WO2009021121A3 - Identification and characterization of hcv replicon variants with reduced susceptibility to a combination of polymerase and protease inhibitors, and methods related thereto - Google Patents

Identification and characterization of hcv replicon variants with reduced susceptibility to a combination of polymerase and protease inhibitors, and methods related thereto Download PDF

Info

Publication number
WO2009021121A3
WO2009021121A3 PCT/US2008/072492 US2008072492W WO2009021121A3 WO 2009021121 A3 WO2009021121 A3 WO 2009021121A3 US 2008072492 W US2008072492 W US 2008072492W WO 2009021121 A3 WO2009021121 A3 WO 2009021121A3
Authority
WO
WIPO (PCT)
Prior art keywords
hepatitis
methods
viral infection
treatment
combination
Prior art date
Application number
PCT/US2008/072492
Other languages
French (fr)
Other versions
WO2009021121A2 (en
WO2009021121A4 (en
Inventor
Michael James Flint
Anita Y.M. Howe
Original Assignee
Wyeth
Viropharma Incorporated
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Wyeth, Viropharma Incorporated filed Critical Wyeth
Publication of WO2009021121A2 publication Critical patent/WO2009021121A2/en
Publication of WO2009021121A3 publication Critical patent/WO2009021121A3/en
Publication of WO2009021121A4 publication Critical patent/WO2009021121A4/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/06—Tripeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/576—Immunoassay; Biospecific binding assay; Materials therefor for hepatitis
    • G01N33/5767—Immunoassay; Biospecific binding assay; Materials therefor for hepatitis non-A, non-B hepatitis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/005—Assays involving biological materials from specific organisms or of a specific nature from viruses
    • G01N2333/08—RNA viruses
    • G01N2333/18—Togaviridae; Flaviviridae
    • G01N2333/183—Flaviviridae, e.g. pestivirus, mucosal disease virus, bovine viral diarrhoea virus, classical swine fever virus (hog cholera virus) or border disease virus
    • G01N2333/186—Hepatitis C; Hepatitis NANB
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2469/00—Immunoassays for the detection of microorganisms
    • G01N2469/10—Detection of antigens from microorganism in sample from host
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/56—Staging of a disease; Further complications associated with the disease

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Communicable Diseases (AREA)
  • Epidemiology (AREA)
  • Biomedical Technology (AREA)
  • Virology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Cell Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Food Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Microbiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biotechnology (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

The present invention provides methods of decreasing the frequency of emergence, decreasing the level of resistance, and delaying the emergence of a treatment-resistant hepatitis C viral infection, by administering to a subject, either in combination or in series, an inhibitor of the hepatitis C RNA-dependent RNA polymerase NS5B, e.g., a benzofuran, such as 5-cyclopropyl-2-(4-fluorophenyl)- 6-[(2-hydroxyethyl)(methylsulfonyl)amino]-N-methyl-l-benzofuran- 3-carboxamide (HCV-796), and an inhibitor of the serine protease NS3, e.g., boceprevir. Additionally, the invention relates to methods of monitoring the course of treatment of a hepatitis C viral infection, methods of monitoring and prognosing a hepatitis C viral infection, and methods of identifying an individual with a decreased likelihood of responding to an anti-hepatitis C viral therapy. These methods use the sequence(s) of HCV nonstructural gene(s) to identify the emergence of a treatment-resistant hepatitis C viral infection, particularly a benzofuran (e.g., HCV-796) and NS3 inhibitor (e.g., boceprevir) treatment- resistant hepatitis C viral infection.
PCT/US2008/072492 2007-08-08 2008-08-07 Identification and characterization of hcv replicon variants with reduced susceptibility to a combination of polymerase and protease inhibitors, and methods related thereto WO2009021121A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US95466507P 2007-08-08 2007-08-08
US60/954,665 2007-08-08

Publications (3)

Publication Number Publication Date
WO2009021121A2 WO2009021121A2 (en) 2009-02-12
WO2009021121A3 true WO2009021121A3 (en) 2009-09-03
WO2009021121A4 WO2009021121A4 (en) 2009-10-29

