Development of an Instrument to Determine Protein Stability at any Desired Temper

描述（由申请人提供）：蛋白质治疗是生物技术和制药行业中增长最快的部分。蛋白质治疗剂包括单克隆抗体、重组蛋白、嵌合蛋白和其它蛋白质受体构建体。预计到2010年销售额将超过700亿美元。蛋白质作为药物开发的一个主要障碍是它们以安全和稳定的形式配制。确定缓冲液、配体和赋形剂条件，使其稳定性最大化并消除蛋白质聚集，这在开发过程中至关重要，通常需要评估数百种条件。由于缺乏能够准确测量蛋白质稳定性/聚集基质的完全自动化仪器，这一耗时的任务变得更加复杂。该提案的目标是开发一种全自动的蛋白质化学变性、荧光/OD仪器，旨在测量多维蛋白质稳定性和聚集基质。在该仪器中，用户将仅需要提供蛋白质和散装制剂溶液。仪器将自动制备所有溶液，执行测量，分析数据并将结果呈现给用户。PHS 398/2590（2004年9月修订，2006年4月重新印发）第1页 公共卫生相关性：该仪器将大大加速蛋白质治疗的发展，并找到一个重要的市场。此外，它将提供一种新的方法来研究蛋白质的稳定性和聚集，并有助于发展对这些问题的更好的科学理解。通过提供一种快速且具有成本效益的方法来测试相关温度下的制剂（储存和生物学），研究人员将有实际的机会测试更多的制剂，并选择最适合任何特定生物制剂的制剂。PHS 398/2590（2004年9月修订，2006年4月重新印发）第1页

DESCRIPTION (provided by applicant): Protein therapeutics is the fastest growing segment in the biotechnology and pharmaceutical industry. Protein therapeutics includes monoclonal antibodies, recombinant proteins, chimeric proteins and other protein receptor constructs. It is expected to reach over $70 billion in sales by 2010. A major hurdle in the development of proteins as pharmaceutical drugs is their formulation in a safe and stable form. The identification of buffer, ligand and excipient conditions that maximize their stability and eliminate protein aggregation is critical during development and often requires the evaluation of hundreds of conditions. This time-consuming task is compounded by the absence of completely automated instruments with the capability of accurately measuring the stability/aggregation matrix of a protein. The goal of this proposal is to develop a fully automated, protein chemical denaturation, fluorescence/OD instrument aimed at measuring multi-dimensional protein stability and aggregation matrices. In this instrument, the user will only need to provide protein and bulk formulation solutions. The instrument will automatically prepare all solutions, perform the measurements, analyze the data and present the results to the user. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page 1 PUBLIC HEALTH RELEVANCE: This instrument will significantly accelerate the development of protein therapeutics and find a significant market. In addition, it will provide a new way to study protein stability and aggregation, and contribute to the development of a better scientific understanding of these issues. By providing a rapid and cost-effective means to test Formulations at relevant temperatures (storage and biological), researchers will have the practical opportunity to test more Formulations and to select the Formulation that is optimal for any specific biologic. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page 1