Treatment of vocal cords with autologous dermal fibroblast formulation
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Publication Number
US-10098914-B2
Publication Date
2018-10-16
Expiration Date
Abstract
Dosage units consist of an autologous cell therapy product composed of fibroblasts grown for each individual to be treated for augmentation or regeneration of vocal cords. The suspension of autologous fibroblasts, grown from a biopsy of each individual's own buccal mucsoa or skin using current good manufacturing practices (CGMP) and standard tissue culture procedures, is supplied in vials containing cryopreserved fibroblasts or precursors thereof, having a purity of at least 98% fibroblasts and a viability of at least 85%, for administration of from one to six mL, preferably two mL administered three times approximately three to six weeks apart, of cells at a concentration of from 1.0-2.0×107 cells/mL.
Core Innovation
The invention relates to autologous cultured dermal fibroblast and/or autologous buccal mucosa fibroblast cell therapy for injection into bilateral vocal fold scarring in a human in need thereof. The method provides a dosage formulation for injecting into the vocal cord or fold, with a defined injection volume and a defined concentration range of autologous human fibroblast cells or precursors thereof. The formulation is characterized by a viability threshold after freezing and thawing, and is supplied as cryopreserved fibroblasts or precursors.
The therapy is based on generating an autologous fibroblast cell product from patient biopsy, including expanding the cells under CGMP, cryopreserving the expanded fibroblasts, and supplying the product with specified purity and viability release parameters. The supplied product includes quality attributes such as at least 85% viable cells after freezing and thawing and a specified purity of fibroblasts. The dosage formulation is characterized by a cell concentration range for injection into the vocal fold.
Administration is described as injection into the vocal cord or fold in a manner that targets the superficial lamina propria or subepithelial cover layer. The dosing described includes multiple treatments spaced over weeks, and delivery is performed under endoscopic visualization with trans-cricothyroid membrane injection. A Phase I clinical trial in the described setting reports safety outcomes and trends toward sustained improvement in mucosal wave grade through 12 months, along with supportive changes in voice questionnaires.
Claims Coverage
The independent claim set centers on treatment of bilateral vocal fold scarring in a human in need thereof by injecting a cryopreserved autologous human fibroblast cell dosage formulation into the vocal cord or fold, with defined injection volume, defined cell concentration, and a viability threshold after freezing and thawing. Four additional inventive features refine the administration, anatomical placement, and procedural context.
Injecting autologous fibroblast dosage into bilateral vocal fold scarring
A method for treatment of bilateral vocal fold scarring in a human in need thereof comprising injecting into the vocal cord or fold from about one mL to six mL of a dosage formulation comprising between 1.0×10^7 cells/mL and 2.7×10^7 cells/mL autologous human fibroblast cells or precursors thereof, at least 85% of which are viable after freezing and thawing.
Injecting within a narrower 1 mL to 2 mL volume range
The method further comprises administering between 1 mL and 2 mL of the dosage formulation.
Layering the cells in the vocal fold subepithelial layer
The method further comprises layering the cells in the vocal fold subepithelial layer.
Providing local anesthetic to the nasal cavity or larynx
The method further comprises providing local anesthetic to the nasal cavity or larynx.
Visualizing the injection site using a fiberoptic laryngoscope and video monitor
The method further comprises visualizing the site of injection using a fiberoptic laryngoscope connected to a video monitor.
Administering one to four doses targeting the superficial lamina propria layer
The method further comprises injecting one, two, three or four treatment doses of 1-2×10^7 cells/mL into the superficial lamina propria layer of each scarred vocal fold.
Overall, the claims focus on bilateral vocal fold scarring treatment by injecting an autologous human fibroblast cell dosage formulation with defined volume and concentration, a freezing-and-thawing viability threshold, and dependent refinements for dose range, placement in the subepithelial or superficial lamina propria layer, visualization, local anesthetic, and multiple-dose administration.
Stated Advantages
Sustained improvement in mucosal wave grade through 12 months in the described Phase I trial.
Safety outcomes in the described Phase I trial, including temporary otalgia in full-thickness scar cases and no serious adverse events or mortality.
Supportive improvements in Voice Handicap Index (VHI) and VAS voice questionnaires through follow-up.
Documented Applications
Treatment of bilateral vocal fold scarring in a human in need thereof by injection of autologous human fibroblast cells or precursors into the vocal cord or fold.
Vocal fold scarring augmentation or regeneration context evaluated in a Phase I clinical trial with videostroboscopy mucosal wave grade assessment through 12 months.
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