Modified oligonucleotides and intermediates useful in nucleic acid therapeutics

• US 5,625,050 A
• Filed: 03/31/1994
• Issued: 04/29/1997
• Est. Priority Date: 03/31/1994
• Status: Expired due to Term

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Beaton, Graham, Fisher, Eric F.
• Primary Examiner(s): Fleisher, Mindy
• Assistant Examiner(s): MCKELVEY, TERRY ALAN
• Application Number:
  US08/221,425
• Time in Patent Office: 1,125 Days
• Field of Search: 536/24.1, 536/25.3, 536/23.1
• US Class Current: 536/24.1
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/16 Purine radicals
• 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

The present invention provides nuclease resistant 3'"'"'-carbon modified oligonucleotides that can be used in the field of nucleic acid therapeutics and diagnostics. The modified oligonucleotides of the present invention have at least one modified internucleotide linkage wherein the divalent oxygen moiety at the 3'"'"'-position of the internucleotide linkage is replaced by a tetravalent carbon moiety. The 3'"'"'-carbon modified internucleotide linkage is preferably a 3'"'"'-methylene or 3'"'"'-hydroxymethylene linkage. Also provided are a method and monomeric nucleoside and nucleotide intermediates for making the modified oligonucleotides of the present invention.

Claims

1. A modified oligonucleotide of between 12 and 60 bases having at least three consecutive 3'"'"'-hydroxymethylene modified internucleotide linkages of the structure:

##STR11## wherein, R⁵ is a counterion, C₁ and C₂ represent the 3'"'"'-position and 5'"'"'-position, respectively, of the nucleoside units which are joined together in said oligonucleotide through said 3'"'"'-hydroxymethylene internucleotide linkages, and one of either X or Y is a hydroxyl (--OH--) group and the other of said X or Y is a hydrogen (--H--) atom.

2. A fully modified oligonucleotide of between 12 and 60 bases having only 3'"'"'-hydroxymethylene modified internucleotide linkages of the structure:

##STR12## wherein, R⁵ is a counterion, C₁ and C₂ represent the 3'"'"'-position and 5'"'"'-position, respectively, of the nucleotide units which are joined together in said oligonucleotide through said 3'"'"'-hydroxymethylene modified internucleotide linkages, and one of either X or Y is a hydroxyl (--OH--) group and the other of said X or Y is a hydrogen (--H--) atom.