Candidate Selection/Developability

Over the years, Legacy has been asked to help identify the most promising peptide and protein drug candidates based on their physicochemical properties. These in-depth developability studies provide the client with recommendations on the suitability of specific candidate molecules within their developmental pipeline. While a range of biophysical methods can be and are used in these activities, we most often employ self-interaction chromatography (SIC) to determine the impact of solution conditions on self-association phenomena (i.e., colloidal stability). Colloidal stability affects protein solubility, aggregation propensity and viscosity behavior at higher concentrations. The information from SIC analyses have been instrumental in guiding solubility optimization activities.

For an overview of SIC, read our published review on the topic:

“Colloidal Behavior of Proteins: Effects of the Second Virial Coefficient on Solubility, Crystallization, and Aggregation of Proteins in Aqueous Solution”, Joseph J. Valente, Robert W. Payne, Mark Cornell Manning, W. William Wilson, and Charles S. Henry, Current Pharm. Biotechnol. 2005, 6: 427-436.

In addition, we have published an interesting case study on optimizing conditions for a high concentration peptide product:

“Second Virial Coefficient Determination of a Therapeutic Peptide by Self-Interaction Chromatography”, Robert W. Payne, Rajiv Nayar, Ralph Tarantino, Sam Del Terzo, John Moschera, Jie Di, David Heilmann, Brian Bray, Mark Cornell Manning, and Charles S. Henry, Biopolymers (Peptide Science) 2006, 84: 527-533.