ANTIBODIES TO TAU
This invention relates to antibodies to tau and methods of use thereof.
1 . An isolated monoclonal anti-tau antibody, wherein the antibody recognizes an epitope within an amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8.
2 . The isolated monoclonal anti-tau antibody of claim 1 , wherein the antibody comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 14 and SEQ ID NO: 15.
3 . The isolated monoclonal anti-tau antibody of claim 1 , wherein the antibody is encoded by a nucleic acid sequence comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO: 12 and SEQ ID NO: 13.
4 . An isolated monoclonal anti-tau antibody, wherein the antibody comprises a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 18 with zero to two amino acid substitutions.
5 . An isolated monoclonal anti-tau antibody, wherein the antibody comprises a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 21 with zero to two amino acid substitutions.
6 . An isolated monoclonal anti-tau antibody of any of the preceding claims, wherein the antibody is selected from the group consisting of a single-chain antibody, an antibody fragment, a chimeric antibody, or a humanized antibody.
7 . An isolated monoclonal anti-tau antibody of claim 1 , wherein the antibody is specifically able to block tau seeding activity in a cellular tau aggregation assay.
8 . A method for reducing the spread of tau aggregation in the brain of a subject, the method comprising administering a pharmacologically effective amount of an isolated monoclonal anti-tau antibody to the subject, wherein the isolated monoclonal anti-tau antibody is an isolated monoclonal anti-tau antibody according to claim 1 .
9 . The method of claim 8 , wherein the method further comprises improving in a subject at least one symptom associated with tau aggregation.
10 . The method of claim 9 , wherein the at least one symptom associated with tau aggregation is selected from the group consisting of tau pathology, impaired cognitive function, altered behavior, abnormal language function, emotional dysregulation, seizures, impaired nervous system structure or function, and an increased risk of development of Alzheimer's disease.
11 . The method of claim 8 , wherein the administration comprises an effective systemic route of administration.
12 . The method of claim 8 , wherein the administration comprises an effective local route of administration, including directly within the central nervous system.
13 . An immunoassay comprising at least two isolated monoclonal anti-tau antibody according to claim 1 .
14 . The immunoassay of claim 13 , wherein the immunoassay comprises at least two captures antibodies and a detection antibody, and wherein each capture antibody is an isolated monoclonal anti-tau antibody that recognizes a tau epitope distinct from the other.
15 . The immunoassay of claim 14 , wherein a first capture antibody is an isolated monoclonal anti-tau antibody that recognizes an epitope within SEQ ID NO: 7, a second capture antibody is an isolated monoclonal anti-tau antibody that recognizes an epitope within SEQ ID NO: 8, and a detection antibody is an isolated monoclonal anti-tau antibody that recognizes an epitope within SEQ ID NO: 8.
16 . A method of measuring the amount of tau aggregate in a sample of a biological fluid obtained from a subject, the method comprising measuring the amount of tau aggregate using an immunoassay of claim 15 .
17 . The method of claim 16 , wherein the tau aggregate is immunoprecipitated from the sample using an isolated monoclonal anti-tau antibody and then the amount of immunoprecipitated tau aggregate is measured.