Phosphorothioate oligonucleotides having modified internucleoside linkages

• US 6,811,975 B2
• Filed: 03/14/2001
• Issued: 11/02/2004
• Est. Priority Date: 07/14/1998
• Status: Expired due to Fees

• Current Assignee: ISIS Pharmaceuticals Incorporated (Ionis Pharmaceuticals, Inc.)
• Original Assignee: ISIS Pharmaceuticals Incorporated (Ionis Pharmaceuticals, Inc.)
• Inventors: Cook, Phillip Dan, Manoharan, Muthiah
• Primary Examiner(s): Epps-Ford, Janet L.
• Application Number:
  US09/805,630
• Publication Number:
  US 20010027251A1
• Time in Patent Office: 1,329 Days
• Field of Search: 536/24.5, 536/24.3, 536/24.31, 536/24.32, 536/24.33, 536/25.3, 536/25.31, 536/26.31, 435/7, 435/6
• US Class Current: 435/6.14
• CPC Class Codes: C07H 19/04 Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
• 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

Novel compounds that mimic and/or modulate the activity of wild-type nucleic acids. In general, the compounds are phosphorothioate oligonucleotides wherein the 5′-terminal internucleoside linkage or the 5′- and 3′-terminal linkages are modified.

Claims

1. A method of assaying a nucleic acid, comprising:

(a) contacting a solution suspected to contain said nucleic acid with a compound comprising a plurality of covalently-bound nucleosides, the compound being capable of binding to said nucleic acid;

said compound having the formula;

2. The method of claim 1 wherein L₁ is a Sp phosphorothioate internucleoside linkage and L₂ is a racemic phosphorothioate internucleoside linkage.

3. The method of claim 1 wherein L₁ and L₂ both are Sp phosphorothioate internucleoside linkages.

4. The method of claim 1 wherein L₁ is a Rp phosphorothioate internucleoside linkage and L₂ is a racemic phosphorothioate internucleoside linkage.

5. The method of claim 1 wherein L₁ and L₂ both are Rp phosphorothioate internucleoside linkages.

6. The method of claim 1 wherein L₁ or L₂ is CH₂—

O—

NR.

7. The method of claim 1 wherein L₁ or L₂ is CH₂—

NR—

O.

8. The method of claim 1 wherein L₁ and L₂ are both CH₂—

O—

NR.

9. The method of claim 1 wherein L₁ and L₂ are both CH₂—

NR—

O.

10. The method of claim 1 wherein R is alkyl.

11. The method of claim 1 wherein R is methyl.

12. The method of claim 1 wherein at least one of said nucleosides includes a ribose sugar portion.

13. The method of claim 1 wherein at least one of said nucleosides includes a deoxyribose sugar portion.

14. The method of claim 1 wherein n is about 5 to about 50.

15. The method of claim 1 wherein n is about 8 to about 30.