                         SEQUENCE LISTING

<110>  VIB VZW
       UNIVERSITEIT GENT
 
<120>  NOVEL INTERLEUKIN-33 INHIBITORS

<130>  RB/IL33/437

<150>  EP 12196262.5
<151>  2012-12-10

<160>  21    

<170>  PatentIn version 3.5

<210>  1
<211>  763
<212>  PRT
<213>  artificial

<220>
<223>  mIL33trap (20xGGS)

<400>  1

Met Gly Leu Leu Trp Tyr Leu Met Ser Leu Ser Phe Tyr Gly Ile Leu 
1               5                   10                  15      


Gln Ser His Ala Ser Glu Arg Cys Asp Asp Trp Gly Leu Asp Thr Met 
            20                  25                  30          


Arg Gln Ile Gln Val Phe Glu Asp Glu Pro Ala Arg Ile Lys Cys Pro 
        35                  40                  45              


Leu Phe Glu His Phe Leu Lys Tyr Asn Tyr Ser Thr Ala His Ser Ser 
    50                  55                  60                  


Gly Leu Thr Leu Ile Trp Tyr Trp Thr Arg Gln Asp Arg Asp Leu Glu 
65                  70                  75                  80  


Glu Pro Ile Asn Phe Arg Leu Pro Glu Asn Arg Ile Ser Lys Glu Lys 
                85                  90                  95      


Asp Val Leu Trp Phe Arg Pro Thr Leu Leu Asn Asp Thr Gly Asn Tyr 
            100                 105                 110         


Thr Cys Met Leu Arg Asn Thr Thr Tyr Cys Ser Lys Val Ala Phe Pro 
        115                 120                 125             


Leu Glu Val Val Gln Lys Asp Ser Cys Phe Asn Ser Ala Met Arg Phe 
    130                 135                 140                 


Pro Val His Lys Met Tyr Ile Glu His Gly Ile His Lys Ile Thr Cys 
145                 150                 155                 160 


Pro Asn Val Asp Gly Tyr Phe Pro Ser Ser Val Lys Pro Ser Val Thr 
                165                 170                 175     


Trp Tyr Lys Gly Cys Thr Glu Ile Val Asp Phe His Asn Val Leu Pro 
            180                 185                 190         


Glu Gly Met Asn Leu Ser Phe Phe Ile Pro Leu Val Ser Asn Asn Gly 
        195                 200                 205             


Asn Tyr Thr Cys Val Val Thr Tyr Pro Glu Asn Gly Arg Leu Phe His 
    210                 215                 220                 


Leu Thr Arg Thr Val Thr Val Lys Val Val Gly Ser Pro Lys Asp Ala 
225                 230                 235                 240 


Leu Pro Pro Gln Ile Tyr Ser Pro Asn Asp Arg Val Val Tyr Glu Lys 
                245                 250                 255     


Glu Pro Gly Glu Glu Leu Val Ile Pro Cys Lys Val Tyr Phe Ser Phe 
            260                 265                 270         


Ile Met Asp Ser His Asn Glu Val Trp Trp Thr Ile Asp Gly Lys Lys 
        275                 280                 285             


Pro Asp Asp Val Thr Val Asp Ile Thr Ile Asn Glu Ser Val Ser Tyr 
    290                 295                 300                 


Ser Ser Thr Glu Asp Glu Thr Arg Thr Gln Ile Leu Ser Ile Lys Lys 
305                 310                 315                 320 


Val Thr Pro Glu Asp Leu Arg Arg Asn Tyr Val Cys His Ala Arg Asn 
                325                 330                 335     


Thr Lys Gly Glu Ala Glu Gln Ala Ala Lys Val Lys Gln Lys Gly Asn 
            340                 345                 350         


Gly Cys Thr Glu Pro Met Thr Leu Ser Arg Gly Gly Ser Gly Gly Ser 
        355                 360                 365             


Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly 
    370                 375                 380                 


Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly 
385                 390                 395                 400 


Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser 
                405                 410                 415     


Gly Gly Ser Gly Gly Ser Leu Gln Leu Gln Ser Lys Ser Ser Trp Gly 
            420                 425                 430         


Leu Glu Asn Glu Ala Leu Ile Val Arg Cys Pro Gln Arg Gly Arg Ser 
        435                 440                 445             


Thr Tyr Pro Val Glu Trp Tyr Tyr Ser Asp Thr Asn Glu Ser Ile Pro 
    450                 455                 460                 


Thr Gln Lys Arg Asn Arg Ile Phe Val Ser Arg Asp Arg Leu Lys Phe 
465                 470                 475                 480 


Leu Pro Ala Arg Val Glu Asp Ser Gly Ile Tyr Ala Cys Val Ile Arg 
                485                 490                 495     


Ser Pro Asn Leu Asn Lys Thr Gly Tyr Leu Asn Val Thr Ile His Lys 
            500                 505                 510         


Lys Pro Pro Ser Cys Asn Ile Pro Asp Tyr Leu Met Tyr Ser Thr Val 
        515                 520                 525             


Arg Gly Ser Asp Lys Asn Phe Lys Ile Thr Cys Pro Thr Ile Asp Leu 
    530                 535                 540                 


