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Immunoprecipitation LC-MS Middle-up Approach for In Vivo Drug-To-Antibody Ratio Determination for Antibody Drug Conjugates

Davis, John and Kagan, Mark and Read, Jessica and Walles, Markus and Hatsis, Panagiotis (2017) Immunoprecipitation LC-MS Middle-up Approach for In Vivo Drug-To-Antibody Ratio Determination for Antibody Drug Conjugates. Bioanalysis.

Abstract

Aim: Drug-to-antibody ratio (DAR) is a critical determinant in the development of antibody drug conjugates (ADCs). This work presents a middle-up approach for DAR analysis providing increased sensitivity and structural information when compared to intact analysis. Methodology/results: Cysteine, engineered cysteine and disulfide linked ADCs, each with two different linker-payloads were dosed to mice. Samples were immunocaptured and digested to scFc and F(ab’)2 fragments. At this point, disulfide linked ADCs were analyzed while cysteine and engineered cysteine ADCs were reduced to LC and Fd’ fragments for analysis. Results were precise, accurate and sensitive, allowing DAR to be determined out to 21 days. Conclusion: This work describes a method that is easily implemented, amenable to high throughput analysis, and does not require specialized reagents or equipment.

Item Type: Article
Date Deposited: 21 Nov 2017 00:45
Last Modified: 21 Nov 2017 00:45
URI: https://oak.novartis.com/id/eprint/33458

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