                         SEQUENCE LISTING

<110>  Bayer Intellectual Property GmbH
 
<120>  Inhibitors of SHP2

<130>  BD 41754

<160>  3     

<170>  PatentIn version 3.5

<210>  1
<211>  597
<212>  PRT
<213>  artificial

<220>
<223>  SHP2  AA sequence Isoform 1

<400>  1

Met Thr Ser Arg Arg Trp Phe His Pro Asn Ile Thr Gly Val Glu Ala 
1               5                   10                  15      


Glu Asn Leu Leu Leu Thr Arg Gly Val Asp Gly Ser Phe Leu Ala Arg 
            20                  25                  30          


Pro Ser Lys Ser Asn Pro Gly Asp Phe Thr Leu Ser Val Arg Arg Asn 
        35                  40                  45              


Gly Ala Val Thr His Ile Lys Ile Gln Asn Thr Gly Asp Tyr Tyr Asp 
    50                  55                  60                  


Leu Tyr Gly Gly Glu Lys Phe Ala Thr Leu Ala Glu Leu Val Gln Tyr 
65                  70                  75                  80  


Tyr Met Glu His His Gly Gln Leu Lys Glu Lys Asn Gly Asp Val Ile 
                85                  90                  95      


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


Phe His Gly His Leu Ser Gly Lys Glu Ala Glu Lys Leu Leu Thr Glu 
        115                 120                 125             


Lys Gly Lys His Gly Ser Phe Leu Val Arg Glu Ser Gln Ser His Pro 
    130                 135                 140                 


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


Asn Asp Gly Lys Ser Lys Val Thr His Val Met Ile Arg Cys Gln Glu 
                165                 170                 175     


Leu Lys Tyr Asp Val Gly Gly Gly Glu Arg Phe Asp Ser Leu Thr Asp 
            180                 185                 190         


Leu Val Glu His Tyr Lys Lys Asn Pro Met Val Glu Thr Leu Gly Thr 
        195                 200                 205             


Val Leu Gln Leu Lys Gln Pro Leu Asn Thr Thr Arg Ile Asn Ala Ala 
    210                 215                 220                 


Glu Ile Glu Ser Arg Val Arg Glu Leu Ser Lys Leu Ala Glu Thr Thr 
225                 230                 235                 240 


Asp Lys Val Lys Gln Gly Phe Trp Glu Glu Phe Glu Thr Leu Gln Gln 
                245                 250                 255     


Gln Glu Cys Lys Leu Leu Tyr Ser Arg Lys Glu Gly Gln Arg Gln Glu 
            260                 265                 270         


Asn Lys Asn Lys Asn Arg Tyr Lys Asn Ile Leu Pro Phe Asp His Thr 
        275                 280                 285             


Arg Val Val Leu His Asp Gly Asp Pro Asn Glu Pro Val Ser Asp Tyr 
    290                 295                 300                 


Ile Asn Ala Asn Ile Ile Met Pro Glu Phe Glu Thr Lys Cys Asn Asn 
305                 310                 315                 320 


Ser Lys Pro Lys Lys Ser Tyr Ile Ala Thr Gln Gly Cys Leu Gln Asn 
                325                 330                 335     


Thr Val Asn Asp Phe Trp Arg Met Val Phe Gln Glu Asn Ser Arg Val 
            340                 345                 350         


Ile Val Met Thr Thr Lys Glu Val Glu Arg Gly Lys Ser Lys Cys Val 
        355                 360                 365             


Lys Tyr Trp Pro Asp Glu Tyr Ala Leu Lys Glu Tyr Gly Val Met Arg 
    370                 375                 380                 


Val Arg Asn Val Lys Glu Ser Ala Ala His Asp Tyr Thr Leu Arg Glu 
385                 390                 395                 400 


Leu Lys Leu Ser Lys Val Gly Gln Ala Leu Leu Gln Gly Asn Thr Glu 
                405                 410                 415     


Arg Thr Val Trp Gln Tyr His Phe Arg Thr Trp Pro Asp His Gly Val 
            420                 425                 430         


Pro Ser Asp Pro Gly Gly Val Leu Asp Phe Leu Glu Glu Val His His 
        435                 440                 445             


Lys Gln Glu Ser Ile Met Asp Ala Gly Pro Val Val Val His Cys Ser 
    450                 455                 460                 


Ala Gly Ile Gly Arg Thr Gly Thr Phe Ile Val Ile Asp Ile Leu Ile 
465                 470                 475                 480 


Asp Ile Ile Arg Glu Lys Gly Val Asp Cys Asp Ile Asp Val Pro Lys 
                485                 490                 495     


Thr Ile Gln Met Val Arg Ser Gln Arg Ser Gly Met Val Gln Thr Glu 
            500                 505                 510         


Ala Gln Tyr Arg Phe Ile Tyr Met Ala Val Gln His Tyr Ile Glu Thr 
        515                 520                 525             


