# US 9,040,038 B2 · Modalities for the treatment of degenerative diseases of the retina

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- Number: US 9,040,038 B2
- Document ID: US9040038B2
- Status: Granted
- Kind: B2
- Application number: 13/858,534
- Filed: 2013-04-08
- Published: 2013-11-28
- Granted: 2015-05-26
- Earliest claimed: 2004-01-23
- Assignees: Ocata Therapeutics, Inc.
- Applicants: Ocata Therapeutics, Inc.
- Inventors: Irina V. Klimanskaya; Robert P. Lanza
- Web page: https://patentgrep.com/patent/US9040038B2

## CPC

- C12N 5/0621: {Eye cells, e.g. cornea, iris pigmented cells (photoreceptors C12N5/062)}
- A61K 35/12: Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells (vaccines or medicinal preparations containing antigens or antibodies A61K39/00)
- 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 35/36: Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells (islets of Langerhans A61K35/39)
- A61K 35/44: Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
- A61K 35/545: Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
- A61P 25/16: Anti-Parkinson drugs
- A61P 27/02: Ophthalmic agents
- A61P 27/06: Antiglaucoma agents or miotics
- C12N 5/062: {Sensory transducers, e.g. photoreceptors; Sensory neurons, e.g. for hearing, taste, smell, pH, touch, temperature, pain}
- C12N 2500/32: Amino acids
- C12N 2500/44: Thiols, e.g. mercaptoethanol
- C12N 2501/01: Modulators of cAMP or cGMP, e.g. non-hydrolysable analogs, phosphodiesterase inhibitors, cholera toxin
- C12N 2501/115: Basic fibroblast growth factor (bFGF, FGF-2)
- C12N 2501/15: Transforming growth factor beta (TGF-β)
- C12N 2501/155: Bone morphogenic proteins [BMP]; Osteogenins; Osteogenic factor; Bone inducing factor
- C12N 2501/235: Leukemia inhibitory factor [LIF]
- C12N 2501/33: Insulin
- C12N 2501/60: Transcription factors
- C12N 2506/02: from embryonic cells
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

This invention relates to methods for improved cell-based therapies for retinal degeneration and for differentiating human embryonic stem cells and human embryo-derived into retinal pigment epithelium (RPE) cells and other retinal progenitor cells.

## Claims

### Claim 1

A method of producing a composition comprising isolated human RPE cells suitable for human therapy, comprising:
(a) culturing human pluripotent cells to form clusters of cells;
(b) culturing the clusters of cells of step (a) under adherent conditions that do not maintain the undifferentiated state of the pluripotent cells for a sufficient time for the appearance of pigmented cells comprising brown pigment dispersed in their cytoplasm; and
(c) isolating and culturing the pigmented cells to form a monolayer comprising cells having a cobblestone, polygonal, epithelial-like appearance and brown pigment dispersed in their cytoplasm, and expressing RPE65 and bestrophin, thereby obtaining human RPE cells.

### Claim 2 (depends on 1)

The method of claim 1 wherein said clusters of cells of step (a) are trypsinized and cultured on adherent plates.

### Claim 3 (depends on 1)

The method of claim 1, wherein the monolayer of step (c) is dissociated to form a suspension of RPE cells suitable for subretinal transplantation in a human patient.

### Claim 4 (depends on 1)

The method of claim 1, wherein the monolayer of step (c) is disposed on a matrix or substrate to form a monolayer of RPE cells suitable for subretinal transplantation in a human patient.