Glycoengineered insect cells for commercial biologics manufacturing

 描述(申请人提供)：治疗性蛋白质，或“生物制品”，代表着1400亿美元的市场，其中包括各种重要的药物，如抗体和激素。许多生物制品的临床疗效是由它们的糖结构或‘多糖’决定的。大多数生物制品是在哺乳动物细胞中制造的，因为它们添加了药物有效发挥作用所需的人型多糖。然而，哺乳动物细胞有一些严重的缺点。例如，建立生产细胞系需要很长时间，哺乳动物细胞可以产生免疫原性多糖。杆状病毒/昆虫细胞系统(BICS)为生物制品生产提供了一种有吸引力的替代系统，因为它缺乏这些缺点。然而，BICS目前受到其无法用人型多糖生产蛋白质的限制。GlycoBac已经开发出对昆虫细胞进行糖化工程的工具和方法，使它们能够将人类类型的多糖添加到重组蛋白质中。在这个SBIR项目的第一阶段，GlycoBac建立了生产几种昆虫细胞系的可行性，这些细胞系可以有效地生产具有临床相关的人型多糖结构的蛋白质。最近，人们发现GlycoBac的昆虫细胞携带着一种以前未知的病毒。在第二阶段，我们将使用GlycoBac最近开发的一种专利方法去除这种不定性剂。这将改善我们糖工程细胞系的生物安全状况，并增加它们在生物制品生产中的价值。我们还将生产两种新的细胞系，将两种不同类型的4-分支多糖添加到蛋白质中。众所周知，这种葡聚糖可以提高某些疫苗和其他生物制品的效力。第二阶段的另一个目标是展示我们新细胞系的稳健性和可扩展性，因为新细胞系商业使用的关键要求将在生产条件下证明是实用的。最后，我们将为两个糖工程细胞系建立细胞库。这些将根据细胞系的性能结合商业前景进行选择。总而言之，我们的项目旨在将糖工程BICS开发成一个多功能平台，具有广泛的实用性，可用于生产安全有效的生物制剂。这一第二阶段SBIR项目的成果预计将是一套昆虫细胞系，可用于生产具有特定人型多糖的广泛生物制剂，这些多糖为特定应用提供最佳效果。建议的产品将作为商业蛋白质制造的新工具具有很高的潜在影响。GlycoBac还将使糖工程BICs可用于学术和工业、基础和应用研究。因此，该项目产生的工具将对人类医学和基础生物医学研究的各个领域产生重大而广泛的影响。

 DESCRIPTION (provided by applicant): Therapeutic proteins, or 'biologics', represent a >$140 billion market that includes a variety of important drugs such as antibodies and hormones. The clinical efficacy of many biologics is determined by their sugar structures, or 'glycans'. Most biologics are manufactured in mammalian cells because they add human-type glycans, which are needed for the drug to function effectively. However, mammalian cells have some serious disadvantages. For example, it takes a long time to establish production cell lines, and mammalian cells can produce immunogenic glycans. The baculovirus / insect cell system (BICS) offers an attractive alternative system for biologics manufacturing, as it lacks these disadvantages. However, the BICS is currently limited by its inability to produce proteins with human-type glycans. GlycoBac has developed tools and methods to 'glycoengineer' insect cells, allowing them to add human-type glycans to recombinant proteins. In Phase I of this SBIR project, GlycoBac established the feasibility of producing several insect cell lines that can efficiently produce proteins with clinically relevant human-type glycan structures. Recently, it was discovered that GlycoBac's insect cells harbor a previously unknown virus. In Phase II, we will remove this adventitious agent using a proprietary method recently developed by GlycoBac. This will improve the biosafety profile of our glycoengineered cell lines and increase their value for biologics production. We will also produce two new cell lines that add two different kinds of 4-branched glycans to proteins. Such glycans are known to improve the efficacy for some vaccines and other biologics. Another Phase II Aim is to demonstrate the robustness and scalability of our new cell lines, as a key requirement for commercial use of the new cell lines will be demonstrated utility under production conditions. Finally, we will generate cell banks for two glycoengineered cell lines. These will be selected based on the performance of the cell lines combined with commercial prospects. In summary, our project is designed to develop glycoengineered BICS into a versatile platform with proven utility for the production of safe and efficacious biologics at production scales. The outcome of this Phase II SBIR project is expected to be a set of insect cell lines that can be used to produce a wide range of biologics with the specific human-type glycans that provide optimal efficacy for a particular application. The proposed products will have high potential impact as new tools for commercial protein manufacturing. GlycoBac also will make glycoengineered BICS available for academic and industrial, basic and applied research. Thus, the tools generated in this project will have a significant and broad impact on human medicine and diverse areas of basic biomedical research.