Humanized antibodies that recognize alpha-synuclein
The present application discloses humanized 1H7 antibodies. The antibodies bind to human alpha synuclein and can be used for treatment and diagnosis of Lewy body disease.
1. A nucleic acid encoding a mature heavy chain variable region and/or a mature light chain variable region of an antibody comprising a mature heavy chain variable region, wherein position H97 by Kabat numbering is C, M, S or T and other residues of the three Kabat CDRs are as defined by SEQ ID NO:44, and the heavy chain variable region is at least 90% identical to SEQ ID NO:44, and a mature light chain variable region comprising the three Kabat CDRs of SEQ ID NO:45, and being at least 90% identical to SEQ ID NO:45, wherein the antibody specifically binds to human alpha synuclein.
2. The nucleic acid of claim 1 , wherein the amino acid sequence of the mature heavy chain variable region is SEQ ID NO:44 and the amino acid sequence of the mature light chain variable region is SEQ ID NO:45 except provided that position L46 (Kabat numbering) is occupied by L or F, and/or position L49 (Kabat numbering) is occupied by Y or C, and/or position L83 (Kabat numbering) is occupied by F or A, and/or position H11 (Kabat numbering) is occupied by V or L, and/or position H28 (Kabat numbering) is occupied by T or S, and/or position H38 (Kabat numbering) is occupied by R or K, and/or position H48 (Kabat numbering) is occupied by M or I, and/or position H67 (Kabat numbering) is occupied by V or A, and/or position H69 (Kabat numbering) is occupied by M or L, and/or position H71 (Kabat numbering) is occupied by T or A, and/or position H91 (Kabat numbering) is occupied by Y or F, and/or H97; (Kabat numbering) is occupied by C or S, and wherein the antibody specifically binds to human alpha synuclein.
3. The nucleic acid of claim 1 , having a heavy chain sequence comprising SEQ ID NO:22 and/or a light chain sequence comprising SEQ ID NO:36.
4. The nucleic acid of claim 1 , having a heavy chain sequence comprising SEQ ID NO:22 and a light chain sequence comprising SEQ ID NO:36.
5. The nucleic acid of claim 1 , wherein the mature heavy chain variable region has an amino acid sequence designated SEQ ID NO:23 and the mature light chain variable region has an amino acid sequence designated SEQ ID NO:37.
6. The nucleic acid of claim 5 , wherein the mature heavy chain variable region is fused to a heavy chain constant region having the amino acid sequence designated SEQ ID NO:52, wherein the C-terminal lysine residue is optionally omitted and the mature light chain constant region is fused to a light chain constant region having the amino acid sequence designated SEQ ID NO:49.
7. The nucleic acid of claim 1 having a sequence comprising any one of SEQ ID NO: 18, 20, 22, 24, 26, 32, 34, 36, or 38.
8. A host cell comprising a vector comprising the nucleic acid of claim 1 or 7 .
9. A method of producing an antibody, comprising culturing cells transformed with nucleic acids encoding the heavy and light chains of the antibody, so that the cells secrete the antibody; and purifying the antibody from cell culture media; wherein the antibody is defined by claim 1 or 7 .