Nano-AB: An Innovative Nano Biomaterial for Rapid, Column-Free Antibody Purification

Project Summary The protein purification market is critical to research and biopharmaceutical production, with monoclonal antibodies (mAbs) comprising approximately 40% of total demand. This highlights a significant need for cost- efficient, scalable, and high-performance purification technologies. Current approaches, such as agarose and macro-porous resins, are hindered by the limitations of their microstructural bases. Agarose resins offer a large liganded surface area, providing potentially high capacity, but suffer from small pores that significantly increase residence time (RT), leading to prolonged processing. Conversely, macro-porous membranes facilitate short RT by providing direct access to column ligands but sacrifice capacity due to their reduced liganded surface area. These fundamental drawbacks reflect an unresolved contradiction in current materials and underscore the need for innovation to enhance efficiency and reduce operational costs. NanoBPI proposes a transformative solution by leveraging advanced polypeptide-based nano-biomaterials to develop Nano-Beads (NanoAbs) charged with Protein A (NanoZ) and Protein G (NanoG) ligands. Unlike traditional micro-dimensional resins, NanoAbs operate at the nanoscale, enabling a non-porous structure with a larger total liganded surface area. This innovation not only addresses the limitations of agarose and macro- porous membranes but also combines their respective advantages, resulting in superior purification performance. In Phase I, we will focus on developing disposable NanoAbs specifically tailored for the research market, where cost, scalability, and processing efficiency are critical. The NanoG variant fills a significant gap, as the current options are limited to agarose beads, which are characterized by prolonged RT and inefficiency in mAb purification. Our Phase I objectives include developing NanoG with a binding capacity of 50–60 mg/mL and overall productivity representing a 4–5-fold improvement over current agarose products. Additionally, we aim to optimize the manufacturing processes for NanoZ and NanoG to reduce downstream processing (DSP) time by at least threefold and achieve a 1.3–1.4-fold increase in mAb purification productivity. These advancements align closely with the objectives of NIH NOSI (NOT-EB-24-001), which emphasizes advancing paradigm- shifting biomaterials-based technologies leading to commercialized products. These advancements will position NanoBPI as a competitive force in the $11.7 billion DSP market, addressing the rising demand for therapeutic proteins and mAbs with cost-effective and scalable solutions tailored to both research and pharmaceutical sectors.