                               SEQUENCE LISTING

<110> NOVARTIS AG
 
<120> 6-6 FUSED BICYCLIC HETEROARYL COMPOUNDS AND THEIR USE AS LATS 
      INHIBITORS

<130> PAT057699-WO-PCT

<140>
<141>

<150> 62/650,232
<151> 2018-03-29

<150> 62/491,475
<151> 2017-04-28

<150> 62/491,484
<151> 2017-04-28

<150> 62/491,573
<151> 2017-04-28

<150> 62/491,526
<151> 2017-04-28

<160> 31    

<170> PatentIn version 3.5

<210> 1
<211> 1130
<212> PRT
<213> Homo sapiens

<400> 1
Met Lys Arg Ser Glu Lys Pro Glu Gly Tyr Arg Gln Met Arg Pro Lys 
1               5                   10                  15      


Thr Phe Pro Ala Ser Asn Tyr Thr Val Ser Ser Arg Gln Met Leu Gln 
            20                  25                  30          


Glu Ile Arg Glu Ser Leu Arg Asn Leu Ser Lys Pro Ser Asp Ala Ala 
        35                  40                  45              


Lys Ala Glu His Asn Met Ser Lys Met Ser Thr Glu Asp Pro Arg Gln 
    50                  55                  60                  


Val Arg Asn Pro Pro Lys Phe Gly Thr His His Lys Ala Leu Gln Glu 
65                  70                  75                  80  


Ile Arg Asn Ser Leu Leu Pro Phe Ala Asn Glu Thr Asn Ser Ser Arg 
                85                  90                  95      


Ser Thr Ser Glu Val Asn Pro Gln Met Leu Gln Asp Leu Gln Ala Ala 
            100                 105                 110         


Gly Phe Asp Glu Asp Met Val Ile Gln Ala Leu Gln Lys Thr Asn Asn 
        115                 120                 125             


Arg Ser Ile Glu Ala Ala Ile Glu Phe Ile Ser Lys Met Ser Tyr Gln 
    130                 135                 140                 


Asp Pro Arg Arg Glu Gln Met Ala Ala Ala Ala Ala Arg Pro Ile Asn 
145                 150                 155                 160 


Ala Ser Met Lys Pro Gly Asn Val Gln Gln Ser Val Asn Arg Lys Gln 
                165                 170                 175     


Ser Trp Lys Gly Ser Lys Glu Ser Leu Val Pro Gln Arg His Gly Pro 
            180                 185                 190         


Pro Leu Gly Glu Ser Val Ala Tyr His Ser Glu Ser Pro Asn Ser Gln 
        195                 200                 205             


Thr Asp Val Gly Arg Pro Leu Ser Gly Ser Gly Ile Ser Ala Phe Val 
    210                 215                 220                 


Gln Ala His Pro Ser Asn Gly Gln Arg Val Asn Pro Pro Pro Pro Pro 
225                 230                 235                 240 


Gln Val Arg Ser Val Thr Pro Pro Pro Pro Pro Arg Gly Gln Thr Pro 
                245                 250                 255     


Pro Pro Arg Gly Thr Thr Pro Pro Pro Pro Ser Trp Glu Pro Asn Ser 
            260                 265                 270         


Gln Thr Lys Arg Tyr Ser Gly Asn Met Glu Tyr Val Ile Ser Arg Ile 
        275                 280                 285             


Ser Pro Val Pro Pro Gly Ala Trp Gln Glu Gly Tyr Pro Pro Pro Pro 
    290                 295                 300                 


Leu Asn Thr Ser Pro Met Asn Pro Pro Asn Gln Gly Gln Arg Gly Ile 
305                 310                 315                 320 


Ser Ser Val Pro Val Gly Arg Gln Pro Ile Ile Met Gln Ser Ser Ser 
                325                 330                 335     


Lys Phe Asn Phe Pro Ser Gly Arg Pro Gly Met Gln Asn Gly Thr Gly 
            340                 345                 350         


Gln Thr Asp Phe Met Ile His Gln Asn Val Val Pro Ala Gly Thr Val 
        355                 360                 365             


Asn Arg Gln Pro Pro Pro Pro Tyr Pro Leu Thr Ala Ala Asn Gly Gln 
    370                 375                 380                 


Ser Pro Ser Ala Leu Gln Thr Gly Gly Ser Ala Ala Pro Ser Ser Tyr 
385                 390                 395                 400 


Thr Asn Gly Ser Ile Pro Gln Ser Met Met Val Pro Asn Arg Asn Ser 
                405                 410                 415     


His Asn Met Glu Leu Tyr Asn Ile Ser Val Pro Gly Leu Gln Thr Asn 
            420                 425                 430         


