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

SBIR 第一阶段：用于提供高浓度蛋白质治疗药物的新配方

• 批准号: 1722066
• 负责人: Paul Brown
• 金额: $ 22.49万
• 依托单位: Elektrofi Inc
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1722066&HistoricalAwards=false
• 关键词: SBIR; Phase; Novel; Formulation; Delivery

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.

该SBIR I期项目旨在通过皮下注射给予高浓度、低粘度溶液，提供简单、方便和快速的蛋白质治疗，从而显著改善患者体验。目前，高浓度抗体溶液的粘度远高于皮下注射的推荐限值。该项目旨在大幅降低高浓度蛋白质制剂的粘度。该项目的成功将大大有利于病人提供一个更短的管理时间的药物，现在需要几个小时的静脉输液。此外，该溶液还可以通过增加剂量减少注射频率来改善已经皮下给药的治疗。这项技术的发展也可以使蛋白质治疗剂的开发具有良好的疗效，但棘手的解决方案的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蛋白质的新配方平台的可行性。该平台将产生含有高浓度蛋白质治疗剂的制剂，由于蛋白质之间分子间相互作用的减少，所述制剂可以以显著降低的粘度递送。因此，该制剂提供了一种皮下注射相容的途径，以高浓度和低粘度递送生物制剂，最终推动从及时静脉内递送方案向简化皮下注射的转变。对皮下递送体积（2 mL）的限制需要抗体浓度远大于100 mg/mL。不幸的是，由于蛋白质分子之间的广泛相互作用，粘度远远超过可接受的进样限度（50 cP）是这种情况的典型特征。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该问题。拟议的工作利用一种新的工艺，仅使用FDA批准的材料温和地配制蛋白质。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。拟议项目将涉及通过以下方式开发平台：（i）确定最佳配方参数，（ii）演示高浓度蛋白质溶液的流变学改进，以及（iii）演示生物结构和活性的保存。