Tyr Asn Trp Thr Ala Pro Val Gln Trp Phe Lys Asn Cys Lys Ala Leu 
545                 550                 555                 560 


Gln Glu Pro Arg Phe Arg Ala His Arg Ser Tyr Leu Phe Ile Asp Asn 
                565                 570                 575     


Val Thr His Asp Asp Glu Gly Asp Tyr Thr Cys Gln Phe Thr His Ala 
            580                 585                 590         


Glu Asn Gly Thr Asn Tyr Ile Val Thr Ala Thr Arg Ser Phe Thr Val 
        595                 600                 605             


Glu Glu Lys Gly Phe Ser Met Phe Pro Val Ile Thr Asn Pro Pro Tyr 
    610                 615                 620                 


Asn His Thr Met Glu Val Glu Ile Gly Lys Pro Ala Ser Ile Ala Cys 
625                 630                 635                 640 


Ser Ala Cys Phe Gly Lys Gly Ser His Phe Leu Ala Asp Val Leu Trp 
                645                 650                 655     


Gln Ile Asn Lys Thr Val Val Gly Asn Phe Gly Glu Ala Arg Ile Gln 
            660                 665                 670         


Glu Glu Glu Gly Arg Asn Glu Ser Ser Ser Asn Asp Met Asp Cys Leu 
        675                 680                 685             


Thr Ser Val Leu Arg Ile Thr Gly Val Thr Glu Lys Asp Leu Ser Leu 
    690                 695                 700                 


Glu Tyr Asp Cys Leu Ala Leu Asn Leu His Gly Met Ile Arg His Thr 
705                 710                 715                 720 


Ile Arg Leu Arg Arg Lys Gln Pro Ser Lys Glu Cys Pro Ser His Ile 
                725                 730                 735     


Ala Ser Arg Gly Pro Phe Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu 
            740                 745                 750         


Asn Met His Thr Gly His His His His His His 
        755                 760             


<210>  2
<211>  737
<212>  PRT
<213>  artificial

<220>
<223>  mIL33trap (12xGGS)

<400>  2

Met Gly Leu Leu Trp Tyr Leu Met Ser Leu Ser Phe Tyr Gly Ile Leu 
1               5                   10                  15      


Gln Ser His Ala Ser Glu Arg Cys Asp Asp Trp Gly Leu Asp Thr Met 
            20                  25                  30          


Arg Gln Ile Gln Val Phe Glu Asp Glu Pro Ala Arg Ile Lys Cys Pro 
        35                  40                  45              


Leu Phe Glu His Phe Leu Lys Tyr Asn Tyr Ser Thr Ala His Ser Ser 
    50                  55                  60                  


Gly Leu Thr Leu Ile Trp Tyr Trp Thr Arg Gln Asp Arg Asp Leu Glu 
65                  70                  75                  80  


Glu Pro Ile Asn Phe Arg Leu Pro Glu Asn Arg Ile Ser Lys Glu Lys 
                85                  90                  95      


Asp Val Leu Trp Phe Arg Pro Thr Leu Leu Asn Asp Thr Gly Asn Tyr 
            100                 105                 110         


Thr Cys Met Leu Arg Asn Thr Thr Tyr Cys Ser Lys Val Ala Phe Pro 
        115                 120                 125             


Leu Glu Val Val Gln Lys Asp Ser Cys Phe Asn Ser Ala Met Arg Phe 
    130                 135                 140                 


Pro Val His Lys Met Tyr Ile Glu His Gly Ile His Lys Ile Thr Cys 
145                 150                 155                 160 


Pro Asn Val Asp Gly Tyr Phe Pro Ser Ser Val Lys Pro Ser Val Thr 
                165                 170                 175     


Trp Tyr Lys Gly Cys Thr Glu Ile Val Asp Phe His Asn Val Leu Pro 
            180                 185                 190         


Glu Gly Met Asn Leu Ser Phe Phe Ile Pro Leu Val Ser Asn Asn Gly 
        195                 200                 205             


Asn Tyr Thr Cys Val Val Thr Tyr Pro Glu Asn Gly Arg Leu Phe His 
    210                 215                 220                 


Leu Thr Arg Thr Val Thr Val Lys Val Val Gly Ser Pro Lys Asp Ala 
225                 230                 235                 240 


Leu Pro Pro Gln Ile Tyr Ser Pro Asn Asp Arg Val Val Tyr Glu Lys 
                245                 250                 255     


Glu Pro Gly Glu Glu Leu Val Ile Pro Cys Lys Val Tyr Phe Ser Phe 
            260                 265                 270         


Ile Met Asp Ser His Asn Glu Val Trp Trp Thr Ile Asp Gly Lys Lys 
        275                 280                 285             


Pro Asp Asp Val Thr Val Asp Ile Thr Ile Asn Glu Ser Val Ser Tyr 
    290                 295                 300                 


Ser Ser Thr Glu Asp Glu Thr Arg Thr Gln Ile Leu Ser Ile Lys Lys 
305                 310                 315                 320 


Val Thr Pro Glu Asp Leu Arg Arg Asn Tyr Val Cys His Ala Arg Asn 
                325                 330                 335     


Thr Lys Gly Glu Ala Glu Gln Ala Ala Lys Val Lys Gln Lys Gly Asn 
            340                 345                 350         


