Regeneron Pharmaceuticals, Inc.

Supriya Patel

Eric L Smith

Samuel H Davis

Tong Zhang

Andrew J Murphy

Erica Pyles

Michael Rosconi

Nina Liu

Chia-Yang Lin

Eric B Smith

Ashique Rafique

Chiayang Lin

Eric Smith

Samuel Davis

Antigen binding molecules (ABMs) comprising Fab domains in non-native configurations, ABM conjugates comprising the ABMs and cytotoxic or cytostatic agents, pharmaceutical compositions containing the ABMs and ABM conjugates, methods of using the ABMs, ABM conjugates and pharmaceutical compositions for treating cancer, nucleic acids encoding the ABMs, cells engineered to express the ABMs, and methods of producing ABMs.

Antigen binding molecule formats

The invention provides antibody heavy chain constant regions with a hinge region modified to reduce binding to Fc&#x3b3; receptors. The modification occurs within positions 233-236 by replacement of natural residues by glycine(s) and/or deletion(s). Such modifications can reduce binding of an antibody bearing such a constant region to Fc&#x3b3; receptors to background levels. The constant regions can be incorporated into any format of antibody or Fc fusion protein. Such antibodies or fusion proteins can be used in methods of treatment, particularly those in which the mechanisms of action of the antibody or Fc fusion protein is not primarily or at all dependent on effector functions, as is the case when an antibody inhibits a receptor-ligand interaction or agonizes a receptor.

Heavy chain constant regions with reduced binding to Fc gamma receptors

Antibodies, antigen-binding proteins and Fc-fusion proteins that comprise recombinant polypeptides containing a chimeric heavy chain constant region sequence are provided that bind to certain Fc receptors however have reduced effector functions. Methods of making constructs for expression of such chimeric Fc-containing antibodies, antigen-binding proteins and Fc-fusion proteins in cell systems, and methods of producing and isolating the chimeric Fc-containing proteins are provided.

Antibodies comprising chimeric constant domains

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Mamaroneck, NY, United States of America

Supriya Patel