Anti-IL-17/TNFR fusion protein IPR: anti-IL-17 antibody/TNFR ECD fusion protein and its uses (Patent Application No.: 201711137039.8, PCT/CN2018/114079)

IL-17 and TNF-α have significant synergistic effects in cell signalling pathways and in promoting inflammatory mediators.  Therefore, it is of great prospect to develop IL-17 and TNF-α bispecific antibodies for autoimmune diseases. Anti-IL-17 and TNFR fusion proteins, there are no immunogenicity problem, would be the world's first anti-IL-17 and TNF-α bispecific antibodies with better efficacy than Taltz if developed successfully.

· Research results on anti-IL-17/TNFR fusion protein

In vitro activity study of anti-IL-17 and TNFR fusion proteins

Gene construction of this project has completed ; stable cells have been screened; the expression amount has reached more thanexpression of more than 1.37 g/L; affinity for IL-17 of 1.05 x 10-11M , affinity for TNF-α of 2.11 x 10-10M, with higher affinity for IL-17 than Abbott's IL-17/TNF-α bispecific antibody ABT-122; and no interaction between IL-17 and TNF-α when combined.  In vitro activity studies showed that IL-17 and TNF-α have significant synergistic effects in cell signalling pathways and promotion of inflammatory mediators. It has a function to inhibit active immune mediators such as CXCL1 and IL-8. It has better biological activity than IL-17 antibody (ixekizumab) and Ixepro alone,  and equivalent with combination of IL-17 antibody and Ixepro.

In vitro studies have shown that BY19.3 has better biological activity than IL-17 antibody (ixekizumab) and Ixepro alone,  Due to its Y-trap structure, BY19.3 is less immunogenic than the other IL-17 and TNF-α bispecific antibodies ABT-122 (ADA, 100%), ABBV-257 (ADA 83.3-100%) and COVA322.