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AssigneeMacroGenics, Inc.
InventorsJeffrey Stavenhagen, Sergey Gorlatov, Christopher Rankin, Nadine Tuaillon
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The present invention relates to molecules, particularly polypeptides, more particularly immunoglobulins (e.g., antibodies), comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, which variant Fc region binds FcγRIIIA and/or FcγRIIA with a greater affinity, relative to a comparable molecule comprising the wild-type Fc region. The molecules of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection. The molecules of the invention are particularly useful for the treatment or prevention of a disease or disorder where an enhanced efficacy of effector cell function (e.g., ADCC) mediated by FcγR is desired, e.g., cancer, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.
A polypeptide comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, such that said polypeptide binds an FcγR with an altered affinity relative to a polypeptide comprising a wild-type Fc region and wherein said at least one amino acid modification comprises a set of substitutions selected from the group consisting of a substitution at position 243 with leucine, at position 292 with proline, at position 300 with leucine, at position 305 with isoleucine, and at position 396 with leucine;
A polypeptide comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, such that said polypeptide specifically binds FcγRIIIA with a greater affinity than a comparable polypeptide comprising the wild-type Fc region binds FcγRIIIA and wherein said at least one amino acid modification comprises a set of substitutions selected from the group consisting of a substitution at position 243 with leucine, at position 292 with proline, at position 300 with leucine, at position 305 with isoleucine, and at position 396 with leucine;
A polypeptide comprising a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, such that said polypeptide specifically binds FcγRIIIA with a greater affinity than a comparable polypeptide comprising the wild-type Fc region binds FcγRIIIA, and said polypeptide further specifically binds FcγRIIB with a lower affinity than a comparable polypeptide comprising the wild-type Fc regions binds FcγRIIB, and wherein said at least one amino acid modification comprises a set of substitutions selected from the group consisting of a substitution at position 243 with leucine, at position 292 with proline, and at position 300 with leucine;
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Dependencies are inferred from the claim text.