Active protease-resistant antibody FC mutants

摘要

The present invention relates to modified Fc-containing molecules including modified antibodies characterized by increased resistance to host and pathogen-derived proteases, ability to interact with FcγR receptors except with FcγRI, and lack of induction of IL-10 secretion by macrophages, and methods of using and making them.

主权项

1. An isolated modified Fc-containing molecule or a fragment thereof comprising a wild type human IgG1 Fc region of SEQ ID NO: 1 comprising a hinge, a CH2 domain and a CH3 domain, wherein
a) the sequence of E233-L234-L235-G236 in the hinge is replaced with P233-V234-A235 with G236 deleted; and b) the CH2 domain comprises at least one substitution selected from S239D/1332E, K326A/E333A, H268F/S324T/1332E, F243L/R292P/Y300L, S239D/H268F/S324T/1332E, S267E/H268F/S324T/1332E, K326A/1332E/E333A, S239D/K326A/E333A, S267E/I332E and G237X/S239D/1332E where X is A, D, P, Q or S; wherein amino acid residues are numbered according to EU numbering.