                         SEQUENCE LISTING

<110>  Novartis Pharma AG
       Lewitzky , Steven
       Meyer , Joanne
       Paulding  , Charles
       Singer, Jonathan
 
<120>  Use of a COX-2 inhibitor for the treatment of a COX-2 dependent 
       disorder in a patient not carrying HLA alleles associated with 
       hepatotoxicity

<130>  52815 PCT

<140>  Herewith
<141>  2009-08-20

<160>  18    

<170>  PatentIn version 3.3

<210>  1
<211>  768
<212>  DNA
<213>  homo sapiens

<400>  1
atgatcctaa acaaagctct gctgctgggg gccctcgctc tgaccaccgt gatgagcccc     60

tgtggaggtg aagacattgt ggctgaccac gttgcctctt gtggtgtaaa cttgtaccag    120

ttttacggtc cctctggcca gtacacccat gaatttgatg gagatgagca gttctacgtg    180

gacctggaga ggaaggagac tgcctggcgg tggcctgagt tcagcaaatt tggaggtttt    240

gacccgcagg gtgcactgag aaacatggct gtggcaaaac acaacttgaa catcatgatt    300

aaacgctaca actctaccgc tgctaccaat gaggttcctg aggtcacagt gttttccaag    360

tctcccgtga cactgggtca gcccaacacc ctcatttgtc ttgtggacaa catctttcct    420

cctgtggtca acatcacatg gctgagcaat gggcagtcag tcacagaagg tgtttctgag    480

accagcttcc tctccaagag tgatcattcc ttcttcaaga tcagttacct caccttcctc    540

ccttctgctg atgagattta tgactgcaag gtggagcact ggggcctgga ccagcctctt    600

ctgaaacact gggagcctga gattccagcc cctatgtcag agctcacaga gactgtggtc    660

tgtgccctgg ggttgtctgt gggcctcatg ggcattgtgg tgggcactgt cttcatcatc    720

caaggcctgc gttcagttgg tgcttccaga caccaagggc cattgtga                 768


<210>  2
<211>  768
<212>  DNA
<213>  homo sapiens

<400>  2
atgatcctaa acaaagctct gctgctgggg gccctcgctc tgaccaccgt gatgagcccc     60

tgtggaggtg aagacattgt ggctgaccac gttgcctctt gtggtgtaaa cttgtaccag    120

ttttacggtc cctctggcca gtacacccat gaatttgatg gagatgagca gttctacgtg    180

gacctggaga ggaaggagac tgcctggcgg tggcctgagt tcagcaaatt tggaggtttt    240

gacccgcagg gtgcactgag aaacatggct gtggcaaaac acaacttgaa catcatgatt    300

aaacgctaca actctaccgc tgctaccaat gaggttcctg aggtcacagt gttttccaag    360

tctcccgtga cactgggtca gcccaacacc ctcatctgtc ttgtggacaa catctttcct    420

cctgtggtca acatcacatg gctgagcaat gggcagtcag tcacagaagg tgtttctgag    480

accagcttcc tctccaagag tgatcattcc ttcttcaaga tcagttacct caccttcctc    540

ccttctgctg atgagattta tgactgcaag gtggagcact ggggcctgga ccagcctctt    600

ctgaaacact gggagcctga gattccagcc cctatgtcag agctcacaga gactgtggtc    660

tgtgccctgg ggttgtctgt gggcctcatg ggcattgtgg tgggcactgt cttcatcatc    720

caaggcctgc gttcagttgg tgcttccaga caccaagggc cattgtga                 768


<210>  3
<211>  768
<212>  DNA
<213>  homo sapiens

<400>  3
atgatcctaa acaaagctct gctgctgggg gccctcgctc tgaccaccgt gatgagcccc     60

