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Antibodies 2018, 7(3), 29; https://doi.org/10.3390/antib7030029

Tuning Relative Polypeptide Expression to Optimize Assembly, Yield and Downstream Processing of Bispecific Antibodies

Novimmune SA, 14 Chemin des Aulx, 1228 Plan-les-Ouates, Switzerland
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Received: 5 July 2018 / Revised: 3 August 2018 / Accepted: 6 August 2018 / Published: 10 August 2018
(This article belongs to the Special Issue Bispecific Antibodies-Opportunities and Challenges)
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Abstract

Bispecific antibodies (bsAbs) are often composed of several polypeptide chains that have to be expressed adequately to enable optimal assembly and yield of the bsAb. κλ bodies are a bispecific format with a native IgG structure, composed of two different light chains that pair with a common heavy chain. Introduction of non-optimal codons into the sequence of a particular polypeptide is an effective strategy for down modulating its expression. Here we applied this strategy but restricted the modification of the codon content to the constant domain of one light chain. This approach facilitates parallel optimization of several bsAbs by using the same modified constant domains. Partial sequence de-optimization reduced expression of the targeted polypeptide. Stable cell pools could be isolated displaying increased bispecific antibody titers as well as changes in the abundance of undesired by-products that require elimination during downstream processing. Thus, modulating the relative expression of polypeptides can have a significant impact on bsAb titer and product related impurities; which are important factors for large scale manufacturing for clinical supply. View Full-Text
Keywords: affinity chromatography; bispecific antibody; codon optimization; co-expression; transient transfection; stable pools; product related impurities affinity chromatography; bispecific antibody; codon optimization; co-expression; transient transfection; stable pools; product related impurities
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Magistrelli, G.; Pontini, G.; Poitevin, Y.; Malinge, P.; Bourguignon, J.; Gauye, F.; Fleury, E.; Plèche, N.; Galissaires, L.; Fischer, N. Tuning Relative Polypeptide Expression to Optimize Assembly, Yield and Downstream Processing of Bispecific Antibodies. Antibodies 2018, 7, 29.

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