Aglycosylated antibodies and the methods of making and using them: WO2008030564.
More than 20 recombinant IgG antibody therapeutics are now licensed for the treatment of a variety of diseases and there are, literally, hundreds under development. Human IgG is a glycoprotein and the presence of oligosaccharides, attached at a single site, can decisively influence the mode of action of recombinant antibody therapeutics (rMAbs) and efficacy can vary depending on the particular oligosaccharide attached. This represents a considerable challenge to the biopharmaceutical industry; however, production vehicles are becoming available that allow for the manufacture of rMAbs bearing preselected oligosaccharides. The patent under review offers a radical alternative approach through the application of protein engineering to generate aglycosylated IgG molecules with restored and/or enhanced effector activities. Removal of the need for glycosylation has the potential to widen, and simplify, the production vehicles that could be used. It remains to be demonstrated that such radical structural changes do not have a negative impact on the stability and immunogenicity of these constructs.
Jefferis
Roy
R
Professor of Molecular Immunology University of Birmingham, Division of Immunity & Infection, B15 2TT UK. R.Jefferis@bham.ac.UK
D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology*; D015195:Drug Design; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology*; D009844:Oligosaccharides / Q000737:chemistry; D010330:Patents as Topic; D011487:Protein Conformation; D015202:Protein Engineering; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D009844:Oligosaccharides; D011994:Recombinant Proteins