tgtggaggtg aagacattgt ggctgaccac gttgcctctt gtggtgtaaa cttgtaccag    120

ttttacggtc cctctggcca gtacacccat gaatttgatg gagatgagca gttctacgtg    180

gacctggaga ggaaggagac tgcctggcgg tggcctgagt tcagcaaatt tggaggtttt    240

gacccgcagg gtgcactgag aaacatggct gtggcaaaac acaacttgaa catcatgatt    300

aaacgctaca actctaccgc tgctaccaat gaggttcctg aggtcacagt gttttccaag    360

tctcccgtga cactgggtca gcccaacacc ctcatttgtc ttgtggacaa catctttcct    420

cctgtggtca acatcacctg gctgagcaat gggcagtcag tcacagaagg tgtttctgag    480

accagcttcc tctccaagag tgatcattcc ttcttcaaga tcagttacct caccttcctc    540

ccttctgctg atgagattta tgactgcaag gtggagcact ggggcctgga ccagcctctt    600

ctgaaacact gggagcctga gattccagcc cctatgtcag agctcacaga gactgtggtc    660

tgtgccctgg ggttgtctgt gggcctcatg ggcattgtgg tgggcactgt cttcatcatc    720

caaggcctgc gttcagttgg tgcttccaga caccaagggc cattgtga                 768


<210>  4
<211>  768
<212>  DNA
<213>  homo sapiens

<400>  4
atgatcctaa acaaagctct gctgctgggg gccctcgctc tgaccactgt gatgagcccc     60

tgtggaggtg aagacattgt ggctgaccac gttgcctctt gtggtgtaaa cttgtaccag    120

ttttacggtc cctctggcca gtacacccat gaatttgatg gagatgagca gttctacgtg    180

gacctggaga ggaaggagac tgcctggcgg tggcctgagt tcagcaaatt tggaggtttt    240

gacccgcagg gtgcactgag aaacatggct gtggcaaaac acaacttgaa catcatgatt    300

aaacgctaca actctaccgc tgctaccaat gaggttcctg aggtcacagt gttttccaag    360

tctcccgtga cactgggtca gcccaacacc ctcatctgtc ttgtggacaa catctttcct    420

cctgtggtca acatcacatg gctgagcaat gggcagtcag tcacagaagg tgtttctgag    480

accagcttcc tctccaagag tgatcattcc ttcttcaaga tcagttacct caccttcctc    540

ccttctgctg atgagattta tgactgcaag gtggagcact ggggcctgga ccagcctctt    600

ctgaaacact gggagcctga gattccagcc cctatgtcag agctcacaga gactgtggtc    660

tgtgccctgg ggttgtctgt gggcctcatg ggcattgtgg tgggcactgt cttcatcatc    720

caaggcctgc gttcagttgg tgcttccaga caccaagggc cattgtga                 768


<210>  5
<211>  254
<212>  PRT
<213>  homo sapiens

<400>  5

Met Ile Leu Asn Lys Ala Leu Leu Leu Gly Ala Leu Ala Leu Thr Thr 
1               5                   10                  15      


Val Met Ser Pro Cys Gly Gly Glu Asp Ile Val Ala Asp His Val Ala 
            20                  25                  30          


Ser Cys Gly Val Asn Leu Tyr Gln Phe Tyr Gly Pro Ser Gly Gln Tyr 
        35                  40                  45              


Thr His Glu Phe Asp Gly Asp Glu Gln Phe Tyr Val Asp Leu Glu Arg 
    50                  55                  60                  


Lys Glu Tyr Ala Trp Arg Trp Pro Glu Phe Ser Lys Phe Gly Gly Phe 
65                  70                  75                  80  


Asp Pro Gln Gly Ala Leu Arg Asn Met Ala Val Ala Lys His Asn Leu 
                85                  90                  95      


Asn Ile Met Ile Lys Arg Tyr Asn Ser Thr Ala Ala Thr Asn Glu Val 
            100                 105                 110         


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


Asn Thr Leu Ile Cys Leu Val Asp Asn Ile Phe Pro Pro Val Val Asn 
    130                 135                 140                 


Ile Thr Trp Leu Ser Asn Gly Gln Ser Val Thr Glu Gly Val Ser Glu 
145                 150                 155                 160 


Thr Ser Phe Leu Ser Lys Ser Asp His Ser Phe Phe Lys Ile Ser Tyr 
                165                 170                 175     


Leu Thr Phe Leu Pro Ser Ala Asp Glu Ile Tyr Asp Cys Lys Val Glu 
            180                 185                 190         


