Fc containing polypeptides with altered glycosylation and reduced effector function
AssigneeGenzyme Corporation
InventorsClark Pan, Huawei Qiu
Life of this patent
Estimating the term…
Abstract
Provided are binding polypeptides (e.g., antibodies), and drug conjugates thereof, comprising an Fc domain with an altered glycosylation profile and reduced effector function. In particular embodiment, the Fc domain comprises: an asparagine residue at amino acid position 298, according to EU numbering; and a serine threonine residue at amino acid position 300, according to EU numbering. Also provided are nucleic acids encoding the antigen-binding polypeptides, recombinant expression vectors and host cells for making such antigen-binding polypeptides. Methods of using the antigen-binding polypeptides disclosed herein to treat disease are also provided.
Claims39
An isolated binding polypeptide comprising an Fc domain, wherein the Fc domain comprises:
- an asparagine residue at amino acid position 298, according to EU numbering;
- and a serine or threonine residue at amino acid position 300, according to EU numbering, and wherein the binding polypeptide has a lower affinity for an Fcγ receptor than a binding polypeptide having a native Fc domain.
An isolated binding polypeptide comprising an Fc domain, wherein the Fc domain comprises:
- a free asparagine residue at amino acid position 298, according to EU numbering;
- and a free serine or threonine residue at amino acid position 300, according to EU numbering.
An isolated binding polypeptide comprising an Fc domain, wherein the Fc domain comprises:
- an N-glycan linked to an asparagine residue at amino acid position 298, according to EU numbering;
- and a free serine or threonine residue at amino acid position 300, according to EU numbering.
An isolated binding polypeptide comprising a human IgG1 Fc domain, wherein the Fc domain comprises:
- an asparagine residue at amino acid position 297, according to EU numbering;
- a glycosylated asparagine residue at amino acid position 298, according to EU numbering;
- an amino acid at position 299, according to EU numbering, wherein said amino acid at position 299 is not proline;
- and a serine or threonine residue at amino acid position 300, according to EU numbering.
An isolated binding polypeptide comprising a human IgG1 Fc domain, wherein the Fc domain comprises:
- an glutamine residue at amino acid position 297, according to EU numbering;
- a glycosylated asparagine residue at amino acid position 298, according to EU numbering;
- an amino acid at position 299, according to EU numbering, wherein said amino acid at position 299 is not proline;
- and a serine or threonine residue at amino acid position 300, according to EU numbering.
An isolated binding polypeptide comprising a human IgG1 Fc domain, wherein the Fc domain comprises:
- an asparagine residue at amino acid position 297, according to EU numbering;
- a glycosylated asparagine residue at amino acid position 298, according to EU numbering;
- an alanine residue at amino acid position 299, according to EU numbering;
- and a serine or threonine residue at amino acid position 300, according to EU numbering.
An isolated binding polypeptide comprising a human IgG4 Fc domain, wherein the Fc domain comprises:
- a glycosylated asparagine residue at amino acid position 298, according to EU numbering;
- an alanine residue at amino acid position 299, according to EU numbering;
- and a serine or threonine residue at amino acid position 300, according to EU numbering.
Dependencies are inferred from the claim text.