                         SEQUENCE LISTING

<110>  Fred Hutchinson Cancer Research Center
       The Board of Trustees of The Leland Stanford Junior 
       University
       Bernstein, Irwin
       Luca, Vincent
       Garcia, Kenan C.
 
<120>  BI SPECIFIC MOLECULE FOR CELL SPECIFIC NOTCH INHIBITION AND 
       RELATED METHODS AND COMPOSITIONS

<130>  FHTM158751

<140>  TBD
<141>  2017-07-11

<150>  62365855
<151>  2016-07-22

<160>  10    

<170>  PatentIn version 3.5

<210>  1
<211>  685
<212>  PRT
<213>  Rattus norvegicus

<400>  1

Met Thr Pro Gly Ser Arg Ser Ala Cys Arg Trp Ala Leu Leu Leu Leu 
1               5                   10                  15      


Ala Val Leu Trp Pro Gln Arg Ala Ala Gly Ser Gly Ile Phe Gln Leu 
            20                  25                  30          


Arg Leu Gln Glu Phe Ala Asn Glu Arg Gly Met Leu Ala Asn Gly Arg 
        35                  40                  45              


Pro Cys Glu Pro Gly Cys Arg Thr Phe Phe Arg Ile Cys Leu Lys His 
    50                  55                  60                  


Tyr Gln Ala Thr Phe Ser Glu Gly Pro Cys Thr Phe Gly Asn Val Ser 
65                  70                  75                  80  


Thr Pro Val Leu Gly Thr Asn Ser Phe Val Ile Arg Asp Lys Asn Ser 
                85                  90                  95      


Gly Ser Gly Arg Asn Pro Leu Gln Leu Pro Phe Asn Phe Thr Trp Pro 
            100                 105                 110         


Gly Thr Phe Ser Leu Asn Ile Gln Ala Trp His Thr Pro Gly Asp Asp 
        115                 120                 125             


Leu Arg Pro Glu Thr Ser Pro Gly Asn Ser Leu Ile Ser Gln Ile Ile 
    130                 135                 140                 


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


Asn Asn Thr Leu Thr Arg Leu Arg Tyr Ser Tyr Arg Val Val Cys Ser 
                165                 170                 175     


Asp Asn Tyr Tyr Gly Asp Ser Cys Ser Arg Leu Cys Lys Lys Arg Asp 
            180                 185                 190         


Asp His Phe Gly His Tyr Glu Cys Gln Pro Asp Gly Ser Leu Ser Cys 
        195                 200                 205             


Leu Pro Gly Trp Thr Gly Lys Tyr Cys Asp Gln Pro Ile Cys Leu Ser 
    210                 215                 220                 


Gly Cys His Glu Gln Asn Gly Tyr Cys Ser Lys Pro Asp Glu Cys Asn 
225                 230                 235                 240 


Cys Arg Pro Gly Trp Gln Gly Pro Leu Cys Asn Glu Cys Ile Pro His 
                245                 250                 255     


Asn Gly Cys Arg His Gly Thr Cys Thr Ile Pro Trp Gln Cys Ala Cys 
            260                 265                 270         


Asp Glu Gly Trp Gly Gly Leu Phe Cys Asp Gln Asp Leu Asn Tyr Cys 
        275                 280                 285             


Thr His His Ser Pro Cys Lys Asn Gly Ser Thr Cys Ser Asn Ser Gly 
    290                 295                 300                 


Pro Arg Gly Tyr Thr Cys Thr Cys Leu Pro Gly Tyr Thr Gly Glu His 
305                 310                 315                 320 


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


Gly Ser Cys Lys Asp His Glu Asn Ser Tyr His Cys Leu Cys Pro Pro 
            340                 345                 350         


Gly Tyr Tyr Gly Gln His Cys Glu His Ser Thr Leu Thr Cys Ala Asp 
        355                 360                 365             


Ser Pro Cys Phe Asn Gly Gly Ser Cys Arg Glu Arg Asn Gln Gly Ala 
    370                 375                 380                 


Ser Tyr Ala Cys Glu Cys Pro Pro Asn Phe Thr Gly Ser Asn Cys Glu 
385                 390                 395                 400 


Lys Lys Val Asp Arg Cys Thr Ser Asn Pro Cys Ala Asn Gly Gly Gln 
                405                 410                 415     


Cys Leu Asn Arg Gly Pro Ser Arg Thr Cys Arg Cys Arg Pro Gly Phe 
            420                 425                 430         


Thr Gly Thr His Cys Glu Leu His Ile Ser Asp Cys Ala Arg Ser Pro 
        435                 440                 445             


Cys Ala His Gly Gly Thr Cys His Asp Leu Glu Asn Gly Pro Val Cys 
    450                 455                 460                 


Thr Cys Pro Ala Gly Phe Ser Gly Arg Arg Cys Glu Val Arg Ile Thr 
465                 470                 475                 480 


Asn Asp Ala Cys Ala Ser Gly Pro Cys Phe Asn Gly Ala Thr Cys Tyr 
                485                 490                 495     


Thr Gly Leu Ser Pro Asn Asn Phe Val Cys Asn Cys Pro Tyr Gly Phe 
            500                 505                 510         


Val Gly Ser Arg Cys Glu Phe Pro Val Gly Leu Pro Pro Ser Phe Pro 
        515                 520                 525             


Trp Val Ala Val Ser Leu Gly Val Gly Leu Val Val Leu Leu Val Leu 
    530                 535                 540                 


Leu Val Met Val Ala Val Ala Val Arg Gln Leu Arg Leu Arg Arg Pro 
545                 550                 555                 560 


Asp Asp Asp Ser Arg Glu Ala Met Asn Asn Leu Ser Asp Phe Gln Lys 
                565                 570                 575     


Asp Asn Leu Ile Pro Ala Ala Gln Leu Lys Asn Thr Asn Gln Lys Lys 
            580                 585                 590         


Glu Leu Glu Val Asp Cys Gly Leu Asp Lys Ser Asn Cys Gly Lys Leu 
        595                 600                 605             


Gln Asn His Thr Leu Asp Tyr Asn Leu Ala Pro Gly Phe Leu Gly Arg 
    610                 615                 620                 


Gly Ser Thr Pro Gly Lys Tyr Pro His Ser Asp Lys Ser Leu Gly Glu 
625                 630                 635                 640 


Lys Val Pro Leu Arg Leu His Ser Glu Lys Pro Ala Cys Arg Ile Ser 
                645                 650                 655     


Ala Ile Cys Ser Pro Arg Asp Ser Met Tyr Gln Ser Val Cys Leu Ile 
            660                 665                 670         


Ser Glu Glu Arg Asn Glu Cys Val Ile Ala Thr Glu Val 
        675                 680                 685 


<210>  2
<211>  257
<212>  PRT
<213>  Rattus norvegicus

<400>  2

Ser Gly Ile Phe Gln Leu Arg Leu Gln Glu Phe Ala Asn Glu Arg Gly 
1               5                   10                  15      


Met Leu Ala Asn Gly Arg Pro Cys Glu Pro Gly Cys Arg Thr Phe Phe 
            20                  25                  30          


Arg Ile Cys Leu Lys His Tyr Gln Ala Thr Phe Ser Glu Gly Pro Cys 
        35                  40                  45              


Thr Phe Gly Asn Val Ser Thr Pro Val Leu Gly Thr Asn Ser Phe Val 
    50                  55                  60                  


Ile Arg Asp Lys Asn Ser Gly Ser Gly Arg Asn Pro Leu Gln Leu Pro 
65                  70                  75                  80  


Phe Asn Phe Thr Trp Pro Gly Thr Phe Ser Leu Asn Ile Gln Ala Trp 
                85                  90                  95      


His Thr Pro Gly Asp Asp Leu Arg Pro Glu Thr Ser Pro Gly Asn Ser 
            100                 105                 110         


Leu Ile Ser Gln Ile Ile Ile Gln Gly Ser Leu Ala Val Gly Lys Asn 
        115                 120                 125             


