2'-O-alkylated oligoribonucleotides and phosphorothioate analogs complementary to portions of the HIV genome

• US 6,034,233 A
• Filed: 11/19/1991
• Issued: 03/07/2000
• Est. Priority Date: 05/04/1990
• Status: Expired due to Term

• Current Assignee: ISIS Pharmaceuticals Incorporated
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Vickers, Timothy A., Ecker, David
• Primary Examiner(s): CRANE, LAWRENCE E
• Application Number:
  US07/794,396
• Time in Patent Office: 3,031 Days
• Field of Search: 536/24.5, 514/44
• US Class Current: 536/24.5
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C12N 15/1132 against retroviridae, e.g. HIV
• CPC Class Codes: C12N 15/63 Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
• CPC Class Codes: C12N 15/67 General methods for enhancing the expression
• CPC Class Codes: C12N 2310/15 Nucleic acids forming more than 2 strands, e.g. TFOs
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2740/16322 New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

Abstract

Methods of modulating the activity of the TAR element of HIV are provided. Oligonucleotides having 6 to 50 bases and at least one 2'"'"'-O alkyl modification and selected sequences are disclosed.

Claims

1. An oligonucleotide having a nucleotide sequence selected from the group consisting of SEQ. ID. No. 1, SEQ. ID. No. 2, SEQ. ID. No. 3, SEQ. ID. No. 5, SEQ. ID. No. 6, SEQ. ID. No. 7, SEQ. ID. No. 8, and SEQ. ID. No. 9 and at least one C₁ to C₉ alkyl or benzyl 2'"'"'-O-modification.

2. An oligonucleotide of claim 1 having at least one phosphorothioate modification.

3. An oligonucleotide of claim 1 in a pharmaceutically acceptable carrier.

4. An oligonucleotide of claim 2 in a pharmaceutically acceptable carrier.

5. The oligonucleotide of claim 1 wherein substantially all 2'"'"' positions are modified with said modifications.

6. The oligonucleotide of claim 1 wherein substantially all 2'"'"' positions are modified with O-methyl groups.

7. The oligonucleotide of claim 1 wherein substantially all 2'"'"' positions are modified with O-methyl groups and substantially all internucleoside linkages are phosphorothioates.