SBIR-STTR Award

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.

This SBIR Phase II project aims to transform intravenous (IV) infusions of biologic medicines into simple subcutaneous (SC) injections. Biologics have improved the treatment of human disease. Unfortunately, their delivery is burdensome. The standard of administration of these biologics is often by IV infusion at low concentrations, which can take multiple hours to deliver, cause patient discomfort, and increase the risk of infection. Although SC injection is preferred, constraints on SC volume (1.5-2.0 mL) would necessitate concentrations much greater than 100 mg/mL, which are often unfeasible. Solutions at concentrations exceeding 100 mg/mL are highly viscous (honey-like), making them difficult to inject and leading to unstable products. This project's microparticle suspension technology can deliver high concentrations while fully preserving the protein structure, function, and efficacy. Transforming the delivery of biologics offers advantages to patients, healthcare providers, payers, and biopharmaceutical companies. Patients will experience less pain and discomfort, save time, have fewer infections, and have better access to biologics. Healthcare providers will be able to process more patients, decrease the chance of complications, and use fewer human resources. Payers will have decreased reimbursement costs. Biopharmaceutical companies will have patented product differentiation and the ability to develop otherwise intractable biologics.This SBIR Phase II project aims to develop a soft atomization manufacturing platform for the production of microparticle suspensions capable of transforming intravenous (IV) infusions of biologics into simple subcutaneous (SC) injections. The standard of administration of biologics is intravenous infusion at low concentrations, which can take hours to deliver, cause patient discomfort, and increase the risk of infection. Although SC injection is preferred, constraints on SC volume (1.5-2.0 mL) necessitate concentrations greater than 100 mg/mL, which are often unfeasible. Solutions at concentrations exceeding 100 mg/mL are highly viscous (honey-like), making them difficult to inject and leading to unstable products. This project's gently processed microparticle suspensions can deliver high concentrations while preserving protein structure and bioactivity, an accomplishment not well-demonstrated with other microparticle technologies. This project aims to advance the readiness level of the innovation by performing process calibration of a bench-scale system, followed by developing and characterizing the resulting particles and suspensions produced on that system. With well-formulated suspensions, in vivo pharmacokinetic and efficacy studies will commence. The project will support the development of manufacturing capabilities towards a goal of transitioning to pilot-scale production. This project aims to offer advantages to patients, healthcare providers, payers, and biopharmaceutical companies.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.