                         SEQUENCE LISTING

<110>  Ventana Medical Systems, Inc.
       University of Leeds
 
<120>  PREDICTION OF RESPONSE TO EPIDERMAL GROWTH FACTOR 
       RECEPTOR-DIRECTED THERAPIES USING EPIREGULIN AND AMPHIREGULIN

<130>  I14269

<160>  3     

<170>  PatentIn version 3.5

<210>  1
<211>  1210
<212>  PRT
<213>  Homo sapiens

<400>  1

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


Ala Leu Cys Pro Ala Ser Arg Ala Leu Glu Glu Lys Lys Val Cys Gln 
            20                  25                  30          


Gly Thr Ser Asn Lys Leu Thr Gln Leu Gly Thr Phe Glu Asp His Phe 
        35                  40                  45              


Leu Ser Leu Gln Arg Met Phe Asn Asn Cys Glu Val Val Leu Gly Asn 
    50                  55                  60                  


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


Thr Ile Gln Glu Val Ala Gly Tyr Val Leu Ile Ala Leu Asn Thr Val 
                85                  90                  95      


Glu Arg Ile Pro Leu Glu Asn Leu Gln Ile Ile Arg Gly Asn Met Tyr 
            100                 105                 110         


Tyr Glu Asn Ser Tyr Ala Leu Ala Val Leu Ser Asn Tyr Asp Ala Asn 
        115                 120                 125             


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


His Gly Ala Val Arg Phe Ser Asn Asn Pro Ala Leu Cys Asn Val Glu 
145                 150                 155                 160 


Ser Ile Gln Trp Arg Asp Ile Val Ser Ser Asp Phe Leu Ser Asn Met 
                165                 170                 175     


Ser Met Asp Phe Gln Asn His Leu Gly Ser Cys Gln Lys Cys Asp Pro 
            180                 185                 190         


Ser Cys Pro Asn Gly Ser Cys Trp Gly Ala Gly Glu Glu Asn Cys Gln 
        195                 200                 205             


Lys Leu Thr Lys Ile Ile Cys Ala Gln Gln Cys Ser Gly Arg Cys Arg 
    210                 215                 220                 


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


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


Glu Ala Thr Cys Lys Asp Thr Cys Pro Pro Leu Met Leu Tyr Asn Pro 
            260                 265                 270         


Thr Thr Tyr Gln Met Asp Val Asn Pro Glu Gly Lys Tyr Ser Phe Gly 
        275                 280                 285             


Ala Thr Cys Val Lys Lys Cys Pro Arg Asn Tyr Val Val Thr Asp His 
    290                 295                 300                 


Gly Ser Cys Val Arg Ala Cys Gly Ala Asp Ser Tyr Glu Met Glu Glu 
305                 310                 315                 320 


Asp Gly Val Arg Lys Cys Lys Lys Cys Glu Gly Pro Cys Arg Lys Val 
                325                 330                 335     


Cys Asn Gly Ile Gly Ile Gly Glu Phe Lys Asp Ser Leu Ser Ile Asn 
            340                 345                 350         


Ala Thr Asn Ile Lys His Phe Lys Asn Cys Thr Ser Ile Ser Gly Asp 
        355                 360                 365             


Leu His Ile Leu Pro Val Ala Phe Arg Gly Asp Ser Phe Thr His Thr 
    370                 375                 380                 


Pro Pro Leu Asp Pro Gln Glu Leu Asp Ile Leu Lys Thr Val Lys Glu 
385                 390                 395                 400 


Ile Thr Gly Phe Leu Leu Ile Gln Ala Trp Pro Glu Asn Arg Thr Asp 
                405                 410                 415     


Leu His Ala Phe Glu Asn Leu Glu Ile Ile Arg Gly Arg Thr Lys Gln 
            420                 425                 430         


His Gly Gln Phe Ser Leu Ala Val Val Ser Leu Asn Ile Thr Ser Leu 
        435                 440                 445             


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


Gly Asn Lys Asn Leu Cys Tyr Ala Asn Thr Ile Asn Trp Lys Lys Leu 
465                 470                 475                 480 


Phe Gly Thr Ser Gly Gln Lys Thr Lys Ile Ile Ser Asn Arg Gly Glu 
                485                 490                 495     


Asn Ser Cys Lys Ala Thr Gly Gln Val Cys His Ala Leu Cys Ser Pro 
            500                 505                 510         


Glu Gly Cys Trp Gly Pro Glu Pro Arg Asp Cys Val Ser Cys Arg Asn 
        515                 520                 525             


Val Ser Arg Gly Arg Glu Cys Val Asp Lys Cys Asn Leu Leu Glu Gly 
    530                 535                 540                 


Glu Pro Arg Glu Phe Val Glu Asn Ser Glu Cys Ile Gln Cys His Pro 
545                 550                 555                 560 


