# US 12,593,837 B2 · Retinal pigment epithelium cell compositions

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- Number: US 12,593,837 B2
- Document ID: US12593837B2
- Status: Granted
- Kind: B2
- Application number: 16/958,399
- Filed: 2018-12-28
- Published: 2021-01-07
- Granted: 2026-04-07
- Earliest claimed: 2017-12-29
- Assignees: Cell Cure Neurosciences Ltd.
- Applicants: Cell Cure Neurosciences Ltd.
- Inventors: Nir Netzer; Ofer Wiser; Bat Shahaf; Orit Gamburg; Lior Rosenberg Belmaker; Dana Hayoun Neeman; Osnat Bohana Kashtan
- Web page: https://patentgrep.com/patent/US12593837B2

## CPC

- A01N 1/122: Preservation or perfusion media
- A01N 1/125: Freeze protecting agents, e.g. cryoprotectants or osmolarity regulators
- A61K 9/0048: {Eye, e.g. artificial tears}
- A61K 9/0051: {Ocular inserts or implants}
- A61K 35/30: Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
- A61K 47/02: Inorganic compounds
- A61K 47/183: {Amino acids, e.g. glycine, EDTA or aspartame}
- A61K 47/20: containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

Presented herein are ready to administer (RTA) retinal pigment epithelium (RPE) cell therapy compositions for the treatment of retinal degenerative diseases and injuries. A method of formulating human RPE cells for administration to a subject directly after thawing and of formulating RPE cell therapy compositions for cryopreservation and administration of the cryopreserved composition to a subject subsequent to thawing are also presented. In another aspect, the RTA composition may be formulated as a thaw and inject (TAI) composition, whereby the composition is administered by injection subsequent to thawing.

## Claims

### Claim 1

A method of treating a retinal degenerative disease in a human subject in need thereof, comprising thawing a frozen retinal pigment epithelium (RPE) cell therapy composition and administering the thawed RPE cell therapy composition to the retina of the subject directly after thawing without washing, reconstitution, or removal of dead cells; wherein the RPE cell therapy composition comprises:
a) a preservation media comprising: adenosine, dextran-40, HEPES (N-(2-hydroxyethyl) piperazine-N′-(2-ethanesulfonic acid)), and between about 4% and about 6% dimethyl sulfoxide (DMSO); and
b) retinal pigment epithelium (RPE) cells.

### Claim 2 (depends on 1)

The method of claim 1, wherein the RPE cell therapy composition comprises between about 100,000 and about 10,000,000 RPE cells/mL.

### Claim 3 (depends on 1)

The method of claim 1, wherein the RPE cell therapy composition comprises between about 2,000,000 and about 5,000,000 RPE cells/mL.

### Claim 4 (depends on 1)

The method of claim 1, wherein the preservation media comprises about 5% DMSO.

### Claim 5 (depends on 1)

The method of claim 1, wherein the preservation media further comprises one or more of: a sugar acid, one or more of a base, an antioxidant, one or more halide salt, a basic salt, phosphate salt, one or more sugars, sugar alcohol, and water.

### Claim 6 (depends on 5)

The method of claim 5, wherein:
a) the sugar acid comprises lactobionic acid, glyceric acid, xylonic acid, gluconic acid, ascorbic acid, neuraminic acid, ketodeoxyoctulosonic acid, glucuronic acid, galacturonic acid, galacturonic acid, iduronic acid, tartaric acid, mucic acid, or saccharic acid;
b) the one or more of a base comprises sodium hydroxide, or potassium hydroxide;
c) the antioxidant comprises L-glutathione, ascorbic acid, lipoic acid, uric acid, a carotene, alpha-tocopherol, or ubiquinol;
d) the one or more halide salt comprises potassium chloride, sodium chloride, or magnesium chloride;
e) the basic salt comprises potassium bicarbonate, sodium bicarbonate, or sodium acetate;
f) the phosphate salt comprises potassium phosphate, sodium phosphate, or potassium phosphate;
g) the one or more sugars comprises dextrose or sucrose; and
h) the sugar alcohol comprises mannitol, sorbitol, erythritol or xylitol.

### Claim 7 (depends on 4)

The method of claim 4, wherein the preservation media further comprises lactobionic acid, sodium hydroxide, L-glutathione, potassium chloride, potassium bicarbonate, potassium phosphate, dextrose, sucrose, mannitol, calcium chloride, magnesium chloride, potassium hydroxide, sodium hydroxide, and water.

### Claim 8 (depends on 1)

The method of claim 1, wherein the preservation media further comprises one or more of a rho kinase (ROCK) inhibitor or nicotinamide (NA).

### Claim 9 (depends on 4)

The method of claim 4, wherein the preservation media further comprises one or more of a rho kinase (ROCK) inhibitor or nicotinamide (NA).

### Claim 10 (depends on 1)

The method of claim 1, wherein the RPE cells express one or more of: bestrophin 1, microphthalmia-associated transcription factor (MITF), ZO-1, paired box gene 6 (PAX-6), cellular retinaldehyde binding protein (CRALBP), melanocytes lineage-specific antigen GP100 (PMEL 17), RPE65, and markers for RPE primary cilia.

### Claim 11 (depends on 1)

The method of claim 1, wherein the RPE cells secrete one or more of basic fibroblast growth factor (bFGF), acidic fibroblast growth factor (aFGF), ciliary neurotrophic factor (CNTF), pigment epithelium-derived factor (PEDF), brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) or one or more anti-inflammatory cytokines.

### Claim 12 (depends on 1)

The method of claim 1, wherein the RPE cells are in a single-cell suspension.

### Claim 13 (depends on 1)

The method of claim 1, wherein at least about 40% to about 100% of the RPE cells are viable after thawing without washing, reconstituting, or removing dead cells.

### Claim 14 (depends on 13)

The method of claim 13, wherein about 95% to about 100% of viable RPE cells are CRALBP+/PMEL17+ after thawing.

### Claim 15 (depends on 4)

The method of claim 4, wherein at least about 40% to about 100% of the RPE cells are viable after thawing without washing, reconstituting, or removing dead cells.

### Claim 16 (depends on 15)

The method of claim 15, wherein about 95% to about 100% of viable RPE cells are CRALBP+/PMEL17+ after thawing.

### Claim 17 (depends on 1)

The method of claim 1, wherein the RPE cells were generated from pluripotent stem cells.

### Claim 18 (depends on 17)

The method of claim 17, wherein the pluripotent stem cells are embryonic stem cells.