IP Library › Granted Patent US 12,709,641
Granted Patent B2
US 12,709,641 · App. 18/046,293 · Granted Aug 18, 2026

Tau binding compounds

Inventors: Todd Carter (Winchester, MA); Jinzhao Hou (Lexington, MA); Vinodhbabu Kurella (Woburn, MA); Allan D. Capili (Somerville, MA); Wencheng Liu (Cambridge, MA); Hiu Yan Chung (Boston, MA); Jerrah Holth (Sudbury, MA); Dillon Kavanagh (Cambridge, MA); Maneesha Anand Paranjpe (Burlington, MA)
Assignee: VOYAGER THERAPEUTICS, INC.
C07K16/18A61K39/3955A61K45/06A61P25/28A61K2039/505C07K2317/14C07K2317/22C07K2317/24C07K2317/31C07K2317/34C07K2317/54C07K2317/55C07K2317/565C07K2317/622C07K2317/76C07K2317/92
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Quick Facts
Patent No.
US 12,709,641
App. No.
18/046,293
Filed
Oct 13, 2022
Granted
Aug 18, 2026
Kind
B2
Art Unit
1675
USPC
424/135.1
Abstract

The present disclosure provides anti-tau antibodies and vectorization thereof (e.g., into AAV particles). Also provided are methods of using anti-tau antibodies and/or AAV particles for prevention, treatment, and/or diagnosis of neurological indications.

Claims (68)

1 . An antibody that binds to tau comprising a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HC CDR1), an HC CDR2, and an HC CDR3, and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LC CDR1), an LC CDR2, and an LC CDR3, wherein:

(i) the HC CDR1 comprises the amino acid sequence, X 1 X 2 WMH wherein X 1 is R or I; and X 2 is Y or F, the HC CDR2 comprises the amino acid sequence of SEQ ID NO: 1184, and the HC CDR3 comprises the amino acid sequence of SEQ ID NO: 410; and the LC CDR1 comprises the amino acid sequence of SEQ ID NO: 1185, the LC CDR2 comprises the amino acid sequence of SEQ ID NO: 1182, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO: 571;

(ii) the HC CDR1 comprises the amino acid sequence of SEQ ID NO: 1186, the HC CDR2 comprises the amino acid sequence of SEQ ID NO: 1187, and the HC CDR3 comprises the amino acid sequence of SEQ ID NO: 1167; and the LC CDR1 comprises the amino acid sequence of SEQ ID NO: 1188, the LC CDR2 comprises the amino acid sequence of RVS, and the LC CDR3 comprises the amino acid sequence of SEQ ID NOs: 571; or

(iii) the HC CDR1 comprises the amino acid sequence of SEQ ID NO: 1180, the HC CDR2 comprises the amino acid sequence of SEQ ID NO: 341, and the HC CDR3 comprises the amino acid sequence of SEQ ID NO: 410; and the LC CDR1 comprises the amino acid sequence of SEQ ID NO: 1181, the LC CDR2 comprises the amino acid sequence of SEQ ID NO: 1182, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO: 571.

2 . The antibody of claim 1 , wherein the HC CDR1 comprises the amino acid sequence of SEQ ID NO: 1147, the HC CDR2 comprises the amino acid sequence of SEQ ID NO: 1148, and the HC CDR3 comprises the amino acid sequence of SEQ ID NO: 410; and the LC CDR1 comprises the amino acid sequence of SEQ ID NO: 474, the LC CDR2 comprises the amino acid sequence of SEQ ID NO: 529, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO 571.

3 . The antibody of claim 1 , wherein the HC CDR1 comprises the amino acid sequence of SEQ ID NO: 1149, the HC CDR2 comprises the amino acid sequence of SEQ ID NO: 1150, and the HC CDR3 comprises the amino acid sequence of SEQ ID NO: 410; and the LC CDR1 comprises the amino acid sequence of SEQ ID NO: 475, the LC CDR2 comprises the amino acid sequence of SEQ ID NO: 530, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO: 571.

4 . The antibody of claim 1 , wherein:

(i) the VH comprises the amino acid sequence of any one of SEQ ID NOs: 21, 22, or 23, or an amino acid sequence having at least 80% sequence identity thereto; or

(ii) the VH comprises an amino acid sequence having no more than 30 modifications of the amino acid sequence of any one of SEQ ID NOs: 21, 22, or 23.

