Title:
THERAPEUTIC AGENT FOR HEPATITIS C CONTAINING RRM2 ANTAGONIST AS ACTIVE INGREDIENT
Document Type and Number:
WIPO Patent Application WO/2012/020836
Kind Code:
A1
Abstract:
The present invention addresses the problem of providing a therapeutic agent for hepatitis C containing an RRM2 antagonist as the active ingredient, an oligoribonucleotide for suppressing the expression of RRM2, a vector for expressing the oligoribonucleotide, and a method for inhibiting the expression of RRM2 by combining the oligoribonucleotide with RRM2 RNA. In order to solve the problem, the present inventors first identified the siRNA sequence that binds to the IRES region of HCV and that exhibits RNAi activity against the ribonucleotide reductase M2 subunit that has been recognized as having an important role in HCV replication, and then reverse transfected the siRNA molecules into persistently HCV-infected cells and measured replicon cytotoxicity. As a result, the siRNA molecules of the present invention were found to exhibit significant HCV replication-suppressing activity.
Inventors:
KOHARA MICHINORI (JP)
TSUKIYAMA-KOHARA KYOKO (JP)
SATOH MASAAKI (JP)
SUDOH MASAYUKI (JP)
TSUKIYAMA-KOHARA KYOKO (JP)
SATOH MASAAKI (JP)
SUDOH MASAYUKI (JP)
Application Number:
PCT/JP2011/068417
Publication Date:
February 16, 2012
Filing Date:
August 12, 2011
Export Citation:
Assignee:
CHUGAI PHARMACEUTICAL CO LTD (JP)
TOKYO METROPOLITAN INST MEDICAL SCIENCE (JP)
UNIV KUMAMOTO NAT UNIV CORP (JP)
KOHARA MICHINORI (JP)
TSUKIYAMA-KOHARA KYOKO (JP)
SATOH MASAAKI (JP)
SUDOH MASAYUKI (JP)
TOKYO METROPOLITAN INST MEDICAL SCIENCE (JP)
UNIV KUMAMOTO NAT UNIV CORP (JP)
KOHARA MICHINORI (JP)
TSUKIYAMA-KOHARA KYOKO (JP)
SATOH MASAAKI (JP)
SUDOH MASAYUKI (JP)
International Classes:
A61K45/00; A61K31/7088; A61K31/713; A61K48/00; A61P31/14; C12N15/113
Foreign References:
| JP2008537551A | 2008-09-18 |
Other References:
HEIDEL J.D. ET AL.: "Potent siRNA inhibitors of ribonucleotide reductase subunit RRM2 reduce cell proliferation in vitro and in vivo", CLINICAL CANCER RESEARCH, vol. 13, no. 7, 2007, pages 2207 - 2215, XP002665151, DOI: doi:10.1158/1078-0432.CCR-06-2218
DUXBURY M.S. ET AL.: "RNA interference targeting the M2 subunit of ribonucleotide reductase enhances pancreatic adenocarcinoma chemosensitivity to gemcitabine", ONCOGENE, vol. 23, no. 8, 2004, pages 1539 - 1548, XP002407219, DOI: doi:10.1038/sj.onc.1207272
LIN Z.P. ET AL.: "Stable suppression of the R2 subunit of ribonucleotide reductase by R2- targeted short interference RNA sensitizes p53 (-/-) HCT-116 colon cancer cells to DNA- damaging agents and ribonucleotide reductase inhibitors", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 279, no. 26, 2004, pages 27030 - 27038, XP002407218, DOI: doi:10.1074/jbc.M402056200
ZHANG Y.W. ET AL.: "Implication of checkpoint kinase-dependent up-regulation of ribonucleotide reductase R2 in DNA damage response", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 284, no. 27, 2009, pages 18085 - 18095
DUXBURY M.S. ET AL.: "RNA interference targeting the M2 subunit of ribonucleotide reductase enhances pancreatic adenocarcinoma chemosensitivity to gemcitabine", ONCOGENE, vol. 23, no. 8, 2004, pages 1539 - 1548, XP002407219, DOI: doi:10.1038/sj.onc.1207272
LIN Z.P. ET AL.: "Stable suppression of the R2 subunit of ribonucleotide reductase by R2- targeted short interference RNA sensitizes p53 (-/-) HCT-116 colon cancer cells to DNA- damaging agents and ribonucleotide reductase inhibitors", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 279, no. 26, 2004, pages 27030 - 27038, XP002407218, DOI: doi:10.1074/jbc.M402056200
ZHANG Y.W. ET AL.: "Implication of checkpoint kinase-dependent up-regulation of ribonucleotide reductase R2 in DNA damage response", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 284, no. 27, 2009, pages 18085 - 18095
Attorney, Agent or Firm:
SHIMIZU, Hatsushi et al. (JP)
Spring water Original aim (JP)
Spring water Original aim (JP)
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