Neonatal Fc receptor (FcRn)-binding polypeptide variants, dimeric Fc binding proteins and methods related thereto
AssigneeBiogen Idec MA Inc.
InventorsGraham K. Farrington, Alexey Alexandrovich Lugovskoy, Werner Meier, John K. Eldredge, Ellen Garber
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Abstract
The compositions and methods of the present invention are based, in part, on our discovery that an effector function mediated by an Fc-containing polypeptide can be altered by modifying one or more amino acid residues within the polypeptide (by, for example, electrostatic optimization). The polypeptides that can be generated according to the methods of the invention are highly variable, and they can include antibodies and fusion proteins that contain an Fc region or a biologically active portion thereof.
Claims17
An IgG Fc-containing polypeptide comprising an altered Fc region, wherein said Fc-containing polypeptide comprises at least one mutation within the Fc region as compared to a starting Fc-containing polypeptide and wherein the at least one mutation is a substitution at EU amino acid position 304 with aspartate or glutamate in combination with a second mutation selected from the group consisting of:
- a substitution at EU amino acid position 284 with aspartate or glutamate;
- a substitution at EU amino acid position 285 with aspartate or glutamate;
- a substitution at EU amino acid position 286 with aspartate or glutamate;
- a substitution at EU amino acid position 288 with a aspartate or glutamate;
- a substitution at EU amino acid position 290 with aspartate or glutamate;
- and
- a substitution at EU amino acid position 305 with aspartate or glutamate,
- wherein the IgG Fc-containing polypeptide binds FcRn with different binding affinity compared to the starting polypeptide that does not contain the mutations.
Dependencies are inferred from the claim text.