Bristol-myers Squibb Compnay

Isis Innovation Limited

Cytomx Therapeutics, Inc.

Bristol Meyers Squibb Company

Lisa K Gilliland

Jeffrey A Ledbetter

Peter S Linsley

Jurgen Bajorath

Mark Raymond Frewin

H Perry Fell

Martha S Hayden

Herman Waldmann

Joyce M Zarling

Luis Richardo Simoes Da Silva Graca

Patricia A Moran

Michael L Diegel

Anthony W Siadak

Alejandro A Aruffo

Diane L Hollenbaugh

Louise Walsh

Masahide Tone

Linda J Harris

Hermann Waldmann

Marcia L Gordon

A pharmaceutical comprising a therapeutic protein that binds to a therapeutic target, the protein being modified with a compound that inhibits binding of the protein to the therapeutic target, the modified protein being effective for reducing an immune response against the protein and for producing a therapeutic effect by binding to the therapeutic target. The therapeutic protein may be an antibody that includes an antibody combining site that binds to the therapeutic target.

Therapeutic antibodies

A pharmaceutical comprising a therapeutic protein that hinds to a therapeutic target, the protein being modified with a compound that inhibits binding of the protein to the therapeutic target, the modified protein being effective for reducing an immune response against the protein and for producing a therapeutic effect by binding to the therapeutic target. The therapeutic protein may be an antibody that includes an antibody combining site that binds to the therapeutic target.

This invention relates to an antibody which is modified version of a therapeutic antibody with affinity for a cell-surface antigen, the antibody having reduced affinity for the antigen compared with the therapeutic antibody as a result of a modification or modifications to the antibody molecule, wherein the antibody is capable of inducing immunological tolerance to the therapeutic antibody. The invention further relates to a method of inducing immunological tolerance to a therapeutic antibody, comprising administering to a patient an antibody which is a modified version of the therapeutic antibody and which has reduced affinity for the antigen as compared with the therapeutic antibody.

Antibody variants

The present invention provides an expression vector encoding monospecific or bispecific fusion protein. In one embodiment the expression vector encodes a monospecific fusion protein, which vector comprises a recombinant monospecific single chain cassette comprising a DNA sequence encoding a first binding domain capable of binding a cell surface antigen. In another embodiment the expression vector encodes a bispecific fusion protein, which vector comprises a recombinant bispecific single chain cassette comprising a DNA sequence encoding a first binding domain capable of binding a cell surface antigen and a DNA sequence encoding a second binding domain capable of binding a cell surface antigen, each domain capable of binding a different antigen. The present invention also provides a method for producing a biologically active monospecific or bispecific fusion protein in a mammalian cell.

Expression vectors encoding bispecific fusion proteins and methods of producing biologically active bispecific fusion proteins in a mammalian cell

The present invention provides novel soluble CTLA4Ig molecules having modified Ig domains.

An anti-CD2 monoclonal antibody according to the present invention can be: (1) a chimeric nonclonal antibody CD2 SFv-Ig produced by expression of the construct cloned in recombinant culture ATCC No. 69277; (2) a monoclonal antibody having complementarity-determining regions identical with those of CD2 SFv-Ig; or (3) a monoclonal antibody competing with CD2 SFv-Ig for binding to CD2 antigen at least about 80% as effectively on a molar basis as CD2 SFv-Ig. Anti-CD2 monoclonal antibodies according to the present invention, as well as other antibodies that can modulate the interactions between T lymphocytes and monocytes, can be used to inhibit the production of HIV-1 by HIV-1-infected T cells in HIV-1-infected patients. In another use, T cells treated in vitro can be reinfused into AIDS patients to increase the proportion of functional non-HIV-1-producing T cells in the patient.

