IP Library › Granted Patent US 9,447,180
Granted Patent B2
US 9,447,180 · App. 14/705,615 · Granted Sep 20, 2016

Methods of treating a tauopathy

Inventors: Irene Griswold-Prenner (South San Francisco, CA); Nancy E. Stagliano (South San Francisco, CA); Vu Cao Dang (South San Francisco, CA)
Assignee: iPierian, Inc.
C07K16/18G01N33/6896A61K2039/505C07K2317/24C07K2317/565C07K2317/567G01N2333/47G01N2800/2814G01N2800/56
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Quick Facts
Patent No.
US 9,447,180
App. No.
14/705,615
Granted
Sep 20, 2016
Kind
B2
Abstract

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.

Claims (67)

1. An isolated nucleic acid comprising a nucleotide sequence encoding light chain variable region complementarity-determining regions (CDRs) 1, 2, and 3 of a humanized antibody that specifically binds an epitope within the N-terminal portion of a human Tau polypeptide, wherein the:

(i) V L CDR1 comprises the amino acid sequence of SEQ ID NO:1;

(ii) V L CDR2 comprises the amino acid sequence of SEQ ID NO:2; and

(iii) V L CDR3 comprises the amino acid sequence of SEQ ID NO:3.

2. An isolated nucleic acid comprising a nucleotide sequence encoding heavy chain variable region complementarity-determining regions (CDRs) 1, 2, and 3 of a humanized antibody that specifically binds an epitope within the N-terminal portion of a human Tau polypeptide, wherein the:

(i) V H CDR1 comprises the amino acid sequence of SEQ ID NO:4;

(ii) V H CDR2 comprises the amino acid sequence of SEQ ID NO:5; and

(iii) V H CDR3 comprises the amino acid sequence of SEQ ID NO:6.

3. An isolated nucleic acid comprising a nucleotide sequence encoding light and heavy chain variable region complementarity-determining regions (CDRs) 1, 2, and 3 of a humanized antibody that specifically binds an epitope within the N-terminal portion of a human Tau polypeptide, wherein the:

(i) V L CDR1 comprises the amino acid sequence of SEQ ID NO:1;

(ii) V L CDR2 comprises the amino acid sequence of SEQ ID NO:2;

(iii) V L CDR3 comprises the amino acid sequence of SEQ ID NO:3;

(iv) V H CDR1 comprises the amino acid sequence of SEQ ID NO:4;

(v) V H CDR2 comprises the amino acid sequence of SEQ ID NO:5; and

(vi) V H CDR3 comprises the amino acid sequence of SEQ ID NO:6.

4. An isolated nucleic acid comprising a nucleotide sequence encoding light chain variable region complementarity-determining regions (CDRs) 1, 2, and 3 of a humanized antibody that specifically binds an epitope within the N-terminal portion of a human Tau polypeptide, wherein the:

(i) V L CDR1 comprises the amino acid sequence of SEQ ID NO:7;

(ii) V L CDR2 comprises the amino acid sequence of SEQ ID NO:8; and

(iii) V L CDR3 comprises the amino acid sequence of SEQ ID NO:9.

5. An isolated nucleic acid comprising a nucleotide sequence encoding heavy chain variable region complementarity-determining regions (CDRs) 1, 2, and 3 of a humanized antibody that specifically binds an epitope within the N-terminal portion of a human Tau polypeptide, wherein the:

(i) V H CDR1 comprises the amino acid sequence of SEQ ID NO:10;

(ii) V H CDR2 comprises the amino acid sequence of SEQ ID NO:11; and

(iii) V H CDR3 comprises the amino acid sequence of SEQ ID NO:12.

6. An isolated nucleic acid comprising a nucleotide sequence encoding light and heavy chain variable region complementarity-determining regions (CDRs) 1, 2, and 3 of a humanized antibody that specifically binds an epitope within the N-terminal portion of a human Tau polypeptide, wherein the:

(i) V L CDR1 comprises the amino acid sequence of SEQ ID NO:7;

(ii) V L CDR2 comprises the amino acid sequence of SEQ ID NO:8;

(iii) V L CDR3 comprises the amino acid sequence of SEQ ID NO:9;

(iv) V H CDR1 comprises the amino acid sequence of SEQ ID NO:10;

(v) V H CDR2 comprises the amino acid sequence of SEQ ID NO:11; and

(vi) V H CDR3 comprises the amino acid sequence of SEQ ID NO:12.