Trp Pro Gln Ser Ser Ser Ala Pro Ala Gln Ser Ser Pro Ser Ser Gly 
        435                 440                 445             


His Glu Ile Pro Thr Trp Gln Pro Asn Ile Pro Val Arg Ser Asn Ser 
    450                 455                 460                 


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


Pro Ser Ala Thr Thr Val Thr Ala Ile Thr Pro Ala Pro Ile Gln Gln 
                485                 490                 495     


Pro Val Lys Ser Met Arg Val Leu Lys Pro Glu Leu Gln Thr Ala Leu 
            500                 505                 510         


Ala Pro Thr His Pro Ser Trp Ile Pro Gln Pro Ile Gln Thr Val Gln 
        515                 520                 525             


Pro Ser Pro Phe Pro Glu Gly Thr Ala Ser Asn Val Thr Val Met Pro 
    530                 535                 540                 


Pro Val Ala Glu Ala Pro Asn Tyr Gln Gly Pro Pro Pro Pro Tyr Pro 
545                 550                 555                 560 


Lys His Leu Leu His Gln Asn Pro Ser Val Pro Pro Tyr Glu Ser Ile 
                565                 570                 575     


Ser Lys Pro Ser Lys Glu Asp Gln Pro Ser Leu Pro Lys Glu Asp Glu 
            580                 585                 590         


Ser Glu Lys Ser Tyr Glu Asn Val Asp Ser Gly Asp Lys Glu Lys Lys 
        595                 600                 605             


Gln Ile Thr Thr Ser Pro Ile Thr Val Arg Lys Asn Lys Lys Asp Glu 
    610                 615                 620                 


Glu Arg Arg Glu Ser Arg Ile Gln Ser Tyr Ser Pro Gln Ala Phe Lys 
625                 630                 635                 640 


Phe Phe Met Glu Gln His Val Glu Asn Val Leu Lys Ser His Gln Gln 
                645                 650                 655     


Arg Leu His Arg Lys Lys Gln Leu Glu Asn Glu Met Met Arg Val Gly 
            660                 665                 670         


Leu Ser Gln Asp Ala Gln Asp Gln Met Arg Lys Met Leu Cys Gln Lys 
        675                 680                 685             


Glu Ser Asn Tyr Ile Arg Leu Lys Arg Ala Lys Met Asp Lys Ser Met 
    690                 695                 700                 


Phe Val Lys Ile Lys Thr Leu Gly Ile Gly Ala Phe Gly Glu Val Cys 
705                 710                 715                 720 


Leu Ala Arg Lys Val Asp Thr Lys Ala Leu Tyr Ala Thr Lys Thr Leu 
                725                 730                 735     


Arg Lys Lys Asp Val Leu Leu Arg Asn Gln Val Ala His Val Lys Ala 
            740                 745                 750         


Glu Arg Asp Ile Leu Ala Glu Ala Asp Asn Glu Trp Val Val Arg Leu 
        755                 760                 765             


Tyr Tyr Ser Phe Gln Asp Lys Asp Asn Leu Tyr Phe Val Met Asp Tyr 
    770                 775                 780                 


Ile Pro Gly Gly Asp Met Met Ser Leu Leu Ile Arg Met Gly Ile Phe 
785                 790                 795                 800 


Pro Glu Ser Leu Ala Arg Phe Tyr Ile Ala Glu Leu Thr Cys Ala Val 
                805                 810                 815     


Glu Ser Val His Lys Met Gly Phe Ile His Arg Asp Ile Lys Pro Asp 
            820                 825                 830         


Asn Ile Leu Ile Asp Arg Asp Gly His Ile Lys Leu Thr Asp Phe Gly 
        835                 840                 845             


Leu Cys Thr Gly Phe Arg Trp Thr His Asp Ser Lys Tyr Tyr Gln Ser 
    850                 855                 860                 


Gly Asp His Pro Arg Gln Asp Ser Met Asp Phe Ser Asn Glu Trp Gly 
865                 870                 875                 880 


Asp Pro Ser Ser Cys Arg Cys Gly Asp Arg Leu Lys Pro Leu Glu Arg 
                885                 890                 895     


Arg Ala Ala Arg Gln His Gln Arg Cys Leu Ala His Ser Leu Val Gly 
            900                 905                 910         


Thr Pro Asn Tyr Ile Ala Pro Glu Val Leu Leu Arg Thr Gly Tyr Thr 
        915                 920                 925             


Gln Leu Cys Asp Trp Trp Ser Val Gly Val Ile Leu Phe Glu Met Leu 
    930                 935                 940                 


Val Gly Gln Pro Pro Phe Leu Ala Gln Thr Pro Leu Glu Thr Gln Met 
945                 950                 955                 960 


