Anti-α-synuclein antibodies and methods of use

1. An isolated anti-α-synuclein antibody comprising three heavy chain hypervariable regions (HVR-H1, HVR-H2, and HVR-H3) and three light chain hypervariable regions (HVR-L1, HVR-L2, and HVR-L3), wherein:

(a) HVR-H1 comprises the amino acid sequence of SEQ ID NO:9;

(b) HVR-H2 comprises the amino acid sequence of SEQ ID NO:10;

(c) HVR-H3 comprises the amino acid sequence of SEQ ID NO:11;

(d) HVR-L1 comprises the amino acid sequence of SEQ ID NO:6;

(e) HVR-L2 comprises the amino acid sequence of SEQ ID NO:7; and

(f) HVR-L3 comprises the amino acid sequence of SEQ ID NO:8.

2. The isolated anti-α-synuclein antibody of claim 1 , comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:3, and the light chain variable region comprises the amino acid sequence of SEQ ID NO:2.

3. The isolated anti-α-synuclein antibody of claim 1 , comprising a light chain variable region comprising the amino acid sequence of SEQ ID NO:2.

4. The isolated anti-α-synuclein antibody of claim 1 , comprising a heavy chain variable region comprises the amino acid sequence of SEQ ID NO:3.

5. An isolated anti-α-synuclein antibody comprising three heavy chain hypervariable regions (HVR-H1, HVR-H2, and HVR-H3) and three light chain hypervariable regions (HVR-L1, HVR-L2, and HVR-L3), wherein:

(a) HVR-H1 comprises the amino acid sequence of SEQ ID NO:15;

(b) HVR-H2 comprises the amino acid sequence of SEQ ID NO:16;

(c) HVR-H3 comprises the amino acid sequence of SEQ ID NO:17;

(d) HVR-L1 comprises the amino acid sequence of SEQ ID NO:12;

(e) HVR-L2 comprises the amino acid sequence of SEQ ID NO:13; and

(f) HVR-L3 comprises the amino acid sequence of SEQ ID NO:14.

6. The isolated anti-α-synuclein antibody of claim 5 , comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:5, and the light chain variable region comprises the amino acid sequence of SEQ ID NO:4.

7. The isolated anti-α-synuclein antibody of claim 5 , comprising a light chain variable region comprising the amino acid sequence of SEQ ID NO:4.

8. The isolated anti-α-synuclein antibody of claim 5 , comprising a heavy chain variable region comprises the amino acid sequence of SEQ ID NO:5.

9. The antibody of claim 1 or claim 5 , wherein the antibody is a monoclonal antibody.

10. The antibody of claim 1 or claim 5 , wherein the antibody is a human, humanized, or chimeric antibody.

11. The antibody of claim 1 or claim 5 , wherein the antibody binds an α-synuclein selected from the group consisting of monomeric α-synuclein and oligomeric α-synuclein.

12. The antibody of claim 1 or claim 5 for use in reducing aggregation or oligomerization of α-synuclein.

13. The antibody of claim 2 or claim 6 for use in reducing aggregation or oligomerization of α-synuclein.

14. A pharmaceutical formulation comprising the antibody of claim 1 or claim 2 and a pharmaceutically acceptable carrier.

15. A pharmaceutical formulation comprising the antibody of claim 5 or claim 6 and a pharmaceutically acceptable carrier.

16. The antibody of claim 1 or claim 5 for use in treating or delaying the onset of a disorder selected from the group consisting of a synucleinopathy, Parkinson's disease, Parkinson's disease dementia, dementia with Lewy bodies, Lewy body disease, juvenile-onset generalized neuroaxonal dystrophy (Hallervorden-Spatz disease), multiple system atrophy, pure autonomic failure, and neurodegeneration with brain iron accumulation type-1.

17. The antibody of claim 2 or claim 6 for use in treating or delaying the onset of a disorder selected from the group consisting of a synucleinopathy, Parkinson's disease, Parkinson's disease dementia, dementia with Lewy bodies, Lewy body disease, juvenile-onset generalized neuroaxonal dystrophy (Hallervorden-Spatz disease), multiple system atrophy, pure autonomic failure, and neurodegeneration with brain iron accumulation type-1.

18. The antibody of claim 1 or claim 5 for use as a medicament.

19. The antibody of claim 2 or claim 6 for use as a medicament.

20. An isolated nucleic acid encoding the antibody of claim 1 or claim 5 .

21. An isolated nucleic acid encoding the antibody of claim 2 or claim 6 .

22. A host cell comprising the nucleic acid of claim 20 .

23. A method of producing an antibody comprising culturing the host cell of claim 22 so that the antibody is produced.

24. A method for treating an individual having a disorder selected from the group consisting of a synucleinopathy, Parkinson's disease, Parkinson's disease dementia, dementia with Lewy bodies, Lewy body disease, juvenile-onset generalized neuroaxonal dystrophy (Hallervorden-Spatz disease), multiple system atrophy, pure autonomic failure, and neurodegeneration with brain iron accumulation type-1, the method comprising administering to the individual an effective amount of the antibody of claim 1 or claim 5 .

25. A method for treating an individual having a disorder selected from the group consisting of a synucleinopathy, Parkinson's disease, Parkinson's disease dementia, dementia with Lewy bodies, Lewy body disease, juvenile-onset generalized neuroaxonal dystrophy (Hallervorden-Spatz disease), multiple system atrophy, pure autonomic failure, and neurodegeneration with brain iron accumulation type-1, the method comprising administering to the individual an effective amount of the antibody of claim 2 or claim 6 .

26. A method for treating or delaying the onset of a disorder selected from the group consisting of a synucleinopathy, Parkinson's disease, Parkinson's disease dementia, dementia with Lewy bodies, Lewy body disease, juvenile-onset generalized neuroaxonal dystrophy (Hallervorden-Spatz disease), multiple system atrophy, pure autonomic failure, and neurodegeneration with brain iron accumulation type-1, the method comprising administering to an individual in need thereof an effective amount of the antibody of claim 1 or claim 5 .

27. A method for treating or delaying the onset of a disorder selected from the group consisting of a synucleinopathy, Parkinson's disease, Parkinson's disease dementia, dementia with Lewy bodies, Lewy body disease, juvenile-onset generalized neuroaxonal dystrophy (Hallervorden-Spatz disease), multiple system atrophy, pure autonomic failure, and neurodegeneration with brain iron accumulation type-1, the method comprising administering to an individual in need thereof an effective amount of the antibody of claim 2 or claim 6 .