Universal Protein Carrier Scaffold for Small Molecules and Peptide Therapeutics

描述（由申请人提供）：该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发展，低分子量小分子和肽通常具有有限的治疗效用，因为药代动力学谱差和快速清除。因此，人们一直致力于开发药物输送系统，包括使用大型生物分子作为载体蛋白。与其他递送方法相比，蛋白质载体具有几个实质性的优势，包括相对较低的脱靶活性，导致较少的副作用。许多这些载体蛋白是重组基因融合与治疗肽感兴趣。另外，用小分子药物或多肽化学修饰载体蛋白也可以使多肽治疗更有效和更持久。蛋白质化学修饰的最佳效益是当修饰是位点特异性的。然而，现有的位点特异性蛋白质修饰方法都不是简单、无毒、适用于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善的肽疗法尚未以这种方式进行优化。红木生物科学公司开发了一种技术平台，使我们能够以一种可控的、特定位点的方式对蛋白质进行化学修饰。最终的结果是在一个点上形成了一个蛋白质。我们相信这项技术可以用来制造一种运载多肽药物的载体蛋白支架。这种支架将是均匀的，易于化学精心制作，并产生具有成本效益，持久的蛋白质偶联疗法，以治疗未满足的医疗需求。如果成功，我们相信这项工作将通过快速使用小分子和肽来改变蛋白质治疗的效用，否则这些小分子和肽将无法用于疾病的治疗。我们的技术将产生更高质量的均质蛋白产品，减少剂量频率导致更低的治疗成本，并且与目前制药行业使用的游离肽药物或其他偶联方法相比，具有更高的特异性生物活性。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，由这笔拨款资助。成功完成本建议的目标将产生接触外部私人资本来源所必需的科学数据。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。红木生物科学公司的醛标签技术可用于制造改良的人血清白蛋白。这些蛋白将附着在肽类药物上，由此产生的偶联物被证明是治疗糖尿病和骨质疏松症的有效、经济的疗法。

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.