Genta Incorporated

Watson Pharmaceuticals, Inc.

Ramesh Prakash

Duane E Ruffner

Zhidong Chen

Christopher M Clemens

Richard Koehn

Inhibitory oligonucleotides are disclosed which are targeted to three specific target regions and subsequences of the target regions found on nucleic acids encoding Bcl-2. These inhibitory oligonucleotides are generally of from about 8 to about 50 nucleotides in length. Specific preferred oligonucleotides are disclosed. The oligonucleotides of the invention may be incorporated into compositions such as pharmaceutical compositions, and may be used in methods for inhibiting the expression of Bcl-2 in a cell or tissue, methods for treating conditions susceptible to modulation of Bcl-2 expression in an organism, and methods for detecting nucleic acid encoding BCL-2.

Inhibitory oligonucleotides targeted to Bcl-2

A composition for intracellular delivery of a chemical agent into an interleukin-2-receptor-bearing cell, e.g. an activated T cell, includes a chemical agent and at least one copy of an interleukin-2-receptor-binding and endocytosis-inducing ligand coupled to a water soluble polymer. The ligand binds to a receptor on the interleukin-2-receptor-bearing cell and elicits endocytosis of the composition. The composition also preferably includes a spacer for coupling the chemical agent and the ligand to the polymer. Chemical agents can include cytotoxins, transforming nucleic acids, gene regulators, labels, antigens, drugs, and the like. A preferred water soluble polymer is a polyalkylene oxide, such as polyethlene glycol and polyethylene oxide, and activated derivatives thereof. The composition can further comprise a carrier such as another water soluble polymer, liposome, or particulate. Methods of using these compositions for delivering a chemical agent in vivo or in vitro are also disclosed. A method of detecting a disease, such as T-cell lymphocytic leukemia, T-cell acute lymphoblastic leukemia, peripheral T-cell lymphoma, Hodgkin's disease, or non-Hodgkin's lymphoma, associated with elevated levels of soluble IL-2 receptor is also disclosed.

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Salt Lake City, UT, United States of America

Ramesh Prakash