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

该SBIR一期项目旨在通过皮下注射高浓度、低粘度溶液，提供简单、方便、快速的蛋白质治疗药物，从而显著改善患者体验。目前，高浓度抗体溶液的粘度远远超过皮下注射的推荐限度。该项目旨在大幅降低高浓度蛋白质配方的粘度。这个项目的成功将极大地造福患者，因为它大大缩短了目前需要数小时静脉输注的药物给药时间。此外，这种溶液还可以通过增加剂量来减少注射频率，从而改善已经进行皮下注射的治疗方法。这项技术的发展也可以使蛋白质疗法的发展有希望的疗效，但棘手的溶液性质或商业上没有吸引力的专利寿命。这个第一阶段项目的目标是建立概念验证数据，支持新的蛋白质配方平台的可行性。该平台将生成含有高浓度蛋白质治疗剂的配方，由于蛋白质之间的分子间相互作用减少，可以以大幅降低的粘度输送。因此，该制剂提供了一种与皮下注射器兼容的途径来输送高浓度、低粘度的生物制剂，最终推动了从及时静脉注射到简化皮下注射的转变。皮下递送量（2ml）的限制要求抗体浓度远高于100mg /mL。不幸的是，由于蛋白质分子之间广泛的相互作用，粘度远远超过可接受的注射极限（50 cP）是典型的这种情况。目前的粘度降低方法试图调节这些相互作用，但尚未实质性地解决这个问题。提出的工作利用一种新工艺，仅使用fda批准的材料轻轻配制蛋白质。这种方法消除了蛋白质-蛋白质相互作用对溶液粘度的影响。拟议的项目将包括通过(i)确定最佳配方参数，（ii）证明高浓度蛋白质溶液的流变学改进，以及（iii）证明生物结构和活性的保存来开发平台。

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.