Sugar modified oligonucleotides that detect and modulate gene expression

• US 6,307,040 B1
• Filed: 09/23/1997
• Issued: 10/23/2001
• Est. Priority Date: 03/05/1992
• Status: Expired due to Fees

• Current Assignee: ISIS Pharmaceuticals Incorporated
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Cook, Philip Dan, Kawasaki, Andrew M.
• Primary Examiner(s): Guzo, David
• Assistant Examiner(s): WANG, ANDREW J
• Application Number:
  US08/936,166
• Time in Patent Office: 1,491 Days
• Field of Search: 536/23.1, 536/24.5, 536/25.3, 435/6, 435/91.1
• US Class Current: 536/24.5
• CPC Class Codes: C07H 19/04 Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
• CPC Class Codes: C07H 19/20 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids

Abstract

Compositions and methods are provided for the treatment and diagnosis of diseases amenable to modulation of the production of selected proteins. In accordance with preferred embodiments, oligonucleotides and oligonucleotide analogs are provided which are specifically hybridizable with a selected sequence of RNA or DNA wherein at least one of the 2′-deoxyfuranosyl moieties of the nucleoside unit is modified. Treatment of HIV, herpes virus, papillomavirus and other infections is provided.

Claims

1. A mixed sequence oligonucleotide having at least one modified 2′

-deoxyfuranosyl moiety modified by substitution with bromo, chloro, iodo, azido, amino, substituted amino, bromomethyl, chloromethyl, iodomethyl, cyanato, bromoalkoxyl, chloroalkoxyl, iodoalkoxyl, alkyl sulfide, alkyl sulfonate, nitrate or nitrite.

3. The oligonucleotide or oligonucleotide analog of claim 1 having from about 5 to about 50 nucleotide bases.

4. The oligonucleotide or oligonucleotide analog of claim 1 wherein said modification is at the 3′

end of said oligonucleotide.

5. The oligonucleotide or oligonucleotide analog of claim 1 wherein at least one of the sugar linking groups is replaced with carbon or ether linkages.

6. The oligonucleotide or oligonucleotide analog of claim 5 wherein a 5′

-methylene group and carbocyclic sugar are removed.

7. The oligonucleotide or oligonucleotide analog of claim 1 further modified such that at least some of the sugar linking groups comprise a phosphorothioate, methyl phosphonate, or phosphate alkylate.

8. The oligonucleotide or oligonucleotide analog of claim 1 in a pharmaceutically acceptable carrier.

2. A mixed sequence oligonucleotide having at least one 2′

-deoxyfuranosyl moiety modified by substitution with alkyl.