His Trp Gly Leu Asp Gln Pro Leu Leu Lys His Glu Pro Glu Ile Pro 
        195                 200                 205             


Ala Pro Met Ser Glu Leu Thr Glu Thr Val Val Cys Ala Leu Gly Leu 
    210                 215                 220                 


Ser Val Gly Leu Met Gly Ile Val Val Gly Thr Val Phe Ile Ile Gln 
225                 230                 235                 240 


Gly Leu Arg Ser Val Gly Ala Ser Arg His Gln Gly Pro Leu 
                245                 250                 


<210>  6
<211>  801
<212>  DNA
<213>  homo sapiens

<400>  6
atggtgtgtc tgaagctccc tggaggctcc tgcatgacag cgctgacagt gacactgatg     60

gtgctgagct ccccactggc tttgtctggg gacacccgac cacgtttcct gtggcagcct    120

aagagggagt gtcatttctt caatgggacg gagcgggtgc ggttcctgga cagatacttc    180

tataaccagg aggagtccgt gcgcttcgac agcgacgtgg gggagttccg ggcggtgacg    240

gagctggggc ggcctgacgc tgagtactgg aacagccaga aggacatcct ggagcaggcg    300

cgggccgcgg tggacaccta ctgcagacac aactacgggg ttgtggagag cttcacagtg    360

cagcggcgag tccaacctaa ggtgactgta tatccttcaa agacccagcc cctgcagcac    420

cacaacctcc tggtctgctc tgtgagtggt ttctatccag gcagcattga agtcaggtgg    480

ttcctgaacg gccaggaaga gaaggctggg atggtgtcca caggcctgat ccagaatgga    540

gactggacct tccagaccct ggtgatgctg gaaacagttc ctcgaagtgg agaggtttac    600

acctgccaag tggagcaccc aagcgtgaca agccctctca cagtggaatg gagagcacgg    660

tctgaatctg cacagagcaa gatgctgagt ggagtcgggg gctttgtgct gggcctgctc    720

ttccttgggg ccgggctgtt catctacttc aggaatcaga aaggacactc tggacttcag    780

ccaacaggat tcctgagctg a                                              801


<210>  7
<211>  266
<212>  DNA
<213>  homo sapiens

<400>  7
cacgtttcct gtggcagcct aagagggagt gtcatttctt caatgggacg gagcgggtgc     60

ggttcctgga cagatacttc tataaccagg aggagtccgt gcgcttcgac agcgacgtgg    120

gggagttccg ggcggtgacg gagctggggc ggcctgacgc tgagtactgg aacagccaga    180

aggacatcct ggagcaggcg cgggccgcgg tggacaccta ctgcagacac aactacggag    240

ttgtggagag cttcacagtg cagcgg                                         266


<210>  8
<211>  266
<212>  DNA
<213>  homo sapiens

<400>  8
cacgtttcct gtggcagcct aagagggagt gtcatttctt caatgggacg gagcgggtgc     60

ggttcctgga cagatacttc tataaccagg aggagtccgt gcgcttcgac agcgacgtgg    120

gggagttccg ggcggtgacg gagctggggc ggcctgacgc tgagtactgg aacagccaga    180

aggacatcct ggagcaggcg cgggccgcgg tggacaccta ttgcagacac aactacgggg    240

ttgtggagag cttcacagtg cagcgg                                         266


<210>  9
<211>  270
<212>  DNA
<213>  homo sapiens

<400>  9
cacgtttcct gtggcagcct aagagggagt gtcatttctt caatgggacg gagcgggtgc     60

ggttcctgga cagatacttc tataaccagg aggagtccgt gcgcttcgac agcgacgtgg    120

gggagttccg ggcggtgacg gagctggggc ggcctgatgc cgagtactgg aacagccaga    180

aggacatcct ggagcaggcg cgggccgcgg tggacaccta ctgcagacac aactacgggg    240

ttgtggagag cttcacagtg cagcggcgag                                     270


<210>  10
<211>  270
<212>  DNA
<213>  homo sapiens

<400>  10
cacgtttcct gtggcagcct aagagggagt gtcatttctt caatgggacc gagcgggtgc     60