Trp Lys Ser Asp Glu Gln Asn Asn Thr Leu Thr Arg Leu Arg Tyr Ser 
    130                 135                 140                 


Tyr Arg Val Val Cys Ser Asp Asn Tyr Tyr Gly Asp Ser Cys Ser Arg 
145                 150                 155                 160 


Leu Cys Lys Lys Arg Asp Asp His Phe Gly His Tyr Glu Cys Gln Pro 
                165                 170                 175     


Asp Gly Ser Leu Ser Cys Leu Pro Gly Trp Thr Gly Lys Tyr Cys Asp 
            180                 185                 190         


Gln Pro Ile Cys Leu Ser Gly Cys His Glu Gln Asn Gly Tyr Cys Ser 
        195                 200                 205             


Lys Pro Asp Glu Cys Asn Cys Arg Pro Gly Trp Gln Gly Pro Leu Cys 
    210                 215                 220                 


Asn Glu Cys Ile Pro His Asn Gly Cys Arg His Gly Thr Cys Thr Ile 
225                 230                 235                 240 


Pro Trp Gln Cys Ala Cys Asp Glu Gly Trp Gly Gly Leu Phe Cys Asp 
                245                 250                 255     


Gln 
    


<210>  3
<211>  257
<212>  PRT
<213>  Rattus norvegicus

<400>  3

Ser Ser Ile Phe Gln Leu Arg Leu Gln Glu Phe Ala Asn Glu Arg Gly 
1               5                   10                  15      


Met Leu Ala Asn Gly Arg Pro Cys Glu Pro Gly Cys Arg Thr Phe Phe 
            20                  25                  30          


Arg Ile Cys Leu Lys His Tyr Gln Ala Thr Phe Ser Glu Gly Pro Cys 
        35                  40                  45              


Thr Phe Gly Asn Val Ser Thr Pro Val Leu Gly Thr Asn Ser Phe Val 
    50                  55                  60                  


Ile Arg Asp Lys Asn Ser Gly Ser Gly Arg Asn Pro Leu Gln Leu Pro 
65                  70                  75                  80  


Leu Asn Phe Thr Trp Pro Gly Thr Phe Ser Leu Ile Ile Gln Ala Trp 
                85                  90                  95      


His Thr Pro Gly Asp Asp Leu Arg Pro Glu Thr Ser Pro Gly Asn Ser 
            100                 105                 110         


Leu Ile Ser Gln Phe Ile Ile Gln Gly Ser Leu Ala Val Gly Lys Asn 
        115                 120                 125             


Trp Lys Ser Asp Glu Gln Asn Asn Thr Leu Thr Arg Leu Arg Tyr Ser 
    130                 135                 140                 


Tyr Arg Val Val Cys Ser Asp Asn Tyr Tyr Gly Asp Ser Cys Ser Arg 
145                 150                 155                 160 


Leu Cys Lys Lys Arg Asp Asp Tyr Phe Gly His Tyr Glu Cys Gln Pro 
                165                 170                 175     


Asp Gly Ser Pro Ser Cys Leu Pro Gly Trp Thr Gly Glu Tyr Cys Asp 
            180                 185                 190         


Gln Pro Ile Cys Leu Ser Gly Cys His Glu Gln Asn Gly Tyr Cys Ser 
        195                 200                 205             


Lys Pro Asp Glu Cys Asn Cys Arg Pro Gly Trp Gln Gly Pro Leu Cys 
    210                 215                 220                 


Asn Glu Cys Ile Pro His Asn Gly Cys Arg His Gly Thr Cys Thr Ile 
225                 230                 235                 240 


Pro Trp Gln Cys Ala Cys Asp Glu Gly Trp Gly Gly Leu Phe Cys Asp 
                245                 250                 255     


Gln 
    


<210>  4
<211>  1219
<212>  PRT
<213>  Rattus norvegicus

<400>  4

Met Arg Ser Pro Arg Thr Arg Gly Arg Pro Gly Arg Pro Leu Ser Leu 
1               5                   10                  15      


Leu Leu Ala Leu Leu Cys Ala Leu Arg Ala Lys Val Cys Gly Ala Ser 
            20                  25                  30          


Gly Gln Phe Glu Leu Glu Ile Leu Ser Met Gln Asn Val Asn Gly Glu 
        35                  40                  45              


Leu Gln Asn Gly Asn Cys Cys Gly Gly Ala Arg Asn Pro Gly Asp Arg 
    50                  55                  60                  


Lys Cys Thr Arg Asp Glu Cys Asp Thr Tyr Phe Lys Val Cys Leu Lys 
65                  70                  75                  80  


Glu Tyr Gln Ser Arg Val Thr Ala Gly Gly Pro Cys Ser Phe Gly Ser 
                85                  90                  95      


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


Arg Gly Asn Asp Arg Asn Arg Ile Val Leu Pro Phe Ser Phe Ala Trp 
        115                 120                 125             


Pro Arg Ser Tyr Thr Leu Leu Val Glu Ala Trp Asp Ser Ser Asn Asp 
    130                 135                 140                 


Thr Ile Gln Pro Asp Ser Ile Ile Glu Lys Ala Ser His Ser Gly Met 
145                 150                 155                 160 


Ile Asn Pro Ser Arg Gln Trp Gln Thr Leu Lys Gln Asn Thr Gly Ile 
                165                 170                 175     


Ala His Phe Glu Tyr Gln Ile Arg Val Thr Cys Asp Asp His Tyr Tyr 
            180                 185                 190         


Gly Phe Gly Cys Asn Lys Phe Cys Arg Pro Arg Asp Asp Phe Phe Gly 
        195                 200                 205             


His Tyr Ala Cys Asp Gln Asn Gly Asn Lys Thr Cys Met Glu Gly Trp 
    210                 215                 220                 


Met Gly Pro Glu Cys Asn Lys Ala Ile Cys Arg Gln Gly Cys Ser Pro 
225                 230                 235                 240 


Lys His Gly Ser Cys Lys Leu Pro Gly Asp Cys Arg Cys Gln Tyr Gly 
                245                 250                 255     


Trp Gln Gly Leu Tyr Cys Asp Lys Cys Ile Pro His Pro Gly Cys Val 
            260                 265                 270         


His Gly Thr Cys Asn Glu Pro Trp Gln Cys Leu Cys Glu Thr Asn Trp 
        275                 280                 285             


Gly Gly Gln Leu Cys Asp Lys Asp Leu Asn Tyr Cys Gly Thr His Gln 
    290                 295                 300                 


Pro Cys Leu Asn Arg Gly Thr Cys Ser Asn Thr Gly Pro Asp Lys Tyr 
305                 310                 315                 320 


Gln Cys Ser Cys Pro Glu Gly Tyr Ser Gly Pro Asn Cys Glu Ile Ala 
                325                 330                 335     


Glu His Ala Cys Leu Ser Asp Pro Cys His Asn Arg Gly Ser Cys Lys 
            340                 345                 350         


Glu Thr Ser Ser Gly Phe Glu Cys Glu Cys Ser Pro Gly Trp Thr Gly 
        355                 360                 365             


Pro Thr Cys Ser Thr Asn Ile Asp Asp Cys Ser Pro Asn Asn Cys Ser 
    370                 375                 380                 


His Gly Gly Thr Cys Gln Asp Leu Val Asn Gly Phe Lys Cys Val Cys 
385                 390                 395                 400 


Pro Pro Gln Trp Thr Gly Lys Thr Cys Gln Leu Asp Ala Asn Glu Cys 
                405                 410                 415     


Glu Ala Lys Pro Cys Val Asn Ala Arg Ser Cys Lys Asn Leu Ile Ala 
            420                 425                 430         


Ser Tyr Tyr Cys Asp Cys Leu Pro Gly Trp Met Gly Gln Asn Cys Asp 
        435                 440                 445             


Ile Asn Ile Asn Asp Cys Leu Gly Gln Cys Gln Asn Asp Ala Ser Cys 
    450                 455                 460                 


