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Claims for Patent: 6,451,991

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Claims 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): Martin; Pierre (Rheinfelden, CH), Altmann; Karl-Heinz (Reinach, CH), Cook; Phillip Dan (Vista, CA), Monia; Brett P. (Carlsbad, CA)
Assignee: ISIS Pharmaceuticals, Inc. (Carlsbad, CA) Novartis AG (CH)
Application Number:08/802,331
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--CH.sub.2 --CH.sub.2 --O--CH.sub.3 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'-OCH.sub.2 --CH.sub.2 --O--CH.sub.3 sugar moieties, a second nucleoside subsequence having adjacent 2'-deoxy sugar moieties, and a third nucleoside subsequence having adjacent 2'-O--CH.sub.2 --CH.sub.2 --O--CH.sub.3 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.
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