Agonist antibody to human thrombopoietin receptor
This invention provides an agonist antibody to a human thrombopoietin receptor (human c-Mpl), and pharmaceutical compositions comprising the same for use in treatment of thrombocytopenia. The disclosed agonist antibody comprises (1) antibody constant regions comprising heavy and light chain constant regions, each of which may optionally contain domain substitutions, or may contain deletions, substitutions, additions, or insertions of amino acid residues, and (2) antibody variable regions capable of binding to and activating a human thrombopoietin receptor. The-agonist antibody further induces colony formation at a concentration of 10,000 ng/ml or lower, and has a maximal activity at least 50% higher than that of PEG-rHuMGDF and an 50% effective concentration (EC50) of 100 nM or less.
1. An agonist antibody to human thrombopoietin receptor (c-Mpl), wherein the agonist antibody comprises:
a heavy chain constant region comprising an amino acid sequence selected from the group consisting of the amino acid sequences shown in SEQ ID NOs: 74-80;
a heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:2 and
a light chain variable region comprising the amino acid sequence shown in SEQ ID NO:3.
2. A pharmaceutical composition comprising the antibody according to claim 1 as an active ingredient.
3. An agent for increasing platelets comprising the antibody according to claim 1 as an active ingredient.
4. A therapeutic agent for thrombocytopenia comprising the antibody according to claim 1 as an active ingredient.