Antisense antiviral compound and method for treating influenza viral infection
First Claim
1. An antiviral compound comprising an oligonucleotide analog having a) a nuclease-resistant backbone, b) 12-40 nucleotide bases, and c) a targeting sequence of at least 12 bases in length that hybridizes to a target region selected from the following:
- i) the 5′
or 3′
terminal 25 bases of a negative sense viral RNA segment of Influenzavirus A, Influenzavirus B and Influenzavirus C, ii) the terminal 25 bases of the 3′
terminus of a positive sense cRNA of Influenzavirus A, Influenzavirus B and Influenzavirus C, and iii) the 50 bases surrounding the AUG start codon of an influenza viral mRNA, wherein said oligonucleotide analog further has;
a) the capability of being actively taken up by mammalian host cells, and b) the ability to form a heteroduplex structure with the viral target region, wherein said heteroduplex structure is;
i) composed of the positive or negative sense strand of the virus and the oligonucleotide compound, and ii) characterized by a Tm of dissociation of at least 45°
C.
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Accused Products
Abstract
The invention provides antisense antiviral compounds and methods of their use and production in inhibition of growth of viruses of the Orthomyxoviridae family and in the treatment of a viral infection. The compounds are particularly useful in the treatment of influenza virus infection in a mammal. The antisense antiviral compounds are substantially uncharged, including partially positively charged, morpholino oligonucleotides having 1) a nuclease resistant backbone, 2) 12-40 nucleotide bases, and 3) a targeting sequence of at least 12 bases in length that hybridizes to a target region selected from the following: a) the 5′ or 3′ terminal 25 bases of the negative sense viral RNA segment of Influenzavirus A, Influenzavirus B and Influenzavirus C; b) the terminal 25 bases of the 3′ terminus of the positive sense cRNA and; and c) the 50 bases surrounding the AUG start codon of an influenza viral mRNA.
74 Citations
12 Claims
-
1. An antiviral compound comprising an oligonucleotide analog having
a) a nuclease-resistant backbone, b) 12-40 nucleotide bases, and c) a targeting sequence of at least 12 bases in length that hybridizes to a target region selected from the following: -
i) the 5′
or 3′
terminal 25 bases of a negative sense viral RNA segment of Influenzavirus A, Influenzavirus B and Influenzavirus C,ii) the terminal 25 bases of the 3′
terminus of a positive sense cRNA of Influenzavirus A, Influenzavirus B and Influenzavirus C, andiii) the 50 bases surrounding the AUG start codon of an influenza viral mRNA, wherein said oligonucleotide analog further has;
a) the capability of being actively taken up by mammalian host cells, and b) the ability to form a heteroduplex structure with the viral target region, wherein said heteroduplex structure is;
i) composed of the positive or negative sense strand of the virus and the oligonucleotide compound, and ii) characterized by a Tm of dissociation of at least 45°
C. - View Dependent Claims (3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
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2. (canceled)
Specification