Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
1998-12-07
2003-04-22
Kemmerer, Elizabeth (Department: 1646)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C514S012200, C424S085100
Reexamination Certificate
active
06551990
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates generally to the field of medicine and, more specifically, to methods of inhibiting ectopic calcification.
2. Background Information
Deposition of calcium crystals in tissues other than teeth or bone, referred to as ectopic calcification, commonly occurs in association with renal failure, cardiovascular disease, diabetes and the aging process. A frequent finding in patients with renal failure, particularly those undergoing long-term hemodialysis and unable to appropriately regulate serum mineral balance, is calcification of internal organs, including the lung, heart, stomach and kidneys. Less commonly, hemodialysis patients develop painful calcified skin lesions that progress to non-healing ulcers or gangrene and may require amputation of the affected limb.
Ectopic calcification is also a common complication of the implantation of bioprosthetic heart valves and is the leading cause of replacement valve failure. Ectopic calcification also occurs in native heart valves and blood vessels in association with atherosclerosis, diabetes and cardiovascular disease. The deposition of minerals in the vasculature narrows the orifices and hardens the walls of the affected valves and blood vessels, resulting in reduced blood flow to the heart and peripheral organs. Therefore, ectopic calcification increases the risk of valve failure, stroke, ischemia and myocardial infarction.
One protein that is abundant at the sites of ectopic calcification, such as in atherosclerotic plaques and in calcified aortic valves, is osteopontin. Osteopontin has several known functions, including promoting cell adhesion, spreading and migration. Osteopontin colocalizes with sites of early calcification in coronary atherosclerotic plaques and its expression increases as atherosclerosis develops. These findings, combined with studies showing that osteopontin has calcium-binding properties in vitro, have led to the suggestion that osteopontin may be involved in ectopic calcification. Previous studies have not addressed the role of osteopontin in ectopic calcification in vivo.
Ectopic calcification, if left untreated, results in increased morbidity and death. Current therapies to normalize serum mineral levels or to inhibit calcification of vascular tissues or implants are of limited efficacy and cause unacceptable side effects.
Thus, there exists a need for an effective method of inhibiting ectopic calcification. The present invention satisfies this need and provides related advantages as well.
SUMMARY OF THE INVENTION
The invention provides a method of inhibiting ectopic calcification in an individual. The method consists of administering to the individual a therapeutically effective amount of osteopontin or a functional fragment thereof. The method can be used to inhibit ectopic calcification associated with a variety of conditions such as atherosclerosis, stenosis, restenosis, prosthetic valve replacement, angioplasty, renal failure, tissue injury, diabetes and aging.
REFERENCES:
patent: 5340934 (1994-08-01), Termine
patent: 5695761 (1997-12-01), Denhardt et al.
patent: 5824651 (1998-10-01), Nanci et al.
patent: 0 705 842 (1996-04-01), None
patent: WO 92/22316 (1992-12-01), None
Barisoni et al., “Osteopontin (OP) mRNA and Protein Expression in Glomerular Disease (GD) Correlates with Tubulo-Interstitial Damage (TID)”J. Am. Soc. NephrolAbstract A2523, 7:1751 (1996).
Bautista et al., “A monoclonal antibody against Osteopontin inhibits RGD-mediated cell adhesion to osteopontin.”Annals New York Academy Sciences, 760:309-311 (1995).
Bautista et al., “Low-Molecular-Weight Variants of Osteopontin Generated by Serine Proteinases in Urine of Patients With Kidney Stones”J. of Cellular Biochemistry61:402-409 (1996).
Bautista et al., “Quantification of Osteopontin in Human Plasma With an ELISA: Basal Levels in Pre- and Postmenopausal Women”Clincal Biochemistry29(3):231-239 (1996).
Boskey, Adele L., “Matrix Proteins and Mineralization: An Overview”,Connective Tissue Research, 35(1-4):357-363[411-417], (1996).
Boskey et al., “Osteopontin-hydroxyapatite interactions in vitro: inhibition of hydroxyapatite formation and growth in a gelatin-gel”,Bone and Mineral, 22:147-159 (1993).
Butler et al., “Osteopontin”,Principles of Bone Biology, 13:167-181 (1996).
Chen et al., “Calcium and Collagen Binding Properties of Osteopontin, Bone Sialoprotein, and Bone Acidic Glycoprotein-75 from Bone”,The Journal of Biological Chemistry, 267(34):24871-24878 (1992).
