Disclosed is a variant of a parent polypeptide including an
Fc fragment, the variant having an increased affinity for the FcRn
receptor, and an increased affinity for at least one
receptor of the
Fc fragment (FcR) chosen from the FcγRI (CD64), FcγRIIIa (CD16a) and FcγRIIa (CD32a) receptors, relative to that of the parent polypeptide, characterised in that it includes: (i) the four mutations 334N, 352S, 378V and 397M; and (ii) at least one
mutation chosen from 434Y, 434S, 226G, P228L, P228R, 230S, 230T, 230L, 241L, 264E, 307P, 315D, 330V, 362R, 389T and 389K; the
numbering being that of the EU index or the Kabat equivalent.