Antisense antiviral compounds and methods for treating a filovirus infection

• US 8,198,429 B2
• Filed: 08/09/2010
• Issued: 06/12/2012
• Est. Priority Date: 08/09/2010
• Status: Active Grant

• Current Assignee: Sarepta Therapeutics, Inc.
• Original Assignee: Avi Biopharma, Inc.
• Inventors: Iversen, Patrick L., Weller, Dwight D.
• Primary Examiner(s): GIBBS, TERRA C
• Application Number:
  US12/853,180
• Publication Number:
  US 20120035136A1
• Time in Patent Office: 673 Days
• Field of Search: 536/23.1, 536/24.3, 536/24.33, 536/24.5
• US Class Current: 536/24.5
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 15/1131 against viruses
• CPC Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: C12N 2310/3233 Morpholino-type ring

Abstract

The present invention provides antisense antiviral compounds, compositions, and methods of their use and production, mainly for inhibiting the replication of viruses of the Filoviridae family, including Ebola and Marburg viruses. The compounds, compositions, and methods also relate to the treatment of viral infections in mammals including primates by Ebola and Marburg viruses. The antisense antiviral compounds include phosphorodiamidate morpholino oligonucleotides (PMOplus) having a nuclease resistant backbone, about 15-40 nucleotide bases, at least two but typically no more than half piperazine-containing intersubunit linkages, and a targeting sequence that is targeted against the AUG start site region of Ebola virus VP35, Ebola virus VP24, Marburg virus VP24, or Marburg virus NP, including combinations and mixtures thereof.

Claims

1. A composition, comprising a first and a second antisense oligonucleotide, wherein each oligonucleotide is composed of morpholino subunits linked by phosphorous-containing intersubunit linkages which join a morpholino nitrogen of one subunit to a 5′

exocyclic carbon of an adjacent subunit in accordance with the structure;

2. The composition of claim 1, comprising an approximately 1:

1 mixture of equivalent concentrations (w/v) of the first and second antisense oligonucleotides.

3. A composition, comprising a first and a second antisense oligonucleotide, wherein each oligonucleotide is composed of morpholino subunits linked by phosphorous-containing intersubunit linkages which join a morpholino nitrogen of one subunit to a 5′

exocyclic carbon of an adjacent subunit in accordance with the structure;

4. The composition of claim 3, comprising an approximately 1:

1 mixture of equivalent concentrations (w/v) of the first and second antisense oligonucleotides.