# US 2014/0193379 A1 · Treatment of vasculopathy with prostacyclin and mesenchymal stem cells

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

- Number: US 2014/0193379 A1
- Document ID: US20140193379A1
- Status: Published application
- Kind: A1
- Application number: 14/149,929
- Filed: 2014-01-08
- Published: 2014-07-10
- Earliest claimed: 2013-01-09
- Assignees: United Therapeutics Corporation
- Applicants: United Therapeutics Corporation
- Inventors: Roger Jeffs; Thomas Petersen; Roger M. Ilagan; Michael Wade
- Web page: https://patentgrep.com/patent/US20140193379A1

## CPC

- A61K 31/5585: having five-membered rings containing oxygen as the only ring hetero atom, e.g. prostacyclin
- A61K 31/557: Eicosanoids, e.g. leukotrienes {or prostaglandins}
- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 9/12: Antihypertensives
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12N 5/0663: {Bone marrow mesenchymal stem cells (BM-MSC)}
- C12N 2501/00: Active agents used in cell culture processes, e.g. differentation
- C12N 2501/02: Compounds of the arachidonic acid pathway, e.g. prostaglandins, leukotrienes
- 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

Provided are methods for treating or preventing vasculopathy in a subject in need thereof, comprising administering to the subject a prostacyclin and a mesenchymal stem cell (MSC) or a MSC-conditioned culture medium or administering to the subject a MSC or a MSC-conditioned culture medium that has treated with prostacyclin. Pharmaceutical compositions suitable for such treatments are also provided.

## Claims

### Claim 1

A method for treating or preventing vasculopathy in a subject in need thereof, comprising administering to the subject a prostacyclin and a composition comprising a mesenchymal stem cell (MSC) or a part of a culture medium that has been in contact with the MSC and contains one or more components of the MSC.

### Claim 2 (depends on 1)

The method of claim 1, wherein the prostacyclin and the composition are administered concurrently.

### Claim 3 (depends on 1)

The method of claim 1, wherein the prostacyclin and the composition are administered separately.

### Claim 4 (depends on 1)

The method of claim 1, further comprising, prior to the administration, contacting the MSC or the part of the culture medium with a prostacyclin.

### Claim 5 (depends on 1)

The method of claim 1, wherein the component(s) of the MSC is selected from the group consisting of an exosome, a microvesicle, a microRNA, a messenger RNA, a non-coding RNA, a mitochondria, a growth factor, and combinations thereof.

### Claim 6 (depends on 1)

The method of claim 1, further comprising administering to the subject an endothelial progenitor cell (EPC).

### Claim 7 (depends on 6)

The method of claim 6, wherein the EPC is obtained from the subject.

### Claim 8 (depends on 6)

The method of claim 6, wherein the EPC is transformed with a nucleic acid that increases the expression of biological activity of a protein selected from the group consisting of endothelial nitric oxide synthase (eNOS), heme oxygenase (HMOX1) and prostacyclin synthase (PTGIS).

### Claim 9 (depends on 8)

The method of claim 8, wherein the nucleic acid encodes the protein.

### Claim 10 (depends on 1)

The method of claim 1, wherein the prostacyclin is selected from the group consisting of epoprostenol, treprostinil, beraprost, ilprost, a PGI2 receptor agonist, and pharmaceutically acceptable salts thereof.

### Claim 11 (depends on 9)

The method of claim 9, wherein the prostacyclin is treprostinil or a pharmaceutically acceptable salt or ester thereof.

### Claim 12 (depends on 1)

The method of claim 1, wherein the MSC is a mesenchymal precursor cell (MPC).

### Claim 13 (depends on 1)

The method of claim 1, wherein the MSC is obtained from bone marrow.

### Claim 14 (depends on 1)

The method of claim 1, wherein the vasculopathy is selected from the group consisting of pulmonary arterial hypertension (PAH), peripheral vascular disease (PVD), critical limb ischemia (CLI), coronary artery disease and diabetic vasculopathy.

### Claim 15

A pharmaceutical composition comprising a therapeutically effective amount of a prostacyclin and a composition comprising a mesenchymal stem cell (MSC) or a part of a culture medium that has been in contact with the MSC and contains one or more components of the MSC and a pharmaceutically acceptable carrier.

### Claim 16 (depends on 15)

The composition of claim 15, wherein the MSC or the part of the culture medium has been in contact with a prostacyclin.

### Claim 17 (depends on 15)

The composition of claim 15, further comprising an endothelial progenitor cell (EPC).

### Claim 18

A method for preparing a composition comprising a mesenchymal stem cell (MSC) or a culture medium that has been in contact with the MSC and contains one or more components of the MSC for in vivo delivery, comprising contacting the MSC with a prostacyclin.

### Claim 19 (depends on 18)

The method of claim 18, wherein the prostacyclin is present in a concentration from about 200 μg/mL to about 300 μg/mL.

### Claim 20 (depends on 18)

A treated composition obtainable by the method of claim 18.