Protein-free fed-batch culture of non-GS NS0 cell lines for production of recombinant antibodies

Authors

  • John E. Burky,

    Corresponding author
    1. Process Sciences and Engineering, PDL BioPharma, Inc., 34700 Campus Drive, Fremont, California 94555; telephone: 510-574-1428; fax: 510-574-1500
    • Process Sciences and Engineering, PDL BioPharma, Inc., 34700 Campus Drive, Fremont, California 94555; telephone: 510-574-1428; fax: 510-574-1500.
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  • Mark C. Wesson,

    1. Process Sciences and Engineering, PDL BioPharma, Inc., 34700 Campus Drive, Fremont, California 94555; telephone: 510-574-1428; fax: 510-574-1500
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  • Amy Young,

    1. Process Sciences and Engineering, PDL BioPharma, Inc., 34700 Campus Drive, Fremont, California 94555; telephone: 510-574-1428; fax: 510-574-1500
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  • Sharyn Farnsworth,

    1. Process Sciences and Engineering, PDL BioPharma, Inc., 34700 Campus Drive, Fremont, California 94555; telephone: 510-574-1428; fax: 510-574-1500
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  • Ben Dionne,

    1. Process Sciences and Engineering, PDL BioPharma, Inc., 34700 Campus Drive, Fremont, California 94555; telephone: 510-574-1428; fax: 510-574-1500
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  • Ying Zhu,

    1. Process Sciences and Engineering, PDL BioPharma, Inc., 34700 Campus Drive, Fremont, California 94555; telephone: 510-574-1428; fax: 510-574-1500
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  • Taymar E. Hartman,

    1. Process Sciences and Engineering, PDL BioPharma, Inc., 34700 Campus Drive, Fremont, California 94555; telephone: 510-574-1428; fax: 510-574-1500
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  • Limin Qu,

    1. Process Sciences and Engineering, PDL BioPharma, Inc., 34700 Campus Drive, Fremont, California 94555; telephone: 510-574-1428; fax: 510-574-1500
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  • Weichang Zhou,

    1. Process Sciences and Engineering, PDL BioPharma, Inc., 34700 Campus Drive, Fremont, California 94555; telephone: 510-574-1428; fax: 510-574-1500
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  • Paul W. Sauer

    1. Process Sciences and Engineering, PDL BioPharma, Inc., 34700 Campus Drive, Fremont, California 94555; telephone: 510-574-1428; fax: 510-574-1500
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Abstract

Presented is a novel antibody production platform based on the fed-batch culture of recombinant, NS0-derived cell lines. A standardized fed-batch cell culture process was developed for five non-GS NS0 cell lines using enriched and optimized protein-free, cholesterol-free, and chemically defined basal and feed media. The process performed reproducibly and scaled faithfully from the 2-L to the 100-L bioreactor scale achieving a volumetric productivity of > 120 mg/L per day. Fed-batch cultures for all five cell lines exhibited significant lactate consumption when the cells entered the stationary or death phase. Peak and final lactate concentrations were low relative to a previously developed fed-batch process (FBP). Such low lactate production and high lactate consumption rates were unanticipated considering the fed-batch culture basal medium has an unconventionally high initial glucose concentration of 15 g/L, and an overall glucose consumption in excess of 17 g/L. The potential of this process platform was further demonstrated through additional media optimization, which has resulted in a final antibody concentration of 2.64 ± 0.19 g/L and volumetric productivity of > 200 mg/L per day in a 13-day FBP for one of the five production cell lines. Use of this standardized protein-free, cholesterol-free NS0 FBP platform enables consistency in development time and cost effectiveness for manufacturing of therapeutic antibodies. Biotechnol. Bioeng. 2007;96: 281–293. © 2006 Wiley Periodicals, Inc.

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