Open-source antibodies from the Institute for Institute for Protein Innovation (IPI) Protein Timothy A. Springer [1,2,3]; Andrew Kruse [2,3]; Joseph Jardine [3] Innovation 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

Open-source Antibody Initiative Nominations for Antibody Discovery Campaigns Proteins, particularly antibodies, have transformed drug discovery and biomedical To facilitate engagement and leverage the collective wisdom of the wider scientific research, serving as important research tools and therapeutics. community, investigators are invited to nominate and lead campaigns directed to Despite their pivotal importance, proteins lag behind DNA and RNA in terms of specific protein families. institutional research support and funding, and protein science has not benefited from Campaigns will also be conducted with companies, other non-profits, or investigators initiatives like the Human Genome Project. wishing to develop therapeutics. To empower protein research and pioneer new therapeutics that improve human IPI will produce target proteins of mouse, human, (zebrafish) species. health, we are developing synthetic antibodies against all ~7,000 extracellular and Collaborators are encouraged to provide a smaller number of reference proteins. 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. 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. Synthetic Yeast Display Antibody Library Platform We also understood that many small laboratories and organizations lack the expertise and resources to create antibody reagents in-house. Antigen Fluorescent tags Thus, we will curate and make publicly available the majority of our antibodies and data, including DNA sequence, protein expression, and functional validation. Fab About the IPI Aga1/2 S. Cerevisiae IgG Grants/ Industry/Biotech Sponsored Research Model for the Institute for Protein Innovation Investigators • >109 antigen-binding fragments (Fab) with synthetic, native-like complementarity determining regions Affi liated Institutions Institute • Assistance in recruitment • Core creation and use • Based on 6 VH genes and 3 VL genes with diversity in CDR-H3 loop and retention • Loop length and diversity to mimic human antibody repertoire Affi liated Investigators Core Investigators & Developers • Single-pass membrane receptors • Glycoprotein discovery and expression Core • Membrane-embedded receptors • Antibody discovery Use • Aga1/2 Fab display platform • Extracellular glycoproteins • Directed evolution Affi liated Institutions • Design, evolution, delivery • Small molecule discovery External Investigators • Can target highly conserved, functionally important epitopes, in contrast to • Analytics and post-translational • Native tissues and cell lines species-specific monoclonal antibodies derived from hybridomas modifi cation • Characterization/analytics Research and Teaching Expertise

Antibody Discovery Pipeline Training Workshop $ Reagents $ Company Creation $

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. Characterization and Validation 1. It will catalyze innovative research in protein science by providing critical tools, lead therapeutics, and technologies for academic and industry scientists Target Protein MACS 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

Workshop ties between academic and industry investigators. Meeting IPI was designed in consultation with stakeholders from the biotechnology, pharmaceutical, and venture capital communities, as well as academic researchers. Antibody Library FACS Cross-reactivity 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 High-throughput antibody discovery campaigns will be directed School, Harvard School of Public Health, Boston Children's Hospital, Brigham and to a set of glycoproteins that are members of the same family. Open-source Women's Hospital, and Dana-Farber Cancer Institute. Database • Leverage deep expertise in production of difficult-to-express Longwood Merck proteins for antigens Beth Israel Center Harvard MIT Deaconess University Broad Institute • Develop high-throughput technology for producing and using protein targets in Medical Center Center for Whitehead Institute Life Sciences antibody screening and selection in parallel Isabella • Select for cross-reactivity with human, mouse, and when possible, zebrafish Stewart Harvard Gardner orthologs to enable use in animal models of disease and as lead therapeutics Boston Children’s Medical Museum Hospital School • Select for reactivity with native proteins, facilitating interrogation of biological Joslin Diabetes Northeastern Center University function. Parallel selections for antibodies to unfolded regions for western blotting Brigham and Women’s and immunohistochemistry Dana Farber Boston Children’s Hospital Cancer Institute Hospital Massachusetts College • Antibodies to specific epitopes may be reserved for therapeutic development via of Pharmacy outlicensing Harvard School Brigham and Women’s Hospital Validation will be conducted by the IPI, partner institutions, and individual investigators Harvard Medical of Dental Medicine School in crowd-sourced international workshops, modeled on the International Leukocyte Harvard School CD Workshops. of Public Health

For updates on our public launch scheduled for the week of May 8th, 2017, please sign up for our mailing list at: www.proteininnovation.org