Bristol-Myers Squibb Compnay

Cytomx Therapeutics, Inc.

John J Engelhardt

Alan J Korman

Mark J Selby

James William West

Changyu Wang

Brenda L Stevens

Shrikant Deshpande

Michael Quigley

Kimberly Ann Tipton

Mary Diane Feingersh

The present invention provides isolated monoclonal antibodies (e.g., humanized and human monoclonal antibodies) that bind to human Inducible T Cell COStimulator (ICOS) and exhibit therapeutically desirable functional properties, e.g., the ability to stimulate human ICOS activity. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells, and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules, and pharmaceutical compositions comprising the antibodies of the invention are also provided. The antibodies of the invention can be used, for example, as an agonist to stimulate or enhance an immune response in a subject, e.g., antigen-specific T cell responses against a tumor or viral antigen. The antibodies of the invention can also be used in combination with other antibodies (e.g., PD-1, PD-L1, and/or CTLA-4 antibodies) to treat, for example, cancer. Accordingly, the antibodies can be used in therapeutic applications and methods to detect ICOS protein.

Anti-ICOS agonist antibodies and uses thereof

The present invention provides anti-CTLA-4 antibodies having enhanced ADCC activity, and their use in treating cancer. In one embodiment, the anti-CTLA-4 antibody is ipilimumab, and ADCC activity is enhanced by introducing G236A, S239D, A330L and I332E mutations ('GASDALIE') into the Fc region of the heavy chain constant domain.

Ipilimumab variant with enhanced ADCC

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Fremont, CA, United States of America

John J Engelhardt