SBIR Phase I: Novel Formulation for the Delivery of High Concentration Protein Therapeutics

This SBIR Phase I project aims to significantly improve the patient experience by providing easy, convenient, and fast delivery of protein therapeutics through the administration of high-concentration, low-viscosity solutions via subcutaneous injection. Currently, high-concentration antibody solutions have viscosities far above the recommended limit for subcutaneous injections. This project aims to drastically lower the viscosities of high-concentration protein formulations. The success of this project would greatly benefit patients by providing a much shorter administration time for drugs that now require hours of intravenous infusion. In addition, this solution can also improve therapies that are already administered subcutaneously by reducing the frequency of injections by increasing dosage. Development of this technology can also enable the development of protein therapeutics with promising efficacy, but intractable solution properties or commercially unattractive patent lives. The goal of this Phase I project is to establish the proof-of-concept data supporting the viability of a new formulation platform for proteins. This platform will generate a formulation containing high concentrations of protein therapeutics which may be delivered at substantially lowered viscosities due to a reduction in the intermolecular interactions among proteins. The formulation thus provides a subcutaneous syringe-compatible route to delivering biologics at high-concentration, and low-viscosity, ultimately driving a shift from timely intravenous delivery protocols to simplified subcutaneous injections. Constraints on subcutaneous delivery volume (<2 mL) necessitate antibody concentrations much greater than 100 mg/mL. Unfortunately, viscosities far beyond the accepted injection limit (50 cP) are typical of this situation due to extensive interaction among the protein molecules. Current viscosity reduction methods attempt to regulate these interactions but have yet to substantially address the issue. The proposed work utilizes a novel process to gently formulate proteins using only FDA-approved materials. This approach eliminates the effect of the protein-protein interactions on the solution viscosity. The proposed project will involve development of the platform through (i) identification of optimal formulation parameters, (ii) demonstration of rheological improvements to high-concentration protein solutions, and (iii) demonstration of preservation of biological structure and activity.