Merrell Pharmaceuticals, Inc.

The Dow Chemical Company

Merrell Dow Pharmaceuticals

Intimax Corporation

Other

Celsus Biopharmaceuticals, Inc.

Alan D Cardin

Michael J Mullins

Richard L Jackson

William A Fordyce

Michael J Fazio

Thomas A Chamberlin

Norton P Peet

A Stanley Tyms

Cornelius L Van Gorp

William Jack Kruper, Jr

Ray E Drumright

Sai P Sunkara

William J Kruper

Nelsen L Lentz

Steven J Busch

Masayuki Mano

Dermatan sulfates and/or O-desulfated heparins useful in treating and preventing heparinoid-induced autoimmune responses, in particular heparin-induced thrombocytopenia (HIT) and its associated disease states. The dermatan sulfates comprise repeating disulfated and/or trisulfated disaccharide units of L-iduronic acid and N-acetyl-D-galactosamine. The O-desulfated heparins comprise heparin molecules selectively O-desulfated at the 2-O and/or 3-O positions of the uronic acid and glucosamine saccharide residues. Particularly effective dermatan sulfate HIT antagonists have a mean molecular weight of from about 2000 to about 10,000 Daltons.

Use of dermatan sulfates and/or desulfated heparins to treat or prevent heparinoid-induced autoimmune responses

Combined use of a heparin cofactor II agonist and a platelet GPIIb/IIIa receptor antagonist to inhibit both platelet aggregation and thrombin generation resulting from disease, injury or responses to wound repairs. The combined use of the heparin cofactor II agonist and the platelet GPIIb/IIIa receptor antagonist can achieve these therapeutic benefits while at the same time minimizing or reducing the risk of hemorrhagic side effects (e.g., prolonged bleeding), and without causing undesired antigenic responses. Moreover, certain subtherapeutic amounts of the heparin cofactor II agonist with certain subtherapeutic amounts of a platelet GPIIb/IIIa receptor antagonist can, in combination, be therapeutically effective in inhibiting both platelet aggregation and thrombin generation.

Combinations of heparin cofactor II agonist and platelet IIb/IIIa antagonist, and uses thereof

A selectively targeted agent comprising a dermatan sulfate having more than about 25% repeating L-iduronic acid&rarr;4,6-di-O-sulfated N-acetyl-D-galactosamine disaccharide units that is covalently attached or bonded to a radioactive metal-ion binding moiety. The targeted agent is useful in preparing radiagnostic and/or radiopharmaceutical agents for diagnostic and/or therapeutic treatment when combined with an appropriate radioactive metal ion such as Tc, Re or Re.

Targeted agents useful for diagnostic and therapeutic applications

The oligomers of the present invention are polyureas, polycarbonates, polyesters or polyamides having a number average molecular weight of <10,000. These oligomers are water-soluble, have a rigid backbone with a predictable anion spacing, and are, pharmaceutically-acceptable. The oligomers are useful for the treatment and/or diagnosis of HSV and HCMV.

Anti-herpes virus and cytomegalovirus polyurea oligomers

The oligomers of the present invention are polythioureas having 3 to 50 recurring units derived from aromatic diamines substituted with anionic groups, and having a number average molecular weight of less than 10,000. These oligomers are water-soluble, preferably have a rigid backbone, and are pharmaceutically-acceptable. The oligomers are useful for the treatment and/or diagnosis of AIDS.

Pharmaceutical formulations comprising polythiourea and methods of use

The narrow poly- or mono-dispersed oligomers of the present invention are polyureas, polycarbonates, polyesters or polyamides having a recurring unit of from 3 to 50. These oligomers are water-soluble, preferably have a rigid backbone, have recurring units coupled by carbonyl linking moieties which have anionic groups, display predominantly linear geometry such that regular spacing between anionic groups exists in an aqueous medium, and are pharmaceutically-acceptable. The narrow poly- or mono-dispersed oligomers are useful for the treatment and/or diagnosis of AIDS and/or ARC or HSV.

Narrow poly-and-mono-dispersed anionic oligomers, and their uses,

Narrow poly- and mono-dispersed anionic oligomers

Sulfonic acid stilbenes block the infection of cells by HIV and these compounds can be used to prevent viral infection.

Sulfonic stilbene compounds in the treatment of viral diseases

Various peptides having affinity for sulfated polysaccharides such as heparin, dextran sulfate and Pentosan polysulfate are bound to resins and used in affinity chromatography to prepare anti-HIV sulfated polysaccharides.

Sulfated polysaccharide fractions having anti-HIV activity

The present invention relates to achiral polyurea oligomers, their uses and formulations as anti-HIV pharmaceuticals and to a process for the preparation of narrow mono- and polydispersed oligomers as an emodiment of the invention. The achiral oligomers are derived from repeating units of the monomer 4,4'-diamino-biphenyl-3,3'-disulfonic acid and are water soluble, have a rigid backbone, possess ordered anionic spacing and have a number average molecular weight of &lt;20,000. The process relates to the synthesis of narrow poly- and mono-dipersed oligomers comprising the steps of: 1) restricting the crude olydispersed anionic oligomer mixture to a narrow polydispersed anionic oligomer mixture to a narrow polydispersed anionic oligomer mixture; and/or 2) isolating the monodispersed anionic oligomer; and 3) optionally converting the narrow poly- or mono-dispersed anionic oligomer salt from Step 1 or 2 to a desired pharmaceutically-acceptable salt, especially a solim or potassium salt. The process steps may be executed whereby step 1 or 2 is done alone, each in combination with Step 3, or all three steps are done.

Anti-HIV achiral polyurea oligomers, a process for creating them,

The oligomers of the present invention are polyamides having a number average molecular weight of &lt;10,000. These oligomers are water-soluble, have a rigid backbone with a predictable anion spacing, and are pharmaceutically-acceptable. The oligomers are useful for the treatment and/or diagnosis of HSV and HCMV.

Anti-herpes virus and cytomegalovirus polyamide oligomers

The preferred oligomers of the present invention are polyureas, polycarbonates, polyesters or polyamides having a number average molecular weight of &lt;10,000. These oligomers are water-soluble, have a rigid backbone, have recurring units coupled by carbonyl linking moieties which have anionic groups, display predominantly linear geomentry such that regular spacing between anionic groups exists in an aqueous medium, and are pharmaceutically-acceptable. The oligomers are useful for the treatment and/or diagnosis of AIDS and ARC.

Method of treating HIV infections with anti-viral formulations

Sulfonic acid stilbenes block the infection of cells by HSV and CMV and these compounds can be used to treat viral infection.

Sulfonic stilbene derivatives in the treatment of viral diseases

Anti-HIV pharmaceutical formulations

The oligomers of the present invention are polyesters having a number average molecular weight of &lt;10,000. These oligomers are water-soluble, have a rigid backbone with a predictable anion spacing, and are pharmaceutically-acceptable. The oligomers are useful for the treatment and/or diagnosis of HSV and HCMV.

Growing community of inventors

Cincinnati, OH, United States of America

Alan D Cardin