IP Library › Granted Patent US 12,703,874
Granted Patent B2
US 12,703,874 · App. 17/628,266 · Granted Aug 11, 2026

Methods of treating hearing loss using a secreted target protein

Inventors: Emmanuel J. Simons (Brookline, MA); Robert Ng (Newton, MA); Danielle R. Lenz (Brookline, MA); Hao Chiang (Somerville, MA)
Assignee: Akouos, Inc.
C12N15/86A61P27/16C07K14/475A61K38/00C07K2319/43C12N2750/14143C12N2830/42
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Quick Facts
Patent No.
US 12,703,874
App. No.
17/628,266
Filed
Jan 19, 2022
Granted
Aug 11, 2026
Kind
B2
Art Unit
1637
USPC
435/69.1
Abstract

Provided herein are compositions that include a single nucleic acid vector or two different nucleic acid vectors, and the use of these compositions to treat hearing loss in a subject.

Claims (58)

1 . A construct comprising:

(i) a cytomegalovirus (CMV) enhancer;

(ii) a chicken β-actin (CBA) promoter;

(iii) a chimeric intron comprising the nucleic acid sequence of SEQ ID NO: 19;

(iv) a coding sequence comprising a first nucleic acid sequence encoding a Norrin Cystine Knot Growth Factor (NDP) protein; and

(v) a polyadenylation sequence.

2 . The construct of claim 1 , wherein the first nucleic acid sequence encoding the NDP protein is an NDP gene.

3 . The construct of claim 1 , further comprising two adeno-associated virus (AAV) inverted terminal repeats (ITRs), wherein the two AAV ITRs flank the CMV enhancer and the polyadenylation sequence.

4 . An AAV particle comprising a construct, wherein the construct comprises:

(i) a cytomegalovirus (CMV) enhancer;

(ii) a chicken β-actin (CBA) promoter;

(iii) a chimeric intron comprising the nucleic acid sequence of SEQ ID NO 19;

(iv) a coding sequence comprising a first nucleic acid sequence encoding a Norrin Cystine Knot Growth Factor (NDP) protein; and

(v) a polyadenylation sequence.

5 . A composition comprising a construct and a pharmaceutically acceptable carrier, diluent or excipient, wherein the construct comprises:

(i) a cytomegalovirus (CMV) enhancer;

(ii) a chicken β-actin (CBA) promoter;

(iii) a chimeric intron comprising the nucleic acid sequence of SEQ ID NO 19;

(iv) a coding sequence comprising a first nucleic acid sequence encoding a Norrin Cystine Knot Growth Factor (NDP) protein; and

(v) a polyadenylation sequence.

6 . A composition comprising an AAV particle and a pharmaceutically acceptable carrier, diluent or excipient, wherein the AAV particle comprises a construct, wherein the construct comprises:

(i) a cytomegalovirus (CMV) enhancer;

(ii) a chicken β-actin (CBA) promoter;

(iii) a chimeric intron comprising the nucleic acid sequence of SEQ ID NO: 19;

(iv) a coding sequence comprising a first nucleic acid sequence encoding a Norrin Cystine Knot Growth Factor (NDP) protein; and

(v) a polyadenylation sequence.

7 . The construct of claim 1 , wherein the coding sequence further comprises a second nucleic acid sequence encoding a secretion signal protein.

8 . The construct of claim 7 , wherein the secretion signal protein comprises an NDP secretion signal protein.

9 . The construct of claim 7 , wherein the second nucleic acid sequence encoding the secretion signal protein is operably linked to the first nucleic acid sequence encoding the NDP protein.

10 . The construct of claim 1 , wherein the construct further comprises a 5′ untranslated region (UTR).

11 . The construct of claim 1 , wherein the construct further comprises a 3′ untranslated region (UTR).

12 . The construct of claim 1 , wherein the polyadenylation sequence is a bovine growth hormone polyadenylation (bGHpA) sequence.

13 . The construct of claim 1 , wherein the CMV enhancer comprises the nucleic acid sequence of SEQ ID NO: 17.

14 . The construct of claim 1 , wherein the CBA promoter comprises the nucleic acid sequence of SEQ ID NO: 18.

15 . The construct of claim 10 , wherein the 5′ UTR comprises the nucleic acid sequence of SEQ ID NO: 14.

16 . The construct of claim 8 , wherein the NDP secretion signal protein comprises the amino acid sequence of SEQ ID NO: 5.

17 . The construct of claim 8 , wherein the NDP secretion signal protein is encoded by the nucleic acid sequence of SEQ ID NO: 6.

18 . The construct of claim 1 , wherein the NDP protein comprises the amino acid sequence of SEQ ID NO: 56.

19 . The construct of claim 11 , wherein the 3′ UTR sequence comprises the nucleic acid sequence of SEQ ID NO: 15.

20 . The construct of claim 12 , wherein the bGHpA sequence comprises the nucleic acid sequence of SEQ ID NO: 23.

21 . The AAV particle of claim 4 , further comprising a capsid, wherein the capsid is or is derived from an AAV2 capsid.

22 . The AAV particle of claim 4 , further comprising a capsid, wherein the capsid is or is derived from an Anc80 capsid.

23 . A kit comprising a composition, wherein the composition comprises (a) a construct or (b) an AAV particle comprising the construct, wherein the construct comprises:

(i) a cytomegalovirus (CMV) enhancer;

(ii) a chicken β-actin (CBA) promoter;

(iii) a chimeric intron comprising the nucleic acid sequence of SEQ ID NO: 19;

(iv) a coding sequence comprising a first nucleic acid sequence encoding a Norrin Cystine Knot Growth Factor (NDP) protein; and

(v) a polyadenylation sequence.

24 . The composition of claim 6 , wherein the composition is a pharmaceutical composition.

25 . The kit of claim 23 , wherein the kit further comprises instructions for performing a method.

26 . The kit of claim 25 , wherein the method is a method of introducing the composition into the inner ear of a subject.

27 . The kit of claim 25 , wherein the method is a method of introducing the composition into the cochlea of a subject.

28 . The kit of claim 25 , wherein the method is a method of introducing the composition into a mammalian cell of a subject.

29 . The kit of claim 28 , wherein the mammalian cell is a cochlear inner hair cell or a cochlear outer hair cell.

30 . The kit of claim 25 , wherein the method is a method of treatment.

31 . The kit of claim 25 , wherein the method is a method of treating deafness or hearing loss.

32 . The kit of claim 23 , wherein the kit further comprises a pre-loaded syringe or a vial, wherein the pre-loaded syringe or the vial comprises the composition, wherein the composition is formulated as an aqueous composition, a solid composition, or a lyophilized composition.

33 . The composition of claim 24 , further comprising a pharmaceutically acceptable carrier.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 15, 2022
From: SIMONS, EMMANUEL J.; NG, ROBERT; LENZ, DANIELLE; CHIANG, HAO
To: AKOUOS, INC.
Reel/Frame 059607/0768 →
Continuity (2)
Provisional Application 62879396 · Jul 26, 2019
Related Publication 20220396806A1 · Dec 15, 2022
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