Lys Val Ile Asn Trp Gln Thr Ser Leu His Ile Pro Pro Gln Ala Lys 
                965                 970                 975     


Leu Ser Pro Glu Ala Ser Asp Leu Ile Ile Lys Leu Cys Arg Gly Pro 
            980                 985                 990         


Glu Asp Arg Leu Gly Lys Asn Gly  Ala Asp Glu Ile Lys  Ala His Pro 
        995                 1000                 1005             


Phe Phe  Lys Thr Ile Asp Phe  Ser Ser Asp Leu Arg  Gln Gln Ser 
    1010                 1015                 1020             


Ala Ser  Tyr Ile Pro Lys Ile  Thr His Pro Thr Asp  Thr Ser Asn 
    1025                 1030                 1035             


Phe Asp  Pro Val Asp Pro Asp  Lys Leu Trp Ser Asp  Asp Asn Glu 
    1040                 1045                 1050             


Glu Glu  Asn Val Asn Asp Thr  Leu Asn Gly Trp Tyr  Lys Asn Gly 
    1055                 1060                 1065             


Lys His  Pro Glu His Ala Phe  Tyr Glu Phe Thr Phe  Arg Arg Phe 
    1070                 1075                 1080             


Phe Asp  Asp Asn Gly Tyr Pro  Tyr Asn Tyr Pro Lys  Pro Ile Glu 
    1085                 1090                 1095             


Tyr Glu  Tyr Ile Asn Ser Gln  Gly Ser Glu Gln Gln  Ser Asp Glu 
    1100                 1105                 1110             


Asp Asp  Gln Asn Thr Gly Ser  Glu Ile Lys Asn Arg  Asp Leu Val 
    1115                 1120                 1125             


Tyr Val  
    1130 


<210> 2
<211> 690
<212> PRT
<213> Homo sapiens

<400> 2
Met Lys Arg Ser Glu Lys Pro Glu Gly Tyr Arg Gln Met Arg Pro Lys 
1               5                   10                  15      


Thr Phe Pro Ala Ser Asn Tyr Thr Val Ser Ser Arg Gln Met Leu Gln 
            20                  25                  30          


Glu Ile Arg Glu Ser Leu Arg Asn Leu Ser Lys Pro Ser Asp Ala Ala 
        35                  40                  45              


Lys Ala Glu His Asn Met Ser Lys Met Ser Thr Glu Asp Pro Arg Gln 
    50                  55                  60                  


Val Arg Asn Pro Pro Lys Phe Gly Thr His His Lys Ala Leu Gln Glu 
65                  70                  75                  80  


Ile Arg Asn Ser Leu Leu Pro Phe Ala Asn Glu Thr Asn Ser Ser Arg 
                85                  90                  95      


Ser Thr Ser Glu Val Asn Pro Gln Met Leu Gln Asp Leu Gln Ala Ala 
            100                 105                 110         


Gly Phe Asp Glu Asp Met Val Ile Gln Ala Leu Gln Lys Thr Asn Asn 
        115                 120                 125             


Arg Ser Ile Glu Ala Ala Ile Glu Phe Ile Ser Lys Met Ser Tyr Gln 
    130                 135                 140                 


Asp Pro Arg Arg Glu Gln Met Ala Ala Ala Ala Ala Arg Pro Ile Asn 
145                 150                 155                 160 


Ala Ser Met Lys Pro Gly Asn Val Gln Gln Ser Val Asn Arg Lys Gln 
                165                 170                 175     


Ser Trp Lys Gly Ser Lys Glu Ser Leu Val Pro Gln Arg His Gly Pro 
            180                 185                 190         


Pro Leu Gly Glu Ser Val Ala Tyr His Ser Glu Ser Pro Asn Ser Gln 
        195                 200                 205             


Thr Asp Val Gly Arg Pro Leu Ser Gly Ser Gly Ile Ser Ala Phe Val 
    210                 215                 220                 


Gln Ala His Pro Ser Asn Gly Gln Arg Val Asn Pro Pro Pro Pro Pro 
225                 230                 235                 240 


Gln Val Arg Ser Val Thr Pro Pro Pro Pro Pro Arg Gly Gln Thr Pro 
                245                 250                 255     


Pro Pro Arg Gly Thr Thr Pro Pro Pro Pro Ser Trp Glu Pro Asn Ser 
            260                 265                 270         


Gln Thr Lys Arg Tyr Ser Gly Asn Met Glu Tyr Val Ile Ser Arg Ile 
        275                 280                 285             


Ser Pro Val Pro Pro Gly Ala Trp Gln Glu Gly Tyr Pro Pro Pro Pro 
    290                 295                 300                 


