PREVENTION AND TREATMENT OF SYNUCLEINOPATHIC AND AMYLOIDOGENIC DISEASE
The invention provides improved agents and methods for treatment of diseases associated with synucleinopathic diseases, including Lewy bodies of alpha-synuclein in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the Lewy body. The methods are particularly useful for prophylactic and therapeutic treatment of Parkinson's disease.
1 - 32 . (canceled)
33 . An antibody specifically binding alpha-synuclein comprising the CDRs of a monoclonal antibody produced by a hybridoma deposited as ATCC accession number PTA-8222.
34 . The antibody of claim 33 wherein the antibody is the monoclonal antibody produced by the hybridoma deposited as ATCC accession number PTA-8222.
35 . The antibody of claim 33 , wherein the antibody is a chimeric or humanized antibody of the monoclonal antibody produced by the hybridoma deposited as ATCC accession number PTA-8222.
36 . The antibody of claim 33 that is an intact antibody.
37 . The antibody of claim 33 that is a binding fragment.
38 . The antibody of claim 37 , wherein the binding fragment is a single-chain antibody, Fab, or F(ab′)2 fragment.
39 . The humanized antibody of claim 35 , wherein the antibody comprises a light chain variable region fused to a light chain constant region and a heavy chain variable region fused to a heavy chain constant region.
40 . The humanized antibody of claim 39 , wherein the heavy chain constant region is of human IgG1 isotype.
41 . The humanized antibody of claim 39 , wherein the heavy chain constant region is of human IgG2 isotype.
42 . The humanized antibody of claim 39 , wherein the heavy chain constant region is of human IgG3 isotype.
43 . The humanized antibody of claim 39 , wherein the heavy chain constant region is of human IgG4 isotype.
44 . A pharmaceutical composition comprising the antibody of claim 33 and a pharmaceutically acceptable carrier.
45 . A method of humanizing an antibody of claim 34 comprising:
determining the amino acid sequence of CDR regions of the monoclonal antibody;
selecting one or more acceptor antibody sequences; and
producing a humanized antibody comprising the CDRs from the monoclonal antibody and variable region frameworks from the one or more acceptor antibody sequences.
46 . A method of producing a chimeric form of a monoclonal antibody produced by a hybridoma deposited as ATCC accession number PTA-8222, comprising:
determining the amino acid sequence of the light and heavy chain variable regions of the monoclonal antibody;
selecting a heavy chain constant region and a light chain constant region;
producing a chimeric antibody comprising a light chain comprising the light chain variable region fused to the light chain constant region, and a heavy chain comprising the heavy chain variable region fused to the heavy chain constant region.
47 . A cell of a hybridoma deposited as ATCC accession number PTA-8222.
48 . A method of detecting the presence or absence of alpha-synuclein in a subject, comprising contacting a biological sample from the subject with an effective amount of the antibody of claim 33 .