IL-18/IL-23 multispecific antigen binding proteins
The present disclosure provides multispecific antigen binding proteins that bind to one or more cytokines, more particularly to pro-inflammatory cytokines. In particular, the present disclosure relates to multispecific antigen binding proteins that comprise an interleukin 18 (IL-18) binding domain and an interleukin 23 (IL-23) binding domain, and the use of said multispecific antigen binding proteins in medicine.
1 . A multispecific antigen binding protein comprising an interleukin 18 (IL-18) binding domain and an interleukin 23 (IL-23) binding domain wherein said multispecific antigen binding protein comprises an IL-18 binding domain comprising a heavy chain of SEQ ID NO: 55 and a light chain of SEQ ID NO: 57, and an IL-23 binding domain comprising a heavy chain of SEQ ID NO: 54 and a light chain of SEQ ID NO:56.
2 . The multispecific antigen binding protein of claim 1 wherein said multispecific antigen binding protein is a bispecific antigen binding protein.
3 . The multispecific antigen binding protein of claim 2 wherein said bispecific antigen binding protein is a bispecific antibody, wherein said bispecific antibody consists of said interleukin 18 (IL-18) binding domain and said interleukin 23 (IL-23) binding domain, and wherein said IL-18 binding domain consists of a heavy chain of SEQ ID NO: 55 and a light chain of SEQ ID NO: 57, and said IL-23 binding domain consists of a heavy chain of SEQ ID NO: 54 and a light chain of SEQ ID NO:56.
4 . The multispecific antigen binding protein of claim 1 wherein said multispecific antigen binding protein down-regulates CXCL13 secretion.
5 . A nucleic acid sequence encoding the multispecific antigen binding protein of claim 4 .
6 . A pharmaceutical composition comprising the multispecific antigen binding protein according to claim 4 and a pharmaceutically acceptable excipient.
7 . A method for the treatment of inflammatory bowel disease (IBD) in a human subject in need thereof comprising administering to said human subject a therapeutically effective amount of a multispecific antigen binding protein, wherein said multispecific antigen binding protein comprises:
(i) an IL-18 binding domain comprising a heavy chain of SEQ ID NO: 55 and a light chain of SEQ ID NO: 57; and
(ii) an IL-23 binding domain comprising a heavy chain of SEQ ID NO: 54 and a light chain of SEQ ID NO:56.
8 . The method according to claim 7 wherein the inflammatory bowel disease (IBD) is ulcerative colitis (UC) or Crohn's Disease (CD).
9 . A method for the treatment of UC or CD in a human subject in need thereof comprising administering to said human subject a therapeutically effective amount of a pharmaceutical composition, wherein said pharmaceutical composition comprises:
(i) a multispecific antigen binding protein comprising an interleukin 18 (IL-18) binding domain and an interleukin 23 (IL-23) binding domain wherein the IL-18 binding domain comprises a heavy chain of SEQ ID NO: 55 and a light chain of SEQ ID NO: 57, and the IL-23 binding domain comprises a heavy chain of SEQ ID NO: 54 and a light chain of SEQ ID NO: 56; and
(ii) a pharmaceutically acceptable excipient.