Gly Cys Thr Glu Pro Met Thr Leu Ser Arg Gly Gly Ser Gly Gly Ser 
        355                 360                 365             


Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly 
    370                 375                 380                 


Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Leu Gln 
385                 390                 395                 400 


Ser Lys Ser Ser Trp Gly Leu Glu Asn Glu Ala Leu Ile Val Arg Cys 
                405                 410                 415     


Pro Gln Arg Gly Arg Ser Thr Tyr Pro Val Glu Trp Tyr Tyr Ser Asp 
            420                 425                 430         


Thr Asn Glu Ser Ile Pro Thr Gln Lys Arg Asn Arg Ile Phe Val Ser 
        435                 440                 445             


Arg Asp Arg Leu Lys Phe Leu Pro Ala Arg Val Glu Asp Ser Gly Ile 
    450                 455                 460                 


Tyr Ala Cys Val Ile Arg Ser Pro Asn Leu Asn Lys Thr Gly Tyr Leu 
465                 470                 475                 480 


Asn Val Thr Ile His Lys Lys Pro Pro Ser Cys Asn Ile Pro Asp Tyr 
                485                 490                 495     


Leu Met Tyr Ser Thr Val Arg Gly Ser Asp Lys Asn Phe Lys Ile Thr 
            500                 505                 510         


Cys Pro Thr Ile Asp Leu Tyr Asn Trp Thr Ala Pro Val Gln Trp Phe 
        515                 520                 525             


Lys Asn Cys Lys Ala Leu Gln Glu Pro Arg Phe Arg Ala His Arg Ser 
    530                 535                 540                 


Tyr Leu Phe Ile Asp Asn Val Thr His Asp Asp Glu Gly Asp Tyr Thr 
545                 550                 555                 560 


Cys Gln Phe Thr His Ala Glu Asn Gly Thr Asn Tyr Ile Val Thr Ala 
                565                 570                 575     


Thr Arg Ser Phe Thr Val Glu Glu Lys Gly Phe Ser Met Phe Pro Val 
            580                 585                 590         


Ile Thr Asn Pro Pro Tyr Asn His Thr Met Glu Val Glu Ile Gly Lys 
        595                 600                 605             


Pro Ala Ser Ile Ala Cys Ser Ala Cys Phe Gly Lys Gly Ser His Phe 
    610                 615                 620                 


Leu Ala Asp Val Leu Trp Gln Ile Asn Lys Thr Val Val Gly Asn Phe 
625                 630                 635                 640 


Gly Glu Ala Arg Ile Gln Glu Glu Glu Gly Arg Asn Glu Ser Ser Ser 
                645                 650                 655     


Asn Asp Met Asp Cys Leu Thr Ser Val Leu Arg Ile Thr Gly Val Thr 
            660                 665                 670         


Glu Lys Asp Leu Ser Leu Glu Tyr Asp Cys Leu Ala Leu Asn Leu His 
        675                 680                 685             


Gly Met Ile Arg His Thr Ile Arg Leu Arg Arg Lys Gln Pro Ser Lys 
    690                 695                 700                 


Glu Cys Pro Ser His Ile Ala Ser Arg Gly Pro Phe Glu Gln Lys Leu 
705                 710                 715                 720 


Ile Ser Glu Glu Asp Leu Asn Met His Thr Gly His His His His His 
                725                 730                 735     


His 
    


<210>  3
<211>  727
<212>  PRT
<213>  artificial

<220>
<223>  mIL33trap (8xGGS)

<400>  3

Met Gly Leu Leu Trp Tyr Leu Met Ser Leu Ser Phe Tyr Gly Ile Leu 
1               5                   10                  15      


Gln Ser His Ala Ser Glu Arg Cys Asp Asp Trp Gly Leu Asp Thr Met 
            20                  25                  30          


Arg Gln Ile Gln Val Phe Glu Asp Glu Pro Ala Arg Ile Lys Cys Pro 
        35                  40                  45              


Leu Phe Glu His Phe Leu Lys Tyr Asn Tyr Ser Thr Ala His Ser Ser 
    50                  55                  60                  


Gly Leu Thr Leu Ile Trp Tyr Trp Thr Arg Gln Asp Arg Asp Leu Glu 
65                  70                  75                  80  


Glu Pro Ile Asn Phe Arg Leu Pro Glu Asn Arg Ile Ser Lys Glu Lys 
                85                  90                  95      


Asp Val Leu Trp Phe Arg Pro Thr Leu Leu Asn Asp Thr Gly Asn Tyr 
            100                 105                 110         


Thr Cys Met Leu Arg Asn Thr Thr Tyr Cys Ser Lys Val Ala Phe Pro 
        115                 120                 125             


Leu Glu Val Val Gln Lys Asp Ser Cys Phe Asn Ser Ala Met Arg Phe 
    130                 135                 140                 


Pro Val His Lys Met Tyr Ile Glu His Gly Ile His Lys Ile Thr Cys 
145                 150                 155                 160 


Pro Asn Val Asp Gly Tyr Phe Pro Ser Ser Val Lys Pro Ser Val Thr 
                165                 170                 175     


Trp Tyr Lys Gly Cys Thr Glu Ile Val Asp Phe His Asn Val Leu Pro 
            180                 185                 190         


