USE OF ADENOSINE DEAMINASE FOR TREATING PULMONARY DISEASE

• US 20080159964A1
• Filed: 12/28/2007
• Published: 07/03/2008
• Est. Priority Date: 12/29/2006
• Status: Abandoned Application

• Current Assignee: Sigma-Tau Rare Diseases S.A., Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Enzon Pharmaceuticals Inc. (Icahn Associates Holding LLC), Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Horak, Ivan, Blackburn, Michael R., Sapra, Puja
• Application Number:
  US11/965,939
• Publication Number:
  US 20080159964A1
• Time in Patent Office: Days
• US Class Current: 424/45
• CPC Class Codes: A61K 38/50 acting on carbon-nitrogen bonds, other than peptide bonds (3.5), e.g. asparaginase
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: 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
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12Y 305/04004 Adenosine deaminase (3.5.4.4)

Abstract

Provided are methods for treating an adenosine deaminase-mediated pulmonary disease such as asthma, pulmonary fibrosis, cystic fibrosis and chronic obstructive pulmonary disease in a mammal in need thereof, by administering and effective amount of a polymer-conjugated adenosine deaminase.

Claims

1. A method of treating an adenosine deaminase-mediated pulmonary disease, comprising administering an effective amount of adenosine deaminase to a mammal in need thereof.

2. The method of claim 1, wherein the pulmonary disease is mediated with an elevated level of adenosine.

3. The method of claim 1, wherein the pulmonary disease is selected from the group consisting of asthma, pulmonary fibrosis, cystic fibrosis and chronic obstructive pulmonary disease.

4. The method of claim 1, wherein the pulmonary disease is a chemotherapy-mediated pulmonary disease.

5. The method of claim 1 wherein the adenosine deaminase is administered by inhalation or parenterally.

6. The method of claim 1, wherein the adenosine deaminase is administered prophylactically, concurrently or subsequently with a chemotherapeutic agent.

7. The method of claim 1, wherein the adenosine deaminase is conjugated to a polyalkylene oxide.

8. The method of claim 7, wherein the polyalkylene oxide-conjugated adenosine deaminase is administered as an aerosol or as a dry powder.

9. The method of claim 1 wherein the adenosine deaminase is obtained from a bovine source.

10. The method of claim 1 wherein the adenosine deaminase is obtained from a human source.

11. The method of claim 1, wherein the adenosine deaminase is a recombinant adenosine deaminase.

12. The method of claim 7, wherein the polyalkylene oxide ranges in size from about 5,000 Daltons to about 45,000 daltons.

13. The method of claim 7, wherein the polyalkylene oxide comprises a straight, branched or multi-arm chain.

14. The method of claim 7, wherein the polyalkylene oxide is polyethylene glycol.

15. The method of claim 14, wherein the adenosine deaminase conjugated to polyethylene glycol is pegademase bovine.

16. The method of claim 1, wherein the amount of adenosine deaminase administered to the mammal is an amount sufficient to maintain plasma ADA activity in the range of from about 15 to about 35 μ

mol/hr/mL.

17. The method of claim 1, wherein the amount of adenosine deaminase administered to the mammal is an amount sufficient to reduce lung adenosine levels to less than about 10 nmoles per mg protein.

18. The method of claim 17, wherein the amount of adenosine deaminase administered to the mammal is an amount sufficient to reduce lung adenosine levels to less than about 5 nmoles per mg protein.

19. The method of claim 1, further comprising administering an effective dose of a second pharmacologically active agent in combination with the adenosine deaminase.

20. The method of claim 19, wherein the second pharmacologically active agent is theophylline or a bronchodilator.

21. The method of claim 19, wherein the bronchodilator is beta-adrenergic bronchodilator.

22. The method of claim 21, wherein the beta-adrenergic bronchodilator is selected from the group consisting of salmeterol, albuterol or terbutaline.

23. A kit for treating pulmonary disease in mammals, comprising adenosine deaminase and instructions for use in the treatment of pulmonary disease.

24. An inhalable formulation, comprising adenosine deaminase and a bronchodilator.

25. An inhaler suitable for use in the treatment of pulmonary conditions, comprising the inhalable formulation of claim 24 and a propellant.