Leu Gln Arg Arg Ile Glu Glu Glu Gln Lys Ser Lys Arg Lys Gly His 
    530                 535                 540                 


Glu Tyr Thr Asn Ile Lys Tyr Ser Leu Ala Asp Gln Thr Ser Gly Asp 
545                 550                 555                 560 


Gln Ser Pro Leu Pro Pro Cys Thr Pro Thr Pro Pro Cys Ala Glu Met 
                565                 570                 575     


Arg Glu Asp Ser Ala Arg Val Tyr Glu Asn Val Gly Leu Met Gln Gln 
            580                 585                 590         


Gln Lys Ser Phe Arg 
        595         


<210>  2
<211>  593
<212>  PRT
<213>  artificial

<220>
<223>  SHP2 AA sequence Isoform 2

<400>  2

Met Thr Ser Arg Arg Trp Phe His Pro Asn Ile Thr Gly Val Glu Ala 
1               5                   10                  15      


Glu Asn Leu Leu Leu Thr Arg Gly Val Asp Gly Ser Phe Leu Ala Arg 
            20                  25                  30          


Pro Ser Lys Ser Asn Pro Gly Asp Phe Thr Leu Ser Val Arg Arg Asn 
        35                  40                  45              


Gly Ala Val Thr His Ile Lys Ile Gln Asn Thr Gly Asp Tyr Tyr Asp 
    50                  55                  60                  


Leu Tyr Gly Gly Glu Lys Phe Ala Thr Leu Ala Glu Leu Val Gln Tyr 
65                  70                  75                  80  


Tyr Met Glu His His Gly Gln Leu Lys Glu Lys Asn Gly Asp Val Ile 
                85                  90                  95      


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


Phe His Gly His Leu Ser Gly Lys Glu Ala Glu Lys Leu Leu Thr Glu 
        115                 120                 125             


Lys Gly Lys His Gly Ser Phe Leu Val Arg Glu Ser Gln Ser His Pro 
    130                 135                 140                 


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


Asn Asp Gly Lys Ser Lys Val Thr His Val Met Ile Arg Cys Gln Glu 
                165                 170                 175     


Leu Lys Tyr Asp Val Gly Gly Gly Glu Arg Phe Asp Ser Leu Thr Asp 
            180                 185                 190         


Leu Val Glu His Tyr Lys Lys Asn Pro Met Val Glu Thr Leu Gly Thr 
        195                 200                 205             


Val Leu Gln Leu Lys Gln Pro Leu Asn Thr Thr Arg Ile Asn Ala Ala 
    210                 215                 220                 


Glu Ile Glu Ser Arg Val Arg Glu Leu Ser Lys Leu Ala Glu Thr Thr 
225                 230                 235                 240 


Asp Lys Val Lys Gln Gly Phe Trp Glu Glu Phe Glu Thr Leu Gln Gln 
                245                 250                 255     


Gln Glu Cys Lys Leu Leu Tyr Ser Arg Lys Glu Gly Gln Arg Gln Glu 
            260                 265                 270         


Asn Lys Asn Lys Asn Arg Tyr Lys Asn Ile Leu Pro Phe Asp His Thr 
        275                 280                 285             


Arg Val Val Leu His Asp Gly Asp Pro Asn Glu Pro Val Ser Asp Tyr 
    290                 295                 300                 


Ile Asn Ala Asn Ile Ile Met Pro Glu Phe Glu Thr Lys Cys Asn Asn 
305                 310                 315                 320 


Ser Lys Pro Lys Lys Ser Tyr Ile Ala Thr Gln Gly Cys Leu Gln Asn 
                325                 330                 335     


Thr Val Asn Asp Phe Trp Arg Met Val Phe Gln Glu Asn Ser Arg Val 
            340                 345                 350         


Ile Val Met Thr Thr Lys Glu Val Glu Arg Gly Lys Ser Lys Cys Val 
        355                 360                 365             


Lys Tyr Trp Pro Asp Glu Tyr Ala Leu Lys Glu Tyr Gly Val Met Arg 
    370                 375                 380                 


Val Arg Asn Val Lys Glu Ser Ala Ala His Asp Tyr Thr Leu Arg Glu 
385                 390                 395                 400 


Leu Lys Leu Ser Lys Val Gly Gln Gly Asn Thr Glu Arg Thr Val Trp 
                405                 410                 415     


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


Gly Gly Val Leu Asp Phe Leu Glu Glu Val His His Lys Gln Glu Ser 
        435                 440                 445             


Ile Met Asp Ala Gly Pro Val Val Val His Cys Ser Ala Gly Ile Gly 
    450                 455                 460                 


Arg Thr Gly Thr Phe Ile Val Ile Asp Ile Leu Ile Asp Ile Ile Arg 
465                 470                 475                 480 


Glu Lys Gly Val Asp Cys Asp Ile Asp Val Pro Lys Thr Ile Gln Met 
                485                 490                 495     


