Claims for Patent: 6,451,991

Summary for Patent: 6,451,991

Title:	Sugar-modified gapped oligonucleotides
Abstract:	Oligonucleotides are provided which have increased nuclease resistance, substituent groups for increasing binding affinity to complementary nucleic acid strand, and subsequences of 2'-deoxy-erythro-pentofuranosyl nucleosides that activate RNase H. Such oligonucleotides are useful for diagnostics and other research purposes, for modulating the expression of a protein in organisms, and for the diagnosis, detection and treatment of other conditions susceptible to ooligonucleotide therapeutics.
Inventor(s):	Pierre Martin, Karl-Heinz Altmann, Phillip Dan Cook, Brett P. Monia
Assignee:	Novartis AG, Ionis Pharmaceuticals Inc
Application Number:	US08/802,331
Patent Claims:	1. An oligonucleotide specifically hybridizable with DNA or RNA said oligonucleotide comprising a linear sequence of covalently-bound nucleoside units, wherein: said sequence comprises a first nucleoside subsequence having adjacent 2′-O—CH2—CH2—O—CH3 sugar moieties and a second nucleoside subsequence having adjacent 2′-deoxy sugar moieties, wherein: said nucleoside units of said first and second subsequences are covalently-bound by phosphorothioate linkages; or said nucleoside units of said first subsequence are covalently-bound by phosphodiester linkages and said nucleoside units of said second subsequence are covalently-bound by phophorothioate linkages; or said nucleoside units of said first subsequence are covalently-bound by phosphorothioate linkages and said nucleoside units of said second subsequence are covalently-bound by phosphodiester linkages. 2. The oligonucleotide of claim 1 wherein said nucleoside units of said first and second subsequences are covalently-bound by phosphorothioate linkages. 3. The oligonucleotide of claim 1 wherein said nucleoside units of said first subsequence are covalently-bound by phosphodiester linkages and said nucleoside units of said second subsequence are covalently-bound by phosphorothioate linkages. 4. The oligonucleotide of claim 1 wherein said nucleoside units of said first subsequence are covalently-bound by phosphorothioate linkages and said nucleoside units of said second subsequence are covalently-bound by phosphodiester linkages. 5. The oligonucleotide of claim 1 wherein said second subsequence comprises at least three nucleoside units. 6. The oligonucleotide of claim 1 wherein said second subsequence comprises at least five nucleoside units. 7. The oligonucleotide of claim 1 having 5 to 50 nucleoside units. 8. An oligonucleotide specifically hybridizable with DNA or RNA said oligonucleotide comprising a linear sequence of covalently-bound nucleoside units, wherein: said sequence comprises a first nucleoside subsequence having adjacent 2′-OCH2—CH2—O—CH3 sugar moieties, a second nucleoside subsequence having adjacent 2′-deoxy sugar moieties, and a third nucleoside subsequence having adjacent 2′-O—CH2—CH2—O—CH3 sugar moieties, wherein said second subsequence is positioned between said first and third subsequences; and the nucleoside units within said first, second, and third subsequences are covalently-bound by phosphodiester or phophorothioate linkages. 9. The oligonucleotide of claim 8 wherein said nucleoside units of said first, second and third subsequences are covalently-bound by phosphorothioate linkages. 10. The oligonucleotide of claim 8 wherein said nucleoside units of said first and thir subsequences are covalently-bound by phosphodiester linkages and said nucleoside units of said second subsequence are covalently-bound by phosphorothioate linkages. 11. The oligonucleotide of claim 8 wherein said nucleoside units of said first and third subsequences are covalently-bound by phosphorothioate linkages and said nucleoside units of said second subsequence are covalently-bound by phosphodiester linkages. 12. The oligonucleotide of claim 8 wherein said second subsequence comprises at least three nucleoside units. 13. The oligonucleotide of claim 8 wherein said second subsequence comprises at least five nucleoside units. 14. The oligonucleotide of claim 8 having 5 to 50 nucleoside units.