Anti-death receptor antibodies and methods of use thereof

Abstract

Provided are monospecific or bispecific antibody molecules that specifically bind to an antigen of a death receptor that is a member of the tumor necrosis factor (TNF) receptor superfamily with an intracellular death domain (TNFR-SF). [Solution] Antibody molecules of the IgG1 isotype are disclosed that have mutations in the Fc region that enhance clustering of the IgG molecules after target binding. The invention also relates to combinations of antibody molecules that bind to different epitopes on one or more specific death receptors. The invention also relates to pharmaceutical compositions containing these molecules and to the treatment of cancer using these compositions.

Claims

1. an Fc region of a human IgG1 isotype; an antigen-binding region that binds to DR4 and comprises a variable heavy chain (VH) region and a variable light chain (VL) region as shown in the amino acid sequences of (VH) SEQ ID NO:13 and (VL) SEQ ID NO:14, respectively; An agonistic antibody comprising: The antibody, wherein the Fc region comprises an E430G mutation at an amino acid position corresponding to position E430 in human IgG1 according to EU numbering.

2. The antibody of claim 1, wherein the Fc region comprises an additional mutation at an amino acid position corresponding to K439 or S440.

3. The antibody of claim 2, wherein the further mutation is selected from K439E or S440K.

4. The antibody of any one of claims 1 to 3, which is a monoclonal antibody.

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