Antisense oligonucleotide compositions and methods for the modulation of JNK proteins

• US 6,133,246 A
• Filed: 04/07/1999
• Issued: 10/17/2000
• Est. Priority Date: 08/13/1997
• Status: Expired due to Term

• Current Assignee: Ionis Pharmaceuticals, Inc.
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Nero, Pamela S., Monia, Brett P., McKay, Robert, Gaarde, William A., Dean, Nicholas
• Primary Examiner(s): Brusca, John S.
• Assistant Examiner(s): SHIBUYA, MARK LANCE
• Application Number:
  US09/287,796
• Time in Patent Office: 559 Days
• Field of Search: 435/6, 435/69.1, 435/91.1, 435/440, 435/325, 435/352, 435/353, 435/354, 435/366, 435/371, 435/375, 435/320.1, 435/183, 435/194, 536/23.1, 536/24.3, 536/24.31, 536/24.33, 536/24.5, 514/44
• US Class Current: 514/44.00A
• 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: 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 2310/334 Modified C
• CPC Class Codes: C12N 2310/3341 5-Methylcytosine
• 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 2310/3515 Lipophilic moiety, e.g. cholesterol
• CPC Class Codes: C12N 2310/3525 MOE, methoxyethoxy
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/158 Expression markers

Abstract

Compositions and methods for the treatment and diagnosis of diseases or disorders amenable to treatment through modulation of expression of a gene encoding a Jun N-terminal kinase (JNK protein) are provided. Oligonucleotide are herein provided which are specifically hybridizable with nucleic acids encoding JNK1, JNK2 and JNK3, as well as other JNK proteins and specific isoforms thereof. Methods of treating animals suffering from diseases or disorders amenable to therapeutic intervention by modulating the expression of one or more JNK proteins with such oligonucleotide are also provided. Methods for the treatment and diagnosis of diseases or disorders associated with aberrant expression of one or more JNK proteins are also provided. Methods for inducing apoptosis and for treating diseases or conditions associated with a reduction in apoptosis are also provided.

Claims

1. A method of treating a human having a disease or condition characterized by a reduction in apoptosis comprising administering to a human a prophylactically or therapeutically effective amount of an antisense oligonucleotide comprising from 8 to 30 nucleotides connected by covalent linkages, wherein said oligonucleotide has a sequence that specifically binds to a nucleic acid encoding a human JNK2 protein and decreases the expression of said human JNK2 protein, so that apoptosis is induced.

2. A method of inducing apoptosis in a cell comprising contacting a cell with with an antisense oligonucleotide comprising from 8 to 30 nucleotides connected by covalent linkages, wherein said oligonucleotide has a sequence that specifically binds to a nucleic acid encoding a JNK2 protein and decreases the expression of said JNK2 protein, so that apoptosis is induced.

3. The method of claim 2 wherein the antisense oligonucleotide has a sequence comprising SEQ ID NO:

31.