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Compositions and methods for restoring or preventing loss of vision caused by disease or traumatic injury

A technology for diseases and retinal damage, applied in drug combinations, sensory diseases, organic active ingredients, etc., can solve problems such as task complexity

Pending Publication Date: 2020-08-07
LINEAGE CELL THERAPEUTICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Synaptic remodeling of neural circuits during late RD further complicates this task

Method used

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  • Compositions and methods for restoring or preventing loss of vision caused by disease or traumatic injury
  • Compositions and methods for restoring or preventing loss of vision caused by disease or traumatic injury
  • Compositions and methods for restoring or preventing loss of vision caused by disease or traumatic injury

Examples

Experimental program
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Effect test

Embodiment 1

[0227] Restoration and improvement in visual perception was demonstrated in rabbits with ocular impact exposure and retinal damage. Subretinal grafts containing only hESC-3D retinal tissue (no biomaterials / scaffolds) were used to treat damaged retinal tissue in rabbits. Following sacrifice, optical coherence tomography (OCT) and histology and immunohistochemistry in live animals were used to demonstrate structural recovery of tissue and vision. Functional recovery was demonstrated in live animals using visual evoked potentials (VEP).

[0228] Human retinal tissue was generated using clinical grade hPSCs (BIOTIME, INC.). Pilot transplantation experiments were performed in rabbits to determine the subretinal transplantation process in a large eye animal model. An ocular impact injury model was generated in rabbits using a shock tube. Multiple pieces of hESC-3D retinal tissue (between about 0.1 and about 1 mm in length) were then transplanted into the subretinal space of each ...

Embodiment 2

[0235] Visual recovery and improvement was demonstrated in rabbits with ocular impact exposure and retinal damage. Subretinal grafts comprising hESC-3D retinal tissue and biodegradable and / or non-biodegradable carriers or scaffolds were used to treat damaged retinal tissue in rabbits. As described herein, subretinal grafts may comprise hESC-3D retinal tissue blocks mounted on thin electrospun nanofiber layers of biomaterial scaffolds to form biological retinal patches. Following sacrifice, optical coherence tomography (OCT) and histology and immunohistochemistry in live animals were used to demonstrate structural recovery of tissue and vision. Functional recovery was demonstrated in live animals using visual evoked potentials (VEP).

[0236] Human retinal tissue was generated using clinical grade hPSCs (BIOTIME, INC.). Pilot transplantation experiments were performed in rabbits to determine the subretinal transplantation process in a large eye animal model. An ocular impact...

Embodiment 3

[0241] The hPSC-retinal progenitors were delivered into the ocular space of rabbits using an eye syringe (ex vivo experiments). Frozen sections of rabbit eyes engrafted with human retinal progenitor cells were stained with anti-human nuclear antibody HNu (red) and whole-nucleus DAPI staining (blue). The presence of human retinal cells (red + blue staining) in the rabbit eye space (blue staining only) delivered by means of an ocular syringe was demonstrated. Figure 5B to Figure 5D Demonstrated that subretinal grafts of human retinal progenitor cells differentiated from human embryonic stem cells (hESCs) can be successfully transplanted into the ocular space of an animal model of megaphthalmia (rabbit), maintaining retinal layer thickness in the adult mammalian retina Up to 3 months, no harmful effects on the recipient retina, and no tumorigenesis. Cells from these grafts migrated and integrated into the recipient retinal layers, strengthening the recipient retina. Such cells...

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Abstract

Bioprosthetic retinal grafts (or devices) comprising stem cell derived tissues and / or cells may be used to slow the progression of retinal degenerative disease, slow the progression of retinal degenerative disease after traumatic injury, slow the progression of age related macular degeneration (AMD), prevent retinal degenerative disease, prevent retinal degenerative disease after traumatic injury,prevent AMD, restore retinal pigment epithelium (RPE), photoreceptor cells (PRCs) and retinal ganglion cells (RGCs) lost from disease, injury or genetic abnormalities, increasing RPE, PRCs and RCGs,treat RPE, PRCs and RCG defects in a subject, or for other purposes. Bioprosthetic retinal grafts may comprise a bioprosthetic carrier or scaffold suitable for implantation into the ocular space of asubject's eye, to form a bioprosthetic retinal patch. In certain embodiments, the bioprosthetic retinal patch may comprise multiple pieces of stem cell derived tissues or cells on a carrier or scaffold, which may be used to treat large areas of retinal degeneration or damage, or for other purposes.

Description

[0001] Cross References to Related Applications [0002] This application claims U.S. Provisional Patent Application Serial No. 62 / 539,542, filed July 31, 2017, U.S. Provisional Patent Application Serial No. 62 / 577,154, filed October 25, 2017, U.S. Provisional Patent Application Serial No. 62 / 577,154, filed November 30, 2017 Priority and benefit of U.S. Provisional Patent Application Serial No. 62 / 593,228, U.S. Provisional Patent Application Serial No. 62 / 646,354, filed March 21, 2018, and U.S. Provisional Patent Application Serial No. 62 / 665,483, filed May 1, 2018, The entire content of each of these documents is hereby incorporated by reference in its entirety. Background technique [0003] Degenerative retinal (RD) diseases, which ultimately lead to photoreceptor (PR) degeneration, are the third leading cause of blindness worldwide. Genetic conditions, age, and trauma (military and civilian) are the leading causes of vision loss associated with retinal degeneration. Once...

Claims

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Application Information

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IPC IPC(8): A61K35/30A61P27/02
CPCA61K35/30A61P27/02A61F2/148A61K31/137A61K35/545A61L27/3604A61L27/3666A61L27/54A61L2430/16A61K35/36
Inventor I·纳松基R·辛格O·库扎尼M·奥诺拉托F·比内特
Owner LINEAGE CELL THERAPEUTICS INC
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