Massachusetts Eye and Ear Infirmary

The Charles Stark Draper Laboratory, Inc.

Akouos, Inc.

Harvard College

University of Southern California

Massachusetts Institute of Technology

Michael J McKenna

William Sewell

Ernest Soonho Kim

Jason Oliver Fiering

Albert Edge

Mark Joseph Mescher

Emmanuel John Simons

Robert Ng

Sharon G Kujawa

Jeffrey T Borenstein

Erin Pararas

Jennifer Ann Lewis

Boris A Kashemirov

David B Kolesky

Konstantina Stankovic

Mark Andrew Skylar-Scott

Shuting Sun

Judith Kempfle

John Rosowski

Aaron K Remenschneider

Daniel J Lee

Woo Seok Kang

Kim Nguyen

Nicole Black

David Jung

Ruwan Kiringoda

Alexander D Valentine

Shyan-Yuan Kao

Robert Samuel Langer

Marc Steven Weinberg

Charles E McKenna

Vishal Tandon

Marcello Peppi

Elliott Kozin

Mark E Keegan

Elliot Kozin

Charles E Mckenna

Andrew Ayoob

Anthony A Mikulec

William F Sewell

Erin E Pararas

This invention relates to drug conjugates useful for localized treatment of diseases or disorders of the middle ear and/or inner ear. Methods of treating diseases or disorders of the middle ear and/or inner ear, pharmaceutical compositions comprising the conjugates, and methods of inhibiting a Tropomyosin receptor kinase are also provided.

Phosphonate-drug conjugates

The present disclosure provides a construct comprising a coding sequence operably linked to a promoter, wherein the coding sequence encodes a vascular endothelial growth factor (VEGF) binding agent or a portion thereof. In some embodiments, a construct is an AAV construct. In some embodiments, an AAV construct is a part of an AAV particle. Compositions comprising constructs and AAV particles described herein can be useful in treating hearing loss, for example, hearing loss associated with vestibular schwannoma.

Anti-VEGF antibody constructs

Provided herein are methods that include introducing into an inner ear of a mammal a therapeutically effective amount of an adeno-associated virus (AAV) vector that includes a nucleotide sequence encoding (a) a polypeptide including an antibody heavy chain variable domain operably linked to a signal peptide and a polypeptide including an antibody light chain variable domain operably linked to a signal peptide; (b) a polypeptide including an antigen-binding antibody fragment operably linked to a signal peptide; or (c) a soluble vascular endothelial growth factor receptor operably linked to a signal peptide.

AAV-mediated delivery of therapeutic antibodies to the inner ear

AAV-mediated delivery of antibodies to the inner ear

This disclosure features artificial tympanic membrane graft devices and two-component bilayer graft devices that include a scaffold having a plurality of ribs made of a first material and a plurality of spaces between the ribs filled or made with the first material, a different, second material, a combination of the first and a second materials, or a combination of a second material and one or more other different materials. The bilayer graft devices have two components or layers. One component, e.g., the underlay graft device, can include a projection, and the second component, e.g., the overlay graft device, can include an opening that corresponds to the projection (or vice versa) so that the opening and the projection can secure the two layers together in a 'lock and key' manner. This disclosure also features methods of making, using, and implanting the three-dimensional artificial tympanic membrane and bilayer graft devices.

Artificial tympanic membrane devices and uses

The present disclosure discussed a handpiece for trans-canal delivery of a therapeutic substance to the inner ear. The handpiece can be inserted into the middle ear via a surgical tympanotomy approach. The handpiece can enable a controlled injection of a therapeutic substance directly through the round window membrane and into the inner ear. The direct delivery of the therapeutic substance to the inner ear can enable the delivery of a precise amount of therapeutic substance into the inner ear. Because the therapeutic substance is delivery directly to the inner ear the delivery of the therapeutic substance is not subject to limitations on molecule size and inconsistent diffusion rates that are present when therapeutic substances are diffused across the round window membrane.

System for inner ear drug delivery via trans-round window membrane injection

The present disclosure provides compositions and methods for treating an auditory disease in a subject in need thereof comprising administering an effective amount of a gel-based precursor that includes an inner ear-specific therapeutic compound directly into the cochlea of the subject.

Method and process for quantitative evaluation of pharmacokinetics, therapeutic effects and safety of delivery of drug compounds to the inner ear for treatment of auditory disease

An implantable drug delivery apparatus for delivering a drug into a bodily fluid in a bodily cavity of a patient over a period of time includes a drug supply reservoir to supply drug into a delivery channel and an actuator for delivering the drug to a predetermined location in the bodily cavity of the patient, such as, for example, a cochlea of a human ear. The drug is loaded into the delivery channel while producing substantially negligible flow at an outlet of the delivery channel.

Drug delivery apparatus

Methods for treating neurodegeneration, e.g., sensorineural hearing loss, or a demyelinating disease, using bisphosphonates, ERK kinase inhibitors, and osteoprotegerin (OPG) proteins or nucleic acids.

Osteoprotegerin in neuroprotection

A medical implant device includes a prosthesis adapted to replace at least a portion of a bone. The prosthesis includes a drug-eluting polymer adapted to deliver a drug to at least a portion of an area surrounding the prosthesis.

Drug-eluting stapes prosthesis

An implantable drug delivery apparatus for delivering a drug into a bodily fluid in a body cavity of a patient over a period of time includes a variable-volume vessel defining a working chamber for receiving a drug and recirculating a therapeutic fluid. The fluid can contain a bodily fluid, such as, for example, perilymph, and a drug. The device allows for the controlled delivery of the therapeutic fluid to a predetermined location in the bodily cavity of the patient, such as, for example, a cochlea of a human ear.

Growing community of inventors

Southborough, MA, United States of America

Michael J McKenna