IP Library Granted Patent US 12,534,739
Granted Patent B2
US 12,534,739 · App. 17/284,074 · Granted Jan 27, 2026

AAV1 vectors and uses thereof for treatment of otic indications

Inventors: Joseph Burns (Newton, MA); Kathryn Ellis (Arlington, MA); Matthew Nguyen (Boston, MA); Adam Palermo (Somerville, MA); Gabriela Pregernig (Boston, MA); Fuxin Shi (Winchester, MA); Jonathon Whitton (Cambridge, MA)
Assignee: Decibel Therapeutics, Inc.
C12N15/86A61K9/0046A61K48/00C12N2750/14143C12N2750/14171
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Quick Facts
Patent No.
US 12,534,739
App. No.
17/284,074
Granted
Jan 27, 2026
Kind
B2
Abstract

The invention provides AAV1 vectors that can be used to transduce multiple inner ear cell types and their use for treatment of hearing loss, deafness, tinnitus, and vestibular dysfunction.

Claims (3)

1 . A method of expressing a polynucleotide that encodes Gap Junction Protein Beta 2 (Gjb2) operably linked to a promoter in developed inner ear cells in a human subject, the method comprising administering to the developed inner ear cells of the subject a serotype 1 adeno-associated virus (AAV1) vector harvested from a cell lysate, the AAV1 vector comprising the polynucleotide, wherein the administering is in an amount that transduces one or more inner ear cell types selected from the group consisting of Border cells, inner phalangeal cells, inner pillar cells, outer pillar cells, first row Deiters' cells, second row Deiters' cells, third row Deiters' cells, Hensen's cells, Claudius cells, interdental cells, basal cells of the stria vascularis, intermediate cells of the stria vascularis, marginal cells of the stria vascularis, and fibrocytes.

2 . The method of claim 1 , wherein the AAV1 vector is administered transtympanically, intratympanically, or injected to the posterior canal of the inner ear of the human subject and through the round window membrane of the human subject.

3 . The method of claim 1 , wherein the polynucleotide encodes Gjb2 operably linked to a GJB2 promoter and the polynucleotide is expressed in one or more of an inner pillar cell, an outer pillar cell, a marginal cell of the stria vascularis, a basal cell of the stria vascularis, an intermediate cell of the stria vascularis, a border cell, an inner phalangeal cell, a first row Deiters' cell, a second row Deiters' cell, a third row Deiters' cell, a Hensen's cell, a Claudius cell, an interdental cell, and a fibrocyte.

