Pushing the drug design envelope


William Dall'Acqua, Ph.D

Antibody Discovery and Protein Engineering R&D Director William Dall’Acqua and Senior Scientist Vaheh Oganesyan are excited. Last month, their collaborative study titled “Structural Insights Into Neonatal Fc Receptor-Based Recycling Mechanisms” was published in the Journal of Biochemical Chemistry, offering an intriguing preview into the future of drug development.

At the core of the study were increased revelations about the molecular basis of the interaction between immunoglobulin (IgG), human serum albumin (HSA) and the neonatal Fc receptor (FcRn). That’s important, says William, because it not only provides valuable knowledge for the field of immunology but also adds to the building blocks of better drug design.

“Understanding the basis of these interactions is crucial to develop biologics that exhibit beneficial pharmacokinetic properties,” he says. “This includes the ability to help design better drugs in any field, such as oncology, immunology and infectious diseases.”

Those insights may have particular meaning for looking closer at the HSA and FcRn interface, an area of study that could reveal powerful information for guiding the design and development of novel drugs.

Vaheh also hopes that the results of the study will offer new engineering clues and lead to a revival of studies aimed at optimizing the IgG/FcRn interaction; an interface, the paper explains, that has been “exhaustively mutated by a plethora of rational design and library-based approaches.”

What’s equally noteworthy is the potential impact of research results on the existing YTE technology—MedImmune’s half-life extension platform. William and his team will now be looking more closely at the functional and structural data that were generated to potentially design the next generation of YTE.

“What our data have allowed us to do is to explain various structural mechanisms by which several mutations—including YTE—result in increased human IgG binding to FcRn,” says William. “Basically, this puts us ahead of the curve and gives us some more information toward creating better molecules.”