Humanized anti-HMGB1 antibody or antigen-binding fragment thereof

摘要

The present invention provides a humanized anti-HMGB1 antibody which specifically binds to a sequence consisting of the C-terminal 8 amino acid residues (EEEDDDDE) of HMGB1 protein and is effective for treatment or prevention of various inflammatory diseases related to this protein, as well as an antigen-binding fragment thereof. The present invention also provides a pharmaceutical composition comprising such an antibody or antigen-binding fragment thereof.

主权项

1. A humanized antibody specifically binding to an amino acid sequence (EEEDDDDE (SEQ ID NO: 60)) present in the C-terminal domain of HMGB1 protein, or an antigen-binding fragment thereof, which capable of neutralizing the biological activity of HMGB1 protein, comprising a heavy chain variable region (VH) and a light chain variable region (VL), wherein
(i) the heavy chain variable region (VH) comprises:
(a) an amino acid sequence of heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 7;(b) an amino acid sequence of heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 8;(c) an amino acid sequence of heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 9;(d) amino acid sequences of SEQ ID Nos: 43, 44, 45, and 46 as amino acid sequences of FR1, FR2, FR3, and FR4, respectively, wherein the amino acid sequences of FR1, FR2, FR3, and FR4 optionally have mutations of deletion, substitution and/or addition of one or several amino acid residues in the amino acid sequences of SEQ ID NOs: 43, 44, 45 and 46, respectively; and (ii) the light chain variable region (VL) comprises:
(a) an amino acid sequence of light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 10,(b) an amino acid sequence of light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 11;(c) an amino acid sequence of light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 12; and(d) the light chain variable region (VL) further comprises the amino acid sequences of SEQ ID Nos: 47, 48, 49 and 50 as amino acid sequences of FR1, FR2, FR3, and FR4, respectively, wherein the amino acids sequences of FR1, FR2, FR3, and FR4 optionally have mutations of deletion, substitution, insertion, and/or addition of one to several amino acid residues in the amino acid sequences of SEQ ID NOs: 47, 48, 49, and 50, respectively.