| 摘要 |
Disclosed is an antigen binding protein which specifically binds to TNF-alpha comprising: (i) CDRH1 of DYAMH, CDRH2 of AITWNSGHIDYADSVEG, CDRH3 of VSYLSTASSLDY, CDRL1 of RASQGIRNYLA, CDRL2 of AASTLQS, and CDRL3 of QRYNRAPYT; and (ii) a neonatal Fc receptor (FcRn) binding portion of a human IgG1 constant domain comprising amino acid substitutions relative to the human IgG1 constant domain wherein the amino acid substitutions are at amino acid residues 252, 254 and 256 numbered according to EU index of Kabat and the substitution at residue 252 is a substitution of met with tyr; residue 254 is a substitution of ser with thr and residue 256 is a substitution of thr with glu: and wherein the antigen binding protein has an increased FcRn binding affinity at pH 6 and/or increased half-life as compared to an IgG comprising the light chain sequence of SEQ ID No. 2 and the heavy chain sequence of SEQ ID No. 12. Also disclosed it the use of such an antigen binding protein in the manufacture of a medicament for the treatment of rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease or Psoriasis. |
