METHODS AND KITS FOR DETERMINING DRUG SENSITIVITY IN PATIENTS INFECTED WITH HCV

• US 20100183555A1
• Filed: 02/04/2008
• Published: 07/22/2010
• Est. Priority Date: 02/05/2007
• Status: Abandoned Application

• Current Assignee: Assistance Publique - Hopitaux De Paris, Inserm (institut national de la sant et de la recherche mdicale, Universite Paris Diderot Paris 7, Universite Rene Descartes
• Original Assignee: Assistance Publique - Hopitaux De Paris, Universite Paris Diderot Paris 7, Universite Rene Descartes
• Inventors: Marcellin, Patrick, Bieche, Ivan, Vidaud, Michel, Asselah, Tarik
• Application Number:
  US12/525,944
• Publication Number:
  US 20100183555A1
• Time in Patent Office: Days
• US Class Current: 424/85.700
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 33/5767 non-A, non-B hepatitis

Abstract

An in vitro method for determining whether a patient infected with HCV is a responder or non-responder to the treatment with interferon-alpha and ribavirin. More specifically, the method includes a step of determining the expression level of the IFI27, CXCL9 and G1P2 genes in a biological sample.

Claims

1. An in vitro method for determining whether a patient infected with HCV is a responder or a non-responder to a pharmaceutical treatment with a combination of interferon-alpha and ribavirin, the said method comprising a step (a) of determining the expression level of the IFI27 and CXCL9 marker genes in a biological sample previously collected from the said patient.

2. The method according to claim 1, wherein step (a) further comprises determining the expression level of the G1P2 marker gene.

3. The method of claim 1 which further comprises a step (b) of comparing, for each marker gene whose expression level has been determined at step (a), (i) the expression level determined at step (a) with (ii) a control reference value previously determined for the said gene in samples from HCV-infected patients selected from the group consisting of from responder patients, non-responder patients, or both.

4. The method of claim 1, wherein the said patient is infected with an HCV of genotype 1.

5. The method of claim 1, wherein, in the combination of interferon-alpha and ribavirin, the said interferon alpha is pegylated.

6. The method of claim 5, wherein, in the combination of interferon-alpha and ribavirin, the said interferon alpha is interferon alpha 2b

7. The method of claim 1, wherein the said biological sample is selected from the group consisting of a liver biopsy, a blood sample or a serum sample.

8. The method of claim 1, wherein, at step (a), the expression level is determined by quantifying the level of mRNA of the said marker genes in the biological sample.

9. The method of claim 8, wherein step (a) comprises the steps of (a1) providing total RNAs collected from the said biological sample, and (a2) subjecting the RNAs to amplification and hybridization to probes specific for the said marker genes.

10. The method of claim 8, wherein, at step (a), the expression level is determined by real-time quantitative or semi-quantitative RT-PCR.

11. The method of claim 1, wherein the expression level is determined, at step (a), by quantifying the level of the proteins encoded by the said marker genes in the said biological sample.

12. The method according to claim 11, wherein the quantification of the level of the proteins encoded by the said marker genes is performed by using a set of antibodies directed against each of the said proteins

15. A method for treating a disease related to an infection with HCV in a patient comprising the steps of:

a) determining whether a patient infected with HCV is a responder or a non responder to a treatment with a combination of interferon-alpha and ribavirin, by performing the in vitro method according to claim 1; and

b) administering a combination of interferon-alpha and ribavirin to the said patient, if the said patient has been determined as consisting of a responder, at step a) above.

16. The method of claim 2 which further comprises a step (b) of comparing, for each marker gene whose expression level has been determined at step (a), (i) the expression level determined at step (a) with (ii) a control reference value previously determined for the said gene in samples from HCV-infected patients selected from the group consisting of from responder patients, non-responder patients, or both.

17. The method of claim 9, wherein, at step (a), the expression level is determined by real-time quantitative or semi-quantitative RT-PCR.

13. A DNA microarray comprising nucleic acids that are specific for IFI27 and CXCL9 genes that are immobilized on a solid support.

14. A DNA microarray according to claim 13 which further comprises nucleic acids that are specific for G1P2 gene.