United Therapeutics Corporation

3m Innovative Properties Company

Gilead Sciences, Inc.

Other

Abbvie Inc.

Abbott Laboratories Corporation

Triangle Pharmaceuticals, Inc.

Yuerong Hu

Devalina Law

Kenneth R. Phares

Kenneth R Phares

Hitesh Batra

Liang Guo

Michael J Jozwiakowski

Raymond D Skwierczynski

Zheng Jane Li

Richard L Miller

Terri F Busch

Robert M Moriarty

John C Hedenstrom

Michael Scannell

Carmen Mitan

Mark Martinez

Kenneth Trofatter, Jr

Devalina  Law

Devaline Law

Provided are novel prodrugs of treprostinil, as well as methods of making and methods of using these prodrugs.

Treprostinil prodrugs

Described herein are crystalline forms of a prostacyclin (IP) receptor agonist compound, as well as pharmaceutical compositions thereof, and methods of use thereof in the treatment of diseases or conditions that would benefit from treatment with a prostacyclin (IP) receptor agonist compound.

Crystalline prostacyclin (IP) receptor agonist and uses thereof

Stable treprostinil prodrugs

There is provided individual polymorphic forms of treprostinil and pharmaceutical formulations comprising the same, methods of making and using the same.

Solid forms of treprostinil

Solid phases of (&#x2212;)-cis-FTC, which are designated herein as amorphous (&#x2212;)-FTC and Forms II and III (&#x2212;)-cis-FTC) are provided that can be distinguished from Form I (&#x2212;)-cis-FTC by X-ray powder diffraction patterns, thermal properties, and methods of manufacture. A hydrated crystalline form of (&#xb1;)-cis-FTC (i.e. racemic cis-FTC), and a dehydrated form of the hydrate, are also provided, and can similarly be distinguished from other forms of FTC by X-ray powder diffraction patterns, thermal properties, and methods of manufacture. These FTC forms can be used in the manufacture of other forms of FTC, or in pharmaceutical compositions. Particularly preferred uses of these forms are in the treatment of HIV or hepatitis B.

Polymorphic and other crystalline forms of cis-FTC

A method of synthesizing stereochemically defined iminocyclitol comprises replacing an intraring oxygen in a cyclic sugar by an intraring imine to form an iminocyclitol, wherein said iminocyclitol has a defined stereochemical configuration different from a stereochemical configuration of the cyclic sugar. The invention also provides combinatorial libraries of iminocyclitol compounds, allowing for diverse C1 and N-substitution. In addition, provided are methods of treating viral infections with iminocyclitols compounds.

Combinatorial library approach to iminocyclitols with biological activity

Moderate moisture levels, such as greater than 3% but no greater than 7%, may be beneficial for solid formulations of certain prostacyclin analogs. Accordingly, a solid formulation containing a prostacyclin analog may be packaged inside a pharmaceutical packaging with such amount of a desiccant or a drying agent that after the storage the solid formulation may have a moderate level of moisture in it.

Solid formulations of prostacyclin analogs

Solid phases of (&minus;)-cis-FTC, which are designated herein as amorphous (&minus;)-FTC and Forms II and III (&minus;)-cis-FTC) are provided that can be distinguished from Form I (&minus;)-cis-FTC by X-ray powder diffraction patterns, thermal properties, and methods of manufacture. A hydrated crystalline form of (&plusmn;)-cis-FTC (i.e. racemic cis-FTC), and a dehydrated form of the hydrate, are also provided, and can similarly be distinguished from other forms of FTC by X-ray powder diffraction patterns, thermal properties, and methods of manufacture. These FTC forms can be used in the manufacture of other forms of FTC, or in pharmaceutical compositions. Particularly preferred uses of these forms are in the treatment of HIV or hepatitis B.

Polymorphic and other crystalline forms cis-FTC

A system for treating a condition associated with a mucosal surface, the system comprising an immune response modifier (IRM) compound chosen from imidazoquinoline amines, imidazopyridine amines, 6,7-fused cycloalkylimidazopyridine amines, imidazonaphthyridine amines, oxazoloquinoline amines, thiazoloquinoline amines, 1,2-bridged imidazoquinoline amines, and pharmaceutically acceptable salts thereof and an applicator device for applying the IRM compound to the mucosal surface. This system of IRM compounds and applicator may be used to treat conditions associated with mucosal surfaces such as cervical dysphasia and cervical intraepithelial neoplasia.

Systems and methods for treating a mucosal surface

Immune response modifier (IRM) compounds&mdash;imidazoquinoline amines, imidazopyridine amines, 6,7-fused cycloalkylimidazopyridine amines, 1,2-bridged imidazoquinoline amines, thiazolo- and oxazolo-quinolinamines and pyridinamines, imidazonaphthyridine and tetrahydroimidazonaphthyridine amines&mdash;are useful for the treatment of conditions at and below the mucosal surfaces by administering a therapeutically effective amount of such compounds to the mucosal surface. Novel pharmaceutical formulations are provided. In one embodiment, the pharmaceutical formulations are advantageous for treatment of cervical conditions such as cervical dysplasias including cervical intraepithelial neoplasias.

Formulations and methods for treatment of mucosal associated conditions with an immune response modifier

Growing community of inventors

Chapel Hill, NC, United States of America

Kenneth R Phares