The crucial role of NMR for understanding biomolecules at Novo Nordisk

NMR spectroscopy plays a vital role in R&D departments of large pharmaceutical companies like Novo Nordisk. This powerful method is essential for the study of purity and stability of peptides and proteins in pharmaceutical product development. Within Novo Nordisk, Andrew Benie serves as a principal scientist in one of the departments with NMR. Their primary focus is devoted to the early stages of drug development, particularly to discover and develop innovative medicines within diabetes, obesity, rare disease and other serious chronic diseases. At Novo Nordisk they have a diverse range of NMR instruments at their disposal, capable of performing a wide variety of essential research operations.

Andrew’s academic background is in chemistry, with a Ph.D. specializing in structural biology using NMR, both completed in London, UK. Following that he spent approximately six years as a postdoc in Germany, initially with intentions of pursuing an academic career.

After his stint in Germany, he moved to the Carlsberg Laboratory in Copenhagen. During this time, an opportunity arose at Novo Nordisk, which involved both small molecule screening and protein NMR, two focal points of his postdoctoral and Ph.D. studies.

In 2007, Andrew accepted a permanent position at Novo Nordisk, He has now served as a principal scientist for over 15 years, a role perfectly suited to his preference for hands-on laboratory work, particularly in the NMR laboratory, while others handle further aspects of the process, ensuring he can focus extensively on NMR.

At Novo Nordisk, Andrew is responsible for all NMR-related activities at his department and the management of the NMR instruments. He steps back only when administrative tasks and approvals are required.

Significance of NMR at Novo Nordisk

The significance of NMR at Novo Nordisk varies across departments. The Biophysics and Formulation departments, where Andrew does his daily work, has access to four NMR instruments – three equipped with cryoprobes and one without. Additionally, five individuals in his group are engaged in NMR research to varying degrees.

In the Chemistry, Manufacturing and Control (CMC) organisation, where documentation is handled, three additional NMR instruments are available, all equipped with cryoprobes. In total, about 10-15 people at Novo Nordisk are involved in NMR work, not counting the many chemists preparing the samples.

NMR spectroscopy at Novo Nordisk A/S encompasses a wide array of applications, covering anything that fits into an NMR tube. While they conduct diverse research at Novo Nordisk A/S, their primary tasks include analyzing surface associations, ensuring purity, and assessing stability In contrast to the typical academic BioNMR lab, structure determination plays a lesser role as more often than not those proteins that give good quality NMR data also crystallise readily.

Andrew’s primary role revolves around the identification and characterisation of peptides and proteins of interest a role that is likely very similar whether at a university or Novo Nordisk A/S. Their primary NMR focus remains on standard proton NMR methods as the final products aren’t isotopically enriched.

Expanding role of biomolecular research at Novo Nordisk A/S

In Andrew’s group at Novo Nordisk A/S, the primary focus is devoted to the study of biomolecules as products, with a historical emphasis on peptides and proteins due to Novo Nordisk A/S’s origin in insulin, a peptide-based hormone.

Novo Nordisk A/S utilizes NMR spectroscopy to analyze the structure of complex biomolecules, enabling the development of more innovative insulin analogs. Thus, NMR plays a crucial role in elucidating protein conformations and interactions, aiding in the design of next-generation diabetes treatments.

Additionally, Novo Nordisk A/S leverages NMR to assess drug formulation stability, ensuring the quality and efficacy of their life-saving products. Recently, they have expanded their research to include RNA and small molecules, but so far Andrew’s research is still primarily focused on proteins and peptides.

One noteworthy research project Andrew has been a part of, involved the quantification of PEG in samples from hemophilia patients, a project that used rather standard NMR, but what made it interesting was that it had immediate, real-world impact by potentially reducing the need for daily injections in these patients, which is important as it is a priority for many Hemophilia patients to reduce the amounts of injections needed in their everyday life (https://doi.org/10.1007/s40259-019-00380-3).

Collaboration

Novo Nordisk A/S frequently collaborates with Aarhus University on NMR projects, mainly due to the absence of in-house solid-state NMR capabilities. When solid-state samples need analysis, Andrew relies on Aarhus University for support. Along these lines, Andrew’s group has had several PhD students collaborating with Professor Frans Mulder, who has since moved to Johannes Kepler University Linz. The extensive history of this partnership shows the benefits of academia and industry collaborating to tackle emerging challenges in biomedical research.

Andrew’s work is primarily centered on the early stages of projects, making it impractical to involve other companies at this early stage.

Strength of Danish NMR research

“The greatest strength of Danish NMR is the annual DANNMR meeting, where everyone gathers for social events. It provides insights into what different people are doing and what’s new in the field. It also helps you identify the right people to collaborate with or seek assistance from”.

“Denmark excels in solid-state NMR, especially for biomolecules. Additionally, SBiNlab is known for its expertise in protein NMR, while DTU specializes in carbohydrates and small molecules (10.1016/j.jmr.2015.11.007). Each university has a strong focus on a particular field of NMR, and they have maintained this expertise for many years. What sets Denmark apart is the spirit of collaboration and willingness to help and share knowledge. Everyone knows everyone, and this camaraderie is a significant advantage“.