Oligonucleotides for modulating RAF kinase having phosphorothioate linkages of high chiral purity

• US 5,654,284 A
• Filed: 06/06/1995
• Issued: 08/05/1997
• Est. Priority Date: 10/15/1991
• Status: Expired due to Term

• Current Assignee: ISIS Pharmaceuticals Incorporated
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Cook, Phillip Dan, Hoke, Glenn
• Primary Examiner(s): Wilson, James O.
• Application Number:
  US08/466,692
• Time in Patent Office: 791 Days
• Field of Search: 514/44, 536/22.1, 536/23.1, 536/23.7, 536/23.72, 536/24.32
• US Class Current: 514/44.00A
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• 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 15/10 Processes for the isolation, preparation or purification of DNA or RNA chemical preparation of DNA or RNA C07H21/00; preparation of non-structural polynucleotides from microorganisms or with enzymes C12P19/34
• 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 15/1131 against viruses
• CPC Class Codes: C12N 15/1132 against retroviridae, e.g. HIV
• CPC Class Codes: C12N 15/1133 against herpetoviridae, e.g. HSV
• CPC Class Codes: C12N 15/1135 against oncogenes or tumor suppressor genes
• CPC Class Codes: C12N 15/1137 against enzymes viral enzymes C12N15/1131; receptors C12N15/1138
• CPC Class Codes: C12P 19/34 Polynucleotides, e.g. nucleic acids, oligoribonucleotides
• CPC Class Codes: C12Q 1/6813 Hybridisation assays
• CPC Class Codes: C12Q 1/6876 Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
• CPC Class Codes: C12Q 1/701 Specific hybridization probes

Abstract

Sequence-specific phosphorothioate oligonucleotides comprising nucleoside units which are joined together by either substantially all Sp or substantially all Rp phosphorothioate intersugar linkages are provided. Such sequence-specific phosphorothioate oligonucleotides having substantially chirally pure intersugar linkages are prepared by enzymatic or chemical synthesis.

Claims

1. An oligonucleotide represented by SEQ ID NO:

9 wherein at least 75% of the nucleoside units are joined together by Sp phosphorothioate 3'"'"' to 5'"'"' linkages.

3. The oligonucleotide of claim 1 wherein all of the nucleoside units are joined together by Sp phosphorothioate 3'"'"' to 5'"'"' linkages.

5. A composition containing an oligonucleotide of claim 1 and an acceptable carrier.

2. An oligonucleotide represented by SEQ ID NO:

9 wherein at least 75% of the nucleoside units are joined together by Rp phosphorothioate 3'"'"' to 5'"'"' linkages.

4. The oligonucleotide of claim 2 wherein all of the nucleoside units are joined together by Rp phosphorothioate 3'"'"' to 5'"'"' linkages.

6. A composition containing an oligonucleotide of claim 2 and an acceptable carrier.