William J Raab

US Patent:

8211655, Jul 3, 2012

Filed:

Feb 11, 2010

Appl. No.:

12/704399

Inventors:

Thomas S. Wehrman - Mountain View CA, US
William Raab - San Francisco CA, US
Chin Yee Loh - Kensington CA, US

Assignee:

Discoverx Corporation - Fremont CA

International Classification:

G01N 33/567
C07K 14/705
C07K 19/00
C12N 15/62

US Classification:

435 72, 435 721, 435 697, 436501, 536 234

Abstract:

A method for determining ligand activation of receptors using cells expressing genetic constructs of a fusion protein of at least a binding domain of an auxiliary protein and a fragment of β-galactosidase, a fusion protein of an endosome-associated protein and a complementary fragment of β-galactosidase, and a wild-type receptor. The receptors are characterized by binding to the auxiliary protein-binding domain upon activation by an agonist and then endocytosing associated with an endosome to which the endosome-associated protein binds. Cells are incubated with a candidate ligand followed by lysis with a lysing medium comprising a substrate for the β-galactosidase. The enzyme product is then detected as a measure of the activation of the receptor.

US Patent:

8569057, Oct 29, 2013

Filed:

Jun 22, 2012

Appl. No.:

13/531230

Inventors:

Thomas S. Wehrman - Mountain View CA, US
Daniel Bassoni - Campbell CA, US
William Raab - San Francisco CA, US

Assignee:

DiscoveRx Corporation - Fremont CA

International Classification:

C12N 5/02

US Classification:

435375

Abstract:

Methods and materials are disclosed for use in an enzyme fragment complementation assay using complementary fragments of β-galactosidase to study the trafficking of proteins in a cell. Compounds that bind to a target peptide have been found to affect protein folding and therefore trafficking. β-Galactosidase fragments, an enzyme donor (ED) and an enzyme acceptor (EA), are fused to a target peptide and to an intracellular compartment protein, wherein the compartment is involved in intracellular trafficking. Contacting the cell with a compound that binds to the target peptide results in enhanced movement of the protein through the cellular trafficking pathway comprised of the endoplasmic reticulum, Golgi apparatus, the plasma membrane, endosomes, etc. Using this approach, compounds that bind to a target peptide and alter its ability to traffic through the normal cellular pathway can be readily detected.

US Patent:

20100041052, Feb 18, 2010

Filed:

Aug 6, 2009

Appl. No.:

12/536667

Inventors:

Wei Feng - Fremont CA, US
William Raab - San Francisco CA, US
Philip Achacoso - Union City CA, US
Thomas Wehrman - East Palo Alto CA, US
Keith R. Olson - Pleasanton CA, US

Assignee:

DISCOVERX CORPORATION - Fremont CA

International Classification:

C12Q 1/68
G01N 33/573

US Classification:

435 6, 435 72

Abstract:

Methods for detecting phosphorylation of receptor tyrosine kinases (“RTKs”) upon activation are provided. The method employs cells comprising two fusion products: (1) an RTK fused to a small fragment of β-galactosidase and (2) a phosphotyrosine binding peptide fused to the large fragment of β-galactosidase, where the 2 fragments weakly complex to form an active enzyme, and optionally a construct for a cytosolic RTK phosphorylating kinase, when the RTK does not autophosphoryate. To detect phosphorylation a β-galactosidase substrate is added to the cells, whereby product formation indicates the occurrence of phosphorylation.

US Patent:

20120040372, Feb 16, 2012

Filed:

Oct 25, 2011

Appl. No.:

13/280919

Inventors:

Wei Feng - Guilin View, SG
William Raab - San Francisco CA, US
Philip Achacoso - Union City CA, US
Thomas Wehrman - Mountain View CA, US
Keith R. Olson - Pleasanton CA, US

Assignee:

DISCOVERX CORPORATION - Fremont CA

International Classification:

G01N 33/573

US Classification:

435 74

Abstract:

Methods for detecting phosphorylation of receptor tyrosine kinases (“RTKs”) upon activation and the modulation of activation by a candidate compound are provided. The method employs cells comprising two fusion products: (1) an RTK fused to a small fragment of β-galactosidase and (2) a phosphotyrosine binding peptide fused to the large fragment of β-galactosidase, where the 2 fragments weakly complex to form an active enzyme, and optionally a construct for a cytosolic RTK phosphorylating kinase, when the RTK does not autophosphoryate. To detect phosphorylation a β-galactosidase substrate is added to the cells, whereby product formation indicates the occurrence of phosphorylation.

US Patent:

20140045194, Feb 13, 2014

Filed:

Oct 21, 2013

Appl. No.:

14/058822

Inventors:

Daniel Bassoni - Campbell CA, US
William Raab - Fremont CA, US

Assignee:

DiscoveRx Corporation - Fremont CA

International Classification:

C12Q 1/34

US Classification:

435 721

Abstract:

Methods and materials are disclosed for use in an enzyme fragment complementation assay using complementary fragments of β-galactosidase to study the trafficking of proteins in a cell. Compounds that bind to a target peptide have been found to affect protein folding and therefore trafficking. β-Galactosidase fragments, an enzyme donor (ED) and an enzyme acceptor (EA), are fused to a target peptide and to an intracellular compartment protein, wherein the compartment is involved in intracellular trafficking. Contacting the cell with a compound that binds to the target peptide results in enhanced movement of the protein through the cellular trafficking pathway comprised of the endoplasmic reticulum, Golgi apparatus, the plasma membrane, endosomes, etc. Using this approach, compounds that bind to a target peptide and alter its ability to traffic through the normal cellular pathway can be readily detected.

US Patent:

20180094322, Apr 5, 2018

Filed:

Aug 23, 2017

Appl. No.:

15/684687

Inventors:

- New York NY, US
Michael F. Clarke - Menlo Park CA, US
Debashis Sahoo - San Diego CA, US
William Joseph Raab - New York NY, US
Luis Enrique Valencia Salazar - New York NY, US

International Classification:

C12Q 1/6886
C12Q 1/6806
C12Q 1/6809
G01N 33/15
C12Q 1/686
A61P 35/00

Abstract:

The present invention provides a biomarker, namely CDX2, and surrogate CDX2 biomarkers, the expression level of which is useful in predicting response of cancer patients to therapy with an EGFR inhibitor.