Oligodeoxynucleotide and its use to induce an immune response

• US 6,977,245 B2
• Filed: 02/06/2002
• Issued: 12/20/2005
• Est. Priority Date: 04/12/1999
• Status: Expired due to Term

• Current Assignee: Uniformed Services University of the Health Sciences (Government of the United States of America)
• Original Assignee: United States Department Of Health And Human Services
• Inventors: Klinman, Dennis, Gursel, Mayda, Verthelyi, Daniela, Ishii, Ken, Mond, James J.
• Primary Examiner(s): Nguyen, Dave Trong
• Application Number:
  US10/068,160
• Publication Number:
  US 20030060440A1
• Time in Patent Office: 1,413 Days
• Field of Search: 536/23.1, 536/25.5, 536/25.6, 514/44
• US Class Current: 514/44.00R
• CPC Class Codes: A61K 2039/55561 CpG containing adjuvants; Oligonucleotide containing adjuvants
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 39/008 Leishmania antigens
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61P 33/02 Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical
• 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

D type CpG oligodeoxynucleotides are provided herein that include a sequence represented by the following formula:
5′X₁X₂X₃Pu₁ Py₂ CpG Pu₃ Py₄ X₄X₅X₆(W)_M(G)_N-3′
wherein the central CpG motif is unmethylated, Pu is a purine nucleotide, Py is a pyrimidine nucleotide, X and W are any nucleotide, M is any integer from 0 to 10, and N is any integer from 4 to 10. Methods of using these oligodeoxynucleotides to induce an immune response are provided.

Claims

1. A substantially pure or isolated oligodeoxynucleotide of between 18 and 30 nucleotides in length, comprising any one of

5′

View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)

2. The stabilized oligodeoxynucleotide of claim 1, wherein the oligodeoxynucleotide is modified to prevent degradation.

3. The stabilized oligodeoxynucleotide of claim 1, wherein the oligodeoxynucleotide has a phosphate backbone modification.

4. The stabilized oligodeoxynucleotide of claim 3, wherein the phosphate backbone modification is a phosphorothioate backbone modification.

5. An oligodeoxynucleotide delivery complex comprising the stabilized oligodeoxynucleotide of claim 1, and a targeting moiety.

6. The stabilized oligodeoxynucleotide delivery complex of claim 5, wherein the targeting moiety is selected from the group consisting of a cholesterol, a virosome, a liposome, a lipid, and a target cell specific binding agent.

7. The oligodeoxynucleotide of delivery complex of claim 5, wherein the stabilized oligodeoxynucleotide and the targeting moiety are covalently linked.

8. A pharmacological composition comprising the stabilized oligodeoxynucleotide of claim 1, and a pharmacologically acceptable carrier.

9. The stabilized oligodeoxynucleotide of claim 1, wherein the stabilized oligonucleotide comprises at least one phosphodiester base.

10. The stabilized oligodeoxynucleotide of claim 9, wherein the stabilized oligonucleotide comprises a plurality of phosphodiester bases.

11. The stabilized oligodeoxynucleotide of claim 9, wherein the stabilized oligonucleotide comprises one or more phosphorothioate bases.

12. The stabilized oligodeoxynucleotide of claim 9, wherein the stabilized oligonucleotide comprises a plurality of phosphorothioate bases.

13. The stabilized oligodeoxynucleotide of claim 1, further comprising at least one additional G in the 5′

far flanking region.