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 nolyneptides comprising Fc variants and their uses. More specifically, Fc variants are described exhibiting reduced effector function. These variantg 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.
Claims19
A polypeptide comprising an Fc variant of a wild-type human IgG Fc region, said Fc variant comprising an amino acid substitution at position Pro329 and at least one further amino acid substitution, wherein the residues are numbered according to the EU index of Kabat, and wherein said polypeptide exhibits a reduced affinity to the human FcγRIDA and/or FcγRIIA and/or FcγRI compared to a polypeptide comprising the wildtype IgG Fc rogion, and wherein the ADCC induced by said polypeptide is reduced to at least 20% of the ADCC induced by the polypeptide comprising a wild-type human IgG Fc region.
Use of a polypeptide comprising an Fc variant of a wild-type human IgG Fc region, said polypeptide having Pro329 of the human IgG Fc region substituted with glycine, wherein the residues are numbered according to the EU index of Kabat, wherein said polypeptide exhibits a reduced affinity to the human FcγRIIIA and FcγRIA for down-modulation of ADCC to at least 20% of the ADCC induced by the polypeptide comprising the wildtype human IgG Fc region, and/or for down-modulation of ADCP.
A method of treating an individual having a disease with a polypeptide, said polypeptide having Pro329 of the human IgG Fc region substituted with Gly, wherein the residues are numbered according to the EU index of Kabat, wherein said polypeptide is characterized by a strongly reduced binding to FcγRIIIA and FcγRIIA compared to a polypeptide comprising a wildtype human IgG Fc region, comprising administering to the individual an effective amount of said polypeptide.
Dependencies are inferred from the claim text.