Glu Cys Leu Pro Gln Ala Met Asn Ile Thr Cys Thr Gly Arg Gly Pro 
                565                 570                 575     


Asp Asn Cys Ile Gln Cys Ala His Tyr Ile Asp Gly Pro His Cys Val 
            580                 585                 590         


Lys Thr Cys Pro Ala Gly Val Met Gly Glu Asn Asn Thr Leu Val Trp 
        595                 600                 605             


Lys Tyr Ala Asp Ala Gly His Val Cys His Leu Cys His Pro Asn Cys 
    610                 615                 620                 


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


Pro Lys Ile Pro Ser Ile Ala Thr Gly Met Val Gly Ala Leu Leu Leu 
                645                 650                 655     


Leu Leu Val Val Ala Leu Gly Ile Gly Leu Phe Met Arg Arg Arg His 
            660                 665                 670         


Ile Val Arg Lys Arg Thr Leu Arg Arg Leu Leu Gln Glu Arg Glu Leu 
        675                 680                 685             


Val Glu Pro Leu Thr Pro Ser Gly Glu Ala Pro Asn Gln Ala Leu Leu 
    690                 695                 700                 


Arg Ile Leu Lys Glu Thr Glu Phe Lys Lys Ile Lys Val Leu Gly Ser 
705                 710                 715                 720 


Gly Ala Phe Gly Thr Val Tyr Lys Gly Leu Trp Ile Pro Glu Gly Glu 
                725                 730                 735     


Lys Val Lys Ile Pro Val Ala Ile Lys Glu Leu Arg Glu Ala Thr Ser 
            740                 745                 750         


Pro Lys Ala Asn Lys Glu Ile Leu Asp Glu Ala Tyr Val Met Ala Ser 
        755                 760                 765             


Val Asp Asn Pro His Val Cys Arg Leu Leu Gly Ile Cys Leu Thr Ser 
    770                 775                 780                 


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


Tyr Val Arg Glu His Lys Asp Asn Ile Gly Ser Gln Tyr Leu Leu Asn 
                805                 810                 815     


Trp Cys Val Gln Ile Ala Lys Gly Met Asn Tyr Leu Glu Asp Arg Arg 
            820                 825                 830         


Leu Val His Arg Asp Leu Ala Ala Arg Asn Val Leu Val Lys Thr Pro 
        835                 840                 845             


Gln His Val Lys Ile Thr Asp Phe Gly Leu Ala Lys Leu Leu Gly Ala 
    850                 855                 860                 


Glu Glu Lys Glu Tyr His Ala Glu Gly Gly Lys Val Pro Ile Lys Trp 
865                 870                 875                 880 


Met Ala Leu Glu Ser Ile Leu His Arg Ile Tyr Thr His Gln Ser Asp 
                885                 890                 895     


Val Trp Ser Tyr Gly Val Thr Val Trp Glu Leu Met Thr Phe Gly Ser 
            900                 905                 910         


Lys Pro Tyr Asp Gly Ile Pro Ala Ser Glu Ile Ser Ser Ile Leu Glu 
        915                 920                 925             


Lys Gly Glu Arg Leu Pro Gln Pro Pro Ile Cys Thr Ile Asp Val Tyr 
    930                 935                 940                 


Met Ile Met Val Lys Cys Trp Met Ile Asp Ala Asp Ser Arg Pro Lys 
945                 950                 955                 960 


Phe Arg Glu Leu Ile Ile Glu Phe Ser Lys Met Ala Arg Asp Pro Gln 
                965                 970                 975     


Arg Tyr Leu Val Ile Gln Gly Asp Glu Arg Met His Leu Pro Ser Pro 
            980                 985                 990         


Thr Asp Ser Asn Phe Tyr Arg Ala  Leu Met Asp Glu Glu  Asp Met Asp 
        995                 1000                 1005             


Asp Val  Val Asp Ala Asp Glu  Tyr Leu Ile Pro Gln  Gln Gly Phe 
    1010                 1015                 1020             


Phe Ser  Ser Pro Ser Thr Ser  Arg Thr Pro Leu Leu  Ser Ser Leu 
    1025                 1030                 1035             


Ser Ala  Thr Ser Asn Asn Ser  Thr Val Ala Cys Ile  Asp Arg Asn 
    1040                 1045                 1050             


Gly Leu  Gln Ser Cys Pro Ile  Lys Glu Asp Ser Phe  Leu Gln Arg 
    1055                 1060                 1065             


Tyr Ser  Ser Asp Pro Thr Gly  Ala Leu Thr Glu Asp  Ser Ile Asp 
    1070                 1075                 1080             


Asp Thr  Phe Leu Pro Val Pro  Glu Tyr Ile Asn Gln  Ser Val Pro 
    1085                 1090                 1095             