Leu Asn Thr Ser Pro Met Asn Pro Pro Asn Gln Gly Gln Arg Gly Ile 
305                 310                 315                 320 


Ser Ser Val Pro Val Gly Arg Gln Pro Ile Ile Met Gln Ser Ser Ser 
                325                 330                 335     


Lys Phe Asn Phe Pro Ser Gly Arg Pro Gly Met Gln Asn Gly Thr Gly 
            340                 345                 350         


Gln Thr Asp Phe Met Ile His Gln Asn Val Val Pro Ala Gly Thr Val 
        355                 360                 365             


Asn Arg Gln Pro Pro Pro Pro Tyr Pro Leu Thr Ala Ala Asn Gly Gln 
    370                 375                 380                 


Ser Pro Ser Ala Leu Gln Thr Gly Gly Ser Ala Ala Pro Ser Ser Tyr 
385                 390                 395                 400 


Thr Asn Gly Ser Ile Pro Gln Ser Met Met Val Pro Asn Arg Asn Ser 
                405                 410                 415     


His Asn Met Glu Leu Tyr Asn Ile Ser Val Pro Gly Leu Gln Thr Asn 
            420                 425                 430         


Trp Pro Gln Ser Ser Ser Ala Pro Ala Gln Ser Ser Pro Ser Ser Gly 
        435                 440                 445             


His Glu Ile Pro Thr Trp Gln Pro Asn Ile Pro Val Arg Ser Asn Ser 
    450                 455                 460                 


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


Pro Ser Ala Thr Thr Val Thr Ala Ile Thr Pro Ala Pro Ile Gln Gln 
                485                 490                 495     


Pro Val Lys Ser Met Arg Val Leu Lys Pro Glu Leu Gln Thr Ala Leu 
            500                 505                 510         


Ala Pro Thr His Pro Ser Trp Ile Pro Gln Pro Ile Gln Thr Val Gln 
        515                 520                 525             


Pro Ser Pro Phe Pro Glu Gly Thr Ala Ser Asn Val Thr Val Met Pro 
    530                 535                 540                 


Pro Val Ala Glu Ala Pro Asn Tyr Gln Gly Pro Pro Pro Pro Tyr Pro 
545                 550                 555                 560 


Lys His Leu Leu His Gln Asn Pro Ser Val Pro Pro Tyr Glu Ser Ile 
                565                 570                 575     


Ser Lys Pro Ser Lys Glu Asp Gln Pro Ser Leu Pro Lys Glu Asp Glu 
            580                 585                 590         


Ser Glu Lys Ser Tyr Glu Asn Val Asp Ser Gly Asp Lys Glu Lys Lys 
        595                 600                 605             


Gln Ile Thr Thr Ser Pro Ile Thr Val Arg Lys Asn Lys Lys Asp Glu 
    610                 615                 620                 


Glu Arg Arg Glu Ser Arg Ile Gln Ser Tyr Ser Pro Gln Ala Phe Lys 
625                 630                 635                 640 


Phe Phe Met Glu Gln His Val Glu Asn Val Leu Lys Ser His Gln Gln 
                645                 650                 655     


Arg Leu His Arg Lys Lys Gln Leu Glu Asn Glu Met Met Arg Val Lys 
            660                 665                 670         


Pro Phe Lys Met Ser Ile Phe Ile Leu Asn His Leu Phe Ala Trp Cys 
        675                 680                 685             


Leu Phe 
    690 


<210> 3
<211> 1088
<212> PRT
<213> Homo sapiens

<400> 3
Met Arg Pro Lys Thr Phe Pro Ala Thr Thr Tyr Ser Gly Asn Ser Arg 
1               5                   10                  15      


Gln Arg Leu Gln Glu Ile Arg Glu Gly Leu Lys Gln Pro Ser Lys Ser 
            20                  25                  30          


Ser Val Gln Gly Leu Pro Ala Gly Pro Asn Ser Asp Thr Ser Leu Asp 
        35                  40                  45              


Ala Lys Val Leu Gly Ser Lys Asp Ala Thr Arg Gln Gln Gln Gln Met 
    50                  55                  60                  


Arg Ala Thr Pro Lys Phe Gly Pro Tyr Gln Lys Ala Leu Arg Glu Ile 
65                  70                  75                  80  


Arg Tyr Ser Leu Leu Pro Phe Ala Asn Glu Ser Gly Thr Ser Ala Ala 
                85                  90                  95      


Ala Glu Val Asn Arg Gln Met Leu Gln Glu Leu Val Asn Ala Gly Cys 
            100                 105                 110         


Asp Gln Glu Met Ala Gly Arg Ala Leu Lys Gln Thr Gly Ser Arg Ser 
        115                 120                 125             


