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AssigneeChugai Seiyaku Kabushiki Kaisha
InventorsTomoyuki Igawa, Taichi Kuramochi, Atsuhiko Maeda, Hirotake Shiraiwa
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By altering amino acid sequences, the present inventors successfully produced constant regions that can confer antibodies with particularly favorable properties for pharmaceutical agents. When used to produce antibodies, the altered constant regions produced according to the present invention significantly reduce heterogeneity. Specifically, the antibody homogeneity can be achieved by using antibody heavy chain and light chain constant regions introduced with alterations provided by the present invention. More specifically, the alterations can prevent the loss of homogeneity of antibody molecules due to disulfide bond differences in the heavy chain. Furthermore, in a preferred embodiment, the present invention can improve antibody pharmacokinetics as well as prevent the loss of homogeneity due to C-terminal deletion in antibody constant region.
An antibody constant region comprising an amino acid sequence in which Cys at position 14 (position 131 in the EU numbering), Arg at position 16 (position 133 in the EU numbering), Cys at position 103 (position 220 in the EU numbering), Glu at position 20 (position 137 in the EU numbering), Ser at position 21 (position 138 in the EU numbering), His at position 147 (position 268 in the EU numbering), Arg at position 234 (position 355 in the EU numbering), and Gln at position 298 (position 419 in the EU numbering) in the amino acid sequence of SEQ ID NO:
An antibody constant region comprising an amino acid sequence in which Cys at position 14 (position 131 in the EU numbering), Arg at position 16 (position 133 in the EU numbering), Cys at position 103 (position 220 in the EU numbering), Glu at position 20 (position 137 in the EU numbering), Ser at position 21 (position 138 in the EU numbering), His at position 147 (position 268 in the EU numbering), Arg at position 234 (position 355 in the EU numbering), Gln at position 298 (position 419 in the EU numbering), Ala at position 209 (position 330 in the EU numbering), Pro at position 210 (position 331 in the EU numbering), and Thr at position 218 (position 339 in the EU numbering) in the amino acid sequence of SEQ ID NO:
A human κ chain constant region comprising at least one Cys at positions 102 to 106.
A human κ chain constant region which does not comprise Cys at position 107.
A human κ chain constant region which comprises at least one Cys at positions 102 to 106 but does not comprise Cys at position 107.
Dependencies are inferred from the claim text.