Novartis Vaccines & Diagnostics, Gmbh

Chiron Corporation

Chrion Corporation

Bret A Shirley

Maninder S Hora

Susan Babuka

Bao-lu Chen

Minna Choe

Melanie Tellers

Kamaljit K Bajwa

Sidney N Wolfe

Dennis Fordham

Irina Esikova

Derek T O'Hagan

Manmohan Singh

Robert V Hageman

Bao-Lu Chen

Improved methods for purification and recovery of interferon-beta (IFN-&#x3b2;) and compositions comprising substantially monomeric IFN-&#x3b2; are provided. In one purification method, substantially purified IFN-&#x3b2; or variant thereof is precipitated and then dissolved in a guanidine hydrochloride (HCl) solution. Renaturation of the protein occurs by dilution with a suitable buffer. A similar purification method absent the precipitation step is also provided. Following renaturation of the IFN-&#x3b2;, residual guanidine HCl is removed by diafiltration or dialysis with a pharmaceutically acceptable buffer to prepare pharmaceutical compositions comprising substantially monomeric IFN-&#x3b2;.

Methods of interferon-&#x3b2; purification and recovery

Stabilized pharmaceutical compositions comprising substantially monomeric interferon-beta (IFN-&#x3b2;) and methods useful in their preparation are provided. The compositions comprise the IFN-&#x3b2; solubilized in a low-ionic-strength formulation that maintains the composition at a pH of about 3.0 to about 5.0. Methods for preparing these compositions, and for increasing solubility of IFN-&#x3b2; in pharmaceutical compositions, are provided.

HSA-free formulations of interferon-Beta

HSA-free formulations of interferon-&#x3b2;

Stabilized FGF compositions are provided. The compositions comprise FGF or variant thereof and at least one reducing agent in an amount sufficient to inhibit FGF oxidation. Methods for increasing stability of FGF or variant thereof in a liquid or lyophilized composition and for increasing storage stability of such a composition are also provided.

Stabilized FGF formulations containing reducing agents

Methods of protein purification and recovery

HSA-free formulations of interferon-beta

A highly concentrated, low salt-containing, biologically active syrup form of IGF-I or variant thereof and methods for its preparation are provided. This novel syrup form of IGF-I has an IGF-I concentration of at least about 250 mg/ml, a density of about 1.0 g/ml to about 1.2 g/ml, and a viscosity of about 13,000 centipoise (cps) to about 19,000 cps, as measured at ambient temperature (23&#xb0; C.). The IGF-I syrup is prepared by precipitating or partitioning IGF-I from solution, preferably by adjusting the solution pH or by use of a solubility enhancer to concentrate IGF-I in solution followed by removal of the solubility enhancer. The precipitated syrup is useful as a means of storing IGF-I in a stable form and as a means of preparing compositions comprising biologically active IGF-I. Pharmaceutical compositions and kits comprising this concentrated IGF-I syrup are provided. The precipitated IGF-I syrup, IGF-I reconstituted from the IGF-I syrup, pharmaceutical compositions, and kits are useful in IGF-I therapy directed to IGF-I-responsive conditions.

IGF-1 composition and its use

Novel IGF-I compositions are described. The compositions include a solubilizing compound comprising a guanidinium group that provides for IGF-I compositions in which IGF-I is highly soluble at pHs of about 5.5 or greater and at refrigerated temperatures.

Compositions providing for increased IGF-I solubility

IGF-I composition and its use

Methods for preparing biodegradable microparticles are provided. Also provided are microparticles prepared by the method which include IGF-1 entrapped therein. The microparticles allow for controlled release of IGF-1 and other polypeptides over prolonged periods of time.

Method for producing sustained-release formulations

Growing community of inventors

Waltham, MA, United States of America

Bret A Shirley