SBIR Phase I: Non-Chromatographic Method for the Purification of Monoclonal Antibodies

这一小型企业创新研究(SBIR)项目的更广泛影响/商业潜力是改进用于纯化单抗的制造技术，单抗是重要的治疗方法，也是研究和诊断中的宝贵工具。每年大约有四种新的抗体药物被批准，虽然它们可以产生巨大的临床结果，有时被誉为“神奇子弹”，但它们往往伴随着高昂的价格。这给患者和保险公司带来了压力，限制了基于抗体的药物的可及性。此外，抗体是加强对生物学理解的关键研究工具。这项研究项目中开发的技术将为从细胞培养中纯化抗体提供一种全新的方法，这种方法将降低成本，提高制造产能，并加快新疗法的上市时间。在商业上，这项技术将颠覆目前的黄金标准-蛋白A树脂-使抗体纯化在所有规模更简单、更快、更便宜：研究、临床和工业。这个SBIR第一阶段项目的智力优势是开发了改进的单抗纯化技术。尽管细胞培养中抗体的上游生产已经大幅提高，但下游纯化没有跟上步伐，导致生产瓶颈和重大的市场机会。SBIR第一阶段项目的目标是证明一种新技术的技术和商业可行性，该技术将亲和力与液-液相分离相结合，从细胞培养污染物中分离抗体。它包括一个抗体结合域，融合到具有刺激反应相行为的生物聚合物上。当这种融合蛋白被加入细胞培养收获中时，它与抗体结合，并在用盐触发相分离后，将抗体从溶液中拉出。纯化的抗体可以通过降低pH从融合中洗脱出来。该项目旨在1)优化再生条件，使融合可以重复使用，2)评估长期稳定性，3)在规模上验证该技术，并与行业黄金标准--蛋白A树脂进行面对面的比较。目标是确定为产品提供长货架期的储存条件，该产品可以重复使用10-100次，而不会影响抗体产量或纯度。该项目的重点是展示该技术在工业生产的单抗中的应用前景，用一种更简单、更具成本效益的方法取代传统的层析步骤。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is to improve manufacturing technology for the purification of monoclonal antibodies, which are important therapeutics as well as valuable tools in research and diagnostics. Approximately four new antibody drugs are approved every year, and while they can have tremendous clinical outcomes and are sometimes heralded as "magic bullets," they often come with a significant price tag. This puts a strain on patients and insurance companies, limiting the accessibility of antibody-based drugs. Furthermore, antibodies are critical research tools that enhance the understanding of biology. The technology developed in this research project will provide a completely novel method for the purification of antibodies from cell culture that will lower cost, increase manufacturing throughput, and accelerate the time to market for new therapeutics. Commercially, this technology will disrupt the current gold standard - Protein A resin - making antibody purification simpler, faster, and cheaper at all scales: research, clinical, and industrial. The intellectual merit of this SBIR Phase I project is to develop technology for improved purification of monoclonal antibodies. Although upstream production of antibodies in cell culture has improved dramatically, downstream purification has not kept pace, resulting in a production bottleneck and a major market opportunity. The objectives of this SBIR Phase I project are to demonstrate technical and commercial feasibility of a new technology that combines affinity with liquid-liquid phase separation to separate antibodies from cell culture contaminants. It involves an antibody-binding domain fused to a biopolymer with stimulus responsive phase behavior. When this fusion protein is added to cell culture harvest, it binds the antibody and, after triggering the phase separation with salt, pulls the antibody out of solution. The purified antibody can then be eluted from the fusion by lowering the pH. This project aims to 1) optimize regeneration conditions so that the fusion can be reused, 2) evaluate long-term stability, and 3) validate the technology at scale and conduct a head-to-head comparison to the industry gold standard, Protein A resin. The goal is to identify storage conditions that provide a long shelf life for a product that can be reused 10-100 times without compromising antibody yield or purity. The focus of the project is to demonstrate promising capabilities of the technology for use in industrially manufactured monoclonal antibodies, replacing conventional chromatography steps with a simpler and more cost-effective method.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.