                         SEQUENCE LISTING

<110>  F. Hoffmann-La Roche AG
 
<120>  Use of a cathepsin S inhibitor against the formation of anti-drug
        antibodies

<130>  P35022-WO

<150>  EP18195251.6
<151>  2018-09-18

<160>  6     

<170>  PatentIn version 3.5

<210>  1
<211>  816
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic construct

<400>  1

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 Gly Thr Phe Ser Ser Tyr 
            20                  25                  30          


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


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


Gln Gly Arg Val 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 Glu Tyr Tyr Arg Gly Pro Tyr Asp Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


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


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


Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 
145                 150                 155                 160 


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


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


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


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


Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly 
225                 230                 235                 240 


Ala Glu Val Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala 
                245                 250                 255     


Ser Gly Gly Thr Phe Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala 
            260                 265                 270         


Pro Gly Gln Gly Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Phe Gly 
        275                 280                 285             


Thr Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala 
    290                 295                 300                 


Asp Lys Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser 
305                 310                 315                 320 


Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Glu Tyr Tyr Arg Gly Pro 
                325                 330                 335     


Tyr Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser 
            340                 345                 350         


Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr 
        355                 360                 365             


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


Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val 
385                 390                 395                 400 


His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser 
                405                 410                 415     


Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile 
            420                 425                 430         


Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val 
        435                 440                 445             


Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 
    450                 455                 460                 


Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
465                 470                 475                 480 


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
                485                 490                 495     


Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
            500                 505                 510         


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
        515                 520                 525             


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
    530                 535                 540                 


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
545                 550                 555                 560 


Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
                565                 570                 575     


Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Asp Glu Leu Thr 
            580                 585                 590         


Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser 
        595                 600                 605             


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
    610                 615                 620                 


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr 
625                 630                 635                 640 


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
                645                 650                 655     


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
            660                 665                 670         


Ser Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        675                 680                 685             


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Leu 
    690                 695                 700                 


Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser 
705                 710                 715                 720 


Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Ala Met Ser Trp Val 
                725                 730                 735     


Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ala Ile Ile Gly 
            740                 745                 750         


Ser Gly Ala Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr 
        755                 760                 765             


Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser 
    770                 775                 780                 


Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Lys Gly Trp Phe 
785                 790                 795                 800 


Gly Gly Phe Asn Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 
                805                 810                 815     


<210>  2
<211>  807
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic construct

<400>  2

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 Gly Thr Phe Ser Ser Tyr 
            20                  25                  30          


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


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


Gln Gly Arg Val 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 Glu Tyr Tyr Arg Gly Pro Tyr Asp Tyr Trp Gly Gln Gly Thr 
            100                 105                 110         


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


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


Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 
145                 150                 155                 160 


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


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


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


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


Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly 
225                 230                 235                 240 


Ala Glu Val Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala 
                245                 250                 255     


Ser Gly Gly Thr Phe Ser Ser Tyr Ala Ile Ser Trp Val Arg Gln Ala 
            260                 265                 270         


Pro Gly Gln Gly Leu Glu Trp Met Gly Gly Ile Ile Pro Ile Phe Gly 
        275                 280                 285             


Thr Ala Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala 
    290                 295                 300                 


Asp Lys Ser Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser 
305                 310                 315                 320 


Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Glu Tyr Tyr Arg Gly Pro 
                325                 330                 335     


Tyr Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser 
            340                 345                 350         


Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr 
        355                 360                 365             


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


Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val 
385                 390                 395                 400 


His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser 
                405                 410                 415     


Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile 
            420                 425                 430         


Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val 
        435                 440                 445             


Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala 
    450                 455                 460                 


Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro 
465                 470                 475                 480 


Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val 
                485                 490                 495     


Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val 
            500                 505                 510         


Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln 
        515                 520                 525             


Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln 
    530                 535                 540                 


Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala 
545                 550                 555                 560 


Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro 
                565                 570                 575     


Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr 
            580                 585                 590         


Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser 
        595                 600                 605             


Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr 
    610                 615                 620                 


Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val 
625                 630                 635                 640 


Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe 
                645                 650                 655     


Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys 
            660                 665                 670         


Ser Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        675                 680                 685             


Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Leu Thr 
    690                 695                 700                 


Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu 
705                 710                 715                 720 


