SEQUENCE LISTING

<110>  Exelixis, Inc.
       Sanofi
       Verderbilt University
       Arteaga, Carlos L.
       Aftab, Dana T.
       Blanc, Veronique
       Chakrabarty, Anindita
       Chiron-Blondel, Marielle
       Nicolazzi, Celine
       Rinehart, Cammie
       Vincent, Loic 


 
<120>  Combinations of Kinase Inhibitors for the Treatment of Cancer

<130>  224990/10-009C-PC/313618

<150>  US 61/363,074
<151>  2010-07-09

<150>  US 61/421,929
<151>  2010-12-10

<160>  22    

<170>  PatentIn version 3.5

<210>  1
<211>  4624
<212>  DNA
<213>  Homo sapiens

<400>  1
ggaggaggtg gaggaggagg gctgcttgag gaagtataag aatgaagttg tgaagctgag       60

attcccctcc attgggaccg gagaaaccag gggagccccc cgggcagccg cgcgcccctt      120

cccacggggc cctttactgc gccgcgcgcc cggcccccac ccctcgcagc accccgcgcc      180

ccgcgccctc ccagccgggt ccagccggag ccatggggcc ggagccgcag tgagcaccat      240

ggagctggcg gccttgtgcc gctgggggct cctcctcgcc ctcttgcccc ccggagccgc      300

gagcacccaa gtgtgcaccg gcacagacat gaagctgcgg ctccctgcca gtcccgagac      360

ccacctggac atgctccgcc acctctacca gggctgccag gtggtgcagg gaaacctgga      420

actcacctac ctgcccacca atgccagcct gtccttcctg caggatatcc aggaggtgca      480

gggctacgtg ctcatcgctc acaaccaagt gaggcaggtc ccactgcaga ggctgcggat      540

tgtgcgaggc acccagctct ttgaggacaa ctatgccctg gccgtgctag acaatggaga      600

cccgctgaac aataccaccc ctgtcacagg ggcctcccca ggaggcctgc gggagctgca      660

gcttcgaagc ctcacagaga tcttgaaagg aggggtcttg atccagcgga acccccagct      720

ctgctaccag gacacgattt tgtggaagga catcttccac aagaacaacc agctggctct      780

cacactgata gacaccaacc gctctcgggc ctgccacccc tgttctccga tgtgtaaggg      840

ctcccgctgc tggggagaga gttctgagga ttgtcagagc ctgacgcgca ctgtctgtgc      900

cggtggctgt gcccgctgca aggggccact gcccactgac tgctgccatg agcagtgtgc      960

tgccggctgc acgggcccca agcactctga ctgcctggcc tgcctccact tcaaccacag     1020

tggcatctgt gagctgcact gcccagccct ggtcacctac aacacagaca cgtttgagtc     1080

catgcccaat cccgagggcc ggtatacatt cggcgccagc tgtgtgactg cctgtcccta     1140

caactacctt tctacggacg tgggatcctg caccctcgtc tgccccctgc acaaccaaga     1200

ggtgacagca gaggatggaa cacagcggtg tgagaagtgc agcaagccct gtgcccgagt     1260

gtgctatggt ctgggcatgg agcacttgcg agaggtgagg gcagttacca gtgccaatat     1320

ccaggagttt gctggctgca agaagatctt tgggagcctg gcatttctgc cggagagctt     1380

tgatggggac ccagcctcca acactgcccc gctccagcca gagcagctcc aagtgtttga     1440

gactctggaa gagatcacag gttacctata catctcagca tggccggaca gcctgcctga     1500

cctcagcgtc ttccagaacc tgcaagtaat ccggggacga attctgcaca atggcgccta     1560

ctcgctgacc ctgcaagggc tgggcatcag ctggctgggg ctgcgctcac tgagggaact     1620

gggcagtgga ctggccctca tccaccataa cacccacctc tgcttcgtgc acacggtgcc     1680

ctgggaccag ctctttcgga acccgcacca agctctgctc cacactgcca accggccaga     1740

ggacgagtgt gtgggcgagg gcctggcctg ccaccagctg tgcgcccgag ggcactgctg     1800

