Phyton Holdings, LLC

Natural Pharmaceuticals, Inc.

The General Hospital Corporation

Bion Inc.

Natural Pharmaccuticals, Inc.

Rex T Gallagher

James Harvey Johnson

Roland R Franke

John S Juchum

Brian A Bucher

Christopher D Howe

Dong S Yang

Barry Joseph Hand

Edward M Desimone, Iii

Marc A Plante

T G Sambandam

James H Johnson

Edward M Desimone

Dasheng Wang

Richard J Pariza

Garner T Haupert, Jr

T G Sambandan

Tg Sambandam

Barry J Haad

Marc A Plant

Edward M De Simone, Iii

James A Johnson

Edward M Iii Desimone

A method of crystallizing docetaxel is disclosed. The method comprises (a) combining docetaxel and at least one solubilizing solvent to obtain a solution, wherein the solubilizing solvent is selected from the group consisting of acetone, methyl-tert-butyl ether, tetrahydrofuran (THF), and acetonitrile and (b) adding an anti-solvent to the solution to obtain a crystalline docetaxel, wherein the anti-solvent is water.

Purification of taxanes

Disclosed is a method of crystallizing docetaxel comprising combining docetaxel and at least one solubilizing solvent to obtain a solution, wherein the solubilizing solvent is methylene chloride and adding an anti-solvent to the solution to obtain a crystalline docetaxel, wherein the anti-solvent is water.

Disclosed is a method of crystallizing a taxane comprising combining the taxane and methylene chloride to obtain a solution and adding an anti-solvent to the solution to obtain a crystalline taxane, wherein the anti-solvent is selected from the group consisting of hexane and heptane.

This invention is directed to a method for isolating and/or purifying one or more taxanes from materials comprising taxanes. In one embodiment, the method comprises the steps of: (a) treating a taxane containing material with an amino containing material attached to a solid matrix, such as a polyethyleneimine-bonded silica chromatographic resin; (b) eluting the desired taxane compound from the resin; and (c) recovering the eluted taxane compound.

Purification of taxanes and taxane mixtures using polyethyleneimine-bonded resins

The invention relates to methods and compositions for converting taxane amides to paclitaxel or other taxanes. In one alternative embodiment, the present invention comprises; (i) selectively protecting at least one OH group of a taxane amide; (ii) contacting the taxane amide with a transition metal compound to reduce the amide; (iii) contacting the reduced amide with an agent capable of substantially removing the transition metal; (iv) contacting the reduced amide with a hydrolyzing amount of acid to form a taxane amine salt in solution; (v) adding a sufficient amount of solvent to solidify the amine salt; and (vi) converting the taxane amine salt into paclitaxel or other taxanes.

Methods and compositions for converting taxane amides to paclitaxel or other taxanes

The invention provides methods and compositions for reductively deoxygenating an amide group at a C-3' position of a taxane molecule followed by subsequent intra-molecular acyl migration of an acyl group to the C-3&#x2032; position.

Conversion of taxane molecules

The invention provides methods and compositions for selectively acylating a specific hydroxyl group in a molecule of interest containing at least two unprotected secondary hydroxyl groups. Although the methods and compositions of the invention have general applicability, they are particularly useful in the selective acylation of taxane molecules.

Selective acylation of secondary hydroxyl groups

The present invention relates to a method of isolating and/or purifying hypothalamic inhibitory factor (HIF) from a sample (e.g., tissue fluid) containing HIF. The present invention provides for isolation of large amounts of HIF using diafiltration, solid phase extraction and immunoaffinity techniques. In one embodiment, the invention relates to a method of purifying hypothalamic inhibitory factor from a sample containing hypothalamic inhibitory factor comprising subjecting the sample to diafiltration, solid phase extraction and immunoaffintiy chromatography. In a particular embodiment, the invention relates to subjecting the sample to diafiltration to produce a diafiltrate of HIF; subjecting the diafiltrate to a first solid phase extraction (SPE) to produce a first fraction of HIF; subjecting the first fraction to immunoaffinity chromatography, wherein an antibody which binds to HIF is coupled to an immunoaffinity column, to produce a second fraction of HIF; subjecting the second fraction of HIF to reverse phase HPLC chromatography to produce a third fraction of HIF; and recovering purified HIF from the third fraction.

Process for large-scale isolation and purification of hypothalamic inhibitory factor

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Hampton, MA, United States of America

Rex T Gallagher