Methods of treating a tauopathy
The present disclosure provides methods of treating a tauopathy, involving administering an anti-Tau antibody. The present disclosure also provides anti-Tau antibodies, and formulations comprising same, for use in the methods.
1. A method of treating a tauopathy in an individual, the method comprising administering to the individual a pharmaceutical composition comprising:
a) a pharmaceutically acceptable excipient suitable for administration to a human; and
b) a humanized antibody that specifically binds an epitope within an N-terminal portion of a human Tau polypeptide, wherein the humanized antibody comprises:
a) a VH variant 1 comprising the amino acid sequence depicted in FIG. 9 (SEQ ID NO:36) and a Vk variant 1 comprising the amino acid sequence depicted in FIG. 13 (SEQ ID NO:40);
b) a VH variant 1 comprising the amino acid sequence depicted in FIG. 9 (SEQ ID NO:36); and a Vk variant 2 comprising the amino acid sequence depicted in FIG. 14 (SEQ ID NO:41);
c) a VH variant 1 comprising the amino acid sequence depicted in FIG. 9 (SEQ ID NO:36); and a Vk variant 3 comprising the amino acid sequence depicted in FIG. 15 (SEQ ID NO:42);
d) a VH variant 1 comprising the amino acid sequence depicted in FIG. 9 (SEQ ID NO:36); and a Vk variant 4 comprising the amino acid sequence depicted in FIG. 16 (SEQ ID NO:43);
e) a VH variant 2 comprising the amino acid sequence depicted in FIG. 10 (SEQ ID NO:37); and a Vk variant 1 comprising the amino acid sequence depicted in FIG. 13 (SEQ ID NO:40);
f) a VH variant 2 comprising the amino acid sequence depicted in FIG. 10 (SEQ ID NO:37); and a Vk variant 2 comprising the amino acid sequence depicted in FIG. 14 (SEQ ID NO:41);
g) a VH variant 2 comprising the amino acid sequence depicted in FIG. 10 (SEQ ID NO:37); and a Vk variant 3 comprising the amino acid sequence depicted in FIG. 15 (SEQ ID NO:42);
h) a VH variant 2 comprising the amino acid sequence depicted in FIG. 10 (SEQ ID NO:37); and a Vk variant 4 comprising the amino acid sequence depicted in FIG. 16 (SEQ ID NO:43);
i) a VH variant 3 comprising the amino acid sequence depicted in FIG. 11 (SEQ ID NO:38); and a Vk variant 1 comprising the amino acid sequence depicted in FIG. 13 (SEQ ID NO:40);
j) a VH variant 3 comprising the amino acid sequence depicted in FIG. 11 (SEQ ID NO:38); and a Vk variant 2 comprising the amino acid sequence depicted in FIG. 14 (SEQ ID NO:41);
k) a VH variant 3 comprising the amino acid sequence depicted in FIG. 11 (SEQ ID NO:38); and a Vk variant 3 comprising the amino acid sequence depicted in FIG. 15 (SEQ ID NO:42);
l) a VH variant 3 comprising the amino acid sequence depicted in FIG. 11 (SEQ ID NO:38); and a Vk variant 4 comprising the amino acid sequence depicted in FIG. 16 (SEQ ID NO:43);
m) a VH variant 4 comprising the amino acid sequence depicted in FIG. 12 (SEQ ID NO:39); and a Vk variant 1 comprising the amino acid sequence depicted in FIG. 13 (SEQ ID NO:40);
n) a VH variant 4 comprising the amino acid sequence depicted in FIG. 12 (SEQ ID NO:39); and a Vk variant 2 comprising the amino acid sequence depicted in FIG. 14 (SEQ ID NO:41);
o) a VH variant 4 comprising the amino acid sequence depicted in FIG. 12 (SEQ ID NO:39); and a Vk variant 3 comprising the amino acid sequence depicted in FIG. 15 (SEQ ID NO:42); or
p) a VH variant 4 comprising the amino acid sequence depicted in FIG. 12 (SEQ ID NO:39); and a Vk variant 4 comprising the amino acid sequence depicted in FIG. 16 (SEQ ID NO:43).
2. The method of claim 1 , wherein said administering is intravenous.
3. The method of claim 1 , wherein said administering is intrathecal.
4. The method of claim 1 , wherein said administering is subcutaneous.
5. The method of claim 1 , wherein the humanized antibody comprises a VH variant 1 comprising the amino acid sequence depicted in FIG. 9 (SEQ ID NO:36) and a Vk variant 1 comprising the amino acid sequence depicted in FIG. 13 (SEQ ID NO:40).
6. The method of claim 1 , wherein the humanized antibody comprises a VH variant 1 comprising the amino acid sequence depicted in FIG. 9 (SEQ ID NO:36) and a Vk variant 2 comprising the amino acid sequence depicted in FIG. 14 (SEQ ID NO:41).
7. The method of claim 1 , wherein the humanized antibody comprises a VH variant 1 comprising the amino acid sequence depicted in FIG. 9 (SEQ ID NO:36) and a Vk variant 3 comprising the amino acid sequence depicted in FIG. 15 (SEQ ID NO:42).
