# US 12,213,996 B2 · Methods of treating optic nerve diseases using neural progenitor cell growth factors

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- Number: US 12,213,996 B2
- Document ID: US12213996B2
- Status: Granted
- Kind: B2
- Application number: 16/966,204
- Filed: 2019-02-01
- Published: 2022-06-09
- Granted: 2025-02-04
- Earliest claimed: 2018-02-02
- Assignees: University of Maryland, Baltimore; Regenerative Research Foundation
- Applicants: University of Maryland, Baltimore; Regenerative Research Foundation; Steven Lance Bernstein; Candace L. Kerr; Sally Temple Stern
- Inventors: Steven Lance Bernstein; Candace L. Kerr; Sally Temple Stern
- Web page: https://patentgrep.com/patent/US12213996B2

## CPC

- 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 38/18: Growth factors; Growth regulators
- A61K 38/1825: {Fibroblast growth factor [FGF]}
- A61K 38/1841: {Transforming growth factor [TGF]}
- A61K 38/185: {Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3}
- A61K 38/1866: {Vascular endothelial growth factor [VEGF]}
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 27/06: Antiglaucoma agents or miotics
- 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

Optic nerve lamina region neural progenitor cells (ONLR-NPCs) are provided. Such cells secrete growth factors and survival factors that can be used in the treatment of optic nerve diseases, such as glaucoma. Also provided are methods of treating or preventing optic nerve diseases, such as glaucoma, using one or more factors secreted by ONLR-NPCs, combinations of factors secreted by ONLR-NPCs, or culture media conditioned by ONLR-NPCs.

## Claims

### Claim 1

A method of treating or preventing an optic nerve disease in a subject comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising one or more of:
(i) a population of optic nerve lamina region-neural progenitor cells (ONLR-NPCs),
(ii) ONLR-NPC conditioned media,
(iii) an ONLR-NPC lysate, and
thereby treating or preventing an optic nerve disease in the subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein the optic nerve disease is selected from the group consisting of open-angle glaucoma, angle-closure glaucoma, optic nerve hypoplasia, optic nerve hypomyelination, regional axonal dysfunction, nonarteritic anterior ischemic optic neuropathy (NAION), and optic neuritis.

### Claim 3 (depends on 1)

The method of claim 1, wherein the composition is administered to the eye of the subject.

### Claim 4 (depends on 1)

The method of claim 1, wherein the composition is administered to the subject via one or more of topical application, subconjunctival injection, intravitreal injection, and retrobulbar injection.

### Claim 5 (depends on 1)

The method of claim 1, wherein the composition administered to the subject is a pharmaceutical formulation comprising a pharmaceutically acceptable carrier.

### Claim 6 (depends on 1)

The method of claim 1, wherein the subject is a human.

### Claim 7 (depends on 1)

The method of claim 1, wherein the ONLR-NPCs are nestin(+), SOX2(+), GFAP(+), NG2(−) cells.

### Claim 8 (depends on 1)

The method of claim 1, wherein the ONLR-NPCs are nestin(+), SOX2(+), GFAP(+), NG2(−), SOX1(+), vimentin(+), BDNF(+) cells.

### Claim 9 (depends on 1)

The method of claim 1, wherein the ONLR-NPCs express one or more of Latent Transforming Growth Factor-Beta 1 (TGF-β1), Connective Tissue Growth Factor (CTGF), Nerve Growth Factor (NGF), Fibroblast Growth Factor (FGF-1), Vascular Endothelial Growth Factor (VEGF), Mesenchymal Astrocyte Neurotrophic Factor (MANF) and Insulin-like Growth Factors-1 and -2 (IGF-1 and IGF-2).

### Claim 10 (depends on 1)

The method of claim 1, wherein the ONLR-NPCs express at least five growth factors selected from the group consisting of VGF, TGFβ1, LTBP1, LTBP2, PDGFB, CTGF, FGF11, NDNF, PDGFC, TGFβ2, NGF, FGF1, Midkine, VEGFA, MANF, IGF-1, and IGF-2.

