SBIR Phase I: New approach for producing increased quantities of human antibodies for research, medical, and biodefense applications

The broader impact /commercial potential of this Small Business Innovation Research (SBIR) project will address the needs of the antibody market for fast and inexpensive production of antibodies. Antibodies are among the most utilized molecular tools in the life sciences, whose applications span a variety of areas in biological science and medicine. The worldwide antibody market was estimated at approximately $40 billion in 2008, and is expected to rise above $68 billion by 2016. The development of new antibodies, however, is a lengthy and expensive process. The goal is to develop a system that significantly reduces the time to develop new antibodies as well as the cost. The proposed system and resulting antibodies may be used as a source of future therapeutics, as components of detection systems in biodefense and medicine, or as affinity purification systems for research and diagnostics. The system will be demonstrated in Phase I with the production of antibodies targeted at botulinum neurotoxin, which will be of value to the biodefense area. This SBIR project aims to develop a system for the fast generation of high quantities of antibodies targeted at specific applications. The main objective in Phase I is to develop a platform that allows robust generation of clones producing high quantities of antibodies without the need for time-consuming and labor-intensive gene amplification techniques, such as the dehydrofolate reductase or the glutamine synthase selection systems. This will be coupled with a previously developed method that allows simultaneous generation of multiple humanized or completely human antibodies for the fast generation of diverse collections of antibodies that can address specific needs existing in each segment of the antibody market. However, clones generated via direct transfection of constructs into secondary cell lines, such as Chinese Hamster Ovary (CHO) and Human Embryo Kidney (HEK), produce substantially lower amounts of antibodies than do conventional hybridomas. The amount of antibodies produced is not sufficient to address the needs in any segment of the antibody market. To address needs existing in all segments of the antibody market, it is proposed to develop a new approach for fast and efficient generation and selection of cell clones whose immunoglobulin production levels will be comparable to those of average hybridomas. In combination with the system for robust assembly of immunoglobulin-encoding constructs, this approach will allow the rapid and robust generation of antibodies adapted for use in specific applications.