T Cell Sciences, Inc.

Harvard College

University of Mississippi

The Johns Hopkins University

The Brigham and Women's Hospital, Inc.

Dana-farber-cancer Institute Inc.

Astra Ab

Avant Immunotherapeutics, Inc.

T Cell Diagnostics, Inc.

Other

Dana Farber Cancer Institute & T Cell Diagnostics, Inc.

Stephen H Ip

Patrick C Kung

Henry C Marsh

Jack L Strominger

Michael B Brenner

Michael S Krangel

Michael F Concino

Barton J Bradbury

Lloyd B Klickstein

Douglas T Fearon

Savvas C Makrides

Gerald R Carson

Robert D Sindelar

Winnie W Wong

Charles William Rittershaus

Wei-Tao Tian

Nancy L Wood

Mary Ellen Snider

Jone-Long Ko

Robert V Skibbens

Larry D Henry

Michael C Brown

Teodoro S Kaufman

Chew Lee

Jonathan G Seidman

Johnathan Seidman

Teodoro Kaufman

Henry C Marsh, Jr

John G Seidman

Henry Clinton Marsh, Jr

Linda A McKeen

Hamid Band

Linda A MacKeen

Linda A Mackeen

The present invention relates to the C3b/C4b receptor (CR1) gene and its encoded protein. The invention also relates to CR1 nucleic acid sequences and fragments thereof comprising 70 nucleotides and their encoded peptides or proteins comprising 24 amino acids. The invention further provides for the expression of the CR1 protein and fragments thereof. The genes and proteins of the invention have uses in diagnosis and therapy of disorders involving complement activity, and various immune system or inflammatory disorders. In specific embodiments of the present invention detailed in the examples sections infra, the cloning, nucleotide sequence, and deduced amino acid sequence of a full-length CR1 cDNA and fragments thereof are described. The expression of the CR1 protein and fragments thereof is also described. Also described is the expression of a secreted CR1 molecule lacking a transmembrane region. The secreted CR1 molecule is shown to be useful in reducing damage caused by inflammation and in reducing myocardial infarct size and preventing reperfusion injury.

Human C3b/C4b receptor (CR1)

The present invention provides purified polypeptides which comprise at least a portion of a &dgr; T cell receptor polypeptide, a &ggr; T cell receptor polypeptide, a &ggr;, &dgr; T cell receptor complex or a &ggr;, &ggr; T cell receptor complex. Substances capable of forming complexes with these polypeptides are also provided. Additionally, methods for detecting T cells which have within them or on their surfaces a polypeptide of the present invention are provided. Moreover, methods for diagnosing immune system abnormalities are provided which comprise measuring in a sample from a subject the number of T cells which have within them or on their surfaces a polypeptide of the present invention.

&ggr;, &dgr; T cell receptor and methods for detection

The present invention relates to monoclonal antibodies which recognize defined regions of the T-cell receptor (TCR). In a specific embodiment, the invention provides monoclonal antibodies which are reactive with a constant region of the alpha chain of the TCR. In particular embodiments, the invention relates to two monoclonal antibodies, termed &agr;F1 and &agr;F2, which react with two different epitopes on the framework region of the &agr; monomer of the TCR molecule. In another specific embodiment, the invention is directed to monoclonal antibodies reactive with a variable region of the beta chain of the TCR. In particular, the invention provides two monoclonal antibodies, termed W112 and 2D1, which react with &bgr; chain variable regions V&bgr;5.3 and V&bgr;8.1, respectively. In another specific embodiment, the invention is directed to monoclonal antibodies reactive with a variable region of the delta chain of the TCR. In particular, the invention provides monoclonal antibody &dgr;TCS1, isotype IgG2a. The monoclonal antibodies of the invention have value in diagnosis and therapy and are useful tools for study of the immune system.

Monoclonal antibodies reactive with defined regions of the T cell antigen receptor

The present invention relates to monoclonal antibodies which recognize defined regions of the T-cell receptor (TCR). In a specific embodiment, the invention provides monoclonal antibodies which are reactive with a constant region of the alpha chain of the TCR. In particular embodiments, the invention relates to two monoclonal antibodies, termed .alpha.F1 and .alpha.F2, which react with two different epitopes on the framework region of the .alpha. monomer of the TCR molecule. In another specific embodiment, the invention is directed to monoclonal antibodies reactive with a variable region of the beta chain of the TCR. In particular, the invention provides two monoclonal antibodies, termed W112 and 2D1, which react with .beta. chain variable regions V.beta.5.3 and V.beta.8.1, respectively. In another specific embodiment, the invention is directed to monoclonal antibodies reactive with a variable region of the delta chain of the TCR. In particular, the invention provides monoclonal antibody .delta.TCS1, isotype IgG2a. The monoclonal antibodies of the invention have value in diagnosis and therapy and are useful tools for study of the immune system.

