Patents by Inventor Gary S. Gray
Gary S. Gray has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Publication number: 20040202650Abstract: 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.Type: ApplicationFiled: December 9, 2003Publication date: October 14, 2004Inventors: John G. Gribben, Gordon J. Freeman, Lee M. Nadler, Paul D. Rennert, Cindy L. Jellis, Edward Greenfield, Gary S. Gray
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Publication number: 20040151725Abstract: CTLA4-immunoglobulin fusion proteins having modified immunoglobulin constant region-mediated effector functions, and nucleic acids encoding the fusion proteins, are described. The CTLA4-immunoglobulin fusion proteins comprise two components: a first peptide having a CTLA4 activity and a second peptide comprising an immunoglobulin constant region which is modified to reduce at least one constant region-mediated biological effector function relative to a CTLA4-IgG1 fusion protein. The nucleic acids of the invention can be integrated into various expression vectors, which in turn can direct the synthesis of the corresponding proteins in a variety of hosts, particularly eukaryotic cells. The CTLA4-immunoglobulin fusion proteins described herein can be administered to a subject to inhibit an interaction between a CTLA4 ligand (e.g., B7-1 and/or B7-2) on an antigen presenting cell and a receptor for the CTLA4 ligand (e.g.Type: ApplicationFiled: March 2, 2004Publication date: August 5, 2004Inventors: Gary S. Gray, Jerry Carson, Kashi Javaherian, Cindy L. Jellis, Paul D. Rennert, Sandra Silver
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Publication number: 20040126781Abstract: Method of inhibiting and diagnosing spontaneous abortion in a subject are provided. The subject methods are based, inter alia, on the administration of an agent that inhibits a costimulatory signal in a T cell such that spontaneous abortion in the subject is inhibited. The subject methods are also based on the levels of adhesion molecules, inflammatory cytokines, and immune cell surface molecules which are altered in spontaneous abortion.Type: ApplicationFiled: June 27, 2003Publication date: July 1, 2004Applicant: GENETICS INSTITUTE, INC.Inventors: Vincent Ling, Gary S. Gray, James C. Keith, Srinivas Maganti
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Patent number: 6750334Abstract: CTLA4-immunoglobulin fusion proteins having modified immunoglobulin constant region-mediated effector functions, and nucleic acids encoding the fusion proteins, are described. The CTLA4-immunoglobulin fusion proteins comprise two components: a first peptide having a CTLA4 activity and a second peptide comprising an immunoglobulin constant region which is modified to reduce at least one constant region-mediated biological effector function relative to a CTLA4-IgG1 fusion protein. The nucleic acids of the invention can be integrated into various expression vectors, which in turn can direct the synthesis of the corresponding proteins in a variety of hosts, particularly eukaryotic cells. The CTLA4-immunoglobulin fusion proteins described herein can be administered to a subject to inhibit an interaction between a CTLA4 ligand (e.g., B7-1 and/or B7-2) on an antigen presenting cell and a receptor for the CTLA4 ligand (e.g.Type: GrantFiled: February 2, 1996Date of Patent: June 15, 2004Assignee: Repligen CorporationInventors: Gary S. Gray, Jerry Carson, Kashi Javaherian, Cindy L. Jellis, Paul D. Rennert, Sandra Silver
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Patent number: 6723705Abstract: Tumor cells modified to express one or more T cell costimulatory molecules are disclosed. Preferred costimulatory molecules are B7-2 and B7-3. The tumor cells of the invention can be modified by transfection with nucleic acid encoding B7-2 and/or B7-3, by using an agent which induces or increases expression of B7-2 and/or B7-3 on the tumor cell or by coupling B7-2 and/or B7-3 to the tumor cell. Tumor cells modified to express B7-2 and/or B7-3 can be further modified to express B7. Tumor cells further modified to express MHC class I and/or class II molecules or in which expression of an MHC associated protein, the invariant chain, is inhibited are also disclosed. The modified tumor cells of the invention can be used in methods for treating a patient with a tumor, preventing or inhibiting metastatic spread of a tumor or preventing or inhibiting recurrence of a tumor.Type: GrantFiled: December 7, 1998Date of Patent: April 20, 2004Assignee: Gentics Institute, Inc.Inventors: Gordon J. Freeman, Lee M. Nadler, Gary S. Gray
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Patent number: 6719972Abstract: 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.Type: GrantFiled: June 3, 1994Date of Patent: April 13, 2004Assignees: Repligen Corporation, Dana-Farber Cancer InstituteInventors: John G. Gribben, Gordon J. Freeman, Lee M. Nadler, Paul Rennert, Cindy L. Jellis, Edward Greenfield, Gary S. Gray
