A scalable low-cost cGMP process for clinical grade production of the HIV inhibitor 5P12-RANTES in Pichia pastoris

Abstract

In the continued absence of an effective anti-HIV vaccine, approximately 2 million new HIV infections occur every year, with over 95% of these in developing countries. Calls have been made for the development of anti-HIV drugs that can be formulated for topical use to prevent HIV transmission during sexual intercourse. Because these drugs are principally destined for use in low-resource regions, achieving production costs that are as low as possible is an absolute requirement. 5P12-RANTES, an analog of the human chemokine protein RANTES/CCL5, is a highly potent HIV entry inhibitor which acts by achieving potent blockade of the principal HIV coreceptor, CCR5. Here we describe the development and optimization of a scalable low-cost production process for 5P12-RANTES based on expression in Pichia pastoris. At pilot (150 L) scale, this cGMP compliant process yielded 30 g of clinical grade 5P12-RANTES. As well as providing sufficient material for the first stage of clinical development, this process represents an important step towards achieving production of 5P12-RANTES at a cost and scale appropriate to meet needs for topical HIV prevention worldwide.

DOI: 10.1016/j.pep.2015.10.011

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Cite this paper

@inproceedings{Cerini2016ASL, title={A scalable low-cost cGMP process for clinical grade production of the HIV inhibitor 5P12-RANTES in Pichia pastoris}, author={Fabrice Cerini and Hubert F Gaertner and Knut R. Madden and Ilya Tolstorukov and Scott Andrew Brown and Bram Laukens and Nico Callewaert and Jay C. Harner and Anna M. Oommen and John T. Harms and Anthony R. Sump and Robert C. Sealock and Dustin Peterson and Scott K. Johnson and Stephan B. Abramson and Michael M. Meagher and Robin E. Offord and Oliver Hartley}, booktitle={Protein expression and purification}, year={2016} }