gggtccaggg cccacccagt gtgtcaactg cagccagttc cttcggggcc aggagtgcgt     1860

ggaggaatgc cgagtactgc aggggctccc cagggagtat gtgaatgcca ggcactgttt     1920

gccgtgccac cctgagtgtc agccccagaa tggctcagtg acctgttttg gaccggaggc     1980

tgaccagtgt gtggcctgtg cccactataa ggaccctccc ttctgcgtgg cccgctgccc     2040

cagcggtgtg aaacctgacc tctcctacat gcccatctgg aagtttccag atgaggaggg     2100

cgcatgccag ccttgcccca tcaactgcac ccactcctgt gtggacctgg atgacaaggg     2160

ctgccccgcc gagcagagag ccagccctct gacgtccatc atctctgcgg tggttggcat     2220

tctgctggtc gtggtcttgg gggtggtctt tgggatcctc atcaagcgac ggcagcagaa     2280

gatccggaag tacacgatgc ggagactgct gcaggaaacg gagctggtgg agccgctgac     2340

acctagcgga gcgatgccca accaggcgca gatgcggatc ctgaaagaga cggagctgag     2400

gaaggtgaag gtgcttggat ctggcgcttt tggcacagtc tacaagggca tctggatccc     2460

tgatggggag aatgtgaaaa ttccagtggc catcaaagtg ttgagggaaa acacatcccc     2520

caaagccaac aaagaaatct tagacgaagc atacgtgatg gctggtgtgg gctccccata     2580

tgtctcccgc cttctgggca tctgcctgac atccacggtg cagctggtga cacagcttat     2640

gccctatggc tgcctcttag accatgtccg ggaaaaccgc ggacgcctgg gctcccagga     2700

cctgctgaac tggtgtatgc agattgccaa ggggatgagc tacctggagg atgtgcggct     2760

cgtacacagg gacttggccg ctcggaacgt gctggtcaag agtcccaacc atgtcaaaat     2820

tacagacttc gggctggctc ggctgctgga cattgacgag acagagtacc atgcagatgg     2880

gggcaaggtg cccatcaagt ggatggcgct ggagtccatt ctccgccggc ggttcaccca     2940

ccagagtgat gtgtggagtt atggtgtgac tgtgtgggag ctgatgactt ttggggccaa     3000

accttacgat gggatcccag cccgggagat ccctgacctg ctggaaaagg gggagcggct     3060

gccccagccc cccatctgca ccattgatgt ctacatgatc atggtcaaat gttggatgat     3120

tgactctgaa tgtcggccaa gattccggga gttggtgtct gaattctccc gcatggccag     3180

ggacccccag cgctttgtgg tcatccagaa tgaggacttg ggcccagcca gtcccttgga     3240

cagcaccttc taccgctcac tgctggagga cgatgacatg ggggacctgg tggatgctga     3300

ggagtatctg gtaccccagc agggcttctt ctgtccagac cctgccccgg gcgctggggg     3360

catggtccac cacaggcacc gcagctcatc taccaggagt ggcggtgggg acctgacact     3420

agggctggag ccctctgaag aggaggcccc caggtctcca ctggcaccct ccgaaggggc     3480

tggctccgat gtatttgatg gtgacctggg aatgggggca gccaaggggc tgcaaagcct     3540

ccccacacat gaccccagcc ctctacagcg gtacagtgag gaccccacag tacccctgcc     3600

ctctgagact gatggctacg ttgcccccct gacctgcagc ccccagcctg aatatgtgaa     3660

ccagccagat gttcggcccc agcccccttc gccccgagag ggccctctgc ctgctgcccg     3720

acctgctggt gccactctgg aaaggcccaa gactctctcc ccagggaaga atggggtcgt     3780

caaagacgtt tttgcctttg ggggtgccgt ggagaacccc gagtacttga caccccaggg     3840

aggagctgcc cctcagcccc accctcctcc tgccttcagc ccagccttcg acaacctcta     3900

ttactgggac caggacccac cagagcgggg ggctccaccc agcaccttca aagggacacc     3960

tacggcagag aacccagagt acctgggtct ggacgtgcca gtgtgaacca gaaggccaag     4020

tccgcagaag ccctgatgtg tcctcaggga gcagggaagg cctgacttct gctggcatca     4080