7. The isolated nucleic acid of claim 6 , wherein the nucleotide sequences encoding the CDRs are interspersed with framework-encoding nucleotide sequences.

8. The isolated nucleic acid of claim 7 , wherein the framework encoding nucleotide sequences are human FR-encoding nucleotide sequences.

9. An isolated nucleic acid comprising a nucleotide sequence encoding a VH variant and/or a Vk variant, wherein:

a) the VH variant comprises the amino acid sequence depicted in FIG. 9 (SEQ ID NO:36) and/or the Vk variant comprises the amino acid sequence depicted in FIG. 13 (SEQ ID NO:40);

b) the VH variant comprises the amino acid sequence depicted in FIG. 9 (SEQ ID NO:36); and/or the Vk variant comprises the amino acid sequence depicted in FIG. 14 (SEQ ID NO:41);

c) the VH variant comprises the amino acid sequence depicted in FIG. 9 (SEQ ID NO:36); and/or the Vk variant comprises the amino acid sequence depicted in FIG. 15 (SEQ ID NO:42);

d) the VH variant comprises the amino acid sequence depicted in FIG. 9 (SEQ ID NO:36); and/or the Vk variant comprises the amino acid sequence depicted in FIG. 16 (SEQ ID NO:43);

e) the VH variant comprises the amino acid sequence depicted in FIG. 10 (SEQ ID NO:37); and/or the Vk variant comprises the amino acid sequence depicted in FIG. 13 (SEQ ID NO:40);

f) the VH variant comprises the amino acid sequence depicted in FIG. 10 (SEQ ID NO:37); and/or the Vk variant comprises the amino acid sequence depicted in FIG. 14 (SEQ ID NO:41);

g) the VH variant comprises the amino acid sequence depicted in FIG. 10 (SEQ ID NO:37); and/or the Vk variant comprises the amino acid sequence depicted in FIG. 15 (SEQ ID NO:42);

h) the VH variant comprises the amino acid sequence depicted in FIG. 10 (SEQ ID NO:37); and/or the Vk variant comprises the amino acid sequence depicted in FIG. 16 (SEQ ID NO:43);

i) the VH variant comprises the amino acid sequence depicted in FIG. 11 (SEQ ID NO:38); and/or the Vk variant comprising the amino acid sequence depicted in FIG. 13 (SEQ ID NO:40);

j) the VH variant comprises the amino acid sequence depicted in FIG. 11 (SEQ ID NO:38); and/or the Vk variant comprises the amino acid sequence depicted in FIG. 14 (SEQ ID NO:41);

k) the VH variant comprises the amino acid sequence depicted in FIG. 11 (SEQ ID NO:38); and/or the Vk variant comprises the amino acid sequence depicted in FIG. 15 (SEQ ID NO:42);

l) the VH variant comprises the amino acid sequence depicted in FIG. 11 (SEQ ID NO:38); and/or the Vk variant comprises the amino acid sequence depicted in FIG. 16 (SEQ ID NO:43);

m) the VH variant comprises the amino acid sequence depicted in FIG. 12 (SEQ ID NO:39); and/or the Vk variant comprises the amino acid sequence depicted in FIG. 13 (SEQ ID NO:40);

n) the VH variant comprises the amino acid sequence depicted in FIG. 12 (SEQ ID NO:39); and/or the Vk variant comprises the amino acid sequence depicted in FIG. 14 (SEQ ID NO:41);

o) the VH variant comprises the amino acid sequence depicted in FIG. 12 (SEQ ID NO:39); and/or the Vk variant comprises the amino acid sequence depicted in FIG. 15 (SEQ ID NO:42); or

p) the VH variant comprises rising the amino acid sequence depicted in FIG. 12 (SEQ ID NO:39); and/or the Vk variant comprising the amino acid sequence depicted in FIG. 16 (SEQ ID NO:43).

10. The isolated nucleic acid of claim 9 , wherein the VH variant comprises the amino acid sequence depicted in FIG. 9 (SEQ ID NO:36) and/or the Vk variant comprises the amino acid sequence depicted in FIG. 13 (SEQ ID NO:40).

11. The isolated nucleic acid of claim 9 , wherein the VH variant comprises the amino acid sequence depicted in FIG. 9 (SEQ ID NO:36) and/or the Vk variant comprises the amino acid sequence depicted in FIG. 14 (SEQ ID NO:41).