Ser Cys Arg Ala Ser Gln Ser Val Thr Ser Ser Tyr Leu Ala Trp Tyr 
                725                 730                 735     


Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Asn Val Gly Ser 
            740                 745                 750         


Arg Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly 
        755                 760                 765             


Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala 
    770                 775                 780                 


Val Tyr Tyr Cys Gln Gln Gly Ile Met Leu Pro Pro Thr Phe Gly Gln 
785                 790                 795                 800 


Gly Thr Lys Val Glu Ile Lys 
                805         


<210>  3
<211>  214
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic construct

<400>  3

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


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


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


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


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


Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Ser Gln Pro Tyr 
                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>  4
<211>  805
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic construct

<400>  4

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


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Thr Gly Tyr 
            20                  25                  30          


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


Gly Arg Met Arg Tyr Asp Gly Asp Thr Tyr Tyr Asn Ser Val Leu Lys 
    50                  55                  60                  


Ser Arg Leu Ser Ile Ser Arg Asp Thr Ser Lys Asn Gln Val Phe Leu 
65                  70                  75                  80  


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


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


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


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


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


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


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


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


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


Gly Gly Gly Gly Ser Gln Val Gln Leu Lys Glu Ser Gly Pro Gly Leu 
225                 230                 235                 240 


Val Gln Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Phe 
                245                 250                 255     


Ser Leu Thr Gly Tyr Asn Leu His Trp Val Arg Gln Pro Pro Gly Lys 
            260                 265                 270         


Gly Leu Glu Trp Met Gly Arg Met Arg Tyr Asp Gly Asp Thr Tyr Tyr 
        275                 280                 285             


Asn Ser Val Leu Lys Ser Arg Leu Ser Ile Ser Arg Asp Thr Ser Lys 
    290                 295                 300                 


Asn Gln Val Phe Leu Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala 
305                 310                 315                 320 


Ile Tyr Tyr Cys Thr Arg Asp Gly Arg Gly Asp Ser Phe Asp Tyr Trp 
                325                 330                 335     


Gly Gln Gly Val Met Val Thr Val Ser Ser Ala Lys Thr Thr Pro Pro 
            340                 345                 350         


Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met 
        355                 360                 365             


Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr 
    370                 375                 380                 


Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro 
385                 390                 395                 400 


Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val 
                405                 410                 415     


Pro Ser Ser Thr Trp Pro Ser Gln Thr Val Thr Cys Asn Val Ala His 
            420                 425                 430         


Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys 
        435                 440                 445             


Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe 
    450                 455                 460                 


Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro 
465                 470                 475                 480 


Lys Val Thr Cys Val Val Val Ala Ile Ser Lys Asp Asp Pro Glu Val 
                485                 490                 495     


Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr 
            500                 505                 510         


Lys Pro Arg Glu Glu Gln Ile Asn Ser Thr Phe Arg Ser Val Ser Glu 
        515                 520                 525             


Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys 
    530                 535                 540                 


Arg Val Asn Ser Ala Ala Phe Gly Ala Pro Ile Glu Lys Thr Ile Ser 
545                 550                 555                 560 


Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro 
                565                 570                 575     


Pro Lys Lys Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile 
            580                 585                 590         


Thr Asn Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly 
        595                 600                 605             


Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Lys Thr Asp 
    610                 615                 620                 


Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser Asn Trp 
625                 630                 635                 640 


Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His 
                645                 650                 655     


Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Gly Gly Gly 
            660                 665                 670         


Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        675                 680                 685             


Ser Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly 
    690                 695                 700                 


Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser 
705                 710                 715                 720 


His Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp 
                725                 730                 735     


Val Ser Ala Ile Trp Ala Ser Gly Glu Gln Tyr Tyr Ala Asp Ser Val 
            740                 745                 750         


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
        755                 760                 765             


Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 
    770                 775                 780                 


Ala Lys Gly Trp Leu Gly Asn Phe Asp Tyr Trp Gly Gln Gly Thr Leu 
785                 790                 795                 800 


Val Thr Val Ser Ser 
                805 


<210>  5
<211>  797
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic construct

<400>  5

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


Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Phe Ser Leu Thr Gly Tyr 
            20                  25                  30          


