Details for Patent: 8,524,676

Title:	Method for treating enterovirus or rhinovirus infection using antisense antiviral compounds
Abstract:	The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Picornaviridae family and in the treatment of a viral infection. The compounds are particularly useful in the treatment of Enterovirus and/or Rhinovirus 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 32 nucleotide region of the viral 5' untranslated region identified by SEQ ID NO:7.
Inventor(s):	Stein; David A. (Corvallis, OR), Bestwick; Richard K. (Corvallis, OR), Iversen; Patrick L. (Corvallis, OR), Weller; Dwight D. (Corvallis, OR)
Assignee:	Sarepta Therapeutics, Inc. (Corvallis, OR)
Filing Date:	Sep 08, 2006
Application Number:	11/517,757
Claims:	1. A method of treating viral infection of mammalian cells by an Enterovirus or Rhinovirus, comprising exposing host cells to an effective amount of an antiviral compound that comprises a morpholino antisense oligonucleotide of between 15 and 25 morpholino subunits having a substantially uncharged, nuclease-resistant backbone containing phosphorodiamidate intersubunit linkages joining a morpholino nitrogen of one subunit to a 5' exocyclic carbon of an adjacent subunit, wherein the morpholino antisense oligonucleotide comprises a targeting sequence of at least 15 nucleotide bases complementary to SEQ ID NO:7 and, conjugated to the morpholino antisense oligonucleotide, an arginine-rich polypeptide effective to promote uptake of the antiviral compound into the host cells, wherein the arginine-rich polypeptide has the sequence of SEQ ID NO:15. 2. The method of claim 1, wherein the morpholino antisense oligonucleotide forms a heteroduplex with its target sequence, wherein the heteroduplex has a T.sub.m of at least 45.degree. C. 3. The method of claim 1, wherein the morpholino antisense oligonucleotide contains an intersubunit linkages in accordance with the structure: ##STR00003## wherein Y.sub.1=O, Z=O, Pj is a purine or pyrimidine base-pairing moiety effective to bind, by base-specific hydrogen bonding, to a base in a polynucleotide, and X is alkyl, alkoxy, thioalkoxy, amino, or --NR.sub.2, where each R is independently hydrogen or methyl. 4. The method of claim 1, wherein the morpholino antisense oligonucleotide contains an intersubunit linkages in accordance with the structure: ##STR00004## wherein Y.sub.1=O, Z=O, Pj is a purine or pyrimidine base-pairing moiety effective to bind, by base-specific hydrogen bonding, to a base in a polynucleotide, and X is alkyl, alkoxy, thioalkoxy, amino, --NR.sub.2, where each R is independently hydrogen or methyl, or 1-piperazine, wherein at least 2 and no more than half of the total number of intersubunit linkages are 1-piperazine. 5. The method of claim 1, wherein the oligonucleotide has at least 15 nucleotide bases contained in SEQ ID NO:10. 6. The method of claim 5, wherein the oligonucleotide is selected from the group consisting of SEQ ID NOS:11, 12, and 13. 7. The method of claim 1, wherein the exposing is by administering to a subject a therapeutically effective amount of the antiviral compound. 8. The method of claim 7, further comprising administering a second antiviral compound to the subject.