David W Liu

US Patent:

6410540, Jun 25, 2002

Filed:

Aug 27, 1999

Appl. No.:

09/385494

Inventors:

R. Richard Goehring - Pipersville PA
Gregory R. Luedtke - Sunnyvale CA
Babu J. Mavunkel - Sunnyvale CA
Sarvajit Chakravarty - Sunnyvale CA
Sundeep Dugar - Bridgewater NJ
George F. Schreiner - Los Altos Hills CA
David Y. Liu - Palo Alto CA
John A. Lewicki - Los Gatos CA

Assignee:

Scios, Inc. - Sunnyvale CA

International Classification:

A61K 3150

US Classification:

51425213, 51425409, 514330

Abstract:

The invention is directed to methods to treat conditions mediated by p38-kinase using compounds of the formula and the pharmaceutically acceptable salts thereof, or a pharmaceutical composition thereof, wherein Z is N or CR , R is a noninterfering substituent, each of X and X is a linker, Ar and Ar are identical or different, and represent optionally substituted C1-C20 hydrocarbyl residues wherein at least one of Ar and Ar is an optionally substituted aryl group, with the proviso that when X is CH or an isostere thereof, X is CO or an isostere thereof, and Ar is optionally substituted phenyl, Ar is other than an optionally substituted indolyl, benzimidazolyl or benzotriazolyl substituent, and wherein said optionally substituted phenyl is not an optionally substituted indolyl, benzimidazolyl, or benzotriazolyl, Y is a noninterfering substituent, wherein n is an integer from 0-4, and wherein m is an integer from 0-4 and 1 is an integer from 0-3.

US Patent:

6541477, Apr 1, 2003

Filed:

Feb 28, 2001

Appl. No.:

09/796997

Inventors:

R. Richard Goehring - Pipersville PA
Babu J. Mavunkel - Sunnyvale CA
David Y. Liu - Palo Alto CA
George F. Schreiner - Los Altos Hills CA
Gregory Leudtke - Sunnyvale CA
John A. Lewicki - Los Gatos CA

Assignee:

Scios, Inc. - Sunnyvale CA

International Classification:

A61K 31495

US Classification:

51425213, 5142541, 514330

Abstract:

The invention is directed to methods for treating conditions mediated by by P38 kinase using compounds of the formula wherein Ar and Ph are limited to specific embodiments or wherein the compound of formula (3) is a compound set forth in FIGS. A- T.

US Patent:

7070928, Jul 4, 2006

Filed:

Mar 19, 2002

Appl. No.:

10/101030

Inventors:

David R. Liu - Lexington MA, US
Zev Gartner - Somerville MA, US
Matthew W. Kanan - Cambridge MA, US

Assignee:

President and Fellows of Harvard College - Cambridge MA

International Classification:

C12Q 1/68

US Classification:

435 6

Abstract:

Nature evolves biological molecules such as proteins through iterated rounds of diversification, selection, and amplification. The present invention provides methods, compositions, and systems for synthesizing, selecting, amplifying, and evolving non-natural molecules based on nucleic acid templates. The sequence of a nucleic acid template is used to direct the synthesis of non-natural molecules such as unnatural polymers and small molecules. Using this method combinatorial libraries of these molecules can be prepared and screened. Upon selection of a molecule, its encoding nucleic acid template may be amplified and/or evolved to yield the same molecule or related molecules for re-screening. The inventive methods and compositions of the present invention allow for the amplification and evolution of non-natural molecules in a manner analogous to the amplification of natural biopolymer such as polynucleotides and protein.

US Patent:

7192739, Mar 20, 2007

Filed:

Mar 30, 2005

Appl. No.:

11/093808

Inventors:

David R. Liu - Lexington MA, US
Allen R. Buskirk - Provo UT, US

Assignee:

President and Fellows of Harvard College - Cambridge MA

International Classification:

C12P 21/06
C12P 21/04

US Classification:

435 691, 435 697

Abstract:

Ligand-dependent inteins allow for modulation of a protein's activity in vivo. Upon binding of the ligand to the ligand-dependent intein inserted into the protein of interest, the hybrid protein undergoes protein splicing removing the intein. The activity of the spliced protein is then restored. A 4-hydroxytamoxifen-dependent intein based on the RecA intein is prepared and demonstrated in a variety of exteins contexts. The invention provides a system for engineering other ligand-dependent inteins and using them, including the ligand-dependent inteins themselves, hybrid proteins with the inserted ligand-dependent inteins, polynucleotides encoding inteins and hybrid proteins, and engineered cells. Kits with the materials and reagents necessary for preparing and using ligand-dependent inteins are also included.