### Claim 11 (depends on 1)

The method of claim 1, wherein the ONLR-NPCs express each of VGF, TGFβ1, LTBP1, LTBP2, PDGFB, CTGF, FGF11, NDNF, PDGFC, TGFβ2, NGF, FGF1, Midkine, VEGFA, MANF, IGF-1, and IGF-2.

### Claim 12 (depends on 1)

The method of claim 1, wherein the ONLR-NPCs express one or more proteins selected from the group consisting of Cell Growth Regulator with Ring Finger Domain 1, Dynein Regulatory Complex Subunit 4, Fibroblast Growth Factor 12, Fibroblast Growth Factor 14, Fibroblast Growth Factor Receptor 4, Growth Arrest and DNA Damage-inducible Protein GADD45 beta, Growth Factor Independent 1 Transcriptional Repressor, Growth Hormone Receptor, Placental Growth Factor, Platelet-derived Growth Factor D/Spinal Cord-Derived Growth Factor B, Platelet-derived Growth Factor Receptor-like Protein, Transforming Growth Factor beta-1 Proprotein, Transforming Growth Factor beta-1-induced Transcript 1 Protein, Upper Zone of Growth Plate and Cartilage Matrix Associated Protein, Vascular Endothelial Growth Factor C and UNC-13 Homolog C.

### Claim 13 (depends on 1)

The method of claim 1, wherein the ONLR-NPCs express each of Cell Growth Regulator with Ring Finger Domain 1, Dynein Regulatory Complex Subunit 4, Fibroblast Growth Factor 12, Fibroblast Growth Factor 14, Fibroblast Growth Factor Receptor 4, Growth Arrest and DNA Damage-inducible Protein GADD45 beta, Growth Factor Independent 1 Transcriptional Repressor, Growth Hormone Receptor, Placental Growth Factor, Platelet-derived Growth Factor D/Spinal Cord-Derived Growth Factor B, Platelet-derived Growth Factor Receptor-like Protein, Transforming Growth Factor beta-1 Proprotein, Transforming Growth Factor beta-1-induced Transcript 1 Protein, Upper Zone of Growth Plate and Cartilage Matrix Associated Protein, Vascular Endothelial Growth Factor C and UNC-13 Homolog C.

### Claim 14 (depends on 1)

The method of claim 1, wherein the composition comprising one or more factors secreted by ONLR-NPCs comprises one or more of Latent Transforming Growth Factor-Beta 1 (TGF-β1), Connective Tissue Growth Factor (CTGF), Nerve Growth Factor (NGF), Fibroblast Growth Factor (FGF-1), Vascular Endothelial Growth Factor (VEGF), Mesenchymal Astrocyte Neurotrophic Factor (MANF) and Insulin-like Growth Factors-1 and -2 (IGF-1 and IGF-2).

### Claim 15 (depends on 1)

The method of claim 1, wherein the composition comprising one or more factors secreted by ONLR-NPCs comprises each of Latent Transforming Growth Factor-Beta 1 (TGF-β1), Connective Tissue Growth Factor (CTGF), Nerve Growth Factor (NGF), Fibroblast Growth Factor (FGF-1), Vascular Endothelial Growth Factor (VEGF), Mesenchymal Astrocyte Neurotrophic Factor (MANF) and Insulin-like Growth Factors-1 and -2 (IGF-1 and IGF-2).

### Claim 16 (depends on 1)

The method of claim 1, wherein the composition comprising one or more factors secreted by ONLR-NPCs comprises at least five of growth factors selected from the group consisting of VGF, TGFβ1, LTBP1, LTBP2, PDGFB, CTGF, FGF11, NDNF, PDGFC, TGFβ2, NGF, FGF1, Midkine, VEGFA, MANF, IGF-1, and IGF-2.

### Claim 17 (depends on 1)

The method of claim 1, wherein the composition comprising one or more factors secreted by ONLR-NPCs comprises each of VGF, TGFβ1, LTBP1, LTBP2, PDGFB, CTGF, FGF11, NDNF, PDGFC, TGFβ2, NGF, FGF1, Midkine, VEGFA, MANF, IGF-1, and IGF-2.