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

这个小企业创新研究（SBIR）项目的更广泛的影响/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种不同的蛋白质或小肽药物已获得FDA批准，用于治疗一系列疾病（如生物制剂、单克隆抗体和凝血因子）。随着进入临床试验的合成肽数量不断增加，蛋白质纯化仍然是一个挑战。2017年，全球蛋白质和多肽药物市场预计将超过1400亿美元，年增长率约为5%。研究表明，该新型蛋白质纯化树脂的可行性有望为药物研究和开发提供一种转化工具，加强对蛋白质/肽结构和功能的研究，并使新蛋白质/肽的发现成为可能。该SBIR一期项目建议开发和商业化基于纳米材料的新型蛋白质纯化树脂，该树脂将提供与蛋白质大小无关的能力，最小的金属浸出，并且相对于现有的固定化金属亲和层析（IMAC）树脂具有更好的稳定性。新树脂将确保更高的纯度和活性分离蛋白与控制表位标签特异性，并减少非特异性相互作用。新树脂将与当前的制造工艺兼容，并适用于批处理、微孔板、传感器芯片和柱格式。目标是证明所提出的技术优于现有的商业树脂，正如理论预测和初步结果所表明的那样。本文将合成新的IMAC树脂，并从金属含量和浸出、蛋白质负载能力、分离蛋白质的纯度和活性以及稳定性等方面对其进行表征。这些树脂将针对每种操作模式进行优化。目的是建立一种分析和制备药物蛋白分离的新平台技术。

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.