Agonist antibody to human thrombopoietin receptor

An agonist antibody, wherein said agonist antibody comprises a heavy chain comprising a constant region and a variable region, and a light chain comprising a constant region and a variable region,

• wherein the heavy- and light-chain variable regions form an antigen-binding domain with agonist activity, and
• wherein the heavy chain constant region comprises all of (i)-(iv):
• i) an upper hinge portion comprising the amino acid sequence of ELKTPLGDTTHT (residues 6-17 of SEQ ID NO:
• 98);
• ii) a middle hinge portion comprising an amino acid sequence selected from the group consisting of (a)-(c):
• (a) CPRCP(EPKSCDTPPPCPRCP)3 (residues 18-67 of SEQ ID NO:
• 98);
• (b) CPRCPEPKSCDTPPPCPRCP (residues 18-37 of SEQ ID NO:
• 102);
• and
• (c) CPRCP (residues 18-22 of SEQ ID NO:
• 103);
• iii) a CH1 region comprising the amino acid sequence of VDKRV (residues 1-5 of SEQ ID NO:
• 96);
• and
• iv) a CH2 region comprising an amino acid sequence selected from the group consisting of APEFEGGP (residues 18-25 of SEQ ID NO:
• 100) and APEFLGGP (residues 18-25 of SEQ ID NO:
• 99);
• or wherein the heavy chain constant region comprises all of (v)-(viii):
• v) an upper hinge portion comprising the amino acid sequence of ESKTPLGDTTHT (residues 6-17 of SEQ ID NO:
• 104);
• vi) a middle hinge portion comprising the amino acid sequence of CPPCP (residues 13-17 of SEQ ID NO:
• 100);
• vii) a CH1 region comprising the amino acid sequence of VDKRV (residues 1-5 of SEQ ID NO:
• 96);
• and
• viii) a CH2 region comprising an amino acid sequence selected from the group consisting of APEFEGGP (residues 18-25 of SEQ ID NO:
• 100) and APEFLGGP (residues 18-25 of SEQ ID NO:
• 99).