Turning the Inner Ear Into Its Own Drug Factory Gene Therapy for the Tumours That Steal Hearing

This application covers a method of treating inner ear disease by injecting a viral vector into the ear that instructs the cells there to manufacture an antibody themselves, rather than delivering the antibody as a drug. The named target is VEGF, the growth factor that feeds the blood supply of vestibular schwannoma, and the applicant is Akouos, the Boston gene therapy company acquired by Eli Lilly in 2022.

The Problem

Sensorineural hearing loss is hearing loss caused by malfunction of the cells of the inner ear, most often the hair cells, and the specification lists the usual causes: loud noise, head trauma, viral infection, autoimmune inner ear disease, inherited hearing loss, ageing, malformations, Meniere’s disease, otosclerosis and tumours.

The tumour case is the one this application is aimed at. A vestibular schwannoma, also called an acoustic neuroma, is a benign, slow growing tumour arising from the Schwann cells that sheathe the vestibulocochlear nerve. It is usually not life threatening, but as it grows it damages hearing and balance, and in neurofibromatosis type 2 these tumours appear on both sides, so patients face the prospect of losing hearing in both ears. The available options are watchful waiting, radiation and surgery, all of which carry their own risk to what hearing remains.

Anti VEGF antibodies work in this setting. Bevacizumab given systemically has been shown to shrink some of these tumours and stabilise hearing. But it has to be infused repeatedly and indefinitely, and blocking VEGF throughout the body brings the familiar systemic problems of that drug class, including hypertension, impaired wound healing and bleeding risk. Treating a benign tumour in one ear with a body wide drug for years is a poor exchange.

The inner ear compounds the difficulty. It is a small, fluid filled, largely enclosed compartment that ordinary systemic drugs reach poorly, which is why so little of an infused dose ends up where it is needed. The same enclosure, though, is what makes it an unusually good target for local treatment.

What This Invention Does

The method introduces into the inner ear a therapeutically effective amount of an adeno associated virus vector carrying a nucleotide sequence that encodes the therapeutic protein. The cells of the inner ear take up the vector and begin producing the protein continuously and locally, so the ear becomes the site of manufacture rather than the destination of a delivery.

Three payload options are claimed. The vector can encode a full antibody, expressed as a heavy chain variable domain polypeptide and a light chain variable domain polypeptide, each operably linked to a signal peptide so the cell secretes them. It can encode a single antigen binding antibody fragment, again with a signal peptide. Or it can encode a soluble VEGF receptor, a decoy that mops up circulating VEGF rather than binding it with an antibody. In each case the specification’s worked target is VEGF, and the stated effect is a reduction in VEGF activity within the ear.

The construct is described in familiar vector engineering terms. The coding sequence can be paired with a promoter, which may be inducible, constitutive or tissue specific, a Kozak sequence to set the translation start, and a polyadenylation signal. These are the control elements that determine how much protein is made, in which cells and for how long.

One embodiment is worth noting because it runs against the usual instinct in antibody engineering. The specification describes an antibody whose Fc region carries amino acid substitutions that decrease its half life relative to a control antibody, or a fragment engineered for shorter in vivo persistence. Most therapeutic antibodies are modified to last longer. Here, if the protein is being produced continuously inside the ear, a short half life is an advantage: it keeps the antibody concentrated where it is made and limits how much escapes into general circulation, preserving the local versus systemic distinction the whole approach depends on.

The claimed uses span increasing antibody levels in the inner ear, reducing VEGF activity in the inner ear, treating inner ear disorders generally, and specifically treating acoustic neuroma, vestibular schwannoma and neurofibromatosis type 2.

Key Features

• AAV delivered antibody genes. The vector carries the coding sequence for an antibody rather than the antibody itself, so the target tissue produces the therapeutic protein on site.
• Three payload formats. Claims cover a full antibody as separate heavy and light chain constructs, a single antigen binding fragment, and a soluble VEGF receptor decoy.
• Signal peptide secretion. Each coding sequence is operably linked to a signal peptide so the transduced cells export the protein into the inner ear fluid instead of retaining it.
• Local rather than systemic exposure. Administration directly into the inner ear confines VEGF blockade to the compartment where the tumour sits, avoiding the systemic effects of infused anti VEGF therapy.
• Deliberately shortened antibody half life. Fc substitutions that reduce persistence are claimed as an embodiment, keeping the antibody local rather than prolonging its circulation.
• Standard vector control elements. Promoter choice across inducible, constitutive and tissue specific options, plus a Kozak sequence and a polyadenylation signal, set the level and location of expression.

Who Is Behind It

Akouos, Inc. was founded in Boston in 2016 to apply adeno associated virus gene therapy to the inner ear, drawing on neurotology, genetics and inner ear drug delivery. It listed on Nasdaq in 2020 and was acquired by Eli Lilly and Company in a transaction announced in October 2022 and completed on 1 December 2022, valued at roughly USD 487 million upfront with contingent value rights taking the total to about USD 610 million. Akouos now operates as a wholly owned subsidiary of Lilly.

The named inventors are the company’s founding scientific and clinical leadership. Emmanuel J. Simons is the co founder, president and chief executive of Akouos. Michael McKenna is the co founder and chief medical officer, an otologist whose clinical career was built at Massachusetts Eye and Ear and Harvard Medical School. Robert Ng is the third named inventor.

The application is a divisional of Australian application 2018392480, and the earliest priority is United States provisional application 62/607,665 filed on 19 December 2017. The programme corresponding to this work is AK antiVEGF, which entered a Phase 1/2 trial in people with unilateral vestibular schwannoma, sponsored by Akouos under Lilly ownership.

Why It Matters

Vestibular schwannoma is not a large market by oncology standards, but it is one where the current options are unattractive enough that a genuinely local treatment would be adopted quickly. Radiation and surgery both risk the hearing they are meant to save, and indefinite systemic bevacizumab is a heavy commitment for a benign tumour. For neurofibromatosis type 2, where bilateral tumours make total deafness a realistic outcome, the case is stronger still.

The technical trend this sits in is the shift from delivering proteins to delivering the instructions for them, and specifically to doing so in anatomically confined compartments. The eye proved the model: the same logic of a small, enclosed, immune privileged space that can be dosed directly has driven most of the successful gene therapy work to date. The inner ear is the obvious next candidate, and Akouos was built around that observation. The half life reducing Fc substitution is a neat illustration of how the design rules invert once the protein is made in place rather than injected.

The filing strategy reflects the acquisition. A 2017 priority carried through to a 2026 Australian divisional is a family being maintained well past the point where the originating company still exists independently, which is what happens when a large pharmaceutical acquirer inherits a portfolio and keeps every jurisdiction alive while a clinical programme is still running. Australia has a solid otology and cochlear implant research base and is a routine trial jurisdiction, so it is not a token filing.

Related Concepts

• Adeno-associated virus – the vector used to carry the antibody genes into inner ear cells.
• Vestibular schwannoma – the tumour this method is aimed at.
• Vascular endothelial growth factor – the signalling protein the expressed antibody blocks.
• Neurofibromatosis type II – the genetic condition that produces schwannomas on both sides.
• Bevacizumab – the systemic anti VEGF antibody this approach is designed to replace locally.
• Sensorineural hearing loss – the broader category of hearing loss the specification addresses.

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AU 2026202084 was published in the Australian Official Journal of Patents on 9 April 2026 and is open for public inspection. Patent applications represent inventions that are sought to be protected and do not necessarily reflect commercially available products.