Meyer, Robina M., Berger, Lukas, Nerkamp, Joerg, Scheler, Stefan, Nehring, Sebastian and Friess, Wolfgang (2021) Identification of Monoclonal Antibody Variants Involved in Aggregate Formation - Part 1: Charge Variants. European journal of pharmaceutics and biopharmaceutics, 158. pp. 123-131. ISSN 1873-3441

Abstract

Biopharmaceutical products contain conformational and chemical variants, that are typically well characterized regarding identity and activity. However, little is known about their self-interaction propensity and tendency to unfold, which are critical characteristics for drug stability and safety. This study aimed to separate and compare charge variants of a monoclonal antibody (mAb) and to identify aggregation prone species. We show a semi-preparative cation exchange method, that we developed to separate the individual
acidic and basic variants from the naive mAb. Additionally, we demonstrate, that the yield and purity of the fractionated charge species, extracted by that method, were suffient for subsequent analysis of aggregate content, conformation stability and selfinteraction. Our analysis revealed a differently behaving acidic variant and confirmed its increased aggregation propensity by molecular modeling. During a stability study, the potentially aggregation prone charge variant posed a limited risk to the DS. We are the first
to look at the stability of single charge variants of biopharmaceuticals, and thus present
manufacturers and regulatory authorities with a method to enhance drug safety.

Item Type:	Article
Keywords:	mAb charge variants, protein aggregation, protein stability, FPLC, light scattering, differential scanning fluorimetry
Date Deposited:	23 Feb 2021 00:45
Last Modified:	23 Feb 2021 00:45
URI:	https://oak.novartis.com/id/eprint/43010