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AssigneeRegeneron Pharmaceuticals, Inc.
InventorsEric Smith, Nicholas J. Papadopoulos
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The present invention provides antibodies that bind to CD3 and methods of using the same. According to certain embodiments, the antibodies of the invention bind human CD3 with high affinity and induce human T cell proliferation. The invention includes antibodies that bind CD3 and induce T cell-mediated killing of tumor cells. According to certain embodiments, the present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD3, and a second antigen-binding molecule that specifically binds human CD20. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of B-cell tumors expressing CD20. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced targeted immune response is desired and/or therapeutically beneficial. For example, the antibodies of the invention are useful for the treatment of various cancers as well as other CD20-related diseases and disorders.
An isolated antibody or antigen-binding fragment thereof that binds human CD3 and (a) induces human T cell proliferation in vitro with an EC50 of less than about 0.33 pM, (b) binds human CD3 and induces T cell-mediated killing of tumor cells in vitro with an EC50 of less than about 2.3 pM, (c) binds human CD3 with a binding dissociation equilibrium constant (KD) of less than about 5 nM as measured in a surface plasmon resonance assay at 25° C., and/or (d) binds human CD3 with a dissociative half-life (t½) of greater than about 10 minutes as measured in a surface plasmon resonance assay at 25° C.
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A method for upmodulating an immune response in a subject, the method comprising administering to the subject an isolated antibody or antigen-binding fragment thereof that binds human CD3 and (a) induces human T cell proliferation in vitro with an EC50 of less than about 0.33 pM, (b) binds human CD3 and induces T cell-mediated killing of tumor cells in vitro with an EC50 of less than about 2.3 pM, (c) binds human CD3 with a binding dissociation equilibrium constant (KD) of less than about 5 nM as measured in a surface plasmon resonance assay at 25° C., and/or (d) binds human CD3 with a dissociative half-life (t½) of greater than about 10 minutes as measured in a surface plasmon resonance assay at 25° C.
A method for treating a tumor in a subject, the method comprising administering to the subject in need thereof an isolated antibody or antigen-binding fragment thereof that binds human CD3 and (a) induces human T cell proliferation in vitro with an EC50 of less than about 0.33 pM, (b) binds human CD3 and induces T cell-mediated killing of tumor cells in vitro with an EC50 of less than about 2.3 pM, (c) binds human CD3 with a binding dissociation equilibrium constant (KD) of less than about 5 nM as measured in a surface plasmon resonance assay at 25° C., and/or (d) binds human CD3 with a dissociative half-life (t½) of greater than about 10 minutes as measured in a surface plasmon resonance assay at 25° C.
A bispecific antigen-binding molecule comprising a first antigen-binding domain that specifically binds human CD3, and a second antigen-binding domain that specifically binds human CD20.
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A method for treating a B-cell cancer in a subject, the method comprising administering to the subject a bispecific antigen-binding molecule comprising a first antigen-binding domain that specifically binds human CD3, and a second antigen-binding domain that specifically binds human CD20, wherein the bispecific antigen-binding molecule (a) induces proliferation of human and cynomolgus peripheral blood mononuclear cells (PBMCs) in vitro, (b) induces IFN-gamma release and CD25 up-regulation in human whole blood, (c) induces T-cell mediated cytotoxicity of human B-cells, (d) induces T-cell mediated cytotoxicity of human B-cells that are resistant to anti-CD20-mediated cytotoxicity, and/or (e) causes a reduction in the number of B cells in a subject below detectable levels by about day 1 after a single administration of the bispecific antigen-binding molecule to the subject at a dose of about 0.01 mg/kg.
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Dependencies are inferred from the claim text.