Gerald R Crabtree

US Patent:

6352830, Mar 5, 2002

Filed:

Jan 15, 1999

Appl. No.:

09/232346

Inventors:

Gerald R. Crabtree - Woodside CA
Jeffrey P. Northrop - Campbell CA
Steffan N. Ho - San Diego CA
William M. Flanagan - Menlo Park CA

Assignee:

The Board of Trustees of the Leland Stanford Junior University - Stanford CA

International Classification:

C12Q 168

US Classification:

435 6, 435 4, 435 71, 435 15, 435 21, 536 241, 536 235, 530350

Abstract:

The invention provides novel polypeptides which are associated with the transcription complex NF-AT, polynucleotides encoding such polypeptides, antibodies which are reactive with such polypeptides, polynucleotide hybridization probes and PCR amplification probes for detecting polynucleotides which encode such polypeptides, transgenes which encode such polypeptides, homologous targeting constructs that encode such polypeptides and/or homologously integrate in or near endogenous genes encoding such polypeptides, nonhuman transgenic animals which comprise functionally disrupted endogenous genes that normally encode such polypeptides, and transgenic nonhuman animals which comprise transgenes encoding such polypeptides. The invention also provides methods for detecting T cells (including activated T cells) in a cellular sample, methods for treating hyperactive or hypoactive T cell conditions, methods for screening for immunomodulatory agents, methods for diagnostic staging of lymphocyte differentiation, methods for producing NF-AT proteins for use as research or diagnostic reagents, methods for producing antibodies reactive with the novel polypeptides, and methods for producing transgenic nonhuman animals. Also included are methods and agents for activation of NF-AT dependent transcription, including agents which interfere with the production, modification of nuclear or cytoplasmic subunits, or the nuclear import of the cytoplasmic subunits.

US Patent:

6372712, Apr 16, 2002

Filed:

May 21, 1999

Appl. No.:

09/316932

Inventors:

Roger Briesewitz - Mountain View CA
Gerald R. Crabtree - Woodside CA
Thomas Wandless - Menlo Park CA
Gregory Thomas Ray - Stanford CA
Kurt William Vogel - Palo Alto CA

Assignee:

The Board of Trustees of the Leland Stanford Jr. University - Palo Alto CA
The Howard Hughes Medical Institute - Chevy Chase MD

International Classification:

A61K 3800

US Classification:

514 2, 424 941, 424 945, 435177, 514 9, 530402, 530812

Abstract:

Bifunctional molecules and methods for their use in the production of binary complexes in a host are provided. The bifunctional molecule is a conjugate of a drug moiety and a presenter protein ligand. The molecular weight of the bifunctional molecule is preferably less than about 5000 daltons, and the drug moiety may have a molecular weight of from about 50 to 2000 daltons. The drug moiety and presenter protein ligand may be covalently linked directly or through a linking group. The drug moiety binds to a drug target such as a protein and the presenter protein ligand binds to a presenter protein that is not the drug target such as extracellular or intracellular protein. Presenter proteins include peptidyl prolyl isomerase (FKBP), Heat Shock Protein 90 (Hsp90), steroid hormone receptors, cytoskeletal proteins, albumin and vitamin receptors. When the presenter protein is FKBP, ligands include FK506, rapamycin and cyclosporin A which may have an introduced functional group such as hydroxyl, amino, carboxyl, aldehyde, carbonate, carbamate, azide, thiol or ester for attaching the drug moiety. In the methods of use, an effective amount of the bifunctional molecule is administered to the host.

US Patent:

6388052, May 14, 2002

Filed:

Mar 9, 1998

Appl. No.:

09/037192

Inventors:

Gerald R. Crabtree - Woodside CA
Jeffrey P. Northrop - Campbell CA
Steffan N. Ho - Menlo Park CA

Assignee:

Board of Trustees of the Leland Stanford Junior University - Stanford CA

International Classification:

C07K 500

US Classification:

530300, 530350, 530351

Abstract:

The invention provides novel polypeptides which are associated with the transcription complex NF-AT, polynucleotides encoding such polypeptides, antibodies which are reactive with such polypeptides, polynucleotide hybridization probes and PCR amplification probes for detecting polynucleotides which encode such polypeptides, transgenes which encode such polypeptides, homologous targeting constructs that encode such polypeptides and/or homologously integrate in or near endogenous genes encoding such polypeptides, nonhuman transgenic animals which comprise functionally disrupted endogenous genes that normally encode such polypeptides, and transgenic nonhuman animals which comprise transgenes encoding such polypeptides. The invention also provides methods for detecting T cells (including activated T cells) in a cellular sample, methods for treating hyperactive or hypoactive T cell conditions, methods for screening for immunomodulatory agents, methods for diagnostic staging of lymphocyte differentiation, methods for producing NF-AT proteins for use as research or diagnostic reagents, methods for producing antibodies reactive with the novel polypeptides, and methods for producing transgenic nonhuman animals.