Diamond et al., “Early and Persistent Up-Regulated Expression of Renal Cortical Osteopontin in Experimental Hydronephrosis”,Am. J. of Pathology146(6):1455-1466 (1995).
Fitzpatrick, et al., “Diffuse Calcification in Human Coronary Arteries”,The Journal of Clinical Investigation, Inc., 94:1597-1604 (1994).
Giachelli et al., “Osteopontin Is Elevated during Neointima Formation in Rat Arteries and Is a Novel Component of Human Atherosclerotic Plaques”,J. Clin. Invest., 92:1686-1696 (1993).
Giachelli et al., “Molecular and Cellular Biology of Osteopontin”,TCM, 5(3):88-95 (1995).
Giachelli et al., “Osteopontin: Potential Roles in Vascular Function and Dystrophic Calcification”,J. Bone Miner Metab, 15:179-183 (1997).
Hirota et al., “Expression of Osteopontin Messenger RNA by Macrophages in Atherosclerotic Plaques”,American Journal of Pathology, 143(4):1003-1008 (1993).
Hunter et al., “Modulation of crystal formation by bone phosphoproteins: structural specificity of the osteopontin-mediated inhibition of hydroxyapatite formation”,Biochem. J., 300:723-728 (1994).
Ikeda et al., “Osteopontin mRNA Is Expressed by Smooth Muscle-derived Foam Cells in Human Atherosclerotic Lesions of the Aorta”,J. Clin. Invest., 92:2814-2820 (1993).
Khanna et al., “Captopril Prevents Increased Urinary and Renal Cortical Osteopontin in Stroke-Prone Spontaneously Hypertensive Rats”J. Am. Soc. Nephrol. Abstract A2452, 7:1737 (1996).
Kiefer et al., “The cDNA and derived amino acid sequence for human osteopontin”,Nucleic Acids Research, 17(8) (1989).
Kim et al., “Dual Mechanisms for the Low Plasma Levels of Truncated Apolipoprotein B Proteins in Familial Hypobetalipoproteinemia”,J. Clin. Invest., 101(6):1468-1477 (1998).
Kleinman et al., “Expression of osteopontin, a urinary inhibitor of stone mineral cyrstal growth, in rat kidney”Kidney International47:1585-1596 (1995).
Kleinman et al., “Upregulation of Osteopontin Expression by Ischemia in Rat Kidney”Annals New York Academy of Sciences760:321-323 (1995).
Liang and Barnes, “Renal expression of osteopontin and alkaline phosphatase correlates with BUN levels in aged rats”Am. J. Physiol. 269:F398-F404 (1995).
Liaw et al., “Neutralizing Antibodies Directed Against Osteopontin Inhibit Rat Carotid Neointimal Thickening After Endothelial Denudation”,Arteriosclerosis, Thrmbosis, and Vascular Biology, 17(1):188-193 (1997).
Liaw et al., “Osteopontin and &bgr;3Integrin Are Coordinately Expressed in Regenerating Endothelium In Vivo and Stimulate Arg-Gly-Asp-Dependent Endothelial Migration In Vitro”,Circulation Research, 77(4):665-672 (1995).
Liaw et al., “Osteopontin Promotes Vascular Cell Adhesion and Spreading and IS Chemotactic for Smooth Muscle Cells In Vitro”,Circulation Research, 74(2):214-224 (1994).
Liaw et al., “The Adhesive and Migratory Effects of Osteopontin Are Mediated via Distinct Cell Surface Integrins”,J. Clin. Invest., 95:713-724 (1995).
Liaw et al., “Altered Wound Healing in Mice Lacking a Functional Osteopontin Gene (sppl)”,J. Clin. Invest., 101(7):1468-1478 (1998).
Magil et al., “Osteopontin in chronic puromycin aminonucleoside nephrosis.”J. Amer. Society Nephrology, 8:1383-1390 (1997).
McKee and Nanci, “Osteopontin at Mineralized Tissue Interfaces in Bone, Teeth, and Osseointegrated Implants: Ultrastructural Distritubion and Implications for Mineralized Tissue Formation, Turnover, and Repair”,Microscopy Research and Technique, 33:141-164 (1996).
McKee and Nanci, “Secretion of Osteopontin by Macrophages and Its Accumulation at Tissue Surfaces During Wound Healing in Minera
Giachelli Cecilia M.
Steitz Susie
Campbell & Flores LLP
Kemmerer Elizabeth
University of Washington
LandOfFree
Methods of inhibiting ectopic calcification does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Methods of inhibiting ectopic calcification, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods of inhibiting ectopic calcification will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3018585