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Use of a generic LC-MS/MS assay to characterize atypical PK profile of a biotherapeutic monoclonal antibody

Law, Wai Siang and Genin, Jean-Christophe and Miess, Christian and Treton, Gwenola and Warren, Andrew Paul and Lloyd, Peter and Dudal, Sherri and Krantz, Carsten (2014) Use of a generic LC-MS/MS assay to characterize atypical PK profile of a biotherapeutic monoclonal antibody. Bioanalysis, 6 (23). pp. 3225-3235. ISSN 1757-6180

Abstract

Background: The fully human monoclonal antibody mAb123 which binds to and neutralizes chemokine motif ligand-21 (CCL21) displays a faster clearance in cynomolgus monkey compared to typical IgG kinetics. Two variants of LC-MS/MS assays were developed to better understand this rapid clearance, previously established by ELISA. Results: Excellent correlation of LC-MS/MS PK data with ELISA data confirmed the rapid clearance of mAb123, indicating that this is an intrinsic property of the molecule. In one study, two animals tested positive for anti-mAb123 antibodies, in one animal these antibodies resulted in lower serum concentrations of mAb123. The LC-MS/MS assay indicates that the underlying reason for this apparent rapid disappearance of mAb123 from serum is due to catabolism, rather than interference of anti-mAb123 antibodies in the ELISA assay. Conclusions: The data illustrate that in cases of unexpected results from ligand binding assays, application of orthogonal bioanalytical techniques such as LC-MS/MS can add value.

Item Type: Article
Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13
URI: https://oak.novartis.com/id/eprint/11458

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