Details for Patent: 7,855,283
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Title: | Antisense antiviral compound and method for treating arenavirus infection |
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. |
Inventor(s): | Iversen; Patrick L. (Corvallis, OR) |
Assignee: | AVI BioPharma, Inc. (Corvallis, OR) |
Filing Date: | Aug 25, 2009 |
Application Number: | 12/547,287 |
Claims: | 1. An antisense oligonucleotide compound comprised of morpholino subunits and phosphorous-containing intersubunit linkages having the following structure (I): ##STR00003## wherein: Y.sub.1.dbd.O; Z.dbd.O; Pi and Pj are independently a purine or pyrimidine base-pairing moiety effective to bind, by base-specific hydrogen bonding, to a base in a polynucleotide; X is alkyl, alkoxy, thioalkoxy, amino, alkyl amino, dialkylamino or piperazynyl; and wherein the antisense oligonucleotide compound: (i) comprises at least one phosphorous-containing intersubunit linkage wherein X is piperazynyl; (ii) contains between 12-40 base-pairing moieties; (iii) comprises a targeting sequence of at least 12 contiguous base-pairing moieties complementary to SEQ ID NO:1; and (iv) optionally comprises a hydrophilic polymer for enhancing the solubility of the antisense oligonucleotide compound; and wherein the antisense oligonucleotide compound is capable of binding to vRNA/vcRNA or mRNA strands of an Arenavirus in the Arenaviridae family to form a heteroduplex structure having a Tm of dissociation of at least 45.degree. C. 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. |