Polypeptide variants
AssigneeGenentech, Inc.
InventorsLeonard G. Presta, Robert Laird Shields
Life of this patent
Estimating the term…
Abstract
A variant of a polypeptide comprising a human IgG Fc region is described, which variant comprises an amino acid substitution at amino acid position 329, or at two or all of amino acid positions 329, 331 and 322 of the human IgG Fc region. Such variants display altered effector function. For example, Clq binding and/or complement dependent cytotoxicity (CDC) activity may be reduced or abolished in the variant polypeptide. The application also describes an immune complex and an assay for determining binding of an analyte, such as an Fc region-containing polypeptide, to a receptor.
Claims23
A variant of a polypeptide comprising a human IgG Fc region, which variant comprises an amino acid substitution at amino acid position 329, or at two or all of amino acid positions 329, 331 and 322 of the human IgG Fc region, where the numbering of the residues in the IgG Fc region is that of the EU index as in Kabat.
A variant of a polypeptide comprising a human IgG Fc region, which variant binds FcγRI, FcγRII, FcγRIII and FcRn but does not activate complement and comprises an amino acid substitution at amino acid position 322 or amino acid position 329, or both amino acid positions of the human IgG Fc region, where the numbering of the residues in the IgG Fc region is that of the EU index as in Kabat.
A method for modifying a polypeptide comprising a human IgG Fc region comprising substituting an amino acid residue at amino acid position 329, or at two or all of amino acid positions 329, 331 and 322 of the human IgG Fc region, where the numbering of the residues in the IgG Fc region is that of the EU index as in Kabat.
A method of treating a mammal suffering from a disorder comprising administering to the mammal a therapeutically effective amount of a variant of a polypeptide comprising a human IgG Fc region, which variant binds FcγRI, FcγRII, FcγRIII and FcRn but does not activate complement and comprises an amino acid substitution at amino acid position 329, 331 or 322 of the human IgG Fc region, where the numbering of the residues in the IgG Fc region is that of the EU index as in Kabat.
An immune complex comprising:
- (a) an Fc region-containing polypeptide;
- (b) a first target molecule which comprises at least two binding sites for the Fc region-containing polypeptide;
- and
- (c) a second target molecule which comprises at least two binding sites for the first target molecule.
A method for determining binding of an analyte to a receptor comprising the following steps performed sequentially:
- (a) forming a molecular complex between the analyte and a first target molecule, wherein the first target molecule comprises at least two binding sites for the analyte;
- and
- (b) determining binding of the molecular complex of step (a) to the receptor.
A kit useful for determining binding of an analyte to a receptor comprising:
- (a) a first target molecule which comprises at least two binding sites for the analyte;
- and
- (b) a second target molecule which comprises at least two binding sites for the first target molecule.
Dependencies are inferred from the claim text.