Methoxyethoxy oligonucleotides for modulation of protein kinase C expression

• US 5,948,898 A
• Filed: 02/14/1996
• Issued: 09/07/1999
• Est. Priority Date: 03/16/1992
• Status: Expired due to Fees

• Current Assignee: ISIS Pharmaceuticals Incorporated
• Original Assignee: ISIS Pharmaceuticals Incorporated, Ciba-Geigy AG (Novartis Ag)
• Inventors: Dean, Nicholas M., Martin, Pierre, Altmann, Karl-Heinz
• Primary Examiner(s): Low, Christopher S.F.
• Application Number:
  US08/601,269
• Time in Patent Office: 1,301 Days
• Field of Search: 514/44, 536/22.1, 536/23.1, 536/23.5, 536/24.1, 536/25.1, 536/25.2, 435/91.1
• US Class Current: 536/23.5
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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 15/1137 against enzymes viral enzymes C12N15/1131; receptors C12N15/1138
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/322 2'-R Modification
• CPC Class Codes: C12N 2310/341 Gapmers, i.e. of the type ===---===
• CPC Class Codes: C12N 2310/346 having a combination of backbone and sugar modifications
• CPC Class Codes: C12N 2310/3521 Methyl
• CPC Class Codes: C12N 2310/3525 MOE, methoxyethoxy
• CPC Class Codes: C12N 2310/3527 Other alkyl chain
• CPC Class Codes: C12N 2310/3533 Halogen
• CPC Class Codes: C12N 9/12 transferring phosphorus containing groups, e.g. kinases (2.7)
• 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 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Y 207/11013 Protein kinase C (2.7.11.13)

Abstract

Compositions and methods are provided for modulating the expression of protein kinase C. Oligonucleotides are provided which are targeted to nucleic acids encoding PKC. The oligonucleotides contain a methoxyethoxy (--O--CH₂ CH₂ OCH₃) modification at the 2'"'"' position of at least one nucleotide. Methods of inhibiting PKC expression and methods of treating conditions associated with expression of PKC using oligonucleotides of the invention are disclosed.

Claims

1. An oligonucleotde up to 50 nucleotide units in length complementary to a polynucleotide encoding protein kinase C-α

, comprising SEQ ID NO;

1, wherein at least one nucleotide of said oligonucleotide comprises a 2'"'"'--O--CH₂ CH₂ OCH₃ modification of its sugar moiety, and wherein said oligonucleotide inhibits protein kinase C-α

expression.

2. The oligonucleotide of claim 1, wherein the intersugar linkages between each of the nucleotides of SEQ ID NO:

1 are phosphorothioate linkages.

3. The oligonucleotide of claim 1, wherein the intersugar linkages between each of the nucleotides of SEQ ID NO:

1 are phosphodiester linkages.

4. The oligonucleotide of claim 1, wherein the intersugar linkages between each of the nucleotides of SEQ ID NO:

1 are a mixture of phosphodiester linkages and phosphorothioate linkages.