12. The isolated nucleic acid of claim 9 , wherein the VH variant comprises the amino acid sequence depicted in FIG. 9 (SEQ ID NO:36) and/or the Vk variant comprises the amino acid sequence depicted in FIG. 15 (SEQ ID NO:42).

13. The isolated nucleic acid of claim 9 , wherein the VH variant comprises the amino acid sequence depicted in FIG. 9 (SEQ ID NO:36) and/or the Vk variant comprises the amino acid sequence depicted in FIG. 16 (SEQ ID NO:43).

14. The isolated nucleic acid of claim 9 , wherein the VH variant comprises the amino acid sequence depicted in FIG. 10 (SEQ ID NO:37) and/or the Vk variant comprises the amino acid sequence depicted in FIG. 13 (SEQ ID NO:40).

15. The isolated nucleic acid of claim 9 , wherein the VH variant comprises the amino acid sequence depicted in FIG. 10 (SEQ ID NO:37) and/or the Vk variant comprises the amino acid sequence depicted in FIG. 14 (SEQ ID NO:41).

16. The isolated nucleic acid of claim 9 , wherein the VH variant comprises the amino acid sequence depicted in FIG. 10 (SEQ ID NO:37) and/or the Vk variant comprises the amino acid sequence depicted in FIG. 15 (SEQ ID NO:42).

17. The isolated nucleic acid of claim 9 , wherein the VH variant comprises the amino acid sequence depicted in FIG. 10 (SEQ ID NO:37) and/or the Vk variant comprises the amino acid sequence depicted in FIG. 16 (SEQ ID NO:43).

18. The isolated nucleic acid of claim 9 , wherein the VH variant comprises the amino acid sequence depicted in FIG. 11 (SEQ ID NO:38) and/or the Vk variant comprising the amino acid sequence depicted in FIG. 13 (SEQ ID NO:40).

19. The isolated nucleic acid of claim 9 , wherein the VH variant comprises the amino acid sequence depicted in FIG. 11 (SEQ ID NO:38) and/or the Vk variant comprises the amino acid sequence depicted in FIG. 14 (SEQ ID NO:41).

20. The isolated nucleic acid of claim 9 , wherein the VH variant comprises the amino acid sequence depicted in FIG. 11 (SEQ ID NO:38) and/or the Vk variant comprises the amino acid sequence depicted in FIG. 15 (SEQ ID NO:42).

21. The isolated nucleic acid of claim 9 , wherein the VH variant comprises the amino acid sequence depicted in FIG. 11 (SEQ ID NO:38) and/or the Vk variant comprises the amino acid sequence depicted in FIG. 16 (SEQ ID NO:43).

22. The isolated nucleic acid of claim 9 , wherein the VH variant comprises the amino acid sequence depicted in FIG. 12 (SEQ ID NO:39) and/or the Vk variant comprises the amino acid sequence depicted in FIG. 13 (SEQ ID NO:40).

23. The isolated nucleic acid of claim 9 , wherein the VH variant comprises the amino acid sequence depicted in FIG. 12 (SEQ ID NO:39) and/or the Vk variant comprises the amino acid sequence depicted in FIG. 14 (SEQ ID NO:41).

24. The isolated nucleic acid of claim 9 , wherein the VH variant comprises the amino acid sequence depicted in FIG. 12 (SEQ ID NO:39) and/or the Vk variant comprises the amino acid sequence depicted in FIG. 15 (SEQ ID NO:42).

25. The isolated nucleic acid of claim 9 , wherein the VH variant comprises the amino acid sequence depicted in FIG. 12 (SEQ ID NO:39) and/or the Vk variant comprising the amino acid sequence depicted in FIG. 16 (SEQ ID NO:43).

26. An expression vector comprising the nucleic acid of claim 9 .

27. A cell transformed with the expression vector of claim 26 .

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 2, 2015
From: GRISWOLD-PRENNER, IRENE; STAGLIANO, NANCY E.; DANG, VU
To: IPIERIAN, INC.
Reel/Frame 035971/0799 →
Continuity (6)
Continuation 14481544 · Sep 9, 2014
Continuation 14281319 · May 19, 2014
Continuation 14154954 · Jan 14, 2014
Provisional Application 61781823 · Mar 14, 2013
Provisional Application 61754085 · Jan 18, 2013
Related Publication 20150232544A1 · Aug 20, 2015