Valens-Poly Sequencing Polyclonal Antibodies for Drug Discovery

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 PUBLIC HEALTH RELEVANCE Characterization of the antibody response to an infection is an important precursor to antibody based drug development Here we propose a tool Valens Poly which directly sequences monoclonal and polyclonal antibodies using mass spectrometry in less than a tenth of the time required by current technologies and will consequently enable novel drug discoveries and shorten drug development timelines