Research

Molecular Biotechnology

, Volume 45, Issue 3, pp 257-266

Open Access This content is freely available online to anyone, anywhere at any time.

Single-Batch Production of Recombinant Human Polyclonal Antibodies

  • Lars S. NielsenAffiliated withSymphogen A/S, Elektrovej
  • , Alexandra BaerAffiliated withSymphogen A/S, Elektrovej
  • , Christian MüllerAffiliated withSymphogen A/S, Elektrovej
  • , Kristian GregersenAffiliated withSymphogen A/S, Elektrovej
  • , Nina T. MønsterAffiliated withSymphogen A/S, Elektrovej
  • , Søren K. RasmussenAffiliated withSymphogen A/S, Elektrovej
  • , Dietmar WeilgunyAffiliated withSymphogen A/S, Elektrovej
  • , Anne B. TolstrupAffiliated withSymphogen A/S, Elektrovej Email author 

Abstract

We have previously described the development and implementation of a strategy for production of recombinant polyclonal antibodies (rpAb) in single batches employing CHO cells generated by site-specific integration, the SympressTM I technology. The SympressTM I technology is implemented at industrial scale, supporting a phase II clinical development program. Production of recombinant proteins by site-specific integration, which is based on incorporation of a single copy of the gene of interest, makes the SympressTM I technology best suited to support niche indications. To improve titers while maintaining a cost-efficient, highly reproducible single-batch manufacturing mode, we have evaluated a number of different approaches. The most successful results were obtained using random integration in a new producer cell termed ECHO, a CHO DG44 cell derivative engineered for improved productivity at Symphogen. This new expression process is termed the SympressTM II technology. Here we describe proof-of-principle data demonstrating the feasibility of the SympressTM II technology for single-batch rpAb manufacturing using two model systems each composed of six target-specific antibodies. The compositional stability and the batch-to-batch reproducibility of rpAb produced by the ECHO cells were at least as good as observed previously using site-specific integration technology. Furthermore, the new process had a significant titer increase.

Keywords

Antibody production Recombinant polyclonal antibodies Clonal cell lines Compositions of cell lines DHFR selection Random integration CHO-DG44 Batch-to-batch consistency Single-batch manufacturing