US Patent:

6875571, Apr 5, 2005

Filed:

Jan 7, 2002

Appl. No.:

10/040430

Inventors:

Gerald R. Crabtree - Woodside CA, US
Jeffrey P. Northrop - Campbell CA, US
Steffan N. Ho - San Diego CA, US
William M. Flanagan - Menlo Park CA, US

Assignee:

The Board of Trustees of the Leland Stanford Junior University - Palo Alto CA

International Classification:

C12Q001/68
C07H021/04
G01N033/53
C07K014/435

US Classification:

435 6, 435 4, 435 71, 435 792, 435 15, 435 21, 536 231, 536 235, 530350

Abstract:

The invention provides novel polypeptides which are associated with the transcription complex NF-AT, polynucleotides encoding such polypeptides, antibodies which are reactive with such polypeptides, polynucleotide hybridization probes and PCR amplification probes for detecting polynucleotides which encode such polypeptides, transgenes which encode such polypeptides, homologous targeting constructs that encode such polypeptides and/or homologously integrate in or near endogenous genes encoding such polypeptides, nonhuman transgenic animals which comprise functionally disrupted endogenous genes that normally encode such polypeptides, and transgenic nonhuman animals which comprise transgenes encoding such polypeptides. The invention also provides methods for detecting T cells (including activated T cells) in a cellular sample, methods for treating hyperactive or hypoactive T cell conditions, methods for screening for immunomodulatory agents, methods for diagnostic staging of lymphocyte differentiation, methods for producing NF-AT proteins for use as research or diagnostic reagents, methods for producing antibodies reactive with the novel polypeptides, and methods for producing transgenic nonhuman animals. Also included are methods and agents for activation of NF-AT dependent transcription, including agents which interfere with the production, modification of nuclear or cytoplasmic subunits, or the nuclear import of the cytoplasmic subunits.

US Patent:

6887842, May 3, 2005

Filed:

Nov 17, 2000

Appl. No.:

09/716841

Inventors:

Roger Briesewitz - Mountain View CA, US
Gerald R. Crabtree - Woodside CA, US
Thomas J. Wandless - Stanford CA, US

Assignee:

The Board of Trustees of the Leland Stanford Junior University - Palo Alto CA

International Classification:

A61K031/00
A61K038/00
C12N011/02
C07K001/00
C07K017/02

US Classification:

514 1, 424 941, 424 945, 435177, 514 2, 530402, 530812

Abstract:

Bifunctional molecules and methods for their use are provided. The subject bifunctional molecules are conjugates of a drug moiety and a pharmacokinetic modulating moiety, where these two moieties are optionally joined by a linking group. The bifunctional molecules are further characterized in that they exhibit at least one modulated pharmacokinetic property upon administration to a host as compared to a free drug control. The subject bifunctional molecules find use in a variety of therapeutic applications.

US Patent:

6891021, May 10, 2005

Filed:

Nov 13, 2001

Appl. No.:

10/054712

Inventors:

Gerald R. Crabtree - Woodside CA, US
Stuart L. Schreiber - Cambridge MA, US
David M. Spencer - Los Altos CA, US
Thomas J. Wandless - Cambridge MA, US
Peter Belshaw - Somerville MA, US

Assignee:

Board of Trustees of the Leland Stanford Junior University - Stanford CA
President and Fellows of Harvard College - Cambridge MA

International Classification:

C07K002/00
C07K004/00

US Classification:

530350, 530300, 435 71, 435 72

Abstract:

We have developed a general procedure for the regulated (inducible) dimerization or oligomerization of intracellular proteins and disclose methods and materials for using that procedure to regulatably initiate cell-specific apoptosis (programmed cell death) in genetically engineered cells.

US Patent:

6921531, Jul 26, 2005

Filed:

Dec 21, 2001

Appl. No.:

10/025936

Inventors:

Roger Briesewitz - Mountain View CA, US
Gerald R. Crabtree - Woodside CA, US
Thomas Wandless - Menlo Park CA, US
Gregory Thomas Ray - Stanford CA, US
Kurt William Vogel - Palo Alto CA, US

Assignee:

The Board of Trustees of the Leland Stanford Junior University - Palo Alto CA
Howard Hughes Medical Institute - Chevy Chase MD

International Classification:

A61K038/52
A61K038/00
C12N011/02
C07K001/00
C07K017/02

US Classification:

424 945, 424 941, 514 2, 514 9, 435177, 530402, 530812

Abstract:

Bifunctional molecules and methods for their use in the production of binary or tripartite complexes in a host are provided. The bifunctional molecule is a conjugate of a drug moiety and a presenter protein ligand. The molecular weight of the bifunctional molecule is less than about 5000 daltons. In the methods, an effective amount of the bifunctional molecule is administered to the host. In certain embodiments the bifunctional molecule binds to the presenter protein and a drug target to produce a tripartite complex, while in other embodiments the bifunctional molecule binds to either the presenter protein or the drug target, but not both, to produce a binary complex The subject methods and compositions find use in a variety of therapeutic applications.

US Patent:

6972193, Dec 6, 2005

Filed:

Dec 17, 1999

Appl. No.:

09/466568

Inventors:

Gerald R. Crabtree - Woodside CA, US
Stuart L. Schreiber - Boston MA, US
David M. Spencer - Houston TX, US
Thomas J. Wandless - Menlo Park CA, US
Steffan N. Ho - San Diego CA, US
Peter Belshaw - Somerville MA, US

Assignee:

Board of Trustees of Leland Stanford Junior University - Stanford CA
President and Fellows of Harvard College - Cambridge MA

International Classification:

C12N005/10
C12N015/62
C12N015/63

US Classification:

435325, 4353201, 435419, 536 234

Abstract:

Dimerization and oligomerization of proteins are general biological control mechanisms that contribute to the activation of cell membrane receptors, transcription factors, vesicle fusion proteins, and other classes of intra- and extracellular proteins. We have developed a general procedure for the regulated (inducible) dimerization or oligomerization of intracellular proteins.