Site-Specific ADC Generation Using SMARTag™ Technology

October 27, 2015

Catalent’s SMARTag™ technology enables biologic innovators to develop more efficacious antibody drug conjugates. It allows site-specific, programmable drug placement using proprietary cytotoxin-linkers/conjugation chemistry in an efficient and scalable process.

 

 

Catalent's SMARTag technology allows for the design of antibody drug conjugates with defined molecular architecture. By combining a flexible payload site selection; novel, versatile aldehyde conjugation chemistry; stable, modular, and adaptable triggers for payload release; and a diverse library of payloads, the technology is compatible with any cell based expression system, such as Catalent's GPEx® mammalian cell line development technology.


SMARTag enables the generation of homogenous and site-specific bioconjugates which have been shown to enhance potency, safety and stability. The technology employs natural post translational modifications found in human cells to create one or more aldehyde tags at designated sites on protein molecules. These chemical handles within the targeting moiety, such as a monoclonal antibody, are then stably conjugated to cytotoxic payloads to prevent their systemic release. The SMARTag platform provides precise payload positioning and defined stoichiometry of payload–protein ratios. The control afforded by the technology enables identification of superior bioconjugate drugs from libraries of differentially designed conjugates.


Recent in-vivo toxicology studies demonstrate that ADCs generated using Catalent's SMARTag platform have a better toxicity profile than a conventional ADC, this together with positive in vivo efficacy results, point to an improved therapeutic index for SMARTag ADCs.