Ile Glu Ala Ala Leu Glu Tyr Ile Ser Lys Met Gly Tyr Leu Asp Pro 
    130                 135                 140                 


Arg Asn Glu Gln Ile Val Arg Val Ile Lys Gln Thr Ser Pro Gly Lys 
145                 150                 155                 160 


Gly Leu Met Pro Thr Pro Val Thr Arg Arg Pro Ser Phe Glu Gly Thr 
                165                 170                 175     


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


Gly Pro Ser Phe Gly Ala Asp Gly Pro Thr Ala Leu Glu Glu Met Pro 
        195                 200                 205             


Arg Pro Tyr Val Asp Tyr Leu Phe Pro Gly Val Gly Pro His Gly Pro 
    210                 215                 220                 


Gly His Gln His Gln His Pro Pro Lys Gly Tyr Gly Ala Ser Val Glu 
225                 230                 235                 240 


Ala Ala Gly Ala His Phe Pro Leu Gln Gly Ala His Tyr Gly Arg Pro 
                245                 250                 255     


His Leu Leu Val Pro Gly Glu Pro Leu Gly Tyr Gly Val Gln Arg Ser 
            260                 265                 270         


Pro Ser Phe Gln Ser Lys Thr Pro Pro Glu Thr Gly Gly Tyr Ala Ser 
        275                 280                 285             


Leu Pro Thr Lys Gly Gln Gly Gly Pro Pro Gly Ala Gly Leu Ala Phe 
    290                 295                 300                 


Pro Pro Pro Ala Ala Gly Leu Tyr Val Pro His Pro His His Lys Gln 
305                 310                 315                 320 


Ala Gly Pro Ala Ala His Gln Leu His Val Leu Gly Ser Arg Ser Gln 
                325                 330                 335     


Val Phe Ala Ser Asp Ser Pro Pro Gln Ser Leu Leu Thr Pro Ser Arg 
            340                 345                 350         


Asn Ser Leu Asn Val Asp Leu Tyr Glu Leu Gly Ser Thr Ser Val Gln 
        355                 360                 365             


Gln Trp Pro Ala Ala Thr Leu Ala Arg Arg Asp Ser Leu Gln Lys Pro 
    370                 375                 380                 


Gly Leu Glu Ala Pro Pro Arg Ala His Val Ala Phe Arg Pro Asp Cys 
385                 390                 395                 400 


Pro Val Pro Ser Arg Thr Asn Ser Phe Asn Ser His Gln Pro Arg Pro 
                405                 410                 415     


Gly Pro Pro Gly Lys Ala Glu Pro Ser Leu Pro Ala Pro Asn Thr Val 
            420                 425                 430         


Thr Ala Val Thr Ala Ala His Ile Leu His Pro Val Lys Ser Val Arg 
        435                 440                 445             


Val Leu Arg Pro Glu Pro Gln Thr Ala Val Gly Pro Ser His Pro Ala 
    450                 455                 460                 


Trp Val Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala Pro Ala 
465                 470                 475                 480 


Ala Glu Gly Leu Asp Ala Lys Glu Glu His Ala Leu Ala Leu Gly Gly 
                485                 490                 495     


Ala Gly Ala Phe Pro Leu Asp Val Glu Tyr Gly Gly Pro Asp Arg Arg 
            500                 505                 510         


Cys Pro Pro Pro Pro Tyr Pro Lys His Leu Leu Leu Arg Ser Lys Ser 
        515                 520                 525             


Glu Gln Tyr Asp Leu Asp Ser Leu Cys Ala Gly Met Glu Gln Ser Leu 
    530                 535                 540                 


Arg Ala Gly Pro Asn Glu Pro Glu Gly Gly Asp Lys Ser Arg Lys Ser 
545                 550                 555                 560 


Ala Lys Gly Asp Lys Gly Gly Lys Asp Lys Lys Gln Ile Gln Thr Ser 
                565                 570                 575     


Pro Val Pro Val Arg Lys Asn Ser Arg Asp Glu Glu Lys Arg Glu Ser 
            580                 585                 590         


Arg Ile Lys Ser Tyr Ser Pro Tyr Ala Phe Lys Phe Phe Met Glu Gln 
        595                 600                 605             


His Val Glu Asn Val Ile Lys Thr Tyr Gln Gln Lys Val Asn Arg Arg 
    610                 615                 620                 


Leu Gln Leu Glu Gln Glu Met Ala Lys Ala Gly Leu Cys Glu Ala Glu 
625                 630                 635                 640 


Gln Glu Gln Met Arg Lys Ile Leu Tyr Gln Lys Glu Ser Asn Tyr Asn 
                645                 650                 655     


