Stable and aggregation free antibody FC molecules through CH3 domain interface engineering
AssigneeAmgen Inc.
InventorsGunasekaran Kannan, Hongxing Zhou
Life of this patent
Estimating the term…
Abstract
The present invention relates to methods of increasing stability and reducing aggregation in compositions comprising antibody Fc molecules and to composition comprising such molecules. Certain amino acid substitutions in the CH3 domain result in increased stability and reduced aggregation of compositions containing polypeptides comprising a CH3 domain, e.g., an antibody or Fc-fusion protein.
Claims17
A polypeptide homodimer comprising an IgG CH3 domain homodimer, wherein said CH3 domain comprises the amino acid sequence set forth in SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, or SEQ ID NO:5 comprising an alanine substitution at Ser364.
A method of reducing aggregation of a polypeptide comprising a CH3 domain having a serine at position 364, said method comprising:
- a) mutating a nucleic acid encoding the polypeptide such that the serine at position 364 is substituted with alanine;
- b) expressing the nucleic acid of a) in a recombinant host cell culture to produce a polypeptide comprising a CH3 domain having an alanine substitution at Ser364;
- c) purifying the polypeptide from the culture, wherein aggregation of the purified polypeptide is less than 10%.
Dependencies are inferred from the claim text.