2′ Modified oligonucleotides

• US 6,476,205 B1
• Filed: 08/10/1998
• Issued: 11/05/2002
• Est. Priority Date: 10/24/1989
• Status: Expired due to Fees

• Current Assignee: ISIS Pharmaceuticals Incorporated (Ionis Pharmaceuticals, Inc.)
• Original Assignee: ISIS Pharmaceuticals Incorporated (Ionis Pharmaceuticals, Inc.)
• Inventors: Matteucci, Mark, Buhr, Chris A.
• Primary Examiner(s): Wilson, James O.
• Application Number:
  US09/131,647
• Time in Patent Office: 1,548 Days
• Field of Search: 536/16.8, 536/26.26, 536/26.6, 536/26.7, 536/26.8, 536/27.21, 536/28.1, 536/28.54, 536/28.53, 536/28.5, 536/23.1, 514/45, 514/46, 514/47, 514/48, 514/49, 514/50, 514/51
• US Class Current: 536/23.1
• CPC Class Codes: C07H 19/04 Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/16 Purine radicals
• 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
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/322 2'-R Modification
• CPC Class Codes: C12N 2310/3517 Marker; Tag
• CPC Class Codes: C12N 2310/3527 Other alkyl chain
• CPC Class Codes: C12N 2310/353 linked to the nucleic acid via an atom other than carbon
• CPC Class Codes: C12N 2310/3535 Nitrogen

Abstract

Oligomers which have substituents on the 2′ position are resistant to oligonucleases and furthermore can be derivatized to deliver reagents or drugs, to carry label, or to provide other properties.

Claims

1. An oligonucleotide having the formula:

or a salt thereof, wherein;

each B independently is a protected or unprotected purine or pyrimidine base in the β

-anomeric configuration;

W₃ and W₄ are each independently H, PO₃<sup>−

2</sup>, a protecting group, or an intermediate moiety in the formation of an internucleotide link which when reacted with the appropriate —

OH results in Z;

n is an integer of 1-200;

each Z is independently is P(O)O, P(O)S or P(O)N(R)₂ provided at least one Z is not P(O)O;

each R is independently H or alkyl (C_1-6);

each A is OCH₃, H, OH, O—

Pr wherein Pr is a protecting group, or X—

Y wherein;

X is O; and

Y is substituted or unsubstituted alkyl (C_2-20) or substituted or unsubstituted alkenyl (C_2-20), wherein the substituents are a halogen, OH, NH₂, SH, —

O—

, —

CH₂CONH₂, —

CH₂COOCH₂CH₃, or CH₂CONHCH₂NH₂; and

at least one A is OCH₃.

2. The oligonucleotide of claim 1 wherein W₃ and W₄ are H.

3. The oligonucleotide of claim 1 wherein at least one Z is P(O)N(R)₂.

4. The oligonucleotide of claim 1 wherein at least one Z is P(O)S.

5. The oligonucleotide of claim 1 wherein at least one A is X—

Y.

6. The oligonucleotide of claim 5 wherein Y is substituted alkyl.