Antisense antiviral compound and method for treating ss/RNA viral infection

• US 10,479,996 B2
• Filed: 11/06/2014
• Issued: 11/19/2019
• Est. Priority Date: 09/16/2004
• Status: Active Grant

• Current Assignee: Sarepta Therapeutics, Inc.
• Original Assignee: Sarepta Therapeutics, Inc.
• Inventors: Iversen, Patrick L., Stein, David A., Weller, Dwight D.
• Primary Examiner(s): Krishnan, Ganapathy
• Application Number:
  US14/535,092
• Publication Number:
  US 20150267202A1
• Time in Patent Office: 1,839 Days
• Field of Search: 514 44, 530322, 536 245
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: C07K 19/00 Hybrid peptides , i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
• CPC Class Codes: C12N 15/111 General methods applicable to biologically active non-coding nucleic acids
• CPC Class Codes: C12N 15/1131 against viruses
• CPC Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: C12N 2310/314 Phosphoramidates
• CPC Class Codes: C12N 2310/3233 Morpholino-type ring
• CPC Class Codes: C12N 2310/3513 Protein; Peptide
• CPC Class Codes: C12N 2310/531 Stem-loop; Hairpin
• CPC Class Codes: C12N 2320/11 for the determination of target sites, i.e. of active nucleic acids
• CPC Class Codes: C12N 2770/00011 Details
• CPC Class Codes: C12N 2770/10011 Arteriviridae
• CPC Class Codes: C12N 2770/12011 Astroviridae
• CPC Class Codes: C12N 2770/16011 Caliciviridae
• CPC Class Codes: C12N 2770/20011 Coronaviridae
• CPC Class Codes: C12N 2770/24011 Flaviviridae
• CPC Class Codes: C12N 2770/28011 Hepeviridae
• CPC Class Codes: C12N 2770/32011 Picornaviridae
• CPC Class Codes: C12N 2770/36011 Togaviridae
• 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

The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Flaviviridae, Picornaviridae, Caliciviridae, Togaviridae, Arteriviridae, Coronaviridae, Astroviridae and Hepeviridae families in the treatment of a viral infection. The antisense antiviral compounds are substantially uncharged morpholino oligonucleotides having a sequence of 12-40 subunits, including at least 12 subunits having a targeting sequence that is complementary to a region associated with stem-loop secondary structure within the 5′-terminal end 40 bases of the positive-sense RNA strand of the virus.

Claims

1. A morpholino subunit of formula:

2. The morpholino subunit of claim 1, wherein Rⁱ is trifluoroacetyl.

3. The morpholino subunit of claim 1, wherein R² is trityl.

4. The morpholino subunit of claim 1, wherein R² is 4-methoxytrityl.

5. The morpholino subunit of claim 1, wherein Z is chloro.

6. The morpholino subunit of claim 1, wherein B is adenine, cytosine, guanine, uracil, thymine, or hypoxanthine.

7. The morpholino subunit of claim 1, wherein B comprises one or more protecting groups.

8. The morpholino subunit of claim 1, wherein B is adenine, cytosine, guanine, uracil, thymine or hypoxanthine, each of which comprise at least one protecting group.

9. The morpholino subunit of claim 1, wherein the morpholino subunit is of formula: