# US 2021/0275583 A1 · Compositions and methods for the treatment of demyelinating conditions

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2021/0275583 A1
- Document ID: US20210275583A1
- Status: Published application
- Kind: A1
- Application number: 17/328,749
- Filed: 2021-05-24
- Published: 2021-09-09
- Earliest claimed: 2017-01-12
- Assignees: Duke University
- Applicants: Duke University
- Inventors: Joanne Kurtzberg; Anthony Fillano; Arjun Saha; Andrew E. Balber; Ana Valverde
- Web page: https://patentgrep.com/patent/US20210275583A1

## CPC

- C12N 5/0645: {Macrophages, e.g. Kuepfer cells in the liver; Monocytes}
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 9/107: Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)}
- A61K 31/573: substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
- 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 35/51: Umbilical cord; Umbilical cord blood; Umbilical stem cells
- A61K 40/10: characterised by the cell type used
- A61K 40/22: Immunosuppressive or immunotolerising
- A61K 40/416: {Antigens related to auto-immune diseases; Preparations to induce self-tolerance}
- A61K 47/06: Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- 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
- A61P 25/00: Drugs for disorders of the nervous system
- C12N 5/0622: {Glial cells, e.g. astrocytes, oligodendrocytes; Schwann cells}
- A61K 2239/31: characterized by the route of administration
- A61K 2239/38: characterised by the dose, timing or administration schedule
- C12N 2501/135: Platelet-derived growth factor [PDGF]
- C12N 2501/165: Vascular endothelial growth factor [VEGF]
- C12N 2501/39: Steroid hormones
- C12N 2501/395: Thyroid hormones
- C12N 2506/1369: from blood-borne mesenchymal stem cells, e.g. MSC from umbilical blood
- 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

The present disclosure provides compositions and methods for treating demyelinating conditions. More particularly, the present disclosure relates to compositions comprising a DUOC-01 cell product; methods for preparing such compositions; and methods of using such compositions for treating demyelinating conditions.

## Claims

### Claim 1

A method of treating a demyelinating condition in a subject in need thereof, the method comprising:
administering to the subject a therapeutically effective amount of a DUOC-HC composition comprising a DUOC-01 cell product formulated in hydrocortisone (HC),
wherein the DUOC-01 cell product comprises cells derived from cord blood mononuclear cells, wherein such cells express one or more of CD45, CD11b, CD14, CD16, CD206, CD163, Iba1, HLA-DR, TREM 2, and iNOS macrophage or microglia markers; and wherein such cells secrete IL-6 and IL-10.

### Claim 2 (depends on 1)

The method of claim 1, wherein the DUOC-01 cells are incubated in Ringer's lactate solution with hydrocortisone thereby obtaining the DUOC-HC composition.

### Claim 3 (depends on 1)

The method of claim 1, wherein the demyelinating condition is multiple sclerosis, leukodystrophy, spinal cord injury, peripheral nerve damage, Parkinson's disease, amyotrophic lateral sclerosis (ALS), or Alzheimer's disease.

### Claim 4 (depends on 1)

The method of claim 1, wherein the DUOC-01 cell product excludes cells expressing CD3.

### Claim 5 (depends on 1)

The method of claim 1, wherein the DUOC-HC composition is administered via local tissue injection or intrathecally.

### Claim 6 (depends on 1)

The method of claim 1, wherein the DUOC-HC composition is administered in a single dose or in multiple doses.

### Claim 7 (depends on 1)

The method of claim 1, wherein the amount of the DUOC-HC composition administered is sufficient to provide about 1×105 to about 1×108 DUOC-01 cells.

### Claim 8 (depends on 1)

The method of claim 1, further comprising:
exposing the cord blood mononuclear cells in a first culture medium to one or more factors selected from: platelet-derived growth factor (PDGF), neurotrophin-3 (NT-3), vascular endothelial growth factor (VEGF), and triiodothyronine (T3); and at least one of serum or plasma for a period of time sufficient to obtain a DUOC-01 cell product;
isolating the DUOC-01 cell product; and
dissolving the DUOC-01 cell product in a pharmaceutically acceptable carrier to obtain the DUOC-HC composition.

### Claim 9 (depends on 8)

The method of claim 8, wherein the exposing is to PDGF, NT-3, VEGF, T3, and serum.

### Claim 10 (depends on 8)

The method of claim 8, wherein the PDGF is present in a concentration of about 1 to about 10 ng/mL; the NT-3 is present in a concentration of about 0.1 to about 5 ng/mL; the VEGF is present in a concentration of about 1 to about 50 ng/mL; and the T3 is present in a concentration of about 10 to about 100 ng/mL.

### Claim 11 (depends on 9)

The method of claim 9, further comprising providing an additional amount of PDGF, NT-3, VEGF, T3, and serum after 7 days and after 17 days.

### Claim 12 (depends on 9)

The method of claim 9, further comprising providing an additional amount of PDGF, NT-3, and VEGF after 14 days.

### Claim 13 (depends on 8)

The method of claim 8, wherein the period of time sufficient to obtain the DUOC-01 cell product is 21 days.

### Claim 14 (depends on 8)

The method of claim 8, wherein the pharmaceutically acceptable carrier is Ringer's lactate solution with hydrocortisone.

### Claim 15

A kit comprising:
a DUOC-HC composition comprising a DUOC-01 cell product formulated in hydrocortisone (HC), wherein DUOC-01 cell product comprises cells derived from cord blood mononuclear cells, wherein such cells express one or more of CD45, CD11b, CD14, CD16, CD206, CD163, Iba1, HLA-DR, TREM 2, and iNOS macrophage or microglia markers; and wherein such cells secrete IL-6 and IL-10; and
a label or instructions for administration of the DUOC-HC composition to treat a demyelinating condition.

### Claim 16 (depends on 15)

The kit of claim 15, wherein the cells overexpress one or more of PDGFA, KITLG/SCF, IGF1, TREM2, MMP9, and MMP12 transcripts.

### Claim 17 (depends on 15)

The kit of claim 15, wherein the amount of the DUOC-HC composition is sufficient to provide about 1×105 to about 1×108 DUOC-01 cells.

### Claim 18 (depends on 15)

The kit of claim 15, wherein the DUOC-01 cell product is obtained by:
exposing the cord blood mononuclear cells in a first culture medium to one or more factors selected from: platelet-derived growth factor (PDGF), neurotrophin-3 (NT-3), vascular endothelial growth factor (VEGF), and triiodothyronine (T3); and at least one of serum or plasma for a period of time sufficient to obtain a DUOC-01 cell product;
isolating the DUOC-01 cell product, and
dissolving the DUOC-01 cell product in a pharmaceutically acceptable carrier to obtain the DUOC-HC composition.

### Claim 19 (depends on 18)

The kit of claim 18, wherein the pharmaceutically acceptable carrier is Ringer's lactate solution with hydrocortisone.

### Claim 20 (depends on 15)

The kit of claim 15, wherein the demyelinating condition is multiple sclerosis, leukodystrophy, peripheral nerve disease, spinal cord injury, Parkinson's disease, amyotrophic lateral sclerosis (ALS), or Alzheimer's disease.