Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1994-05-02
1997-11-11
Schain, Howard E.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
604 53, 604269, 604265, 604266, A61M 3100, C07K 1400
Patent
active
056864094
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The present invention relates to use of a viral protein, SERP-1, its analogs and biologically active fragments in the prevention of vascular intimal hyperplasia and restenosis following arterial recannalization intervention procedures. The present invention also contemplates the use of SERP-1 in the prevention of primary atheromatous plaque formation.
Cellular proliferation and connective tissue deposition associated with atherosclerotic plaque growth produce arterial occlusion, heart attack, stroke, and peripheral occlusion. Recurrence of atherosclerotic lesions (restenosis) occurs after all known interventional procedures designed to open occluded arteries (Jaser and balloon angioplasty, atherectomy, and stent implantation) and remains a significant medical problem. Restenosis is detected in 20-50% of cases within six months, irrespective of the interventional device chosen and 50% of vein grafts occlude within ten years after surgery. Detre et al., 1989 Am J Cardiol 80:421-428; Topol et al., 1993 NEJM 329:221-227; Schatz et al., 1991 JACC 17:155B-159B (abstr).; Ellis et al., 1992 DWM JACC 19:275-277. Restenosis, which usually occurs in the two week to six month post operative period is distinguished from abrupt reclosure of a blood vessel (vasospasm) which occurs immediately after surgery.
The precise trigger for recurrent atherosclerosis is still unknown, but local arterial damage induced during interventional treatment has been demonstrated to produce focal areas of inflammation. At sites of endothelial injury and subsequent restenosis, the inflammatory response becomes over-expressed resulting in intimal cellular proliferation and overly exuberant tissue growth. Dzau et al., 1993 Circulation 87:705-719; Ross, R. 1993 Nature 362:801-809; Fuster et al., 1992 NEJM 326:242-250, 310-318; Marx J., 1990 Science 248:1491-1493; Blanckenhorn et al., 1989 Circulation 79:1-7; Schwartz et al., 1992 JACC 20:1284-1293; Libby et al., 1992 J Cell Biochem 16A:2 (abstract); Westlin et al., 1991 Am J Pathol 142:117-125; Faruqi et al., 1993 Br Heart J 69:S19-S29; Hansson GK, 1993 Br Heart J 69:S38-S41; Ellis et al., DWM JACC 19:275-277; Schwartz et al., 1992 JACC 19:267-274. Inflammatory reactions associated with local intimal injury are also believed to be responsible for the initiation of de novo (primary) plaque development in many cases.
The stimulus for smooth muscle cell or monocyte proliferation, which is believed to initiate atheroma development (Schatz et al., 1991JACC 17:155B-159B(abstr); Ross,R. 1993 Nature 362: 801-809.) has been variously attributed to trauma (Helin et al., 1971 Atherosclerosis 13:319-331; Watanabe, Y. 1980 Aterosclerosis 13:319-331), hyperlipidemia (Wantanabe, Y. 1980; Goldstein et al., 1979 Nature 279:679-685), auto-immune reactions (See eg., Lopes-Virella et al., 1985 G. Clin. Immunol. Path. 37:377-386; Nitkin et al., 1985 JACC f: 243-245) and viral or autocrine induction of benign smooth muscle tumors (Minick et al., 1973 GE Am. J. Pathol 73:265-325; Benditt et al., 1973 PNAS 70: 1753-1756; Simons et al., 1992 Nature 359:67-70). Endothelial damage secondary to any of the interventional devices currently used to re-open occluded arteries (laser, balloon, atherectomy, or stent) generally initiates a local inflammatory reaction. This endothelial damage and the associated inflammatory response is believed to be the underlying source for the stimulus to cellular proliferation and restenosis. After localized intimal damage has occurred, circulating cells such as platelets, monocytes, and T cells adhere to the area of injury and become activated (Pruzanski et al., 1991 Immunol Today 12:143-146; Poston et al., 1992 Am. J. Pathol 140:665-673). Thus, the act of mechanically opening a stenosed artery produces a sequence of events involving the inflammatory and immune systems that frequently results in regrowth of plaque at the site of injury, i.e., restenosis. Similar processes are believed to effect the production of cellular proliferation in other inflammatory based d
REFERENCES:
patent: 5171217 (1992-12-01), March et al.
