Our Recombinant Polyclonal Antibody Technology

Inovan has developed an antibody discovery and expression methodology that can facilitate investigation of therapeutic antibodies and vaccines for emerging infectious diseases. While therapeutic mAbs are increasingly being prescribed and developed, they almost always fail in infectious disease. Thus, the next generation in immunotherapies is combination antibody therapies. Human recombinant polyclonal antibody (pAb) therapies hold greater promise as a treatment options due to their efficacy and robustness against difficult to treat pathogens especially with the emergence of pandemic viruses and multi-resistant strains of bacteria. Inovan is using a methodology developed by Dr. Coljee to screen large panels of human mAbs for immediate use pAB therapeutics. By combining antibody repertoire sequencing with multiplexed experimental data from biosensors and in vitro efficacy assays, our technology promises to hurdle some of the limitations of antibody drug treatments.

 

Polyclonal Antibodies as a Therapy

The next generation in immunotherapies is combination antibody therapies or human recombinant polyclonal antibody (pAb) therapies. pAb therapies are mixtures of antibodies used to treat disease and have been around for decades. The oldest being intravenous immunoglobulins (IVIG) which are human blood-derived products. Before the development of antibiotics,   human and animal serum was widely used as a treatment for infectious diseases. Targeting multiple epitopes and antigens make polyclonal antibodies uniquely suited to treat viral and bacterial infections. pABs are not that different from immunoglobulins except we removed some of the weaknesses immunoglobulins have. Immunoglobulins consist of mostly irrelevant antibodies, some that bind and actually promote disease, and some that bind and that aid in the clearance of the pathogen or prevent it from entering uninfected cells. In a pAB, we rationally select only antibodies that have shown, either single or in combinations, to help eliminate the pathogen or its effects and we test to ensure the final set of antibodies going into the pAB is as fully effective as we can make it. The data supporting the pAB concept is reflected inherently in the success of immunoglobulins.


An emerging appreciation of the broad effector mechanisms of action that are induced by antibodies, beyond binding, is providing a framework for the rational design of effective monoclonal therapeutics or next-generation vaccines. The design is based on defined correlates of protective immunity, often consisting of neutralizing antibody titers. These approaches can be engineered into combination therapies to improve efficacy with multiple mechanisms of action to avoid drug resistance. In many diseases, these engineering combination antibody therapies are likely the best and maybe the only efficacious treatment against emergent and/or complex pathogenic diseases.

 

Human Recombinant Polyclonal Antibody Discovery Platform

Inovan's antibody discovery platform allows for rapid screening of human antibodies against whole pathogens, their antigens, and/or vaccines. Cognate pairs (the original pairing of the antibody heavy and light chains as it was in the human body it derived from) are maintained in this platform, thereby preserving the integrity of the original antibody. In the process, plasma cells are cloned and then screened by Luminex technology for antigen or infected cell surface binding, we focus on plasma cells because they are the pinnacle of B cell development, thus tend to have the highest affinities. Memory B cells are also isolated but generally studied by NGS in bulk rather than through single cell cloning providing context to which plasma cells are induced to respond to a vaccine or a pathogen. When needed, the memory B cells are FACS sorted to find the rare cells to a specific antigen/epitope before single cell cloning.

Initially appropriate human donors are selected (vaccinated, healthy exposed, or convalescent) and blood is drawn (A) to isolate peripheral blood mononuclear cells (PBMCs). The PBMCs are isolated by Ficoll gradient and the antibody expressing cells are identified by cell surface markers (CD19+,CD38+, and either kappa or lambda +) and single cell sorted into 96-well plates (B). Using high fidelity polymerases the heavy and light (both kappa and lambda) chains are amplified in an automated process. The antibodies are then assembled into linear expression cassettes, which include leaders to direct antibody secretion and IgG1 (or other heavy chain constant regions) by overlap polymerase chain reaction (PCR), thus avoiding the time and cost of cloning (C). Heavy and light chain antibody cassettes are then transfected into a human cell line, which secretes correctly glycosylated human antibodies (D). Antibody-containing supernatants are screened by Luminex against a panel of antigens of interest, including purified known antigens, formalin-fixed cells of a variety of strains of the pathogen of interest (to identify antibodies against surface antigens), and supernatants containing the exoproteome from the pathogen of interest (E). Shown is representative data for a 96-well plate of antibodies. Boxed wells are positive and negative controls. Hits above background are shaded green, and potential hits near background are shaded yellow.

 

The Inovan Team

We wouldn’t be able to take Inovan to the next level without our incredible team who collaborate together to make each project come to life. Read below to learn more about the incredible Inovan team.

Meredith Schroeder, Ph.D.

Chief Executive Officer

Dr. Meredith Schroeder leads business activities as well as research and development at Inovan. Dr. Schroeder has expertise in microbiology, focused on antibiotic discovery and development.

Vincent W. Coljee, Ph.D.

Chief Scientific Officer

Dr. Vincent Coljee leads R&D activities and product development and design at. Dr. Coljee is a Harvard researcher with a diverse background spanning biophysics, chemistry to various sub-disciplines of biology and therapeutics. He is an expert in single B/plasma cell cloning, human B/plasma cell sequencing and monoclonal antibodies (mAB) and polyclonal antibodies (pAB) production. Concurrently to his academic track, he has worked in the biotech industry since 2000 and been part of two startups from inception. At Symphogen A/S he invented and developed their antibody discovery and expression technology platforms and he was the founder and CSO of Excelimmune, Inc, where he developed a next generation antibody discovery and expression platform. He has developed many different pABs against pathogens, such as RSV, flu, smallpox, S. aureus and B. pertussis.

Benjamin Brooks, Ph.D.

Chief Business Officer

Dr. Ben Brooks leads business activities and operations at Inovan. Dr Brooks is an expert in epitope characterization and possesses extensive product development and vaccine humoral response experience. In addition to his role at Inovan, Dr. Brooks is Assistant Professor of Biomedical Sciences at Rocky Vista University. His academic efforts have focused on using biosensors to characterize protein-protein interactions and developing software for protein sequence/structure/function studies to improve protein engineering. Dr. Brooks has been involved in the management of several tech start-up ventures and developed a high-throughput surface plasmon resonance biosensor at Carterra, Inc.

 

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