Arg Asp Leu Val Asn Gly Tyr Arg Cys Ile Cys Pro Pro Gly Tyr Ala 
465                 470                 475                 480 


Gly Asp His Cys Glu Arg Asp Ile Asp Glu Cys Ala Ser Asn Pro Cys 
                485                 490                 495     


Leu Asn Gly Gly His Cys Gln Asn Glu Ile Asn Arg Phe Gln Cys Leu 
            500                 505                 510         


Cys Pro Thr Gly Phe Ser Gly Asn Leu Cys Gln Leu Asp Ile Asp Tyr 
        515                 520                 525             


Cys Glu Pro Asn Pro Cys Gln Asn Gly Ala Gln Cys Tyr Asn Arg Ala 
    530                 535                 540                 


Ser Asp Tyr Phe Cys Lys Cys Pro Glu Asp Tyr Glu Gly Lys Asn Cys 
545                 550                 555                 560 


Ser His Leu Lys Asp His Cys Arg Thr Thr Pro Cys Glu Val Ile Asp 
                565                 570                 575     


Ser Cys Thr Val Ala Met Ala Ser Asn Asp Thr Pro Glu Gly Val Arg 
            580                 585                 590         


Tyr Ile Ser Ser Asn Val Cys Gly Pro His Gly Lys Cys Lys Ser Glu 
        595                 600                 605             


Ser Gly Gly Lys Phe Thr Cys Asp Cys Asn Lys Gly Phe Thr Gly Thr 
    610                 615                 620                 


Tyr Cys His Glu Asn Ile Asn Asp Cys Glu Gly Asn Pro Cys Thr Asn 
625                 630                 635                 640 


Gly Gly Thr Cys Ile Asp Gly Val Asn Ser Tyr Lys Cys Ile Cys Ser 
                645                 650                 655     


Asp Gly Trp Glu Gly Ala His Cys Glu Asn Asn Ile Asn Asp Cys Ser 
            660                 665                 670         


Gln Asn Pro Cys His Tyr Gly Gly Thr Cys Arg Asp Leu Val Asn Asp 
        675                 680                 685             


Phe Tyr Cys Asp Cys Lys Asn Gly Trp Lys Gly Lys Thr Cys His Ser 
    690                 695                 700                 


Arg Asp Ser Gln Cys Asp Glu Ala Thr Cys Asn Asn Gly Gly Thr Cys 
705                 710                 715                 720 


Tyr Asp Glu Val Asp Thr Phe Lys Cys Met Cys Pro Gly Gly Trp Glu 
                725                 730                 735     


Gly Thr Thr Cys Asn Ile Ala Arg Asn Ser Ser Cys Leu Pro Asn Pro 
            740                 745                 750         


Cys His Asn Gly Gly Thr Cys Val Val Asn Gly Asp Ser Phe Thr Cys 
        755                 760                 765             


Val Cys Lys Glu Gly Trp Glu Gly Pro Ile Cys Thr Gln Asn Thr Asn 
    770                 775                 780                 


Asp Cys Ser Pro His Pro Cys Tyr Asn Ser Gly Thr Cys Val Asp Gly 
785                 790                 795                 800 


Asp Asn Trp Tyr Arg Cys Glu Cys Ala Pro Gly Phe Ala Gly Pro Asp 
                805                 810                 815     


Cys Arg Ile Asn Ile Asn Glu Cys Gln Ser Ser Pro Cys Ala Phe Gly 
            820                 825                 830         


Ala Thr Cys Val Asp Glu Ile Asn Gly Tyr Gln Cys Ile Cys Pro Pro 
        835                 840                 845             


Gly His Ser Gly Ala Lys Cys His Glu Val Ser Gly Arg Ser Cys Ile 
    850                 855                 860                 


Thr Met Gly Arg Val Ile Leu Asp Gly Ala Lys Trp Asp Asp Asp Cys 
865                 870                 875                 880 


Asn Thr Cys Gln Cys Leu Asn Gly Arg Val Ala Cys Ser Lys Val Trp 
                885                 890                 895     


Cys Gly Pro Arg Pro Cys Gln Leu His Lys Gly His Gly Glu Cys Pro 
            900                 905                 910         


Asn Gly Gln Ser Cys Ile Pro Val Leu Asp Asp Gln Cys Phe Val Arg 
        915                 920                 925             


Pro Cys Thr Gly Ala Gly Glu Cys Arg Ser Ser Ser Leu Gln Pro Val 
    930                 935                 940                 


Lys Thr Lys Cys Thr Ser Asp Ser Tyr Tyr Gln Asp Asn Cys Ala Asn 
945                 950                 955                 960 


Ile Thr Phe Thr Phe Asn Lys Glu Met Met Ser Pro Gly Leu Thr Thr 
                965                 970                 975     


Glu His Ile Cys Ser Glu Leu Arg Asn Leu Asn Ile Leu Lys Asn Val 
            980                 985                 990         


Ser Ala Glu Tyr Ser Ile Tyr Ile  Ala Cys Glu Pro Ser  Leu Ser Ala 
        995                 1000                 1005             


Asn Asn  Glu Ile His Val Ala  Ile Ser Ala Glu Asp  Ile Arg Asp 
    1010                 1015                 1020             


Asp Gly  Asn Pro Val Lys Glu  Ile Thr Asp Lys Ile  Ile Asp Leu 
    1025                 1030                 1035             


Val Ser  Lys Arg Asp Gly Asn  Ser Ser Leu Ile Ala  Ala Val Ala 
    1040                 1045                 1050             


Glu Val  Arg Val Gln Arg Arg  Pro Leu Lys Asn Arg  Thr Asp Phe 
    1055                 1060                 1065             


Leu Val  Pro Leu Leu Ser Ser  Val Leu Thr Val Ala  Trp Val Cys 
    1070                 1075                 1080             


Cys Leu  Val Thr Ala Phe Tyr  Trp Cys Val Arg Lys  Arg Arg Arg 
    1085                 1090                 1095             


Lys Pro  Ser Ser His Thr His  Ser Ala Pro Glu Asp  Asn Thr Thr 
    1100                 1105                 1110             


Asn Asn  Val Arg Glu Gln Leu  Asn Gln Ile Lys Asn  Pro Ile Glu 
    1115                 1120                 1125             


Lys His  Gly Ala Asn Thr Val  Pro Ile Lys Asp Tyr  Glu Asn Lys 
    1130                 1135                 1140             


Asn Ser  Lys Met Ser Lys Ile  Arg Thr His Asn Ser  Glu Val Glu 
    1145                 1150                 1155             


Glu Asp  Asp Met Asp Lys His  Gln Gln Lys Val Arg  Phe Ala Lys 
    1160                 1165                 1170             


Gln Pro  Val Tyr Thr Leu Val  Asp Arg Glu Glu Lys  Ala Pro Ser 
    1175                 1180                 1185             


Gly Thr  Pro Thr Lys His Pro  Asn Trp Thr Asn Lys  Gln Asp Asn 
    1190                 1195                 1200             


Arg Asp  Leu Glu Ser Ala Gln  Ser Leu Asn Arg Met  Glu Tyr Ile 
    1205                 1210                 1215             


Val 
    


<210>  5
<211>  264
<212>  PRT
<213>  Rattus norvegicus

<400>  5

Ser Gly Gln Phe Glu Leu Glu Ile Leu Ser Met Gln Asn Val Asn Gly 
1               5                   10                  15      


Glu Leu Gln Asn Gly Asn Cys Cys Gly Gly Ala Arg Asn Pro Gly Asp 
            20                  25                  30          


Arg Lys Cys Thr Arg Asp Glu Cys Asp Thr Tyr Phe Lys Val Cys Leu 
        35                  40                  45              


Lys Glu Tyr Gln Ser Arg Val Thr Ala Gly Gly Pro Cys Ser Phe Gly 
    50                  55                  60                  


Ser Gly Ser Thr Pro Val Ile Gly Gly Asn Thr Phe Asn Leu Lys Ala 
65                  70                  75                  80  


