Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1996-07-11
1998-12-29
Houtteman, Scott W.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
536 245, A61K 4800
Patent
active
058542230
ABSTRACT:
This invention provides methods of inhibiting proliferation, migration and heterotypic adhesion of vascular smooth muscle cells which comprise contacting the vascular smooth muscle cells with an amount of a phosphorothioate oligonucleotide moiety effective to inhibit the proliferation, migration or heterotypic adhesion of the vascular smooth muscle cells. This invention provides methods of inhibiting neointimal formation after balloon injury, percutaneous transluminal coronary angioplasty restenosis, and coronary artery stent restenosis in a subject which comprise administering to the subject an amount of a phosphorothioate oligonucleotide moiety effective to inhibit neointimal formation, percutaneous transluminal coronary angioplasty restenosis, or coronary artery stent restenosis in the subject. This invention further provides pharmaceutical compositions effective for treating the conditions recited above.
REFERENCES:
Jarvis et al., RNA, 2:419-428, 1996.
Bennett, M. R., et al., "Inhibition of Vascular Smooth Muscle Cell Proliferation In Vitro and In Vivo by C-MYC Antisense Oligodeoxynucleotides", J. Clin. Invest. (1994) 93(2): 820-828 (Exhibit B).
Biro, S., et al., "Inhibitory effects of antisense oligodeoxynucleotides targeting c-myc mRNA on smooth muscle cell proliferation and migration", Proc. Natl. Acad. Sci. U.S.A. (1993) 90(2): 654-658 (Exhibit C).
Brown, K. E., et al., "Expression of the c-myb Proto-oncogene in Bovine Vascular Smooth Muscle Cells", J. Biol. Chem. (1992) 267(7): 4625-4630 (Exhibit D).
Burgess, T.L., "The antiproliferation activity of c-myb and c-myc antisense oligonucleotides in smooth muscle cells is caused by a nonantisense mechanism", Proc. Natl. Acad. Sci. U.S.A. (1995) 92(9): 4051-4055 (Exhibit E).
Ebbecke, M., et al., "Antiproliferative effects of c-myc antisense oligonucleotide on human arterial smooth muscle cells", Basic Res. Cardiol. (1992) 87(6): 585-591 (Exhibit F).
Morishita, R., et al., "Pharmacokinetics of antisense oligodeoxyribonucleotides (cyclin B.sub.1 and CDC 2 kinase) in the vessel wall in vivo: enhanced therapeutic utility for restenosis by HVJ-liposome delivery", Gene (1994) 149: 13-19 (Exhibit G).
Shi, Y., et al., "Downregulation of c-myc Expression by Antisense Oligonucleotides Inhibits Proliferation of Human Smooth Muscle Cells", Circulation (1993) 88(3): 1190-1195 (Exhibit H).
Shi, Y., et al., "Transcatheter Delivery of c-myc Antisense Oligomers Reduces Neointimal Formation in a Porcine Model of Coronary Artery Balloon Injury", Circulation Research, 90(2): 944-951 (Exhibit I).
Simons, M. and Rosenberg, R.D., "Antisense Nonmuscle Myosin Heavy Chain and c-myb Oligonucleotides Suppress Smooth Muscle Cell Proliferation In Vitro", Circ. Res. (1992) 70(4): 835-843 (Exhibit J).
Simons, M., et al., "Antisense c-myb oligonucleotides inhibit intimal arterial smooth muscle cell accumulation in vivo", Nature (1992) 359: 67-70 (Exhibit K).
Stein, C.A. and Cheng, Y.C., "Antisense Oligonucleotides as Therapeutic Agents-Is the Bullet Really Magical?", Science (1993) 261: 1004-1011 (Exhibit L).
Villa, A., et al, "Effects of Antisense c-myb Oligonucleotides on Vascular Smooth Muscle Cell Proliferation and Response to Vessel Wall Injury", Circulation Research (1995) 76(4): 505-513 (Exhibit M).
Rabbani LeRoy
Stein Cy
Houtteman Scott W.
The Trustees of Columbia University in the City of New York
White John P.
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