Immunostimulatory nucleic acid molecules

• US 20030050261A1
• Filed: 03/27/2001
• Published: 03/13/2003
• Est. Priority Date: 07/15/1994
• Status: Abandoned Application

• Current Assignee: Health and Human Services United States of America As Represented By The SEC, University of Iowa Research Foundation
• Original Assignee: Health and Human Services United States of America As Represented By The SEC
• Inventors: Krieg, Arthur M., Klinman, Dennis, Steinberg, Alfred D., Kline, Joel
• Application Number:
  US09/818,918
• Publication Number:
  US 20030050261A1
• Time in Patent Office: Days
• US Class Current: 514/44
• CPC Class Codes: A61K 2039/55561 CpG containing adjuvants; Oligonucleotide containing adjuvants
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/4706 4-Aminoquinolines; 8-Aminoquinolines, e.g. chloroquine, primaquine
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 31/711 Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
• CPC Class Codes: A61K 31/7125 Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• 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 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 33/00 : Antiparasitic agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/04 : Immunostimulants
• 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 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: C07H 21/00 : Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• 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: C12Q 1/68 : involving nucleic acids
• 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

Nucleic acids containing unmethylated CpG dinucleotides and therapeutic utilities based on their ability to stimulate an immune response and to redirect a Th2 response to a Th1 response in a subject are disclosed. Methods for treating atopic diseases, including atopic dermatitis, are disclosed.

Claims

1. A method for treating an atopic condition, comprising administering to a subject in need of treatment of an atopic condition an immunostimulatory nucleic acid, comprising:

5′

X₁CGX₂ 3′

wherein the immunostimulatory nucleic acid includes at least 8 nucleotides and wherein c is unmethylated and wherein X₁ and X₂ are nucleotides, in an effective amount to treat the atopic condition;

2. The method of claim 1, wherein the atopic condition is atopic dermatitis.

3. The method of claim 1, wherein X₁ is selected from the group consisting of A, G, and T, and wherein X₂ is selected from the group consisting of C and T.

4. The method of claim 1, further comprising administering to the subject an allergen in conjunction with the administering of the immunostimulatory nucleic acid.

5. The method of claim 1, wherein the immunostimulatory nucleic acid comprises

5′ X₁X₂CGX₃X₄ 3′

wherein C is unmethylated and wherein X₁, X₂, X₃, and X₄ are nucleotides.

6. The method of claim 5, wherein X₁X₂ is selected from the group consisting of GpT, GpG, GpA and ApA.

7. The method of claim 5, wherein X₃X₄ is selected from the group consisting of TpT and CpT.

8. The method of claim 5, wherein X₁X₂ is selected from the group consisting of GpT, GpG, GpA and ApA and wherein X₃X₄ is selected from the group consisting of TpT and CpT.

9. The method of claim 5, wherein 5′

X₁X₂CGX₃X₄ 3′

is not a palindrome.

10. The method of claim 5, wherein the immunostimulatory nucleic acid comprises a sequence selected from the group consisting of

11. The method of claim 1, wherein the immunostimulatory nucleic acid is a synthetic nucleic acid molecule.

12. The method of claim 1, wherein the immunostimulatory nucleic acid is 8 to 100 nucleotides in length.

13. The method of claim 1, wherein the immunostimulatory nucleic acid is 8 to 40 nucleotides in length.

14. The method of claim 1, wherein the immunostimulatory nucleic acid is a stabilized nucleic acid molecule.

15. The method of claim 14, wherein the immunostimulatory nucleic acid includes a phosphate backbone modification which is a phosphorothioate or phosphorodithioate modification.

16. The method of claim 1, wherein the immunostimulatory nucleic acid is administered to the subject orally.

17. The method of claim 1, wherein the immunostimulatory nucleic acid is administered to the subject transdermally.

18. The method of claim 1, wherein the immunostimulatory nucleic acid is administered to the subject by injection.