Ser Arg Gly Asn Asp Arg Asn Arg Ile Val Leu Pro Phe Ser Phe Ala 
                85                  90                  95      


Trp Pro Arg Ser Tyr Thr Leu Leu Val Glu Ala Trp Asp Ser Ser Asn 
            100                 105                 110         


Asp Thr Ile Gln Pro Asp Ser Ile Ile Glu Lys Ala Ser His Ser Gly 
        115                 120                 125             


Met Ile Asn Pro Ser Arg Gln Trp Gln Thr Leu Lys Gln Asn Thr Gly 
    130                 135                 140                 


Ile Ala His Phe Glu Tyr Gln Ile Arg Val Thr Cys Asp Asp His Tyr 
145                 150                 155                 160 


Tyr Gly Phe Gly Cys Asn Lys Phe Cys Arg Pro Arg Asp Asp Phe Phe 
                165                 170                 175     


Gly His Tyr Ala Cys Asp Gln Asn Gly Asn Lys Thr Cys Met Glu Gly 
            180                 185                 190         


Trp Met Gly Pro Glu Cys Asn Lys Ala Ile Cys Arg Gln Gly Cys Ser 
        195                 200                 205             


Pro Lys His Gly Ser Cys Lys Leu Pro Gly Asp Cys Arg Cys Gln Tyr 
    210                 215                 220                 


Gly Trp Gln Gly Leu Tyr Cys Asp Lys Cys Ile Pro His Pro Gly Cys 
225                 230                 235                 240 


Val His Gly Thr Cys Asn Glu Pro Trp Gln Cys Leu Cys Glu Thr Asn 
                245                 250                 255     


Trp Gly Gly Gln Leu Cys Asp Lys 
            260                 


<210>  6
<211>  317
<212>  PRT
<213>  Homo sapiens

<400>  6

Tyr Phe Glu Leu Gln Leu Ser Ala Leu Arg Asn Val Asn Gly Glu Leu 
1               5                   10                  15      


Leu Ser Gly Ala Cys Cys Asp Gly Asp Gly Arg Thr Thr Arg Ala Gly 
            20                  25                  30          


Gly Cys Gly His Asp Glu Cys Asp Thr Tyr Val Arg Val Cys Leu Lys 
        35                  40                  45              


Glu Tyr Gln Ala Lys Val Thr Pro Thr Gly Pro Cys Ser Tyr Gly His 
    50                  55                  60                  


Gly Ala Thr Pro Val Leu Gly Gly Asn Ser Phe Tyr Leu Pro Pro Ala 
65                  70                  75                  80  


Gly Ala Ala Gly Asp Arg Ala Arg Ala Arg Ala Arg Ala Gly Gly Asp 
                85                  90                  95      


Gln Asp Pro Gly Leu Val Val Ile Pro Phe Gln Phe Ala Trp Pro Arg 
            100                 105                 110         


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


Pro Asn Glu Glu Leu Leu Ile Glu Arg Val Ser His Ala Gly Met Ile 
    130                 135                 140                 


Asn Pro Glu Asp Arg Trp Lys Ser Leu His Phe Ser Gly His Val Ala 
145                 150                 155                 160 


His Leu Glu Leu Gln Ile Arg Val Arg Cys Asp Glu Asn Tyr Tyr Ser 
                165                 170                 175     


Ala Thr Cys Asn Lys Phe Cys Arg Pro Arg Asn Asp Phe Phe Gly His 
            180                 185                 190         


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


Gly Lys Glu Cys Lys Glu Ala Val Cys Lys Gln Gly Cys Asn Leu Leu 
    210                 215                 220                 


His Gly Gly Cys Thr Val Pro Gly Glu Cys Arg Cys Ser Tyr Gly Trp 
225                 230                 235                 240 


Gln Gly Arg Phe Cys Asp Glu Cys Val Pro Tyr Pro Gly Cys Val His 
                245                 250                 255     


Gly Ser Cys Val Glu Pro Trp Gln Cys Asn Cys Glu Thr Asn Trp Gly 
            260                 265                 270         


Gly Leu Leu Cys Asp Lys Asp Leu Asn Tyr Cys Gly Ser His His Pro 
        275                 280                 285             


Cys Thr Asn Gly Gly Thr Cys Ile Asn Ala Glu Pro Asp Gln Tyr Arg 
    290                 295                 300                 


Cys Thr Cys Pro Asp Gly Tyr Ser Gly Arg Asn Cys Glu 
305                 310                 315         


<210>  7
<211>  305
<212>  PRT
<213>  Homo sapiens

<400>  7

Ser Gly Val Phe Glu Leu Lys Leu Gln Glu Phe Val Asn Lys Lys Gly 
1               5                   10                  15      


Leu Leu Gly Asn Arg Asn Cys Cys Arg Gly Gly Ala Gly Pro Pro Pro 
            20                  25                  30          


Cys Ala Cys Arg Thr Phe Phe Arg Val Cys Leu Lys His Tyr Gln Ala 
        35                  40                  45              


Ser Val Ser Pro Glu Pro Pro Cys Thr Tyr Gly Ser Ala Val Thr Pro 
    50                  55                  60                  


Val Leu Gly Val Asp Ser Phe Ser Leu Pro Asp Gly Gly Gly Ala Asp 
65                  70                  75                  80  


Ser Ala Phe Ser Asn Pro Ile Arg Phe Pro Phe Gly Phe Thr Trp Pro 
                85                  90                  95      


Gly Thr Phe Ser Leu Ile Ile Glu Ala Leu His Thr Asp Ser Pro Asp 
            100                 105                 110         


Asp Leu Ala Thr Glu Asn Pro Glu Arg Leu Ile Ser Arg Leu Ala Thr 
        115                 120                 125             


Gln Arg His Leu Thr Val Gly Glu Glu Trp Ser Gln Asp Leu His Ser 
    130                 135                 140                 


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


His Tyr Tyr Gly Glu Gly Cys Ser Val Phe Cys Arg Pro Arg Asp Asp 
                165                 170                 175     


Ala Phe Gly His Phe Thr Cys Gly Glu Arg Gly Glu Lys Val Cys Asn 
            180                 185                 190         


Pro Gly Trp Lys Gly Pro Tyr Cys Thr Glu Pro Ile Cys Leu Pro Gly 
        195                 200                 205             


Cys Asp Glu Gln His Gly Phe Cys Asp Lys Pro Gly Glu Cys Lys Cys 
    210                 215                 220                 


Arg Val Gly Trp Gln Gly Arg Tyr Cys Asp Glu Cys Ile Arg Tyr Pro 
225                 230                 235                 240 


Gly Cys Leu His Gly Thr Cys Gln Gln Pro Trp Gln Cys Asn Cys Gln 
                245                 250                 255     


Glu Gly Trp Gly Gly Leu Phe Cys Asn Gln Asp Leu Asn Tyr Cys Thr 
            260                 265                 270         


His His Lys Pro Cys Lys Asn Gly Ala Thr Cys Thr Asn Thr Gly Gln 
        275                 280                 285             


Gly Ser Tyr Thr Cys Ser Cys Arg Pro Gly Tyr Thr Gly Ala Thr Cys 
    290                 295                 300                 


Glu 
305 


<210>  8
<211>  2555
<212>  PRT
<213>  Homo sapiens

<400>  8

Met Pro Pro Leu Leu Ala Pro Leu Leu Cys Leu Ala Leu Leu Pro Ala 
1               5                   10                  15      


Leu Ala Ala Arg Gly Pro Arg Cys Ser Gln Pro Gly Glu Thr Cys Leu 
            20                  25                  30          


Asn Gly Gly Lys Cys Glu Ala Ala Asn Gly Thr Glu Ala Cys Val Cys 
        35                  40                  45              


Gly Gly Ala Phe Val Gly Pro Arg Cys Gln Asp Pro Asn Pro Cys Leu 
    50                  55                  60                  


Ser Thr Pro Cys Lys Asn Ala Gly Thr Cys His Val Val Asp Arg Arg 
65                  70                  75                  80  


