Associate Principal Scientist Merck & Co. Inc Cranbury, New Jersey
Multispecific proteins come in variety of formats such as bi- and tri-specific antibodies, dual-variable domain antibodies, cross-mAbs, etc. These multivalent proteins are engineered to interact with multiple therapeutic target proteins with high specificity. Multi-domain proteins can be created by linking together a variety of high affinity antibody fragments. . In this work, we use NMR spectroscopy to study the solution behavior of multivalent VHH molecule, comprised of three flexibly linked heavy-chain only domains that show dramatic stabilization against accelerated degradation in the presence of sucrose. A collection of NMR fingerprinting and profiling methods were used to simultaneously monitor the protein solution behavior and capture details of protein-excipient interactions. We provide a framework to characterize and begin to understand the role of molecular flexibility in protein stabilization with potential applications in design of novel therapeutic protein scaffolds that include multivalent proteins, fusion proteins, antibody-drug conjugates and proteins modified with flexible lipids.
Learning Objectives:
Greater understanding of protein-excipient interactions
Utilize NMR spectroscopy in a novel way to interrogate protein excipient interactions.
Learn about the behavior of the novel therapeutic proteins