Wyatt Technology Europe to participate in the “Marie Skłodowska-Curie” protein formulation consortium


Dierk Roessner, Ph.D. - December 16, 2015

Opportunity for 15 graduate researchers to apply for 3-year PhD scholarships that include unique opportunities for interdisciplinary collaboration with industry: http://www.pippi.kemi.dtu.dk/Jobs

The potential advantages of protein-based drugs lay in their combination of high specificity and potency, with relatively few side effects compared to small organic molecule drugs. However, biologics such as therapeutic proteins do need to overcome some important challenges. One often underestimated aspect of the development of proteinaceous medicines is the formulation effort. Currently, there exists a lack of high-value knowledge regarding the unique requirements of protein formulation conditions that produce stable drug products. Although literature on formulation of select biologics such as monoclonal antibodies and insulin variants does exist, there is a comparatively limited amount of literature available on the formulation of other proteins. And yet the latter biotherapeutics do present significant challenges for the formulation scientist, including physical and chemical heterogeneity and instability, conformational flexibility and the possibility of specific and non-specific self-association. Furthermore, there is a lack of experienced formulations scientists in Europe who can utilize the published literature in an effective way to provide problem solving expertise.

In order to close the gap, scientists in the fields of structural biology, biophysics, protein formulation and stability have formed a consortium within the European Union's Horizon 2020 framework, Protein-excipient Interactions and Protein-Protein Interactions in formulation (PIPPI). PIPPI’s goal is to apply an interdisciplinary approach to a mechanistic understanding of protein stability. Another key objective of PIPPI is to train a new generation of innovative and entrepreneurial early-stage researchers (ESRs) who will develop methodologies and tools to guide the formulation of robust biologics. To achieve these ends, the ESRs will contribute collaboratively to a comprehensive database relating physicochemical and structural properties of biologics, formulation conditions, and their impact on stability. This approach will not only provide an excellent platform to train a new generation of formulation scientists, but also establish paradigms for designing new formulation strategies and thereby secure the leading edge of EU expertise.

Wyatt Technology Europe is please to take part in this program by supervising the ESR tackling Aggregation Kinetics. Our aim is to develop a toolkit for predicting protein aggregation, a complex process that involves multiple pathways with various rate-controlling steps. These include the formation of small populations of partially unfolded molecules, which are difficult to isolate and study, as well as colloidal protein-protein-interactions. The precursors evolve into a full spectrum of protein aggregates of different size, shape and chemical properties, which need to be studied over time to understand individual kinetics. Wyatt’s approach to the problem involves establishing and applying automated methods of quantifying aggregation kinetics, incorporating time-resolved fluorescence, static and dynamic light scattering and special size exclusion chromatography - multi angle laser light scattering setups with modified sampling systems. Additional experimental techniques such as asymmetrical flow field-flow-fractionation and raster-image correlation spectroscopy will provide additional details about time-evolution of monomer and oligomer species. Aspiring graduate students interested in joining this project should apply via http://www.pippi.kemi.dtu.dk/Jobs.