Glu Gly Met Asn Leu Ser Phe Phe Ile Pro Leu Val Ser Asn Asn Gly 
        195                 200                 205             


Asn Tyr Thr Cys Val Val Thr Tyr Pro Glu Asn Gly Arg Leu Phe His 
    210                 215                 220                 


Leu Thr Arg Thr Val Thr Val Lys Val Val Gly Ser Pro Lys Asp Ala 
225                 230                 235                 240 


Leu Pro Pro Gln Ile Tyr Ser Pro Asn Asp Arg Val Val Tyr Glu Lys 
                245                 250                 255     


Glu Pro Gly Glu Glu Leu Val Ile Pro Cys Lys Val Tyr Phe Ser Phe 
            260                 265                 270         


Ile Met Asp Ser His Asn Glu Val Trp Trp Thr Ile Asp Gly Lys Lys 
        275                 280                 285             


Pro Asp Asp Val Thr Val Asp Ile Thr Ile Asn Glu Ser Val Ser Tyr 
    290                 295                 300                 


Ser Ser Thr Glu Asp Glu Thr Arg Thr Gln Ile Leu Ser Ile Lys Lys 
305                 310                 315                 320 


Val Thr Pro Glu Asp Leu Arg Arg Asn Tyr Val Cys His Ala Arg Asn 
                325                 330                 335     


Thr Lys Gly Glu Ala Glu Gln Ala Ala Lys Val Lys Gln Lys Gly Asn 
            340                 345                 350         


Gly Cys Thr Glu Pro Met Thr Leu Ser Arg Gly Gly Ser Gly Gly Ser 
        355                 360                 365             


Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly 
    370                 375                 380                 


Gly Ser Leu Gln Leu Gln Ser Lys Ser Ser Trp Gly Leu Glu Asn Glu 
385                 390                 395                 400 


Ala Leu Ile Val Arg Cys Pro Gln Arg Gly Arg Ser Thr Tyr Pro Val 
                405                 410                 415     


Glu Trp Tyr Tyr Ser Asp Thr Asn Glu Ser Ile Pro Thr Gln Lys Arg 
            420                 425                 430         


Asn Arg Ile Phe Val Ser Arg Asp Arg Leu Lys Phe Leu Pro Ala Arg 
        435                 440                 445             


Val Glu Asp Ser Gly Ile Tyr Ala Cys Val Ile Arg Ser Pro Asn Leu 
    450                 455                 460                 


Asn Lys Thr Gly Tyr Leu Asn Val Thr Ile His Lys Lys Pro Pro Ser 
465                 470                 475                 480 


Cys Asn Ile Pro Asp Tyr Leu Met Tyr Ser Thr Val Arg Gly Ser Asp 
                485                 490                 495     


Lys Asn Phe Lys Ile Thr Cys Pro Thr Ile Asp Leu Tyr Asn Trp Thr 
            500                 505                 510         


Ala Pro Val Gln Trp Phe Lys Asn Cys Lys Ala Leu Gln Glu Pro Arg 
        515                 520                 525             


Phe Arg Ala His Arg Ser Tyr Leu Phe Ile Asp Asn Val Thr His Asp 
    530                 535                 540                 


Asp Glu Gly Asp Tyr Thr Cys Gln Phe Thr His Ala Glu Asn Gly Thr 
545                 550                 555                 560 


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


Phe Ser Met Phe Pro Val Ile Thr Asn Pro Pro Tyr Asn His Thr Met 
            580                 585                 590         


Glu Val Glu Ile Gly Lys Pro Ala Ser Ile Ala Cys Ser Ala Cys Phe 
        595                 600                 605             


Gly Lys Gly Ser His Phe Leu Ala Asp Val Leu Trp Gln Ile Asn Lys 
    610                 615                 620                 


Thr Val Val Gly Asn Phe Gly Glu Ala Arg Ile Gln Glu Glu Glu Gly 
625                 630                 635                 640 


Arg Asn Glu Ser Ser Ser Asn Asp Met Asp Cys Leu Thr Ser Val Leu 
                645                 650                 655     


Arg Ile Thr Gly Val Thr Glu Lys Asp Leu Ser Leu Glu Tyr Asp Cys 
            660                 665                 670         


Leu Ala Leu Asn Leu His Gly Met Ile Arg His Thr Ile Arg Leu Arg 
        675                 680                 685             


Arg Lys Gln Pro Ser Lys Glu Cys Pro Ser His Ile Ala Ser Arg Gly 
    690                 695                 700                 


Pro Phe Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Asn Met His Thr 
705                 710                 715                 720 


Gly His His His His His His 
                725         


<210>  4
<211>  359
<212>  PRT
<213>  homo sapiens

<400>  4

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


Ala Ala Lys Phe Ser Lys Gln Ser Trp Gly Leu Glu Asn Glu Ala Leu 
            20                  25                  30          


Ile Val Arg Cys Pro Arg Gln Gly Lys Pro Ser Tyr Thr Val Asp Trp 
        35                  40                  45              


Tyr Tyr Ser Gln Thr Asn Lys Ser Ile Pro Thr Gln Glu Arg Asn Arg 
    50                  55                  60                  


