Compositions and methods for preventing the proliferation and epithelial-mesenchymal transition of epithelial cells
Inventors
Tseng, Scheffer • Tan, Ek Kia • He, Hua
Assignees
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Publication Number
US-11318169-B2
Publication Date
2022-05-03
Expiration Date
Abstract
Compositions and preparations of fetal support tissue that prevent or reduce the proliferation and epithelial-mesenchymal transition (EMT) of epithelial cells, wherein the epithelial cells may be human epithelial cells and the human epithelial cells may be conjunctival, retinal, corneal, limbal, or renal epithelial cells. Methods of preventing or reducing the proliferation, cell migration, and EMT of epithelial cells in an individual in need thereof, wherein the epithelial cells may be human epithelial cells and the human epithelial cells may be conjunctival, retinal, corneal, limbal, or renal epithelial cells. Methods of preventing or treating proliferative vitreoretinopathy in an individual in need thereof.
Core Innovation
The invention relates to fetal support tissue preparations formulated with a pharmaceutically acceptable diluent, excipient, vehicle, or carrier for preventing or reducing proliferation, cell migration, and epithelial-mesenchymal transition (EMT) of epithelial cells. The fetal support tissue preparation comprises a heavy chain–hyaluronic acid/pentraxin 3 complex (HC-HA/PTX3), and the composition is administered as a therapeutically effective amount to an individual who has experienced retinal detachment.
The core composition component is HC-HA/PTX3, including a complex formed from heavy chain–hyaluronic acid and pentraxin 3. The heavy chain is described as an inter-α-trypsin inhibitor heavy chain associated with pentraxin 3 and formed through association processes involving TSG-6. The described characterization of amniotic membrane extracts includes HA/proteins and the presence of IαI heavy chains, TSG-6, PTX3, TSP-1, and Smad7.
The documented scope includes preventing or reducing epithelial proliferation, migration, and EMT in contexts including proliferative vitreoretinopathy (PVR) and other EMT-associated diseases mentioned as having canonical Wnt and TGF-β/Smad signaling involvement. The described mechanism includes suppression of canonical Wnt and TGF-β/Smad signaling, described as growth-factor/cytokine antagonism, and effects on Smad2/3 nuclear translocation. The disclosed compositions are described as injectable and local ocular compositions with formats including gel, solution, and suspension.
Claims Coverage
The partial claim set provided includes one independent claim. It contains three principal inventive elements: preventing or reducing proliferation, cell migration, and epithelial-mesenchymal transition (EMT), together with administering a therapeutically effective amount of a composition containing a fetal support tissue preparation with HC-HA/PTX3 and a pharmaceutically acceptable diluent, excipient, vehicle, or carrier.
Preventing or reducing epithelial processes after retinal detachment
A method for preventing or reducing proliferation, cell migration, or epithelial-mesenchymal transition (EMT) of epithelial cells in an individual who has experienced retinal detachment by administering a therapeutically effective amount of a composition.
Fetal support tissue preparation comprising HC-HA/PTX3
The composition comprises a preparation of fetal support tissue wherein the preparation comprises heavy chain-hyaluronic acid/pentraxin 3 complex (HC-HA/PTX3).
Pharmaceutically acceptable diluent, excipient, vehicle, or carrier
The composition further comprises a pharmaceutically acceptable diluent, excipient, vehicle, or carrier, thereby preventing or reducing the proliferation, cell migration, or EMT of epithelial cells.
Across the provided independent claim, the inventive coverage centers on administering a therapeutically effective amount to an individual after retinal detachment, using a composition that includes a fetal support tissue preparation containing HC-HA/PTX3 together with a pharmaceutically acceptable diluent, excipient, vehicle, or carrier to prevent or reduce epithelial cell proliferation, cell migration, or EMT.
Stated Advantages
Prevents or reduces proliferation of epithelial cells.
Prevents or reduces cell migration of epithelial cells.
Prevents or reduces epithelial-mesenchymal transition (EMT) of epithelial cells.
Documented Applications
Proliferative vitreoretinopathy (PVR) and EMT-associated diseases are described in the document as relevant contexts for preventing or reducing epithelial proliferation, migration, and EMT.
Other disease or disorder examples explicitly mentioned include proliferative diabetic retinopathy, fibrotic lesions, and retro-corneal membrane.
Ocular local administration is described for multiple ocular injection routes including intraocular, subretinal, intravitreal, periocular, subconjunctival, retrobulbar, intracameral, and sub-Tenon’s injections.
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