Chapter 3: Enabling Biologics Combination Products: Device Ability in Protein Therapeutics

Most of the biological products currently in development or entering the market are some form of combination products for rapid systemic administration. This has prompted the adoption of a patient-centric approach during development, where convenience to patient is a critical differentiation factor. Therefore, the device ability potential of the candidate molecules emerging from discovery research should be de-risked before moving into development. Important aspects to evaluate are the tendency of constructs to have good solution energetic as measured by several surrogate techniques such as virial coefficients in diluted solutions and the binding energy extracted from induced liquid-liquid phase separation. Low positive binding free energy indicates strong attractive inter-protein interactions, low protein solubility, and therefore high probability of self-association. Equilibrium binding thermodynamics allows dissecting the contribution of solution variables and proper linkages for a combination product. It is also shown that lyogels can be created from silk protein, with superior sustain release profile by modulating hydrophobic and hydrophilic interactions between lyogel and the loaded protein.