David W Lockhart

US Patent:

6344316, Feb 5, 2002

Filed:

Jun 25, 1997

Appl. No.:

08/882649

Inventors:

David J. Lockhart - Santa Clara CA
Mark Chee - Palo Alto CA
Kevin Gunderson - Palo Alto CA
Lisa Wodicka - Santa Clara CA
Maureen T. Cronin - Los Altos CA
Danny Lee - San Jose CA
Huu M. Tran - San Jose CA
Hajime Matsuzaki - Palo Alto CA

Assignee:

Affymetrix, Inc. - Santa Clara CA

International Classification:

C12Q 168

US Classification:

435 6, 536 243

Abstract:

The present invention provides a simplified method for identifying differences in nucleic acid abundances (e. g. , expression levels) between two or more samples. The methods involve providing an array containing a large number (e. g. greater than 1,000) of arbitrarily selected different oligonucleotide probes where the sequence and location of each different probe is known. Nucleic acid samples (e. g. mRNA) from two or more samples are hybridized to the probe arrays and the pattern of hybridization is detected. Differences in the hybridization patterns between the samples indicates differences in expression of various genes between those samples. This invention also provides a method of end-labeling a nucleic acid. In one embodiment, the method involves providing a nucleic acid, providing a labeled oligonucleotide and then enzymatically ligating the oligonucleotide to the nucleic acid. Thus, for example, where the nucleic acid is an RNA, a labeled oligoribonucleotide can be ligated using an RNA ligase.

US Patent:

6361947, Mar 26, 2002

Filed:

Oct 27, 1999

Appl. No.:

09/428350

Inventors:

Shoulian Dong - San Jose CA
Robert J. Lipshutz - Palo Alto CA
David J. Lockhart - Del Mar CA

Assignee:

Affymetrix, Inc. - Santa Clara CA

International Classification:

C12Q 168

US Classification:

435 6, 536 231

Abstract:

The present invention provides for novel methods of sample preparation and analysis involving reproducibly reducing the complexity of a nucleic sample. The invention further provides for analysis of the above sample by hybridization to an array which may be specifically designed to interrogate the desired fragments for particular characteristics, such as, for example, the presence or absence of a polymorphism. The invention further provides for novel methods of using a computer system to model enzymatic reactions in order to determine experimental conditions before conducting actual experiments.

US Patent:

6410229, Jun 25, 2002

Filed:

Dec 14, 1998

Appl. No.:

09/212004

Inventors:

David J. Lockhart - Santa Clara CA
Eugene L. Brown - Newton Highlands MA
Gordon G. Wong - Brookline MA
Mark S. Chee - Palo Alto CA
Thomas R. Gingeras - Encinitas CA

Assignee:

Affymetrix, Inc. - Santa Clara CA

International Classification:

C12Q 168

US Classification:

435 6, 536 231, 536 243, 536 2431, 536 2432, 536 2433, 536 232, 536 235, 536 253

Abstract:

This invention provides methods of monitoring the expression levels of a multiplicity of genes. The methods involve hybridizing a nucleic acid sample to a high density array of oligonucleotide probes where the high density array contains oligonucleotide probes complementary to subsequences of target nucleic acids in the nucleic acid sample. In one embodiment, the method involves providing a pool of target nucleic acids comprising RNA transcripts of one or more target genes, or nucleic acids derived from the RNA transcripts, hybridizing said pool of nucleic acids to an array of oligonucleotide probes immobilized on surface, where the array comprising more than 100 different oligonucleotides and each different oligonucleotide is localized in a predetermined region of the surface, the density of the different oligonucleotides is greater than about 60 different oligonucleotides per 1 cm , and the olignucleotide probes are complementary to the RNA transcripts or nucleic acids derived from the RNA transcripts; and quantifying the hybridized nucleic acids in the array.

US Patent:

6482591, Nov 19, 2002

Filed:

Apr 3, 1998

Appl. No.:

09/054969

Inventors:

David J. Lockhart - Santa Clara CA
Dirk Vetter - Freiburg, DE
Martin Diggelmann - Niederdorf, CH

Assignee:

Affymetrix, Inc. - Santa Clara CA

International Classification:

C12Q 168

US Classification:

435 6, 435DIG 36, 435DIG 40, 435DIG 42, 436518, 536 231, 536 243, 530300

Abstract:

Libraries of unimolecular, double-stranded oligonucleotides on a solid support. These libraries are useful in pharmaceutical discovery for the screening of numerous biological samples for specific interactions between the double-stranded oligonucleotides, and peptides, proteins, drugs and RNA. In a related aspect, the present invention provides libraries of conformationally restricted probes on a solid support. The probes are restricted in their movement and flexibility using double-stranded oligonucleotides as scaffolding. The probes are also useful in various screening procedures associated with drug discovery and diagnosis. The present invention further provides methods for the preparation and screening of the above libraries.

