GEX® cell line for production of complex biopharmaceuticals
For standard IgG1-antibodies, CHO-expression systems combined with platform fed-batch process fermentation are very productive and cost effective. For de-fucosylated antibodies, for scaffolds and highly and potential fully human glycosylated proteins our proprietary human GEX® cell line in combination with perfusion technology is the system of choice.
CHO-Cell Line Development with external partners
In cooperation with reliable partners, we develop high level stable expression CHO cell lines suitable for fed-batch.
For cultivation, we use commercially available animal component free and/or chemically defined cell culture media and feeds. We make sure that a proper documentation of the cell line history and generation is made available for our customers.
Human Cell Line Development GEX®
GlycoExpress® (GEX®) is an expression platform for expression of a variety of different biopharmaceuticals with fully human glycosylation. Additionally, the technology allows the optimization of glycosylation to improve activity and/or other properties like bioavailability, stability, and/or immunogenicity for better clinical performance. It is based on proprietary human cell lines generated by glyco-engineering and biotechnologically, optimized for both product optimization and fast, high reproducible and high yield glycoprotein production.
Glycotope GEX® technology provides an expression technology platform proven for:
- Antibodies of different isotypes
(e.g IgG1, IgG2, IgM, IgA)
- Defucoslyated antibodies
- Bispecific antibodies
- Complex glycosylated antibodies
- Protein hormones
GEX® has regulatory approval by FDA, EMA and German regulatory authorities (PEI, BfArM) for manufacturing of biopharmaceuticals. For GEX® no viruses, nor viral particles, nor reverse transcriptase activity have been detected with any of the large test panels performed so far. Regulatory bodies (US and EU) stated that the cell line characterization performed is in accordance to appropriate guidance and is adequate for production of biopharmaceuticals for clinical studies and market entry.
Process Platform with Superior Economy
- Platform manufacturing process with reliable outcome
- Minimized batch-to-batch variations
- Homogenous, stable and fully human glycosylation patterns
- Stable protein quality resulting in reduced downstream costs
- Minimal product aggregation at increased yields
- Cost effective large scale production
Key Features of GEX® Expression and Process Platform
- Derived from a human blood cell immortalized spontaneously
- Bioprocess based on perfusion
- High productivity for glyco-optimized products (R&D): (total yield per 40 day perfusion run per L bioreactor volume)
~15-22 g/L IgG antibody (ADCC enhanced)
~10-15 g/L IgA antibody
~3 g/L IgM antibody
~0.2 g/L for protein hormones
~4 g/L for human blood factors
- High density: ~up to 5*107 cells/ml
- Fast cell division: ~24 h
- Stable expression: ~100% of starting productivity for at least 10 weeks (without selection pressure)
- High shear force resistance
The full GEX® cell line development, glycooptimization process and production can be performed at Glycotope. This set up ensures all know-how and optimal quality and speed for the transition into clinical development. To date, more than 40 GMP production runs have been performed, showing unique reproducibility with no measurable differences between batches, batch sizes, process adaptions, scales and production sites, all of which guarantees flexible and reliable production with highly reproducible quality. These GMP runs include various bioreactor sizes of up to 1000 L.
Optimization of Glycosylation
Glycosylation strongly affects key biotherapeutics properties such as bioactivity, solubility, stability, serum half-life and immunogenicity/antigenicity. Thus, modification and control of glycosylation are both important in developing such therapeutics. Glycosylation is dependent on the host cell line. Biotherapeutic glycoproteins produced in hamster or mouse cell lines carry non-human and significantly different glycosylation, in some cases this leads to severe immunogenic reactions.
This screening and high yield production platform is based upon proprietary glyco-engineered human cell lines for the development and production of biotherapeutics with a human and optimized glycosylation.
GlycoExpress® toolbox of glyco-engineered proprietary human cell lines for fast & high yield expression of higher active antibodies & glycoprotein biopharmaceuticals
GEX® is today the only platform that provides the opportunity to combine several features to maximize the ADCC (antibody-dependent cell-mediated cytotoxicity) activity of fully human glyco-optimized monoclonal antibodies. The combination of minimizing fucosylation, maximizing galactosylation and branching enables ADCC activity to be maximally increased.