Methods for inhibiting the production of HIV-1 retrovirus using monoclonal antibodies and Fv specific for CD2 antigen

The present invention provides an expression vector encoding monospecific or bispecific fusion protein. In one embodiment the expression vector encodes a monospecific fusion protein, which vector comprises a recombinant monospecific single chain cassette comprising a DNA sequence encoding a first binding domain capable of binding a cell surface antigen. In another embodiment the expression vector encodes a bispecific fusion protein, which vector comprises a recombinant bispecific single chain cassette comprising a DNA sequence encoding a first binding domain capable of binding a cell surface antigen and a DNA sequence encoding a second binding domain capable of binding a cell surface antigen, each domain capable of binding a different antigen. The present invention also provides a method for producing a biologically active monospecific or bispecific fusion protein in a mammalian cell. This method comprises: (a) transfecting the mammalian cell with the recombinant expression vector of the invention; (b) culturing the mammalian cell so transfected in step (a); and (c) recovering the biologically active bispecific fusion protein so as produced by the cultured mammalian cell.

Expression vectors encoding bispecific fusion proteins and methods of

The present invention relates to novel antibody heteroconjugates and bispecific antibodies and methods and compositions and their use in the enhancement or inhibition of activation and function of T or B lymphocytes. The heteroconjugates are comprised of at least two antibody molecules cross-linked to each other, each molecule being reactive with a different lymphocyte antigen on the same cell. The invention also provides bispecific antibodies comprising a first binding region reactive with an antigen on a lymphocyte and a second binding region reactive with a different antigen on the lymphocyte. The heteroconjugates, bispecific antibodies, methods and compositions of this invention are therefore useful in the regulation of lymphocyte function, resulting in the improvement of cellular immune responses in various disease states.

Antibody heteroconjugates and bispecific antibodies for use in

The present invention provides monoclonal antibodies, antigen binding fragment and recombinant binding proteins specific for human gp39. These antibodies are specific for at least eight different epitopes on gp39. Hybridomas secreting specific antibodies which bind to these epitopes are also provided. Further, the present invention discloses the amino acid sequence of immunoglobulin light and heavy chain variable regions which bind to epitopes of gp39 and provide sFv and humanized antibodies which bind gp39. Also, provided are pharmaceutical compositions comprising the monoclonal antibodies, antigen binding fragments and recombinant binding proteins which bind gp39 and methods for using these compositions in diagnosing disease states, inhibiting B cell activation and for treating immunological disorders, such as autoimmune diseases, allergic responses, organ rejection and graft-versus-host disease. Antibodies of the present invention can also be used to image cells which express gp39 on their surface, such as tumor cells (e.g., lymphoma) and to target therapeutic agents to target cells.

Monoclonal antibodies specific for different epitopes of human GP39 and

An anti-CD2 monoclonal antibody according to the present invention can be: (1) a chimeric monoclonal antibody CD2 SFv-Ig produced by expression of the construct cloned in recombinant Escherichia coli culture ATCC No. 69277; (2) a monoclonal antibody having complementarity-determining regions identical with those of CD2 SFv-Ig; or (3) a monoclonal antibody competing with CD2 SFv-Ig for binding to CD2 antigen at least about 80% as effectively on a molar basis as CD2 SFv-Ig. Anti-CD2 monoclonal antibodies according to the present invention, as well as other antibodies that can modulate the interactions between T lymphocytes and monocytes, can be used to inhibit the production of HIV-1 by HIV-1-infected T cells in HIV-1-infected patients. In another use, T cells treated in vitro can be reinfused into AIDS patients to increase the proportion of functional, non-HIV-1-producing T cells in the patient.

Monoclonal antibodies and FV specific for CD2 antigen

The present invention provides an expression vector encoding monospecific or bispecific fusion protein. In one embodiment the expression vector encodes a monospecific fusion protein, which vector comprises a recombinant monospecific single chain cassette comprising a DNA sequence encoding a first binding domain capable of binding a cell surface antigen.

Growing community of inventors

Oxford, United Kingdom

Lisa K Gilliland