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


Asp Ser Gly Ile Tyr Thr Cys Ile Val Arg Ser Pro Thr Phe Asn Arg 
                85                  90                  95      


Thr Gly Tyr Ala Asn Val Thr Ile Tyr Lys Lys Gln Ser Asp Cys Asn 
            100                 105                 110         


Val Pro Asp Tyr Leu Met Tyr Ser Thr Val Ser Gly Ser Glu Lys Asn 
        115                 120                 125             


Ser Lys Ile Tyr Cys Pro Thr Ile Asp Leu Tyr Asn Trp Thr Ala Pro 
    130                 135                 140                 


Leu Glu Trp Phe Lys Asn Cys Gln Ala Leu Gln Gly Ser Arg Tyr Arg 
145                 150                 155                 160 


Ala His Lys Ser Phe Leu Val Ile Asp Asn Val Met Thr Glu Asp Ala 
                165                 170                 175     


Gly Asp Tyr Thr Cys Lys Phe Ile His Asn Glu Asn Gly Ala Asn Tyr 
            180                 185                 190         


Ser Val Thr Ala Thr Arg Ser Phe Thr Val Lys Asp Glu Gln Gly Phe 
        195                 200                 205             


Ser Leu Phe Pro Val Ile Gly Ala Pro Ala Gln Asn Glu Ile Lys Glu 
    210                 215                 220                 


Val Glu Ile Gly Lys Asn Ala Asn Leu Thr Cys Ser Ala Cys Phe Gly 
225                 230                 235                 240 


Lys Gly Thr Gln Phe Leu Ala Ala Val Leu Trp Gln Leu Asn Gly Thr 
                245                 250                 255     


Lys Ile Thr Asp Phe Gly Glu Pro Arg Ile Gln Gln Glu Glu Gly Gln 
            260                 265                 270         


Asn Gln Ser Phe Ser Asn Gly Leu Ala Cys Leu Asp Met Val Leu Arg 
        275                 280                 285             


Ile Ala Asp Val Lys Glu Glu Asp Leu Leu Leu Gln Tyr Asp Cys Leu 
    290                 295                 300                 


Ala Leu Asn Leu His Gly Leu Arg Arg His Thr Val Arg Leu Ser Arg 
305                 310                 315                 320 


Lys Asn Pro Ser Lys Glu Cys Phe Ser Arg Pro Leu Glu Ser Arg Gly 
                325                 330                 335     


Pro Phe Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Asn Met His Thr 
            340                 345                 350         


Gly His His His His His His 
        355                 


<210>  5
<211>  382
<212>  PRT
<213>  Homo sapiens

<400>  5

Met Thr Leu Leu Trp Cys Val Val Ser Leu Tyr Phe Tyr Gly Ile Leu 
1               5                   10                  15      


Gln Ser Asp Ala Ser Glu Arg Cys Asp Asp Trp Gly Leu Asp Thr Met 
            20                  25                  30          


Arg Gln Ile Gln Val Phe Glu Asp Glu Pro Ala Arg Ile Lys Cys Pro 
        35                  40                  45              


Leu Phe Glu His Phe Leu Lys Phe Asn Tyr Ser Thr Ala His Ser Ala 
    50                  55                  60                  


Gly Leu Thr Leu Ile Trp Tyr Trp Thr Arg Gln Asp Arg Asp Leu Glu 
65                  70                  75                  80  


Glu Pro Ile Asn Phe Arg Leu Pro Glu Asn Arg Ile Ser Lys Glu Lys 
                85                  90                  95      


Asp Val Leu Trp Phe Arg Pro Thr Leu Leu Asn Asp Thr Gly Asn Tyr 
            100                 105                 110         


Thr Cys Met Leu Arg Asn Thr Thr Tyr Cys Ser Lys Val Ala Phe Pro 
        115                 120                 125             


Leu Glu Val Val Gln Lys Asp Ser Cys Phe Asn Ser Pro Met Lys Leu 
    130                 135                 140                 


Pro Val His Lys Leu Tyr Ile Glu Tyr Gly Ile Gln Arg Ile Thr Cys 
145                 150                 155                 160 


Pro Asn Val Asp Gly Tyr Phe Pro Ser Ser Val Lys Pro Thr Ile Thr 
                165                 170                 175     


Trp Tyr Met Gly Cys Tyr Lys Ile Gln Asn Phe Asn Asn Val Ile Pro 
            180                 185                 190         


Glu Gly Met Asn Leu Ser Phe Leu Ile Ala Leu Ile Ser Asn Asn Gly 
        195                 200                 205             


Asn Tyr Thr Cys Val Val Thr Tyr Pro Glu Asn Gly Arg Thr Phe His 
    210                 215                 220                 


Leu Thr Arg Thr Leu Thr Val Lys Val Val Gly Ser Pro Lys Asn Ala 
225                 230                 235                 240 


Val Pro Pro Val Ile His Ser Pro Asn Asp His Val Val Tyr Glu Lys 
                245                 250                 255     


Glu Pro Gly Glu Glu Leu Leu Ile Pro Cys Thr Val Tyr Phe Ser Phe 
            260                 265                 270         


Leu Met Asp Ser Arg Asn Glu Val Trp Trp Thr Ile Asp Gly Lys Lys 
        275                 280                 285             


