys Lys Ser Ser Gln Ser Leu Leu Tyr Ser 
            20                  25                  30          


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


Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 
    50                  55                  60                  


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


Ile Ser Ser Val Lys Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln 
                85                  90                  95      


Tyr Tyr Ser Tyr Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile 
            100                 105                 110         


Lys 
    


<210> 21
<211> 127
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 21
Glu 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 Pro Phe Thr Ser Thr 
            20                  25                  30          


Gly Ile Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


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


Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser Lys Asn Thr Ala 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 Thr Tyr Gly Ile Tyr Asp Thr Tyr Asp Met Tyr Thr Glu Tyr 
            100                 105                 110         


Val Met Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120                 125         


<210> 22
<211> 107
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 22
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


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


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


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


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


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


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


<210> 23
<211> 123
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 23
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys 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 Leu Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Gly Arg Ile Arg Ser Lys Ile Asp Gly Gly Thr Thr Asp Tyr Ala Ala 
    50                  55                  60                  


Pro Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr 
65                  70                  75                  80  


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


Tyr Cys Ala Arg Asp Arg Ser Pro Ser Asp Ser Ser Ala Phe Ala Ile 
            100                 105                 110         


Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
        115                 120             


<210> 24
<211> 107
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 24
Asp Ile Glu Leu Thr Gln Pro Pro Ser Val Ser Val Ser Pro Gly Gln 
1               5                   10                  15      


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


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


Asp Asp Asn Asp 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 Asp Ser Leu Ser Val Val 
                85                  90                  95      


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


<210> 25
<211> 113
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 25
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu 
1               5                   10                  15      


Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Asn Tyr 
            20                  25                  30          


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


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


Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr 
65                  70                  75                  80  


Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys 
                85                  90                  95      


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


Ser 
    


<210> 26
<211> 108
<212> PRT
<213> Artificial Sequence

<220>
<223> Description of Artificial Sequence: Synthetic
      polypeptide

<400> 26
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 
1               5                   10                  15      


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


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


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


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


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


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


