Jefferis Roy
Professor of Molecular Immunology University of Birmingham, Division of Immunity & Infection, B15 2TT UK.
Expert Opin Ther Pat. 2009 Jan;19(1):101-5. doi: 10.1517/13543770802592408.
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.
目前已有20多种重组IgG抗体疗法获批用于治疗多种疾病，实际上，还有数百种正处于研发阶段。人IgG是一种糖蛋白，寡糖在单一位点的附着能够决定性地影响重组抗体疗法（rMAbs）的作用方式，其疗效会因所附着的特定寡糖而有所不同。这对生物制药行业构成了相当大的挑战；然而，现在已有生产载体可用于制造带有预先选定寡糖的rMAbs。正在审查的这项专利提供了一种激进的替代方法，即通过应用蛋白质工程来生成具有恢复和/或增强效应子活性的无糖基化IgG分子。消除糖基化需求有可能拓宽并简化可使用的生产载体。仍有待证明的是，这种激进的结构变化不会对这些构建体的稳定性和免疫原性产生负面影响。
