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 reducing the level of amyloid beta in a neuronal cell and/or an extracellular fluid in an individual, the method comprising administering to the individual:
a humanized antibody that binds an epitope within an extracellular tau (eTau) polypeptide in an amount effective to reduce the level of amyloid beta in the neuronal cell and/or the extracellular fluid in the individual,
wherein said administering is effective to reduce the level of amyloid beta in the neuronal cell and/or the extracellular fluid in the individual.
2. The method of claim 1 , wherein the antibody binds an epitope within amino acids 1-158 of eTau.
3. The method of claim 1 , wherein the antibody binds an epitope within amino acids 2-68 of eTau.
4. The method of claim 1 , wherein the antibody binds an epitope within amino acids 15-24 of eTau.
5. The method of claim 1 , wherein the epitope is within a Tau polypeptide having at least 95% amino acid sequence identity to SEQ ID NO:48 (eTau4).
6. The method of claim 1 , wherein the antibody binds a linear epitope.
7. The method of claim 1 , wherein the antibody binds specifically to the epitope independently of phosphorylation of amino acids within the epitope.
8. The method of claim 1 , wherein the antibody competes for binding to the epitope with an antibody that comprises:
a) a light chain region comprising:
i) a VL CDR1 comprising the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:7;
(ii) a VL CDR2 comprising the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:8; and
(iii) a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3 or SEQ ID NO:9;
and
b) a heavy chain region comprising:
(i) a VH CDR1 comprising the amino acid sequence of SEQ ID NO:4 or SEQ ID NO:10;
(ii) a VH CDR2 comprising the amino acid sequence of SEQ ID NO:5 or SEQ ID NO:11; and
(iii) a VH CDR3 comprising the amino acid sequence of SEQ ID NO:6 or SEQ ID NO:12.
9. The method of claim 1 , wherein the humanized antibody comprises a heavy chain region of the isotype IgG1, IgG2, IgG3, or IgG4.
10. The method of claim 1 , wherein the humanized antibody is a Fv, scFv, Fab, F(ab′)2, or Fab′.
11. The method of claim 1 , wherein said administering is via an intravenous, intrathecal, or subcutaneous route of administration.
12. The method of claim 1 , wherein the extracellular fluid is cerebrospinal fluid, interstitial fluid, blood, or a blood fraction.
13. The method of claim 1 , wherein the antibody comprises:
a) a light chain region comprising:
i) a VL CDR1 comprising the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:7;
(ii) a VL CDR2 comprising the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:8; and
(iii) a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3 or SEQ ID NO:9;
and
b) a heavy chain region comprising:
(i) a VH CDR1 comprising the amino acid sequence of SEQ ID NO:4 or SEQ ID NO:10;
(ii) a VH CDR2 comprising the amino acid sequence of SEQ ID NO:5 or SEQ ID NO:11; and
(iii) a VH CDR3 comprising the amino acid sequence of SEQ ID NO:6 or SEQ ID NO:12.
14. A method of treating a disease associated with amyloid beta accumulation in an individual, the method comprising administering to the individual:
an effective amount of a humanized antibody that binds an epitope within an extracellular tau (eTau) polypeptide,
wherein said administering is effective to reduce the level of amyloid beta in a neuronal cell and/or an extracellular fluid in the individual by at least 10% compared with the level of amyloid beta in the neuronal cell and/or the extracellular fluid before treatment with the antibody.
15. The method of claim 14 , wherein the antibody binds an epitope within amino acids 1-158 of eTau.
16. The method of claim 14 , wherein the antibody binds an epitope within amino acids 2-68 of eTau.
17. The method of claim 14 , wherein the antibody binds an epitope within amino acids 15-24 of eTau.
18. The method of claim 14 , wherein the epitope is within a Tau polypeptide having at least 95% amino acid sequence identity to SEQ ID NO:48 (eTau4).
19. The method of claim 14 , wherein the antibody binds a linear epitope.
20. The method of claim 14 , wherein the antibody binds specifically to the epitope independently of phosphorylation of amino acids within the epitope.
21. The method of claim 14 , wherein the antibody competes for binding to the epitope with an antibody that comprises:
a) a light chain region comprising:
i) a VL CDR1 comprising the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:7;
(ii) a VL CDR2 comprising the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:8; and
(iii) a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3 or SEQ ID NO:9;
and
b) a heavy chain region comprising:
(i) a VH CDR1 comprising the amino acid sequence of SEQ ID NO:4 or SEQ ID NO:10;
(ii) a VH CDR2 comprising the amino acid sequence of SEQ ID NO:5 or SEQ ID NO:11; and
(iii) a VH CDR3 comprising the amino acid sequence of SEQ ID NO:6 or SEQ ID NO:12.
22. The method of claim 14 , wherein the humanized antibody comprises a heavy chain region of the isotype IgG1, IgG2, IgG3, or IgG4.
23. The method of claim 14 , wherein the humanized antibody is a Fv, scFv, Fab, F(ab′)2, or Fab′.
24. The method of claim 14 , wherein said administering is via an intravenous, intrathecal, or subcutaneous route of administration.
25. The method of claim 14 , wherein the extracellular fluid is cerebrospinal fluid, interstitial fluid, blood, or a blood fraction.
26. The method of claim 14 , wherein the antibody comprises:
a) a light chain region comprising:
i) a VL CDR1 comprising the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:7;
(ii) a VL CDR2 comprising the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:8; and
(iii) a VL CDR3 comprising the amino acid sequence of SEQ ID NO:3 or SEQ ID NO:9;
and
b) a heavy chain region comprising:
(i) a VH CDR1 comprising the amino acid sequence of SEQ ID NO:4 or SEQ ID NO:10;
(ii) a VH CDR2 comprising the amino acid sequence of SEQ ID NO:5 or SEQ ID NO:11; and
(iii) a VH CDR3 comprising the amino acid sequence of SEQ ID NO:6 or SEQ ID NO:12.
27. The method of claim 14 , wherein the disease is Alzheimer's disease.
28. A method of reducing the level of amyloid beta in an extracellular fluid in an individual, the method comprising administering to the individual a pharmaceutical composition comprising:
a) a humanized antibody that binds an epitope within an extracellular tau (eTau) polypeptide in an amount effective to reduce the level of amyloid beta in the extracellular fluid in the individual; and
b) a pharmaceutically acceptable carrier,
wherein said administering is effective to reduce the level of amyloid beta in the extracellular fluid in the individual.