| abstract |
The present invention provides an agonist antibody against human thrombopoietin receptor (aka human c-Mpl). Specifically, the amino acid sequence of the heavy region of the antibody in which the normal region of the antibody replaces the domain of the heavy chain normal region between (1) the heavy chain normal region and the light chain normal region of the human antibody, and (2) the subclass of the human antibody. The amino acid sequence of the normal region of a human antibody light chain, or (3) an amino acid sequence of which one or several amino acid residues are deleted, substituted, added or inserted in the amino acid sequence of (1) or (2) above. Has an amino acid sequence and also the variable region of the antibody has the ability to bind to and activate the human thrombopoietin receptor, (a) 10,000 ng / mL in a CFU-MK colony formation assay using human umbilical cord blood CD34 + cells Inducing colony formation at the following concentrations, and (b) proliferation assays using UT7 / TPO cells, wherein the maximum activity is at least 50% of PEG-rHuMGDF and is also 50% effective (EC50) that provides an agonist antibody, and a pharmaceutical composition for treatment of thrombocytopenia comprising the antibody to the human thrombopoietin receptor having the nature of things than 100nM. |