agaggtggga gggccctccg accacttcca ggggaacctg ccatgccagg aacctgtcct     4140

aaggaacctt ccttcctgct tgagttccca gatggctgga aggggtccag cctcgttgga     4200

agaggaacag cactggggag tctttgtgga ttctgaggcc ctgcccaatg agactctagg     4260

gtccagtgga tgccacagcc cagcttggcc ctttccttcc agatcctggg tactgaaagc     4320

cttagggaag ctggcctgag aggggaagcg gccctaaggg agtgtctaag aacaaaagcg     4380

acccattcag agactgtccc tgaaacctag tactgccccc catgaggaag gaacagcaat     4440

ggtgtcagta tccaggcttt gtacagagtg cttttctgtt tagtttttac tttttttgtt     4500

ttgttttttt aaagatgaaa taaagaccca gggggagaat gggtgttgta tggggaggca     4560

agtgtggggg gtccttctcc acacccactt tgtccatttg caaatatatt ttggaaaaca     4620

gcta                                                                  4624


<210>  2
<211>  1254
<212>  PRT
<213>  Homo sapiens

<400>  2

Met Glu Leu Ala Ala Leu Cys Arg Trp Gly Leu Leu Leu Ala Leu Leu 
1               5                   10                  15      


Pro Pro Gly Ala Ala Ser Thr Gln Val Cys Thr Gly Thr Asp Met Lys 
            20                  25                  30          


Leu Arg Leu Pro Ala Ser Pro Glu Thr His Leu Asp Met Leu Arg His 
        35                  40                  45              


Leu Tyr Gln Gly Cys Gln Val Val Gln Gly Asn Leu Glu Leu Thr Tyr 
    50                  55                  60                  


Leu Pro Thr Asn Ala Ser Leu Ser Phe Leu Gln Asp Ile Gln Glu Val 
65                  70                  75                  80  


Gln Gly Tyr Val Leu Ile Ala His Asn Gln Val Arg Gln Val Pro Leu 
                85                  90                  95      


Gln Arg Leu Arg Ile Val Gly Thr Gln Leu Phe Glu Asp Asn Tyr Ala 
            100                 105                 110         


Leu Ala Val Leu Asp Asn Gly Asp Pro Leu Asn Asn Thr Thr Pro Val 
        115                 120                 125             


Thr Gly Ala Ser Pro Gly Gly Leu Arg Glu Leu Gln Leu Arg Ser Leu 
    130                 135                 140                 


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


Cys Tyr Gln Asp Thr Ile Leu Trp Lys Asp Ile Phe His Lys Asn Asn 
                165                 170                 175     


Gln Leu Ala Leu Thr Leu Ile Asp Thr Asn Arg Ser Arg Ala Cys His 
            180                 185                 190         


Pro Cys Ser Pro Met Cys Lys Gly Ser Arg Cys Trp Gly Glu Ser Ser 
        195                 200                 205             


Glu Asp Cys Gln Ser Leu Thr Arg Thr Val Cys Ala Gly Gly Cys Ala 
    210                 215                 220                 


Arg Cys Lys Gly Pro Leu Pro Thr Asp Cys Cys His Glu Gln Cys Ala 
225                 230                 235                 240 


Ala Gly Cys Thr Gly Pro Lys His Ser Asp Cys Leu Ala Cys Leu His 
                245                 250                 255     


