# US 2014/0154209 A1 · Polymorphisms associated with non-response to a hepatitis c treatment or susceptibility to non-spontaneous hepatitis c clearance > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0154209 A1 - Document ID: US20140154209A1 - Status: Published application - Kind: A1 - Application number: 14/125,885 - Filed: 2012-06-29 - Published: 2014-06-05 - Earliest claimed: 2011-06-30 - Assignees: Centre Hospitalier Universitaire Vaudois - Inventors: Stephanie Bibert; Pierre-Yves Bochud - Web page: https://patentgrep.com/patent/US20140154209A1 ## CPC - C12Q 1/707: {non-A, non-B Hepatitis, excluding hepatitis D} - C12Q 1/6883: for diseases caused by alterations of genetic material - C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism - C12Q 2600/154: Methylation markers - C12Q 2600/156: Polymorphic or mutational markers - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES ## Abstract The present invention relates to in vitro methods of determining a susceptibility to non-response to a hepatitis C treatment or a susceptibility to non spontaneous hepatitis C clearance in a subject infected with hepatitis C. ## Claims ### Claim 1 A method of determining a susceptibility of non-response to a hepatitis C treatment in a subject suffering from chronic hepatitis C, said method comprising determining, in a nucleic acid sample isolated from a biological sample obtained from said subject, the presence or absence of at least one methylation associated polymorphism within the 5′ region upstream from the transcription start of the IL28B/A locus. ### Claim 2 (depends on 1) The method of claim 1, wherein said at least one methylation associated polymorphism is in a CpG region. ### Claim 3 (depends on 2) The method of claim 2, wherein the CpG region is located on chromosome 19 between base pairs 39738000 and 39739500. ### Claim 4 (depends on 1) The method of claim 1, wherein the presence of the at least one methylation associated polymorphism is an indication that said subject has an increased or decreased susceptibility to non-response to a hepatitis C treatment. ### Claim 5 (depends on 4) The method of claim 4, wherein the at least one methylation associated polymorphism, which presence is an indication that said subject has an increased susceptibility to nonresponse to a hepatitis C treatment, is selected from the group consisting of rs67272382 T/−, rs67272382−/−, rs74597329 T/G, rs74597329 G/G, rs4803221 C/G and rs4803221 G/G. ### Claim 6 (depends on 1) The method of claim 1, wherein the at least one methylation associated polymorphism is in complete or strong linkage disequilibrium with at least one SNP selected from the group consisting of rs12979860 and rs8099917. ### Claim 7 (depends on 1) The method of claim 1, wherein the hepatitis C treatment is an interferon based treatment or a non-interferon based treatment. ### Claim 8 (depends on 7) The method of claim 7, wherein the interferon based treatment is selected from the group consisting of IFNα, IFNλ and any pegylated-interferon. ### Claim 9 (depends on 7) The method of claim 7, wherein the non-interferon based treatment is selected from the group consisting of an antiprotease drug, an antiviral drug and any combination thereof. ### Claim 10 (depends on 7) The method of claim 7, wherein the interferon based treatment is combined with ribavirin and/or an antiprotease drug and/or an antiviral drug and/or any combination thereof. ### Claim 11 (depends on 7) The method of claim 7, wherein the interferon based treatment is combined with an antiprotease drug and/or an antiviral drug and/or any combination thereof. ### Claim 12 (depends on 9) The method of claim 9, wherein the antiviral drug is a cyclophylin inhibitor. ### Claim 13 (depends on 9) The method of claim 9, wherein the antiprotease drug is selected from the group consisting of an NS3-4A protease inhibitor, an HCV NS5B inhibitor and an HCV NS5A inhibitor. ### Claim 14 (depends on 1) The method of claim 1, wherein said chronic hepatitis C is caused by a viral genotype 1, 2, 3, 4, 5 or 6 of HCV. ### Claim 15 (depends on 1) The method of claim 1, further comprising determining the HCV viral genotype in a nucleic acid sample isolated from a biological sample of said subject. ### Claim 16 A method of determining a susceptibility to non-spontaneous hepatitis C clearance in a subject infected with hepatitis C, said method comprising determining, in a nucleic acid sample isolated from a biological sample obtained from said subject, the presence or absence of at least one methylation associated polymorphism within the 5′ region upstream from the transcription start of the IL28B/A locus. ### Claim 17 (depends on 16) The method of claim 16, wherein said at least one methylation associated polymorphism is in a CpG region. ### Claim 18 (depends on 17) The method of claim 17, wherein the CpG region is located on chromosome 19 between base pairs 39738000 and 39739500. ### Claim 19 (depends on 16) The method of claim 16, wherein the presence of the at least one methylation associated polymorphism is an indication that said subject has an increased susceptibility to non-spontaneous