Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Reexamination Certificate
2011-03-22
2011-03-22
Bowman, Amy (Department: 1635)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
C514S04400A, C435S320100, C536S023100
Reexamination Certificate
active
07910722
ABSTRACT:
Small interfering RNAs (siRNAs) or small hairpin RNA (shRNAs) and compositions comprising same are provided that specifically target human cyclophilin A (CyPA) to effectively inhibit Hepatitis C (HCV) infection in a cell. Such siRNA and shRNAs may have a length of from about 19 to about 29 contiguous nucleotides corresponding to a specific region of human cyclophilin A (CyPA) cDNA of from about nucleotide 155 to about nucleotide 183 having particular potency against CyPA and HCV. Such siRNA and shRNAs may be formulated as naked compositions or as pharmaceutical compositions. DNA polynucleotides, plasmids, and viral or non-viral vectors are also provided that encode siRNA or shRNA molecules, which may be delivered directly to cells or in combination with known delivery agents, such as lipids, polymers, encapsulated lipid particles, such as liposomes. Methods for treating, managing inhibiting, preventing, etc., HCV infection using such siRNA and shRNAs and compositions comprising same are also provided.
REFERENCES:
patent: 4235871 (1980-11-01), Papahadjopoulos et al.
patent: 4501728 (1985-02-01), Geho et al.
patent: 4837028 (1989-06-01), Allen
patent: 4920016 (1990-04-01), Allen et al.
patent: 5019369 (1991-05-01), Presant et al.
patent: 2008/0113351 (2008-05-01), Naito et al.
patent: 2008/0113369 (2008-05-01), Khvorova et al.
patent: 2008/0113370 (2008-05-01), Khvorova et al.
patent: 2008/0113371 (2008-05-01), Khvorova et al.
patent: 2008/0113930 (2008-05-01), Tan et al.
patent: 2008/0113931 (2008-05-01), Constien
patent: 2008/0114281 (2008-05-01), Birchall et al.
Scherer et al., Approaches for the sequence-specific knockdown of mRNA, 2003, Nat. Biotechnol., 21(12), pp. 1457-1465.
Mahato et al., Modulation of gene expression by antisense and antigene oligodeoxynucleotides and small interfering RNA, Jan. 2005, Expert Opinion on Drug Delivery, vol. 2, No. 1, pp. 3-28.
Zhang et al., Targeted Gene Silencing by Small Interfering RNA-Based Knock-Down Technology, 2004, Current Pharmaceutical Biotechnology, vol. 5, p. 1-7.
Barik, S., “Immunophilins: for the love of proteins”, Cell. Mol. Life Sci. 63:2889-2900, (2006).
Bergsma, D.J., et al., The cyclophilin multigene family of peptidyl-prolyl isomerases. Characterization of three separate human isoforms. J. Biol. Chem. 266; 23204-23214, (1991).
Binder, M., et al., “Identification of determinants involved in initiation of hepatitis C virus RNA synthesis by using intergenotypic replicase chimeras”, J. Virol. 81:5270-5283, (2007).
Braaten, D., et al., “The hydrophobic pocket of cyclophilin is the binding site for the human immunodeficiency virus type 1 Gag polyprotein”, J. Virol, 71:2107-2113, (1997).
Braaten, D., et al., “Cyclophilin A regulates HIV-1 infectivity, as demonstrated by gene targeting in human T cells”, EMBO J. 20:1300-1309, (2001).
Cai, Z., et al., “Robust production of infectious hepatitis C virus (HCV) from stably HCV cDNA-transfected human hepatoma cells”, J. Virol. 70:13963-13973, (2005).
Evans, M.J., et al., “Phosphorylation of hepatitis C virus nonstructural protein 5A modulates its protein interactions and viral RNA replication”, Proc. Natl. Acad. Sci. USA 101:13038-13043, (2004).
Fernandes, F., et al., Sensitivity of hepatitis C virus to cyclosporine A depends on nonstructural proteins NS5A and NS5B. Hepatology 46: 1026-1033, (2007).
Gamble, T.R., et al., “Crystal structure of human cyclophilin A bound to the amino-terminal domain of HIV-1 capsid”, Cell 87:1285-1294, (1996).
Gosert, R., et al., Identification of the hepatitis C virus RNA replication complex in Huh-7 cells harboring subgenomic replicons, J. Virol. 77:5487-5492, (2003).
Hamamoto, I., et al. “Human VAP-B is involved in hepatitis C virus replication through interation with NS5A and NS5B”, J. Virol, 79:13473-13482, (2005).
