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Is hydrophobic interaction chromatography the most suitable technique to characterize site-specific antibody-drug conjugates?

D’ATRI, Valentina and Pell, Reinhard and Clarke, Adrian and GUILLARME, Davy and FEKETE, Szabolcs (2019) Is hydrophobic interaction chromatography the most suitable technique to characterize site-specific antibody-drug conjugates? Journal of Chromatography A, 1586. pp. 149-153. ISSN 0021-9673

Abstract

Antibody drug conjugates (ADCs) belong to the fastest growing class of therapeutic agents for cancer therapy. In preclinical and clinical studies, there is a significant number of site-specific ADCs (also known as third generation ADCs), which are more homogeneous than their previous generations. These new ADC formats in which the inter-chain disulphide bridges (hinge cysteines) are not reduced also need to be deeply characterized. In particular, various quality attributes (QAs) have to be determined, such as free antibody level, average drug to antibody ratio (DAR) and drug distribution. In this contribution, we have demonstrated that these QAs can be determined using reversed phase liquid chromatography (RPLC) for the native ADCs, rather than the historical hydrophobic interaction chromatography (HIC) widely used for hinged cysteines ADC products. In addition, the RPLC approach can be directly coupled to mass spectrometry (MS) for identification of molecular species.
„The authors received feedback by the reviewers of Journal of Chromatography A and have addressed their minor comments. The changes are tracked in the change history of attached word document (i.e. the final manuscript for re-submission).
Regarding changes of IP relevant data, only the logD value of the linker-payload had to be added (due to a reviewer`s request). However, this is considered acceptable, since no other data on the antibody or the linker-payload (such as chemical structures or physical-chemical properties) are shown.”

Item Type: Article
Keywords: Site-specific antibody drug conjugates, Hydrophobic interaction chromatography, Reversed phase liquid chromatography, Mass spectrometry, Biopharmaceuticals
Date Deposited: 30 Apr 2019 00:45
Last Modified: 30 Apr 2019 00:45
URI: https://oak.novartis.com/id/eprint/37540

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