The advent of Protein A chromatography has streamlined the development of downstream processes for mAbs. However, for most biologic molecules, no corollary affinity purification step exists, necessitating the development of lengthy purification trains. Our goal is to address this shortcoming by creating robust, low-cost peptide affinity ligands for any given biologic target. Using a combination of rational peptide library design and iterative high throughput screening at several scales, we are able to produce a set of lead peptide sequences. These lead compounds are then evaluated chromatographically for their ability to purify the target molecule from clarified cell culture fluid (CCF). Based on these results, a single peptide resin is selected for optimization with respect to synthesis chemistry, ligand density and column operation. In this work, we show the application of our design strategy to the development of affinity ligands for human Growth Hormone (hGH). The resulting peptide resin is used to purify hGH from <i>Pichia Pastoris</i> CCF and is compared to a commercial antibody column in the same process. This work illustrates the potential power of well-designed, synthetic affinity ligands in commercial biomanufacturing.

Design and optimization of peptide affinity resins for downstream processing

249th National Meeting (2015)

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