Jeffrey H Stack

US Patent:

7465738, Dec 16, 2008

Filed:

Jun 16, 2004

Appl. No.:

10/869498

Inventors:

Jill Jarecki - San Diego CA, US
Xiaocun Chen - San Diego CA, US
Dennis James Hurley - San Marcos CA, US
Lewis R. Makings - Encinitas CA, US
Mark T. Miller - San Diego CA, US
Brian Pollok - Middleton WI, US
Jeffrey H. Stack - San Diego CA, US
Michael A. Whitney - San Diego CA, US

Assignee:

Vertex Pharmaceuticals Incorporated - Cambridge MA

International Classification:

A61K 31/517
A61K 31/55
C07D 239/72

US Classification:

5142662, 5142664, 544284, 544291

Abstract:

The present invention relates to compounds useful as promoters of the SMN2 gene. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of Spinal Muscular Atrophy.

US Patent:

7824850, Nov 2, 2010

Filed:

Jun 22, 2007

Appl. No.:

11/821562

Inventors:

Jeffrey Stack - San Diego CA, US
Michael Whitney - San Diego CA, US
Andrew B. Cubitt - San Diego CA, US
Brian Pollok - San Diego CA, US

Assignee:

Aurora Biosciences Corporation - San Diego CA

International Classification:

C12Q 1/00
C07K 14/00

US Classification:

435 4, 530350

Abstract:

This invention is directed towards methods of destabilizing proteins in living cells, and their use for the development of novel assays. In one embodiment, the invention comprises the use of non-cleavable multimerized ubiquitin fusion proteins to destabilize a target protein, such as a reporter moiety. In one aspect of this method the constructs also comprises a linker that operatively couples the reporter moiety to the multimerized ubiquitin fusion protein. In this embodiment, enzymatic modification of the linker results in a modulation of the coupling of the reporter protein to the multimerized ubiquitin domains resulting in a change in the stability of the reporter moiety. The level of the reporter moiety in the cell can then be used as a measure of the enzymatic activity in the cell. In another embodiment the invention provides for a generalized way of coordinately regulating the cellular concentration of a plurality of target proteins. In one aspect of this method, the target proteins are operatively coupled to a ubiquitin fusion protein via a linker containing a protease cleavage site.

US Patent:

7262005, Aug 28, 2007

Filed:

Feb 4, 2000

Appl. No.:

09/498098

Inventors:

Jeffrey Stack - San Diego CA, US
Michael Whitney - San Diego CA, US
Andrew B. Cubitt - San Diego CA, US
Brian Pollok - San Diego CA, US

Assignee:

Aurora Biosciences Corporation - San Diego CA

International Classification:

C12Q 1/68

US Classification:

435 6, 435325, 536 234

Abstract:

This invention is directed towards methods of destabilizing proteins in living cells, and their use for the development of novel assays. In one embodiment, the invention comprises the use of non-cleavable multimerized ubiquitin fusion proteins to destabilize a target protein, such as a reporter moiety. In one aspect of this method the constructs also comprises a linker that operatively couples the reporter moiety to the multimerized ubiquitin fusion protein. In this embodiment, enzymatic modification of the linker results in a modulation of the coupling of the reporter protein to the multimerized ubiquitin domains resulting in a change in the stability of the reporter moiety. The level of the reporter moiety in the cell can then be used as a measure of the enzymatic activity in the cell. In another embodiment the invention provides for a generalized way of coordinately regulating the cellular concentration of a plurality of target proteins. In one aspect of this method, the target proteins are operatively coupled to a ubiquitin fusion protein via a linker containing a protease cleavage site.

US Patent:

20110191873, Aug 4, 2011

Filed:

Nov 2, 2010

Appl. No.:

12/938179

Inventors:

Jeffrey Stack - San Diego CA, US
Michael Whitney - San Diego CA, US
Andrew B. Cubitt - San Diego CA, US
Brian Pollok - San Diego CA, US

International Classification:

A01K 67/00
C12N 5/10
C07H 21/04
C12N 1/00
C07K 19/00
A01H 5/00
C12Q 1/02
C12Q 1/37
C12Q 1/42
C12Q 1/48
C12Q 1/66
C12N 5/07
C12N 5/071
C12N 5/04

US Classification:

800 13, 435325, 435410, 536 234, 435243, 530350, 800298, 435 29, 435 23, 435 21, 435 15, 435 8, 435375, 435348

Abstract:

This invention is directed towards methods of destabilizing proteins in living cells, and their use for the development of novel assays. In one embodiment, the invention comprises the use of non-cleavable multimerized ubiquitin fusion proteins to destabilize a target protein, such as a reporter moiety. In one aspect of this method the constructs also comprises a linker that operatively couples the reporter moiety to the multimerized ubiquitin fusion protein. In this embodiment, enzymatic modification of the linker results in a modulation of the coupling of the reporter protein to the multimerized ubiquitin domains resulting in a change in the stability of the reporter moiety. The level of the reporter moiety in the cell can then be used as a measure of the enzymatic activity in the cell. In another embodiment the invention provides for a generalized way of coordinately regulating the cellular concentration of a plurality of target proteins. In one aspect of this method, the target proteins are operatively coupled to a ubiquitin fusion protein via a linker containing a protease cleavage site. Cleavage of the linker by a protease results in uncoupling of the target protein from the multimerized ubiquitin construct, and results in an increase in the stability and concentration of the target protein.