Christopher V Nicchitta

US Patent:

7598355, Oct 6, 2009

Filed:

Aug 1, 2002

Appl. No.:

10/210333

Inventors:

Christopher V. Nicchitta - Durham NC, US
James J. Wassenberg - Durham NC, US
Robyn C. Reed - Durham NC, US

Assignee:

Duke University - Durham NC

International Classification:

C07K 1/22

US Classification:

530413, 530412, 530417, 530415, 530350

Abstract:

The present invention discloses characterization of interactions between ligands and Hsp90 proteins, including GRP94, wherein ligand binding to the N-terminal nucleotide binding domain of GRP94 elicits a conformational change that converts the GRP94 from an inactive to an active conformation, and wherein the chaperone and peptide-binding activities of the GRP94 are markedly stimulated. Also disclosed are purification, screening, and therapeutic methods pertaining to the biological activity of GRP94, and in some instances HSP90, based upon the characterization of ligand interactions of Hsp90 peptide-binding proteins, including GRP94.

US Patent:

7691969, Apr 6, 2010

Filed:

Sep 30, 2002

Appl. No.:

10/260104

Inventors:

Daniel T. Gewirth - Durham NC, US
Christopher V. Nicchitta - Durham NC, US

Assignee:

Duke University - Durham NC

International Classification:

C07K 14/00
G01N 31/00

US Classification:

530350, 436 4

Abstract:

An isolated GRP94 ligand binding domain polypeptide, a three-dimensional crystal structure of the same, and methods of using the same to design modulators of Hsp90 proteins.

US Patent:

7991601, Aug 2, 2011

Filed:

Apr 5, 2010

Appl. No.:

12/754423

Inventors:

Daniel T. Gewirth - Buffalo NY, US
Christopher V. Nicchitta - Durham NC, US

Assignee:

Duke University - Durham NC

International Classification:

G06G 7/58
G01N 23/00

US Classification:

703 11, 702 19

Abstract:

An isolated GRP94 ligand binding domain polypeptide, a three-dimensional crystal structure of the same, and methods of using the same to design modulators of Hsp90 proteins.

US Patent:

8404805, Mar 26, 2013

Filed:

Oct 5, 2009

Appl. No.:

12/573618

Inventors:

Christopher V. Nicchitta - Durham NC, US
James J. Wassenberg - Durham NC, US
Robyn C. Reed - Durham NC, US

Assignee:

Duke University - Durham NC

International Classification:

C07K 14/435

US Classification:

530350, 5142631

Abstract:

The presently disclosed subject matter discloses characterization of interactions between ligands and Hsp90 proteins, including GRP94, wherein ligand binding to the N-terminal nucleotide binding domain of GRP94 elicits a conformational change that converts the GRP94 from an inactive to an active conformation, and wherein the chaperone and peptide-binding activities of the GRP94 are markedly stimulated. Also disclosed are purification, screening, and therapeutic methods pertaining to the biological activity of GRP94, and in some instances HSP90, based upon the characterization of ligand interactions of Hsp90 peptide-binding proteins, including GRP94.

US Patent:

20020058609, May 16, 2002

Filed:

Feb 26, 1999

Appl. No.:

09/261473

Inventors:

ELI GILBOA - DURHAM NC, US
SMITA K. NAIR - DURHAM NC, US
CHRISTOPHER V. NICCHITTA - DURHAM NC, US

International Classification:

A01N037/18
A61K038/00
A61K039/00
C07K002/00
C07K004/00
C07K005/00
C07K007/00
C07K014/00
C07K016/00
C07K017/00
C07K001/00

US Classification:

514/002000, 530/300000, 530/350000

Abstract:

A method of eliciting an immune response in a vertebrate subject. The method includes the administration to a vertebrate subject of a composition including an amount of a purified complex including calreticulin bound to an antigenic molecule to elicit an immune response to the antigenic molecule in the vertebrate subject. Therapeutic methods, compositions and kits are also disclosed wherein the elicited immune response is utilized as a treatment for cancer and for infectious diseases.

US Patent:

20020160496, Oct 31, 2002

Filed:

Oct 1, 2001

Appl. No.:

09/968436

Inventors:

Daniel Gewirth - Durham NC, US
Christopher Nicchitta - Durham NC, US

International Classification:

C12N009/64
C07H021/04
C12P021/02
C12N005/06

US Classification:

435/226000, 435/320100, 435/325000, 435/069100, 536/023200

Abstract:

An isolated GRP94 ligand binding domain polypeptide, an isolated polynucleotide encoding the same, and methods of using the same to identify modulators of Hsp90 proteins.

US Patent:

20030216315, Nov 20, 2003

Filed:

Feb 13, 2003

Appl. No.:

10/367093

Inventors:

Christopher Nicchitta - Durham NC, US
Julie Baker-LePain - Durham NC, US

Assignee:

Duke University

International Classification:

A61K038/17
C07K014/71

US Classification:

514/012000, 530/350000

Abstract:

A recombinant stress response polypeptide that lacks an antigen binding domain, and methods for using the recombinant stress response polypeptide to elicit an immune response, for example an anti-tumor response, in a subject.

US Patent:

20080160636, Jul 3, 2008

Filed:

Jun 22, 2007

Appl. No.:

11/821459

Inventors:

Daniel T. Gewirth - Durham NC, US
Christopher V. Nicchitta - Durham NC, US

Assignee:

Duke University - Durham NC

International Classification:

G01N 33/566
C07K 14/00
C07K 16/18

US Classification:

436501, 530350, 5303879, 5303873

Abstract:

An isolated GRP94 ligand binding domain polypeptide. In some embodiments, the isolated GRP94 ligand binding domain polypeptide includes (a) an amino acid sequence encoded by a nucleic acid molecule that includes a nucleotide sequence selected from among: (i) nucleotides 310-1116 of SEQ ID NO: 1; (ii) nucleotides 142-948 of SEQ ID NO: 3; (iii) nucleotides 142-948 of SEQ ID NO: 5; and (iv) an amino acid sequence encoded by a nucleotide sequence at least 95% identical to any of (i)-(iii); (b) an amino acid sequence selected from among (v) amino acids 69-337 of SEQ ID NO: 2; (vi) amino acids 48-316 of SEQ ID NO: 4; (vii) amino acids 48-316 of SEQ ID NO: 6; and (viii) an amino acid sequence at least 95% identical to any of (iv)-(vi); or (c) an amino acid sequence that is immunologically cross-reactive with an antibody that specifically binds to a polypeptide consisting of an amino acid sequence as set forth in any one of (a) and (b), wherein the GRP94 ligand binding domain (LBD) polypeptide binds a GRP94 ligand selected from the group consisting of 4,4′-dianilino-1,1-binaphthyl-5,5-disulfonic acid (bis-ANS) and N-ethylcarboxamidoadenosine (NECA). Also disclosed are isolated polynucleotides encoding the disclosed polypeptides and methods of using the same to identify modulators of Hsp90 proteins.