Immunostimulatory nucleic acids for the treatment of asthma and allergy

• US 20030087848A1
• Filed: 02/02/2001
• Published: 05/08/2003
• Est. Priority Date: 02/03/2000
• Status: Active Grant

• Current Assignee: Deanna M. Petersen, Robert L. Bratzler, Yves Fouron
• Original Assignee: Coley Pharmaceutical Group, Inc. (Pfizer Inc.)
• Inventors: Bratzler, Robert L., Petersen, Deanna M., Fouron, Yves
• Granted Patent: US 7,585,847 B2
• Time in Patent Office: Days
• US Class Current: 514/44
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/473 ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/557 Eicosanoids, e.g. leukotrienes or prostaglandins
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61K 31/7105 Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• CPC Class Codes: C12N 15/117 Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
• CPC Class Codes: C12N 2310/17 Immunomodulatory nucleic acids
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2320/31 Combination therapy

Abstract

The invention involves administration of an immunostimulatory nucleic acid alone or in combination with an asthma/allergy medicament for the treatment or prevention of asthma and allergy in subjects. The combination of drugs are administered in synergistic amounts or in various dosages or at various time schedules. The invention also relates to kits and compositions concerning the combination of drugs.

Claims

1. A method for treating or preventing allergy or asthma, comprising

administering to a subject a poly-G nucleic acid in an effective amount for treating or preventing allergy or asthma.

2. The method of claim 1, wherein the poly-G nucleic acid comprises the following formula:

5′

X₁X₂GGGX₃X₄3′

wherein X₁, X₂, X₃, and X4 are nucleotides.

3. The method of claim 2, wherein at least one of X₃ and X₄ are a G.

4. The method of claim 2, wherein both of X₃ and X₄ are a G.

5. The method of claim 1, wherein the poly-G nucleic acid comprises the following formula:

5′

GGGNGGG 3′

wherein N represents between 0 and 20 nucleotides.

6. The method of claim 1, wherein the poly-G nucleic acid comprises the following formula:

5′

GGGNGGGNGGG 3′

wherein N represents between 0 and 20 nucleotides.

7. The method of claim 1, wherein the poly-G nucleic acid is free of unmethylated CG dinucleotides

8. The method of claim 7, wherein the poly-G nucleic acid is selected from the group consisting of SEQ ID NO 95-133.

9. The method of claim 1, wherein the poly-G nucleic acid includes at least one unmethylated CG dinucleotide.

10. The method of claim 9, wherein the poly-G nucleic acid is selected from the group consisting of SEQ ID NO:

46, SEQ ID NO;

47, SEQ ID NO;

58, and SEQ ID NO;

61.

11. A composition comprising a poly-G nucleic acid in an aerosol formulation.

12. A method for treating or preventing asthma or allergy in a hypo-responsive subject, comprising:

administering to a hypo-responsive subject having asthma or allergy or at risk of developing asthma or allergy an immunostimulatory nucleic acid in an effective amount for treating or preventing asthma or allergy.

13. The method of claim 12, wherein the hypo-responsive subject is hypo-responsive to an asthma/allergy medicament.

14. The method of claim 12, wherein the hypo-responsive subject is selected from the group consisting of a subject who is refractory to an asthma/allergy medicament, a subject who is a non-responder to an asthma/allergy medicament, an elderly subject and a neonatal subject.

15. The method of claim 12, wherein the immunostimulatory nucleic acid has a modified backbone.

16. The method of claim 15, wherein the modified backbone is a phosphate modified backbone.

17. The method of claim 16, wherein the phosphate modified backbone is a phosphorothioate modified backbone.

18. The method of claim 12, wherein the immunostimulatory nucleic acid is a CpG nucleic acid.

19. The method of claim 18, wherein the immunostimulatory nucleic acid is a T-rich nucleic acid.

20. The method of claim 18, wherein the immunostimulatory nucleic acid is a poly-G nucleic acid.

21. The method of claim 12, further comprising administering to the hypo-responsive subject an asthma/allergy medicament.

22. The method of claim 21, wherein the asthma/allergy medicament is administered in a sub-therapeutic amount.

23. The method of claim 21, wherein the asthma/allergy medicament is an asthma medicament.

24. The method of claim 21, wherein the asthma/allergy medicament is an allergy medicament.

25. The method of claim 21, wherein the asthma/allergy medicament is selected from the group consisting of a steroid and an immunomodulator.

26. The method of claim 25, wherein the steroid is selected from the group consisting of beclomethasone, fluticasone, tramcinolone, budesonide, and budesonide.

27. The method of claim 25, wherein the immunomodulator is selected from the group consisting of an anti-inflammatory agent, a leukotriene antagonist, an IL-4 mutein, a soluble IL-4 receptor, an immunosuppressant, anti-IL-4 antibody, an IL-4 antagonist, an anti-IL-5 antibody, a soluble IL-13 receptor-Fc fusion protein, an anti-IL-9 antibody, a CCR3 antagonist, a CCR5 antagonist, a VLA-4 inhibitor, and a downregulator of IgE.

28. The method of claim 27, wherein the downregulator of IgE is an anti-Ig antibody or a fragment thereof.

29. The method of claim 27, wherein the immunosuppressant is a tolerizing peptide vaccine.

30. The method of claim 21, wherein the asthma/allergy medicament is a medicament selected from the group consisting of a PDE-4 inhibitor, a bronchodilator/beta-2 agonist, a K⁺ channel opener, a VLA-4 antagonist, a neurokin antagonist, a TXA2 synthesis inhibitor, Xanthanine, an arachidonic acid antagonist, a 5 lipoxygenase inhibitor, a thromboxin A2 receptor antagonist, a thromboxane A2 antagonist, an inhibitor of 5-lipox activation protein, and a protease inhibitor.

31. The method of claim 30, wherein the bronchodilator/beta-2 agonist is selected from the group consisting of salmeterol, salbutamol, terbutaline, D2522/formoterol, fenoterol and orciprenaline.

32. The method of claim 21, wherein the asthma/allergy medicament is a medicament selected from the group consisting of an anti-histamine and a prostaglandin inducer.

33. The method of claim 32, wherein the anti-histamine is selected from the group consisting of loratidine, cetirizine, buclizine, ceterizine analogues, fexofenadine, terfenadine, desloratadine, norastemizole, epinastine, ebastine, ebastine, astemizole, levocabastine, azelastine, tranilast, terfenadine, mizolastine, betatastine, CS 560 and HSR 609.

34. The method of claim 32, wherein the prostaglandin inducer is S-5751.

35. The method of claim 21, wherein the immunostimulatory nucleic acid is administered concurrently with the asthma/allergy medicament.

36. A method for preventing asthma or allergy in a subject at risk of developing asthma or allergy, comprising:

administering to a subject at risk of developing asthma or allergy an effective amount of an immunostimulatory nucleic acid substantially prior to an asthmatic or an allergic event.