Antibody Fc variants
First Claim
1. An isolated polypeptide comprising an Fc variant of a wild-type human IgG1 Fc region or a wild-type human IgG4 Fc region, said Fc variant comprising an amino acid substitution at position Pro329 with glycine or arginine and at least one further amino acid substitution, wherein said at least one further amino acid substitution is L234A and L235A of the human IgG1 Fc region or S228P and L235E of the human IgG4 Fc region wherein the residues are numbered according to the EU index of Kabat, and wherein said polypeptide exhibits a reduced affinity to human Fcγ
- RIIIA, and Fcγ
RIIA, and Fcγ
RI compared to the polypeptide comprising the wildtype IgG Fc region, wherein the affinity to each of human Fcγ
RIIIA, and Fcγ
RIIA, and Fcγ
RI is reduced by 1.15 fold to 100 fold compared to the polypeptide comprising the wildtype IgG Fc region, and wherein the antibody-dependent cell-mediated cytotoxicity (ADCC) induced by said polypeptide is 0-20% of the ADCC induced by the polypeptide comprising the 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
8 Claims
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1. An isolated polypeptide comprising an Fc variant of a wild-type human IgG1 Fc region or a wild-type human IgG4 Fc region, said Fc variant comprising an amino acid substitution at position Pro329 with glycine or arginine and at least one further amino acid substitution, wherein said at least one further amino acid substitution is L234A and L235A of the human IgG1 Fc region or S228P and L235E of the human IgG4 Fc region wherein the residues are numbered according to the EU index of Kabat, and wherein said polypeptide exhibits a reduced affinity to human Fcγ
- RIIIA, and Fcγ
RIIA, and Fcγ
RI compared to the polypeptide comprising the wildtype IgG Fc region, wherein the affinity to each of human Fcγ
RIIIA, and Fcγ
RIIA, and Fcγ
RI is reduced by 1.15 fold to 100 fold compared to the polypeptide comprising the wildtype IgG Fc region, and wherein the antibody-dependent cell-mediated cytotoxicity (ADCC) induced by said polypeptide is 0-20% of the ADCC induced by the polypeptide comprising the wild-type human IgG Fc region. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8)
- RIIIA, and Fcγ
Specification