Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant

US 20030091599A1
Filed: 11/20/2002
Published: 05/15/2003
Est. Priority Date: 03/10/1997
Status: Active Grant

First Claim

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1. A method for treating a subject infected with hepatitis virus comprising:

administering to a subject infected with hepatitis virus, wherein the subject is a non-responder or hypo-responder, an oligonucleotide, having a sequence including at least the following formula;

5′

X₁X₂CGX₃X₄3′

wherein the oligonucleotide includes at least 8 nucleotides wherein c is unmethylated and wherein X₁X₂and X₃X₄are nucleotides, in an effective amount to produce an immune response against the hepatitis virus.

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Abstract

The present invention relates generally to adjuvants, and in particular to methods and products utilizing a synergistic combination of immunostimulatory oligonucleotides having at least one unmethylated CpG dinucleotide (CpG ODN) and a non-nucleic acid adjuvant. Such combinations of adjuvants may be used with an antigen or alone. The present invention also relates to methods and products utilizing immunostimulatory oligonucleotides having at least one unmethylated CpG dinucleotide (CpG ODN) for induction of cellular immunity in infants.

321 Citations

21 Claims

1. A method for treating a subject infected with hepatitis virus comprising:
- administering to a subject infected with hepatitis virus, wherein the subject is a non-responder or hypo-responder, an oligonucleotide, having a sequence including at least the following formula;
  
  5′
  
  X₁X₂CGX₃X₄3′
  
  wherein the oligonucleotide includes at least 8 nucleotides wherein c is unmethylated and wherein X₁X₂and X₃X₄are nucleotides, in an effective amount to produce an immune response against the hepatitis virus.
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21)
- - 2. The method of claim 1, further comprising administering a non-nucleic acid adjuvant.
  - 3. The method of claim 1, further comprising administering an antigen.
  - 4. The method of claim 2, wherein the non-nucleic acid adjuvant is an immune stimulating adjuvant.
  - 5. The method of claim 4, wherein the immune stimulating adjuvant is selected from the group consisting of saponins, PCPP polymer, derivatives of lipopolysaccharides, MPL, MDP, t-MDP, OM-174 and Leishmania elongation factor.
  - 6. The method of claim 2, wherein the non-nucleic acid adjuvant is an adjuvant that creates a depo effect and stimulates the immune system.
  - 7. The method of claim 6, wherein the adjuvant that creates a depo effect and stimulates the immune system is selected from the group consisting of ISCOMS, SB-AS2, SB-AS4, non-ionic block copolymers, and SAF (Syntex Adjuvant Formulation).
  - 8. The method of claim 1, wherein the 5′
    - X₁X₂CGX₃X₄3′
      
      sequence is a non-palindromic sequence.
  - 9. The method of claim 1, wherein the nucleic acid includes a backbone having at least one phosphate backbone modification.
  - 10. The method of claim 9, wherein the phosphate backbone modification is a modification of the first two internucleotide linkages of the 5′
    - end of the nucleic acid.
  - 11. The method of claim 9, wherein the phosphate backbone modification is a modification of the last two internucleotide linkages of the 3′
    - end of the nucleic acid.
  - 12. The method of claim 1, wherein the oligonucleotide is 8 to 100 nucleotides in legnth.
  - 13. The method of claim 9, wherein the phosphate backbone modification is a phosphorothioate or phosphorodithioate modification.
  - 14. The method of claim 1, wherein X₁X₂are nucleotides selected from the group consisting of:
    - GpT, GpG, GpA, ApA, ApT, ApG, CpT, CpA, CpG, TpA, TpT, and TpG; and
      
      X₃X₄are nucleotides selected from the group consisting of;
      
      TpT, CpT, ApT, TpG, ApG, CpG, TpC, ApC, CpC, TpA, ApA, and CpA.
  - 15. The method of claim 1, wherein X₁X₂are selected from the group consisting of GpA and GpT and X₃X₄are TpT.
  - 16. The method of claim 1, wherein X₁X₂are both purines and X₃X₄are both pyrimidines.
  - 17. The method of claim 1, wherein X₂is a T and X₃is a pyrimidine.
  - 18. The method of claim 1, wherein the oligonucleotide is 8 to 40 nucleotides in length.
  - 19. The method of claim 1, wherein the oligonucleotide is a synthetic oligonucleotide.
  - 20. The method of claim 1, wherein the hepatitis virus is hepatitis B.
  - 21. The method of claim 1, wherein the hepatitis virus is hepatitis C.

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Current Assignee
Ottawa Hospital Research Institute (Ottawa Hospital), University of Iowa Research Foundation
Original Assignee
Coley Pharmaceutical GmbH (Pfizer Inc.)
Inventors
Krieg, Arthur M., Davis, Heather L., Schorr, Joachim

Granted Patent

US 8,202,688 B2
Time in Patent Office

Days
Field of Search
US Class Current

424/278.1
CPC Class Codes

A61K 2039/523   expressing foreign proteins

A61K 2039/53   DNA (RNA) vaccination

A61K 2039/55505   Inorganic adjuvants

A61K 2039/5555   Muramyl dipeptides

A61K 2039/55561   CpG containing adjuvants; O...

A61K 2039/55566   Emulsions, e.g. Freund's ad...

A61K 2039/55572   Lipopolysaccharides; Lipid ...

A61K 2039/57   characterised by the type o...

A61K 39/12   Viral antigens

A61K 39/292   Serum hepatitis virus, hepa...

A61K 39/39   characterised by the immuno...

C12N 2730/10134   Use of virus or viral compo...

Y02A 50/30   Against vector-borne diseas...

Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant

First Claim

6 Assignments

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Abstract

321 Citations

21 Claims

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Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant

First Claim

6 Assignments

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0 Petitions

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Accused Products

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Abstract

321 Citations

21 Claims

Specification

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Solutions

Use Cases

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