Edward A Greenfield, 67160 Poskus St, Stoughton, MA 02072

6719972, Apr 13, 2004

Jun 3, 1994

08/253783

John G. Gribben - Brookline MA
Gordon J. Freeman - Brookline MA
Lee M. Nadler - Newton MA
Paul Rennert - Holliston MA
Cindy L. Jellis - Londonderry NH
Edward Greenfield - Randolph MA
Gary S. Gray - Brookline MA

Repligen Corporation - Cambridge MA
Dana-Farber Cancer Institute - Boston MA

A61K 39395

4241541, 4241301, 4241331, 4241341, 4241391, 4241411, 4241431, 4241441, 4241451, 4241531, 4241731, 5303871, 5303873, 5303879, 5303881, 5303882, 53038822, 5303887, 53038873, 53038875

Isolated ligands which bind a molecule expressed on the surface of T cells and induce antigen specific apoptosis in activated T cells are disclosed. Preferably, the T cell surface molecule is CTLA4 and the ligand is a monoclonal anti-CTLA4 antibody that binds to an epitope of CTLA4 distinct from the binding sites of B7-1 and B7-2. Upon binding of the antibody to CTLA4 on an activated T cell, in the presence of an antigenic signal, antigen specific apoptosis is induced. The invention also describes a novel natural CTLA4 ligand, distinct from B7-1 and B7-2, which mediates induction of apoptosis. Pharmaceutical compositions of anti-CTLA4 antibodies or other isolated CTLA4 ligands which can be administered to subjects to induce T cell apoptosis, thereby clonally deleting antigen specific. T cells, such as alloreactive T cells in transplantation situations or autoreactive T cells in autoimmune disorders, are also disclosed. Methods for inducing T cell apoptosis in vitro with an anti-CTLA4 antibody or other ligand of the invention together with an antigen specific signal are also disclosed, e. g.

7470428, Dec 30, 2008

Jan 30, 2003

10/354447

Vijay Kuchroo - Newton MA, US
Laurent Monney - Bulle, CH
Jason L. Gaglia - Boston MA, US
Edward A. Greenfield - Stoughton MA, US
Gordon J. Freeman - Brookline MA, US
Hanspeter Waldner - Cambridge MA, US

The Brigham and Women's Hospital, Inc. - Boston MA
Dana-Farber Cancer Institute - Boston MA

A61K 39/395

4241301, 4241391, 4241371, 514 2

The present invention provides compositions and methods useful for promoting or reducing T-cell trafficking to a target tissue. Also provided are compositions and methods useful for promoting or inhibiting antigen-presenting cell (APC) activation. The invention is related to discovery of functional characteristics of TIM-3, a molecule that is preferentially expressed on the surface of Th1 cells. The methods are useful for treating disorders including cancer, infectious disease, allergy, asthma, and autoimmune disease.

7592007, Sep 22, 2009

Dec 9, 2003

10/732847

John G. Gribben - Brookline MA, US
Gordon J. Freeman - Brookline MA, US
Lee M. Nadler - Newton MA, US
Paul Rennert - Holliston MA, US
Cindy L. Jellis - Londonderry NH, US
Edward Greenfield - Randolph MA, US
Gary S. Gray - Brookline MA, US

Dana-Farber Cancer Institute, Inc. - Boston MA
Genetics Institute, LLC - Cambridge MA

A61K 39/395
C07K 16/28

4241541, 4241301, 4241331, 4241341, 4241391, 4241411, 4241431, 4241441, 4241451, 4241531, 4241731, 5303871, 5303873, 5303881, 5303882, 53038822, 5303887, 53038873, 53038875

Isolated ligands which bind a molecule expressed on the surface of T cells and induce antigen specific apoptosis in activated T cells are disclosed. Preferably, the T cell surface molecule is CTLA4 and the ligand is a monoclonal anti-CTLA4 antibody that binds to an epitope of CTLA4 distinct from the binding sites of B7-1 and B7-2. Upon binding of the antibody to CTLA4 on an activated T cell, in the presence of an antigenic signal, antigen specific apoptosis is induced. The invention also describes a novel natural CTLA4 ligand, distinct from B7-1 and B7-2, which mediates induction of apoptosis. Pharmaceutical compositions of anti-CTLA4 antibodies or other isolated CTLA4 ligands which can be administered to subjects to induce T cell apoptosis, thereby clonally deleting antigen specific T cells, such as alloreactive T cells in transplantation situations or autoreactive T cells in autoimmune disorders, are also disclosed. Methods for inducing T cell apoptosis in vitro with an anti-CTLA4 antibody or other ligand of the invention together with an antigen specific signal are also disclosed, e. g. , for use in purging alloreactive T cells from donor bone marrow prior to bone marrow transplantation to inhibit graft versus host disease.

