GlycoExpress™ and GlycoOptimization
Modification and control of glycosylation is turning into a pivotal aspect in the development of biotherapeutics, as it is strongly affecting key properties such as the bioactivity, solubility, stability, serum half-life and immunogenicity/antigenicity. As it is applied by the host cell line largely independent of the protein´s amino acid sequence, biotherapeutics produced in hamster or mouse cell lines carry a non-human and considerably different glycosylation that leads in some cases to severe immunogenic reactions.
GlycoExpress™ (GEX™) offers
- Human cell lines for production of human biotherapeutics with human glycosylation and
- A toolbox of human glycoengineered cell lines to glycooptimize biotherapeutics with largely improved bioactivity and bioavailability and no immunogenicity.
Applicable are all glycoproteins, e.g. antibodies, growth factors, protein hormones, blood factors, cytokines, and enzymes, and mixtures of glycoproteins, such as cellular and viral vaccines.
- A fully human glycosylation and other human posttranslational modifications
- Screening for the optimal glycosylation of a given protein (glycooptimization)
- Rapid generation of serum-free, high yield production cell clones that are suitable for a GMP production process.
In the case of several products and case studies projects the bioactivity and bioavailability of antibodies, growth factors and vaccines improved and expressed with GlycoExpress™ was increased up to 1000 fold.
In this example, for a glycooptimized antibody the antibody dependent cellular cytotoxicity (ADCC) has been increased manifold compared to the original antibody. The level of ADCC depends on the phenotype (V/V, V/F or F/F) of a FcγIIIa-receptor polymorphism, causing the original antibody that is not glycooptimized to be effective in just about 30% of the population. The increase in ADCC due to superior glycosylation in turn renders the improved antibody suitable for treatment of all patient sub-populations.
The approval of the lead antibody GT-MAB 2.5-GEX™ to initiate clinical trials has been obtained in November 2009, clinical phase I is currently ongoing with first results expected for summer 2010. The second generation antibody GT-MAB 5.2-GEX™ is scheduled to enter the clinic in Q2/Q3 2010.
The GlycoExpress™ technology is protected by a number of patents permitting the protection of new generations of biologics and biopharmaceuticals with a new patent.
The glycoengineered human cell lines of the GlycoExpress™ toolbox are purely suspension cells of leukemic origin and have been designed to differ in their glycosylation capabilities. This allows the expression of a protein with a variety of complex N- and O-glycans (e.g. high or low percentages of sialylation, fucosylation and galactosylation) and in-process glycosylation adjustment (e.g. gradual degrees of sialylation or fucosylation from 0% to the naturally permitted maximum).
The biotechnological features of all GlycoExpress™ cell lines are superior to standard CHO cells, especially with regard to productivity, doubling time, robustness and cell densities. They are easy to transfect stably and transiently and to clone at the single cell level under serum free conditions. Proprietary vector and gene amplification systems, automatic cell cloning and selection by the ClonePixFL lead very fast to high yield cell clones. The cell lines are not transformed virally and are free of any infectious particles, mycoplasma or viruses as analyzed after deposition of a master cell bank under GMP.