ggttcctgga cagatacttc tataaccagg aggagtccgt gcgcttcgac agcgacgtgg    120

gggagttccg ggcggtgacg gagctggggc ggcctgacgc tgagtactgg aacagccaga    180

aggacatcct ggagcaggcg cgggccgcgg tggacaccta ctgcagacac aactacgggg    240

ttgtggagag cttcacagtg cagcggcgag                                     270


<210>  11
<211>  270
<212>  DNA
<213>  homo sapiens

<400>  11
cacgtttcct gtggcagcct aagagggagt gtcatttctt caatgggacg gagcgggtgc     60

ggttcctgga cagatacttc tataaccagg aggagtccgt gcgcttcgac agcgacgtgg    120

gggagttccg ggcggtgacg gagctggggc ggcctgacgc tgaatactgg aacagccaga    180

aggacatcct ggagcaggcg cgggccgcgg tggacaccta ctgcagacac aactacgggg    240

ttgtggagag cttcacagtg cagcggcgag                                     270


<210>  12
<211>  263
<212>  PRT
<213>  homo sapiens

<400>  12

Met Val Cys Leu Lys Leu Pro Gly Gly Ser Cys Met Thr Ala Leu Thr 
1               5                   10                  15      


Val Thr Leu Met Val Leu Ser Ser Pro Leu Ala Leu Ser Gly Asp Thr 
            20                  25                  30          


Arg Pro Arg Phe Leu Trp Gln Pro Lys Arg Glu Cys His Phe Phe Asn 
        35                  40                  45              


Gly Thr Glu Arg Val Arg Phe Leu Asp Arg Tyr Phe Tyr Asn Gln Glu 
    50                  55                  60                  


Glu Ser Val Arg Phe Asp Ser Asp Val Gly Glu Phe Arg Ala Val Thr 
65                  70                  75                  80  


Glu Leu Gly Arg Pro Asp Ala Glu Trp Asn Ser Gln Lys Asp Ile Leu 
                85                  90                  95      


Glu Gln Ala Arg Ala Ala Val Asp Thr Tyr Cys Arg His Asn Tyr Gly 
            100                 105                 110         


Val Val Glu Ser Phe Thr Val Gln Arg Arg Val Gln Pro Lys Val Thr 
        115                 120                 125             


Val Tyr Pro Ser Lys Thr Gln Pro Leu Gln His His Asn Leu Leu Val 
    130                 135                 140                 


Ser Val Ser Gly Phe Tyr Pro Gly Ser Ile Glu Val Arg Trp Phe Leu 
145                 150                 155                 160 


Asn Gly Gln Glu Glu Lys Ala Gly Met Val Ser Thr Gly Leu Ile Gln 
                165                 170                 175     


Asn Gly Asp Trp Thr Phe Gln Thr Leu Val Met Leu Glu Thr Val Pro 
            180                 185                 190         


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


Ser Pro Thr Val Glu Trp Arg Ala Arg Ser Glu Ser Ala Gln Ser Lys 
    210                 215                 220                 


Met Leu Ser Gly Val Gly Gly Phe Val Leu Gly Leu Leu Phe Leu Gly 
225                 230                 235                 240 


Ala Gly Leu Phe Ile Tyr Phe Arg Asn Gln Lys Gly His Ser Gly Leu 
                245                 250                 255     


Gln Pro Thr Gly Phe Leu Ser 
            260             


<210>  13
<211>  786
<212>  DNA
<213>  homo sapiens

<400>  13
atgtcttgga agaaggcttt gcggatcccc ggagaccttc gggtagcaac tgtcaccttg     60

