Methods of treating or preventing respiratory conditions

• US 10,028,979 B2
• Filed: 12/12/2013
• Issued: 07/24/2018
• Est. Priority Date: 12/12/2012
• Status: Active Grant

• Current Assignee: Mesoblast, Inc. (Mesoblast Ltd.)
• Original Assignee: Mesoblast, Inc. (Mesoblast Ltd.)
• Inventors: Itescu, Silviu, Krishnan, Ravi, Ghosh, Peter
• Primary Examiner(s): Shen, Bin
• Application Number:
  US14/650,171
• Publication Number:
  US 20150306146A1
• Time in Patent Office: 1,685 Days
• 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: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: C12N 5/0663 Bone marrow mesenchymal stem cells (BM-MSC)

Abstract

The present disclosure provides methods of treating or preventing respiratory condition and/or for treating an IgE-mediated allergy and/or for reducing an allergic response to an allergen and/or for inducing anergy to an allergen in a subject and/or improving lung function in a subject suffering from an allergy comprising administering to a subject a population of cells enriched for STRO-1⁺ cells and/or progeny thereof and/or soluble factors derived therefrom.

Claims

1. A method of treating a respiratory condition in a human subject, the method comprising administering to the human subject a population of human cells enriched for STRO-1^bright mesenchymal precursor cells or progeny thereof.

2. The method of claim 1, wherein the respiratory condition is an acute respiratory condition or a chronic respiratory condition.

3. The method of claim 1, wherein the respiratory condition is an inflammatory respiratory condition, an obstructive respiratory condition or a restrictive respiratory condition.

4. The method of claim 3, wherein the respiratory condition is an obstructive respiratory condition or an inflammatory lung condition.

5. The method of claim 4, wherein the respiratory condition is asthma.

6. The method of claim 5, wherein the asthma is acute asthma, chronic asthma, severe asthma and/or refractory asthma.

7. The method of claim 6, wherein the asthma is long acting beta agonist (LABA) refractory asthma or steroid refractory asthma.

8. The method of claim 5, wherein the asthma is acute asthma.

9. The method of claim 5, wherein the asthma is refractory asthma.

10. The method of claim 3, wherein the respiratory condition is a restrictive respiratory condition.

11. The method of claim 10, wherein the respiratory condition is idiopathic pulmonary fibrosis.

12. The method of claim 1, wherein the condition is allergy to house dust mite allergen (HDM) and the allergen is HDM.

13. The method of claim 1, wherein the population enriched for STRO-1^bright mesenchymal precursor cells or progeny thereof is administered systemically.

14. The method of claim 13, wherein the population enriched for STRO-1^bright mesenchymal precursor cells or progeny thereof is administered intravenously or intranasally.

15. The method of claim 1, wherein the population enriched for STRO-1^bright mesenchymal precursor cells or progeny thereof is administered a plurality of times.

16. The method of claim 1, comprising administering a further dose of the population when one or more of the following occurs:

(i) a subject begins to persistently wheeze and/or cough and/or have chest tightness and/or have difficulty breathing;

(ii) a subject shows one or more of the following when assessed by spirometer;

a) 20% difference on at least three days in a week for at least two weeks;

b)≥

20% improvement of peak flow following treatment with;

10 minutes of inhaled β

-agonist;

six weeks of inhaled corticosteroid;

14 days of 30 mg prednisolone;

c) ≥

20% decrease in peak flow following exposure to a trigger;

(iii) bronchoscopy showing abnormal cells and/or foreign substances and/or blockages in the respiratory tract of a subject;

or

(iv) chest CT scan showing abnormalities of the blood vessels in the lungs, accumulation of blood or fluid in the lungs, bronchiectasis, pleural effusion or pneumonia.

17. The method of claim 1, comprising administering a dose of the population sufficient to achieve one or more of the following:

(i) improved bronchial hyperresponsiveness;

(ii) reduced eosinophil infiltration of the lung or bronchoalveolar lavage fluid;

(iii) reduced neutrophil infiltration of the lung or bronchoalveolar lavage fluid;

(iv) reduced late asthmatic response;

(v) reduced early asthmatic response; and

/or

(vi) reduced lung remodeling/fibrosis.

18. The method of claim 1, comprising administering between 1×

10⁶ to 150×

10⁶ STRO-1^bright mesenchymal precursor cells or progeny thereof.

19. The method of claim 1, comprising administering a whole body dose of STRO-1^bright mesenchymal precursor cells or progeny thereof.

20. The method of claim 19, comprising administering 150×

10⁶ STRO-1^bright mesenchymal precursor cells or progeny thereof in 10 mL to the human subject.

21. The method of claim 1, wherein the population enriched for STRO-1^bright mesenchymal precursor cells or progeny cells is allogeneic.

22. The method of claim 1, wherein the respiratory condition is an IgE-mediated respiratory allergic response to an allergen that causes a respiratory condition in humans.