Combination of FcγRIIB-specific antibodies and CD20-specific antibodies and methods of use thereof

摘要

The present invention relates to methods of treatment, prevention, management or amelioration of one or more symptoms of diseases or disorders associated with CD20 expression that encompass administration of a combination of: (A) one or more antibodies that specifically bind FcγRIIB, particularly human FcγRIIB, with greater affinity than said antibodies bind FcγRIIA, and (B) one or more antibodies that specifically bind to CD20. Such methods include methods of treating, preventing, managing or ameliorating one or more symptoms of a B cell related disease or disorder or an inflammatory disorder. The invention also provides pharmaceutical compositions comprising an anti-FcγRIIB antibody and an anti-CD20 antibody.

主权项

1. A pharmaceutical composition comprising:
(A) an effective amount of a first isolated antibody or an antigen-binding fragment thereof that comprises a variable domain that specifically binds the extracellular domain of native human FcγRIIB with greater affinity than said antibody or fragment thereof binds native human FcγRIIA, wherein said first isolated antibody comprises:
(1) a heavy chain variable domain having the amino acid sequence of SEQ ID NO:24, SEQ ID NO:28, SEQ ID NO:60, or SEQ ID NO:68; and(2) a light chain variable domain having the amino acid sequence of SEQ ID NO:62;or(1) a heavy chain variable domain having the amino acid sequence of SEQ ID NO:60, or SEQ ID NO:68; and(2) a light chain variable domain having the amino acid sequence of SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:26 or SEQ ID NO:62; and (B) an effective amount of a second isolated antibody or an antigen-binding fragment thereof that comprises a variable domain that comprises three light chain CDRs and three heavy chain CDRs, wherein said variable domain specifically binds human CD20; and (C) a pharmaceutically acceptable carrier; wherein said effective amounts of said first and second antibodies or said fragments thereof cause said pharmaceutical composition to mediate a synergistically increased tumor volume reduction relative to the additive tumor volume reductions mediated by:
(1) a pharmaceutical composition comprising said effective amount of said first antibody or fragment thereof but lacking said effective amount of said second antibody or fragment thereof; and(2) a pharmaceutical composition comprising said effective amount of said second antibody or fragment thereof but lacking said effective amount of said first antibody or fragment thereof.