Identifying and modulating aggregation propensity in bio-pharmaceuticals

Lead Research Organisation: University of Leeds
Department Name: Sch of Molecular & Cellular Biology

Abstract

The UK is a major stakeholder in biopharmaceutical development and production, a sector that had sales of £105 billion in 2012. Bio-pharmaceuticals (biologics) offer major therapeutic advantages (high affinity and biocompatibility) over conventional small molecule drugs but nonetheless, pose enormous challenges in their development, production, formulation and storage. A major hurdle to be overcome is the reversible or irreversible self-association (aggregation) of biologics resulting in the failure of promising candidate biologics even at very late stages in the development pipeline. The ability to identify sequences likely to aggregate either inherently or during production, transport or storage is of crucial importance to the biologics industry, yet is currently beyond our capability.

An in vivo selection method has been developed by the applicants at Leeds to quantify the aggregation propensity of single chain Fv (scFv) variants of bio-pharmaceuticals. Here we will assess the potential of this method to rank candidate for the development/formulation of a large number of IP-free antibodies (50-200) developed by UCB which also have detailed bio-physical data. This will allow any correlations between aggregation propensity and standard biophysical analyses (if any) to be identified.

If successful, this screen could revolutionise the landscape for the sector, especially in the application of complex systems such as antibodies. The ability to reliably predict bioprocessability removes a bottleneck in biologic development, facilitating commercialisation. The complementary team is assembled from academia and a large biopharmaceutical company and is thus ideally placed to undertake a feasibility study of this nature.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011151/1 30/09/2015 29/09/2023
2111946 Studentship BB/M011151/1 30/09/2018 31/12/2022 Romany Mclure