ANTIBODY Fc VARIANTS
First Claim
1. A polypeptide comprising an Fc variant of a wild-type human IgG Fc region, said Fc variant comprising an amino acid substitution at position Pro329 and at least one further amino acid substitution, wherein the residues are numbered according to the EU index of Kabat, and wherein said polypeptide exhibits a reduced affinity to one or more of human Fcγ
- RIIIA, Fcγ
RIIA, and Fcγ
RI compared to the polypeptide comprising the wildtype IgG Fc region, and wherein the antibody-dependent cell-mediated cytotoxicity (ADCC) induced by said polypeptide is reduced to at least 20% of the ADCC induced by the polypeptide comprising a wild-type human IgG Fc region.
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Accused Products
Abstract
The invention relates to engineered polypeptides comprising Fc variants and their uses. More specifically, Fc variants are described exhibiting reduced effector function. These variants cause a benefit for a patient suffering from a disease which could be treated with an antibody for which it is desirable to reduce the effector function elicited by antibodies.
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Citations
23 Claims
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1. A polypeptide comprising an Fc variant of a wild-type human IgG Fc region, said Fc variant comprising an amino acid substitution at position Pro329 and at least one further amino acid substitution, wherein the residues are numbered according to the EU index of Kabat, and wherein said polypeptide exhibits a reduced affinity to one or more of human Fcγ
- RIIIA, Fcγ
RIIA, and Fcγ
RI compared to the polypeptide comprising the wildtype IgG Fc region, and wherein the antibody-dependent cell-mediated cytotoxicity (ADCC) induced by said polypeptide is reduced to at least 20% of the ADCC induced by the polypeptide comprising a wild-type human IgG Fc region. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 11, 12, 14, 20, 21)
- RIIIA, Fcγ
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10. (canceled)
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13. (canceled)
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15. A method for down-modulating ADCC comprising a polypeptide comprising an Fc variant of a wild-type human IgG Fc region, said polypeptide having Pro329 of the human IgG Fc region substituted with glycine, wherein the residues are numbered according to the EU index of Kabat, wherein said polypeptide exhibits a reduced affinity to the human Fcγ
- RIIIA and Fcγ
RIIA, wherein ADCC is down-modulated to at least 20% of the ADCC induced by the polypeptide comprising the wildtype human IgG Fc region. - View Dependent Claims (16, 17, 22)
- RIIIA and Fcγ
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18. A method of treating an individual having a disease with a polypeptide, said polypeptide having Pro329 of the human IgG Fc region substituted with Gly, wherein the residues are numbered according to the EU index of Kabat, wherein said polypeptide is characterized by a strongly reduced binding to Fcγ
- RIIIA and Fcγ
RIIA compared to the polypeptide comprising a wildtype human IgG Fc region, comprising administering to the individual an effective amount of said polypeptide. - View Dependent Claims (19)
- RIIIA and Fcγ
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23. A method for down-modulating ADCP comprising a polypeptide comprising an Fc variant of a wild-type human IgG Fc region, said polypeptide having Pro329 of the human IgG Fc region substituted with glycine, wherein the residues are numbered according to the EU index of Kabat, wherein said polypeptide exhibits a reduced affinity to the human Fcγ
- RIIIA and Fcγ
RIIA.
- RIIIA and Fcγ
Specification