Drug – bio-affecting and body treating compositions – Enzyme or coenzyme containing – Hydrolases
Reexamination Certificate
1998-04-01
2001-11-13
Saunders, David (Department: 1644)
Drug, bio-affecting and body treating compositions
Enzyme or coenzyme containing
Hydrolases
C435S069100, C514S008100, C424S094100
Reexamination Certificate
active
06315995
ABSTRACT:
Throughout this application, various publications are referenced following certain Examples and within the Detailed Description of the Invention section. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein.
BACKGROUND OF THE INVENTION
As described in Colman et al., Editors,
Hemostasis and Thrombosis
, Third Edition, J.B. Lippincott Company, Philadelphia, 1994, pages 33-36, 62-63 and 94-105, human Factor IX is a 415 amino acid glycoprotein (Mr≈57,000, 17% carbohydrate). Factor IX is a proenzyme that has no catalytic activity. During the coagulation cascade, it is cleaved by Factor XIa to produce catalytically active Factor IXa. A wide variety of Factor IX gene mutations are found in patients with hemophilia B. Among these are mutations in the enzyme active site, including a Ser365 to Arg mutation and mutations near His221. (Colman et al., page 63) These mutations affect the ability of the active site to proteolytically cleave its Factor X substrate. Mutations of Gly363 to Val were found to be functionally normal but unable to activate Factor X (Colman et al., page 104).
The gene for Factor IX has been identified, cDNA for Factor IX has been isolated, sequenced, and cloned into expression vectors, and recombinant Factor IX has been expressed. See, for example, Durachi et al., “Isolation and characterization of a cDNA coding for human Factor IX,” Proc. Natl. Acad. Sci. USA 79: 6461, 1982 (GenBank Accession Nos. J00136 and 182690); Choo et al., “Molecular cloning of the gene for human anti-haemophilic factor Factor IX,” Nature 299: 178, 1982; Anson et al., “the gene structure of human anti-haemophilic factor Factor IX,” EMBO J. 3:1053, 1984; Yshitake et al., “Nucleotide Sequence of the gene for human Factor IX,” Biochemistry 24:3736, 1985 (GenBank Accession No. 182,613); Anson et al., “Expression of active human clotting Factor IX from recombinant DNA clones in mammalian cells,” Nature 315:683,1985; Busby et al., “Expression of active human Factor IX in transfected cells,” Nature 316:271, 1985; de la Salle et al., “Active gamma carboxylated human Factor IX expressed using recombinant DNA techniques,” Nature 316: 268, 1985; and Kaufman et al., “Expression, purification, and characterization of recombinant gamma-carboxylated factor IX synthesized in Chinese hamster ovary cells,” J. Biol. Chem. 261:9622, 1986. See also Brownlee et al., UK Patent Application GB 2 125 409 A, published Mar. 7, 1984; Anson et al., U.S. Pat. No. 5,171,569, issued Dec. 15, 1992; Muelien U.S. Pat. No. 5,521,070, issued May 284 1996; Kaufman et al., U.S. Pat. No. 4,770,999, issued Sep. 13, 1988; and Barr et al., U.S. Pat. No. 5,460,950, issued Oct. 24, 1995.
In addition, Benedict et al. (1994) Texas Heart Institute Journal Vol 21, No. 1, pp 85-90 disclose that infusion of Factor IXai at concentrations sufficient to inhibit intravenous coagulation did not produce bleeding significantly different from that in control animals. Therefore, the invention disclosed herein was unexpected in view of this report.
SUMMARY OF THE INVENTION
The present invention provides a method for treating an ischemic disorder in a subject which comprises administering to the subject a pharmaceutically acceptable form of a Factor IXa compound in a sufficient amount over a sufficient period of time to inhibit coagulation so as to treat the ischemic disorder in the subject. The present invention provides a method for treating an ischemic disorder in a subject which comprises administering to the subject a pharmaceutically acceptable form of inactivated Factor IXa in a sufficient amount over a sufficient period of time to inhibit coagulation so as to treat the ischemic disorder in the subject.
REFERENCES:
patent: 4711848 (1987-12-01), Insley
patent: 2141642 (1995-03-01), None
Brandstetter et al., PNAS 92:9796-800, 1995.*
Benedict, C.R., et al. (1994) “Endothelial-Dependent Procoagulant and Anticoagulant Mechanisms,”Texas Heart Journal,21: 86-90.