Arg Leu Lys Arg Ala Lys Met Asp Lys Ser Met Phe Val Lys Ile Lys 
            660                 665                 670         


Thr Leu Gly Ile Gly Ala Phe Gly Glu Val Cys Leu Ala Cys Lys Val 
        675                 680                 685             


Asp Thr His Ala Leu Tyr Ala Met Lys Thr Leu Arg Lys Lys Asp Val 
    690                 695                 700                 


Leu Asn Arg Asn Gln Val Ala His Val Lys Ala Glu Arg Asp Ile Leu 
705                 710                 715                 720 


Ala Glu Ala Asp Asn Glu Trp Val Val Lys Leu Tyr Tyr Ser Phe Gln 
                725                 730                 735     


Asp Lys Asp Ser Leu Tyr Phe Val Met Asp Tyr Ile Pro Gly Gly Asp 
            740                 745                 750         


Met Met Ser Leu Leu Ile Arg Met Glu Val Phe Pro Glu His Leu Ala 
        755                 760                 765             


Arg Phe Tyr Ile Ala Glu Leu Thr Leu Ala Ile Glu Ser Val His Lys 
    770                 775                 780                 


Met Gly Phe Ile His Arg Asp Ile Lys Pro Asp Asn Ile Leu Ile Asp 
785                 790                 795                 800 


Leu Asp Gly His Ile Lys Leu Thr Asp Phe Gly Leu Cys Thr Gly Phe 
                805                 810                 815     


Arg Trp Thr His Asn Ser Lys Tyr Tyr Gln Lys Gly Ser His Val Arg 
            820                 825                 830         


Gln Asp Ser Met Glu Pro Ser Asp Leu Trp Asp Asp Val Ser Asn Cys 
        835                 840                 845             


Arg Cys Gly Asp Arg Leu Lys Thr Leu Glu Gln Arg Ala Arg Lys Gln 
    850                 855                 860                 


His Gln Arg Cys Leu Ala His Ser Leu Val Gly Thr Pro Asn Tyr Ile 
865                 870                 875                 880 


Ala Pro Glu Val Leu Leu Arg Lys Gly Tyr Thr Gln Leu Cys Asp Trp 
                885                 890                 895     


Trp Ser Val Gly Val Ile Leu Phe Glu Met Leu Val Gly Gln Pro Pro 
            900                 905                 910         


Phe Leu Ala Pro Thr Pro Thr Glu Thr Gln Leu Lys Val Ile Asn Trp 
        915                 920                 925             


Glu Asn Thr Leu His Ile Pro Ala Gln Val Lys Leu Ser Pro Glu Ala 
    930                 935                 940                 


Arg Asp Leu Ile Thr Lys Leu Cys Cys Ser Ala Asp His Arg Leu Gly 
945                 950                 955                 960 


Arg Asn Gly Ala Asp Asp Leu Lys Ala His Pro Phe Phe Ser Ala Ile 
                965                 970                 975     


Asp Phe Ser Ser Asp Ile Arg Lys Gln Pro Ala Pro Tyr Val Pro Thr 
            980                 985                 990         


Ile Ser His Pro Met Asp Thr Ser  Asn Phe Asp Pro Val  Asp Glu Glu 
        995                 1000                 1005             


Ser Pro  Trp Asn Asp Ala Ser  Glu Gly Ser Thr Lys  Ala Trp Asp 
    1010                 1015                 1020             


Thr Leu  Thr Ser Pro Asn Asn  Lys His Pro Glu His  Ala Phe Tyr 
    1025                 1030                 1035             


Glu Phe  Thr Phe Arg Arg Phe  Phe Asp Asp Asn Gly  Tyr Pro Phe 
    1040                 1045                 1050             


Arg Cys  Pro Lys Pro Ser Gly  Ala Glu Ala Ser Gln  Ala Glu Ser 
    1055                 1060                 1065             


Ser Asp  Leu Glu Ser Ser Asp  Leu Val Asp Gln Thr  Glu Gly Cys 
    1070                 1075                 1080             


Gln Pro  Val Tyr Val 
    1085             


<210> 4
<211> 5
<212> DNA
<213> Unknown

<220>
<221> source
<223> /note="Description of Unknown: 
      Target sequence"


<220>
<221> modified_base
<222> (1)..(1)
<223> a, c, t, g, unknown or other

<220>
<221> modified_base
<222> (4)..(4)
<223> a, c, t, g, unknown or other

<400> 4
nggng                                                                    5


<210> 5
<211> 7
<212> DNA
<213> Unknown

<220>
<221> source
<223> /note="Description of Unknown: 
      Target sequence"


<220>
<221> modified_base
<222> (1)..(2)
<223> a, c, t, g, unknown or other

<400> 5
nnagaaw                                                                  7


