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AssigneeGenentech, Inc.
InventorsGregory A. Lazar, James Ernst, Jasvinder Atwal, Shraddha Shirish Sadekar, Yanli Yang, Shan Chung
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Biological macromolecules have tremendous potential for the treatment of disease of the central nervous system (CNS), however, the presence of the blood brain barrier (BBB) makes achieving a therapeutically relevant antibody concentration extremely challenging. Antibodies with enhanced neutral pH affinity for the neonatal Fc receptor demonstrate improved accumulation in the brain. Variants disclosed herein also enhanced exposure in engineered mouse models. Using an anti-BACE1 antibody, these Fc variants significantly reduced the levels of brain Abeta.
A method of treating a neurological disorder comprising administering an antibody or an Fc conjugate comprising a modified IgG Fc to a subject in need thereof, wherein the antibody or the Fc conjugate is active in an in vitro transcytosis assay, wherein the in vitro transcytosis assay comprises cells that express FcRn.
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A method of delivering an antibody or an Fc conjugate to the brain of a subject comprising administering to the subject an antibody comprising a modified IgG Fc to a subject in need thereof, wherein the antibody or the Fc conjugate is active in an in vitro transcytosis assay, wherein the in vitro transcytosis assay comprises cells that express FcRn.
A method of increasing brain exposure to an antibody or an Fc conjugate comprising administering to a subject an antibody comprising a modified IgG Fc to a subject in need thereof, wherein the antibody or the Fc conjugate is active in an in vitro transcytosis assay, wherein the in vitro transcytosis assay comprises cells that express FcRn.
A method of increasing transport of an antibody or an Fc conjugate across the blood brain barrier (BBB) comprising administering to a subject an antibody comprising a modified IgG Fc to a subject in need thereof, wherein the antibody or the Fc conjugate is active in an in vitro transcytosis assay, wherein the in vitro transcytosis assay comprises cells that express FcRn.
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An isolated antibody that binds to a brain antigen, wherein the antibody comprises a modified IgG Fc, wherein the antibody is active in an in vitro transcytosis assay, wherein the in vitro transcytosis assay comprises cells that express FcRn.
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An Fc conjugate comprising a modified IgG Fc, wherein the Fc conjugate is active in an in vitro transcytosis assay, wherein the in vitro transcytosis assay comprises cells that express FcRn.
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Dependencies are inferred from the claim text.