Software for Determining Proteoform Heterogeneity and Protein Expression Fidelity

Gennext Technologies, Inc., Half Moon Bay CA

Investigators

Abstract

The importance of large protein drugs (biopharmaceuticals) and their generic counterparts, known as biosimilars, has created a need for improved analytics to facilitate biopharmaceutical research and to combat adverse drug reactions. The recombinant protein expression process is inherently prone to low-level errors resulting in sequence variants caused by amino acid misincorporation, which are observed in both native and expressed proteins. The expression system and culturing conditions can influence protein product quality attributes, such as translational fidelity and post-translational modifications. These protein variants (those arising from sequence variants and post-translational modifications) impact product quality in a number of ways that include altered function, activity, ligand/substrate binding, and perturbed protein folding leading to protein aggregation, decreased serum half-life, and diminished therapeutic efficacy to name but a few consequences. An additional concern for biopharmaceuticals is that sequence variants can potentially induce an undesired immune response. Worries for efficacy and patient safety necessitates the need to characterize these low-level protein variants. The detection and quantification of protein variants are challenging currently extremely challenging. The goal of this Phase I STTR will evaluate the feasibility of a new software package to identify and quantify low-level protein variants. Upon successful completion of our program, we will demonstrate the transformative nature of our new technology to positively impact biopharmaceutical research.