Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Reexamination Certificate
2006-12-12
2006-12-12
Vogel, Nancy (Department: 1636)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
C435S254110, C435S254210
Reexamination Certificate
active
07148006
ABSTRACT:
The present invention relates to novel methods for identifying antiviral agents which selectively interfere with viral proteins that override the interferon(IFN)-induced cellular defense mechanisms against viral infection. In particular, the present invention relates to screening assays that identify agents which selectively inhibit the interaction between viral proteins containing an interferon sensitivity determining region (ISDR) and IFN-induced PKR protein kinase. The present invention more particularly relates to screening assays that identify agents which selectively inhibit the interaction between hepatitis C virus (HCV) nonstructural 5A protein (NS5A), which contains an ISDR, and IFN-induced PKR protein kinase. The interaction between the viral ISDR and IFN-induced PKR protein kinase results in the override of IFN-induced cellular defense mechanisms to combat viral infection. Therefore the agents identified using the assays of the invention may have utility as antiviral agents.
REFERENCES:
patent: 5679342 (1997-10-01), Houghton et al.
patent: 6030785 (2000-02-01), Katze et al.
patent: 6326151 (2001-12-01), Katze et al.
patent: WO 94/23041 (1994-10-01), None
Branch, A.D. “A good antisense molecule is hard to find,” TIBS, 23:45-50 (1998).
Gura, T. “Systems for identifying new drugs are often faulty,” Science, 278:1041-1042 (1997).
Alter, 1995, “Epidemiology of hepatitis C in the West,” Semin. Liver dis. 15(1): 5-14.
Baber et al., 1994, “The 58-kilodalton inhibitor of the interferon-induced double-stranded RNA-activated protein kinase is a tetratricopeptide repeat protein with oncogenic properties,” Proc. Natl. Acad. Sci. USA 91(10): 4278-82.
Beattie et al., 1991, “Vaccina virus-encoded e1F-2α homolog abrogates the antiviral effect of interferon,” Virology 183:419-422.
Beattie et al., 1995, “Distinct pattern of IFN sensitivity observed in cells infected with Vaccina K3L and E3L mutant viruses,” Virology 210:254-263.
Bukh et al., 1995, “Genetic heterogeneity of hepatitis C virus: quasispecies and genotypes,” Semin. Liver Dis. 15(1): 41-63.
Carroll et al., 1993, “Recombinant vaccina virus K3L gene product prevents activation of double-stranded RNA-dependent, initiation factor 2α-specific protein kinase,” J. Biol. Chem. 26: 12837-12842.
Craig et al., 1996, “The kinase insert domain of interferon-induced protein kinase PKR is required for activity but not for interaction with the pseudosubstrate K3L,” J. Biol. Chem. 271(40): 24526-33.
Cuthbert, 1994, “Hepatitis C: progress and problems,” Clin. Microbiol. Rev. 7(4): 505-32.
Davidson et al., 1995, “Survey of major genotypes and subtypes of hepatitis C virus using RFLP of sequences amplified from the 5′non-coding region,” J. Gen. Virol. 76(Pt. 5):1197-204.
Dever et al., 1993, “Mammalian eukaryotic initiation factor 2α kinases functionally substitute for GCN2 protein kinase in the GCN4 translational control mechanism of yeast,” Proc. Natl. Acad. Sci. USA 90:4616-4620.
Di Bisceglie, 1995, “Hepatitis C and hepatocellular carcinoma,” Semin. Liver Dis. 15(1):64-9.
Enomoto et al., 1995, “Comparison of full-length sequences of interferon-sensitive and resistant hepatitis C virus 1b. sensitivity to interferon is conferred by amino acid substitution in the NS5A region,” J. Clin. Invest. 96(1): 224-30.
Enomoto et al., 1996, “Mutation in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis C virus 1b infection,” N. Engl. J. Med. 334(2):77-81.
Fields and Song, 1989, A novel genetic system to detect protein-protein interactions. Nature, 340(6230): 245-6.
Fried et al., 1995, “Therapy of hepatitis C,” Semin. Liver Dis. 15(1): 82-91.
Gale Jr. et al., 1996, “Interaction of the interferon-induced PKR proteins kinase with inhibitory proteins P58IPKand Vaccina virus K3L is mediated by unique domains: implications for kinase regulation,” Mol. Cell. Biol. 16:4172-4181.
