Bristol-myers Squibb Compnay

The General Hospital Corporation

Duke University

Other

Dartmouth College

Emory University

Bristol-myers Squibb

Alejandro A Aruffo

Jeffrey A Ledbetter

Anthony W Siadak

Brian Seed

Randolph J Noelle

Jurgen Bajorath

Diane Hollenbaugh

Barton F Haynes

Peter S Linsley

Teresa M Foy

Michael A Bowen

Dhavalkumar D Patel

Barbara A Thorne

Diane L Hollenbaugh

Linda Harris

Karen K Berry

Alain Martel

Nitin Krishnaji Damle

Jacques Banville

Hans Marquardt

David Camerini

David Simmons

Ivan Stamenkovic

Jeffry Dean Watkins

Siegfried Stengelin

William D Huse

Mark A Kay

Herren Wu

Lieping Chen

Karl E Hellstrom

Ingegerd E Hellstrom

Lisa K Gilliland

Gary L Schieven

H Perry Fell

Christian P Larsen

Leander Lauffer

Robert S Mittler

Thomas C Pearson

Walter W Shuford

Kelly L Bennett

John E Skonier

Janet Allen

Carmen Oquendo

Martine Amiot

Christopher B Wilson

John Marken

Marcia L Gordon

Linda J Harris

John A Gebe

N Jan Chalupny

Dale L Bodian

Gary C Starling

Edith A Wolff

Brad W Greenfield

A simple and highly efficient method for cloning cDNAs including CD27 (SEQ ID NO:28) from mammalian expression libraries based on transient expression in mammalian host cells has been discovered. Novel expression vectors allowing highly efficient construction of mammalian cDNA libraries are disclosed. The cloning method of the invention which has been used to clone genes for cell surface antigens of human lymphocytes, has general application in gene cloning. Cell surface antigens cloned according to the present invention have been purified, and the nucleotide and amino acid sequences determined. These antigens have diagnostic and therapeutic utility in immune-mediated infections in mammals, including humans.

Rapid immunoselection cloning method

Novel articifial proteoglycans containing a GAG assembly site and a control sequence required for assembly, method for enhancing the biological activity of a glycosaminoglycan binding protein using artificial proteoglycans, DNA constructs of artificial proteoglycans. The artificial proteoglycans of the present invention are useful for preparations of adjuvants for vaccination, for targeting of chemokines to non-immunogenic tumor cells to enhance cellular anti-tumor response, for preparations designed to help promote wound healing, and for treatment of immunological disorders,including rheumatoid arthritis, asthma, chronic obstructive pulmonary disorder, Lupus, inflammatory bowel disease, psoriasis, osteoarthritis, and HIV infection.

Artificial proteoglycans

The present invention relates to a counter-receptor, termed CD40CR, for the CD40 B-cell antigen, and to soluble ligands for this receptor, including fusion molecules comprising at least a portion of CD40 protein. It is based, at least in part, on the discovery that a soluble CD40/immunoglobulin fusion protein was able to inhibit helper T-cell mediated B-cell activation by binding to a novel 39 kD protein receptor on helper T-cell membranes. The present invention provides for a substantially purified CD40CR receptor; for soluble ligands of CD40CR, including antibodies as well as fusion molecules comprising at least a portion of CD40 protein; and for methods of controlling B-cell activation which may be especially useful in the treatment of allergy or autoimmune disease.

CD40 receptor ligands

A method for the treatment of T cell mediated disorders is described. The method involves administering to a subject a therapeutically effective amount of an anti-human CD40 antibody. Disease states suitable for treatment with this method include graft versus host disease and transplant rejection and auto immune disease such as type I diabetes, psoriasis, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and myesthenia gravis.

Methods of using antibodies against human CD40

The present invention relates to a counter-receptor, termed CD40CR, for the CD40 B-cell antigen, and to soluble ligands for this receptor, including fusion molecules comprising at least a portion of CD40 protein. It is based, at least in part, on the discovery that a soluble CD40/immunoglobulin fusion protein or antibody specific for gp39 on T cells was able to inhibit helper T-cell mediated B-cell activation by binding to a novel 39 kD protein receptor on helper T-cell membranes. The present invention provides for a substantially purified CD40CR receptor; for soluble ligands of CD40CR, including antibodies as well as fusion molecules comprising at least a portion of CD40 protein; and for methods of controlling B-cell activation which may be especially useful in the treatment of allergy or autoimmune disease, including graft-versus-host disease and rheumatoid arthritis.

