Mesenchymal stem cells and uses therefor

• US 9,694,035 B2
• Filed: 07/17/2014
• Issued: 07/04/2017
• Est. Priority Date: 03/22/2004
• Status: Active Grant

• Current Assignee: Mesoblast International Srl
• Original Assignee: Mesoblast International SARL (Mesoblast Ltd.)
• Inventors: Aggarwal, Sudeepta, Varney, Timothy, Pittenger, Mark F.
• Primary Examiner(s): Long, Scott
• Assistant Examiner(s): Hiriyanna, Kelaginamane T
• Application Number:
  US14/334,128
• Publication Number:
  US 20150017132A1
• Time in Patent Office: 1,083 Days
• Field of Search: 424 937
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• 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 38/2026 IL-4
• CPC Class Codes: A61K 38/2066 IL-10
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C12N 5/0662 : Stem cells
• CPC Class Codes: C12N 5/0663 : Bone marrow mesenchymal stem cells (BM-MSC)
• CPC Class Codes: C12N 5/0664 : Dental pulp stem cells, Dental follicle stem cells
• CPC Class Codes: C12N 5/0665 : Blood-borne mesenchymal stem cells, e.g. from umbilical cord blood
• CPC Class Codes: C12N 5/0666 : Mesenchymal stem cells from hair follicles
• CPC Class Codes: C12N 5/0667 : Adipose-derived stem cells [ADSC]; Adipose stromal stem cells
• CPC Class Codes: C12N 5/0668 : Mesenchymal stem cells from other natural sources
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Methods of treating autoimmune diseases, allergic responses, cancer, or inflammatory diseases in an animal, promoting wound healing, repairing epithelial damage and promoting angiogenesis in an organ or tissue of an animal by administering to the animal mesenchymal stem cells in an effective amount.

Claims

1. A method of reducing inflammation in the gastrointestinal tract of a patient in need thereof, comprising the step of intravenously or intraarterially administering to a human suffering from inflammation of the gastrointestinal tract a suspension of cells in an amount effective to reduce the inflammation, wherein the cells are genetically unmodified allogeneic mesenchymal stem cells, wherein the suspension of mesenchymal stem cells is at least 95% homogeneous and wherein the mesenchymal stem cells express CD73 and CD105.

2. The method of claim 1, wherein the patient suffers from Crohn'"'"'s disease, inflammatory bowel disease, gastrointestinal graft-versus-host disease (GVHD), or autoimmune gastritis.

3. The method of claim 2, wherein the patient suffers from gastrointestinal graft-versus-host disease.

4. The method of claim 3, wherein the patient was refractory to one or more treatments to GVHD.

5. The method of claim 1, wherein the suspension further comprises an acceptable pharmaceutical carrier.

6. The method of claim 5, wherein the acceptable pharmaceutical carrier is a pharmaceutically acceptable liquid medium for injection.

7. The method of claim 1, wherein the suspension is administered in an amount of from about 1×

10⁵ cells/kg to about 1×

10⁷ cells/kg.

8. The method of claim 1, wherein the suspension is administered in an amount of from about 1×

10⁶ cells/kg to about 5×

10⁶ cells/kg.

9. The method of claim 1, wherein the suspension is administered in an amount of about 3×

10⁶ cells/kg.

10. The method of claim 1, wherein the method comprises increasing production or secretion of an anti-inflammatory cytokines interleukin-4 or interleukin-10.

11. The method of claim 1, wherein the method comprises reducing production or secretion of a pro-inflammatory cytokine in a human in need thereof.

12. The method of claim 2, wherein the patient suffers from inflammatory bowel disease.

13. The method of claim 11, wherein the pro-inflammatory cytokine that is reduced in production or secretion is selected from the group consisting of interferon-γ

, TNF-α

, and IL-17.