Immunostimulatory nucleic acids for the treatment of asthma and allergy

• US 7,585,847 B2
• Filed: 02/02/2001
• Issued: 09/08/2009
• Est. Priority Date: 02/03/2000
• Status: Expired due to Fees

• Current Assignee: Coley Pharmaceutical Group, Inc. (Pfizer Inc.)
• Original Assignee: Coley Pharmaceutical Group, Inc. (Pfizer Inc.)
• Inventors: Fouron, Yves, Bratzler, Robert L., Petersen, Deanna M.
• Primary Examiner(s): MINNIFIELD, NITA M
• Application Number:
  US09/776,479
• Publication Number:
  US 20030087848A1
• Time in Patent Office: 3,140 Days
• Field of Search: 514/44, 536/23.1, 536/23.5, 536/24.5, 424/275.1
• US Class Current: 514/44.00R
• 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 an asthmatic event in a hypo-responsive subject having allergic asthma, comprising:

administering to a hypo-responsive subject having allergic asthma a CpG immunostimulatory nucleic acid having the formula

5′

N₁X₁X₂CGX₃X₄N₂ 3′

wherein the cytosine of the CG dinucleotide is unmethylated, X₁ and X₂ are both purines and X₃ and X₄ are both pyrimidines, and N₁ and N₂ are nucleic acid sequences composed of 0-25 nucleotides each, in an effective amount for treating an asthmatic event,

wherein the hypo-responsive subject is refractory to an asthma/allergy medicament, and

wherein the CpG immunostimulatory nucleic acid is 8-100 nucleotides.

2. The method of claim 1, wherein the immunostimulatory nucleic acid has a modified backbone.

3. The method of claim 2, wherein the modified backbone is a phosphate modified backbone.

4. The method of claim 3, wherein the phosphate modified backbone is a phosphorothioate modified backbone.

5. The method of claim 1, further comprising administering to the hypo-responsive subject an asthma/allergy medicament.

6. The method of claim 5, wherein the asthma/allergy medicament is administered in a sub-therapeutic amount.

7. The method of claim 5, wherein the asthma/allergy medicament is an asthma medicament.

8. The method of claim 5, wherein the asthma/allergy medicament is an allergy medicament.

9. The method of claim 5, wherein the asthma/allergy medicament is selected from the group consisting of a steroid and an immunomodulator.

10. The method of claim 9, wherein the steroid is selected from the group consisting of beclomethasone, fluticasone, tramcinolone, budesonide and budesonide.

11. The method of claim 9, 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, an 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.

12. The method of claim 11, wherein the downregulator of IgE is an anti-Ig antibody or a fragment thereof.

13. The method of claim 11, wherein the immunosuppressant is a tolerizing peptide vaccine.

14. The method of claim 5, 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 thromboxane A2 synthesis inhibitor, xanthanine, an arachidonic acid antagonist, a 5 lipoxygenase inhibitor, a thromboxane A2 receptor antagonist, a thromboxane A2 antagonist, an inhibitor of 5-lipox activation protein and a protease inhibitor.

15. The method of claim 14, wherein the bronchodilator/beta-2 agonist is selected from the group consisting of salmeterol, salbutamol, terbutaline, D2522/formoterol, fenoterol and orciprenaline.

16. The method of claim 5, wherein the asthma/allergy medicament is a medicament selected from the group consisting of an anti-histamine and a prostaglandin inducer.

17. The method of claim 16, wherein the anti-histamine is selected from the group consisting of loratidine, cetirizine, buclizine, a ceterizine analogue, fexofenadine, terfenadine, desloratadine, norastemizole, epinastine, ebastine, ebastine, astemizole, levocabastine, azelastine, tranilast, terfenadine, mizolastine, betatastine, CS 560 and HSR 609.

18. The method of claim 16, wherein the prostaglandin inducer is S-5751.

19. The method of claim 5, wherein the immunostimulatory nucleic acid is administered concurrently with the asthma/allergy medicament.

20. The method of claim 1, wherein X₁X₂ are GA.

21. The method of claim 20, wherein X₃X₄ are TT.