Phe Asn His Ser Gly Ile Cys Glu Leu His Cys Pro Ala Leu Val Thr 
            260                 265                 270         


Tyr Asn Thr Asp Thr Phe Glu Ser Met Pro Asn Pro Glu Gly Arg Tyr 
        275                 280                 285             


Thr Phe Gly Ala Ser Cys Val Thr Ala Cys Pro Tyr Asn Tyr Leu Ser 
    290                 295                 300                 


Thr Asp Val Gly Ser Cys Thr Leu Val Cys Pro Leu His Asn Gln Glu 
305                 310                 315                 320 


Val Thr Ala Glu Asp Gly Thr Gln Arg Cys Glu Lys Cys Ser Lys Pro 
                325                 330                 335     


Cys Ala Arg Val Cys Tyr Gly Leu Gly Met Glu His Leu Arg Glu Val 
            340                 345                 350         


Arg Ala Val Thr Ser Ala Asn Ile Gln Glu Phe Ala Gly Cys Lys Lys 
        355                 360                 365             


Ile Phe Gly Ser Leu Ala Phe Leu Pro Glu Ser Phe Asp Gly Asp Pro 
    370                 375                 380                 


Ala Ser Asn Thr Ala Pro Leu Gln Pro Glu Gln Leu Gln Val Phe Glu 
385                 390                 395                 400 


Thr Leu Glu Glu Ile Thr Gly Tyr Leu Tyr Ile Ser Ala Trp Pro Asp 
                405                 410                 415     


Ser Leu Pro Asp Leu Ser Val Phe Gln Asn Leu Gln Val Ile Arg Gly 
            420                 425                 430         


Arg Ile Leu His Asn Gly Ala Tyr Ser Leu Thr Leu Gln Gly Leu Gly 
        435                 440                 445             


Ile Ser Trp Leu Gly Leu Arg Ser Leu Arg Glu Leu Gly Ser Gly Leu 
    450                 455                 460                 


Ala Leu Ile His His Asn Thr His Leu Cys Phe Val His Thr Val Pro 
465                 470                 475                 480 


Trp Asp Gln Leu Phe Arg Asn Pro His Gln Ala Leu Leu His Thr Ala 
                485                 490                 495     


Asn Arg Pro Glu Asp Glu Cys Val Gly Glu Gly Leu Ala Cys His Gln 
            500                 505                 510         


Leu Cys Ala Arg Gly His Cys Trp Gly Pro Gly Pro Thr Gln Cys Val 
        515                 520                 525             


Asn Cys Ser Gln Phe Leu Arg Gly Gln Glu Cys Val Glu Glu Cys Arg 
    530                 535                 540                 


Val Leu Gln Gly Leu Pro Arg Glu Tyr Val Asn Ala Arg His Cys Leu 
545                 550                 555                 560 


Pro Cys His Pro Glu Cys Gln Pro Gln Asn Gly Ser Val Thr Cys Phe 
                565                 570                 575     


Gly Pro Glu Ala Asp Gln Cys Val Ala Cys Ala His Tyr Lys Asp Pro 
            580                 585                 590         


Pro Phe Cys Val Ala Arg Cys Pro Ser Gly Val Lys Pro Asp Leu Ser 
        595                 600                 605             


Tyr Met Pro Ile Trp Lys Phe Pro Asp Glu Glu Gly Ala Cys Gln Pro 
    610                 615                 620                 


Cys Pro Ile Asn Cys Thr His Ser Cys Val Asp Leu Asp Asp Lys Gly 
625                 630                 635                 640 


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


Val Val Gly Ile Leu Leu Val Val Val Leu Gly Val Val Phe Gly Ile 
            660                 665                 670         


Leu Ile Lys Arg Arg Gln Gln Lys Ile Arg Lys Tyr Thr Met Arg Arg 
        675                 680                 685             


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


Met Pro Asn Gln Ala Gln Met Arg Ile Leu Lys Glu Thr Glu Leu Arg 
705                 710                 715                 720 


