Valens-Poly Sequencing Polyclonal Antibodies for Drug Discovery

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 DESCRIPTION (provided by applicant): Antibodies are ideal drug candidates due to high specificity for target molecules. Monoclonal antibodies represent one of the fastest growing segments of the drug market, however, recent attention has focused on polyclonal antibodies and monoclonal mixtures to reduce the opportunity for a disease to become drug resistant. Polyclonal antibodies sampled from disease survivors offer a wealth of new drug candidates. Direct proteomic sequencing of the circulating antibodies is the fastest method to determine the antibody response to a disease, and is a prerequisite for drug development. Previously, we created a mass spectrometry-based, monoclonal antibody sequencing tool, Valens, which we will extend in order to sequence complex antibody samples containing polyclonal antibodies or mixtures of monoclonal antibodies. Current technologies for developing drugs from circulating polyclonal antibodies require weeks of lab time, while our tool, Valens-Poly, will reduce that time to just days. Chemical modifications to the antibody, such as oxidation and deamidation, may impact the bioactivity and be the result of improper handling. Valens-Poly will identify sites of modification in order to improve quality control of drug candidates. Finally, we will create an interactive interface for Valens-Poly so that it may integrate expert human knowledge with the automated sequencing algorithms. Our tool will also utilize datasets that complement mass spectrometry when available, including Edman degradation-produced N-terminal sequences or next generation sequencing of transcripts.