Composition 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-10342831-B2
Publication Date
2019-07-09
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 derived injectable compositions and non-solid formulations for treating Proliferative Vitreoretinopathy (PVR) or preventing PVR after retinal detachment. The compositions prevent or reduce epithelial cell proliferation, epithelial cell migration, and epithelial-mesenchymal transition (EMT). The formulation uses high-molecular-weight hyaluronan cross-linked to inter-α-trypsin inhibitor heavy chain (HC-HA) and associated pentraxin 3 (HC-HA/PTX3).
The compositions include substantially isolated HC-HA/PTX3, reconstituted HC-HA/PTX3, and combinations thereof, including extract-derived preparations. The document links the effect to suppression of canonical Wnt signaling (β-catenin/TCF-LEF) and suppression of TGF-β/Smad signaling pathways. Components discussed in the characterization include HA, IαI heavy chains, PTX-3, and associated proteins including TSG-6 and TSP-1, as well as Smad7.
The document further addresses target epithelial cell types and includes embodiments involving retinal pigment epithelial (RPE) cells and other epithelial targets described as epithelial cells. The stated biological outcome is reduction of epithelial processes relevant to PVR, including proliferation, migration, and EMT, and the document reports findings in a rabbit PVR model using HC-HA/PTX3. The report also discusses characterization and cellular-level observations consistent with the anti-proliferative and anti-migratory effects described.
Claims Coverage
The partial content identifies two independent claims. Across both independent claims, a therapeutically effective injectable composition centered on substantially isolated and/or reconstituted HC-HA/PTX3 is used to treat PVR or prevent PVR after retinal detachment, with one independent claim limited to HC-HA/PTX3 plus a pharmaceutically acceptable diluent, excipient, vehicle, or carrier and the other allowing an additional therapeutic agent.
Injectable HC-HA/PTX3-based composition for PVR treatment or prevention
Administering to an individual having PVR or who has experienced retinal detachment a therapeutically effective amount of an injectable composition consisting essentially of substantially isolated heavy chain-hyaluronic acid/pentraxin 3 complex (HC-HA/PTX3) and/or reconstituted HC-HA/PTX3, together with a pharmaceutically acceptable diluent, excipient, vehicle, or carrier, thereby treating PVR or preventing PVR.
HC-HA/PTX3-based injectable composition with an additional therapeutic agent
Administering to an individual having PVR or who has experienced retinal detachment a therapeutically effective amount of an injectable composition consisting essentially of substantially isolated HC-HA/PTX3 and/or reconstituted HC-HA/PTX3, an additional therapeutic agent, and a pharmaceutically acceptable diluent, excipient, vehicle, or carrier, thereby treating or preventing PVR.
Overall claim coverage centers on administering therapeutically effective amounts of an injectable HC-HA/PTX3 composition to treat PVR or prevent PVR after retinal detachment, with one independent claim limiting the composition to HC-HA/PTX3 plus a pharmaceutically acceptable diluent, excipient, vehicle, or carrier and the other permitting inclusion of an additional therapeutic agent.
Stated Advantages
Treats Proliferative Vitreoretinopathy (PVR) in an individual having PVR.
Prevents PVR in an individual who has experienced retinal detachment.
Prevents or reduces epithelial cell proliferation, cell migration, and epithelial-mesenchymal transition (EMT) associated with PVR.
Documented Applications
Treatment of Proliferative Vitreoretinopathy (PVR) in an individual having PVR.
Prevention of PVR in an individual who has experienced retinal detachment.
Use in contexts targeting epithelial cell proliferation, epithelial cell migration, and epithelial-mesenchymal transition (EMT), including embodiments involving retinal pigment epithelial (RPE) cells.
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