<210> 6
<211> 5
<212> DNA
<213> Unknown

<220>
<221> source
<223> /note="Description of Unknown: 
      Target sequence"


<220>
<221> modified_base
<222> (1)..(2)
<223> a, c, t, g, unknown or other

<400> 6
nngrr                                                                    5


<210> 7
<211> 8
<212> DNA
<213> Unknown

<220>
<221> source
<223> /note="Description of Unknown: 
      Target sequence"


<220>
<221> modified_base
<222> (1)..(4)
<223> a, c, t, g, unknown or other

<400> 7
nnnngatt                                                                 8


<210> 8
<211> 7
<212> PRT
<213> Simian virus 40

<400> 8
Pro Lys Lys Lys Arg Lys Val 
1               5           


<210> 9
<211> 42
<212> RNA
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      oligonucleotide"


<220>
<221> modified_base
<222> (1)..(20)
<223> a, c, u, g, unknown or other

<400> 9
nnnnnnnnnn nnnnnnnnnn guuuuagagc uaugcuguuu ug                          42


<210> 10
<211> 86
<212> RNA
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      oligonucleotide"


<220>
<221> misc_feature
<222> (80)..(86)
<223> /note="This region may encompass 1-7 nucleotides"

<220>
<221> misc_feature
<222> (80)..(86)
<223> /note="This region may or may not be present"

<220> 
<221> source
<223> /note="See specification as filed for detailed description of
      substitutions and preferred embodiments"

<400> 10
aacuuaccaa ggaacagcau agcaaguuaa aauaaggcua guccguuauc aacuugaaaa       60

aguggcaccg agucggugcu uuuuuu                                            86


<210> 11
<211> 74
<212> RNA
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      oligonucleotide"


<220>
<221> misc_feature
<222> (68)..(74)
<223> /note="This region may encompass 1-7 nucleotides"

<220>
<221> misc_feature
<222> (68)..(74)
<223> /note="This region may or may not be present"

<220> 
<221> source
<223> /note="See specification as filed for detailed description of
      substitutions and preferred embodiments"

<400> 11
aacagcauag caaguuaaaa uaaggcuagu ccguuaucaa cuugaaaaag uggcaccgag       60

ucggugcuuu uuuu                                                         74


<210> 12
<211> 102
<212> RNA
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      polynucleotide"


<220>
<221> modified_base
<222> (1)..(19)
<223> a, c, u, g, unknown or other

<220>
<221> misc_feature
<222> (96)..(102)
<223> /note="This region may encompass 1-7 nucleotides"

<220>
<221> misc_feature
<222> (96)..(102)
<223> /note="This region may or may not be present"

<220> 
<221> source
<223> /note="See specification as filed for detailed description of
      substitutions and preferred embodiments"

<400> 12
nnnnnnnnnn nnnnnnnnng uuuuagagcu agaaauagca aguuaaaaua aggcuagucc       60

guuaucaacu ugaaaaagug gcaccgaguc ggugcuuuuu uu                         102


<210> 13
<211> 21
<212> DNA
<213> Unknown

<220>
<221> source
<223> /note="Description of Unknown: 
      Target sequence"


<220>
<221> modified_base
<222> (1)..(18)
<223> a, c, t, or g

<220>
<221> modified_base
<222> (19)..(19)
<223> a, c, t, g, unknown or other

<400> 13
nnnnnnnnnn nnnnnnnnng g                                                 21


<210> 14
<211> 19
<212> DNA
<213> Unknown

<220>
<221> source
<223> /note="Description of Unknown: 
      Target sequence"


<220>
<221> modified_base
<222> (1)..(16)
<223> a, c, t, or g

<220>
<221> modified_base
<222> (17)..(17)
<223> a, c, t, g, unknown or other

<400> 14
nnnnnnnnnn nnnnnnngg                                                    19


<210> 15
<211> 21
<212> DNA
<213> Unknown

<220>
<221> source
<223> /note="Description of Unknown: 
      Target sequence"


<220>
<221> modified_base
<222> (1)..(14)
<223> a, c, t, or g

<220>
<221> modified_base
<222> (15)..(16)
<223> a, c, t, g, unknown or other

<400> 15
nnnnnnnnnn nnnnnnagaa w                                                 21


<210> 16
<211> 21
<212> DNA
<213> Unknown

<220>
<221> source
<223> /note="Description of Unknown: 
      Target sequence"


<220>
<221> modified_base
<222> (1)..(14)
<223> a, c, t, or g

<220>
<221> modified_base
<222> (15)..(16)
<223> a, c, t, g, unknown or other

<400> 16
nnnnnnnnnn nnnnnnagaa w                                                 21