Family

ID=40235922

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2008/072492 WO2009021121A2 (en) 2007-08-08 2008-08-07 Identification and characterization of hcv replicon variants with reduced susceptibility to a combination of polymerase and protease inhibitors, and methods related thereto

Country Status (1)

Country Link
WO (1) WO2009021121A2 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2337583A1 (en) 2008-09-17 2011-06-29 Boehringer Ingelheim International GmbH Combination of hcv ns3 protease inhibitor with interferon and ribavirin
MX2012004971A (en) 2009-10-30 2012-06-12 Boehringer Ingelheim Int Dosage regimens for hcv combination therapy comprising bi201335, interferon alpha and ribavirin.
MX2013003060A (en) * 2010-09-30 2013-05-30 Boehringer Ingelheim Int Combination therapy for treating hcv infection.

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007092645A2 (en) * 2006-02-09 2007-08-16 Schering Corporation Novel hcv inhibitor combinations and methods
US20070274951A1 (en) * 2006-02-09 2007-11-29 Xiao Tong Combinations comprising HCV protease inhibitor(s) and HCV polymerase inhibitor(s), and methods of treatment related thereto

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007092645A2 (en) * 2006-02-09 2007-08-16 Schering Corporation Novel hcv inhibitor combinations and methods
US20070274951A1 (en) * 2006-02-09 2007-11-29 Xiao Tong Combinations comprising HCV protease inhibitor(s) and HCV polymerase inhibitor(s), and methods of treatment related thereto

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
HOWE ET AL: "[432] FAVORABLE CROSS-RESISTANCE PROFILE OF TWO NOVEL HEPATITIS C VIRUS INHIBITORS, SCH-503034 AND HCV-796, AND ENHANCED ANTI-REPLICON ACTIVITY MEDIATED BY THE COMBINED USE OF BOTH COMPOUNDS", JOURNAL OF HEPATOLOGY, MUNKSGAARD INTERNATIONAL PUBLISHERS, COPENHAGEN, DK, vol. 46, 1 April 2007 (2007-04-01), pages S165, XP022087772, ISSN: 0168-8278 *
HUANG ET AL: "Recent development of therapeutics for chronic HCV infection", ANTIVIRAL RESEARCH, ELSEVIER SCIENCE BV., AMSTERDAM, NL, vol. 71, no. 2-3, 1 September 2006 (2006-09-01), pages 351 - 362, XP005605099, ISSN: 0166-3542 *
NEYTS ET AL: "Selective inhibitors of hepatitis C virus replication", ANTIVIRAL RESEARCH, ELSEVIER SCIENCE BV., AMSTERDAM, NL, vol. 71, no. 2-3, 1 September 2006 (2006-09-01), pages 363 - 371, XP005605100, ISSN: 0166-3542 *
RALSTON ROBERT ET AL: "Favorable cross-resistance profile of HCV-796 and sch-503034 and enhanced anti-replicon activity mediated by combination treatment", GASTROENTEROLOGY, vol. 132, no. 4, Suppl. 2, April 2007 (2007-04-01), DIGESTIVE DISEASE WEEK MEETING/108TH ANNUAL MEETING OF THE AMERICAN-GASTROENTEROLOGICAL-ASSOCIATION; WASHINGTON, DC, USA; MAY 19 24, 2007, pages A738, XP009111024, ISSN: 0016-5085 *
SEIWERT ET AL: "[439] ADDITIVE TO SYNERGISTIC ANTIVIRAL EFFECTS OF AN NS3/4A PROTEASE INHIBITOR (ITMN-191) AND AN NS5B RNA-DEPENDENT RNA POLYMERASE INHIBITOR (R1479) IN AN HCV REPLICON SYSTEM", JOURNAL OF HEPATOLOGY, MUNKSGAARD INTERNATIONAL PUBLISHERS, COPENHAGEN, DK, vol. 46, 1 April 2007 (2007-04-01), pages S167, XP022087779, ISSN: 0168-8278 *
SMITH R E T: "Hepatitis C virus therapies", NATURE REVIEWS DRUG DISCOVERY 200609 GB, vol. 5, no. 9, September 2006 (2006-09-01), pages 715 - 716, XP007906887, ISSN: 1474-1776 1474-1784 *
TONG ET AL: "Characterization of resistance mutations against HCV ketoamide protease inhibitors", ANTIVIRAL RESEARCH, ELSEVIER SCIENCE BV., AMSTERDAM, NL, vol. 77, no. 3, 28 December 2007 (2007-12-28), pages 177 - 185, XP022454773, ISSN: 0166-3542 *
TONG X ET AL: "Identification and analysis of fitness of resistance mutations against the HCV protease inhibitor SCH 503034", ANTIVIRAL RESEARCH, ELSEVIER SCIENCE BV., AMSTERDAM, NL, vol. 70, no. 2, 1 June 2006 (2006-06-01), pages 28 - 38, XP025031470, ISSN: 0166-3542, [retrieved on 20060601] *

