Universal Protein Carrier Scaffold for Small Molecules and Peptide Therapeutics

描述（由申请人提供）：本申请涉及广泛的挑战领域（06）使能技术和特定的挑战主题，06-EB-102，生物医学技术和系统的开发低分子量小分子和肽通常由于药代动力学特征差和清除速度快而具有有限的治疗效用。因此，已经有大量的努力集中在药物递送系统的开发上，包括使用大生物分子作为载体蛋白。蛋白质载体提供了几个实质性的优势，包括相对较低的脱靶活性，导致更少的副作用。这些载体蛋白中的许多是与感兴趣的治疗肽的重组基因融合物。或者，用小分子药物或肽化学加工载体蛋白也可以使肽治疗剂更有效和更持久。当修饰是位点特异性的时，实现了蛋白质化学修饰的最佳益处。然而，现有的位点特异性蛋白质修饰方法都不是简单、无毒且适用于在哺乳动物或细菌细胞中表达的蛋白质。因此，可以通过化学修饰来改进的肽治疗剂尚未以这种方式进行优化。Redwood Bioscience Inc开发了一个技术平台，使我们能够以可控的、位点特异性的方式对蛋白质进行化学修饰。最终的结果是蛋白质在一个单一的点。我们相信这项技术可以用来产生一个载体蛋白支架肽类药物的交付。这种支架将是同质的，易于化学加工，并导致具有成本效益的，持久的蛋白质缀合物疗法，以治疗未满足的医疗需求。如果成功，我们相信这项工作将改变蛋白质治疗的效用，使小分子和肽的快速使用成为可能，否则这些小分子和肽将无法用于治疗疾病。我们的技术将产生更高质量的同质蛋白质产品，降低剂量频率，从而降低治疗成本，并且与游离肽药物或制药行业目前使用的其他缀合方法相比具有更高的比生物活性。这项研究最初将由一个由三名化学家和生物学家组成的团队进行，并通过这笔赠款获得资助。成功完成本提案中的目标将产生所需的科学数据，以便接触外部私人资本来源。这将使我们能够发展公司，进一步发展我们的商业目标，并雇用更多的全职科学和支持人员。Redwood Bioscience的生物标记技术可用于创建修饰的人血清白蛋白。这些蛋白质将被连接到基于肽的药物上，所得的缀合物被证明是有效的，具有成本效益的糖尿病和骨质疏松症治疗方法。

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (06) Enabling Technologies and specific Challenge Topic, 06-EB-102, Development of biomedical technologies and systems Low molecular weight small molecules and peptides often have limited therapeutic utility because of poor pharmacokinetic profile and rapid clearance. As a result, there has been a large effort focused on the development of drug delivery systems, including using large biomolecules as carrier proteins. Protein carriers offer several substantial advantages over other delivery methods including relatively low off-target activity, resulting in fewer side effects. Many of these carrier proteins are recombinant genetic fusions with a therapeutic peptide of interest. Alternately, chemically elaborating carrier proteins with small molecule drugs or peptides can also render the peptide therapeutic more potent and longer lasting. The optimal benefit of protein chemical modification is achieved when the modification is site-specific. However, none of the existing methods for site-specific protein modification are simple, non-toxic, and applicable to proteins expressed in either mammalian or bacterial cells. As a consequence, peptide therapeutics that could be improved by chemical modification have yet to be optimized in this manner. Redwood Bioscience Inc. has developed a technology platform that allows us to chemically modify proteins in a controlled, site-specific manner. The end result is a protein elaborated at a single point. We believe this technology can be used to generate a carrier protein scaffold for delivery of peptide drugs. This scaffold will be homogenous, easy to chemically elaborate, and result in cost-effective, long-lasting protein conjugate therapies to treat unmet medical needs. If successful, we believe this work will change the utility of protein therapeutics by enabling rapid use of small molecules and peptides that otherwise would not be useful as treatment for disease. Our technology will yield higher quality homogenous protein products, reduced dosage frequency resulting in lower treatment costs, and with higher specific biological activity compared to the free peptide drugs or other conjugation methods currently used in the pharmaceutical industry. The research is to be initially carried out by a team of three chemists and biologists, to be funded through this grant. Successful completion of the aims in this proposal will generate the required scientific data necessary to approach outside private sources of capital. This will allow us to grow the company and further develop our commercial targets and hire additional full time scientific and support staff. Redwood Bioscience's aldehyde-tag technology can be applied to create modified human serum albumin proteins. These proteins will be attached to peptide-based drugs and the resulting conjugates demonstrated to be efficacious, cost-effective therapies for diabetes and osteoporosis.