Monoclonal antibodies reactive with defined regions of the T cell

The present invention relates to the C3b/C4b receptor (CR1) gene and its encoded protein. The invention further provides for the expression of the CR1 protein and fragments thereof. The genes and proteins of the invention have uses in diagnosis and therapy of disorders involving complement activity, and various immune system or inflammatory disorders. In specific embodiments of the present invention detailed in the examples sections infra, the cloning, nucleotide sequence, and deduced amino acid sequence of a full-length CR1 cDNA and fragments thereof are described. The expression of the CR1 protein and fragments thereof is also described. Also described is the expression of a secreted CR1 molecule lacking a transmembrane region. The secreted CR1 molecule is shown to be useful in reducing damage caused by inflammation and in reducing myocardial infarct size and preventing reperfusion injury.

Human complement receptor type 1 (CR1). Nucleic acid molecules encoding full-length CR1 protein and fragments thereof having complement regulatory activity are described, as well as recombinant CR1 protein and polypeptides, vectors for their expression, and cell lines expressing or bearing DNA molecules encoding such proteins and polypeptides, including a soluble CR1 polypeptide consisting of the extracellular 30 short consensus repeat domains of the mature CR1 protein. The nucleic acids and polypeptides described are useful in diagnosis and treatment of disorders involving complement activity and inflammation. Compositions useful in therapeutic applications are also disclosed.

The present invention is directed to compounds which suppress immune responses and/or selectively inhibit complement. These compounds contain an aromatic ring and are substituted dihydrobenzofurans, spirobenzofuran-2(3H)-cycloalkanes, and their open chain intermediates. The compounds of the present invention, and the pharmaceutically acceptable salts thereof, interrupt the proteolytic processing of C5 to bioactive components, exhibit immunosuppressive activities, and have therapeutic utility in the amelioration of disease and disorders mediated by complement and/or immune activity.

Compounds that inhibit complement and/or suppress immune activity

The present invention is directed to compounds which suppress immune responses and/or selectivly inhibit complement. These compounds contain an aromatic ring and are substituted dihydrobenzofurans, spirobenzofuran-2(3H)-cycloalkanes, and their open chain intermediates. The compounds of the present invention, and the phamaceutically acceptable salts thereof, interrupt the proteolytic processing of C5 to bioactive components, exhibit immunosuppressive activites, and have therapeutic utility in the amelioration of disease and disorders mediated by complement and/or immune activity.

Compounds which inhibit complement and/or suppress immune activity

The present invention provides purified polypeptides which comprise at least a portion of a .delta. T cell receptor polypeptide, a .gamma. T cell receptor polypeptide, a .gamma., .delta. T cell receptor complex or a .gamma., .gamma. T cell receptor complex. Substances capable of forming complexes with these polypeptides are also provided. Additionally, methods for detecting T cells which have within them or on their surfaces a polypeptide of the present invention are provided. Moreover, methods for diagnosing immune system abnormalities are provided which comprise measuring in a sample from a subject the number of T cells which have within them or on their surfaces a polypeptide of the present invention.

.gamma., .delta. T cell receptor and methods for detection

Method of treating complement mediated disorders

Cell-free or released T cell antigen receptors, immunoassays which allow the detection of the released T cell antigen receptor in cell culture supernatants, cell lysates, and biological fluids, as well as diagnostic and therapeutic compositions and methods for monitoring and treating certain diseases or disorders which elicit or involve a T cell response are described. The released T cell antigen receptors described herein differ from the cell membrane bound antigen receptors and appear to exist in a variety of forms, some of which may be complexed with other T cell determinants such as the T3 antigen. Despite the size heterogeneity of the released T cell antigen receptors or receptor/complexes, these may be reliably identified using anti-receptor antibodies, including, but not limited to, anti-major framework, anti-minor frarmework and anti-clonotypic antibodies which define particular epitopes of the released T cell receptor or receptor/complex. The immunoassays described herein may be used to test for the presence of the released receptor or receptor/complex in biological samples and may be used to diagnose or monitor patients with disorders or diseases that elicit or involve T cell response who exhibit elevated serum level of the receptor or receptor/complex. In addition, the cell free T cell antigen receptors themselves may be used diagnostically and/or therapeutically for diseases or conditions that are not easily addressed using immunoglobulins.

Cell free T cell antigen receptor beta chain and its clinical utilities

Growing community of inventors

Sudbury, MA, United States of America

Stephen H Ip