Gly Val Ala Asp Tyr Ala Cys Ser Cys Ala Leu Gly Phe Ser Gly Pro 
                85                  90                  95      


Leu Cys Leu Thr Pro Leu Asp Asn Ala Cys Leu Thr Asn Pro Cys Arg 
            100                 105                 110         


Asn Gly Gly Thr Cys Asp Leu Leu Thr Leu Thr Glu Tyr Lys Cys Arg 
        115                 120                 125             


Cys Pro Pro Gly Trp Ser Gly Lys Ser Cys Gln Gln Ala Asp Pro Cys 
    130                 135                 140                 


Ala Ser Asn Pro Cys Ala Asn Gly Gly Gln Cys Leu Pro Phe Glu Ala 
145                 150                 155                 160 


Ser Tyr Ile Cys His Cys Pro Pro Ser Phe His Gly Pro Thr Cys Arg 
                165                 170                 175     


Gln Asp Val Asn Glu Cys Gly Gln Lys Pro Gly Leu Cys Arg His Gly 
            180                 185                 190         


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


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


Ser Pro Cys Gln Asn Gly Gly Thr Cys Arg Pro Thr Gly Asp Val Thr 
225                 230                 235                 240 


His Glu Cys Ala Cys Leu Pro Gly Phe Thr Gly Gln Asn Cys Glu Glu 
                245                 250                 255     


Asn Ile Asp Asp Cys Pro Gly Asn Asn Cys Lys Asn Gly Gly Ala Cys 
            260                 265                 270         


Val Asp Gly Val Asn Thr Tyr Asn Cys Arg Cys Pro Pro Glu Trp Thr 
        275                 280                 285             


Gly Gln Tyr Cys Thr Glu Asp Val Asp Glu Cys Gln Leu Met Pro Asn 
    290                 295                 300                 


Ala Cys Gln Asn Gly Gly Thr Cys His Asn Thr His Gly Gly Tyr Asn 
305                 310                 315                 320 


Cys Val Cys Val Asn Gly Trp Thr Gly Glu Asp Cys Ser Glu Asn Ile 
                325                 330                 335     


Asp Asp Cys Ala Ser Ala Ala Cys Phe His Gly Ala Thr Cys His Asp 
            340                 345                 350         


Arg Val Ala Ser Phe Tyr Cys Glu Cys Pro His Gly Arg Thr Gly Leu 
        355                 360                 365             


Leu Cys His Leu Asn Asp Ala Cys Ile Ser Asn Pro Cys Asn Glu Gly 
    370                 375                 380                 


Ser Asn Cys Asp Thr Asn Pro Val Asn Gly Lys Ala Ile Cys Thr Cys 
385                 390                 395                 400 


Pro Ser Gly Tyr Thr Gly Pro Ala Cys Ser Gln Asp Val Asp Glu Cys 
                405                 410                 415     


Ser Leu Gly Ala Asn Pro Cys Glu His Ala Gly Lys Cys Ile Asn Thr 
            420                 425                 430         


Leu Gly Ser Phe Glu Cys Gln Cys Leu Gln Gly Tyr Thr Gly Pro Arg 
        435                 440                 445             


Cys Glu Ile Asp Val Asn Glu Cys Val Ser Asn Pro Cys Gln Asn Asp 
    450                 455                 460                 


Ala Thr Cys Leu Asp Gln Ile Gly Glu Phe Gln Cys Ile Cys Met Pro 
465                 470                 475                 480 


Gly Tyr Glu Gly Val His Cys Glu Val Asn Thr Asp Glu Cys Ala Ser 
                485                 490                 495     


Ser Pro Cys Leu His Asn Gly Arg Cys Leu Asp Lys Ile Asn Glu Phe 
            500                 505                 510         


Gln Cys Glu Cys Pro Thr Gly Phe Thr Gly His Leu Cys Gln Tyr Asp 
        515                 520                 525             


Val Asp Glu Cys Ala Ser Thr Pro Cys Lys Asn Gly Ala Lys Cys Leu 
    530                 535                 540                 


Asp Gly Pro Asn Thr Tyr Thr Cys Val Cys Thr Glu Gly Tyr Thr Gly 
545                 550                 555                 560 


Thr His Cys Glu Val Asp Ile Asp Glu Cys Asp Pro Asp Pro Cys His 
                565                 570                 575     


Tyr Gly Ser Cys Lys Asp Gly Val Ala Thr Phe Thr Cys Leu Cys Arg 
            580                 585                 590         


Pro Gly Tyr Thr Gly His His Cys Glu Thr Asn Ile Asn Glu Cys Ser 
        595                 600                 605             


Ser Gln Pro Cys Arg His Gly Gly Thr Cys Gln Asp Arg Asp Asn Ala 
    610                 615                 620                 


Tyr Leu Cys Phe Cys Leu Lys Gly Thr Thr Gly Pro Asn Cys Glu Ile 
625                 630                 635                 640 


Asn Leu Asp Asp Cys Ala Ser Ser Pro Cys Asp Ser Gly Thr Cys Leu 
                645                 650                 655     


Asp Lys Ile Asp Gly Tyr Glu Cys Ala Cys Glu Pro Gly Tyr Thr Gly 
            660                 665                 670         


Ser Met Cys Asn Ile Asn Ile Asp Glu Cys Ala Gly Asn Pro Cys His 
        675                 680                 685             


Asn Gly Gly Thr Cys Glu Asp Gly Ile Asn Gly Phe Thr Cys Arg Cys 
    690                 695                 700                 


Pro Glu Gly Tyr His Asp Pro Thr Cys Leu Ser Glu Val Asn Glu Cys 
705                 710                 715                 720 


Asn Ser Asn Pro Cys Val His Gly Ala Cys Arg Asp Ser Leu Asn Gly 
                725                 730                 735     


Tyr Lys Cys Asp Cys Asp Pro Gly Trp Ser Gly Thr Asn Cys Asp Ile 
            740                 745                 750         


Asn Asn Asn Glu Cys Glu Ser Asn Pro Cys Val Asn Gly Gly Thr Cys 
        755                 760                 765             


Lys Asp Met Thr Ser Gly Tyr Val Cys Thr Cys Arg Glu Gly Phe Ser 
    770                 775                 780                 


Gly Pro Asn Cys Gln Thr Asn Ile Asn Glu Cys Ala Ser Asn Pro Cys 
785                 790                 795                 800 


Leu Asn Gln Gly Thr Cys Ile Asp Asp Val Ala Gly Tyr Lys Cys Asn 
                805                 810                 815     


Cys Leu Leu Pro Tyr Thr Gly Ala Thr Cys Glu Val Val Leu Ala Pro 
            820                 825                 830         


Cys Ala Pro Ser Pro Cys Arg Asn Gly Gly Glu Cys Arg Gln Ser Glu 
        835                 840                 845             


Asp Tyr Glu Ser Phe Ser Cys Val Cys Pro Thr Gly Trp Gln Gly Gln 
    850                 855                 860                 


Thr Cys Glu Val Asp Ile Asn Glu Cys Val Leu Ser Pro Cys Arg His 
865                 870                 875                 880 


Gly Ala Ser Cys Gln Asn Thr His Gly Gly Tyr Arg Cys His Cys Gln 
                885                 890                 895     


Ala Gly Tyr Ser Gly Arg Asn Cys Glu Thr Asp Ile Asp Asp Cys Arg 
            900                 905                 910         


Pro Asn Pro Cys His Asn Gly Gly Ser Cys Thr Asp Gly Ile Asn Thr 
        915                 920                 925             


Ala Phe Cys Asp Cys Leu Pro Gly Phe Arg Gly Thr Phe Cys Glu Glu 
    930                 935                 940                 


Asp Ile Asn Glu Cys Ala Ser Asp Pro Cys Arg Asn Gly Ala Asn Cys 
945                 950                 955                 960 


Thr Asp Cys Val Asp Ser Tyr Thr Cys Thr Cys Pro Ala Gly Phe Ser 
                965                 970                 975     


