Details for Patent: 7,507,196

Title:	Antisense antiviral compounds and methods for treating a filovirus infection
Abstract:	The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Filoviridae family, and in the treatment of a viral infection. The compounds and methods relate to the treatment of viral infections in mammals including primates by Ebola and Marburg viruses. The antisense antiviral compounds are morpholino oligonucleotides having: a) a nuclease resistant backbone, b) 15-40 nucleotide bases, and c) a targeting sequence of at least 15 bases in length that hybridizes to a target region selected from the following: i) the AUG start site region of VP35, as exemplified by SEQ ID NOS:67-71 or ii) the AUG start site region of VP24, as exemplified by SEQ ID NOS:72-76.
Inventor(s):	Stein; David A. (Corvallis, OR), Iversen; Patrick L. (Corvallis, OR), Bavari; Sina (Frederick, MD), Weller; Dwight D. (Corvallis, OR)
Assignee:	AVI Biopharma, Inc. (Corvallis, OR)
Filing Date:	May 11, 2006
Application Number:	11/433,840
Claims:	1. A method of treating Filovirus infection in a subject, comprising: administering to a subject a therapeutically effective amount of an antiviral composition of an antisense oligomer, wherein the oligomer comprises: 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, wherein at least 2 and no more than half of the total number of intersubunit linkages are positively charged at physiological pH; and a targeting sequence which forms a heteroduplex with a target sequence of the AUG start-site region of a positive-strand mRNA for Filovirus viral protein 35 (VP35); wherein the antisense oligomer inhibits virus production. 2. The method of claim 1, wherein the targeting sequence forms a heteroduplex with the AUG start-site region defined by SEQ ID NO:1. 3. The method of claim 2, wherein the targeting sequence is complementary to at least 12 contiguous bases of the sequence of SEQ ID NO:1. 4. The method of claim 2, wherein the oligomer has between 12-40 subunits. 5. The method of claim 2, wherein the heteroduplex has a Tm of dissociation of at least 45.degree. C. 6. The method of any one of claims 1 to 5, wherein the morpholino subunits are joined by intersubunit linkages in accordance with the structure: ##STR00003## wherein Y.sub.1.dbd.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 selected from alkyl alkoxy; thioalkoxy; --NR.sub.2, wherein each R is independently H or lower alkyl; or 1-piperizino. 7. The method of claim 1, wherein the Filovirus is ebola virus. 8. The method of claim 7, wherein the ebola virus is viral strain ebola Zaire.