Gale et al., 1997, “Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein,” Virology 230(2): 217-27.
Germandis et al., 1997, “Is there an interferon sensitivity determining region (ISDR) in the NS5A gene of hepatitis C virus,” J. Hepatol. 26:93 (abstract P/C01/66).
Hoofnagle, 1994, “Therapy of acute and chronic viral hepatitis,” Adv. intern. Med. 39:241-75.
Hu et al., 1990, “Sequence requirements for coiled-coils: analysis with lambda repressor-GCN4 leucine zipper fusions,” Science 250 (4986): 1400-3.
Hu, 1995, “Repressor fusions as a tool to study protein-protein interactions,” Structure 3(5): 431-3.
Kato et al., 1990, “Molecular cloning of the human hepatitis C virus genome from Japanese patients with non-A, non-B hepatitis,” Proc. Natl. Acad. Sci. USA 87(24): 9524-8.
Katze et al., 1987, “Adenovirus VAI RNA complexes with the 68,000 Mr protein kinase to regulate its autophosphorylation and activity,” EMBO J. 6:689-697.
Katze et al., 1991, “Functional expression and RNA binding analysis of the interferon-induced, double-stranded RNA-activated, 68,000-Mr protein kinase in a cell-free system,” Mol. Cell. Biol. 11(11):5497-505.
Kumar et al., 1988, “Studies on the role of the 2′-5′-oligoadenylate synthetase-Rnase L pathway in beta interferon-mediated inhibition of encephalomyocarditis virus replication,” J. Virol. 62:3175-3181.
Lee et al., 1994, “The 58,000-dalton cellular inhibitor of the interferon-induced double-stranded RNA-activated protein kinase (PKR) is a member of the tetratricopeptide repeat family of protein,” Mol. Cell. Biol. 14:2331-2342.
Lee et al., 1990, “Purification and partial characterization of a of a cellular inhibitor of the interferon-induced protein kinase of Mr 68,000 from influenza virus-infected cells,” Proc. Natl. Acad. Sci. USA 87:6208-6212.
Mansell and Locarnini, 1995, “Epidermiology of hepatitis C in the East”, Semin. Liver Dis. 15(1):15-32.
McMillan et al., 1995, “HIV-1 Tat directly interacts with the interferon-induced, double-stranded RNA-dependent kinase, PKR,” Virology 213: 413-424.
Meurs et al., 1990, “Molecular cloning and characterization of the human double -stranded RNA-activated protein kinase induced by interferon,” Cell 62:379-390.
Okamoto et al., 1992, “Typing hepatitis C virus by polymerase chain reaction with type-specific primers: application to clinical surveys and tracing infectious sources,” J. Gen. Virol. 73 (Pt. 3): 673-9.
Romano et al., 1995, “Structured requirements for double-stranded RNA binding, dimerization, and activation of the human e1F-2α kinase DAI in Saccharomyces cerevisiae,” Mol. Cell. Biol. 15:365-378.
Sen and Ransohoff, 1993, “Interferon-induced antiviral actions and their regulation,” Adv. Virus Res. 42:57-107.
Sen et al., 1992, “The interferon system,” J. Biol. Chem. 267:5017-5020.
Tang et al., 1996, “The 58-kDa cellular inhibitor of the double stranded RNA-dependent protein kinase requires the tetratricopeptide repeat 6 and DnaJ motifs to stimulate protein synthesis in vivo,” J. Biol. Chem. 271(45):28660-6.
Tomita et al., 1981, “Suppressive effects of interferon on cell fusion by Sendai virus,” J. Gen. Virol. 55:289-295.
Whitaker-Dowling et al., 1983, :Interferon-mediated inhibition of virus penetration, Proc. Natl. Acad. Sci. USA 80:1083-1086.
Wymann et al., 1996, “Wortmannin inactivates phosphoinositide 3-kinase by covalent modification of Lys-802, a residue involved in the phosphate reaction,” Mol. Cell. Biol. 16:1722-10733.
Asabe, Shin-Ichi, et al.; “The N-Terminal Region of Hepatitis C Virus-Encoded NS5A Is
Gale Michael J.
Katze Michael G.
Townsend and Townsend / and Crew LLP
University of Washington
Vogel Nancy
LandOfFree
Screening methods to identify agents that selectively... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Screening methods to identify agents that selectively..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Screening methods to identify agents that selectively... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3675825