5 . The antibody of claim 1 , wherein:

(i) the VL comprises the amino acid sequence of any one of SEQ ID NOs: 93, 94, or 95, or an amino acid sequence at least 80% identical thereto; or

(ii) the VL comprises an amino acid sequence having no more than 30 modifications of the amino acid sequence of any one of SEQ ID NOs: 93, 94, or 95.

6 . The antibody of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 22, or an amino acid sequence at least 80% identical thereto; and the VL comprises the amino acid sequence of SEQ ID NO: 94, or an amino acid sequence at least 80% identical thereto.

7 . The antibody of claim 1 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 23, or an amino acid sequence at least 80% identical thereto; and the VL comprises the amino acid sequence of SEQ ID NO: 95, or an amino acid sequence at least 80% identical thereto.

8 . The antibody of claim 1 , wherein the nucleotide sequence encoding the VH comprises the nucleotide sequence of any one of SEQ ID NOs: 167, 168, or 169, or a nucleotide sequence at least 80% identical thereto.

9 . The antibody of claim 1 , wherein the nucleotide sequence encoding the VL comprises the nucleotide sequence of any one of SEQ ID NOs: 241, 242, or 243, or a nucleotide sequence at least 80% identical thereto.

10 . The antibody of claim 1 , wherein the nucleotide sequence encoding the VH comprises the nucleotide sequence of SEQ ID NO: 167, or a nucleotide sequence at least 80% identical thereto; and the nucleotide sequence encoding the VL comprises the nucleotide sequence of SEQ ID NO: 241, or a nucleotide sequence at least 80% identical thereto.

11 . The antibody of claim 1 , wherein the nucleotide sequence encoding the VH comprises the nucleotide sequence of SEQ ID NO: 168, or a nucleotide sequence at least 80% identical thereto; and the nucleotide sequence encoding the VL comprises the nucleotide sequence of SEQ ID NO: 242, or a nucleotide sequence at least 80% identical thereto.

12 . The antibody of claim 1 , wherein the nucleotide sequence encoding the VH comprises the nucleotide sequence of SEQ ID NO: 169, or a nucleotide sequence at least 80% identical thereto; and the nucleotide sequence encoding the VL comprises the nucleotide sequence of SEQ ID NO: 243, or a nucleotide sequence at least 80% identical thereto.

13 . The antibody of claim 1 , comprising:

(i) a heavy chain constant region selected from human IgG1, human IgG2, human IgG3, and human IgG4, murine IgG1, murine IgG2a, murine IgG2b, murine IgG2c, and murine IgG3; and

(ii) a light chain constant region chosen from the light chain constant regions of kappa or lambda.

14 . The antibody of claim 1 , comprising a human IgG4 heavy chain constant region and a human kappa light chain constant region.

15 . The antibody of claim 1 , which binds the C-terminus of a tau protein.

16 . The antibody of claim 1 , which binds a tau protein comprising one or more phosphorylated residues.

17 . The antibody of claim 1 , which

(i) binds enriched paired helical filament tau protein (ePHF);

(ii) binds an epitope comprising a region formed by a complex of at least two tau proteins;

(iii) binds to a tau protein with a dissociation constant (K D ) of less than about 120 nM; and/or

(iv) reduces or inhibits aggregation of tau.

18 . A vector comprising a nucleic acid encoding the antibody of claim 1 .

19 . A host cell comprising a nucleic acid encoding the antibody of claim 1 .

20 . The host cell of claim 19 , wherein the host cell is an insect cell, a bacterial cell or a mammalian cell.

21 . A method of producing an antibody, the method comprising culturing the host cell of claim 20 under conditions suitable for gene expression.

22 . A pharmaceutical composition comprising the antibody of claim 1 , and a pharmaceutically acceptable excipient.

23 . An antibody that binds to tau comprising a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HC CDR1), an HC CDR2, and an HC CDR3, and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LC CDR1), an LC CDR2, and an LC CDR3, wherein:

(i) the HC CDR1 comprises the amino acid sequence of SEQ ID NO: 1144, the HC CDR2 comprises the amino acid sequence of SEQ ID NO: 1145, and the HC CDR3 comprises the amino acid sequence of SEQ ID NO: 410; and the LC CDR1 comprises the amino acid sequence of SEQ ID NO: 1146, the LC CDR2 comprises the amino acid sequence of SEQ ID NO: 529, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO: 571;

