HUMANIZED ANTl-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, 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 or an amino acid sequence having mutations of deletion, substitution, insertion and/or addition of one to several amino acid residues in 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 or an amino acid sequence having mutations of deletion, substitution, insertion and/or addition of one to several amino acid residues in the amino acid sequence of SEQ ID NO: 8; and (c) an amino acid sequence of heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 9 or an amino acid sequence having mutations of deletion, substitution, insertion and/or addition of one to several amino acid residues in the amino acid sequence of SEQ ID NO: 9, 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 or an amino acid sequence having mutations of deletion, substitution, insertion and/or addition of one to several amino acid residues in 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 or an amino acid sequence having mutations of deletion, substitution, insertion and/or addition of one to several amino acid residues in the amino acid sequence of SEQ ID NO: 11; and (c) an amino acid sequence of light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 12 or an amino acid sequence having mutations of deletion, substitution, insertion and/or addition of one to several amino acid residues in the amino acid sequence of SEQ ID NO: 12.