Antibody Fc variants
AssigneeRoche Glycart AG
InventorsMonika Baehner, Stefan Jenewein, Manfred Kubbies, Ekkehard Moessner, Tilman Schlothauer
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Abstract
The invention relates to engineered polypeptides comprising Fc variants and their uses. More specifically, Fc variants are described exhibiting reduced effector function. These variants cause a benefit for a patient suffering from a disease which could be treated with an antibody for which it is desirable to reduce the effector function elicited by antibodies.
Claims8
An isolated polypeptide comprising an Fc variant of a wild-type human IgG1 Fc region or a wild-type human IgG4 Fc region, said Fc variant comprising an amino acid substitution at position Pro329 with glycine or arginine and at least one further amino acid substitution, wherein said at least one further amino acid substitution is L234A and L235A of the human IgG1 Fc region or S228P and L235E of the human IgG4 Fc region wherein the residues are numbered according to the EU index of Kabat, and wherein said polypeptide exhibits a reduced affinity to human FcγRIIIA, and FcγRIIA, and FcγRI compared to the polypeptide comprising the wildtype IgG Fc region, wherein the affinity to each of human FcγRIIIA, and FcγRIIA, and FcγRI is reduced by 1.15 fold to 100 fold compared to the polypeptide comprising the wildtype IgG Fc region, and wherein the antibody-dependent cell-mediated cytotoxicity (ADCC) induced by said polypeptide is 0-20% of the ADCC induced by the polypeptide comprising the wild-type human IgG Fc region.
Dependencies are inferred from the claim text.