US 12,264,317 B2
Compositions and methods for treating non-age-associated hearing impairment in a human subject
Emmanuel John Simons, Brookline, MA (US); Ellen Reisinger, Dußlingen (DE); Sebastian Kügler, Göttingen (DE); and Hanan Al-Moyed, Göttingen (DE)
Assigned to Akouos, Inc., Boston, MA (US)
Filed by Akouos, Inc., Boston, MA (US)
Filed on Jul. 18, 2024, as Appl. No. 18/777,187.
Application 18/777,187 is a continuation of application No. 18/458,752, filed on Aug. 30, 2023, granted, now 12,071,627.
Application 18/458,752 is a continuation of application No. 17/929,647, filed on Sep. 2, 2022, granted, now 11,781,145, issued on Oct. 10, 2023.
Application 17/929,647 is a continuation of application No. 17/378,606, filed on Jul. 16, 2021, granted, now 11,525,139, issued on Dec. 13, 2022.
Application 17/378,606 is a continuation of application No. 16/327,396, abandoned, previously published as PCT/US2017/048257, filed on Aug. 23, 2017.
Claims priority of provisional application 62/494,866, filed on Aug. 23, 2016.
Prior Publication US 2024/0384276 A1, Nov. 21, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 15/52 (2006.01); A01K 67/0276 (2024.01); A61K 38/17 (2006.01); A61K 48/00 (2006.01); A61P 27/16 (2006.01); C07K 14/47 (2006.01); C12N 5/0793 (2010.01); C12N 9/16 (2006.01); C12N 15/65 (2006.01); C12N 15/86 (2006.01); C12N 15/90 (2006.01)
CPC C12N 15/52 (2013.01) [A01K 67/0276 (2013.01); A61K 38/1709 (2013.01); A61K 48/0075 (2013.01); A61P 27/16 (2018.01); C07K 14/47 (2013.01); C12N 5/062 (2013.01); C12N 9/16 (2013.01); C12N 15/65 (2013.01); C12N 15/86 (2013.01); C12N 15/902 (2013.01); A01K 2217/075 (2013.01); A01K 2227/103 (2013.01); A01K 2267/03 (2013.01); C12N 2310/20 (2017.05); C12N 2750/14143 (2013.01); C12N 2830/008 (2013.01); C12Y 301/03001 (2013.01)] 30 Claims
 
1. A method of treating otoferlin related hearing loss in a subject, comprising administering to the subject a plurality of AAV vectors comprising:
a) a first AAV vector comprising a 5′ inverted terminal repeat (ITR), a 3′ ITR, a F1 phage recombinogenic region, and a promoter operably linked to a portion of a gene encoding an otoferlin polypeptide; and
b) a second AAV vector comprising a 5′ ITR, a 3′ ITR, a F1 phage recombinogenic region, and a portion of the gene encoding an otoferlin polypeptide;
wherein the first AAV vector and the second AAV vector are capable of constituting a full-length otoferlin messenger RNA in the subject;
wherein the first and second AAV vectors each include a total number of nucleotides of up to about 5kb; and
wherein the otoferlin related hearing loss is associated with reduced expression, lack of expression, or dysfunction of otoferlin.
 
19. A method of treating otoferlin related hearing loss in a subject, comprising administering to the subject a plurality of AAV vectors comprising:
a) a first AAV vector comprising (i) a promoter, (ii) a portion of a gene encoding an otoferlin polypeptide, (iii) a splicing donor signal sequence, (iv) a 77 base pair F1 phage recombinogenic region, and (v) 5′ and 3′ ITRs; and
b) a second AAV vector comprising (i) a 77 base pair F1 phage recombinogenic region, (ii) a splicing acceptor signal sequence, (iii) a portion of the gene encoding an otoferlin polypeptide, (iv) a polyadenylation signal, and (v) 5′ and 3′ ITRs;
wherein the first AAV vector and the second AAV vector are capable of constituting a full-length otoferlin messenger RNA in the subject;
wherein the first and second AAV vectors each include a total number of nucleotides of up to about 5 kb; and
wherein the otoferlin related hearing loss is associated with reduced expression, lack of expression, or dysfunction of otoferlin.