Gly Ile His Cys Glu Asn Asn Thr Pro Asp Cys Thr Glu Ser Ser Cys 
            980                 985                 990         


Phe Asn Gly Gly Thr Cys Val Asp  Gly Ile Asn Ser Phe  Thr Cys Leu 
        995                 1000                 1005             


Cys Pro  Pro Gly Phe Thr Gly  Ser Tyr Cys Gln His  Asp Val Asn 
    1010                 1015                 1020             


Glu Cys  Asp Ser Gln Pro Cys  Leu His Gly Gly Thr  Cys Gln Asp 
    1025                 1030                 1035             


Gly Cys  Gly Ser Tyr Arg Cys  Thr Cys Pro Gln Gly  Tyr Thr Gly 
    1040                 1045                 1050             


Pro Asn  Cys Gln Asn Leu Val  His Trp Cys Asp Ser  Ser Pro Cys 
    1055                 1060                 1065             


Lys Asn  Gly Gly Lys Cys Trp  Gln Thr His Thr Gln  Tyr Arg Cys 
    1070                 1075                 1080             


Glu Cys  Pro Ser Gly Trp Thr  Gly Leu Tyr Cys Asp  Val Pro Ser 
    1085                 1090                 1095             


Val Ser  Cys Glu Val Ala Ala  Gln Arg Gln Gly Val  Asp Val Ala 
    1100                 1105                 1110             


Arg Leu  Cys Gln His Gly Gly  Leu Cys Val Asp Ala  Gly Asn Thr 
    1115                 1120                 1125             


His His  Cys Arg Cys Gln Ala  Gly Tyr Thr Gly Ser  Tyr Cys Glu 
    1130                 1135                 1140             


Asp Leu  Val Asp Glu Cys Ser  Pro Ser Pro Cys Gln  Asn Gly Ala 
    1145                 1150                 1155             


Thr Cys  Thr Asp Tyr Leu Gly  Gly Tyr Ser Cys Lys  Cys Val Ala 
    1160                 1165                 1170             


Gly Tyr  His Gly Val Asn Cys  Ser Glu Glu Ile Asp  Glu Cys Leu 
    1175                 1180                 1185             


Ser His  Pro Cys Gln Asn Gly  Gly Thr Cys Leu Asp  Leu Pro Asn 
    1190                 1195                 1200             


Thr Tyr  Lys Cys Ser Cys Pro  Arg Gly Thr Gln Gly  Val His Cys 
    1205                 1210                 1215             


Glu Ile  Asn Val Asp Asp Cys  Asn Pro Pro Val Asp  Pro Val Ser 
    1220                 1225                 1230             


Arg Ser  Pro Lys Cys Phe Asn  Asn Gly Thr Cys Val  Asp Gln Val 
    1235                 1240                 1245             


Gly Gly  Tyr Ser Cys Thr Cys  Pro Pro Gly Phe Val  Gly Glu Arg 
    1250                 1255                 1260             


Cys Glu  Gly Asp Val Asn Glu  Cys Leu Ser Asn Pro  Cys Asp Ala 
    1265                 1270                 1275             


Arg Gly  Thr Gln Asn Cys Val  Gln Arg Val Asn Asp  Phe His Cys 
    1280                 1285                 1290             


Glu Cys  Arg Ala Gly His Thr  Gly Arg Arg Cys Glu  Ser Val Ile 
    1295                 1300                 1305             


Asn Gly  Cys Lys Gly Lys Pro  Cys Lys Asn Gly Gly  Thr Cys Ala 
    1310                 1315                 1320             


Val Ala  Ser Asn Thr Ala Arg  Gly Phe Ile Cys Lys  Cys Pro Ala 
    1325                 1330                 1335             


Gly Phe  Glu Gly Ala Thr Cys  Glu Asn Asp Ala Arg  Thr Cys Gly 
    1340                 1345                 1350             


Ser Leu  Arg Cys Leu Asn Gly  Gly Thr Cys Ile Ser  Gly Pro Arg 
    1355                 1360                 1365             


Ser Pro  Thr Cys Leu Cys Leu  Gly Pro Phe Thr Gly  Pro Glu Cys 
    1370                 1375                 1380             


Gln Phe  Pro Ala Ser Ser Pro  Cys Leu Gly Gly Asn  Pro Cys Tyr 
    1385                 1390                 1395             


Asn Gln  Gly Thr Cys Glu Pro  Thr Ser Glu Ser Pro  Phe Tyr Arg 
    1400                 1405                 1410             


Cys Leu  Cys Pro Ala Lys Phe  Asn Gly Leu Leu Cys  His Ile Leu 
    1415                 1420                 1425             


Asp Tyr  Ser Phe Gly Gly Gly  Ala Gly Arg Asp Ile  Pro Pro Pro 
    1430                 1435                 1440             


Leu Ile  Glu Glu Ala Cys Glu  Leu Pro Glu Cys Gln  Glu Asp Ala 
    1445                 1450                 1455             


Gly Asn  Lys Val Cys Ser Leu  Gln Cys Asn Asn His  Ala Cys Gly 
    1460                 1465                 1470             


Trp Asp  Gly Gly Asp Cys Ser  Leu Asn Phe Asn Asp  Pro Trp Lys 
    1475                 1480                 1485             


Asn Cys  Thr Gln Ser Leu Gln  Cys Trp Lys Tyr Phe  Ser Asp Gly 
    1490                 1495                 1500             


His Cys  Asp Ser Gln Cys Asn  Ser Ala Gly Cys Leu  Phe Asp Gly 
    1505                 1510                 1515             


Phe Asp  Cys Gln Arg Ala Glu  Gly Gln Cys Asn Pro  Leu Tyr Asp 
    1520                 1525                 1530             


Gln Tyr  Cys Lys Asp His Phe  Ser Asp Gly His Cys  Asp Gln Gly 
    1535                 1540                 1545             


Cys Asn  Ser Ala Glu Cys Glu  Trp Asp Gly Leu Asp  Cys Ala Glu 
    1550                 1555                 1560             


His Val  Pro Glu Arg Leu Ala  Ala Gly Thr Leu Val  Val Val Val 
    1565                 1570                 1575             


Leu Met  Pro Pro Glu Gln Leu  Arg Asn Ser Ser Phe  His Phe Leu 
    1580                 1585                 1590             


Arg Glu  Leu Ser Arg Val Leu  His Thr Asn Val Val  Phe Lys Arg 
    1595                 1600                 1605             


Asp Ala  His Gly Gln Gln Met  Ile Phe Pro Tyr Tyr  Gly Arg Glu 
    1610                 1615                 1620             


Glu Glu  Leu Arg Lys His Pro  Ile Lys Arg Ala Ala  Glu Gly Trp 
    1625                 1630                 1635             


Ala Ala  Pro Asp Ala Leu Leu  Gly Gln Val Lys Ala  Ser Leu Leu 
    1640                 1645                 1650             


Pro Gly  Gly Ser Glu Gly Gly  Arg Arg Arg Arg Glu  Leu Asp Pro 
    1655                 1660                 1665             


Met Asp  Val Arg Gly Ser Ile  Val Tyr Leu Glu Ile  Asp Asn Arg 
    1670                 1675                 1680             


Gln Cys  Val Gln Ala Ser Ser  Gln Cys Phe Gln Ser  Ala Thr Asp 
    1685                 1690                 1695             


Val Ala  Ala Phe Leu Gly Ala  Leu Ala Ser Leu Gly  Ser Leu Asn 
    1700                 1705                 1710             


Ile Pro  Tyr Lys Ile Glu Ala  Val Gln Ser Glu Thr  Val Glu Pro 
    1715                 1720                 1725             


Pro Pro  Pro Ala Gln Leu His  Phe Met Tyr Val Ala  Ala Ala Ala 
    1730                 1735                 1740             


Phe Val  Leu Leu Phe Phe Val  Gly Cys Gly Val Leu  Leu Ser Arg 
    1745                 1750                 1755             


