Antibody Fc Mutants with Ablated Effector Functions
AssigneeJanssen Biotech, Inc.
InventorsWilliam Strohl, Omid Vafa
Life of this patent
Estimating the term…
Abstract
Antibody and other Fc-containing molecules with variations in the Fc region reduce binding to Fc gamma receptors and resulting activity and can be used in the treatment of various diseases and disorders.
Claims17
An Fc-containing molecule having decreased affinity for at least one Fcγ receptor as compared to a wildtype Fc, comprising an antibody Fc domain with a mutated IgG constant region, wherein amino acid residues 233, 234, 235, 237, and 238 defined by the EU numbering system, comprise a sequence selected from PAAAP (SEQ ID NO:
- 4), PAAAS (SEQ ID NO:5), and SAAAS (SEQ ID NO:6).
A recombinant polypeptide based binding molecule comprising:
- (i) a binding domain capable of binding a target molecule, and (ii) an Fc domain having an amino acid sequence substantially homologous to all or part of a CH2 and CH3 constant domains of a human immunoglobulin heavy chain and wherein residues 233, 234, 235, 237, and 238 defined by the EU numbering system, comprise an amino acid sequence selected from PAAAP, PAAAS, and SAAAS;
- wherein the binding molecule is capable of binding the target molecule without triggering significant complement dependent lysis, or cell mediated destruction of the target.
An Fc-containing molecule having decreased affinity for Fcγ receptors as compared to a wildtype Fc, comprising an antibody Fc domain based on an IgG2 constant region, wherein amino acid residues 233, 234, 235, 237, and 238 defined by the EU numbering system, comprise a sequence selected from PAAAP, PAAAS, and SAAAS and further comprising mutations H268A or H268Q, V309L, A330S and P331S as defined by the EU numbering system.
A method of altering binding of an IgG2 based Fc-containing molecule to Fcγ receptors as compared to a wildtype IgG2 based Fc, comprising altering the sequence of an Fc domain based on an IgG2 constant region at residues 233, 234, 235, 237, and 238 defined by the EU numbering system, to comprise a sequence selected from PAAAP, PAAAS, and SAAAS, and comprise mutations H268A or H268Q, V309L, A330S and P331S.
Any invention described herein.
Dependencies are inferred from the claim text.