8101176, Jan 24, 2012

Nov 24, 2008

12/276977

Vijay K. Kuchroo - Newton Center MA, US
Laurent Monney - Cambridge MA, US
Jason L. Gaglia - Boston MA, US
Edward A. Greenfield - Stoughton MA, US
Gordon J. Freeman - Brookline MA, US
Hanspeter Waldner - Cambridge MA, US

The Brigham and Women's Hospital, Inc. - Boston MA
Dana-Farber Cancer Institute, Inc. - Boston MA

A61K 39/395

4241301, 4241391, 4241371

The present invention provides compositions and methods useful for promoting or reducing T-cell trafficking to a target tissue. Also provided are compositions and methods useful for promoting or inhibiting antigen-presenting cell (APC) activation. The invention is related to discovery of functional characteristics of TIM-3, a molecule that is preferentially expressed on the surface of Th1 cells. The methods are useful for treating disorders including cancer, infectious disease, allergy, asthma, and autoimmune disease.

2011011, May 12, 2011

Oct 22, 2010

12/910393

Samuel S. Nam - Haverhill MA, US
Edward A. Greenfield - Stoughton MA, US
Theresa L. O'Keefe - Waltham MA, US
Shixin Qin - Lexington MA, US
John Babcook - Vancouver, CA

A61K 39/395
C07K 16/40
C07H 21/00
C12N 5/10
C12P 21/00
G01N 33/573
A61P 35/00

4241331, 5303891, 5303873, 4241581, 536 2353, 435325, 435 696, 435 74

Antibodies and antigen-binding fragments of antibodies that bind GCC are disclosed. The antibodies bind an extracellular domain of GCC and can be internalized. In some embodiments, the antibodies are humanized, chimeric or human. Nucleic acids and vectors encoding the antibodies or portions thereof, recombinant cells that contain the nucleic acids, and compositions comprising the antibodies or antigen-binding fragments are also disclosed. The invention also provides therapeutic and diagnostic methods utilizing the antibodies and antigen-binding fragments provided herein.

2012031, Dec 13, 2012

Dec 20, 2011

13/331387

Vijay K. Kuchroo - Newton Center MA, US
Laurent Monney - Bulle, CH
Jason L. Gaglia - Boston MA, US
Edward A. Greenfield - Stoughton MA, US
Gordon J. Freeman - Brookline MA, US
Hanspeter Waldner - Lemoyne PA, US

DANA-FARBER CANCER INSTITUTE, INC. - Boston MA
THE BRIGHAM AND WOMEN'S HOSPITAL, INC. - Boston MA

A61K 39/395
C12N 5/0783

4241721, 435375

The present invention provides compositions and methods useful for promoting or reducing T-cell trafficking to a target tissue. Also provided are compositions and methods useful for promoting or inhibiting antigen-presenting cell (APC) activation. The invention is related to discovery of functional characteristics of TIM-3, a molecule that is preferentially expressed on the surface of Th1 cells. The methods are useful for treating disorders including cancer, infectious disease, allergy, asthma, and autoimmune disease.

6130316, Oct 10, 2000

Jul 26, 1994

8/280757

Gordon J. Freeman - Brookline MA
Lee M. Nadler - Newton MA
Gary S. Gray - Brookline MA
Edward Greenfield - Randolph MA

Dana Farber Cancer Institute - Boston MA
Replingen Corporation - Cambridge MA

C07K 1900
C07K 14705
C07H 2100

530350

Nucleic acids encoding novel CTLA4/CD28 ligands which costimulate T cell activation are disclosed. In one embodiment, the nucleic acid has a sequence which encodes a B lymphocyte antigen, B7-2. Preferably, the nucleic acid is a DNA molecule comprising at least a portion of a nucleotide sequence shown in FIG. 8, SEQ ID NO:1 or FIG. 14, SEQ ID NO:23. The nucleic acid sequences of the invention can be integrated into various expression vectors, which in turn direct the synthesis of the corresponding proteins or peptides in a variety of hosts, particularly eukaryotic cells, such as mammalian and insect cell culture. Also disclosed are host cells transformed to produce proteins or peptides encoded by the nucleic acid sequences of the invention and isolated proteins and peptides which comprise at least a portion of a novel B lymphocyte antigen. Proteins and peptides described herein can be administered to subjects to enhance or suppress T cell-mediated immune responses.

6207156, Mar 27, 2001

Mar 18, 1998

9/040953

Vijay K. Kuchroo - Newton MA
Edward A. Greenfield - Stoughton MA

Brigham and Women's Hospital, Inc. - Boston MA

A61K39/395
7
C07K16/28
7
C12N5/12

4241541

The present invention relates to methods and products for immunotherapy resulting in the stimulation of T-cell proliferation. The products of the invention are peptides that bind to CTLA-4 and co-stimulate the proliferation of T-cells by inhibiting the binding of B7 to CTLA-4. Pharmaceutical compositions including such peptides are also provided. The invention further provides in vitro and in vivo therapeutic methods employing the peptides of the invention.