US Patent:

7223545, May 29, 2007

Filed:

Sep 24, 2004

Appl. No.:

10/949163

Inventors:

David R. Liu - Lexington MA, US
Zev J. Gartner - Somerville MA, US
Matthew W. Kanan - Cambridge MA, US

Assignee:

President and Fellows of Harvard College - Cambridge MA

International Classification:

C12Q 1/68
C12P 19/34
C07H 21/02
C07H 21/04
C07K 1/00

US Classification:

435 6, 435 911, 435 912, 536 231, 536 243, 536 2431, 536 2432, 536 2433, 530350

Abstract:

Nature evolves biological molecules such as proteins through iterated rounds of diversification, selection, and amplification. The present invention provides methods, compositions, and systems for synthesizing, selecting, amplifying, and evolving non-natural molecules based on nucleic acid templates. The sequence of a nucleic acid template is used to direct the synthesis of non-natural molecules such as unnatural polymers and small molecules. Using this method combinatorial libraries of these molecules can be prepared and screened. Upon selection of a molecule, its encoding nucleic acid template may be amplified and/or evolved to yield the same molecule or related molecules for re-screening. The inventive methods and compositions of the present invention allow for the amplification and evolution of non-natural molecules in a manner analogous to the amplification of natural biopolymer such as polynucleotides and protein.

US Patent:

7442160, Oct 28, 2008

Filed:

May 31, 2005

Appl. No.:

11/141542

Inventors:

David R. Liu - Lexington MA, US
Zev J. Gartner - Somerville MA, US
Matthew W. Kanan - Cambridge MA, US

Assignee:

President and Fellows of Harvard College - Cambridge MA

International Classification:

C40B 30/04
C40B 10/00
C40B 30/08
C40B 40/00
C40B 50/10
C40B 70/00
C12Q 1/68
C07H 21/02

US Classification:

506 9, 506 1, 506 11, 506 13, 506 28, 506 41, 435 6, 435 912, 536 231

Abstract:

Nature evolves biological molecules such as proteins through iterated rounds of diversification, selection, and amplification. The present invention provides methods, compositions, and systems for synthesizing, selecting, amplifying, and evolving non-natural molecules based on nucleic acid templates. The sequence of a nucleic acid template is used to direct the synthesis of non-natural molecules such as unnatural polymers and small molecules. Using this method combinatorial libraries of these molecules can be prepared and screened. Upon selection of a molecule, its encoding nucleic acid template may be amplified and/or evolved to yield the same molecule or related molecules for re-screening. The inventive methods and compositions of the present invention allow for the amplification and evolution of non-natural molecules in a manner analogous to the amplification of natural biopolymer such as polynucleotides and protein.

US Patent:

7476500, Jan 13, 2009

Filed:

Mar 19, 2002

Appl. No.:

10/102056

Inventors:

David R. Liu - Lexington MA, US
Zev Gartner - Somerville MA, US
Daniel M. Rosenbaum - Cambridge MA, US
Mathias Gruen - Jena, DE
Jeffrey Doyon - Allston MA, US

Assignee:

President and Fellows of Harvard College - Cambridge MA

International Classification:

C12Q 1/68
C12N 9/22

US Classification:

435 6, 435199

Abstract:

The present invention provides in vivo systems in which activity of a biological cleavage enzyme, such as a site-specific recombinase, a homing endonuclease, or an intein, is linked to cell viability and therefore can be selected. The invention further provides methods of making cells in which the activity of a biological cleavage enzyme is linked to viability, as well as methods of identifying new biological cleavage enzymes, including enzymes having altered site specificity, using such cells.

US Patent:

7476734, Jan 13, 2009

Filed:

Dec 6, 2005

Appl. No.:

11/295155

Inventors:

David R. Liu - Lexington MA, US

Assignee:

Helicos Biosciences Corporation - Cambridge MA

International Classification:

C07H 19/04
C07H 19/20

US Classification:

536 2621, 536 221, 536 253, 536 2532, 536 261, 536 262

Abstract:

The invention provides nucleotide analogs for use in sequencing nucleic acid molecules.