Antibodies to alpha-synuclein
The invention provides methods for detecting alpha-synuclein. The invention also identifies preferred epitopes of alpha synuclein for use in such detection, and provides antibodies specifically binding to such epitopes.
1. A hybridoma producing a monoclonal antibody selected from the group consisting of 6H7, 8A5, 9E4, and 1H7.
2. A humanized or chimeric version of a monoclonal antibody selected from the group consisting of 6H7, 8A5, 9E4, and 1H7.
3. The antibody of claim 2 , wherein the antibody has an isotype of human IgG1.
4. The humanized or chimeric antibody of claim 2 , wherein the antibody has the CDRs of monoclonal antibody 6H7.
5. The humanized or chimeric antibody of claim 2 , wherein the antibody has the CDRs of monoclonal antibody 8A5.
6. The humanized or chimeric antibody of claim 2 , wherein the antibody has the CDRs of monoclonal antibody 9E4.
7. The humanized or chimeric antibody of claim 2 , wherein the antibody has the CDRs of monoclonal antibody 1H7.
8. A method of humanizing a donor monoclonal antibody selected from the group consisting of 6H7, 8A5, 9E4, and 1H7, comprising:
providing a DNA encoding the variable domains of a donor antibody selected from the group consisting of 6H7, 8A5, 9E4, and 1H7;
determining the amino acid sequence of the CDR regions of the donor monoclonal antibody from the DNA;
selecting human acceptor antibody sequences; and
producing a humanized antibody comprising the CDRs from the donor antibody and variable region frameworks from the human acceptor antibody sequences, optionally wherein one or more variable region framework residues from the human acceptor antibody sequences are substituted.
9. A method of producing a chimeric form of a monoclonal antibody selected from the group consisting of 6H7, 8A5, 9E4, and 1H7 comprising:
providing DNA encoding the variable domains of a monoclonal antibody selected from the group consisting of 6H7, 8A5, 9E4, and 1H7;
determining the amino acid sequence of the light and heavy chain variable regions of the monoclonal antibody from the DNA;
selecting heavy and light chain constant regions from an acceptor antibody;
producing a chimeric antibody comprising a light chain comprising the light chain variable region of the monoclonal antibody fused to the light chain constant region, and a heavy chain comprising the heavy chain variable region of the monoclonal antibody fused to the heavy chain constant region.