Lys Arg  Arg Arg Gln His Gly  Gln Leu Trp Phe Pro  Glu Gly Phe 
    1760                 1765                 1770             


Lys Val  Ser Glu Ala Ser Lys  Lys Lys Arg Arg Glu  Pro Leu Gly 
    1775                 1780                 1785             


Glu Asp  Ser Val Gly Leu Lys  Pro Leu Lys Asn Ala  Ser Asp Gly 
    1790                 1795                 1800             


Ala Leu  Met Asp Asp Asn Gln  Asn Glu Trp Gly Asp  Glu Asp Leu 
    1805                 1810                 1815             


Glu Thr  Lys Lys Phe Arg Phe  Glu Glu Pro Val Val  Leu Pro Asp 
    1820                 1825                 1830             


Leu Asp  Asp Gln Thr Asp His  Arg Gln Trp Thr Gln  Gln His Leu 
    1835                 1840                 1845             


Asp Ala  Ala Asp Leu Arg Met  Ser Ala Met Ala Pro  Thr Pro Pro 
    1850                 1855                 1860             


Gln Gly  Glu Val Asp Ala Asp  Cys Met Asp Val Asn  Val Arg Gly 
    1865                 1870                 1875             


Pro Asp  Gly Phe Thr Pro Leu  Met Ile Ala Ser Cys  Ser Gly Gly 
    1880                 1885                 1890             


Gly Leu  Glu Thr Gly Asn Ser  Glu Glu Glu Glu Asp  Ala Pro Ala 
    1895                 1900                 1905             


Val Ile  Ser Asp Phe Ile Tyr  Gln Gly Ala Ser Leu  His Asn Gln 
    1910                 1915                 1920             


Thr Asp  Arg Thr Gly Glu Thr  Ala Leu His Leu Ala  Ala Arg Tyr 
    1925                 1930                 1935             


Ser Arg  Ser Asp Ala Ala Lys  Arg Leu Leu Glu Ala  Ser Ala Asp 
    1940                 1945                 1950             


Ala Asn  Ile Gln Asp Asn Met  Gly Arg Thr Pro Leu  His Ala Ala 
    1955                 1960                 1965             


Val Ser  Ala Asp Ala Gln Gly  Val Phe Gln Ile Leu  Ile Arg Asn 
    1970                 1975                 1980             


Arg Ala  Thr Asp Leu Asp Ala  Arg Met His Asp Gly  Thr Thr Pro 
    1985                 1990                 1995             


Leu Ile  Leu Ala Ala Arg Leu  Ala Val Glu Gly Met  Leu Glu Asp 
    2000                 2005                 2010             


Leu Ile  Asn Ser His Ala Asp  Val Asn Ala Val Asp  Asp Leu Gly 
    2015                 2020                 2025             


Lys Ser  Ala Leu His Trp Ala  Ala Ala Val Asn Asn  Val Asp Ala 
    2030                 2035                 2040             


Ala Val  Val Leu Leu Lys Asn  Gly Ala Asn Lys Asp  Met Gln Asn 
    2045                 2050                 2055             


Asn Arg  Glu Glu Thr Pro Leu  Phe Leu Ala Ala Arg  Glu Gly Ser 
    2060                 2065                 2070             


Tyr Glu  Thr Ala Lys Val Leu  Leu Asp His Phe Ala  Asn Arg Asp 
    2075                 2080                 2085             


Ile Thr  Asp His Met Asp Arg  Leu Pro Arg Asp Ile  Ala Gln Glu 
    2090                 2095                 2100             


Arg Met  His His Asp Ile Val  Arg Leu Leu Asp Glu  Tyr Asn Leu 
    2105                 2110                 2115             


Val Arg  Ser Pro Gln Leu His  Gly Ala Pro Leu Gly  Gly Thr Pro 
    2120                 2125                 2130             


Thr Leu  Ser Pro Pro Leu Cys  Ser Pro Asn Gly Tyr  Leu Gly Ser 
    2135                 2140                 2145             


Leu Lys  Pro Gly Val Gln Gly  Lys Lys Val Arg Lys  Pro Ser Ser 
    2150                 2155                 2160             


Lys Gly  Leu Ala Cys Gly Ser  Lys Glu Ala Lys Asp  Leu Lys Ala 
    2165                 2170                 2175             


Arg Arg  Lys Lys Ser Gln Asp  Gly Lys Gly Cys Leu  Leu Asp Ser 
    2180                 2185                 2190             


Ser Gly  Met Leu Ser Pro Val  Asp Ser Leu Glu Ser  Pro His Gly 
    2195                 2200                 2205             


Tyr Leu  Ser Asp Val Ala Ser  Pro Pro Leu Leu Pro  Ser Pro Phe 
    2210                 2215                 2220             


Gln Gln  Ser Pro Ser Val Pro  Leu Asn His Leu Pro  Gly Met Pro 
    2225                 2230                 2235             


Asp Thr  His Leu Gly Ile Gly  His Leu Asn Val Ala  Ala Lys Pro 
    2240                 2245                 2250             


Glu Met  Ala Ala Leu Gly Gly  Gly Gly Arg Leu Ala  Phe Glu Thr 
    2255                 2260                 2265             


Gly Pro  Pro Arg Leu Ser His  Leu Pro Val Ala Ser  Gly Thr Ser 
    2270                 2275                 2280             


Thr Val  Leu Gly Ser Ser Ser  Gly Gly Ala Leu Asn  Phe Thr Val 
    2285                 2290                 2295             


Gly Gly  Ser Thr Ser Leu Asn  Gly Gln Cys Glu Trp  Leu Ser Arg 
    2300                 2305                 2310             


Leu Gln  Ser Gly Met Val Pro  Asn Gln Tyr Asn Pro  Leu Arg Gly 
    2315                 2320                 2325             


Ser Val  Ala Pro Gly Pro Leu  Ser Thr Gln Ala Pro  Ser Leu Gln 
    2330                 2335                 2340             


His Gly  Met Val Gly Pro Leu  His Ser Ser Leu Ala  Ala Ser Ala 
    2345                 2350                 2355             


Leu Ser  Gln Met Met Ser Tyr  Gln Gly Leu Pro Ser  Thr Arg Leu 
    2360                 2365                 2370             


Ala Thr  Gln Pro His Leu Val  Gln Thr Gln Gln Val  Gln Pro Gln 
    2375                 2380                 2385             


Asn Leu  Gln Met Gln Gln Gln  Asn Leu Gln Pro Ala  Asn Ile Gln 
    2390                 2395                 2400             


Gln Gln  Gln Ser Leu Gln Pro  Pro Pro Pro Pro Pro  Gln Pro His 
    2405                 2410                 2415             


Leu Gly  Val Ser Ser Ala Ala  Ser Gly His Leu Gly  Arg Ser Phe 
    2420                 2425                 2430             


Leu Ser  Gly Glu Pro Ser Gln  Ala Asp Val Gln Pro  Leu Gly Pro 
    2435                 2440                 2445             


Ser Ser  Leu Ala Val His Thr  Ile Leu Pro Gln Glu  Ser Pro Ala 
    2450                 2455                 2460             


Leu Pro  Thr Ser Leu Pro Ser  Ser Leu Val Pro Pro  Val Thr Ala 
    2465                 2470                 2475             


Ala Gln  Phe Leu Thr Pro Pro  Ser Gln His Ser Tyr  Ser Ser Pro 
    2480                 2485                 2490             


Val Asp  Asn Thr Pro Ser His  Gln Leu Gln Val Pro  Glu His Pro 
    2495                 2500                 2505             


Phe Leu  Thr Pro Ser Pro Glu  Ser Pro Asp Gln Trp  Ser Ser Ser 
    2510                 2515                 2520             


Ser Pro  His Ser Asn Val Ser  Asp Trp Ser Glu Gly  Val Ser Ser 
    2525                 2530                 2535             


Pro Pro  Thr Ser Met Gln Ser  Gln Ile Ala Arg Ile  Pro Glu Ala 
    2540                 2545                 2550             


