Develop Systems for Manufacturing 100,000,000 Doses of an Emergency Pharmaceutical (e.g. Vaccine or Monoclonal Antibody) Within 2 Months of Product Identification

Baldwin, Toby; Estell, Dave; Fung, Janice; Lin, Cherry; Pucci, Jeff P.; Razo, Jennifer; Rider, Beverly; Throndset, William; Trimbur, Don; Gastel, Frans Van; Wang, Huaming; Ward, Mick

doi:10.21236/ada455424

Cited by 2 publications

(4 citation statements)

References 10 publications

(11 reference statements)

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“…Protease degradation is clearly an issue in these strains. Titers in the fermentation of T. reesei expressing Herceptin can diminish from over 4 g/L at 66 hr to less than 1 g/L by 167 hr (Baldwin et al, ). Deletion of six protease genes can mitigate the degradation of HC antibody (Landowski et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…Filamentous fungi are used extensively to produce industrial enzymes and examples of monoclonal antibody expression have been shown in several hosts including T. reesei (Baldwin et al, ). Historically, the expression of heterologous proteins in filamentous fungi has used random integration.…”

Section: Antibody Production In Alternative Hostsmentioning

confidence: 99%

“…A second configuration (Figure b) used a carrier protein to help facilitate the secretion of the HC or LC independently (Baldwin et al, ; Ward, Wilson, Kodama, Rey, & Berka, ). Native carrier proteins can increase expression of heterologous proteins in various filamentous fungi, including the use of cellobiohydrolase 1 (CBHI) in T. reesei (Keränen & Penttilä, ) and glucoamylase A (GlaA) in A. oryzae (Tsuchiya, Gomi, Kitamoto, Kumagai, & Tamura, ; Ward et al, ).…”

Section: Antibody Production In Alternative Hostsmentioning

confidence: 99%

Section: Filamentous Fungimentioning

confidence: 99%

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Challenging the workhorse: Comparative analysis of eukaryotic micro‐organisms for expressing monoclonal antibodies

Jiang

Horwitz

Wright

et al. 2019

Biotech & Bioengineering

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For commercial protein therapeutics, Chinese hamster ovary (CHO) cells have an established history of safety, proven capability to express a wide range of therapeutic proteins and high volumetric productivities. Expanding global markets for therapeutic proteins and increasing concerns for broadened access of these medicines has catalyzed consideration of alternative approaches to this platform. Reaching these objectives likely will require an order of magnitude increase in volumetric productivity and a corresponding reduction in the costs of manufacture. For CHO‐based manufacturing, achieving this combination of targeted improvements presents challenges. Based on a holistic analysis, the choice of host cells was identified as the single most influential factor for both increasing productivity and decreasing costs. Here we evaluated eight wild‐type eukaryotic micro‐organisms with prior histories of recombinant protein expression. The evaluation focused on assessing the potential of each host, and their corresponding phyla, with respect to key attributes relevant for manufacturing, namely (a) growth rates in industry‐relevant media, (b) adaptability to modern techniques for genome editing, and (c) initial characterization of product quality. These characterizations showed that multiple organisms may be suitable for production with appropriate engineering and development and highlighted that yeast in general present advantages for rapid genome engineering and development cycles.

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Section: Discussionmentioning

confidence: 99%

Section: Antibody Production In Alternative Hostsmentioning

confidence: 99%