IgG1 Fc MUTANTS WITH ABLATED EFFECTOR FUNCTIONS
AssigneeCovagen AG
InventorsSimon Brack, Isabella Attinger-Toller, Fabian Buller, Dragan Grabulovski, Julian Bertschinger, Adrian Zumsteg
Life of this patent
Estimating the term…
Abstract
Antibody and other Fc-containing molecules with variations in the Fc region with reduced binding to C1q and Fc gamma receptors are provided, which can be used in the treatment of various diseases and disorders.
Claims20
A recombinant IgG Fc-containing molecule, comprising a CH2 domain in which the amino acid at position 265 is different from aspartic acid (D), the amino acid at position 297 is different from asparagine (N), and the amino acid at position 329 is different from proline (P), wherein
- the molecule has reduced binding to C1q and to at least one Fcγ receptor (FcγR), as compared to a wild-type IgG1 Fc-containing molecule that comprises D at position 265, N at position 297 and P at position 329,
- and wherein the numbering is indicated by the EU index as in Kabat.
A method of making a recombinant IgG1 Fc-containing molecule, comprising a CH2 domain in which amino acids at position 265, 297, and 329 indicated by the EU index as in Kabat are replaced by other amino acids, the method comprising the steps of:
- a. providing a nucleic acid encoding a wild-type IgG1 Fc-containing molecule,
- b. modifying the nucleic acid provided in step (a) so as to obtain a nucleic acid encoding a recombinant IgG1 Fc-containing molecule wherein the amino acids at position 265, 297, and 329 are replaced with amino acids other than D, N and P, respectively, and
- c. expressing the nucleic acid obtaining in step (b) in a host cell and recovering the said mutant.
A recombinant polypeptide comprising
- a. at least one binding domain capable of binding a target molecule;
- and
- b. an IgG1 Fc domain wherein the amino acids at positions 265, 297, and 329 according to the EU index as in Kabat are different from D, N, and P, respectively,
- wherein the polypeptide is capable of binding the target molecule without triggering significant lymphocyte activation, complement dependent lysis, and/or cell mediated destruction of the target molecule and/or of a cell that expresses the target molecule on its surface.
Dependencies are inferred from the claim text.