Value Proposition
· Enhanced Research Capabilities: Provides five distinct human monoclonal antibodies that enhance PAD4 activity for in vitro and in vivo experimental assays, enabling researchers to study PAD4's function in autoimmune diseases such as rheumatoid arthritis.
· Scalable Production: Utilizes commercially available immortalized human cell lines for recombinant expression, facilitating the production of large quantities of agonistic anti-PAD4 antibodies.
· Novel Therapeutic Development: Enables the development and screening of PAD4 inhibition therapies that can effectively overcome agonistic anti-PAD4 antibody activity.
· Accelerated Therapeutic Development: Reduces R&D time and costs by providing standardized, reproducible agonistic anti-PAD4 antibodies that enable the creation of clinically relevant animal models.
· Patient Stratification: May facilitate identification of rheumatoid arthritis patients with severe erosive disease and pulmonary involvement who are most likely to benefit from anti-PAD4-targeted therapies.
Unmet Need
· In rheumatoid arthritis, a subset of patients develops agonistic autoantibodies against PAD4, an enzyme that modifies joint proteins through citrullination. These antibodies hyperactivate PAD4, leading to increased protein citrullination and amplified inflammation as the immune system attacks these altered proteins.
· Patients with agonistic anti-PAD4 antibodies experience more severe rheumatoid arthritis, such as joint erosion and pulmonary involvement. This makes these antibodies both potential biomarkers for disease severity and promising targets for identifying patients who would benefit from specialized anti-PAD4 treatments.
· However, obtaining unlimited quantities of purified agonistic antibodies from rheumatoid arthritis patients has been a significant limitation, hampering the ability to develop clinically relevant animal models, screen for PAD4 inhibitor therapies that can overcome agonistic antibody activity, and conduct comprehensive and efficient preclinical testing. Thus, there exists a strong need to develop a reliable, scalable source of agonistic anti-PAD4 antibodies.
Technology Description
· Current approaches rely on obtaining agonistic anti-PAD4 antibodies directly from rheumatoid arthritis patients, severely limiting the quantities available for research and therapeutic development. Researchers at Johns Hopkins have addressed this limitation by cloning the genes encoding five distinct PAD4-enhancing antibodies from rheumatoid arthritis patient cells and establishing a recombinant production system using commercially available immortalized human cell lines.
Stage of Development
· Available for licensing.
Data Availability
· Data available upon request.
Relevant Publications
Shi, J., Darrah, E., Sims, G. P., Mustelin, T., Sampson, K., Konig, M. F., Bingham, C. O., 3rd, Rosen, A., & Andrade, F. (2018). Affinity maturation shapes the function of agonistic antibodies to peptidylarginine deiminase type 4 in rheumatoid arthritis. Annals of the rheumatic diseases, 77(1), 141–148. https://doi.org/10.1136/annrheumdis-2017-211489
Won, T., Naik, P., Wood, M. K., Wang, H., Talor, M. V., Shi, J., Bracamonte-Baran, W., Thomas, M. A., Jaime, C. M., Jo, W., Ray, S., Foss, C. A., Andrade, F., Čiháková, D., & Darrah, E. (2025). Anti-Peptidylarginine Deiminase 4 Autoantibodies Derived From Patients With Rheumatoid Arthritis Exert Pathogenic Effects by Activating Monocytes and Exacerbating Inflammatory Arthritis. Arthritis & rheumatology (Hoboken, N.J.), 77(9), 1150–1165. https://doi.org/10.1002/art.43168