Val Arg Ser Gln Arg Ser Gly Met Val Gln Thr Glu Ala Gln Tyr Arg 
            500                 505                 510         


Phe Ile Tyr Met Ala Val Gln His Tyr Ile Glu Thr Leu Gln Arg Arg 
        515                 520                 525             


Ile Glu Glu Glu Gln Lys Ser Lys Arg Lys Gly His Glu Tyr Thr Asn 
    530                 535                 540                 


Ile Lys Tyr Ser Leu Ala Asp Gln Thr Ser Gly Asp Gln Ser Pro Leu 
545                 550                 555                 560 


Pro Pro Cys Thr Pro Thr Pro Pro Cys Ala Glu Met Arg Glu Asp Ser 
                565                 570                 575     


Ala Arg Val Tyr Glu Asn Val Gly Leu Met Gln Gln Gln Lys Ser Phe 
            580                 585                 590         


Arg 
    


<210>  3
<211>  460
<212>  PRT
<213>  artificial

<220>
<223>  SHP2 AA sequence Isoform 3

<400>  3

Met Thr Ser Arg Arg Trp Phe His Pro Asn Ile Thr Gly Val Glu Ala 
1               5                   10                  15      


Glu Asn Leu Leu Leu Thr Arg Gly Val Asp Gly Ser Phe Leu Ala Arg 
            20                  25                  30          


Pro Ser Lys Ser Asn Pro Gly Asp Phe Thr Leu Ser Val Arg Arg Asn 
        35                  40                  45              


Gly Ala Val Thr His Ile Lys Ile Gln Asn Thr Gly Asp Tyr Tyr Asp 
    50                  55                  60                  


Leu Tyr Gly Gly Glu Lys Phe Ala Thr Leu Ala Glu Leu Val Gln Tyr 
65                  70                  75                  80  


Tyr Met Glu His His Gly Gln Leu Lys Glu Lys Asn Gly Asp Val Ile 
                85                  90                  95      


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


Phe His Gly His Leu Ser Gly Lys Glu Ala Glu Lys Leu Leu Thr Glu 
        115                 120                 125             


Lys Gly Lys His Gly Ser Phe Leu Val Arg Glu Ser Gln Ser His Pro 
    130                 135                 140                 


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


Asn Asp Gly Lys Ser Lys Val Thr His Val Met Ile Arg Cys Gln Glu 
                165                 170                 175     


Leu Lys Tyr Asp Val Gly Gly Gly Glu Arg Phe Asp Ser Leu Thr Asp 
            180                 185                 190         


Leu Val Glu His Tyr Lys Lys Asn Pro Met Val Glu Thr Leu Gly Thr 
        195                 200                 205             


Val Leu Gln Leu Lys Gln Pro Leu Asn Thr Thr Arg Ile Asn Ala Ala 
    210                 215                 220                 


Glu Ile Glu Ser Arg Val Arg Glu Leu Ser Lys Leu Ala Glu Thr Thr 
225                 230                 235                 240 


Asp Lys Val Lys Gln Gly Phe Trp Glu Glu Phe Glu Thr Leu Gln Gln 
                245                 250                 255     


Gln Glu Cys Lys Leu Leu Tyr Ser Arg Lys Glu Gly Gln Arg Gln Glu 
            260                 265                 270         


Asn Lys Asn Lys Asn Arg Tyr Lys Asn Ile Leu Pro Phe Asp His Thr 
        275                 280                 285             


Arg Val Val Leu His Asp Gly Asp Pro Asn Glu Pro Val Ser Asp Tyr 
    290                 295                 300                 


Ile Asn Ala Asn Ile Ile Met Pro Glu Phe Glu Thr Lys Cys Asn Asn 
305                 310                 315                 320 


Ser Lys Pro Lys Lys Ser Tyr Ile Ala Thr Gln Gly Cys Leu Gln Asn 
                325                 330                 335     


Thr Val Asn Asp Phe Trp Arg Met Val Phe Gln Glu Asn Ser Arg Val 
            340                 345                 350         


Ile Val Met Thr Thr Lys Glu Val Glu Arg Gly Lys Ser Lys Cys Val 
        355                 360                 365             


Lys Tyr Trp Pro Asp Glu Tyr Ala Leu Lys Glu Tyr Gly Val Met Arg 
    370                 375                 380                 


Val Arg Asn Val Lys Glu Ser Ala Ala His Asp Tyr Thr Leu Arg Glu 
385                 390                 395                 400 


Leu Lys Leu Ser Lys Val Gly Gln Gly Asn Thr Glu Arg Thr Val Trp 
                405                 410                 415     


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


Gly Gly Val Leu Asp Phe Leu Glu Glu Val His His Lys Gln Glu Ser 
        435                 440                 445             


Ile Met Asp Ala Gly Pro Val Val Val His Cys Arg 
    450                 455                 460 