atgctggcga tgctgagctc cctactggct gagggcagag actctcccga ggatttcgtg    120

ttccagttta agggcatgtg ctacttcacc aacgggacgg agcgcgtgcg tcttgtgacc    180

agatacatct ataaccgaga ggagtacgcg cgcttcgaca gcgacgtggg ggtgtaccgc    240

gcggtgacgc cgcaggggcg gcctgatgcc gagtactgga acagccagaa ggaagtcctg    300

gaggggaccc gggcggagtt ggacacggtg tgcagacaca actacgaggt ggcgttccgc    360

gggatcttgc agaggagagt ggagcccaca gtgaccatct ccccatccag gacagaggcc    420

ctcaaccacc acaacctgct ggtctgctcg gtgacagatt tctatccagg ccagatcaaa    480

gtccggtggt ttcggaatga tcaggaggag acagccggcg ttgtgtccac cccccttatt    540

aggaatggtg actggacttt ccagatcctg gtgatgctgg aaatgactcc ccagcgtgga    600

gatgtctaca cctgccacgt ggagcacccc agcctccaga gccccatcac cgtggagtgg    660

cgggctcagt ctgaatctgc ccagagcaag atgctgagtg gcgttggagg cttcgtgctg    720

gggctgatct tccttgggct gggccttatc atccgtcaaa ggagtcagaa agggcttctg    780

cactga                                                               786


<210>  14
<211>  270
<212>  DNA
<213>  homo sapiens

<400>  14
aggatttcgt gttccagttt aagggcatgt gctacttcac caacgggacg gagcgcgtgc     60

gtcttgtgac cagatacatc tataaccgag aggagtacgc acgcttcgac agcgacgtgg    120

gggtgtaccg cgcggtgacg ccgcaggggc ggcctgatgc cgagtactgg aacagccaga    180

aggaagtcct ggaggggacc cgggcggagt tggacacggt gtgcagacac aactacgagg    240

tggcgttccg cgggatcttg cagaggagag                                     270


<210>  15
<211>  261
<212>  PRT
<213>  homo sapiens

<400>  15

Met Ser Trp Lys Lys Ala Leu Arg Ile Pro Gly Asp Leu Arg Val Ala 
1               5                   10                  15      


Thr Val Thr Leu Met Leu Ala Met Leu Ser Ser Leu Leu Ala Glu Gly 
            20                  25                  30          


Arg Asp Ser Pro Glu Asp Phe Val Phe Gln Phe Lys Gly Met Cys Tyr 
        35                  40                  45              


Phe Thr Asn Gly Thr Glu Arg Val Arg Leu Val Thr Arg Tyr Ile Tyr 
    50                  55                  60                  


Asn Arg Glu Glu Tyr Ala Arg Phe Asp Ser Asp Val Gly Val Tyr Arg 
65                  70                  75                  80  


Ala Val Tyr Pro Gln Gly Arg Pro Asp Ala Glu Tyr Trp Asn Ser Gln 
                85                  90                  95      


Lys Glu Val Leu Glu Gly Thr Arg Ala Glu Leu Asp Thr Val Cys Arg 
            100                 105                 110         


His Asn Tyr Glu Val Ala Phe Arg Gly Ile Leu Gln Arg Arg Val Glu 
        115                 120                 125             


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


Asn Leu Leu Val Cys Ser Val Thr Asp Phe Tyr Pro Gly Gln Ile Lys 
145                 150                 155                 160 


Val Arg Trp Phe Arg Asn Asp Gln Glu Glu Thr Ala Gly Val Val Ser 
                165                 170                 175     


Thr Pro Leu Ile Arg Asn Gly Asp Trp Thr Phe Gln Ile Leu Val Met 
            180                 185                 190         


Leu Glu Met Thr Pro Gln Arg Gly Asp Val Tyr Thr Cys His Val Glu 
        195                 200                 205             


His Pro Ser Leu Gln Ser Pro Ile Thr Val Glu Trp Arg Ala Gln Ser 
    210                 215                 220                 


Glu Ser Ala Gln Ser Lys Met Leu Ser Gly Val Gly Gly Phe Val Leu 
225                 230                 235                 240 


Gly Leu Ile Phe Leu Gly Leu Gly Leu Ile Ile Arg Gln Arg Ser Gln 
                245                 250                 255     