Handschumacher, R.E., et al., “Cyclophilin: a specific cytosolic binding protein for cyclosporine A,” Science, 226:544-547, (1984).
Inoue, K., et al., “Evaluation of a cyclophilin inhibitor in hepatitis C virus-infected chimeric mice in vivo”, Hepatology 45:921-928, (2007).
Ishii, N., et al., “Diverse effects of cyclosporine on hepatitis C virus strain replication”, J. Virol. 80:4510-4520, (2006).
Ke., H., et al., “Crystal structure of murine cyclophilin C complexed with immunosuppressive drug cyclosporine A”, Proc. Natl. Acad. Sci., USA, 90:11850-11854, (1993).
Kozutsumi, Y., The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose-regulated proteins. Nature 332:462-464, (1988).
Lindenbach, B.D., et al., “Complete replication of hepatitis C virus in cell culture”, Science 309:623-626, (2005).
Lindenbach, B.D., et al. “Unravelling hepatitis C virus replication from genome to function”, Nature 436:933-938, (2005).
Liu, J., et al., “Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes”, Cell 66:807-815, (1991).
Luban, J., “Cyclophilin A, TRIM5, and resistance to human immunodeficiency virus type 1 infection”, J. Virol. 81:1054-1061. (2007).
Luban, J., et al., “Human immunodeficiency virus type 1 Gag protein binds to cyclophilins A and B,” Cell 73:1067-1078, (1993).
Ma, S., et al. “NIM811, a cyclophilin inhibitor, exhibits potent in vitro activity against hepatitis C virus alone or in combination with alpha interfero,” Antimicrob. Agents Chemother. 50:2976-2982, (2006).
Mikol, V., et al., X-ray structure of a cyclophilin B/cyclosporine complex: comparison with cyclophilin A and delineation of its calcineurin-binding doman, Proc. Natl. Acad Sci. USA 91:5183-5186, (1994).
Miyanari, Y., et al. “Hepatitis C virus non-structural proteins in the probable membranous compartment function in viral genome replication. J. Biol. Chem,” 278:50301-50308, (2003).
Moradpour, D., et al. “Insertion of green florescent protein into nonstructural protein 5A allows direct visualization of functional hepatitis C virus replication complexes,” J. Virol. 78:7400-7409, (2004).
Munro, S., et al., “An Hsp70-like protein in the ER: identity with the 78 kd glucose-regulated protein and immunoglobulin heavy chain binding protein,” Cell 46:291-300, (1986).
Nakagawa, M., et al., “Specific inhibition of hepatitis C virus replication by cyclosporine A,” Biochem Biophys. Res. Commun. 313:42-47, (2004).
Nakagawa, M., et al., “Suppression of hepatitis C virus replication by cyclosporine a is mediated by blockade of cyclophilins”, Gastroenterology 129:1031-1041, (2005).
Nelson, H.B., et al., “The effect of cell growth of hepatitis C virus (HCV) replication and a mechanism of cell confluence-based inhibition of HCV RNA and protein expression”, J. Virol. 80:1181-1190, (2006).
Neri, P., et al., “NMR studies of [U-13C] cyclosporine A bound to human cyclophilin B,” FEBS Lett. 290:195-199, (1991).
Okamoto, T., et al., “Hepatitis C virus RNA replication is regulated by FKBPS and Hsp90,” EMBO J. 25:5015-5025, (2006).
Paeshuyse, J., et al., “The non-immunosupressive cyclosporine DEBIO-025 is a potent inhibitor of hepatitis C virus replication in vitro”, Hepatology 43:761-770, (2006).
Paslaru, L., et al., GRP78 induction by cyclosporin A in human HeLa cells, FEBS Lett. 350:304-308, (1994).
Pfugli, G., et al., “X-ray structure of a decameric cyclophilin-cyclosporin crystal complex”, Nature 361:91-94, (1993).
Quinkert, D., et al., “Quantitative analysis of the hepatitis C virus replication complex”, J. Virol. 79:13594-13605, (2005).
Robida, J.M., et al., “Characterization of hepatitis C virus subgenomic replicon resistance to cyclosporine in vitro”, J. Virol. 81:5829-5840, (2007).
Salonen, A., et al., “Viral RNA replication in association with cellular membranes”, Curr. Top. Microbiol. Immuno
Bowman Amy
Florida State University Research Foundation
Jagtiani Ajay A.
Vedder Price P.C.
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