IP Library › Granted Patent US 10,752,679
Granted Patent B2
US 10,752,679 · App. 16/092,439 · Granted Aug 25, 2020

Tau immunotherapy

Inventors: Peter Seubert (San Francisco, CA); Philip James Dolan, III (Foster City, CA); Yue Liu (Foster City, CA); Robin Barbour (Walnut Creek, CA)
Assignee: PROTHENA BIOSCIENCES LIMITED
C07K16/18A61P25/28C07K2317/24C07K2317/92C07K2317/94
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Quick Facts
Patent No.
US 10,752,679
App. No.
16/092,439
Granted
Aug 25, 2020
Kind
B2
Abstract

The invention provides antibodies to tau. The antibodies inhibit or delay tau-associated pathologies and associated symptomatic deterioration.

Claims (30)

1. An antibody that binds to human tau comprising a mature heavy chain variable region having an amino acid sequence at least 90% identical to SEQ ID NO:35 and a mature light chain variable region at least 90% identical to SEQ ID NO:36 or SEQ ID NO:39 provided position L9 is S.

2. The antibody of claim 1 comprising three Kabat CDRs of SEQ ID NO:15 and three Kabat CDRs of SEQ ID NO:22.

3. The antibody of claim 2 , provided positions H13, H28, H48 and H91 are occupied by K, P, M and F respectively and at least two of positions L1, L4, L36 and L43 is occupied by N, L, F and S respectively.

4. The antibody of claim 3 , provided positions H 13 , H 28 , H 48 and H91 are occupied by K, P, M and F respectively, and at least three of positions L1, L4, L36 and L43 are occupied by N, L, F and S respectively.

5. The antibody of claim 4 , provided positions H13, H28, H48 and H91 are occupied by K, P, M and F respectively, and positions L1, L4, L36 and L43 are occupied by N, L, F and S respectively.

6. The antibody of claim 4 , provided positions H13, H28, H48and H91 are occupied by K, P, M and F respectively, and positions L1, L4, L36 and L43 are occupied by D, L, F and S respectively.

7. The antibody of claim 1 , wherein position H1 is occupied by E.

8. The antibody of claim 1 , comprising a mature heavy chain variable region having an amino acid sequence at least 95% identical to SEQ ID NO:35 and a mature light chain variable region at least 95% identical to SEQ ID NO:36 or SEQ ID NO: 39.

9. The antibody of claim 1 , wherein the mature heavy chain variable region is fused to a heavy chain constant region and the mature light chain variable region is fused to a light chain constant region.

10. The antibody of claim 1 , wherein the heavy chain constant region is a mutant form of natural human constant region which has reduced binding to an Fcγ receptor relative to the natural human constant region.

11. The antibody of claim 1 , wherein the heavy chain constant region is of IgG1 isotype, and the light chain constant region is a kappa light chain.

12. The antibody of claim 1 , wherein the mature heavy chain variable region has an amino acid sequence designated SEQ ID NO:35 and the mature light chain variable region has an amino acid sequence designated SEQ ID NO:36.

13. The antibody of claim 1 , wherein the antibody is conjugated to a cytotoxic or cytostatic agent.

14. The antibody of claim 1 , wherein the antibody is a Fab fragment.

15. A nucleic acid encoding the heavy and/or light chains of an antibody as described in claim 1 .

16. The nucleic acid of claim 15 , further comprising a segment encoding a human IgG1 constant region.

17. The nucleic acid of claim 16 , wherein the IgG1constant region has a sequence of SEQ ID NO:29 provided the C-terminal lysine can be omitted.

18. The nucleic acid of claim 17 , wherein the segment encoding the IgG1 constant region has a nucleotide sequence of SEQ ID NO:30 or 31.

19. The nucleic acid of claim 15 , further comprising a segment encoding a human kappa constant region.

20. The nucleic acid of claim 19 , wherein the kappa constant region has the sequence of SEQ ID NO:32.

21. The nucleic acid of claim 20 , wherein the nucleic acid encoding the kappa constant region has the sequence of SEQ ID NO:33 or 34.

22. A pharmaceutical composition comprising an antibody of claim 1 and a pharmaceutically acceptable carrier.

23. A method of treating or effecting prophylaxis of Alzheimer's disease, wherein effecting prophylaxis reduces the risk, lessens the severity or delays the onset of at least one sign or symptom of the disease, comprising administering an effective regime of an antibody as defined in claim 1 and thereby treating or effecting prophylaxis of Alzheimer's disease.

24. A method of treating or effecting prophylaxis of a disease associated with tau, wherein effecting prophylaxis reduces the risk, lessens the severity or delays the onset of at least one sign or symptom of the disease, comprising administering an effective regime of an antibody as defined in 1 and thereby treating or effecting prophylaxis of the disease.

25. The method of claim 24 , wherein the disease is a neurological disease.

26. A method of reducing aberrant transmission of tau comprising administering an effective regime of an antibody as defined in claim 1 , and thereby reducing transmission of tau.

27. A method of inducing phagocytosis of tau comprising administering an effective regime of an antibody as defined in claim 1 and thereby inducing phagocytosis of tau.

28. A method of inhibiting tau aggregation or deposition comprising administering an effective regime of an antibody as defined in claim 1 thereby inhibiting tau aggregation or deposition.

29. A method of inhibiting formation of tau tangles comprising administering an effective regime of an antibody as defined in claim 1 .

30. The antibody of claim 11 , wherein the heavy chain constant region has the sequence of SEQ ID NO:29 with or without the C-terminal lysine and the light chain constant region has the sequence of SEQ ID NO:32.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 31, 2020
From: SEUBERT, PETER; DOLAN, PHILIP JAMES, III; LIU, YUE; BARBOUR, ROBIN
To: PROTHENA BIOSCIENCES INC
Reel/Frame 051680/0440 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 31, 2020
From: PROTHENA BIOSCIENCES INC
To: PROTHENA BIOSCIENCES LIMITED
Reel/Frame 051680/0518 →
Continuity (2)
Provisional Application 62330786 · May 2, 2016
Related Publication 20190322728A1 · Oct 24, 2019
Cited By (3)
US 12,195,525 US 12,479,910 US 12,735,507