hepatitis C clearance. ### Claim 20 (depends on 16) The method of claim 16, wherein the at least one methylation associated polymorphism, which presence is an indication that said subject has an increased susceptibility to non-spontaneous hepatitis C clearance, is selected from the group consisting of rs67272382 T/−, rs67272382−/−, rs74597329 T/G, rs74597329 G/G, rs4803221 C/G and rs4803221 G/G. ### Claim 21 (depends on 16) The method of claim 16, wherein the at least one methylation associated polymorphism is in complete or strong linkage disequilibrium with at least one SNP selected from the group consisting of rs12979860, rs12979860, rs12979860, rs8099917, rs8099917, and rs8099917. ### Claim 22 (depends on 16) The method of claim 16, wherein said chronic hepatitis C is caused by a viral genotype 1, 2, 3, 4, 5 or 6 of HCV. ### Claim 23 (depends on 16) The method of claim 16, further comprising determining the HCV viral genotype in a nucleic acid sample isolated from a biological sample of said subject. ### Claim 24 (depends on 1) A kit for determining a susceptibility to non-response to a hepatitis C treatment in a subject suffering from chronic hepatitis C according to the method of claim 1, said kit comprising i) reagents for selectively detecting the presence or absence of at least one methylation associated polymorphism within the 5′ region upstream from the transcription start of the IL28B/A locus ii) instructions for use. ### Claim 25 (depends on 1) A kit for determining a susceptibility to non-spontaneous hepatitis C clearance in a subject infected with hepatitis C according to the method of claim 1, said kit comprising i) reagents for selectively detecting the presence or absence of at least one methylation associated polymorphism within the 5′ region upstream from the transcription start of the IL28B/A locus and ii) instructions for use. ### Claim 26 (depends on 24) The kit of claim 24, wherein the reagents further comprise another primer, set of primers, or array of primers, directed to detect the viral genotype. ### Claim 27 A method of treating a patient for hepatitis C, comprising i) determining the presence or absence of at least one methylation associated polymorphism within the 5′ region upstream from the transcription start of the IL28B/A locus in a nucleic acid sample isolated from a biological sample obtained from said patient, ii) and treating the patient based upon whether said one methylation associated polymorphism within the 5′ region upstream from the transcription start of the IL28B/A locus is associated with increased susceptibility to non-response to hepatitis C treatment. ### Claim 28 A method of treating a patient for hepatitis C, comprising i) determining the presence or absence of at least one methylation associated polymorphism within the 5′ region upstream from the transcription start of the IL28B/A locus in a nucleic acid sample isolated from a biological sample obtained from said patient, ii) determining the HCV viral genotype in a nucleic acid sample isolated from a biological sample obtained from said patient, iii) and treating the patient based upon whether said one methylation associated polymorphism within the 5′ region upstream from the transcription start of the IL28B/A locus is associated with increased susceptibility to non-response to hepatitis C treatment. ### Claim 29 A method of assessing a susceptibility to non-response to a hepatitis C treatment in a subject suffering from hepatitis C, said method comprising: i) distinguishing in said subjects those having a susceptibility to non-response to a hepatitis C treatment by determining the presence or absence of at least one methylation associated polymorphism within the 5′ region upstream from the transcription start of the IL28B/A locus in a nucleic acid sample isolated from a biological sample obtained from said patient, the presence of said at least one methylation associated polymorphism being an indication that said subject has an increased susceptibility to non-response to a hepatitis C treatment, ii) establishing a hepatitis C treatment regimen. ### Claim 30 A method of assessing a susceptibility to non-response to a hepatitis C treatment in a subject suffering from hepatitis C, said method comprising: i) distinguishing in said subjects those having a susceptibility to non-response to a hepatitis C treatment by determining the presence or absence of at least one methylation associated polymorphism within the 5′ region upstream from the transcription start of the IL28B/A locus in a nucleic acid sample isolated from a biological sample obtained from said subject, the presence of said one methylation associated polymorphism being an indication that said subject has an increased susceptibility to non-response to a hepatitis C treatment, and the HCV viral genotype, the presence of genotype 1 and/or 4 being an indication that said subject has an increased susceptibility to non-response to a hepatitis C treatment, ii) establishing a hepatitis C treatment regimen. ### Claim 31 (depends on 27) The method of claim 27, wherein the subject suffers from chronic hepatitis C or acute hepatitis C.