(ii) the HC CDR1 comprises the amino acid sequence of SEQ ID NO: 1165, the HC CDR2 comprises the amino acid sequence of SEQ ID NO: 1166, and the HC CDR3 comprises the amino acid sequence of SEQ ID NO: 1167; and the LC CDR1 comprises the amino acid sequence of SEQ ID NO: 473, the LC CDR2 comprises the amino acid sequence of RVS, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO: 571; or

(iii) the HC CDR1 comprises the amino acid sequence of SEQ ID NO: 314, the HC CDR2 comprises the amino acid sequence of SEQ ID NO: 341, and the HC CDR3 comprises the amino acid sequence of SEQ ID NO: 410; and the LC CDR1 comprises the amino acid sequence of SEQ ID NO: 1154, the LC CDR2 comprises the amino acid sequence of SEQ ID NO: 529, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO: 571.

24 . The antibody of claim 23 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 21, or an amino acid sequence at least 80% identical thereto; and the VL comprises the amino acid sequence of SEQ ID NO: 93, or an amino acid sequence at least 80% identical thereto.

25 . The antibody of claim 23 , which is a full length antibody, a bispecific antibody, an Fab, an F(ab′) 2 , an Fv, or a single chain Fv fragment (scFv).

26 . The antibody of claim 23 , which is a humanized antibody.

27 . The antibody of claim 23 , wherein the HC CDR1 comprises the amino acid sequence of SEQ ID NO: 1144, the HC CDR2 comprises the amino acid sequence of SEQ ID NO: 1145, and the HC CDR3 comprises the amino acid sequence of SEQ ID NO: 410; and the LC CDR1 comprises the amino acid sequence of SEQ ID NO: 1146, the LC CDR2 comprises the amino acid sequence of SEQ ID NO: 529, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO: 571.

28 . The antibody of claim 27 , comprising a human IgG4 heavy chain constant region and a human kappa light chain constant region.

29 . A vector comprising a nucleic acid encoding the antibody of claim 27 .

30 . A host cell comprising a nucleic acid encoding the antibody of claim 27 .

31 . The host cell of claim 30 , wherein the host cell is an insect cell, a bacterial cell or a mammalian cell.

32 . A method of producing an antibody, the method comprising culturing the host cell of claim 30 under conditions suitable for gene expression.

33 . A pharmaceutical composition comprising the antibody of claim 27 , and a pharmaceutically acceptable excipient.

34 . A nucleic acid encoding the antibody of claim 23 .

35 . A nucleic acid encoding an antibody that binds to tau comprising a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HC CDR1), an HC CDR2, and an HC CDR3, and a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LC CDR1), an LC CDR2, and an LC CDR3, wherein:

(i) the HC CDR1 comprises the amino acid sequence of X 1 X 2 WMH wherein X 1 is R or I; and X 2 is Y or F, the HC CDR2 comprises the amino acid sequence of SEQ ID NO: 1184, and the HC CDR3 comprises the amino acid sequence of SEQ ID NO: 410; and the LC CDR1 comprises the amino acid sequence of SEQ ID NO: 1185, the LC CDR2 comprises the amino acid sequence of SEQ ID NO: 1182, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO: 571;

(ii) the HC CDR1 comprises the amino acid sequence of SEQ ID NO: 1186, the HC CDR2 comprises the amino acid sequence of SEQ ID NO: 1187, and the HC CDR3 comprises the amino acid sequence of SEQ ID NO: 1167; and the LC CDR1 comprises the amino acid sequence of SEQ ID NO: 1188, the LC CDR2 comprises the amino acid sequence of RVS, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO: 571; or

(iii) the HC CDR1 comprises the amino acid sequence of SEQ ID NO: 1180, the HC CDR2 comprises the amino acid sequence of SEQ ID NO: 341, and the HC CDR3 comprises the amino acid sequence of SEQ ID NO: 410; and the LC CDR1 comprises the amino acid sequence of SEQ ID NO: 1181, the LC CDR2 comprises the amino acid sequence of SEQ ID NO: 1182, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO: 571.

