Biogen Idec, Inc.

Idec Pharmaceuticals Corporation

Other

Idec Pharmaceutical Corporation

Nabil Hanna

Darrell R Anderson

Roland A Newman

Peter Brams

Mitchell E Reff

William H Rastetter

Amelia Nancy Black

Ronald W Raab

Eduardo Agustin Padlan

Cheryl Janne Heard

William S Shestowsky

John E Leonard

Kandasamy Hariharan

Gary R Braslawsky

William S Kloetzer

Paul Chinn

Michael J LaBarre

Eduardo A Padian

Tri B Huynh

Disclosed herein are methods of depleting peripheral blood B cells in a human host comprising administering to the host an immunologically active anti-CD20 antibody in an amount effective to deplete peripheral blood B cells in the host.

Expression and use of anti-CD20 Antibodies

The present invention relates to the identification of antibodies which are specific to human B7.1 antigen (CD80) and which are capable of inhibiting the binding of B7.1 to a CD28 receptor and which are not capable of inhibiting the binding of B7.1 to a CTLA-4 receptor. Two of these antibodies, 16C10 and 7C10, significantly inhibit the production of IL-2, in spite of the existence of a second activating ligand B7.2 (CD86). Blocking of the primary activation signal between CD28 and B7.1 (CD80) with these antibodies while allowing the unimpaired or coincident interaction of CTLA-4 and B7.1 and/or B7.2 represents a combined antagonistic effect on positive co-stimulation with an agonistic effect on negative signalling. These antibodies may be used as specific immunosuppressants, e.g., for the treatment of autoimmune diseases and to prevent organ transplant rejection.

Methods of inducing immunosuppression by administering 7C10 and 16C10 CD80-specific antibodies

Methods of treating rheumatoid arthritis with 7C10 and 16C10 CD80-specific antibodies

Methods of producing 7C10 and 16C10 CD80-specific antibodies

Methods of inhibiting IL-2 production by T cells by administering 7C10 and 16C10 CD80-specific antibodies

Chimeric antibodies specific to human CD4 antigen, DNA encoding, pharmaceutical compositions containing and use thereof as therapeutic agents are taught. These chimeric antibodies contain Old World monkey variable sequences and human constant domain sequences, preferably human gamma 1, gamma 4 or mutated forms thereof. These antibodies possess desirable therapeutic properties including low antigenicity, reduced (or absent) T cell depleting activity, good affinity to human CD4 and enhanced stability (in vivo half-life).

Recombinant anti-CD4 antibodies for human therapy

Host cells expressing 7C10 and 16C10 CD80-specific antibodies

Disclosed are chimeric, immunologically active, isolated, and radiolabeled antibodies directed against the CD20 antigen. The antibodies are useful for treating and diagnosing B cell disorders.

Anti-CD20 antibodies

The present invention relates to the identification of antibodies which are specific to human B7.1 antigen (CD80) and which are capable of inhibiting the binding of B7.1 to a CD28 receptor and which are not capable of inhibiting the binding of B7.1 to a CTLA-4 receptor. Two of these antibodies, 16C10 and 7C10, significantly inhibit the production of IL-2, in spite of the existence of a second activating ligand B7.2 (CD86). Blocking of the primary activation signal between CD28 and B7.1 (CD80) with these antibodies while allowing the unimpaired or coincident interaction of CTLA-I and b7.1 and/or B7.2 represents a combined antagonistic effect on positive co-stimulation with an agonistic effect on negative signalling. These antibodies may be used as specific immunosuppressants, e.g., for the treatment of autoimmune diseases and to prevent organ transplant rejection.

7C10 and 16C10 CD80-specific antibodies

The present invention relates to the identification of antibodies which are specific to human B7.1 antigen (CD80) and which are capable of inhibiting the binding of B7.1 to a CD28 receptor and which are not capable of inhibiting the binding of B7.1 to a CTLA-4 receptor. Two of these antibodies, 16C10 and 7C10, significantly inhibit the production of IL-2, in spite of the existence of a second activating ligand B7.2 (CD86). Blocking of the primary activation signal between CD28 and B7.1 (CD80) with these antibodies while allowing the unimpaired or coincident interaction of CTLA-4 and B7.1 and/or B7.2 represents a combined antagonistic effect on positive co-stimulation with an agonistic effect on negative signaling. These antibodies may be used as specific immunosuppressants, e.g., for the treatment of autoimmune diseases and to prevent organ transplant rejection.

Nucleic acids encoding 7C10 and 16C10 CD80-specific antibodies

Disclosed are immunologically active antibodies directed against the CD20 antigen, as well as host cells comprising nucleic acid sequences encoding the light chains and heavy chains of immunologically active antibodies wherein the cell is capable of expressing and secreting an immunologically active chimeric anti-CD20 antibody and methods of using such host cells to make purified antibodies. The antibodies are useful for treating and diagnosing B cell disorders.

Expression and use of anti-CD20 antibodies

The present invention relates to the identification of macaque antibodies to human B7.1 and B7.2 by screening of phage display libraries or monkey heterohybridomas obtained using B lymphocytes from B7.1 and/or B7.2 immunized monkeys. More specifically, the invention provides four monkey monoclonal antibodies 7B6, 16C10, 7C10 and 20C9 which inhibit the B7:CD28 pathway and thereby function as effective immunosuppressants. The invention further provides the complete DNA and amino acid sequences of the light and heavy chain of three PRIMATIZED&#xae; antibodies derived from those monkey monoclonal antibodies which bind B7.1 and possibly B7.2, PRIMATIZED&#xae; 7C10, PRIMATIZED&#xae; 7B6 and PRIMATIZED&#xae; 16C10. These PRIMATIZED&#xae; and monkey antibodies may be used as specific immunosuppressants, e.g., for the treatment of autoimmune diseases and to prevent organ transplant rejection.

Anti-CD80 antibodies

Methods, compositions and kits comprising dimeric antibodies for the treatment of neoplastic, autoimmune or other disorders are provided. The dimeric antibodies of the instant invention may comprise two antibody molecules (HL) having the same antigen binding specificity (homodimers) or, alternatively, may comprise two different antibody molecules having binding specificity for two distinct antigens (heterodimers). In preferred embodiments the antibody molecules comprising the dimers are non-covalently associated.

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The specification provides methods of preparing high-affinity antibodies to a macrophage migration inhibitory factor (MIF) in animals in which the MIF gene has been homozygously knocked-out (MIF). Also provided are methods of preparing hybridomas which produce the anti-MIF antibodies, methods of administering the antibodies to treat inflammatory or cancerous conditions and/or diseases modulated by MIF, as well as compositions comprising said high-affinity anti-MIF antibodies.

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Rancho Santa Fe, CA, United States of America

Nabil Hanna