Genta Incorporated

Eleos, Inc.

Smith Holdings, LLC

Jbl Scientific, Inc.

Iris International, Inc.

Robert E Klem

Timothy Andrew Riley

Dayton T Reardan

Raymond P Warrell, Jr

Mark A Reynolds

Larry J Smith

Edward Jablonski

Jack B Jiang

Raymond P Warrell

Howard Fingert

Kollengode K Ramaswamy

William Marvin

Lloyd Robert Snyder

William B Marvin

Russ Saunders

Covalently reactive antigen analogs are disclosed herein. The antigens of the invention may be used to stimulate production of catalytic antibodies specific for predetermined antigens associated with particular medical disorders. The antigen analogs may also be used to permanently inactivate endogenously produced catalytic antibodies produced in certain autoimmune diseases as well as in certain lymphoproliferative disorders. Also provided are methods for modulating the efficacy of nucleic acid based therapeutics.

Methods for modulating the efficacy of nucleic acid based therapies

The present invention is directed to the use of bcl-2 antisense oligomers to treat and prevent bcl-2 related disorders. These disorders include cancers, tumors, carcinomas and cell-proliferative related disorders. In one embodiment of the invention, a bcl-2 antisense oligomer is administered at high doses. The present invention is also directed to a method of preventing or treating a bcl-2 related disorder, in particular cancer, comprising administering a bcl-2 antisense oligomer for short periods of time. The present invention is further drawn to the use of bcl-2 antisense oligomers to increase the sensitivity of a subject to cancer therapeutics. The present invention also relates to pharmaceutical compositions comprising one or more bcl-2 antisense oligomers, which may comprise one or more cancer therapeutic agents.

Methods of treatment of a bcl-2 disorder using bcl-2 antisense oligomers

Provided are novel tri(alkylcarboxylato) gallium (III) compounds, exemplified by tripalmitato gallium (III), methods for making them, pharmaceutical compositions containing them, and methods of using the pharmaceutical compositions.

Tri(alkylcarboxylato)gallium (III) products and pharmaceutical compositions containing them

The present invention is directed to hybrid oligomers comprising a cyclic AMP response element (CRE) sequence and a sequence that hybridizes to a bcl-2 pre-mRNA or mRNA, and pharmaceutical compositions comprising such hybrids. The present invention is also directed to the use of CRE decoy oligomers, comprising a CRE consensus sequence, and bcl-2 antisense oligomers in combination therapies, and the use of bcl-2/CRE hybrid oligomers, to treat or prevent cell-proliferative related disorders, including hyperplasias, cancers, tumors and carcinomas. In one embodiment, the invention relates to therapeutic protocols comprising the administration of a CRE decoy oligomer and a bcl-2 antisense oligomer for the treatment of cell-proliferative related disorders. In another embodiment, the invention relates to therapeutic protocols comprising the administration of a bcl-2 antisense/CRE decoy (bcl-2/CRE) hybrid oligomer for the treatment of cell-proliferative related disorders.

Methods and compositions for treating a cell-proliferative disorder using CRE decoy oligomers, BCL-2 antisense oligomers, and hybrid oligomers thereof

Methods for purifying an oligomer by normal phase column chromatography on a support selected from polyhydroxyethyl aspartamide, hydrophilic silica and silica from an oligomer impurity having a different nucleoside sequence are described. These methods are based upon the different retention times of the oligomer and the impurity on the column.

Process for the purification of oligomers

Methods of synthesizing oligomers using low water oxidizer reagents which result in high coupling efficiencies are provided. These methods are suitable for larger scale preparations of methylphosphonate oligomers.

Process for the synthesis of oligonucleotides and analogs with low water

Polymeric reagents useful in the solid phase synthesis of oligomers are provided. These polymeric reagents are suitably loaded with nucleosidyl moieties and do not undergo non-specific chain elongation.

Organic polymer reagents for solid phase synthesis of oligonucleotides

Novel benzothiazole derivatives having a fluorescence inhibiting group linked by an enzyme cleavable bond and methods for their synthesis are provided. Upon cleavage of the enzyme-cleavable bond, a strongly fluorescent reaction product is produced. These compounds may be used to detect enzymatic activity. The fluorescent reaction products are detectable at an attomolar level using a fluorometer.

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Rancho Santa Fe, CA, United States of America

Robert E Klem