Developing protein drugs has been a challenge because of an inherent tendency to aggregate. Ultimately, this hinders their potency and safety profiles, which isn’t optimal for patients. But, we believe we may have a solution to this challenge through the use of nuclear magnetic resonance (NMR) analytics.
Recently, we announced a new research initiative with Professor Bruce Yu at the University of Maryland, School of Pharmacy (UMSOP) to use NMR analytics to characterize protein formulations. What that offers is twofold: First, we will jointly work on this technique to develop a rapid, non-destructive method to analyze and improve the quality of our protein drugs; and, second, we have the opportunity to advance this science collaboratively with a local academic institution.
While there are a number of techniques available to analyze protein aggregation, we’ve been stymied by the limitations of having to remove samples from their containers. That restricts our ability to assess aggregation since the drug has already been packaged. Our goal, along with our colleagues at UMSOP, is to develop a simple and fast method for doing these assessments through a drug’s lifetime—from formulation to point of care—as well as providing a potential end-of-expiration specification for protein drugs.
Water proton NMR potentially offers us a better understanding of the physical stability of protein formulations. Water is used as the solvent in every protein liquid formulation. In fact, water is the main component of the majority of biopharmaceutical solutions, and its protein NMR is very strong. So, this gives us wide applicability. And, it’s a technique that has advantages over existing methods because it allows for non-destructive testing of samples at high protein concentrations inside of sealed vials.
So far, we’ve made some important observations in our investigations—including that the transverse relaxation rate (R2) of water in biomaterials could be used as a probe of its environment. This observation and others pave the way to an innovative approach that will allow us to monitor protein transformations in aqueous solutions (aggregation, assembly, etc.) non-invasively, without dilutions or even opening the vial.
Ultimately, our hope for this research collaboration with UMSOP is to develop high-quality drugs for patients. But, it also fulfills an important corporate initiative to establish impactful scientific partnerships with local universities who have similar goals that focus on strong science and better medicines.