Open-source antibodies from the Institute for Protein Innovation (IPI) Timothy A. Springer [1,2,3]; Andrew Kruse [2,3]; Joseph Jardine [3] Affiliations: [1] Program in Cellular and Molecular Medicine (PCMM), Boston Children’s Hospital, Boston MA 02115; [2] Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston MA 02115; [3] Institute for Protein Innovation, Boston MA 02115 For updates on our public launch scheduled for the week of May 8 th , 2017, please sign up for our mailing list at: www.proteininnovation.org Institute for Protein Innovation Synthetic Yeast Display Antibody Library Platform • >10 9 antigen-binding fragments (Fab) with synthetic, native-like complementarity determining regions • Based on 6 VH genes and 3 VL genes with diversity in CDR-H3 loop • Loop length and diversity to mimic human antibody repertoire • Aga1/2 Fab display platform • Can target highly conserved, functionally important epitopes, in contrast to species-specific monoclonal antibodies derived from hybridomas S. Cerevisiae Antigen Fab IgG Aga1/2 Fluorescent tags Antibody Discovery Pipeline High-throughput antibody discovery campaigns will be directed to a set of glycoproteins that are members of the same family. • Leverage deep expertise in production of difficult-to-express proteins for antigens • Develop high-throughput technology for producing and using protein targets in antibody screening and selection in parallel • Select for cross-reactivity with human, mouse, and when possible, zebrafish orthologs to enable use in animal models of disease and as lead therapeutics • Select for reactivity with native proteins, facilitating interrogation of biological function. Parallel selections for antibodies to unfolded regions for western blotting and immunohistochemistry • Antibodies to specific epitopes may be reserved for therapeutic development via outlicensing Validation will be conducted by the IPI, partner institutions, and individual investigators in crowd-sourced international workshops, modeled on the International Leukocyte CD Workshops. Nominations for Antibody Discovery Campaigns To facilitate engagement and leverage the collective wisdom of the wider scientific community, investigators are invited to nominate and lead campaigns directed to specific protein families. Campaigns will also be conducted with companies, other non-profits, or investigators wishing to develop therapeutics. IPI will produce target proteins of mouse, human, (zebrafish) species. Collaborators are encouraged to provide a smaller number of reference proteins. About the IPI Target Protein MACS FACS Antibody Library Cross-reactivity Open-source Database Workshop Meeting Characterization and Validation The IPI is a newly founded 503c non-profit that will forge the missing link between genomics and health care by serving as a foundry for protein tools and therapeutics. 1. It will catalyze innovative research in protein science by providing critical tools, lead therapeutics, and technologies for academic and industry scientists 2. It will create an unparalleled environment for training and teaching the next generation of innovators and entrepreneurs in protein drug development 3. It will serve as a cross-institutional and cross-disciplinary organization to forge new ties between academic and industry investigators. IPI was designed in consultation with stakeholders from the biotechnology, pharmaceutical, and venture capital communities, as well as academic researchers. The institute is located in the heart of the Boston Longwood Medical Area in close proximity to world-class research and medical institutions including Harvard Medical School, Harvard School of Public Health, Boston Children's Hospital, Brigham and Women's Hospital, and Dana-Farber Cancer Institute. Beth Israel Deaconess Medical Center Beth Israel Deaconess Medical Center Boston Children’s Hospital Boston Children’s Hospital Dana Farber Cancer Institute Dana Farber Cancer Institute Joslin Diabetes Center Joslin Diabetes Center Harvard Medical School Harvard Medical School Harvard Medical School Harvard Medical School Harvard School of Public Health Harvard School of Public Health Harvard School of Dental Medicine Harvard School of Dental Medicine Massachusetts College of Pharmacy Massachusetts College of Pharmacy Northeastern University Northeastern University Merck Merck MIT Broad Institute Whitehead Institute MIT Broad Institute Whitehead Institute Harvard University Harvard University Center for Life Sciences Center for Life Sciences Brigham and Women’s Hospital Brigham and Women’s Hospital Longwood Center Longwood Center Brigham and Women’s Hospital Brigham and Women’s Hospital Isabella Stewart Gardner Museum Isabella Stewart Gardner Museum Boston Children’s Hospital Boston Children’s Hospital Why Open-source? Early on, we recognized that the lack of freely-available libraries of well-validated antibodies was hindering scientific progress and drug discovery. We also understood that many small laboratories and organizations lack the expertise and resources to create antibody reagents in-house. Thus, we will curate and make publicly available the majority of our antibodies and data, including DNA sequence, protein expression, and functional validation. Affiliated Institutions • Assistance in recruitment and retention Research and T eaching Affiliated Investigators • Single-pass membrane receptors • Membrane-embedded receptors • Extracellular glycoproteins • Design, evolution, delivery • Analytics and post-translational modification Grants/ Sponsored Research Industry/Biotech Investigators Institute • Core creation and use Expertise Core Investigators & Developers • Glycoprotein discovery and expression • Antibody discovery • Directed evolution • Small molecule discovery • Native tissues and cell lines • Characterization/analytics Affiliated Institutions External Investigators Core Use Training Workshop $ Reagents $ Company Creation $ Model for the Institute for Protein Innovation Open-source Antibody Initiative Proteins, particularly antibodies, have transformed drug discovery and biomedical research, serving as important research tools and therapeutics. Despite their pivotal importance, proteins lag behind DNA and RNA in terms of institutional research support and funding, and protein science has not benefited from initiatives like the Human Genome Project. To empower protein research and pioneer new therapeutics that improve human health, we are developing synthetic antibodies against all ~7,000 extracellular and secreted protein in humans. Importantly, these antibodies will be well-validated and open-source, to both enable research and address the reproducibility crisis plaguing biomedical research.