Pro Asp Asp Ile Thr Ile Asp Val Thr Ile Asn Glu Ser Ile Ser His 
    290                 295                 300                 


Ser Arg Thr Glu Asp Glu Thr Arg Thr Gln Ile Leu Ser Ile Lys Lys 
305                 310                 315                 320 


Val Thr Ser Glu Asp Leu Lys Arg Ser Tyr Val Cys His Ala Arg Ser 
                325                 330                 335     


Ala Lys Gly Glu Val Ala Lys Ala Ala Lys Val Lys Gln Lys Gly Asn 
            340                 345                 350         


Arg Cys Gly Gln Ser Arg Gly Pro Phe Glu Gln Lys Leu Ile Ser Glu 
        355                 360                 365             


Glu Asp Leu Asn Met His Thr Gly His His His His His His 
    370                 375                 380         


<210>  6
<211>  761
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Fusion protein

<400>  6

Met Thr Leu Leu Trp Cys Val Val Ser Leu Tyr Phe Tyr Gly Ile Leu 
1               5                   10                  15      


Gln Ser Asp Ala Ser Glu Arg Cys Asp Asp Trp Gly Leu Asp Thr Met 
            20                  25                  30          


Arg Gln Ile Gln Val Phe Glu Asp Glu Pro Ala Arg Ile Lys Cys Pro 
        35                  40                  45              


Leu Phe Glu His Phe Leu Lys Phe Asn Tyr Ser Thr Ala His Ser Ala 
    50                  55                  60                  


Gly Leu Thr Leu Ile Trp Tyr Trp Thr Arg Gln Asp Arg Asp Leu Glu 
65                  70                  75                  80  


Glu Pro Ile Asn Phe Arg Leu Pro Glu Asn Arg Ile Ser Lys Glu Lys 
                85                  90                  95      


Asp Val Leu Trp Phe Arg Pro Thr Leu Leu Asn Asp Thr Gly Asn Tyr 
            100                 105                 110         


Thr Cys Met Leu Arg Asn Thr Thr Tyr Cys Ser Lys Val Ala Phe Pro 
        115                 120                 125             


Leu Glu Val Val Gln Lys Asp Ser Cys Phe Asn Ser Pro Met Lys Leu 
    130                 135                 140                 


Pro Val His Lys Leu Tyr Ile Glu Tyr Gly Ile Gln Arg Ile Thr Cys 
145                 150                 155                 160 


Pro Asn Val Asp Gly Tyr Phe Pro Ser Ser Val Lys Pro Thr Ile Thr 
                165                 170                 175     


Trp Tyr Met Gly Cys Tyr Lys Ile Gln Asn Phe Asn Asn Val Ile Pro 
            180                 185                 190         


Glu Gly Met Asn Leu Ser Phe Leu Ile Ala Leu Ile Ser Asn Asn Gly 
        195                 200                 205             


Asn Tyr Thr Cys Val Val Thr Tyr Pro Glu Asn Gly Arg Thr Phe His 
    210                 215                 220                 


Leu Thr Arg Thr Leu Thr Val Lys Val Val Gly Ser Pro Lys Asn Ala 
225                 230                 235                 240 


Val Pro Pro Val Ile His Ser Pro Asn Asp His Val Val Tyr Glu Lys 
                245                 250                 255     


Glu Pro Gly Glu Glu Leu Leu Ile Pro Cys Thr Val Tyr Phe Ser Phe 
            260                 265                 270         


Leu Met Asp Ser Arg Asn Glu Val Trp Trp Thr Ile Asp Gly Lys Lys 
        275                 280                 285             


Pro Asp Asp Ile Thr Ile Asp Val Thr Ile Asn Glu Ser Ile Ser His 
    290                 295                 300                 


Ser Arg Thr Glu Asp Glu Thr Arg Thr Gln Ile Leu Ser Ile Lys Lys 
305                 310                 315                 320 


Val Thr Ser Glu Asp Leu Lys Arg Ser Tyr Val Cys His Ala Arg Ser 
                325                 330                 335     


Ala Lys Gly Glu Val Ala Lys Ala Ala Lys Val Lys Gln Lys Gly Asn 
            340                 345                 350         


Arg Cys Gly Gln Ser Arg Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly 
        355                 360                 365             


Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly 
    370                 375                 380                 


Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser 
385                 390                 395                 400 


Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly 
                405                 410                 415     


Gly Ser Leu His Lys Phe Ser Lys Gln Ser Trp Gly Leu Glu Asn Glu 
            420                 425                 430         


Ala Leu Ile Val Arg Cys Pro Arg Gln Gly Lys Pro Ser Tyr Thr Val 
        435                 440                 445             


Asp Trp Tyr Tyr Ser Gln Thr Asn Lys Ser Ile Pro Thr Gln Glu Arg 
    450                 455                 460                 


Asn Arg Val Phe Ala Ser Gly Gln Leu Leu Lys Phe Leu Pro Ala Ala 
465                 470                 475                 480 


Val Ala Asp Ser Gly Ile Tyr Thr Cys Ile Val Arg Ser Pro Thr Phe 
                485                 490                 495     


Asn Arg Thr Gly Tyr Ala Asn Val Thr Ile Tyr Lys Lys Gln Ser Asp 
            500                 505                 510         


