SBIR Phase I: A New Class of Immobilized Metal Affinity Chromatography Resins

SBIR 第一阶段：一类新型固定金属亲和色谱树脂

• 批准号: 1746198
• 负责人: NVS DINESH K BHUPATHIRAJU
• 金额: $ 22.5万
• 依托单位: Bionanotech LLC
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1746198&HistoricalAwards=false
• 关键词: SBIR; Phase; New; Class; Immobilized

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project will be to develop protein purification nanotechnology and materials for biopharmaceutical applications. Over 150 different protein or small peptide-based drugs have received FDA approval to treat an array of diseases (e.g., biologics, monoclonal antibodies, and blood clotting factors). Protein purification remains a challenge as the number of synthetic peptides entering clinical trials continues to grow. The global protein and peptide drug market is projected to exceed $140 billion in 2017 with an annual growth rate of ~5%. Demonstration of the feasibility of the proposed new protein purification resins is expected to provide a transformational tool for drug research and development, enhance research in protein/peptide structure and function, and enable the discovery of new proteins/peptides. This SBIR Phase I project proposes to develop and commercialize new protein purification resins based on nanomaterials that will afford capacity independent of protein size, minimal metal leaching, and better stability with respect to existing immobilized metal affinity chromatography (IMAC) resins for protein purification. The new resins will ensure greater purity and activity of isolated proteins with control of epitope-tag specificity, and minimize non-specific interactions. The new resins will be compatible with current manufacturing processes and applicable in batch, microplate, sensor chip, and column formats. The goal is to demonstrate that the proposed technology is superior to existing commercial resins, as suggested by theoretical predictions and preliminary results. The new IMAC resins will be synthesized and characterized in terms of metal content and leaching, protein loading capacity, purity and activity of proteins isolated, and stability. These resins will be optimized for each mode of operation. The goal is to establish a new platform technology for analytic and preparative drug protein isolation.

这一小型企业创新研究(SBIR)项目的更广泛影响/商业潜力将是开发用于生物制药应用的蛋白质纯化纳米技术和材料。超过150种不同的基于蛋白质或小肽的药物已获得FDA批准，用于治疗一系列疾病(例如，生物制品、单抗和凝血因子)。随着进入临床试验的合成肽的数量持续增长，蛋白质纯化仍然是一个挑战。预计2017年全球蛋白质和多肽药物市场规模将超过1400亿美元，年增长率约为5%。新蛋白质纯化树脂的可行性论证有望为药物研究和开发提供一种转化工具，加强蛋白质/肽结构和功能的研究，并使新蛋白质/肽的发现成为可能。这个SBIR第一阶段项目建议开发和商业化基于纳米材料的新的蛋白质纯化树脂，这种树脂将提供与蛋白质大小无关的容量、最小的金属浸出以及与现有的用于蛋白质纯化的固定化金属亲和层析(IMAC)树脂相比更好的稳定性。新的树脂将通过控制表位标签的特异性来确保分离蛋白的更高纯度和活性，并将非特异性相互作用降至最低。新树脂将与目前的制造工艺兼容，并适用于批次、微型板、传感器芯片和柱形式。理论预测和初步结果表明，所提出的技术优于现有的商业树脂。将合成新的iMac树脂，并从金属含量和浸出量、蛋白质载量、分离蛋白质的纯度和活性以及稳定性等方面进行表征。这些树脂将针对每种操作模式进行优化。其目标是建立一种新的分析和制备药物蛋白分离的平台技术。