Lys Val Lys Val Leu Gly Ser Gly Ala Phe Gly Thr Val Tyr Lys Gly 
                725                 730                 735     


Ile Trp Ile Pro Asp Gly Glu Asn Val Lys Ile Pro Val Ala Ile Lys 
            740                 745                 750         


Val Leu Arg Glu Asn Thr Ser Pro Lys Ala Asn Lys Glu Ile Leu Asp 
        755                 760                 765             


Glu Ala Tyr Val Met Ala Gly Val Gly Ser Pro Tyr Val Ser Arg Leu 
    770                 775                 780                 


Leu Gly Ile Cys Leu Thr Ser Thr Val Gln Leu Val Thr Gln Leu Met 
785                 790                 795                 800 


Pro Tyr Gly Cys Leu Leu Asp His Val Arg Glu Asn Arg Gly Arg Leu 
                805                 810                 815     


Gly Ser Gln Asp Leu Leu Asn Trp Cys Met Gln Ile Ala Lys Gly Met 
            820                 825                 830         


Ser Tyr Leu Glu Asp Val Arg Leu Val His Arg Asp Leu Ala Ala Arg 
        835                 840                 845             


Asn Val Leu Val Lys Ser Pro Asn His Val Lys Ile Thr Asp Phe Gly 
    850                 855                 860                 


Leu Ala Arg Leu Leu Asp Ile Asp Glu Thr Glu Tyr His Ala Asp Gly 
865                 870                 875                 880 


Gly Lys Val Pro Ile Lys Trp Met Ala Leu Glu Ser Ile Leu Arg Arg 
                885                 890                 895     


Arg Phe Thr His Gln Ser Asp Val Trp Ser Tyr Gly Val Thr Val Trp 
            900                 905                 910         


Glu Leu Met Thr Phe Gly Ala Lys Pro Tyr Asp Gly Ile Pro Ala Arg 
        915                 920                 925             


Glu Ile Pro Asp Leu Leu Glu Lys Gly Glu Arg Leu Pro Gln Pro Pro 
    930                 935                 940                 


Ile Cys Thr Ile Asp Val Tyr Met Ile Met Val Lys Cys Trp Met Ile 
945                 950                 955                 960 


Asp Ser Glu Cys Arg Pro Arg Phe Arg Glu Leu Val Ser Glu Phe Ser 
                965                 970                 975     


Arg Met Ala Arg Asp Pro Gln Arg Phe Val Val Ile Gln Asn Glu Asp 
            980                 985                 990         


Leu Gly Pro Ala Ser Pro Leu Asp  Ser Thr Phe Tyr Arg  Ser Leu Leu 
        995                 1000                 1005             


Glu Asp  Asp Asp Met Gly Asp  Leu Val Asp Ala Glu  Glu Tyr Leu 
    1010                 1015                 1020             


Val Pro  Gln Gln Gly Phe Phe  Cys Pro Asp Pro Ala  Pro Gly Ala 
    1025                 1030                 1035             


Gly Gly  Met Val His His Arg  His Arg Ser Ser Ser  Thr Arg Ser 
    1040                 1045                 1050             


Gly Gly  Gly Asp Leu Thr Leu  Gly Leu Glu Pro Ser  Glu Glu Glu 
    1055                 1060                 1065             


Ala Pro  Arg Ser Pro Leu Ala  Pro Ser Glu Gly Ala  Gly Ser Asp 
    1070                 1075                 1080             


Val Phe  Asp Gly Asp Leu Gly  Met Gly Ala Ala Lys  Gly Leu Gln 
    1085                 1090                 1095             


Ser Leu  Pro Thr His Asp Pro  Ser Pro Leu Gln Arg  Tyr Ser Glu 
    1100                 1105                 1110             


Asp Pro  Thr Val Pro Leu Pro  Ser Glu Thr Asp Gly  Tyr Val Ala 
    1115                 1120                 1125             


