Prosthesis (i.e. – artificial body members) – parts thereof – or ai – Arterial prosthesis – Having plural layers
Reexamination Certificate
2000-06-05
2003-08-12
McDermott, Corrine (Department: 3738)
Prosthesis (i.e., artificial body members), parts thereof, or ai
Arterial prosthesis
Having plural layers
C623S001420
Reexamination Certificate
active
06605115
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to methods and compositions for inhibiting cardiovascular cell proliferation. The invention provides methods for improving the longevity and quality of arterial grafts, for enhancing vascular NO production, and for reducing post-graft intimal hyperplasia, stenosis, and restenosis.
References
Best, P. J. et al.,
Arterioscler. Thromb. Vasc. Biol
. 19:14-22 (1999).
Boger, R. H. et al., “Asymmetric Dimethylarginine (ADMA): A Novel Risk Factor for Endothelial Dysfunction. Its Role in Hypercholestrolemia”,
Circulation
98:1842-1847 (1998).
Cooke, J. P. and Dzau, V. J., “Nitric Oxide Synthase: Role in the Genesis of Vascular Disease”,
Ann. Rev. Med
. 48:489-509 (1997).
Cooke, J. P. et al.,
Ann. Rev. Med
. 48:489-509 (1997).
D'Aniello, A. et al., “Further Study on the Specificity of D-Amino Acid Oxidase and D-Aspartase Oxidase and Time Course for Complete Oxidation of D-Amino Acid”,
Comp. Biochem. Physiol.[B]
105: 731-734 (1993).
Dattilo, J. B. et al., “Inducible Nitric Oxide Synthase Expression in Human Vein Grafts”,
Am. J. Surg
. 174:177-180 (1997).
Demeyer, G. R. Y. and Bult, H., “Mechanisms of Neointima Formation—Lessons from Experimental Models”,
Vasc. Med
. 2:179-189 (1997).
Deves, R. and Boyd, C. A., “Transporters for Cationic Amino Acids in Animal Cells: Discovery, Structure, and Function”,
Physiol. Rev
. 78:485-545 (1998).
Edelman, E. R. et al.,
Circ. Res
. 76(2):176-182 (1995).
Garg, U. C. and Hassid, A., “Nitric Oxide-Generating Vasodilators and 8-Bromocyclic Guanosine Monophosphate Inhibit Mitogenesis and Proliferation of Cultured Rat Vascular Smooth Muscle Cells”,
J. Clin. Invest
. 83(5):1774-7 (May 1989).
Guoyao, W. U. and Morris, S. M. “Arginine Metabolism: Nitric Oxide and Beyond”,
Biochem. J
. 366:1-17 (1998).
Hansson, G. K. et al., “Arterial Smooth Muscle Cells Express Nitric Oxide Synthase in Response to Endothelial Injury”,
J. Exp. Med
. 180:733-738 (1994).
Harrison, D. G., “Cellular and Molecular Mechanisms of Endothelial Cell Dysfunction”
J. Clin. Invest
. 100:2153-2157 (1997).
Hill, C. M. et al., “Exploration of Requirements for Peptide Binding to HLA DRB1.0101 and DRB1.0401
”, J. Immunol
. 152:2890-2895 (1994).
Himmelfarb, J.,
Curr. Opin. Nephrol. Hypertens
. 8(5):569-72 (September 1999).
Isselhard, W. et al.,
Thoracic and Cardiovascular Surg
. 28 (5):329-36 (1980).
Kraiss, L. W. et al., “Response of the Arterial Wall to Injury and Intimal Hyperplasia”, in
The Basic Science of Vascular Disease
, Sumpio et al., Eds., Futura Publishing, NY, N.Y., Pp.289-317 (1997).
Lloyd, J. D. and Bloch, K. D., “The Vascular Biology of Nitric Oxide and its Role in Atherogenesis”,
Ann. Rev. Med
. 47:365-375 (1996).
Morris, S. M. and Billiar, T. R., “New Insights into the Regulation of Inducible Nitric Oxide Synthesis”,
Am. J. Physiol
. 266:E829-E839 (1994).
Motwani, J. G. et al.,
Circulation
97:916-931 (1998).
Nagase, S. et al., “A Novel Nonenzymatic Pathway for Generation of Nitric Oxide by the Reaction of Hydrogen Peroxide and D- or L-Arginine”,
Biochem. Biophys. Res. Commun
. 233:150-153 (1997).
Radomski, M. W. et al. “An L-Arginine/Nitric Oxide Pathway Present in Human Platelets Regulates Aggregation”,
Proc. Natl. Acad. Sci. USA
87:5193-5197 (1990).
Tsao, P. S. et al., “Fluid Flow Inhibits Endothelial Adhesiveness. Nitric Oxide and Transcriptional Regulation of VCAM-1
”, Circulation
94:1682-1689 (1996).
