Immunoglobulin Fc polypeptides
First Claim
1. A polypeptide comprising an aglycosylated antibody Fc domain capable of binding a human FcR polypeptide, wherein the Fc domain comprises an amino acid substitution at amino acids 382 and 428 and at least one additional substitution at any of the following amino acids:
- 241, 251, 266, 269, 276, 279, 286, 295, 297, 300, 315, 325, 328, 330, 332, 338, 340, 341, 348, 369, 378, 392, 424 and/or 434, where said amino acids are designated according to the Kabat numbering system.
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Accused Products
Abstract
Methods and compositions involving polypeptides having an aglycosylated antibody Fc domain. In certain embodiments, polypeptides have an aglycosylated Fc domain that contains one or more substitutions compared to a native Fc domain. Additionally, some embodiments involve an Fc domain that is binds some Fc receptors but not others. For example, polypeptides are provided with an aglycosylated Fe domain that selectively binds FcγRI at a level within 2-fold of a glycosylated Fc domain, but that is significantly reduced for binding to other Fc receptors. Furthermore, methods and compositions are provided for promoting antibody-dependent cell-mediated toxicity (ADCC) using a polypeptide having a modified aglycosylated Fc domain and a second non-Fc binding domain, which can be an antigen binding region of an antibody or a non-antigen binding region. Some embodiments concern antibodies with such polypeptides, which may have the same or different non-Fc binding domain.
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Citations
37 Claims
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1. A polypeptide comprising an aglycosylated antibody Fc domain capable of binding a human FcR polypeptide, wherein the Fc domain comprises an amino acid substitution at amino acids 382 and 428 and at least one additional substitution at any of the following amino acids:
- 241, 251, 266, 269, 276, 279, 286, 295, 297, 300, 315, 325, 328, 330, 332, 338, 340, 341, 348, 369, 378, 392, 424 and/or 434, where said amino acids are designated according to the Kabat numbering system.
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34)
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35. A method for preparing an aglycosylated polypeptide comprising:
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a) obtaining a host cell capable of expressing an aglycosylated antibody comprising an Fc domain capable of binding an FcR polypeptide, wherein the Fc domain comprises an amino acid substitution at amino acids 382 and 428 and at least one additional substitution of any of the following amino acids;
241, 251, 266, 269, 276, 279, 286, 295, 297, 300, 315, 325, 328, 330, 332, 338, 340, 341, 348, 369, 378, 392, 424 and/or 434;b) incubating the host cell in culture under conditions to promote expression of the aglycosylated antibody; and
,c) purifying expressed antibody from the host cell. - View Dependent Claims (36, 37)
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Specification