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 8th, 2017, please sign up for our mailing list at: www.proteininnovation.org

Institute forProtein Innovation

Synthetic Yeast Display Antibody Library Platform

• >109 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

IgGAga1/2

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 CampaignsTo 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

FACSAntibody Library Cross-reactivity

Open-sourceDatabase

WorkshopMeeting

Characterizationand 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 scientists2. It will create an unparalleled environment for training and teaching the next

generation of innovators and entrepreneurs in protein drug development3. 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 IsraelDeaconess

Medical Center

Beth IsraelDeaconess

Medical Center

Boston Children’sHospital

Boston Children’sHospital

Dana FarberCancer Institute

Dana FarberCancer Institute

Joslin DiabetesCenter

Joslin DiabetesCenter

HarvardMedicalSchool

HarvardMedicalSchool

Harvard MedicalSchool

Harvard MedicalSchool

Harvard Schoolof Public HealthHarvard Schoolof Public Health

Harvard Schoolof Dental Medicine

Harvard Schoolof Dental Medicine

Massachusetts College

of Pharmacy

Massachusetts College

of Pharmacy

NortheasternUniversity

NortheasternUniversity

MerckMerckMIT

Broad InstituteWhitehead Institute

MITBroad Institute

Whitehead Institute

HarvardUniversityHarvard

UniversityCenter for

Life SciencesCenter for

Life Sciences

Brigham and Women’s HospitalBrigham and Women’s Hospital

Longwood Center

Longwood Center

Brigham and Women’s Hospital

Brigham and Women’s Hospital

Isabella StewartGardner Museum

Isabella StewartGardner MuseumBoston Children’s

HospitalBoston 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.

Affi liated Institutions• Assistance in recruitment

and retention

Research and Teaching

Affi liated Investigators• Single-pass membrane receptors• Membrane-embedded receptors• Extracellular glycoproteins• Design, evolution, delivery• Analytics and post-translational

modifi cation

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

Affi liated InstitutionsExternal Investigators

CoreUse

Training Workshop $ Reagents $ Company Creation $

Model for the Institute for Protein Innovation

Open-source Antibody InitiativeProteins, 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.