Phe Lys  
    2555 


<210>  9
<211>  243
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  Anti-CD33 single-chain variable fragment

<400>  9

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


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


Ser Asn Ile His Trp Val Lys Gln Ser Arg Gly Lys Ser Leu Glu Trp 
        35                  40                  45              


Ile Gly Tyr Ile Tyr Pro Tyr Asn Gly Gly Thr Asp Tyr Asn Gln Lys 
    50                  55                  60                  


Phe Lys Asn Lys Ala Thr Leu Thr Val Asp Asn Pro Ser Ser Thr Ala 
65                  70                  75                  80  


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


Cys Val Asn Gly Asn Pro Trp Leu Ala Tyr Trp Gly Gln Gly Thr Leu 
            100                 105                 110         


Val Thr Val Ser Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly 
        115                 120                 125             


Gly Gly Gly Ser Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala 
    130                 135                 140                 


Val Ser Leu Gly Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser 
145                 150                 155                 160 


Leu Asp Asn Tyr Gly Ile Arg Phe Leu Thr Trp Phe Gln Gln Arg Pro 
                165                 170                 175     


Gly Gln Pro Pro Lys Leu Leu Ile Tyr Ala Ala Ser Asn Gln Gly Ser 
            180                 185                 190         


Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Ser 
        195                 200                 205             


Leu Asn Ile His Pro Met Glu Glu Asp Asp Thr Ala Ile Tyr Phe Cys 
    210                 215                 220                 


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


Glu Ile Lys 
            


<210>  10
<211>  765
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  ANti-CD33 single-chain variable fragment

<400>  10

Ser Ser Ile Phe Gln Leu Arg Leu Gln Glu Phe Ala Asn Glu Arg Gly 
1               5                   10                  15      


Met Leu Ala Asn Gly Arg Pro Cys Glu Pro Gly Cys Arg Thr Phe Phe 
            20                  25                  30          


Arg Ile Cys Leu Lys His Tyr Gln Ala Thr Phe Ser Glu Gly Pro Cys 
        35                  40                  45              


Thr Phe Gly Asn Val Ser Thr Pro Val Leu Gly Thr Asn Ser Phe Val 
    50                  55                  60                  


Ile Arg Asp Lys Asn Ser Gly Ser Gly Arg Asn Pro Leu Gln Leu Pro 
65                  70                  75                  80  


Leu Asn Phe Thr Trp Pro Gly Thr Phe Ser Leu Ile Ile Gln Ala Trp 
                85                  90                  95      


His Thr Pro Gly Asp Asp Leu Arg Pro Glu Thr Ser Pro Gly Asn Ser 
            100                 105                 110         


Leu Ile Ser Gln Phe Ile Ile Gln Gly Ser Leu Ala Val Gly Lys Asn 
        115                 120                 125             


Trp Lys Ser Asp Glu Gln Asn Asn Thr Leu Thr Arg Leu Arg Tyr Ser 
    130                 135                 140                 


Tyr Arg Val Val Cys Ser Asp Asn Tyr Tyr Gly Asp Ser Cys Ser Arg 
145                 150                 155                 160 


Leu Cys Lys Lys Arg Asp Asp Tyr Phe Gly His Tyr Glu Cys Gln Pro 
                165                 170                 175     


Asp Gly Ser Pro Ser Cys Leu Pro Gly Trp Thr Gly Glu Tyr Cys Asp 
            180                 185                 190         


Gln Pro Ile Cys Leu Ser Gly Cys His Glu Gln Asn Gly Tyr Cys Ser 
        195                 200                 205             


Lys Pro Asp Glu Cys Asn Cys Arg Pro Gly Trp Gln Gly Pro Leu Cys 
    210                 215                 220                 


Asn Glu Cys Ile Pro His Asn Gly Cys Arg His Gly Thr Cys Thr Ile 
225                 230                 235                 240 


Pro Trp Gln Cys Ala Cys Asp Glu Gly Trp Gly Gly Leu Phe Cys Asp 
                245                 250                 255     


Gln Asp Leu Asn Tyr Cys Thr His His Ser Pro Cys Lys Asn Gly Ser 
            260                 265                 270         


Thr Cys Ser Asn Ser Gly Pro Arg Gly Tyr Thr Cys Thr Cys Leu Pro 
        275                 280                 285             


Gly Tyr Thr Gly Glu His Cys Glu Leu Glu Leu Ser Lys Cys Ala Ser 
    290                 295                 300                 


Asn Pro Cys Arg Asn Gly Gly Ser Cys Lys Asp His Glu Asn Ser Tyr 
305                 310                 315                 320 


His Cys Leu Cys Pro Pro Gly Tyr Tyr Gly Gln His Cys Glu His Ser 
                325                 330                 335     


Thr Leu Thr Cys Ala Asp Ser Pro Cys Phe Asn Gly Gly Ser Cys Arg 
            340                 345                 350         


Glu Arg Asn Gln Gly Ala Ser Tyr Ala Cys Glu Cys Pro Pro Asn Phe 
        355                 360                 365             


Thr Gly Ser Asn Cys Glu Lys Lys Val Asp Arg Cys Thr Ser Asn Pro 
    370                 375                 380                 


Cys Ala Asn Gly Gly Gln Cys Leu Asn Arg Gly Pro Ser Arg Thr Cys 
385                 390                 395                 400 


Arg Cys Arg Pro Gly Phe Thr Gly Thr His Cys Glu Leu His Ile Ser 
                405                 410                 415     


Asp Cys Ala Arg Ser Pro Cys Ala His Gly Gly Thr Cys His Asp Leu 
            420                 425                 430         


Glu Asn Gly Pro Val Cys Thr Cys Pro Ala Gly Phe Ser Gly Arg Arg 
        435                 440                 445             


Cys Glu Val Arg Ile Thr Asn Asp Ala Cys Ala Ser Gly Pro Cys Phe 
    450                 455                 460                 


Asn Gly Ala Thr Cys Tyr Thr Gly Leu Ser Pro Asn Asn Phe Val Cys 
465                 470                 475                 480 


Asn Cys Pro Tyr Gly Phe Val Gly Ser Arg Cys Glu Gly Ser Gly Ser 
                485                 490                 495     


Gly Ser Gly Ser Gly Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu 
            500                 505                 510         


Val Val Lys Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly 
        515                 520                 525             


Tyr Thr Ile Thr Asp Ser Asn Ile His Trp Val Lys Gln Ser Arg Gly 
    530                 535                 540                 


Lys Ser Leu Glu Trp Ile Gly Tyr Ile Tyr Pro Tyr Asn Gly Gly Thr 
545                 550                 555                 560 


Asp Tyr Asn Gln Lys Phe Lys Asn Lys Ala Thr Leu Thr Val Asp Asn 
                565                 570                 575     


Pro Ser Ser Thr Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp 
            580                 585                 590         


Ser Ala Val Tyr Tyr Cys Val Asn Gly Asn Pro Trp Leu Ala Tyr Trp 
        595                 600                 605             


Gly Gln Gly Thr Leu Val Thr Val Ser Ala Gly Gly Gly Gly Ser Gly 
    610                 615                 620                 


Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Val Leu Thr Gln Ser 
625                 630                 635                 640 


Pro Ala Ser Leu Ala Val Ser Leu Gly Gln Arg Ala Thr Ile Ser Cys 
                645                 650                 655     


Arg Ala Ser Glu Ser Leu Asp Asn Tyr Gly Ile Arg Phe Leu Thr Trp 
            660                 665                 670         


Phe Gln Gln Arg Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Ala Ala 
        675                 680                 685             


Ser Asn Gln Gly Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser 
    690                 695                 700                 


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


Ala Ile Tyr Phe Cys Gln Gln Thr Lys Glu Val Pro Trp Ser Phe Gly 
                725                 730                 735     


Gly Gly Thr Lys Leu Glu Ile Lys Glu Gln Lys Leu Ile Ser Glu Glu 
            740                 745                 750         


Asp Leu Ala Ala Ala His His His His His His His His 
        755                 760                 765 


