Antibody Drug Conjugates are a novel therapeutic class of compounds which utilize highly-specific monoclonal antibodies to target the delivery of highly potent small molecules to therapeutics targets. This targeted delivery allows the highly potent therapeutics to be used at low levels which minimizes their toxicity while achieving superior efficacy. Along with these benefits of antibody-drug conjugates comes more complexity in the form of a drug containing both functional small molecule and large molecule components. For this reason, novel approaches and analytical techniques are required to characterize antibody drug conjugates during their synthesis (conjugation) as well as during formulation and storage. For instance, one of the most critical assays for an antibody drug conjugates is the measuring the small molecule to large molecule ratio (the drug-to-antibody or DAR assay); several analytical techniques have been developed for measurement of DAR ratios and the benefits and shortcomings of each will be discussed as will other analytical characterization techniques. For stability of antibody drug conjugates, assessing the stability of the small molecule while conjugated to a monoclonal antibody is exceedingly important but has proven to be remarkably difficult. We have employed a surrogate model to mimic conjugated drugs in monoclonal antibody formulations. In this model, N-acetyl cysteine is conjugated to the free drug (or linker drug) to reproduce the same conjugation motif without the additional bulk of the antibody. As will be presented, the stability and degradation of the conjugated drug in this model was used to predict the stability of the small molecule in the antibody drug conjugate itself.

Analytical characterization of antibody-drug conjugates

248th National Meeting (2014)

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