Assignments (7)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 4, 2022
From: PREGERNIG, GABRIELA
To: DECIBEL THERAPEUTICS, INC.
Reel/Frame 059169/0191 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 4, 2022
From: SHI, FUXIN
To: DECIBEL THERAPEUTICS, INC.
Reel/Frame 059169/0243 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 4, 2022
From: PALERMO, ADAM
To: DECIBEL THERAPEUTICS, INC.
Reel/Frame 059169/0404 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 4, 2022
From: WHITTON, JONATHON
To: DECIBEL THERAPEUTICS, INC.
Reel/Frame 059169/0512 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 4, 2022
From: NGUYEN, MATTHEW
To: DECIBEL THERAPEUTICS, INC.
Reel/Frame 059169/0546 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 4, 2022
From: BURNS, JOSEPH
To: DECIBEL THERAPEUTICS, INC.
Reel/Frame 059169/0757 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 4, 2022
From: ELLIS, KATHRYN
To: DECIBEL THERAPEUTICS, INC.
Reel/Frame 059170/0215 →
Continuity (3)
Provisional Application 62911885 · Oct 7, 2019
Provisional Application 62744604 · Oct 11, 2018
Related Publication 20210355504A1 · Nov 18, 2021
References Cited (53)
US 20100297084A1 · Bennett et al. · 2010 [cited by applicant]
US 20110171202A1 · Bance · 2011 [cited by applicant]
US 20130095071A1 · Bance et al. · 2013 [cited by applicant]
US 20140309288A1 · Brenner et al. · 2014 [cited by applicant]
US 20150209406A1 · Chen · 2015 [cited by applicant]
US 20170072015A1 · Schwartz et al. · 2017 [cited by applicant]
US 20170239332A1 · Burns et al. · 2017 [cited by applicant]
US 20170327557A1 · Chen · 2017 [cited by applicant]
US 20170340754A1 · Chen et al. · 2017 [cited by applicant]
US 20180055908A1 · Petit et al. · 2018 [cited by applicant]
US 20180080023A1 · Jackson et al. · 2018 [cited by applicant]
WO WO2006033689A2 · 2006 [cited by applicant]
WO WO2016073900A1 · 2016 [cited by applicant]
WO WO2016077687A1 · 2016 [cited by applicant]
WO WO2017072498A1 · 2017 [cited by applicant]
WO WO2017100791A1 · 2017 [cited by examiner]
WO WO2017136764A1 · 2017 [cited by applicant]
WO WO2017189753A1 · 2017 [cited by applicant]
WO WO2018039375A1 · 2018 [cited by applicant]
WO WO2018145111A1 · 2018 [cited by applicant]
WO WO2018170402A1 · 2018 [cited by applicant]
WO WO2019200016A1 · 2019 [cited by applicant]
Iizuka, Takashi, et al. “Perinatal Gjb2 gene transfer rescues hearing in a mouse model of hereditary deafness.” Human molecular genetics 24.13 (2015): 3651-3661. (Year: 2015). [cited by examiner]
Daya et al, Gene Therapy Using Adeno-Associated Virus Vectors, Clin. Microbiol. Rev. 21(4): 583-593, 2008 (Year: 2008). [cited by examiner]
Fumoto et al , Targeted Gene Delivery: Importance of Administration Routes, INTECH, Novel Gene Therapy Approaches, p. 3-31; editors Wei and Good, publisher Books on Demand, 2013 (Year: 2013). [cited by examiner]
Maguire et al, Viral vectors for gene delivery to the inner ear, Hearing Research 394: e107927, 13 pages, doi.org/10.1016/j.heares.2020.107927, 2020 (Year: 2020). [cited by examiner]
Iizuka, Takashi, et al. “Noninvasive in vivo delivery of transgene via adeno-associated virus into supporting cells of the neonatal mouse cochlea.” Human gene therapy 19.4 (2008): 384-390. (Year: 2008). [cited by examiner]
Liu, Qiang, et al. “The prevalence of neutralizing antibodies against AAV serotype 1 in healthy subjects in China: implications for gene therapy and vaccines using AAV1 vector.” Journal of medical virology 85.9 (2013): … [cited by examiner]
Akil et al., “Restoration of Hearing in the VGLUT3 Knockout Mouse Using Virally Mediated Gene Therapy,” Neuron. 75:283-293 (2012). [cited by applicant]
Bedrosian et al., “In Vivo Delivery of Recombinant Viruses to the Fetal Murine Cochlea: Transduction Characteristics and Long-Term Effects on Auditory Function,” Mol Ther. 14(3):328-335 (2006). [cited by applicant]
Chang et al., “Virally mediated Konq1 gene replacement therapy in the immature scala media restores hearing in a mouse model of human Jervell and Lange-Nielsen deafness syndrome,” EMBO Molecular Medicine. (2015) (10 pag… [cited by applicant]