Lys Arg  Pro Ala Gly Ser Val  Gln Asn Pro Val Tyr  His Asn Gln 
    1100                 1105                 1110             


Pro Leu  Asn Pro Ala Pro Ser  Arg Asp Pro His Tyr  Gln Asp Pro 
    1115                 1120                 1125             


His Ser  Thr Ala Val Gly Asn  Pro Glu Tyr Leu Asn  Thr Val Gln 
    1130                 1135                 1140             


Pro Thr  Cys Val Asn Ser Thr  Phe Asp Ser Pro Ala  His Trp Ala 
    1145                 1150                 1155             


Gln Lys  Gly Ser His Gln Ile  Ser Leu Asp Asn Pro  Asp Tyr Gln 
    1160                 1165                 1170             


Gln Asp  Phe Phe Pro Lys Glu  Ala Lys Pro Asn Gly  Ile Phe Lys 
    1175                 1180                 1185             


Gly Ser  Thr Ala Glu Asn Ala  Glu Tyr Leu Arg Val  Ala Pro Gln 
    1190                 1195                 1200             


Ser Ser  Glu Phe Ile Gly Ala  
    1205                 1210 


<210>  2
<211>  169
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Thr Ala Gly Arg Arg Met Glu Met Leu Cys Ala Gly Arg Val Pro 
1               5                   10                  15      


Ala Leu Leu Leu Cys Leu Gly Phe His Leu Leu Gln Ala Val Leu Ser 
            20                  25                  30          


Thr Thr Val Ile Pro Ser Cys Ile Pro Gly Glu Ser Ser Asp Asn Cys 
        35                  40                  45              


Thr Ala Leu Val Gln Thr Glu Asp Asn Pro Arg Val Ala Gln Val Ser 
    50                  55                  60                  


Ile Thr Lys Cys Ser Ser Asp Met Asn Gly Tyr Cys Leu His Gly Gln 
65                  70                  75                  80  


Cys Ile Tyr Leu Val Asp Met Ser Gln Asn Tyr Cys Arg Cys Glu Val 
                85                  90                  95      


Gly Tyr Thr Gly Val Arg Cys Glu His Phe Phe Leu Thr Val His Gln 
            100                 105                 110         


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


Phe Leu Ile Thr Val Val Gly Ser Thr Tyr Tyr Phe Cys Arg Trp Tyr 
    130                 135                 140                 


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


Ser Gly Asp Pro Glu Leu Pro Gln Val 
                165                 


<210>  3
<211>  252
<212>  PRT
<213>  Homo sapiens

<400>  3

Met Arg Ala Pro Leu Leu Pro Pro Ala Pro Val Val Leu Ser Leu Leu 
1               5                   10                  15      


Ile Leu Gly Ser Gly His Tyr Ala Ala Gly Leu Asp Leu Asn Asp Thr 
            20                  25                  30          


Tyr Ser Gly Lys Arg Glu Pro Phe Ser Gly Asp His Ser Ala Asp Gly 
        35                  40                  45              


Phe Glu Val Thr Ser Arg Ser Glu Met Ser Ser Gly Ser Glu Ile Ser 
    50                  55                  60                  


Pro Val Ser Glu Met Pro Ser Ser Ser Glu Pro Ser Ser Gly Ala Asp 
65                  70                  75                  80  


Tyr Asp Tyr Ser Glu Glu Tyr Asp Asn Glu Pro Gln Ile Pro Gly Tyr 
                85                  90                  95      


Ile Val Asp Asp Ser Val Arg Val Glu Gln Val Val Lys Pro Pro Gln 
            100                 105                 110         


Asn Lys Thr Glu Ser Glu Asn Thr Ser Asp Lys Pro Lys Arg Lys Lys 
        115                 120                 125             


Lys Gly Gly Lys Asn Gly Lys Asn Arg Arg Asn Arg Lys Lys Lys Asn 
    130                 135                 140                 


Pro Cys Asn Ala Glu Phe Gln Asn Phe Cys Ile His Gly Glu Cys Lys 
145                 150                 155                 160 


Tyr Ile Glu His Leu Glu Ala Val Thr Cys Lys Cys Gln Gln Glu Tyr 
                165                 170                 175     


Phe Gly Glu Arg Cys Gly Glu Lys Ser Met Lys Thr His Ser Met Ile 
            180                 185                 190         


Asp Ser Ser Leu Ser Lys Ile Ala Leu Ala Ala Ile Ala Ala Phe Met 
        195                 200                 205             


Ser Ala Val Ile Leu Thr Ala Val Ala Val Ile Thr Val Gln Leu Arg 
    210                 215                 220                 


Arg Gln Tyr Val Arg Lys Tyr Glu Gly Glu Ala Glu Glu Arg Lys Lys 
225                 230                 235                 240 


Leu Arg Gln Glu Asn Gly Asn Val His Ala Ile Ala 
                245                 250         


