Treatment of pulmonary arterial hypertension with prostacyclin-treated endothelial progenitor cells

• US 10,016,463 B2
• Filed: 07/30/2013
• Issued: 07/10/2018
• Est. Priority Date: 08/01/2012
• Status: Active Grant

• Current Assignee: United Therapeutics Corporation
• Original Assignee: United Therapeutics Corporation
• Inventors: Jeffs, Roger, Petersen, Thomas, Ilagan, Roger M., Wade, Michael
• Primary Examiner(s): Lankford, Blaine
• Application Number:
  US14/418,557
• Publication Number:
  US 20150216909A1
• Time in Patent Office: 1,806 Days
• Field of Search: None
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/5585 having five-membered rings containing oxygen as the only ring hetero atom, e.g. prostacyclin
• CPC Class Codes: A61K 35/02 from inanimate materials carbon A61K33/44
• CPC Class Codes: A61K 35/14 Blood; Artificial blood perfluorocarbons A61K31/02; umbilical cord blood A61K35/51; haemoglobin A61K38/42
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 35/44 Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C12N 2501/999 Small molecules not provided for elsewhere
• CPC Class Codes: C12N 5/0692 Stem cells; Progenitor cells; Precursor cells
• CPC Class Codes: F04C 2270/041 Controlled or regulated

Abstract

The current application is directed to a method for treating pulmonary arterial hypertension (PAH), comprising: providing isolated endothelial progenitor cells (EPCs); treating the EPCs with prostacyclin, wherein the treated EPCs exhibit a hyperproliferative phenotype with enhanced angiogenic property; and administering a composition comprising the treated EPCs into a subject suffering from PAH.

Claims

1. A method for treating pulmonary hypertension, comprising:

providing isolated endothelial progenitor cells (EPCs), wherein the EPCs are isolated from a human being, a tissue, or cell culture;

treating the isolated EPCs in vitro or ex vivo with a prostacyclin during expansion of the EPCs, wherein the treated EPCs exhibit a hyperproliferative phenotype with enhanced angiogenic activity; and

administering a composition comprising the treated EPCs to a subject suffering from pulmonary hypertension.

2. The method of claim 1, wherein the prostacyclin is selected from the group consisting of epoprostenol sodium, treprostinil, and iloprost.

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

4. The method of claim 1, wherein the EPCs are autologous.

5. The method of claim 1, wherein the EPCs are isolated from the blood of the subject suffering from pulmonary hypertension.

6. The method of claim 1, wherein the EPCs are endothelial colony forming cells.

7. The method of claim 1, wherein the EPCs are genetically modified.

8. The method of claim 1, wherein the composition is a pharmaceutical composition further comprising at least one pharmaceutically-acceptable carrier.

9. The method of claim 1, wherein the composition further comprises at least one therapeutic agent other than EPCs.

10. The method of claim 1, wherein administering the composition promotes pulmonary vascular repair.

11. The method of claim 1, wherein the composition is co-administered with at least one growth factor.

12. The method of claim 11, wherein the growth factor is selected from the group consisting of FGF, VEGF-A, VEGF-B, BMP-4, and TGF-Beta.

13. The method of claim 1, wherein the composition is co-administered with (i) mesenchymal stem cells or (ii) a culture medium that has been in contact with mesenchymal stem cells and that contains one or more components thereof.

14. The method of claim 1, wherein the composition is co-administered with a prostacyclin.

15. The method of claim 5, wherein the subjected is pretreated with a prostacyclin before the isolation of the EPCs.

16. The method of claim 1, wherein the prostacyclin is treprostinil.