GlycoOptimization for Fully Human and Largely Improved Biopharmaceutical Antibodies and Proteins

The vast majority of therapeutic proteins are, by nature, glycosylated. In the last years the attached glycans attracts more and more attention since an increasing number of data are available showing that glycosylation greatly affects the biopharmaceutical characteristics of the product. This article focuses on the novel GlycoExpress technology that allows to screen for the optimal glycosylation of any protein and to produce the glycooptimized biopharmaceutical for clinical use. GlycoExpress is a toolbox of human, glyco-engineered cell lines to express any protein with fully human glycosylation and in a variety of differentially glycosylated isoforms. In a number of in vitro and in vivo assays the optimally glycosylated protein is identified and the corresponding cell line is further developed for GMP-production of that glycooptimized biopharmaceutical. Twelve proteins have been successfully glycooptimized so far with four antibodies and one protein hormone in late preclinical/early clinical development. Glycooptimization improved these biologics up to several hundred folds in respect to activity, bioavailability, immunogenicity and/or patient coverage. And it is expected that in the near future a number of novel biotherapeutics will be developed whose therapeutic or economic benefit rests upon a fully human and optimized glycosylation.