ANTIVIRAL OLIGONUCLEOTIDES TARGETING VIRAL FAMILIES

• US 20090156527A1
• Filed: 04/09/2008
• Published: 06/18/2009
• Est. Priority Date: 09/13/2002
• Status: Active Grant

• Current Assignee: Replicor Inc.
• Original Assignee: Replicor Inc.
• Inventors: VAILLANT, Andrew, JUTEAU, Jean-Marc
• Granted Patent: US 8,008,270 B2
• Time in Patent Office: Days
• US Class Current: 514/44.R
• 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. A method for the prophylaxis or treatment of a viral infection in a subject, comprising administering to a subject in need of such treatment a therapeutically effective amount of at least one pharmacologically acceptable phosphorothioated oligonucleotide at least 30 nucleotides in length, wherein the anti-viral activity of said oligonucleotide occurs principally by a non-sequence complementary mode of action, and wherein the virus is different from HIV-1 and HIV-2.

2. The method of claim 1, wherein said oligonucleotide comprises a homopolymer sequence of at least 10 contiguous nucleotides selected from the group consisting of A, C, G, T, and any other synthetic or naturally-occurring base.

3. The method of claim 1, wherein said oligonucleotide is a homopolymer comprising nucleotides selected from the group consisting of A, C, T, and any other synthetic or naturally-occurring base.

4. The method of claim 1, wherein said oligonucleotide comprises a sequence of at least 10 contiguous nucleotides wherein said sequence is a repetitive sequence that alternates between two different nucleotides selected from the group consisting of A, T, G, C, and any other synthetic or naturally-occurring base.

5. The method of claim 1, wherein the entire sequence of said oligonucleotide is a repetitive sequence that alternates between two different nucleotides selected from the group consisting of A, T, G, C and any other synthetic or naturally-occurring base

6. The method of claim 1, wherein said oligonucleotide comprises at least one additional modification other than a phosphorothioation to its chemical structure.

7. The method of claim 1, wherein said oligonucleotide comprises at least one 5-methylcytosine

8. The method of claim 1, wherein said oligonucleotide comprises at least one modification selected from the group consisting of 2′

-O-methyl, 2′

-methoxyethyl and 2′

-fluoro.

9. The method of claim 1, wherein the sequence said oligonucleotide is not complementary to any equal length portion of a viral genome sequence or viral mRNA over the entire length of said equal length portion.