36 . The nucleic acid of claim 35 , wherein:

(i) the nucleotide sequence encoding the VH comprises any one of SEQ ID NOs: 167, 168, or 169, or a nucleotide sequence at least 80% identical thereto; and/or the nucleotide sequence encoding the VL comprises any one of SEQ ID NOs: 241, 242, or 243, or a nucleotide sequence at least 80% identical thereto;

(ii) the nucleotide sequence encoding the VH comprises SEQ ID NO: 167, or a nucleotide sequence at least 80% identical thereto; and/or the nucleotide sequence encoding the VL comprises SEQ ID NO: 241, or a nucleotide sequence at least 80% identical thereto;

(iii) the nucleotide sequence encoding the VH comprises SEQ ID NO: 168, or a nucleotide sequence at least 80% identical thereto; and/or the nucleotide sequence encoding the VL comprises SEQ ID NO: 242, or a nucleotide sequence at least 80% identical thereto; or

(iv) the nucleotide sequence encoding the VH comprises SEQ ID NO: 169, or a nucleotide sequence at least 80% identical thereto; and/or the nucleotide sequence encoding the VL comprises SEQ ID NO: 243, or a nucleotide sequence at least 80% identical thereto.

37 . The nucleic acid of claim 35 , wherein the HC CDR1 comprises the amino acid sequence of SEQ ID NO: 1144, the HC CDR2 comprises the amino acid sequence of SEQ ID NO: 1145, and the HC CDR3 comprises the amino acid sequence of SEQ ID NO: 410; and the LC CDR1 comprises the amino acid sequence of SEQ ID NO: 1146, the LC CDR2 comprises the amino acid sequence of SEQ ID NO: 529, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO: 571.

38 . The nucleic acid of claim 37 , wherein the encoded VH comprises the amino acid sequence of SEQ ID NO: 21, or an amino acid sequence at least 80% identical thereto; and the encoded VL comprises the amino acid sequence of SEQ ID NO: 93, or an amino acid sequence at least 80% identical thereto.

39 . The nucleic acid of claim 35 , wherein the HC CDR1 comprises the amino acid sequence of SEQ ID NO: 1147, the HC CDR2 comprises the amino acid sequence of SEQ ID NO: 1148, and the HC CDR3 comprises the amino acid sequence of SEQ ID NO: 410; and the LC CDR1 comprises the amino acid sequence of SEQ ID NO: 474, the LC CDR2 comprises the amino acid sequence of SEQ ID NO: 529, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO 571.

40 . The nucleic acid of claim 35 , wherein the HC CDR1 comprises the amino acid sequence of SEQ ID NO: 1149, the HC CDR2 comprises the amino acid sequence of SEQ ID NO: 1150, and the HC CDR3 comprises the amino acid sequence of SEQ ID NO: 410; and the LC CDR1 comprises the amino acid sequence of SEQ ID NO: 475, the LC CDR2 comprises the amino acid sequence of SEQ ID NO: 530, and the LC CDR3 comprises the amino acid sequence of SEQ ID NO: 571.

41 . The nucleic acid of claim 35 , wherein:

(i) the encoded VH comprises the amino acid sequence of any one of SEQ ID NOs: 21, 22, or 23, or an amino acid sequence having at least 80% sequence identity thereto; and/or

(ii) the encoded VL comprises the amino acid sequence of any one of SEQ ID NOs: 93, 94, or 95, or an amino acid sequence at least 80% identical thereto.

42 . The nucleic acid of claim 35 , wherein the encoded VH comprises the amino acid sequence of SEQ ID NO: 22, or an amino acid sequence at least 80% identical thereto; and the encoded VL comprises the amino acid sequence of SEQ ID NO: 94, or an amino acid sequence at least 80% identical thereto.

43 . The nucleic acid of claim 35 , wherein the encoded VH comprises the amino acid sequence of SEQ ID NO: 23, or an amino acid sequence at least 80% identical thereto; and the encoded VL comprises the amino acid sequence of SEQ ID NO: 95, or an amino acid sequence at least 80% identical thereto.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 1, 2022
From: PARANJPE, MANEESHA ANAND
To: VOYAGER THERAPEUTICS, INC.
Reel/Frame 061935/0296 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 18, 2022
From: CARTER, TODD; HOU, JINZHAO; KURELLA, VINODHBABU; CAPILI, ALLAN D.; LIU, WENCHENG; CHUNG, HIU YAN; HOLTH, JERRAH; KAVANAGH, DILLON
To: VOYAGER THERAPEUTICS, INC.
Reel/Frame 061450/0772 →
Continuity (4)
Continuation PCTUS2021027346 · Apr 14, 2021
Provisional Application 63162976 · Mar 18, 2021
Provisional Application 63010261 · Apr 15, 2020
Related Publication 20230192830A1 · Jun 22, 2023
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