Inhibiting B cell activation with soluble CD40 or fusion proteins thereof

The invention provides antibodies and other binding agents that bind specifically to SRCR domains of human CD6 (hCD6) and have advantageous properties, including the capacity to substantially inhibit binding of activated leukocyte adhesion molecule (ALCAM) to hCD6. The binding agents of the invention are useful, inter alia, in methods for screening peptides and drugs that also bind to hCD6 and/or modulate ALCAM binding to hCD6, as well as in diagnostic and therapeutic methods for management and treatment of inflammatory and autoimmune diseases.

Monoclonal antibodies to human CD6

The Applicants have discovered humanized anti-human CD40 antibodies which block the interaction between gp39 and CD40. The anti-CD40 antibodies of the present invention are effective in modulating humoral immune responses against T cell-dependent antigens, collagen induced arthritis, and skin transplantation, and are also useful for their anti-inflammatory properties.

Antibodies against human CD40

A method of treating graft-vs-host diseases by administration of bone marrow and an anti-gp39 antibody specific to human gp39 is provided.

Method of treating graft-versus-host disease with anti-GP39 antibodies and bone marrow cells

A simple and highly efficient method for cloning cDNAs from mammalian expression libraries based on transient expression in mammalian host cells has been discovered. Novel expression vectors allowing highly efficient construction of mammalian cDNA libraries are disclosed. The cloning method of the invention which has been used to clone genes for cell surface antigens of human lymphocytes, has general application in gene cloning. Cell surface antigens cloned according to the present invention have been purified, and the nucleotide and amino acid sequences determined. These antigens have diagnostic and therapeutic utility in immune-mediated infections in mammals, including humans.

Nucleic acid encoding CD28

The instant invention discloses the unexpected result that two anti-4-1BB monoclonal antibodies can inhibit both primary and secondary humoral responses to at least T-cell dependent antigens in vivo. Such antibodies provide a novel approach to immunosuppression and cancer therapy in vivo.

Methods and compositions for immunomodulation

The Applicants have discovered a novel antibody, more specifically a chimerized anti-human CD40 monoclonal antibody, which blocks the interaction between gp39 and CD40. The anti-CD40 antibodies of the present invention are effective in modulating humoral immune responses against T cell-dependent antigens, collagen induced arthritis, and skin transplantation, and are also useful for their anti-inflammatory properties.

A new polypeptide from the scavenger receptor cysteine-rich family, termed Sp.alpha. herein, as well as polynucleotides encoding Sp.alpha. and methods of recombinantly producing the same, are disclosed. In addition, antibodies reactive with Sp.alpha. are provided, as are methods of using antibodies that bind to Sp.alpha. for modulating the interaction between Sp.alpha. and its receptor. Immunoassay kits containing the anti-Sp.alpha. antibodies are also provided.

Sp.alpha.: a novel scavenger receptor cysteine-rich domain-containing

The present invention relates, in general, to CD6 and, in particular, to a CD6 ligand present on the surface of thymic epithelial cells, monocytes, activated T cells and a variety of other cell types. The invention further relates to methods of inhibiting the interaction of CD6 and the CD6 ligand, and to methods of screening compounds for their ability to inhibit that interaction. The invention also relates to antibodies, and binding fragments thereof, specific for CD6 ligand.

Anti-CD6 ligand antibodies

The invention provides a method for enhancing the expression of a gene of interest by a cell, the cell (a) comprises a recombinant nucleic acid sequence encoding and (b) is capable of expressing the gene of interest, the method comprising contacting the cell with an amount of a soluble CTLA4 molecule effective to enhance the expression of the gene of interest by the cell.

Methods for prolonging the expression of a heterologous gene of interest

The present invention relates to an isolated nucleic acid molecule having a sequence that encodes a CD6 ligand present on the surface of thymic epithelial cells, monocytes, activated T cells and a variety of other cell types. The invention further relates to a construct containing the nucleic acid molecule and to a host cell comprising same. Further, the invention relates to a method of producing a CD6 ligand.

CD6 ligand encoding sequence

Growing community of inventors

Edmonds, WA, United States of America

Alejandro A Aruffo