Antisense antiviral compound and method for treating arenavirus infection

• US 7,855,283 B2
• Filed: 08/25/2009
• Issued: 12/21/2010
• Est. Priority Date: 03/07/2006
• Status: Expired due to Fees

• Current Assignee: Sarepta Therapeutics, Inc.
• Original Assignee: Avi Biopharma, Inc.
• Inventors: Iversen, Patrick L.
• Primary Examiner(s): McGarry; Sean
• Assistant Examiner(s): GIBBS, TERRA C
• Application Number:
  US12/547,287
• Publication Number:
  US 20100063133A1
• Time in Patent Office: 483 Days
• Field of Search: 536/23.1, 536/24.3, 536/24.33, 536/24.5, 514/44
• US Class Current: 536/24.5
• CPC Class Codes: C12N 15/1131 against viruses
• CPC Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: C12N 2310/3145 with the nitrogen in 3' or 5'-position
• CPC Class Codes: C12N 2310/3233 Morpholino-type ring
• CPC Class Codes: C12N 2310/3513 Protein; Peptide
• CPC Class Codes: C12N 2760/10011 Arenaviridae

Abstract

The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Arenaviridae family and in the treatment of a viral infection. The compounds are particularly useful in the treatment of Arenavirus infection in a mammal. The antisense antiviral compounds are substantially uncharged morpholino oligonucleotides have a sequence of 12-40 subunits, including at least 12 subunits having a targeting sequence that is complementary to a region associated with viral RNA sequences within a 19 nucleotide region of the 5′-terminal regions of the viral RNA, viral complementary RNA and/or mRNA identified by SEQ ID NO:1.

Claims

1. An antisense oligonucleotide compound comprised of morpholino subunits and phosphorous-containing intersubunit linkages having the following structure (I):

2. The antisense oligonucleotide compound of claim 1, wherein X is dimethylamino when X is not piperazynyl.

3. The antisense oligonucleotide compound of claim 1, wherein X in at least 80% of the phosphorous-containing intersubunit linkages is not piperazynyl.

4. The antisense oligonucleotide compound of claim 1, wherein the antisense oligonucleotide compound contains between 14-24 base-pairing moieties.

5. The antisense oligonucleotide compound of claim 1, wherein the antisense oligonucleotide compound comprises a targeting sequence of 19 contiguous base-pairing moieties complementary to SEQ ID NO:

1.

6. The antisense oligonucleotide compound of claim 1, wherein the antisense oligonucleotide compound comprises a polyethyleneglycol moiety for enhancing the solubility of the antisense oligonucleotide compound.

7. A composition comprising the antisense oligonucleotide of claim 1 and a pharmaceutically acceptable carrier.

8. The antisense oligonucleotide compound of claim 4, wherein the targeting sequence has 20 base-pairing moieties.