Pro Leu  Thr Cys Ser Pro Gln  Pro Glu Tyr Val Asn  Gln Pro Asp 
    1130                 1135                 1140             


Val Arg  Pro Gln Pro Pro Ser  Pro Arg Glu Gly Pro  Leu Pro Ala 
    1145                 1150                 1155             


Ala Arg  Pro Ala Gly Ala Thr  Leu Glu Arg Pro Lys  Thr Leu Ser 
    1160                 1165                 1170             


Pro Gly  Lys Asn Gly Val Val  Lys Asp Val Phe Ala  Phe Gly Gly 
    1175                 1180                 1185             


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


Pro Gln  Pro His Pro Pro Pro  Ala Phe Ser Pro Ala  Phe Asp Asn 
    1205                 1210                 1215             


Leu Tyr  Tyr Trp Asp Gln Asp  Pro Pro Glu Arg Gly  Ala Pro Pro 
    1220                 1225                 1230             


Ser Thr  Phe Lys Gly Thr Pro  Thr Ala Glu Asn Pro  Glu Tyr Leu 
    1235                 1240                 1245             


Gly Leu  Asp Val Pro Val 
    1250                 


<210>  3
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  HER2 siRNA inhibitor forward sequence

<400>  3
ccuggaacuc accuaccugd tdt                                               23


<210>  4
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  HER2 siRNA inhibitor reverse sequence

<400>  4
cagguaggug aguuccaggd tdt                                               23


<210>  5
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  HER2 siRNA inhibitor forward sequence

<400>  5
cuaccuuucu acggacgugd tdt                                               23


<210>  6
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  HER2 siRNA inhibitor reverse sequence

<400>  6
cacguccgua gaaagguagd tdt                                               23


<210>  7
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  HER2 siRNA inhibitor forward sequence

<400>  7
gauccggaag uacacgaugd tdt                                               23


<210>  8
<211>  23
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  HER2 siRNA inhibitor reverse sequence

<400>  8
caucguguac uuccggaucd tdt                                               23


<210>  9
<211>  5
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  anti-ErbB3 antibody VH CDR1

<400>  9

His Tyr Val Met Ala 
1               5   


<210>  10
<211>  17
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  anti-ErbB3 antibody VH CDR2

<400>  10

Ser Ile Ser Ser Ser Gly Gly Trp Thr Leu Tyr Ala Asp Ser Val Lys 
1               5                   10                  15      


Gly 
    


<210>  11
<211>  10
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  anti-ErbB3 antibody VH CDR3

<400>  11

Gly Leu Lys Met Ala Thr Ile Phe Asp Tyr 
1               5                   10  


<210>  12
<211>  14
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  anti-ErbB3 antibody VL CDR1

<400>  12

Thr Gly Thr Ser Ser Asp Val Gly Ser Tyr Asn Val Val Ser 
1               5                   10                  


<210>  13
<211>  7
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  anti-ErbB3 antibody VL CDR2

<400>  13

Glu Val Ser Gln Arg Pro Ser 
1               5           


<210>  14
<211>  11
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  anti-ErbB3 antibody VL CDR3

<400>  14

Cys Ser Tyr Ala Gly Ser Ser Ile Phe Val Ile 
1               5                   10      


<210>  15
<211>  118
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VH anti-ErbB3 antibody

<400>  15

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ala Tyr 
            20                  25                  30          


Asn Met Arg Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Val Ile Tyr Pro Ser Gly Gly Ala Thr Arg Tyr Ala Asp Ser Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  


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


Ala Arg Gly Tyr Tyr Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr 
            100                 105                 110         


Leu Val Thr Val Ser Ser 
        115             


<210>  16
<211>  110
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  VL anti-ErbB3 antibody of SEQ ID No: 15

<400>  16

Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln 
1               5                   10                  15      


