Optimization of Protein Therapeutic Formulations

描述(由申请人提供)：这项建议涉及开发和验证一种新的方法，以改进和加快生物制药(即疫苗、单抗和其他治疗性蛋白质)的发现。生物制药被用来治疗各种传染病和慢性病。这项拟议的研究旨在建立一种新的范式，以快速提高生物制药的溶解度和物理稳定性。该范例将使用从制药公司获得的一个或多个候选疫苗以及与骨矿化和骨质疏松症有关的骨保护素(OPG)蛋白质进行评估。根据2008年6月发布的最新数据监测报告，蛋白质疗法是药物发现的第二大领域。自2000年以来，所有批准的新药中有超过25%是生物制药，但开发生物制药是一项既耗时又昂贵的工作。生物制药的发展要求蛋白质疗法是高度溶解的，因为大量的蛋白质必须通过小体积的溶液注射到患者体内。制药和生物技术公司投入大量时间和资源开发合适的配方，使所需的蛋白质能够在不引起蛋白质不稳定的情况下浓缩到高水平。这一配方开发过程往往是蛋白质治疗发现过程中的主要瓶颈。这项建议涉及使用现有技术和一种新的高通量技术来提供有关蛋白质在不同溶液条件(配方)下的溶解度和稳定性的信息。这些信息将被用来训练人工神经网络程序，以预测提供改善蛋白质溶解度和稳定性的全新溶液条件。如果成功，这一能力将加速和提高为制药、生物技术、政府和学术界正在开发的生物制药开发临床有用配方的能力。这也将有利于任何希望提高所表达蛋白质的溶解性和物理稳定性的蛋白质表达研究组织(表达水或膜蛋白)。它将减少开发新疫苗、单抗和其他蛋白质疗法所需的成本和时间。可溶性治疗公司打算通过与工业界、学术界和政府的研究人员建立合作关系，支持作为CRO的生物制药研究。预计随着行业合作伙伴认识到该公司的新技术的优势，它将导致非独家许可和战略合作伙伴关系。 与公共卫生相关：这项建议涉及开发和验证一种新的方法，以改进和加速发现生物药物(即疫苗、单抗和其他治疗性蛋白质)。生物制药被用来治疗各种传染病和慢性病。这项拟议的研究旨在建立一种新的范式，以快速提高生物制药的溶解度和物理稳定性。该范例将使用从制药公司获得的一个或多个候选疫苗以及与骨矿化和骨质疏松症有关的骨保护素(OPG)蛋白质进行评估。根据2008年6月发布的最新数据监测报告，蛋白质疗法是药物发现的第二大领域。自2000年以来，所有批准的新药中有超过25%是生物制药，但开发生物制药是一项既耗时又昂贵的工作。生物制药的发展要求蛋白质疗法是高度溶解的，因为大量的蛋白质必须通过小体积的溶液注射到患者体内。制药和生物技术公司投入大量时间和资源开发合适的配方，使所需的蛋白质能够在不引起蛋白质不稳定的情况下浓缩到高水平。这一配方开发过程往往是蛋白质治疗发现过程中的主要瓶颈。这项建议涉及使用现有技术和一种新的高通量技术来提供有关蛋白质在不同溶液条件(配方)下的溶解度和稳定性的信息。如果成功，这一能力将加速和提高为制药、生物技术、政府和学术界正在开发的生物制药开发临床有用配方的能力。Sole Treeutics LLC打算通过与产业界、学术界和政府的研究人员建立合作关系，以合同研究的方式支持生物制药研究。预计随着行业合作伙伴认识到该公司的新技术的优势，它将导致非独家许可和战略合作伙伴关系。

DESCRIPTION (provided by applicant): This proposal involves the development and validation of a novel approach to improve and accelerate the discovery of biopharmaceuticals (i.e. vaccines, monoclonal antibodies and other therapeutic proteins). Biopharmaceuticals are used to treat a variety of infectious and chronic diseases. The proposed research is intended to establish a new paradigm for rapidly improving the solubility and physical stability of biopharmaceuticals. The paradigm will be evaluated using one or more vaccine candidates obtained from a pharmaceutical company as well as the protein osteoprotegerin (OPG), which is involved in bone mineralization and osteoporosis. According to the latest Data-Monitor Report published in June, 2008, protein therapeutics represents the second largest segment in pharmaceutical drug discovery. Since 2000, more than 25% of all new drugs approved have been biopharmaceuticals but there development is a time-consuming and costly endeavor. The development of biopharmaceuticals requires that the protein therapeutic is highly soluble since a substantial amount of the protein must be injected in patients via a small volume of solution. Pharmaceutical and biotechnology companies devote significant time and resources developing suitable formulations that allow the desired protein to be concentrated to high levels without inducing instability in the protein. This process of formulation development is often the major bottleneck in the protein therapeutic discovery process. This proposal involves the use of existing technologies and a novel high-throughput technology to provide information regarding a protein's solubility and stability in different solution conditions (formulations). The information will be used to train an artificial neural network program to predict totally new solution conditions that provide improved protein solubility and stability. If successful, this capability will accelerate and improve the ability to develop clinically useful formulations for biopharmaceuticals being developed by pharmaceutical, biotechnology, government and academic communities. It will also benefit any protein expression research organization (expressing aqueous or membrane proteins) that desires improved solubility and physical stability of expressed protein. It will reduce the cost and time required to develop new vaccines, monoclonal antibodies and other protein therapeutics. Soluble Therapeutics, LLC intends to support biopharmaceutical research as a CRO by establishing collaborative relationships with researchers from industry, academia and the government. It is expected that as industrial partners realize the advantages the company's novel technology it will lead to non-exclusive licenses and strategic partnerships. PUBLIC HEALTH RELEVANCE: This proposal involves the development and validation of a novel approach to improve and accelerate the discovery of biopharmaceuticals (i.e. vaccines, monoclonal antibodies and other therapeutic proteins). Biopharmaceuticals are used to treat a variety of infectious and chronic diseases. The proposed research is intended to establish a new paradigm for rapidly improving the solubility and physical stability of biopharmaceuticals. The paradigm will be evaluated using one or more vaccine candidates obtained from a pharmaceutical company as well as the protein osteoprotegerin (OPG), which is involved in bone mineralization and osteoporosis. According to the latest Data-Monitor Report published in June, 2008, protein therapeutics represents the second largest segment in pharmaceutical drug discovery. Since 2000, more than 25% of all new drugs approved have been biopharmaceuticals but there development is a time-consuming and costly endeavor. The development of biopharmaceuticals requires that the protein therapeutic is highly soluble since a substantial amount of the protein must be injected in patients via a small volume of solution. Pharmaceutical and biotechnology companies devote significant time and resources developing suitable formulations that allow the desired protein to be concentrated to high levels without inducing instability in the protein. This process of formulation development is often the major bottleneck in the protein therapeutic discovery process. This proposal involves the use of existing technologies and a novel high-throughput technology to provide information regarding a protein's solubility and stability in different solution conditions (formulations). If successful, this capability will accelerate and improve the ability to develop clinically useful formulations for biopharmaceuticals being developed by pharmaceutical, biotechnology, government and academic communities. Soluble Therapeutics, LLC intends to support biopharmaceutical research as via contract research by establishing collaborative relationships with researchers from industry, academia and the government. It is expected that as industrial partners realize the advantages the company's novel technology it will lead to non-exclusive licenses and strategic partnerships.