Cys Asn Val Pro Asp Tyr Leu Met Tyr Ser Thr Val Ser Gly Ser Glu 
        515                 520                 525             


Lys Asn Ser Lys Ile Tyr Cys Pro Thr Ile Asp Leu Tyr Asn Trp Thr 
    530                 535                 540                 


Ala Pro Leu Glu Trp Phe Lys Asn Cys Gln Ala Leu Gln Gly Ser Arg 
545                 550                 555                 560 


Tyr Arg Ala His Lys Ser Phe Leu Val Ile Asp Asn Val Met Thr Glu 
                565                 570                 575     


Asp Ala Gly Asp Tyr Thr Cys Lys Phe Ile His Asn Glu Asn Gly Ala 
            580                 585                 590         


Asn Tyr Ser Val Thr Ala Thr Arg Ser Phe Thr Val Lys Asp Glu Gln 
        595                 600                 605             


Gly Phe Ser Leu Phe Pro Val Ile Gly Ala Pro Ala Gln Asn Glu Ile 
    610                 615                 620                 


Lys Glu Val Glu Ile Gly Lys Asn Ala Asn Leu Thr Cys Ser Ala Cys 
625                 630                 635                 640 


Phe Gly Lys Gly Thr Gln Phe Leu Ala Ala Val Leu Trp Gln Leu Asn 
                645                 650                 655     


Gly Thr Lys Ile Thr Asp Phe Gly Glu Pro Arg Ile Gln Gln Glu Glu 
            660                 665                 670         


Gly Gln Asn Gln Ser Phe Ser Asn Gly Leu Ala Cys Leu Asp Met Val 
        675                 680                 685             


Leu Arg Ile Ala Asp Val Lys Glu Glu Asp Leu Leu Leu Gln Tyr Asp 
    690                 695                 700                 


Cys Leu Ala Leu Asn Leu His Gly Leu Arg Arg His Thr Val Arg Leu 
705                 710                 715                 720 


Ser Arg Lys Asn Pro Ser Lys Glu Cys Phe Ser Arg Pro Leu Glu Ser 
                725                 730                 735     


Arg Gly Pro Phe Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Asn Met 
            740                 745                 750         


His Thr Gly His His His His His His 
        755                 760     


<210>  7
<211>  725
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Fusion protein

<400>  7

Met Thr Leu Leu Trp Cys Val Val Ser Leu Tyr Phe Tyr Gly Ile Leu 
1               5                   10                  15      


Gln Ser Asp Ala Ser Glu Arg Cys Asp Asp Trp Gly Leu Asp Thr Met 
            20                  25                  30          


Arg Gln Ile Gln Val Phe Glu Asp Glu Pro Ala Arg Ile Lys Cys Pro 
        35                  40                  45              


Leu Phe Glu His Phe Leu Lys Phe Asn Tyr Ser Thr Ala His Ser Ala 
    50                  55                  60                  


Gly Leu Thr Leu Ile Trp Tyr Trp Thr Arg Gln Asp Arg Asp Leu Glu 
65                  70                  75                  80  


Glu Pro Ile Asn Phe Arg Leu Pro Glu Asn Arg Ile Ser Lys Glu Lys 
                85                  90                  95      


Asp Val Leu Trp Phe Arg Pro Thr Leu Leu Asn Asp Thr Gly Asn Tyr 
            100                 105                 110         


Thr Cys Met Leu Arg Asn Thr Thr Tyr Cys Ser Lys Val Ala Phe Pro 
        115                 120                 125             


Leu Glu Val Val Gln Lys Asp Ser Cys Phe Asn Ser Pro Met Lys Leu 
    130                 135                 140                 


Pro Val His Lys Leu Tyr Ile Glu Tyr Gly Ile Gln Arg Ile Thr Cys 
145                 150                 155                 160 


Pro Asn Val Asp Gly Tyr Phe Pro Ser Ser Val Lys Pro Thr Ile Thr 
                165                 170                 175     


Trp Tyr Met Gly Cys Tyr Lys Ile Gln Asn Phe Asn Asn Val Ile Pro 
            180                 185                 190         


Glu Gly Met Asn Leu Ser Phe Leu Ile Ala Leu Ile Ser Asn Asn Gly 
        195                 200                 205             


Asn Tyr Thr Cys Val Val Thr Tyr Pro Glu Asn Gly Arg Thr Phe His 
    210                 215                 220                 


Leu Thr Arg Thr Leu Thr Val Lys Val Val Gly Ser Pro Lys Asn Ala 
225                 230                 235                 240 


Val Pro Pro Val Ile His Ser Pro Asn Asp His Val Val Tyr Glu Lys 
                245                 250                 255     


Glu Pro Gly Glu Glu Leu Leu Ile Pro Cys Thr Val Tyr Phe Ser Phe 
            260                 265                 270         


Leu Met Asp Ser Arg Asn Glu Val Trp Trp Thr Ile Asp Gly Lys Lys 
        275                 280                 285             


Pro Asp Asp Ile Thr Ile Asp Val Thr Ile Asn Glu Ser Ile Ser His 
    290                 295                 300                 


Ser Arg Thr Glu Asp Glu Thr Arg Thr Gln Ile Leu Ser Ile Lys Lys 
305                 310                 315                 320 


