Antiviral oligonucleotides

• US 20090099110A1
• Filed: 02/28/2008
• Published: 04/16/2009
• Est. Priority Date: 09/13/2002
• Status: Active Grant

• Current Assignee: Replicor Inc.
• Original Assignee: Replicor Inc.
• Inventors: Juteau, Jean-Marc, Vaillant, Andrew
• Granted Patent: US 8,008,269 B2
• Time in Patent Office: Days
• US Class Current: 514/44.00R
• 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 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C12N 15/11 DNA or RNA fragments; Modified forms thereof DNA or RNA not used in recombinant technology, C07H21/00; Non-coding nucleic acids having a biological activity
• CPC Class Codes: C12N 15/115 Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith ; Nucleic acids binding to non-nucleic acids, e.g. aptamers
• CPC Class Codes: C12N 2310/3125 Methylphosphonates
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/351 Conjugate
• CPC Class Codes: C12N 2310/3521 Methyl
• 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

Random sequence oligonucleotides that have antiviral activity are described, along with their use as antiviral agents. In many cases, the oligonucleotides are greater than 40 nucleotides in length. Also described are methods for the prophylaxis or treatment of a viral infection in a human or animal, and a method for the prophylaxis treatment of cancer caused by oncoviruses in a human or animal. The methods typically involve administering to a human or animal in need of such treatment, a pharmacologically acceptable, therapeutically effective amount of at least oligonucleotide that does not act by a sequence complementary mode of action.

Claims

1. An antiviral oligonucleotide formulation comprising at least one antiviral oligonucleotide, wherein said oligonucleotide:

i) comprises at least one phosphorothioate linkage;

ii) is at least 29 nucleotides in length;

iii) is not complementary to any portion of a genome sequence of a virus; and

iv) is not complementary to a viral mRNA;

wherein the antiviral activity of said oligonucleotide occurs principally by a non-sequence complementary mode of action.

2. The oligonucleotide formulation of claim 1, wherein said oligonucleotide further:

v) comprises bases selected from the group consisting of A, C, T and U;

vi) does not form hairpins; and

vii) does not contain palindromic sequences.

3. The oligonucleotide formulation of claim 2, wherein said oligonucleotide is at least 35 nucleotides in length.

4. The oligonucleotide formulation of claim 2, wherein said oligonucleotide is at least 40 nucleotides in length.

5. The oligonucleotide formulation of claim 2, wherein said oligonucleotide comprises at least one 5-methylcytosine.

6. The oligonucleotide formulation of claim 2, wherein said oligonucleotide comprises at least one other modification to its chemical structure.

7. The oligonucleotide formulation of claim 2, wherein said oligonucleotide targets a DNA virus.

8. The oligonucleotide formulation of claim 2, wherein said oligonucleotide targets a RNA virus.

9. The oligonucleotide formulation of claim 2, wherein said oligonucleotide is double stranded.

10. The oligonucleotide formulation of claim 2 wherein said formulation further comprises a delivery system.

11. The oligonucleotide formulation of claim 2, wherein said oligonucleotide binds to one or more viral components.

12. An antiviral pharmaceutical composition comprising a therapeutically effective amount of at least one pharmacologically acceptable antiviral oligonucleotide formulation according to claim 2;

and a pharmaceutically acceptable carrier.

13. The antiviral pharmaceutical composition of claim 12, adapted for delivery by a mode selected from the group consisting of intraocular injection, oral ingestion, enteral application, inhalation, topical application, subcutaneous injection, intramuscular injection, intraperitoneal injection, intrathecal injection, intratrachael injection, and intravenous injection.

14. A kit comprising at least antiviral oligonucleotide formulation according to claim 2 in a labeled package and the label on said package indicates that said antiviral oligonucleotide can be used against at least one virus.

15. The kit of claim 14, wherein said kit is approved by a regulatory agency for use in humans.