# US 10,869,899 B2 · Isolated cells and populations comprising same for the treatment of CNS diseases

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- Number: US 10,869,899 B2
- Document ID: US10869899B2
- Status: Granted
- Kind: B2
- Application number: 15/820,521
- Filed: 2017-11-22
- Published: 2018-04-26
- Granted: 2020-12-22
- Earliest claimed: 2005-06-16
- Assignees: Ramot at Tel-Aviv University Ltd.
- Applicants: Ramot at Tel-Aviv University Ltd.
- Inventors: Daniel Offen; Merav Bahat-Stromza; Eldad Melamed
- Web page: https://patentgrep.com/patent/US10869899B2

## CPC

- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- 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
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/02: for peripheral neuropathies
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- C12N 5/0622: {Glial cells, e.g. astrocytes, oligodendrocytes; Schwann cells}
- C12N 2501/11: Epidermal growth factor [EGF]
- C12N 2501/115: Basic fibroblast growth factor (bFGF, FGF-2)
- C12N 2501/135: Platelet-derived growth factor [PDGF]
- C12N 2501/40: Regulators of development
- C12N 2506/1353: from bone marrow mesenchymal stem cells (BM-MSC)
- 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
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

An isolated human cell and populations thereof is provided comprising at least one astrocytic phenotype and at least one mesenchymal stem cell phenotype, wherein the mesenchymal stem cell phenotype is not an astrocytic phenotype.

## Claims

### Claim 1

An isolated cell population comprising human cells which express CD90, and secrete glial derived neurotrophic factor (GDNF), wherein a secretion of said GDNF is at least 2 times greater than a basal secretion of said GDNF in non-differentiated mesenchymal stem cells, wherein the cell population is non-genetically modified, and wherein the cell population has been differentiated ex vivo from human mesenchymal stem cells.

### Claim 2 (depends on 1)

The isolated cell population of claim 1, wherein said human cells co-express said CD90 and glial fibrillary acidic protein (GFAP).

### Claim 3 (depends on 1)

The isolated cell population of claim 1, wherein a secretion of said GDNF is at least 5 times greater than a basal secretion of said neurotrophic factor in said non-differentiated mesenchymal stem cells.

### Claim 4 (depends on 1)

The isolated cell population of claim 1, wherein said human cells have a star-shaped body.

### Claim 5 (depends on 1)

The isolated cell population of claim 1, further secreting at least one neurotrophic factor selected from the group consisting of brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4/5, Neurturin (NTN), Persephin, artemin (ART), ciliary neurotrophic factor (CNTF), insulin growth factor-I (IGF-1) and Neublastin.

### Claim 6 (depends on 1)

The isolated cell population of claim 1, wherein a secretion of said GDNF is upregulated by IL-1 beta and/or cabergoline.

### Claim 7 (depends on 1)

A pharmaceutical composition comprising the isolated cell population of claim 1.

### Claim 8 (depends on 7)

A device comprising the pharmaceutical composition of claim 7, the device being adapted for administration of the isolated cell population into the spinal cord.

### Claim 9 (depends on 7)

A device comprising the pharmaceutical composition of claim 7, the device being adapted for administration of the isolated cell population into the brain.

### Claim 10 (depends on 7)

A device comprising the pharmaceutical composition of claim 7, the device being adapted for intramuscular administration of the isolated cell population.