<210> 17
<211> 23
<212> DNA
<213> Unknown

<220>
<221> source
<223> /note="Description of Unknown: 
      Target sequence"


<220>
<221> modified_base
<222> (1)..(18)
<223> a, c, t, or g

<220>
<221> modified_base
<222> (19)..(19)
<223> a, c, t, g, unknown or other

<220>
<221> modified_base
<222> (22)..(22)
<223> a, c, t, g, unknown or other

<400> 17
nnnnnnnnnn nnnnnnnnng gng                                               23


<210> 18
<211> 16
<212> DNA
<213> Unknown

<220>
<221> source
<223> /note="Description of Unknown: 
      Target sequence"


<220>
<221> modified_base
<222> (1)..(11)
<223> a, c, t, or g

<220>
<221> modified_base
<222> (12)..(12)
<223> a, c, t, g, unknown or other

<220>
<221> modified_base
<222> (15)..(15)
<223> a, c, t, g, unknown or other

<400> 18
nnnnnnnnnn nnggng                                                       16


<210> 19
<211> 8
<212> DNA
<213> Unknown

<220>
<221> source
<223> /note="Description of Unknown: 
      Target sequence"


<220>
<221> modified_base
<222> (1)..(4)
<223> a, c, t, g, unknown or other

<400> 19
nnnngatt                                                                 8


<210> 20
<211> 8
<212> DNA
<213> Unknown

<220>
<221> source
<223> /note="Description of Unknown: 
      Target sequence"


<220>
<221> modified_base
<222> (1)..(4)
<223> a, c, t, g, unknown or other

<400> 20
nnnngctt                                                                 8


<210> 21
<211> 6
<212> DNA
<213> Unknown

<220>
<221> source
<223> /note="Description of Unknown: 
      Target sequence"


<220>
<221> modified_base
<222> (1)..(2)
<223> a, c, t, g, unknown or other

<400> 21
nngrrt                                                                   6


<210> 22
<211> 6
<212> DNA
<213> Unknown

<220>
<221> source
<223> /note="Description of Unknown: 
      Target sequence"


<220>
<221> modified_base
<222> (1)..(2)
<223> a, c, t, g, unknown or other

<400> 22
nngrrv                                                                   6


<210> 23
<211> 9
<212> PRT
<213> Unknown

<220>
<221> source
<223> /note="Description of Unknown: 
      'LAGLIDADG' family peptide motif sequence"

<400> 23
Leu Ala Gly Leu Ile Asp Ala Asp Gly 
1               5                   


<210> 24
<211> 10
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      peptide"

<400> 24
Lys Lys Leu Arg Arg Thr Leu Ser Val Ala 
1               5                   10  


<210> 25
<211> 6
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      6xHis tag"

<400> 25
His His His His His His 
1               5       


<210> 26
<211> 8
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      8xHis tag"

<400> 26
His His His His His His His His 
1               5               


<210> 27
<211> 11
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      peptide"


<220>
<221> MOD_RES
<222> (1)..(1)
<223> Norvaline

<400> 27
Xaa Lys Lys Arg Asn Arg Arg Leu Ser Val Ala 
1               5                   10      


<210> 28
<211> 8
<212> PRT
<213> Artificial Sequence

<220>
<221> source
<223> /note="Description of Artificial Sequence: Synthetic
      peptide"

<400> 28
Asp Tyr Lys Asp Asp Asp Asp Lys 
1               5               


<210> 29
<211> 13
<212> DNA
<213> Unknown

<220>
<221> source
<223> /note="Description of Unknown: 
      Target sequence"


<220>
<221> modified_base
<222> (1)..(6)
<223> a, c, t, or g

<220>
<221> modified_base
<222> (7)..(8)
<223> a, c, t, g, unknown or other

<400> 29
nnnnnnnnag aaw                                                          13


<210> 30
<211> 18
<212> DNA
<213> Unknown

<220>
<221> source
<223> /note="Description of Unknown: 
      Target sequence"


<220>
<221> modified_base
<222> (1)..(11)
<223> a, c, t, or g

<220>
<221> modified_base
<222> (12)..(13)
<223> a, c, t, g, unknown or other

<400> 30
nnnnnnnnnn nnnagaaw                                                     18


<210> 31
<211> 25
<212> DNA
<213> Unknown

<220>
<221> source
<223> /note="Description of Unknown: 
      Target sequence"


<220>
<221> modified_base
<222> (1)..(20)
<223> a, c, t, or g

<220>
<221> modified_base
<222> (21)..(21)
<223> a, c, t, g, unknown or other

<220>
<221> modified_base
<222> (24)..(24)
<223> a, c, t, g, unknown or other

<400> 31
nnnnnnnnnn nnnnnnnnnn nggng                                             25

