Columbia University

Tokai Pharmaceuticals, Inc.

Washington University

Aronex Pharmaceuticals, Inc.

Cy Aaron Stein

David S Casebier

Jodie Pope Morrison

Seth Lederman

Robert F Rando

Patricia Rockwell

Joshua O Ojwang

Martin B Wax

Paul Cossum

LeRoy Rabbani

Luba Benimetskaya

Gregory Sullivan

Nancy Guzzo-Pernell

Described herein are compounds, methods of making such compounds, pharmaceutical compositions, and medicaments comprising such compounds, and methods of using such compounds to treat androgen receptor mediated diseases or conditions. The present invention provides therapies and therapeutic regimens for the treatment of prostate cancer.

Treatment of prostate cancer

Described herein are compounds, methods of making such compounds, pharmaceutical compositions, and medicaments comprising such compounds, and methods of using such compounds to treat androgen receptor mediated diseases or conditions. Such compounds include inhibitors of cytochrome C17-hydroxylase/C-lyase such as 3-&#x3b2;-Hydroxy-17-(1H-benzimidazol-1-yl)androsta-5,16-diene.

This invention provides an antisense oligonucleotide or analog thereof comprising 10 or more contiguous bases or base analogs from the sequence of bases of sequence A, B, C, D, E, F, G, H, I, J, K, L, or M of FIG.This invention also provides the above-described antisense oligonucleotides, wherein the nucleotide sequence comprises nucleotide sequence A, A', B, C, C&#x2032;, D, E, E, E&#x2032;, F, G, G&#x2032;, H, H&#x2032;, I, I&#x2032;, J, K, K&#x2032;, L, L&#x2032;, M, or M&#x2032; of FIGS.A andB. This invention also provides the above-described antisense oligonucleotides, wherein the oligonucleotide is encapsulated in a liposome or nanoparticle. This invention also provides the above-described antisense oligonucleotides, wherein the phosphate backbone comprises phosphorothioate bonds. In addition, this invention provides a method of treating cancer, comprising introducing into a tumor cell an effective amount of the the above-described antisense oligonucleotide, thereby reducing the levels of bcl-xL protein produced and treating cancer. This invention also provides the above-described methods, wherein the introducing comprises using porphyrin or lipofectin as a delivery agent. This invention also provides the above-described pharmaceutical compositions, wherein the oligonucleotide is encapsulated in a liposome or nanoparticle. This invention further provides the above-described pharmaceutical compositions, wherein the pharmaceutical composition comprises tetra meso-(4-methylpyridyl)porphine or tetra meso-(anilinium)porphine or a combination thereof.

Oligonucleotide inhibitors of bcl-xL

The present invention provides a peptide that can complex with an oligonucleotide, e.g. an antisense oligonucleotide, and deliver it into a cell. The present invention also provides compositions comprising a complex of such a peptide and an oligonucleotide and methods of delivering an oligonucleotide into a cell and of inhibiting protein expression using such compositions. The present invention also provides a method of making such a complex, a method of sensitizing cells to anti-cancer agents such as paclitaxel, and pharmaceutical compositions.

Peptides that deliver antisense oligonucleotides which downregulate protein expression in cells

The present invention provides antisense phosphorothioate oligonucleotides that specifically inhibit the translation of heparanase. The invention also provides various methods of reducing angiogenesis and metastasis of tumors in a subject using said antisense phosphorothioate oligonucleotides. Finally the invention provides pharmaceutical compositions comprising the said antisense phosphorothioate oligonucleotides as active ingredients.

Phosphorothioate antisense heparanase oligonucleotides

The present invention provides methods of stimulating or inhibiting intracellular phosphorylation of tyrosine by a heparin-binding receptor which comprises contacting a cell having on its surface the heparin-binding receptor with a phosphorothioate oligonucleotide moiety of suitable length and base composition, such phosphorothioate oligonucleotide moiety being present in an effective amount. The invention further provides a method of inhibiting the formation of blood vessels in a subject which comprises administering to the subject an amount of a phosphorothioate oligonucleotide moiety of suitable length and base composition. The invention also provides a method of inhibiting proliferation of cells having a malignant phenotype in a subject which comprises administering to the subject an amount of a phosphorothioate oligonucleotide moiety of suitable length and base composition.

Methods of affecting intracellular phosphorylation of tyrosine using

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.

S-DC28 as an antirestenosis agent after balloon injury

The present invention provides phosphorothioate oligonucleotide moieties comprising a phosphorothioate oligonucleotide comprising the sequence G.sub.m X.sub.n G.sub.p, wherein G is guanosine; X is thymidine, adenosine or cytidine, or a combination thereof; each of m, n and p is independently an integer greater than 2; the phosphorothioate oligonucleotide moiety being capable of binding to a V3 loop of HIV envelope glycoprotein. The invention further provides for a method of inhibiting HIV activity. The invention also provides for a method of inhibiting HIV activity in a subject. The invention further provides for a method of treating an HIV related disorder in a subject. Finally, the invention provides a pharmaceutical composition comprising a phosphorothioate oligonucleotide moiety and a pharmaceutically acceptable carrier.

Phosphorothioate oligonucleotides that bind to the V3-loop and uses

The present invention provides a method of treating glaucoma which comprises administering to a subject an effective amount of an oligonucleotide which may be substituted or modified in its phosphate, sugar, or base, so as to decrease intraocular pressure and thereby treat the glaucoma.

Growing community of inventors

New City, NY, United States of America

Cy Aaron Stein