Abstract: The present disclosure provides methods of treating an antibody-mediated disorder (e.g., an autoimmune disease) using an FcRn antagonist, e.g., a binding polypeptide (e.g., an antibody and/or an immunoadhesin), comprising a modified Fc domain. The present disclosure also provides methods of enhancing diagnostic imaging using an FcRn antagonist disclosed herein. The present disclosure further provides methods of reducing exposure of normal tissue to a radiolabeled antibody during diagnostic imaging using an FcRn antagonist disclosed herein. Methods comprising administering to a subject a therapeutically effective amount of an FcRn antagonist disclosed herein are also provided.

Abstract: The present disclosure provides Fc domain variant polypeptides, including effector-competent Fc domain variants. The present disclosure also provides Fc domain variant polypeptides comprising at least one substitution or at least two substitutions at amino acid positions 251, 267, 268, 298, 314, 330, 339, 373, and 376, according to EU numbering, as compared to a Fc domain parent polypeptide. The present disclosure also provides nucleic acids encoding Fc domain variant polypeptides and host cells for making Fc domain variant polypeptides. Methods for increasing the yield of Fc domain variant polypeptides, and methods of using Fc domain variant polypeptides to treat disease, are also provided.

Abstract: The present disclosure provides methods of treating an antibody-mediated disorder (e.g., an autoimmune disease) using an FcRn antagonist, e.g., a binding polypeptide (e.g., an antibody and/or an immunoadhesin), comprising a modified Fc domain. The present disclosure also provides methods of enhancing diagnostic imaging using an FcRn antagonist disclosed herein. The present disclosure further provides methods of reducing exposure of normal tissue to a radiolabeled antibody during diagnostic imaging using an FcRn antagonist disclosed herein. Methods comprising administering to a subject a therapeutically effective amount of an FcRn antagonist disclosed herein are also provided.

Abstract: The present disclosure provides binding polypeptides (e.g., antibodies and immunoadhesins) comprising a modified Fc domain. The present disclosure also provides nucleic acids encoding the binding polypeptides, recombinant expression vectors, and host cells for making such binding polypeptides. Methods of using the binding polypeptides disclosed herein to treat disease are also provided.