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Biologic drugs that neutralize excess IL-1\u03b2 activity, such as canakinumab, have been effective in treating IL-1\u03b2-mediated diseases. This article reports the discovery and development of a novel humanized anti-IL-1\u03b2 antibody, designated as TAVO103A, which exhibited potent binding affinities to human and monkey IL-1\u03b2. TAVO103A demonstrated more potent neutralization of IL-1\u03b2 activities compared to canakinumab in multiple assays, including tests on the IL-1\u03b2-driven signal transduction cascade, inflammatory cytokine release from MRC-5 cells, chemokine release from A549 cells, and the proliferation of D10.G4.1 helper T cells. Ex vivo studies showed that TAVO103A effectively neutralized IL-1\u03b2-mediated release of pro-inflammatory cytokines from peripheral blood mononuclear cells. In addition, TAVO103A exhibited dose-dependent efficacy in a knee joint inflammation mouse model. TAVO103A underwent Fc engineering to reduce binding to Fc\u03b3 receptors, increase affinity to FcRn receptors, and enhance its resistance to proteolytic degradation. In a Phase 1 study, TAVO103A was found to be safe, well tolerated, and demonstrated a median half-life of 63 days in healthy subjects. By recognizing a different epitope, TAVO103A provided more potent neutralization of IL-1\u03b2 activities, a longer circulating half-life, and improved safety profiles compared to canakinumab, positioning it to be a potential best-in-class therapeutic option for various IL-1\u03b2-mediated diseases.<\/jats:p>","DOI":"10.1093\/cei\/uxaf009","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T23:23:08Z","timestamp":1739488988000},"source":"Crossref","is-referenced-by-count":3,"title":["Discovery and Phase 1 study of a novel monoclonal antibody against human IL-1\u03b2 for the treatment of IL-1\u03b2-mediated diseases"],"prefix":"10.1093","volume":"219","author":[{"given":"Minseon","family":"Cho","sequence":"first","affiliation":[{"name":"Tavotek Biotherapeutics Inc. , Ambler, PA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan H","family":"Tam","sequence":"additional","affiliation":[{"name":"Tavotek 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