abstract |
Provided is a variant polypeptide of a parent polypeptide comprising an Fc region, wherein the Fc region of the variant polypeptide comprises: a modified first amino acid residue at position 299 of the Fc region, the first amino acid residue having a preferred side chain chemistry selected from: (a) a side chain chemistry comprising a cysteine thiol, (b) a chemistry of sufficient steric bulk such that the polypeptide displays reduced effector function; and (c) a side chain chemistry of sufficient electrostatic charge such that the polypeptide displays reduced effector function; and a second amino acid residue at position 297 of the Fc region, the second amino acid having reduced glycosylation, wherein the variant polypeptide has reduced effector function as compared to the parent polypeptide. Further provided are corresponding nucleic acids, vectors containing the nucleic acids and uses of the composition for the manufacture of medicaments to treat various diseases. |