SBIR-STTR Award

Therapeutic antibodies have had a profound impact on treatment of many types of cancer and autoimmune diseases. As a result, five of the top ten best selling drugs of 2016 were therapeutic antibodies. More than seventy therapeutic antibodies have been approved, and over six hundred antibody-based products are in clinical development. However, antibodies are extremely expensive to produce, and large amounts of antibody are required to achieve clinical efficacy. During our market research through the prestigious I-Corps program, all of the industry experts interviewed cited Protein A chromatography as the largest pain point in antibody manufacturing. The Z-Domain of Protein A specifically binds the constant region of human antibodies, and thus can be immobilized on a resin or membrane and used to purify a wide variety of therapeutic antibodies. The two largest concerns were (i) the cost of Protein A-modified chromatography resins or membranes and (ii) the time lost to lengthy cleaning procedures. The goal of the proposed studies is to use new material and immobilization technology to produce a low cost, single use Z-Domain immobilized membrane with high binding capacity and flow rate. Our single- pot materials synthesis approach eliminates a work-intensive, failure-prone step from materials production, reducing the cost of membrane production and making single use application feasible. In addition, this technology can increase binding capacity by nearly 1,000-fold, enabling its application for large-scale purifications. Furthermore, these materials significantly stabilize incorporated proteins, facilitating use and improving storage. The proposed studies of this proposal are designed to validate this approach in three value-added milestones: Measure static and dynamic binding capacity (Aim 1), examine antibody purity (Aim 2), and assess the durability of the materials (Aim 3), all necessary steps in product development.

Public Health Relevance Statement:
Therapeutic antibodies have had a profound impact on the treatment of many diseases, but are extremely expensive to produce. Novel materials developed by Bondwell Technologies, Inc. have the potential to dramatically increase binding capacity in a low-cost, single-use product. The proposed studies will validate this technology as an antibody purification platform.

Project Terms:
Age; Amino Acid Sequence; Antibodies; Antibody Formation; Autoimmune Diseases; base; Binding; cancer therapy; cancer type; Chemicals; Chimeric Proteins; Chromatography; clinical development; clinical efficacy; commercialization; cost; crosslink; Data; design; Disease; Drug Costs; drug production; Ensure; Escherichia coli; Failure; Fluorescence; Goals; Healthcare; Human; Immobilization; Immunoglobulin Constant Region; Immunoglobulin G; improved; Industry; Industry Standard; Innovation Corps; Interview; Kinetics; Link; Market Research; Measures; Membrane; membrane activity; Methods; novel; novel strategies; Pain; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Plant Resins; polypeptide; Procedures; Process; product development; Production; Productivity; program costs; programs; Property; Protein Binding Domain; Proteins; Protocols documentation; Relationship-Building; scale up; Staphylococcal Protein A; Structure; Surface; System; Techniques; Technology; Tertiary Protein Structure; Testing; Texas; Therapeutic; Therapeutic antibodies; Time; Universities; Work

Therapeutic antibodies have had a profound impact on treatment of many types of cancer andautoimmune diseases with many new therapeutics in development. However, antibodies areextremely expensive to produce, and large amounts of antibody are required to achieve clinicalefficacy. In our 268 interviews with industry experts and extensive research of the literature,Protein A-based purification is the largest pain point in mAb manufacturing. The Protein A marketwas $600 million in 2019 and is projected to grow to over $1 billion by 2026. This market can bedivided into the classical resins that have dominated the market and new alternatives whichinclude membranes. There is a strong desire to move away from resins; however, a lack ofalternatives with superior performance have prevented this. Our Phase I data demonstrate thatwe have considerable advantages over incumbent suppliers by providing a high binding capacity,high-flow, single-use membrane that doesn't rely on crosslinking. At the end of Phase II, we willproduce our minimally viable product: a low-cost, high-capacity, single-use antibody purificationmembrane that has been validated by key industry players and ready to be displayedinternationally. To do this we will accomplish the following Aims: 1) Industrial Scale Production ofprotein monomers 2) Optimize efficiency of electrospun membrane 3) Testing with IndustryPartners. The slow adoption rate of new technologies, preference for brand reputation,compliance with FDA SOPs, global supply risk, and long runway to revenue lead to start-upssimilar to ours being acquired before any sales occur. Therefore, our goal is not to manufactureand sell this product but to pursue an early exit through licensing, partnership with, or acquisitionby, established companies. To accomplish this, we will leverage the data generated from industrypartners during this Phase II proposal to generate high profile scientific publications andpresentations at leading conferences.

Public Health Relevance Statement:
Therapeutic antibodies have had a profound impact on the treatment of many diseases, but are extremely expensive to produce. Novel materials developed by Bondwell Technologies, Inc. have the potential to dramatically increase binding capacity in a low-cost, single-use product. The proposed studies will expand efficiency of the membrane filters validated in the Phase I study. Membrane efficiency and industrial optimization will allow testing by our established Industry partners.

Project Terms:
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