Arg Val Thr Ile Ser Cys Ser Gly Ser Asp Ser Asn Ile Gly Arg Asn 
            20                  25                  30          


Tyr Ile Tyr Trp Tyr Gln Gln Phe Pro Gly Thr Ala Pro Lys Leu Leu 
        35                  40                  45              


Ile Tyr Arg Asn Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Ile Ser 
    50                  55                  60                  


Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Arg 
65                  70                  75                  80  


Ser Glu Asp Glu Ala Glu Tyr His Cys Gly Thr Trp Asp Asp Ser Leu 
                85                  90                  95      


Ser Gly Pro Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 
            100                 105                 110 


<210>  17
<211>  445
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  MM-121 antibody - heavy chain

<400>  17

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


Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser His Tyr 
            20                  25                  30          


Val Met Ala Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 
        35                  40                  45              


Ser Ser Ile Ser Ser Ser Gly Gly Trp Thr Leu Tyr Ala Asp Ser Val 
    50                  55                  60                  


Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr 
65                  70                  75                  80  


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


Thr Arg Gly Leu Lys Met Ala Thr Ile Phe Asp Tyr Trp Gly Gln Gly 
            100                 105                 110         


Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe 
        115                 120                 125             


Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu 
    130                 135                 140                 


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


Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu 
                165                 170                 175     


Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser 
            180                 185                 190         


Ser Asn Phe Gly Thr Gln Thr Tyr Thr Cys Asn Val Asp His Lys Pro 
        195                 200                 205             


Ser Asn Thr Lys Val Asp Lys Thr Val Glu Arg Lys Cys Cys Val Glu 
    210                 215                 220                 


Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser Val Phe Leu 
225                 230                 235                 240 


Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu 
                245                 250                 255     


Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Gln 
            260                 265                 270         


Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys 
        275                 280                 285             


Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val Leu 
    290                 295                 300                 


Thr Val Val His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys 
305                 310                 315                 320 


Val Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys 
                325                 330                 335     


Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser 
            340                 345                 350         


Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys 
        355                 360                 365             


Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln 
    370                 375                 380                 


Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Met Leu Asp Ser Asp Gly 
385                 390                 395                 400 


Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln 
                405                 410                 415     


Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 
            420                 425                 430         


His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys 
        435                 440                 445 


<210>  18
<211>  217
<212>  PRT
<213>  Artificial Sequence

<220>
<223>  MM-121 antibody - light chain

<400>  18

Gln Ser Ala Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro Gly Gln 
1               5                   10                  15      


Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Ser Tyr 
            20                  25                  30          


Asn Val Val Ser Trp Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu 
        35                  40                  45              


Ile Ile Tyr Glu Val Ser Gln Arg Pro Ser Gly Val Ser Asn Arg Phe 
    50                  55                  60                  


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


Gln Thr Glu Asp Glu Ala Asp Tyr Tyr Cys Cys Ser Tyr Ala Gly Ser 
                85                  90                  95      


Ser Ile Phe Val Ile Phe Gly Gly Gly Thr Lys Val Thr Val Leu Gly 
            100                 105                 110         


Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu 
        115                 120                 125             


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


Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala Asp Gly Ser Pro Val 
145                 150                 155                 160 


Lys Val Gly Val Glu Thr Thr Lys Pro Ser Lys Gln Ser Asn Asn Lys 
                165                 170                 175     


Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser 
            180                 185                 190         


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


Lys Thr Val Ala Pro Ala Glu Cys Ser 
    210                 215         


<210>  19
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  FoxO1 sense strand

<400>  19
ccauggacaa caacaguaat t                                                 21


<210>  20
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  FoxO3a sense strand

<400>  20
gccuugucga auucugucat t                                                 21


<210>  21
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  IGF-IR sense strand

<400>  21
ggagaauaau ccaguccuat t                                                 21


<210>  22
<211>  21
<212>  DNA
<213>  Artificial Sequence

<220>
<223>  InsR sense strand

<400>  22
gaacgauguu ggacucauat t                                                 21 