Modified fc polypeptides with enhanced sialylation
AssigneeNuvig Therapeutics, Inc.
InventorsPamela B. Conley, Greg P. Coffey, Mark J. Karbarz
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Abstract
The present disclosure relates to compositions containing highly sialylated immunoglobulin Fc polypeptides having an amino acid substitution from phenylalanine to an aliphatic amino acid residue, such as alanine, at amino acid residue 241 of the Fc heavy chain. Further disclosed are methods of manufacturing the highly sialylated Fc polypeptides in a recombinant expression system. Also disclosed are methods of using the disclosed compositions for the treatment of an inflammatory disease or disorder.
Claims104
A population of modified Fc polypeptides, each modified Fc polypeptide having (i) an amino acid sequence at least 75% identical to the sequence of SEQ ID NO:
- 2 and (ii) an aliphatic amino acid residue at position 241 (numbered according to Kabat;
- corresponding to amino acid residue 32 of SEQ ID NO:
- 2), comprising:
- at least 60% of the modified Fc polypeptides having a sialic acid (SA) moiety attached to an N-glycan of the Fc polypeptide via an α(2,6) linkage.
A population of modified Fc polypeptides, each modified Fc polypeptide having (i) an amino acid sequence at least 75% identical to the sequence of SEQ ID NO:
- 2 and (ii) an aliphatic amino acid residue at position 241 (numbered according to Kabat;
- corresponding to amino acid residue 32 of SEQ ID NO:
- 2), comprising:
- about 40% of the modified Fc polypeptides having a SA moiety attached to the N-glycan of the Fc polypeptide via an α(2,3) linkage.
A nucleic acid expression vector, comprising:
- (a) a first expression cassette, comprising:
- a first mammalian promoter operably linked to a polynucleotide encoding a modified Fc polypeptide having:
- (i) an amino acid sequence at least 75% identical to the sequence of SEQ ID NO:
- 2 and (ii) an aliphatic amino acid residue at position 241 (numbered according to Kabat;
- corresponding to amino acid residue 32 of SEQ ID NO:
- 2);
- and
- (b) a second expression cassette, comprising:
- a second mammalian promoter operably linked to a polynucleotide encoding a beta-galactoside alpha-2,6-sialyltransferase 1 (ST6GAL1) enzyme.
Dependencies are inferred from the claim text.