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Publication number: 20040001829Abstract: Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR)/CD3 complex or the CD2 surface protein. To induce proliferation of an activated population T cells, an accessory molecule on the surface of the T cells, such as CD28, is stimulated with a ligand which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.Type: ApplicationFiled: March 17, 2003Publication date: January 1, 2004Inventors: Carl H. June, Craig B. Thompson, Gary J. Nabel, Gary S. Gray, Paul D. Rennert
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Patent number: 6613327Abstract: Methods of inhibiting and diagnosing spontaneous abortion in a subject are provided. The subject methods are based, inter alia, on the administration of an agent that inhibits a CD28-C mediated costimulatory signal in a T cell such that spontaneous abortion in the subject is inhibited. The subject methods are also based on the levels of adhesion molecules, inflammatory cytokines, and immune cell surface molecules which are altered in spontaneous abortion.Type: GrantFiled: July 28, 2000Date of Patent: September 2, 2003Assignee: Genetics Institute, Inc.Inventors: Vincent Ling, Gary S. Gray, James C. Keith, Srinivas Maganti
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Publication number: 20030161827Abstract: The invention provides methods for downmodulating the immune response in a subject undergoing transplantation comprising administering to the subject at least one antibody that recognizes a B7 antigen according to specific treatment protocols.Type: ApplicationFiled: September 5, 2002Publication date: August 28, 2003Inventors: Abbie Cheryl Celnicker, Gary S. Gray, Stuart Friedrich, Allan Kirk, Garvin Warner, Bernard Hausen, Randall E. Morris
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Therapeutic compositions for inhibiting the interactions of B7-1 and B7-2 with their natural ligands
Patent number: 6605279Abstract: Disclosed is a composition for inhibiting the interactions of B7-1 and B7-2 with their natural ligands. Such compositions comprise an antibody specific for B7-2 and an antibody specific for B7-1, in a pharmaceutically acceptable carrier. The composition may be formulated for either separate or combined administration of the antibody components. The antibodies may be monoclonal antibodies, or humanized antibodies. Preferred antibodies are disclosed.Type: GrantFiled: October 22, 1999Date of Patent: August 12, 2003Assignees: Genetics Institute, Inc., Dana-Farber Cancer InstituteInventors: Gordon J. Freeman, Lee M. Nadler, Gary S. Gray -
Publication number: 20030099643Abstract: Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR)/CD3 complex or the CD2 surface protein. To induce proliferation of an activated population T cells, an accessory molecule on the surface of the T cells, such as CD28, is stimulated with a ligand which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.Type: ApplicationFiled: July 8, 1999Publication date: May 29, 2003Inventors: CARL H. JUNE, CRAIG B. THOMPSON, GARY J. NABEL, GARY S. GRAY, PAUL D. RENNERT
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Publication number: 20030054371Abstract: The invention relates to polymorphic markers within the costimulatory receptor gene locus. These markers are characterized by sets of oligonucleotide primers according to the invention useful in PCR amplification and DNA segment resolution.Type: ApplicationFiled: February 27, 2002Publication date: March 20, 2003Applicant: Genetics Institute, Inc.Inventors: Vincent Ling, Paul Wu, Gary S. Gray
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Patent number: 6534055Abstract: Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR)/CD3 complex or the CD2 surface protein. To induce proliferation of an activated population T cells, an accessory molecule on the surface of the T cells, such as CD28, is stimulated with a ligand which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.Type: GrantFiled: May 4, 1995Date of Patent: March 18, 2003Assignee: Genetics Institute, Inc.Inventors: Carl H. June, Craig B. Thompson, Gary J. Nabel, Gary S. Gray, Paul D. Rennert
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Publication number: 20020176855Abstract: The invention relates to a humanized anti-B7-2 antibody that comprises a variable region of nonhuman origin and at least a portion of an immunoglobulin of human origin. The invention also pertains to methods of treatment for various autoimmune diseases, transplant rejection, inflammatory disorders and infectious diseases by administering humanized anti-B7-2 and/or anti-B7-1 antibodies.Type: ApplicationFiled: February 12, 1999Publication date: November 28, 2002Inventors: MAN SUNG CO, MAXIMILIANO VASQUEZ, BEATRIZ CARRENO, ABBIE CHERYL CELNIKER, MARY COLLINS, SAMUEL GOLDMAN, GARY S. GRAY, ANDREA KNIGHT, DENISE O'HARA, BONITA RUP, GEERTRUIDA M. VELDMAN
