Anti-Human IL-36R (Spesolimab) - 100 mg

All|Recombinant Antibodies>Biosimilar Recombinant Antibodies|Primary Monoclonal Antibodies

2 - 8°C Wet Ice

Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening disease characterizedby the extensive eruption of skin pustules where approximately half of these flares requirehospitalization1. IL-36 signaling is particularly important in GPP pathogenesis2. IL-36 cytokinesplay a key role in epithelial innate immunity along with the heterodimeric receptor IL-36R. IL-36R ligands are over-expressed in lesional GPP skin and a feed-forward loop of unopposed IL-36 signaling can occur. IL-36R signaling has also been implicated in psoriatic and rheumatoidarthritis, asthma, chronic obstructive pulmonary disease, and inflammatory bowel disease3. IL-36R is therefore a target of immunotherapy1, 3. BI-655130 (Spesolimab) is a humanized monoclonal antibody that binds specifically to IL-36R, blocking IL-36 signaling and thus preventing cognate ligands IL-36 α, β and γ from activatingIL-36R1. This ultimately prevents the activation of pro-inflammatory and pro-fibrotic pathways. BI-655130 (Spesolimab) was generated by immunizing mice with recombinant human IL-36R4.Hybridomas were produced by fusion to PAI myeloma cells. Functionally potent monoclonalantibodies were identified by screening for blockade of NFκB activation induced by IL-36ligands in an ovarian epithelial cell line expressing endogenous functional IL-36R. The murineantibody with the best properties (MAB92) was humanized as BI-655130 (Spesolimab) by sub-cloning the mouse variable region with human constant domains and optimizing. Epitopemapping shows significant protection of residues 9 to 14, 96 to 110, 113 to 119, 149 to 154 and177 to 186 on IL-36R, which coincides with domain 2. Substantial differences exist betweenhuman and cynomolgus monkey in the lead-binding epitope and Spesolimab does not cross-reactwith the cynomolgus IL-36R. Spesolimab also does not cross-react with rhesus, marmoset, mouse, rat, minipig, or hamster IL-36R.

≥ 5.0 mg/ml

IL-36R is expressed predominantly on cells of epithelial origin as well asdendritic cells, CD4+ T cells, intestinal lymphocytes, and synovial fibroblasts.