Val Thr Ser Glu Asp Leu Lys Arg Ser Tyr Val Cys His Ala Arg Ser 
                325                 330                 335     


Ala Lys Gly Glu Val Ala Lys Ala Ala Lys Val Lys Gln Lys Gly Asn 
            340                 345                 350         


Arg Cys Gly Gln Ser Arg Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly 
        355                 360                 365             


Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Gly Gly Ser Leu His 
    370                 375                 380                 


Lys Phe Ser Lys Gln Ser Trp Gly Leu Glu Asn Glu Ala Leu Ile Val 
385                 390                 395                 400 


Arg Cys Pro Arg Gln Gly Lys Pro Ser Tyr Thr Val Asp Trp Tyr Tyr 
                405                 410                 415     


Ser Gln Thr Asn Lys Ser Ile Pro Thr Gln Glu Arg Asn Arg Val Phe 
            420                 425                 430         


Ala Ser Gly Gln Leu Leu Lys Phe Leu Pro Ala Ala Val Ala Asp Ser 
        435                 440                 445             


Gly Ile Tyr Thr Cys Ile Val Arg Ser Pro Thr Phe Asn Arg Thr Gly 
    450                 455                 460                 


Tyr Ala Asn Val Thr Ile Tyr Lys Lys Gln Ser Asp Cys Asn Val Pro 
465                 470                 475                 480 


Asp Tyr Leu Met Tyr Ser Thr Val Ser Gly Ser Glu Lys Asn Ser Lys 
                485                 490                 495     


Ile Tyr Cys Pro Thr Ile Asp Leu Tyr Asn Trp Thr Ala Pro Leu Glu 
            500                 505                 510         


Trp Phe Lys Asn Cys Gln Ala Leu Gln Gly Ser Arg Tyr Arg Ala His 
        515                 520                 525             


Lys Ser Phe Leu Val Ile Asp Asn Val Met Thr Glu Asp Ala Gly Asp 
    530                 535                 540                 


Tyr Thr Cys Lys Phe Ile His Asn Glu Asn Gly Ala Asn Tyr Ser Val 
545                 550                 555                 560 


Thr Ala Thr Arg Ser Phe Thr Val Lys Asp Glu Gln Gly Phe Ser Leu 
                565                 570                 575     


Phe Pro Val Ile Gly Ala Pro Ala Gln Asn Glu Ile Lys Glu Val Glu 
            580                 585                 590         


Ile Gly Lys Asn Ala Asn Leu Thr Cys Ser Ala Cys Phe Gly Lys Gly 
        595                 600                 605             


Thr Gln Phe Leu Ala Ala Val Leu Trp Gln Leu Asn Gly Thr Lys Ile 
    610                 615                 620                 


Thr Asp Phe Gly Glu Pro Arg Ile Gln Gln Glu Glu Gly Gln Asn Gln 
625                 630                 635                 640 


Ser Phe Ser Asn Gly Leu Ala Cys Leu Asp Met Val Leu Arg Ile Ala 
                645                 650                 655     


Asp Val Lys Glu Glu Asp Leu Leu Leu Gln Tyr Asp Cys Leu Ala Leu 
            660                 665                 670         


Asn Leu His Gly Leu Arg Arg His Thr Val Arg Leu Ser Arg Lys Asn 
        675                 680                 685             


Pro Ser Lys Glu Cys Phe Ser Arg Pro Leu Glu Ser Arg Gly Pro Phe 
    690                 695                 700                 


Glu Gln Lys Leu Ile Ser Glu Glu Asp Leu Asn Met His Thr Gly His 
705                 710                 715                 720 


His His His His His 
                725 


<210>  8
<211>  31
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  8
agttctagaa tgattgacag acagagaatg g                                      31


<210>  9
<211>  30
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  9
taatctagaa gcaatgtgtg agggacactc                                        30


<210>  10
<211>  32
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  10
aattctagaa aagtgtttca ggtctaagca tg                                     32


<210>  11
<211>  30
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  11
ttcgaattca tgggacttct gtggtatttg                                        30


<210>  12
<211>  28
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  12
agatctagac agagtcatcg gctcggtg                                          28


<210>  13
<211>  30
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  13
cagctgcaga gtaaatcgtc ctggggtctg                                        30


<210>  14
<211>  32
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  14
atcgatatcg tttaaactca atggtgatgg tg                                     32


<210>  15
<211>  29
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  15
agatctagag gagggagtgg tggctctgg                                         29


<210>  16
<211>  29
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  16
cagctgcagg ctcccaccac tccctccag                                         29


<210>  17
<211>  34
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  17
tccggatcca tggggttttg gatcttagca attc                                   34


<210>  18
<211>  38
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  18
taagcggccg cgagaaacac tccttacttg gatttttc                               38


<210>  19
<211>  33
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  19
ttcgaattca tgacacttct gtggtgtgta gtg                                    33


<210>  20
<211>  33
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  20
atttctagac tgaccgcatc tattaccttt ctg                                    33


<210>  21
<211>  32
<212>  DNA
<213>  artificial

<220>
<223>  Primer

<400>  21
catatgcata agtttagtaa acaatcatgg gg                                     32