Liu et al., (1993) "A Novel Viral Anti-Inflammatory Protein, SERP-1, Reduces Intimal Hyperplasia in Cholesterol-Fed Rabbits after Balloon Angioplasty" Abstracts from the 66th Scientific Sessions, Georgia World Congress Center, Atlanta, GA and Supplement to Circulation 88 (4) (2):181 (Abstract No. 0420).
Lucas et al., (1994) "A Unique Viral Anti-Inflammatory Protein, SERP-1, Reduces Intimal Hyperplasia in Cholesterol Fed Rabbits After Angioplasty" Journal of Cellular Biochemistry Suppl. 18A:286 (Abstract No. E315).
Upton et al., (1986) "A Novel Member of the Serpin Superfamily is encoded on a Circular Plasmid-like DNA Species Isolated from Tabbit Cells" FEBS Letters 207 (1):115-120.
PCT Search Report: PCT/US9403895.
Abst. from 66th Scientific Sessions, Circulation, vol. 88, No. 4(2) Oct., 1993 p. I81, Abst. 0420.
Abst. from J. of Cellular Biochem., vol. 0, No. 18A, 4 Jan., 1994, New York, N.Y. p. 286, Abst. #E315.
H. Vernon Anderson (1993) "Restenosis After Coronary Angioplasty" Disease-a-Month vol. XXXIX, No. 9, pp. 613-672, Roger Bone, ed., Mosby, St. Louis, MO.
Steven R. Bailey (1993) Coronary Restenosis After Angioplasty, J. Intensive Care Medicine, 6(3):105-114.
Lovquist et al (1993) Pathophysiological Mechanisms For Restenosis Following Coronary Angioplasty: Possible Preventive Alternatives, J. Internal Medicine 233:215-226.
Franklin et al. (1993) Pharmacologic Prevention of Restenosis After Coronary Angioplasty: Review of the Randomized Clinical Trials, Coronary Artery Disease 4(3)233-242.
Linda R. Gooding (1992) Virus Proteins That Counteract Host Immune Defenses, Cell 71:5-7.
Herrman et al. (1993) Pharmacological Approaches to the Prevention of Restenosis Following Angioplasty, The Search for the Holy Grail? (Part I) Drugs 46(1):18-52.
Herrman et al. (1993) Pharmacological Approaches to the Prevention of Restenosis Following Angioplasty, The Search for the Holy Grail? (Part II) Drugs 46(2):249-262.
Lomas et al. (1993) Inhibition of Plasmin, Urokinase, Tissue Plasminogen Activator, and Cls by Myxoma Virus Serine Proteinase Inhibitor, J. Biol. Chem. 268(1)516-521.
Macen et al. (1993) SERPl, A Serine Proteinase Inhibitor Encoded by Myxoma Virus, is a Secreted Glycoprotein that Interferes with Inflammation, Virology 195:348-363.
Schwartz et al. (1990) Restenosis After Balloon Angioplasty, A Practical Proliferative Model in Porcine Coronary Arteries, Circulation 82:(6)2190-2200.
Simons et al. (1992) Antisense c-myb Oligonucleotides Inhibit Intimal Arterial Smooth Muscle Cell Accumulation In Vivo, Nature 359:67-70.
Upton et al. (1990) Myxoma Virus and Malignant Rabbit Fibroma Virus Encode a Serpin-like Protein Important for Virus Virulence, Virology 179:618-631.
Upton et al. (1992) Encoding of a Homolog of the IFN-.sub.y Receptor by Myxoma Virus, Science 258:1369-1372.
Wanibuchi et al. (1993) Is the Watanabe Heritable Hyper-lipidemic Rabbit a Suitable Experimental Model for Percutaneous Transluminal Coronary Angioplasty in Humans? JACC 21(6)1490-1496.
Lucas Alexandra
McFadden D. Grant
Research Corporation Technologies Inc.
Schain Howard E.
Touzeau P. Lynn
LandOfFree
Antirestenosis protein does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Antirestenosis protein, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Antirestenosis protein will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1229086