Bristol-Myers Squibb Compnay

Timothy M Malloy

Sailesh A Varia

Krishnaswamy Srinivas Raghavan

Andrea Panaggio

Rebanta Bandyopadhyay

Jack Z Gougoutas

John D DiMarco

Michael A Galella

Martha Davidovich

Denis Favreau

Zhenrong Guo

Imre M Vitez

Sailesh Amilal Varia

Marvin Barry Cohen

Michael Galella

A process for formulating certain epothilone analogs for parenteral administration is disclosed wherein the analog is dissolved in a mixture of at least 50% by volume tertiary-butanol in water, the mixture is lyophilized, the resulting lyophilized product is packaged in one vial with a sufficient amount of solvent comprising anhydrous ethanol and a suitable nonionic surfactant in a second vial. All steps are carried out with protection from light. In use, the contents of the second or diluent vial are added to the lyophilized product and mixed to constitute the epothilone analog and the resulting solution is diluted with a suitable diluent to produce a solution for intravenous injection containing the epothilone analog in a concentration of from about 0.1 mg/mL to about 0.9 mg/mL. A preferred surfactant is polyethoxylated castor oil and a preferred diluent is Lactated Ringer's Injection.

Parenteral formulation for epothilone analogs

The invention relates to methods of increasing the bioavailability of orally administered epothilones. Epothilones administered by the methods of the invention are sufficiently bioavailable to have a pharmacological effect. The invention further relates to pharmaceutical compositions, pharmaceutical dosage forms, and kits for use in the methods of the invention.

Pharmaceutical compositions, dosage forms and methods for oral administration of epothilones

There are provided in accordance with the present invention two crystalline polymorphs, designated Form A and Form B, respectively, as well as mixtures thereof, of an epothilone analog represented by the formula Also provided are methods of forming the novel polymorphs, therapeutic methods utilizing them and pharmaceutical dosage forms containing them.

Polymorphs of an epothilone analog

There are provided in accordance with the present invention two crystalline polymorphs, designated Form A and Form B, respectively, as well as mixtures thereof, of an epothilone analog represented by the formulaAlso provided are methods of forming the novel polymorphs, therapeutic methods utilizing them and pharmaceutical dosage forms containing them.

Methods of administering epothilone analogs for the treatment of cancer

The invention relates to methods of increasing the bioavailability of orally administered epothilones. Epothilones administered by the methods of the invention are sufficiently bioavailable to have a pharmacological effect The invention further relates to pharmaceutical compositions, pharmaceutical dosage forms, and kits for use in the methods of the invention.

A ras-farnesyltransferase inhibitor complex formed of ras-farnesyltransferase inhibitor or a pharmaceutically acceptable salt thereof, of the formula I

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Yardley, PA, United States of America

Timothy M Malloy