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


Gly Arg Met Arg Tyr Asp Gly Asp Thr Tyr Tyr Asn Ser Val Leu Lys 
    50                  55                  60                  


Ser Arg Leu Ser Ile Ser Arg Asp Thr Ser Lys Asn Gln Val Phe Leu 
65                  70                  75                  80  


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


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


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


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


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


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


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


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


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


Gly Gly Gly Gly Ser Gln Val Gln Leu Lys Glu Ser Gly Pro Gly Leu 
225                 230                 235                 240 


Val Gln Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Phe 
                245                 250                 255     


Ser Leu Thr Gly Tyr Asn Leu His Trp Val Arg Gln Pro Pro Gly Lys 
            260                 265                 270         


Gly Leu Glu Trp Met Gly Arg Met Arg Tyr Asp Gly Asp Thr Tyr Tyr 
        275                 280                 285             


Asn Ser Val Leu Lys Ser Arg Leu Ser Ile Ser Arg Asp Thr Ser Lys 
    290                 295                 300                 


Asn Gln Val Phe Leu Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala 
305                 310                 315                 320 


Ile Tyr Tyr Cys Thr Arg Asp Gly Arg Gly Asp Ser Phe Asp Tyr Trp 
                325                 330                 335     


Gly Gln Gly Val Met Val Thr Val Ser Ser Ala Lys Thr Thr Pro Pro 
            340                 345                 350         


Ser Val Tyr Pro Leu Ala Pro Gly Ser Ala Ala Gln Thr Asn Ser Met 
        355                 360                 365             


Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr 
    370                 375                 380                 


Val Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro 
385                 390                 395                 400 


Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val 
                405                 410                 415     


Pro Ser Ser Thr Trp Pro Ser Gln Thr Val Thr Cys Asn Val Ala His 
            420                 425                 430         


Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Val Pro Arg Asp Cys 
        435                 440                 445             


Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser Val Phe 
    450                 455                 460                 


Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu Thr Pro 
465                 470                 475                 480 


Lys Val Thr Cys Val Val Val Ala Ile Ser Lys Asp Asp Pro Glu Val 
                485                 490                 495     


Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala Gln Thr 
            500                 505                 510         


Lys Pro Arg Glu Glu Gln Ile Asn Ser Thr Phe Arg Ser Val Ser Glu 
        515                 520                 525             


Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe Lys Cys 
    530                 535                 540                 


Arg Val Asn Ser Ala Ala Phe Gly Ala Pro Ile Glu Lys Thr Ile Ser 
545                 550                 555                 560 


Lys Thr Lys Gly Arg Pro Lys Ala Pro Gln Val Tyr Thr Ile Pro Pro 
                565                 570                 575     


Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr Cys Met Ile 
            580                 585                 590         


Thr Asn Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp Asn Gly 
        595                 600                 605             


Gln Pro Ala Glu Asn Tyr Asp Asn Thr Gln Pro Ile Met Asp Thr Asp 
    610                 615                 620                 


Gly Ser Tyr Phe Val Tyr Ser Asp Leu Asn Val Gln Lys Ser Asn Trp 
625                 630                 635                 640 


Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu Gly Leu His 
                645                 650                 655     


Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Gly Gly Gly 
            660                 665                 670         


Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        675                 680                 685             


Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro 
    690                 695                 700                 


Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Arg 
705                 710                 715                 720 


Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu 
                725                 730                 735     


Leu Ile Ile Gly Ala Ser Thr Arg Ala Thr Gly Ile Pro Asp Arg Phe 
            740                 745                 750         


Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu 
        755                 760                 765             


Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Gly Gln Val Ile 
    770                 775                 780                 


Pro Pro Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 
785                 790                 795         


<210>  6
<211>  219
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Synthetic construct

<400>  6

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


Glu Ser Ala Ser Ile Thr Cys Arg Ser Ser Gln Ser Leu Val Tyr Lys 
            20                  25                  30          


Asp Gly Gln Thr Tyr Leu Asn Trp Phe Leu Gln Arg Pro Gly Gln Ser 
        35                  40                  45              


Pro Gln Leu Leu Thr Tyr Trp Met Ser Thr Arg Ala Ser Gly Val Ser 
    50                  55                  60                  


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


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


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


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


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


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


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


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


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


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


