IMMUNOSTIMULATORY NUCLEIC ACIDS

• US 20090191188A1
• Filed: 02/26/2009
• Published: 07/30/2009
• Est. Priority Date: 09/25/1999
• Status: Abandoned Application

• Current Assignee: Coley Pharmaceutical GmbH (Pfizer Inc.), University of Iowa Research Foundation
• Original Assignee: Coley Pharmaceutical GmbH (Pfizer Inc.), University of Iowa Research Foundation
• Inventors: Schetter, Christian, Krieg, Arthur M., Vollmer, Jorg
• Application Number:
  US12/393,866
• Publication Number:
  US 20090191188A1
• Time in Patent Office: Days
• US Class Current: 424/130.1
• CPC Class Codes: A61K 2039/55561 CpG containing adjuvants; Oligonucleotide containing adjuvants
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• 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: A61K 31/7125 Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
• CPC Class Codes: A61K 39/39 characterised by the immunostimulating additives, e.g. chemical adjuvants
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14

Abstract

The invention relates to immunostimulatory nucleic acid compositions and methods of using the compositions. The T-rich nucleic acids contain poly T sequences and/or have greater than 25% T nucleotide residues. The TG nucleic acids have TG dinucleotides. The C-rich nucleic acids have at least one poly-C region and/ore greater than 50% c nucleotides. These immunostimulatory nucleic acids function in a similar manner to nucleic acids containing CpG motifs. The invention also encompasses preferred CpG nucleic acids.

Claims

1. A method of stimulating an immune response comprising

administering an immunostimulatory nucleic acid to a non-rodent subject in an amount effective to induce an immune response in the non-rodent subject, wherein the immunostimulatory nucleic acid is greater than 60% T, contains a CpG dinucleotide, and is 8-100 nucleotides in length.

3. The method of claim 1, wherein the immunostimulatory nucleic acid is a poly T nucleic acid comprising

5′

TTTT3′

.

4. The method of claim 3, wherein the poly T nucleic acid comprises

5′

X₁X₂TTTTX₃X₄3′

wherein X₁, X₂, X₃ and X₄ are nucleotides.

5. The method of claim 3, wherein the immunostimulatory nucleic acid comprises a plurality of poly T nucleic acid motifs.

6. The method of claim 4, wherein X₁X₂ is TT.

7. The method of claim 4, wherein X₃X₄ is TT.

15. The method of claim 1, wherein the immunostimulatory nucleic acid comprises a nucleotide composition of greater than 80% T.

18. The method of claim 1, wherein the immunostimulatory nucleic acid has a nucleotide backbone which includes at least one backbone modification.

19. The method of claim 18, wherein the backbone modification is a phosphorothioate modification.

20. The method of claim 18, wherein the nucleotide backbone is chimeric.

21. The method of claim 18, wherein the nucleotide backbone is entirely modified.

34. The method of claim 1, wherein the immune response is a mucosal immune response.

35. The method of claim 1, wherein the immune response is a systemic immune response.

37. The method of claim 1, further comprising exposing the subject to an antigen and wherein the immune response is an antigen-specific immune response.

52. The method of claim 1, wherein the subject is a human.

54. The method of claim 1, further comprising administering an antibody specific for a cell surface antigen, and wherein the immune response results in antigen dependent cellular cytotoxicity (ADCC).

76. The method of claim 1, wherein the immunostimulatory nucleic acid is administered on a regular basis.

77. The method of claim 1, wherein the immune response is an innate immune response.

95. A pharmaceutical composition comprising an effective amount for stimulating an immune response of an isolated the immunostimulatory nucleic acid of claim 1, and a pharmaceutically acceptable carrier.

96. A composition of matter, comprising the immunostimulatory nucleic acid of claim 1, and a pharmaceutically acceptable carrier.

2. (canceled)

8-14. -14. (canceled)

16-17. -17. (canceled)

22-33. -33. (canceled)

36. (canceled)

38-51. -51. (canceled)

53. (canceled)

55-75. -75. (canceled)

78. A composition comprising

a sustained release device including an immunostimulatory nucleic acid, wherein the immunostimulatory nucleic acid is free of unmethylated CpG motifs and is a T-rich nucleic acid.

79. (canceled)

80. A composition of a nutritional supplement comprising

an immunostimulatory nucleic acid in a delivery device selected from the group consisting of a capsule, a pill, and a sublingual tablet, wherein the immunostimulatory nucleic acid is free of unmethylated CpG motifs and is a T-rich nucleic acid.

81. (canceled)

82. A composition comprising

an immunostimulatory nucleic acid and an antigen, wherein the immunostimulatory nucleic acid is free of unmethylated CpG motifs and is a T-rich nucleic acid.

83. A composition comprising

an immunostimulatory nucleic acid and another therapeutic agent selected from the group consisting of:

an anti-microbial agent, an anti-cancer agent, an asthma/allergy medicament, wherein the immunostimulatory nucleic acid is free of unmethylated CpG motifs and is a T-rich nucleic acid.

84-94. -94. (canceled)

97-101. -101. (canceled)

102. A composition comprising

an immunostimulatory nucleic acid consisting essentially of:

5′

M₁TCGTCGTTM₂3′

wherein at least one of the Cs is unmethylated, wherein M₁ is a nucleic acid having at least one nucleotide, wherein M₂ is a nucleic acid having between 0 and 50 nucleotides, and wherein the immunostimulatory nucleic acid has less than 100 nucleotides.

103. A pharmaceutical composition comprising

an immunostimulatory nucleic acid comprising:

5′

TCGTCGTT3′

wherein at least one of the Cs is unmethylated, wherein the immunostimulatory nucleic acid has less than 100 nucleotides and a phosphodiester backbone,

and a sustained release device.

104-106. -106. (canceled)