Sidney N Wolfe

6994847, Feb 7, 2006

Nov 7, 2001

10/010448

Sidney N. Wolfe - Lafayette CA, US
Maninder S. Hora - Danville CA, US

Chiron Corporation - Emeryville CA

A61K 38/21
A61K 39/00
C12N 9/96
C07K 14/00

424 856, 4241981, 435188, 530412, 530422, 530351

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

7544354, Jun 9, 2009

Oct 25, 2001

10/035420

Sidney N. Wolfe - Lafayette CA, US
Bret A. Shirley - Waltham MA, US
Susan Babuka - Oakland CA, US
Dennis Fordham - Richmond CA, US
Irina Esikova - Fremont CA, US

Novartis Vaccines and Diagnostics - Emeryville CA

A61K 38/21
C07K 17/00

424 856, 424 851, 530351

Improved methods for purification and recovery of interferon-beta (IFN-β) and compositions comprising substantially monomeric IFN-β are provided. In one purification method, substantially purified IFN-β 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-β, residual guanidine HCl is removed by diafiltration or dialysis with a pharmaceutically acceptable buffer to prepare pharmaceutical compositions comprising substantially monomeric IFN-β.

7662369, Feb 16, 2010

Jul 22, 2005

11/188257

Sidney N. Wolfe - Lafayette CA, US
Maninder S. Hora - Danville CA, US

Novartis AG - Basel

A61K 38/21
C07K 14/00
A61K 38/00

424 856, 530351, 514 2

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

8388942, Mar 5, 2013

Apr 29, 2008

12/150530

Sidney N Wolfe - Lafayette CA, US
Bret A Shirley - Waltham MA, US
Susan Babuka - Oakland CA, US
Dennis Fordham - Richmond CA, US
Irina Esikova - Fremont CA, US

Novartis Vaccines and Diagnostics, Inc. - Emeryville CA

A61K 38/21
C07K 14/565

424 856, 530351

Improved methods for purification and recovery of interferon-beta (IFN-β) and compositions comprising substantially monomeric IFN-β are provided. In one purification method, substantially purified IFN-β 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-β, residual guanidine HCl is removed by diafiltration or dialysis with a pharmaceutically acceptable buffer to prepare pharmaceutical compositions comprising substantially monomeric IFN-β.

20030124139, Jul 3, 2003

Nov 20, 2002

10/148559

Irina Esikova - Fremont CA, US
Sidney Wolfe - Alameda CA, US
James Thomson - Berkeley CA, US
Maninder Hora - Danville CA, US

A61K039/00

424/185100

The present invention is directed to compositions and methods for the preparation of biological molecules, in particular MenC-CRM 197. Biological molecules dissolved in dissolution buffers comprising at least one amorphous excipient and an amorphous buffer exhibit reduced aggregation and proteolytic breakdown.

20040115169, Jun 17, 2004

Dec 31, 2003

10/750076

Sidney Wolfe - Lafayette CA, US
Bret Shirley - Waltham MA, US
Susan Babuka - Oakland CA, US
Dennis Fordham - Richmond CA, US
Irina Esikova - Fremont CA, US

Chiron Corporation - Emeryville CA

A61K038/21
C07K014/56

424/085600, 530/351000

Improved methods for purification and recovery of interferon-beta (IFN-) and compositions comprising substantially monomeric IFN- are provided. In one purification method, substantially purified IFN- 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-, residual guanidine HCl is removed by diafiltration or dialysis with a pharmaceutically acceptable buffer to prepare pharmaceutical compositions comprising substantially monomeric IFN-.

51625075, Nov 10, 1992

Sep 12, 1989

7/406365

Sidney N. Wolfe - El Cerrito CA
Glenn J. Dorin - San Rafael CA
John T. Davis - Berkeley CA
Flint Smith - Gardon Grove CA
Amy Lim - Hercules CA
Robert Weissburg - Oakland CA

Cetus Corporation - Emeryville CA

C07K 300
C07K 312

530412

A process for recovering highly pure, recombinant IL-2 from transformed microorganisms in which the cells are disrupted; impure recombinant IL-2 is isolated in the form of refractile bodies from the disruptate; the impure IL-2 is dissolved and denatured with at least 6M guanidine hydrochloride containing a reducing agent; the reduced IL-2 is precipitated and resolubilized; the reduced solubilized IL-2 therein is oxidized by a controlled oxidation; the oxidized IL-2 is refolded by reducing the concentration of guanidine hydrochloride in the solution; and the oxidized, refolded IL-2 is further purified by ion exchange chromatography or hydrophobic interaction chromatography and ion exchange chromatography.

45307873, Jul 23, 1985

Oct 17, 1984

6/661902

Ze'ev Shaked - Berkeley CA
Sidney N. Wolfe - Richmond CA

Cetus Corporation - Emeryville CA

C07G 700
A61K 4502

260112R

Method of oxidizing reduced cysteine-containing microbially produced synthetic proteins, such as synthetic IFN-. beta. or synthetic IL-2, in a controlled manner so that the synthetic proteins have the same disulfide bridging as their native counterparts. The oxidation employs o-iodosobenzoate as oxidizing agent and is carried out in an aqueous medium at a pH at least about one-half pH unit less than the pK. sub. a of the cysteines to be oxidized, a synthetic protein concentration of less than about 5 mg/ml, and an oxidizing agent:protein mol ratio that is at least stoichiometric, provided that the oxidizing agent is in excess in the terminal portion of the reaction.