Connolly E. S. Jr. et al. (1996) Cerebral Protection in Homozygous Null ICAM-1 Mice After Middle Cerebral Artery Occlusion,J. Clin. Invest.,97: 209-216.
Pinsky, D. J. et al. (1996) Hypoxia-induced Exocytosis of Endothelial Cell Weibel-Palade Bodies, a mechanism for rapid neutrophil recruitment after cardiac preservation,J. Clin. Invest.,97: 493-500.
Connolly, E. S. Jr. et al. (1996) “Procedural and Strain-related Variables Significantly Affect Outcome in a Murine Model of Focal Cerebral Ischemia.”Neurosurgery,38: 523-532.
Benedict, C. R. et al. (1991) “Active Site-Blocked Factor IXa Prevents Intravascular Thrombus Formation in the Coronary Vasculature Without Inhibiting Extravascular Coagulation in a Canine Thrombosis Model,”J. Clin. Invest.,88: 1760-1765.
Kim, J. S. et al. (1995) “Adhesive Glycoproteins CD11a and CD18 are Upregulated in the Leukocytes from Patients with Ischemic Stroke and Transient Ischemic Attacks,”Journal of the Neurological Sciences,128: 45-50.
Mayevsky, A. et al. (1995) “Multiparametic Monitoring of the Awake Brain Exposed to Carbon Monoxide.”J. Appl. Physiol,,78: 1188-1196.
Bronner, L. L. et al. (1995) “Preliminary Prevention of Stroke.”The New England J. Med.,333: 1392-1400.
Fassbender, K. et al. (1995) “Circulating Selectin-and Immunoglobulin-Type Adhesion Molecules in Acute Ischemic Stroke.”Stroke,26: 1361-1364.
Seekamp, A. et al. (1994) “Role of Selectins in Local and Remote Tissue Injury Following Ischemia and Reperfusion,”Am. J. Pathol.,44: 592-598.
Jerome, S. N. et al. (1994) “P-selectin and ICAM-1-Dependent Adherence Reactions: Role in the Genesis of Postichemic No-Reflow.”Am. J. Physiol.,226: H1316-H1321.
Schroeter, M. et al. (1994) “Local Immune Responses in the Rat Cerebral Cortex after Middle Cerebral Artery Occlusion.”J. Neuroimmunol.,55: 195-203.
Okada, Y. et al. (1994) “P-selectin and Intercellular Adhesion Molecule-1 Expression After Focal Brain Ischemia and Reperfusion.”Stroke,25: 202-211.
Dawson, T. M. & Snyder, S. H. (1994) “Gases as Biological Messengers: Nitric Oxide and Carbon Monoxide in the Brain.”J. Neuroscience,14(9): 5147-5159.
Carlos, T. M. & Harlan, J. M. (1994) “Leukocyte-Endothelial Adhesion Molecules.”Blood,24: 2068-2102.
Verma, A. et al. (1993) “Carbon Monoxide: A Putative Neural Messenger.”Science,259: 381-384.
Weyrich, A. S. et al. (1993) “In Vivo Neutralization of P-Selectin Protects Feline Heart Endothelium in Myocardial Ischemia and Reperfusion Injury.”J. Clin. Invest.,91: 2620-2629.
Brown, S. D. & Piantadosi, C. A. et al. (1992) “Recovery of Energy Metabolism in Rat After Carbon Monoxide Hyposia.”J. Clin. Invest.,89: 666-672.
Kochaneck, P. M. & Hallenbeck, J. M. (1992) “Polymorphonuclear Leukocytes and Monocytes/Macrophages in the Pathogenesis of Cerebral Ischemia and Stroke.”Stroke,23: 1367-1379.
Ishimaru, H. et al. (1991) “Effects of Successive Carbon Monoxide Exposures on Delayed Neuronal Death in Mice Under the Maintenance of Normal Body Temperature.”Biochem. Biophys. Res. Comm.,179(2): 836-840.
Pinsky David J.
Rose Eric
Schmidt Ann Marie
Solomon Robert A.
Stern David
Cooper & Dunham LLP
DeCloux Amy
Saunders David
The Trustees of Columbia University in the City of New York
White John P.
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