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Patent number: 6444792Abstract: CTLA4-immunoglobulin fusion proteins having modified immunoglobulin constant region-mediated effector functions, and nucleic acids encoding the fusion proteins, are described. The CTLA4-immunoglobulin fusion proteins comprise two components: a first peptide having a CTLA4 activity and a second peptide comprising an immunoglobulin constant region which is modified to reduce at least one constant region-mediated biological effector function relative to a CTLA4-IgG1 fusion protein. The nucleic acids of the invention can be integrated into various expression vectors, which in turn can direct the synthesis of the corresponding proteins in a variety of hosts, particularly eukaryotic cells. The CTLA4-immunoglobulin fusion proteins described herein can be administered to a subject to inhibit an interaction between a CTLA4 ligand (e.g., B7-1 and/or B7-2) on an antigen presenting cell and a receptor for the CTLA4 ligand (e.g.Type: GrantFiled: January 8, 1999Date of Patent: September 3, 2002Assignee: Repligen CorporationInventors: Gary S. Gray, Jerry Carson, Kashi Javaherian, Paul D. Rennert, Sandra Silver
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Publication number: 20020115214Abstract: Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR)/CD3 complex or the CD2 surface protein. To induce proliferation of an activated population T cells, an accessory molecule on the surface of the T cells, such as CD28, is stimulated with a ligand which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.Type: ApplicationFiled: January 26, 1996Publication date: August 22, 2002Inventors: CARL H. JUNE, CRAIG B. THOMPSON, GARY J. NABEL, GARY S. GRAY, PAUL D. RENNERT
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Publication number: 20020114814Abstract: CTLA4-immunoglobulin fusion proteins having modified immunoglobulin constant region-mediated effector functions, and nucleic acids encoding the fusion proteins, are described. The CTLA4-immunoglobulin fusion proteins comprise two components: a first peptide having a CTLA4 activity and a second peptide comprising an immunoglobulin constant region which is modified to reduce at least one constant region-mediated biological effector function relative to a CTLA4-IgG1 fusion protein. The nucleic acids of the invention can be integrated into various expression vectors, which in turn can direct the synthesis of the corresponding proteins in a variety of hosts, particularly eukaryotic cells. The CTLA4-immunoglobulin fusion proteins described herein can be administered to a subject to inhibit an interaction between a CTLA4 ligand (e.g., B7-1 and/or B7-2) on an antigen presenting cell and a receptor for the CTLA4 ligand (e.g.Type: ApplicationFiled: December 20, 2001Publication date: August 22, 2002Inventors: Gary S. Gray, Jerry Carson, Kashi Javaherian, Paul D. Rennert, Sandra Silver
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Publication number: 20020086414Abstract: 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.Type: ApplicationFiled: October 22, 1999Publication date: July 4, 2002Inventors: GORDON J. FREEMAN, LEE M. NADLER, GARY S. GRAY
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Publication number: 20020076407Abstract: Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR)/CD3 complex or the CD2 surface protein. To induce proliferation of an activated population T cells, an accessory molecule on the surface of the T cells, such as CD28, is stimulated with a ligand which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.Type: ApplicationFiled: October 29, 1998Publication date: June 20, 2002Inventors: CARL H. JUNE, CRAIG B. THOMPSON, GARY J. NABEL, GARY S. GRAY, PAUL D. RENNERT, GORDON J. FREEMAN
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Publication number: 20020039581Abstract: The invention provides an antibody-toxic moiety conjugates comprising an antibody that specifically recognizes a molecule expressed on the surface of a T cell which is expressed only on T cells and is only expressed transiently on T cells upon T cell activation. Preferably, the T cell molecule is CTLA4. The invention further provides anti-CTLA4 antibodies and humanized forms thereof.Type: ApplicationFiled: January 26, 2001Publication date: April 4, 2002Inventors: Beatriz M. Carreno, Clive Wood, Katherine Turner, Mary Collins, Gary S. Gray, Donna Morris, Denise O'Hara, Paul R. Hinton, Naoya Tsurushita