Humanized antibodies that recognize alpha-synuclein
The present application discloses humanized 9E4 antibodies. The antibodies bind to human alpha synuclein and can be used for immunotherapy of Lewy body disease.
1. An antibody that binds alpha synuclein, comprising a mature heavy chain variable region having the amino acid sequence of SEQ ID NO: 11 and a mature light chain variable region having the amino acid sequence of SEQ ID NO:4 except provided that position L36 (Kabat numbering) can be occupied by Y or F, position L83 (Kabat numbering) can be occupied by F or L, position H73 (Kabat numbering) can be occupied by N or D and position H93 (Kabat numbering) can be occupied by A or S.
2. The antibody of claim 1 , wherein the mature heavy chain variable region has the amino acid sequence designated SEQ ID NO:10.
3. The antibody of claim 1 , wherein the mature light chain variable region has the amino acid sequence designated SEQ ID NO:5.
4. The antibody of claim 1 , wherein position H73 (Kabat numbering) is occupied by D and position H93 (Kabat numbering) is occupied by A.
5. The antibody of claim 1 , wherein the mature variable light chain has the amino acid sequence of SEQ ID NO:3, 4 or 5 and the mature variable heavy chain has the amino acid sequence of SEQ ID NO:8, 9 or 10.
6. The antibody of claim 5 , comprising a heavy chain constant region having the amino acid sequence of SEQ ID NO:32.
7. The antibody of claim 5 , comprising a light chain constant region having the amino acid sequence of SEQ ID NO:13.
8. An antibody that binds alpha synuclein, comprising a humanized heavy chain comprising the three Kabat CDRs of SEQ ID NO:11 and a humanized light chain comprising the three CDRs of SEQ ID NO:4 provided that position L36 (Kabat numbering) is occupied by F and/or position L83 (Kabat numbering) is occupied by L and/or position H73 (Kabat numbering) is occupied by D, and/or position H93 (Kabat numbering) is occupied by S.
9. The antibody of claim 8 , comprising a mature heavy chain variable region having the amino acid sequence designated SEQ ID NO:10 and a mature light chain variable region having the amino acid sequence designated SEQ ID NO:5.
10. The antibody of claim 8 , wherein position L36 (Kabat numbering) is occupied by F and position L83 (Kabat numbering) is occupied by L.
11. The antibody of claim 8 , provided that position L36 (Kabat numbering) is occupied by F.
12. The antibody of claim 8 , provided that position L83 (Kabat numbering) is occupied by L.
13. The antibody of claim 8 , provided that position H73 (Kabat numbering) is occupied by D.
14. The antibody of claim 1 or 8 , comprising a heavy chain constant region of human IgG1 isotype.
15. A pharmaceutical composition comprising an antibody as defined by claim 1 or 8 .
16. The antibody of claim 1 or 8 that is a Fab fragment.