Also Published As

Publication number Publication date
WO2009021121A2 (en) 2009-02-12
WO2009021121A4 (en) 2009-10-29

Similar Documents

Publication Publication Date Title
WO2008024763A3 (en) Identification and characterization of hcv replicon variants with reduced susceptibility to hcv-796, and methods related thereto
Sim et al. Genomic approaches for understanding dengue: insights from the virus, vector, and host
Beaucourt et al. Ribavirin: a drug active against many viruses with multiple effects on virus replication and propagation. Molecular basis of ribavirin resistance
EA200900969A1 (en) MACROCYCLIC INHIBITORS OF HEPATITIS C PROTEASE
DK1747023T3 (en) Methods and compositions for reducing HCV virus genomes in a target cell
WO2003105770A3 (en) Carbocyclic nucleoside analogs as rna-antivirals
WO2005123087A3 (en) C-purine nucleoside analogs as inhibitors of rna-dependent rna viral polymerase
WO2011123645A3 (en) Nucleoside phosphoramidates
EA200700243A1 (en) METHODS OF TREATMENT OF HEPATITIS C
WO2004007512A3 (en) Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase
WO2004000858A3 (en) Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase
WO2004003138A3 (en) Nucleoside derivatives as inhibitors of rna-dependent rna viral polymerase
WO2006012078A3 (en) Nucleoside aryl phosphoramidates for the treatment of rna-dependent rna viral infection
WO2011156543A3 (en) Inhibitors of hcv ns5a protein
NZ703416A (en) Macrocyclic proline derived hcv serine protease inhibitors
WO2006130626A3 (en) Method for modulating activity of hcv protease through use of a novel hcv protease inhibitor to reduce duration of treatment period
IL192919A0 (en) Inhibitors of hepatitis c virus rna-dependent rna polymerase, and compositions and treatments using the same
MX2009008872A (en) Macrocyclic compounds as hcv ns3 protease inhibitors.
TW201129370A (en) Hepatitis C inhibitor compounds
WO2007089618A3 (en) Hepatitis c serine protease inhibitors and uses therefor
WO2010055164A3 (en) Isoquinolone derivatives as inhibitors of plavivirus replication
WO2007092645A3 (en) Novel hcv inhibitor combinations and methods
ATE507293T1 (en) CONSERVED HBV AND HCV SEQUENCES SUITABLE FOR GENE SILENCING
EP2504344A4 (en) Hepatitis c inhibitor compounds
CL2013000670A1 (en) Method for treating a hepatitis c virus (hcv) infection comprising administering a hsv serine protease ns3 inhibitor, an hnv ns5b arn-dependent arn polymerase inhibitor and optionally ribavirin; pharmaceutical composition; case; and its use for the treatment of a hcv infection.

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 08826931

Country of ref document: EP

Kind code of ref document: A2

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 08826931

Country of ref document: EP

Kind code of ref document: A2