Tsao, P. S. et al., “Nitric Oxide Regulates Monocyte Chemotactic Protein-1
”, Circulation
96:934-940 (1997).
Wang, Q. et al., “The in vivo Unidirectional Conversion of Nitro-D-Arginine to Nitro-L-Arginine”,
J. Pharmacol. Exp. Ther
. 288:270-273 (1999).
Wolf, A. et al., “Dietary L-Arginine Supplementation Normalized Platelet Aggregation in Hypercholesterolemic Humans”,
J. Am. Coll. Cardiol
. 29:479-485 (1997).
Woods, J. D. and Port, F. K.,
Nephrol. Dial. Transplant
. 12(4):657-9 (April 1997).
BACKGROUND OF THE INVENTION
Myointimal hyperplasia is a vascular response to injury that contributes to the development of vein graft disease, restenosis after angioplasty, and atherosclerosis (Motwani et al., 1998). Myointimal hyperplasia involves the migration and proliferation of vascular smooth muscle cells (VSMC) as well as the elaboration of extracellular matrix in the intima (DeMeyer et al., 1997; Kraiss et al., 1997). Vascular nitric oxide (NO), an endogenous regulator of vascular function, opposes the development of myointima formation by inhibiting VSMC proliferation and by inducing VSMC apoptosis (Cooke et al., 1997; Best et al., 1999). Failure of endogenous biological processes to control myointimal hyperplasia can lead to formation of vascular occlusions which seriously compromise tissue function.
Autologous vein grafting constitutes a major tool in coronary bypass procedures. About 400,000 to 500,000 first-time coronary graft procedures are performed every year in the United States alone. Although patient survival rates exceed 90% over the first five years after treatment, about 20% to 40% of the grafts fail during this time due to occlusive phenomena. Thus, 80,000-100,000 graft replacement procedures are needed in the U.S. yearly to avoid premature mortality. Vascular occlusive phenomena also lead to failures in other vascular grafts, such as arterial-venous anastomosis used for kidney dialysis, and in organ transplants.
In light of the significant costs to patients and insurers engendered by repeated graft procedures, there is a need to improve the longevity and quality of first-time vascular grafts. Ideally, such a procedure should be simple to carry out, without requiring extensive manipulation or lengthy processing. Furthermore, the procedure preferably involves materials that are relatively easy to prepare in therapeutically effective forms.
SUMMARY OF THE INVENTION
In one aspect, the invention provides a method for inhibiting trauma-induced intimal hyperplasia in a blood vessel. In accordance with the method, a polymer consisting of from 6 to about 30 amino acid subunits, wherein at least 50% of the subunits are arginine, and containing at least six contiguous arginine subunits, contained in a pharmaceutically acceptable vehicle, is contacted with the vessel, typically with the interior of the vessel. Such contacting is effective to reduce the level of intimal hyperplasia in and/or adjacent to the vessel, relative to the level of intimal hyperplasia that would occur in the absence of the contacting.
The hyperplasia-inducing trauma may comprise an incision to the vessel, excessive or prolonged pressure applied to the vessel, transplant of an organ containing the vessel, or a combination thereof. The contacting may occur prior to the trauma (as in preparation of a vessel segment for grafting), concurrent with, or following the trauma (as in an angioplasty procedure). The vessel may be a vessel conduit to be grafted into (as in a bypass procedure) or onto (as in an anastomosis) an endogenous vessel, or it can be an endogenous vessel receiving a graft. Also included are vein “patches” used in arterial repair. In preferred embodiments, the above noted procedures take place in a human subject.
The invention provides, for example, a method for repairing an arterial vessel site in a human subject. Accordingly, an isolated vessel conduit, such as a saphenous vein segment or an internal mammary artery segment, is contacted with a polymer as described above, in a pharmaceutically acceptable vehicle, and the vessel conduit is then grafted into a selected arterial vessel site in need of repair.
In one embodiment, the vessel is a vein which undergoes an arterial venous anastomosis procedure for the purpose of dialysis. In another embodiment, the vessel is subjected to angioplasty. In a further embodiment, the vessel is contained within a transplanted organ, such as, for example, a heart or kidney, where the contacting is preferably carried out by immersion of the organ in a solution of the polymer.
Preferably, at least 70%, and more preferably at least 90%, of the subunits in the polyme
Cooke John P.
Fathman Garrison C.
Kown Murray H.
Robbins Robert C.
Rothbard Jonathan B.
Barrett Thomas
Board of Trustees of the Leland Stanford Junior University
Eberle Shelley P.
Reed Dianne E.
Reed & Eberle LLP
LandOfFree
Method and composition for inhibiting cardiovascular cell... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method and composition for inhibiting cardiovascular cell..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method and composition for inhibiting cardiovascular cell... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3095604