Anti-Human IL-36R (Spesolimab) – Fc Muted™

Recombinant human IL-36R

This biosimilar antibody is aseptically packaged and formulated in 0.01 M phosphate buffered saline (150 mM NaCl) PBS pH 7.2 - 7.4 with no carrier protein, potassium, calcium or preservatives added. Due to inherent biochemical properties of antibodies, certain products may be prone to precipitation over time. Precipitation may be removed by aseptic centrifugation and/or filtration.

Liquid

Recombinant biosimilar antibodies are manufactured in an animal free facility using only in vitro protein free cell culture techniques and are purified by a multi-step process including the use of protein A or G to assure extremely low levels of endotoxins, leachable protein A or aggregates.

To protect mouse colonies from infection by pathogens and to assure that experimental preclinical data is not affected by such pathogens, all of Leinco’s recombinant biosimilar antibodies are tested and guaranteed to be negative for all pathogens in the IDEXX IMPACT I Mouse Profile.

Functional grade biosimilar antibodies may be stored sterile as received at 2-8°C for up to one month. For longer term storage, aseptically aliquot in working volumes without diluting and store at -80°C. Avoid Repeated Freeze Thaw Cycles.

Research Use Only

2 – 8° C Wet Ice

This non-therapeutic biosimilar antibody uses the same variable region sequence as the therapeutic antibody Spesolimab. BI-655130 (Spesolimab) is an interleukin-36 (IL-36) receptor antagonist.

Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening disease characterized by the extensive eruption of skin pustules where approximately half of these flares require hospitalization¹. IL-36 signaling is particularly important in GPP pathogenesis². IL-36 cytokines play 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 rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, and inflammatory bowel disease³. IL- 36R is therefore a target of immunotherapy^1,3.

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 activating IL-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 monoclonal antibodies were identified by screening for blockade of NFκB activation induced by IL-36 ligands in an ovarian epithelial cell line expressing endogenous functional IL-36R. The murine antibody with the best properties (MAB92) was humanized as BI-655130 (Spesolimab) by sub- cloning the mouse variable region with human constant domains and optimizing. Epitope mapping shows significant protection of residues 9 to 14, 96 to 110, 113 to 119, 149 to 154 and 177 to 186 on IL-36R, which coincides with domain 2. Substantial differences exist between human and cynomolgus monkey in the lead-binding epitope and Spesolimab does not cross-react with the cynomolgus IL-36R. Spesolimab also does not cross-react with rhesus, marmoset, mouse, rat, minipig, or hamster IL-36R.

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

IL-36α, IL-36β, IL-36γ, IL-36 receptor antagonist, IL1RAP

1 Blair HA. Drugs. 82(17):1681-1686. 2022.
2 Burden AD. Expert Rev Clin Immunol. 19(5):473-481. 2023.
3 Ahlberg J, Giragossian C, Li H, et al. MAbs. 11(5):956-964. 2019.
4 Ganesan R, Raymond EL, Mennerich D, et al. MAbs. 9(7):1143-1154. 2017.
5 Baum P, Visvanathan S, Garcet S, et al. J Allergy Clin Immunol. 149(4):1402-1412. 2022.
6 Morita A, Strober B, Burden AD, et al. Lancet. 402(10412):1541-1551. 2023.