Modified Antibody Constant Regions
AssigneeChugai Seiyaku Kabushiki Kaisha
InventorsTaichi Kuramochi, Shigero Tanba, Tomoyuki Igawa, Atsuhiko Maeda, Kiyoaki Sakata, Mika Endoh
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Abstract
The present inventors successfully provided constant regions capable of enhancing the agonist activity of antibodies through amino acid sequence alterations. Specifically, agonist activity was found to be enhanced in antibodies having a constant region in which amino acids of the antibody heavy chain constant region are substituted or deleted, or antibodies having a constant region in which the hinge region amino acids are substituted. Use of such antibodies as pharmaceutical formulations can provide pharmaceutical formulations with improved performance.
Claims34
An antibody constant region that comprises an amino acid sequence comprising deletion of at least one amino acid in the upper hinge region in the amino acid sequence of SEQ ID NO:
- 32 (IgG1 constant region).
An antibody constant region comprising the amino acid sequence of SEQ ID NO:
- 20 (M97), the amino acid sequence of SEQ ID NO:
- 22 (M98), the amino acid sequence of SEQ ID NO:
- 24 (M101), the amino acid sequence of SEQ ID NO:
- 26 (M132), the amino acid sequence of SEQ ID NO:
- 45 (M146), the amino acid sequence of SEQ ID NO:
- 33 (M148), the amino acid sequence of SEQ ID NO:
- 34 (M152), the amino acid sequence of SEQ ID NO:
- 39 (M167), the amino acid sequence of SEQ ID NO:
- 40 (M168), the amino acid sequence of SEQ ID NO:
- 37 (M169), or the amino acid sequence of SEQ ID NO:
- 38 (M154).
-26. (canceled)
An agonistic antibody comprising an antibody constant region with deletion or substitution with other amino acids of at least one amino acid in the heavy chain upper hinge region of human IgG1, which is also an antibody with enhanced agonist activity compared to the activity before introduction of said deletion or substitution.
A method of enhancing agonist activity of an antibody, comprising the step of deleting or substituting with other amino acids at least one amino acid of the upper hinge region of the heavy chain in human IgG1.
A method of enhancing agonist activity of an antibody, comprising the step of deleting at least one amino acid selected from Lys at position 218, Ser at position 219, Asp at position 221, Lys at position 222, Thr at position 223, His at position 224, and Thr at position 225 (EU numbering) in the amino acid sequence of SEQ ID NO:
- 32 (IgG1 constant region).
Dependencies are inferred from the claim text.