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 defucosylated antibodies, and highly and potential fully human glycosylated proteins our proprietary human GEX® cell line in combination with perfusion technology is the system of choice.

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 glycoengineering 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., IgG, IgM, IgA)
  • Defucosylated antibodies
  • Bispecific antibodies/ fragments (e.g., NK-cell/ T-cell recruiters)
  • Difficult-to-express and complex glyco-sylated proteins (e.g., rhSP-D and others)
  • Blood factors (e.g., FVII)
  • Protein hormones (e.g., FSH, HCG)
  • Fusion proteins with extended serum half-life
  • Enzymes (e.g., for enzyme replacement therapy)
Dr. Doreen Weigelt
t: +49 (0)30 9489 2600

Regulatory Approval/Endorsement

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

  • Human cell line with stable expression
  • Platform manufacturing process with reliable outcome, stable product quality, esp. glycosylation and minimized batch-to batch variations
  • High productivity for glycooptimized products (R&D):

The complete 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 with GEX® cell lines within different projects, 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 biotherapeutic’s properties such as bioactivity, solubility, stability, serum half-life and immunogenicity. 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

used for products were high sialylation and high core fucosylation is required
used for products were high sialylation and high core fucosylation is required
allows gradual adjustment of the sialylation degree for screening of the optimal content of sialic acid on the product
allows gradual adjustment of the fucosylation degree for screening of the optimal content of fucose for the respective product
Further glycoengineered cell lines are continuously developed (e.g. a cell line for the production of glycoproteins with high amount of mannose-6-phosphate or SialoMax additionally glycoengineered to eliminate N-glycan linked GalNAc for products with further reduced serum clearance)
mAbExpress®
used for products were high sialylation and high core fucosylation is required
SialoMax®
used for products were high sialylation and high core fucosylation is required
SialoFlex®
allows gradual adjustment of the sialylation degree for screening of the optimal content of sialic acid on the product
FucoFlex®
allows gradual adjustment of the fucosylation degree for screening of the optimal content of fucose for the respective product
Other
Further glycoengineered cell lines are continuously developed (e.g. a cell line for the production of glycoproteins with high amount of mannose-6-phosphate or SialoMax additionally glycoengineered to eliminate N-glycan linked GalNAc for products with further reduced serum clearance)

ADCC improvement

GEX® is the platform of choice that provides the opportunity to combine several features to maximize the ADCC (antibody-dependent cell-mediated cytotoxicity) activity of fully human glycooptimized monoclonal antibodies. The combination of minimizing fucosylation, maximizing galactosylation and branching enables ADCC activity to be maximally increased.

CHO Cell Line Development with external partners

Despite development in GEX® cells, we offer development in customers’ own cell lines. In cooperation with reliable partners, we develop high level stable expression CHO, NSO, SP2/0 and other cell lines suitable for fed-batch or perfusion processes.

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.

 

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