Technology Overview
Our core technology consists of methods and intellectual property for rapidly identifying and characterizing proteases with altered specificity (Alterase™ Therapeutics) or improving the enzymatic and/or pharmacological properties of marketed proteases. These include a bioinformatics component for identifying potential targets and corresponding therapeutic protease candidates; a suite of protease scaffold domains; mutagenesis, expression, and assay technologies; protease profiling technology to elucidate structure-activity relationships for recognition of substrates; and selections and screens to discover novel, highly selective proteases. In our improved, second generation pro-coagulant protease programs (e.g., FVIIa), Catalyst has developed a discovery engine that includes protein engineering, protein production, multiple assays and in vivo models that are specifically directed towards hemostasis and hemophilia.
The figure below represents the process we use to create Alterases that can cleave and inactivate a therapeutic target. Briefly, rational design and combinatorial mutagenesis are used to generate libraries of mutants. Selected variants are screened for improved activity and specificity, and the most promising mutants are tested for efficacy in both cell-based assays and animal models. If necessary (for example, when extremely stringent specificity is desired), this process can be used iteratively - mutants can be subjected to this process multiple times (i.e., "evolved") to obtain the desired activity and specificity. This core technology is amenable to automation and facilitates rapid identification of potential biopharmaceuticals.
