Enhanced expression of a biosimilar monoclonal antibody with a novel NS0 platform

Biotechnology Progress
Darryl SampeyWilliam E Bentley

Abstract

The precise product quality and lower cost of goods demands of the growing biosimilars industry are driving biomanufacturing innovation. Biosimilar cell lines that produce complex glycoproteins such as monoclonal antibodies must be both highly productive and express a product with critical quality attributes closely matching those of the innovator reference. In this work, a biomanufacturing platform is described that harnesses the commercially-established NS0 host cell in new ways to create stable, highly productive cell lines with characteristics meeting the current demands. A cholesterol metabolic selection marker and implementation strategy that can be generically applied are shown to yield high expressing cell lines as well as eliminate the need for cholesterol addition, which has been a significant barrier in both stainless steel reactors as well as in single-use plastic systems. Additionally, for the first time, a multiplex selection strategy was implemented that served to increase NS0 cell line specific productivity >10-fold and volumetric yields >6-fold. The best overall performing cell line had a Qp of 28.5 picograms per cell per day and was rapidly adapted to a lean production medium. Yields in l-glutamine fed-batch s...Continue Reading

References

Dec 1, 1988·In Vitro Cellular & Developmental Biology : Journal of the Tissue Culture Association·J D SatoC J Welsh
Apr 1, 1996·Current Opinion in Biotechnology·G Georgiou, P Valax
Jun 16, 2001·Biotechnology and Bioengineering·R R Balcarcel, G Stephanopoulos
Sep 29, 2005·Biotechnology and Bioengineering·Gargi SethWei-Shou Hu
Jul 11, 2006·Advanced Drug Delivery Reviews·John R Birch, Andrew J Racher
Oct 6, 2006·European Journal of Clinical Pharmacology·A CeciI Wong
Oct 13, 2006·Nature Biotechnology·Gary Walsh, Roy Jefferis
Feb 15, 2007·Journal of Bioscience and Bioengineering·Jessica OkonkowskiMichel Chartrain
Mar 1, 1998·Cytotechnology·R L DuttonM Moo-Young
Mar 30, 2012·BMJ : British Medical Journal·Deborah Cohen
May 24, 2012·Biotechnology & Genetic Engineering Reviews·Darius GhaderiAjit Varki
Apr 5, 2013·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Asterios S TsiftsoglouChristian K Schneider
Jan 1, 2012·Pharmaceuticals·Jun Wang, Shein-Chung Chow

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Citations

Dec 2, 2018·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Venkata Gayatri DharaMichael J Betenbaugh

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