Immunostimulatory nucleic acids

• US 8,283,328 B2
• Filed: 08/19/2003
• Issued: 10/09/2012
• Est. Priority Date: 08/19/2002
• Status: Active Grant

• Current Assignee: Coley Pharmaceutical GmbH (Pfizer Inc.)
• Original Assignee: Coley Pharmaceutical GmbH (Pfizer Inc.), Coley Pharmaceutical Group, Inc. (Pfizer Inc.)
• Inventors: Krieg, Arthur M., Lipford, Grayson, Samulowitz, Ulrike, Vollmer, Jörg, Uhlmann, Eugen, Rankin, Robert, Jurk, Marion
• Primary Examiner(s): Minnifield, Nita M
• Assistant Examiner(s): Archie, Nina
• Application Number:
  US10/644,052
• Publication Number:
  US 20050059619A1
• Time in Patent Office: 3,339 Days
• Field of Search: None
• US Class Current: 514/44.R
• CPC Class Codes: A61K 2039/55561 CpG containing adjuvants; Oligonucleotide containing adjuvants
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial 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: C07H 19/00 Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
• 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: C07H 21/02 with ribosyl as saccharide radical
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical
• CPC Class Codes: C12N 15/117 Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
• CPC Class Codes: C12N 2310/312 Phosphonates
• CPC Class Codes: C12N 2310/3125 Methylphosphonates
• CPC Class Codes: C12N 2310/313 : Phosphorodithioates
• CPC Class Codes: C12N 2310/315 : Phosphorothioates
• CPC Class Codes: C12N 2310/336 : Modified G
• CPC Class Codes: C12N 2310/345 : having at least two different backbone modifications

Abstract

The invention relates to a class of soft or semi-soft CpG immunostimulatory oligonucleotides that are useful for stimulating an immune response.

Claims

1. An oligonucleotide having the following structure:

2. The oligonucleotide of claim 1, wherein the oligonucleotide consists essentially of 5′

3. The oligonucleotide of claim 1, wherein the oligonucleotide consists of

5. A pharmaceutical composition comprising an oligonucleotide as defined in claim 1 and a pharmaceutically acceptable carrier.

4. An oligonucleotide having the following structure:

6. A pharmaceutical composition comprising an oligonucleotide as defined in claim 4 and a pharmaceutically acceptable carrier.

7. An immunostimulatory oligonucleotide having at least two internal cytosine-guanine (CG) dinucleotides, wherein C is unmethylated cytidine, and G is guanosine, wherein the at least two internal CG dinucleotides have phosphodiester internucleotide linkages, wherein optionally each additional internal CG dinucleotide has a phosphodiester or stabilized internucleotide linkage, wherein all other internucleotide linkages are stabilized with a phosphorothioate internucleotide linkage, and wherein the immunostimulatory oligonucleotide is 6-100 nucleotides long.

8. The oligonucleotide of claim 7, wherein the immunostimulatory oligonucleotide comprises a plurality of internal CG dinucleotides having a phosphodiester internucleotide linkage.

9. The oligonucleotide of claim 7, wherein the immunostimulatory oligonucleotide is a B-Class immunostimulatory oligonucleotide.

10. The oligonucleotide of claim 7, wherein the immunostimulatory oligonucleotide is not an antisense oligonucleotide, triple-helix-forming oligonucleotide, or ribozyme.

11. The oligonucleotide of claim 7, wherein the oligonucleotide has a backbone comprising deoxyribose or ribose.