Selection of lead antibody candidates is a highly involved process with many facets, with the ultimate aim of generating highly efficacious and safe molecule, which can be efficiently developed into a product. Development teams are often tasked with prioritizing multiple characteristics to screen for, with a very limited amount of protein. High concentration formulations are being developed to cater to a broad range of indications, as well as improving patient compliance and convenience. Viscosity of such formulations could be a major challenge, limiting the delivery routes and methods of administration.<br/>The nature of interactions in high concertation solutions are known to be complex and rather protein specific. Here, we evaluated viscosities of a number of antibodies at &gt; 140 mg/mL across a range of temperatures. Biophysical characterization was carried out using fluorimetry, calorimetry, light scattering and Raman spectroscopy to understand interactions, which influence conformational stability and viscosity at different temperatures. With concentration, impact of protein packing on hydrodynamic radius and conformational stability was analyzed. Computational parameters based on antibody sequence and homology models were used to predict biophysical properties and interactions. Mechanistic insights on interactions driving viscosity would allow developmental teams to select lead candidates with favorable viscosity profiles.

Developability of antibodies: Viscosity of high concentration formulations

255th National Meeting (2018)

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