IMMUNOGLOBULIN FC POLYPEPTIDES
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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 Fc 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
116 Claims
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1-67. -67. (canceled)
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68. A method for screening for an aglycosylated polypeptide having an Fc domain that binds a specific Fcγ
- R polypeptides comprising;
a) obtaining a population of Gram negative bacterial cells, cells of which population express a aglycosylated polypeptide comprising an Fc domain in their periplasm, wherein the population expresses a plurality of different Fc domains; b) contacting the bacterial cells with a first FcR polypeptide under conditions to allow contact between the Fcγ
R polypeptide and the aglycosylated Fc domains, wherein the Fcγ
R polypeptide is Fcγ
RIa, Fcγ
RIIa, Fcγ
RIIb, Fcγ
RIIc, Fcγ
RIIIa, Fcγ
RIIIb, or Fcα
RI;c) selecting at least one bacterial cell based on binding of the aglycosylated Fc domain to the first FcR polypeptide. - View Dependent Claims (69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115)
- R polypeptides comprising;
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116. (canceled)
Specification