Lys Gly Leu Leu His 
            260     


<210>  16
<211>  801
<212>  DNA
<213>  homo sapiens

<400>  16
atggtgtgtc tgaagctccc tggaggttcc tacatggcaa agctgacagt gacactgatg     60

gtgctgagct ccccactggc tttggctggg gacacccgac cacgtttctt gcagcaggat    120

aagtatgagt gtcatttctt caacgggacg gagcgggtgc ggttcctgca cagagacatc    180

tataaccaag aggaggactt gcgcttcgac agcgacgtgg gggagtaccg ggcggtgacg    240

gagctggggc ggcctgacgc tgagtactgg aacagccaga aggacttcct ggaagacagg    300

cgcgccgcgg tggacaccta ctgcagacac aactacgggg ttggtgagag cttcacagtg    360

cagcggcgag ttgagcctaa ggtgactgtg tatcctgcaa ggacccagac cctgcagcac    420

cacaacctcc tggtctgctc tgtgaatggt ttctatccag gcagcattga agtcaggtgg    480

ttccggaaca gccaggaaga gaaggctggg gtggtgtcca caggcctgat tcagaatgga    540

gactggacct tccagaccct ggtgatgctg gaaacagttc ctcgaagtgg agaggtttac    600

acctgccaag tggagcaccc aagcgtgacg agccctctca cagtggaatg gagagcacag    660

tctgaatctg cacagagcaa gatgctgagt ggagtcgggg gctttgtgct gggcctgctc    720

ttccttgggg ccgggctatt catctacttc aagaatcaga aagggcactc tggacttcac    780

ccaacaggac tcgtgagctg a                                              801


<210>  17
<211>  257
<212>  DNA
<213>  homo sapiens

<400>  17
cacgtttctt gcagcaggat aagtatgagt gtcatttctt caacgggacg gagcgggtgc     60

ggttcctgca cagagacatc tataaccaag aggaggactt gcgcttcgac agcgacgtgg    120

gggagtaccg ggcggtgacg gagctggggc ggcctgacgc tgagtactgg aacagccaga    180

aggacttcct ggaagacagg cgggccgcgg tggacaccta ctgcagacac aactacgggg    240

ttggtgagag cttcaca                                                   257


<210>  18
<211>  267
<212>  PRT
<213>  homo sapiens

<400>  18

Met Val Cys Leu Lys Leu Pro Gly Gly Ser Tyr Met Ala Lys Leu Thr 
1               5                   10                  15      


Val Thr Leu Met Val Leu Ser Ser Pro Pro Leu Ala Leu Ala Gly Asp 
            20                  25                  30          


Thr Arg Pro Arg Phe Leu Gln Gln Asp Lys Tyr Glu Cys His Phe Phe 
        35                  40                  45              


Asn Gly Thr Glu Arg Val Arg Phe Leu His Arg Asp Ile Tyr Asn Gln 
    50                  55                  60                  


Glu Glu Asp Leu Arg Phe Asp Ser Asp Val Gly Glu Tyr Arg Ala Val 
65                  70                  75                  80  


Thr Glu Leu Gly Arg Pro Asp Ala Glu Tyr Trp Asn Ser Gln Lys Asp 
                85                  90                  95      


Phe Leu Glu Asp Arg Arg Ala Ala Val Asp Thr Tyr Cys Arg His Asn 
            100                 105                 110         


Tyr Gly Val Gly Glu Ser Phe Thr Val Gln Arg Arg Val Glu Pro Lys 
        115                 120                 125             


Val Thr Val Tyr Pro Ala Arg Thr Gln Thr Leu Gln His His Asn Leu 
    130                 135                 140                 


Leu Val Cys Ser Val Asn Gly Phe Tyr Pro Gly Ser Ile Glu Val Arg 
145                 150                 155                 160 


Trp Phe Arg Asn Ser Gln Glu Glu Lys Ala Gly Val Val Ser Thr Gly 
                165                 170                 175     


Leu Ile Gln Asn Gly Asp Trp Thr Phe Gln Thr Leu Val Met Leu Glu 
            180                 185                 190         


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


Ser Val Thr Ser Pro Leu Thr Val Glu Trp Arg Ala Gln Ser Glu Ser 
    210                 215                 220                 


Ala Gln Ser Lys Met Leu Ser Gly Val Gly Gly Phe Val Leu Gly Leu 
225                 230                 235                 240 


Leu Phe Leu Gly Ala Gly Leu Phe Ile Tyr Phe Lys Asn Gln Lys Gly 
                245                 250                 255     


His Ser Gly Leu His Pro Thr Gly Leu Val Ser 
            260                 265         