US Patent:

6495320, Dec 17, 2002

Filed:

Jul 21, 1999

Appl. No.:

09/358664

Inventors:

David J. Lockhart - Mountain View CA
Chao-Qiang Lai - Belmont MA
Kevin L. Gunderson - Encinitas CA

Assignee:

Affymetrix, Inc. - Santa Clara CA

International Classification:

C12Q 168

US Classification:

435 6, 435 912, 435 9151, 536 243

Abstract:

The even length proportional amplification of nucleic acids can increase the amount of nucleic acids while preserving the relative abundance of the individual nucleic acid species, or portions thereof, in the original sample. An even length proportionally amplified nucleic acid preparation may be analyzed in a gene expression monitoring system, preferably involving a nucleic acid probe array.

US Patent:

6548257, Apr 15, 2003

Filed:

Aug 22, 2001

Appl. No.:

09/935365

Inventors:

David J. Lockhart - Santa Clara CA
Eugene L. Brown - Newtown Highlands MA
Gordon G. Wong - Brookline MA
Mark Chee - Palo Alto CA
Thomas R. Gingeras - Encinitas CA

Assignee:

Affymetrix, Inc. - Santa Clara CA

International Classification:

C12Q 168

US Classification:

435 6, 536 231, 536 243, 536 2431, 536 2432, 536 2433

Abstract:

This invention provides methods of monitoring the expression levels of a multiplicity of genes. The methods involve hybridizing a nucleic acid sample to a high density array of oligonucleotide probes where the high density array contains oligonucleotide probes complementary to subsequences of target nucleic acids in the nucleic acid sample. In one embodiment, the method involves providing a pool of target nucleic acids comprising RNA transcripts of one or more target genes, or nucleic acids derived from the RNA transcripts, hybridizing said pool of nucleic acids to an array of oligonucleotide probes immobilized on surface, where the array comprising more than 100 different oligonucleotides and each different oligonucleotide is localized in a predetermined region of the surface, the density of the different oligonucleotides is greater than about 60 different oligonucleotides per 1 cm , and the olignucleotide probes are complementary to the RNA transcripts or nucleic acids derived from the RNA transcripts; and quantifying the hybridized nucleic acids in the array.

US Patent:

6573044, Jun 3, 2003

Filed:

Dec 22, 1998

Appl. No.:

09/221406

Inventors:

Nathanael S. Gray - Berkeley CA
Peter Schultz - Oakland CA
Lisa Wodicka - Santa Clara CA
Laurent Meijer - Roscoff, FR
David J. Lockhart - Mountain View CA

Assignee:

The Regents of the University of California - Oakland CA
Affymetrix, Inc. - Santa Clara CA
Centre National de la Recherche Scientifique - Paris

International Classification:

C12Q 168

US Classification:

435 6, 435 912, 435DIG 17, 544268, 544276, 544277

Abstract:

The generation of selective inhibitors for specific protein kinases would provide new tools for analyzing signal transduction pathways and possibly new therapeutic agents. We have invented an approach to the development of selective protein kinase inhibitors based on the unexpected binding mode of 2,6,9-trisubstituted purines to the ATP binding site of human CDK2. The most potent inhibitor, purvalanol B (IC =6 nM), binds with a 30-fold greater affinity than the known CDK2 inhibitor, flavopiridol. The cellular effects of this class of compounds were examined and compared to those of flavopiridol by monitoring changes in mRNA expression levels for all genes in treated cells of using high-density oligonucleotide probe arrays.

US Patent:

6576425, Jun 10, 2003

Filed:

Feb 8, 2001

Appl. No.:

09/781537

Inventors:

Glenn McGall - Mountain View CA
Anthony D. Barone - Santa Clara CA
Martin Diggelmann - Arlesheim, CH
David J. Lockhart - Santa Clara CA
Ann Maria Caviani Pease - Sunnyvale CA
Mark Chee - Palo Alto CA

Assignee:

Affymetrix, Inc. - Santa Clara CA

International Classification:

C12Q 168

US Classification:

435 6, 536 221, 536 231, 536 253, 536 2532, 436518, 436527, 436528

Abstract:

Methods for testing oligonucleotide arrays are disclosed including methods for testing the efficiency of nucleotide coupling; methods for testing amounts of deprotected oligonucleotides; methods for determining amounts of depurinated oligonucleotides; and methods of detecting the presence of cleavable structural features, such as double-stranded nucleic acids.