Novartis Vaccines & Diagnostics, Gmbh

Novartis Ag

Chiron Corporation

Sidney N Wolfe

Maninder S Hora

Bret A Shirley

Susan Babuka

Irina Esikova

Dennis Fordham

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 formulations comprising IFN-&#x3b2; and highly purified mannitol are provided. The highly purified mannitol stabilizes the compositions by reducing the formation of IFN-&#x3b2; adducts in comparison with IFN-&#x3b2; formulated with mannitol that has not been highly purified. Methods for increasing the stability of IFN-&#x3b2; or a variant thereof in a liquid or lyophilized composition and for increasing storage stability of such a composition are also provided.

Stabilized interferon compositions

Methods of protein purification and recovery

Growing community of inventors

Lafayette, CA, United States of America

Sidney N Wolfe