Emptoz et al., “Local gene therapy durably restores vestibular function in a mouse model of Usher syndrome type 1G,” PNAS 114.(36):9695-9700 (2017). [cited by applicant]
International Search Report and Written Opinion for International Application No. PCT/US2019/055979, dated Jan. 16, 2020 (33 pages). [cited by applicant]
Kesser et al., “Gene Transfer in Human Vestibular Epithelia and the Prospects for Inner Ear Gene Therapy,” Laryngoscope. 118(5):821-831 (2008). [cited by applicant]
Kilpatrick et al., “Adeno-associated virus-mediated gene delivery into the scala media of the normal and deafened adult mouse ear,” Gene Ther. 18(6):569-578 (2011). [cited by applicant]
Landegger et al., “A synthetic AAV vector enables safe and efficient gene transfer to the mammalian inner ear,” Nat Biotechnol. 35(3) :280-284 (2017). [cited by applicant]
Li et al., “SLC26A4 Targeted to the Endolymphatic Sac Rescues Hearing and Balance in Slc26a4 Mutant Mice,” PLoS Genet. 9(7): e1003641 (2013) (18 pages). [cited by applicant]
Liu et al., “Promoter effects of adeno-associated viral vector for transgene expression in the cochlea in vivo,” Exp Mol Med. 39(2):170-175 (2007). [cited by applicant]
Liu et al., “Specific and Efficient Transduction of Cochlear Inner Hair Cells with Recombinant Adeno-associated Virus Type 3 Vector,” Mol Ther. 12(4):725-733 (2005). [cited by applicant]
Liu et al., “Protection Against Aminoglycoside-induced Ototoxicity by Regulated AAV Vector-mediated GDNF Gene Transfer Into the Cochlea,” Mol Ther. 16(3):474-480 (2008). [cited by applicant]
Luebke et al., “Adenoviral and AAV-Meditated Gene Transfer to the Inner Ear: Role of Serotype, Promoter, and Viral Load on In Vivo and In Vitro Infection Efficiencies,” Adv Ortorhinolaryngol. 66:87-98 (2009). [cited by applicant]
Shi et al., “Adeno-associated virus transformation into the normal miniature pig and the normal guinea pigs cochlea via scala tympani,” Acta Oto-Laryngologica. 137(9):910-916 (2017). [cited by applicant]
Shu et al., “Identification of Adeno-Associated Viral Vectors That Target Neonatal and Adult Mammalian Inner Ear Cell Subtypes,” Human Gene Therapy. 27(9):687-699 (2016). [cited by applicant]
Stone et al., “Adeno-associated Virus-Mediated Gene Transfer to Hair Cells and Support Cells of the Murine Cochlea,” Mol Ther. 11(6):843-848 (2005). [cited by applicant]
Askew et al., “Adeno-associated virus gene replacement for recessive inner ear dysfunction: Progress and challenges,” Hear Res. 394:107947 (2020) (13 pages). [cited by applicant]
Yu et al., “Virally expressed connexin26 restores gap junction function in the cochlea of conditional Gjb2 knockout mice,” Gene Ther. 21(1):71-80 (2014). [cited by applicant]
Zhang et al., “Cochlear Gene Therapy for Sensorineural Hearing Loss: Current Status and Major Remaining Hurdles for Translational Success,” Front Mol Neurosci. 11:221 (Jun. 2018) (15 pages). [cited by applicant]
Anthwal et al., “The development of the mammalian outer and middle ear,” J. Anat. 228(2):217-232 (Feb. 2016). [cited by applicant]
Hordeaux et al., “The Neurotropic Properties of AAV-PHP.B Are Limited to C57BL/6J Mice,” Mol. Therapy. 26(3):664-668 (Mar. 2018). [cited by applicant]
Lim et al., “Developmental Morphology of the Mouse Inner Ear: A scanning electron microscopic observation,” Acta Oto-Laryngologica. 99(sup422): 5-69 (1985). [cited by applicant]
Lalwani et al., “Long-term in vivo cochlear transgene expression mediated by recombinant adeno-associated virus,” Gene Ther. 5(2): 277-281 (1998). [cited by applicant]
Tucker et al., “Mapping the distribution of stem/progenitor cells across the mouse middle ear during homeostasis and inflammation,” Development. 145(1): dev154393 (Jan. 2018) (9 pages). [cited by applicant]
Walters et al., “Postnatal development, maturation and aging in the mouse cochlea and their effects on hair cell regeneration,” available in PMC Mar. 1, 2014, published in final edited form as: Hear Res. 297: 68-83 (Mar… [cited by applicant]