8. The method of claim 1 , wherein the humanized antibody comprises a VH variant 1 comprising the amino acid sequence depicted in FIG. 9 (SEQ ID NO:36) and a Vk variant 4 comprising the amino acid sequence depicted in FIG. 16 (SEQ ID NO:43).
9. The method of claim 1 , wherein the humanized antibody comprises a VH variant 2 comprising the amino acid sequence depicted in FIG. 10 (SEQ ID NO:37) and a Vk variant 1 comprising the amino acid sequence depicted in FIG. 13 (SEQ ID NO:40).
10. The method of claim 1 , wherein the humanized antibody comprises a VH variant 2 comprising the amino acid sequence depicted in FIG. 10 (SEQ ID NO:37) and a Vk variant 2 comprising the amino acid sequence depicted in FIG. 14 (SEQ ID NO:41).
11. The method of claim 1 , wherein the humanized antibody comprises a VH variant 2 comprising the amino acid sequence depicted in FIG. 10 (SEQ ID NO:37) and a Vk variant 3 comprising the amino acid sequence depicted in FIG. 15 (SEQ ID NO:42).
12. The method of claim 1 , wherein the humanized antibody comprises a VH variant 2 comprising the amino acid sequence depicted in FIG. 10 (SEQ ID NO:37) and a Vk variant 4 comprising the amino acid sequence depicted in FIG. 16 (SEQ ID NO:43).
13. The method of claim 1 , wherein the humanized antibody comprises a VH variant 3 comprising the amino acid sequence depicted in FIG. 11 (SEQ ID NO:38) and a Vk variant 1 comprising the amino acid sequence depicted in FIG. 13 (SEQ ID NO:40).
14. The method of claim 1 , wherein the humanized antibody comprises a VH variant 3 comprising the amino acid sequence depicted in FIG. 11 (SEQ ID NO:38) and a Vk variant 2 comprising the amino acid sequence depicted in FIG. 14 (SEQ ID NO:41).
15. The method of claim 1 , wherein the humanized antibody comprises a VH variant 3 comprising the amino acid sequence depicted in FIG. 11 (SEQ ID NO:38) and a Vk variant 3 comprising the amino acid sequence depicted in FIG. 15 (SEQ ID NO:42).
16. The method of claim 1 , wherein the humanized antibody comprises a VH variant 3 comprising the amino acid sequence depicted in FIG. 11 (SEQ ID NO:38) and a Vk variant 4 comprising the amino acid sequence depicted in FIG. 16 (SEQ ID NO:43).
17. The method of claim 1 , wherein the humanized antibody comprises a VH variant 4 comprising the amino acid sequence depicted in FIG. 12 (SEQ ID NO:39) and a Vk variant 1 comprising the amino acid sequence depicted in FIG. 13 (SEQ ID NO:40).
18. The method of claim 1 , wherein the humanized antibody comprises a VH variant 4 comprising the amino acid sequence depicted in FIG. 12 (SEQ ID NO:39) and a Vk variant 2 comprising the amino acid sequence depicted in FIG. 14 (SEQ ID NO:41).
19. The method of claim 1 , wherein the humanized antibody comprises a VH variant 4 comprising the amino acid sequence depicted in FIG. 12 (SEQ ID NO:39) and a Vk variant 3 comprising the amino acid sequence depicted in FIG. 15 (SEQ ID NO:42).
20. The method of claim 1 , wherein the humanized antibody comprises a VH variant 4 comprising the amino acid sequence depicted in FIG. 12 (SEQ ID NO:39) and a Vk variant 4 comprising the amino acid sequence depicted in FIG. 16 (SEQ ID NO:43).
21. The method of claim 1 , wherein the tauopathy is selected from the group consisting of Alzheimer's disease, Pick's disease, Frontotemporal dementia (FTD), Frontotemporal dementia with Parkinsonism linked to chromosome 17, Progressive supranuclear palsy (PSP), Corticobasal degeneration (CBD), Subacute sclerosing panencephalitis, amyotrophic lateral sclerosis/parkinsonism-dementia complex, argyrophilic grain dementia, British type amyloid angiopathy, cerebral amyloid angiopathy, Creutzfeldt-Jakob disease, dementia pugilistica, diffuse neurofibrillary tangles with calcification, Down's syndrome, frontotemporal lobar degeneration, Gerstmann-Straussler-Scheinker disease, Hallervorden-Spatz disease, inclusion body myositis, multiple system atrophy, myotonic dystrophy, Niemann-Pick disease type C, non-Guamanian motor neuron disease with neurofibrillary tangles, postencephalitic parkinsonism, prion protein cerebral amyloid angiopathy, progressive subcortical gliosis, Tangle only dementia, multi-infarct dementia, ischemic stroke, chronic traumatic encephalopathy (CTE), traumatic brain injury (TBI), and stroke.
22. The method of claim 21 , wherein the tauopathy is PSP.