Antisense modulation of X-linked inhibitor of apoptosis expression

• US 6,087,173 A
• Filed: 09/09/1999
• Issued: 07/11/2000
• Est. Priority Date: 09/09/1999
• Status: Expired due to Term

• Current Assignee: Ionis Pharmaceuticals, Inc.
• Original Assignee: ISIS Pharmaceuticals Incorporated (Ionis Pharmaceuticals, Inc.)
• Inventors: Bennett, C. Frank, Cowsert, Lex M., Ackermann, Elizabeth J.
• Primary Examiner(s): Brusca, John S.
• Assistant Examiner(s): McGarry, Sean
• Application Number:
  US09/392,580
• Time in Patent Office: 306 Days
• Field of Search: 435/6, 435/375, 435/455, 514/44, 536/231, 536/24.1, 536/24.5
• US Class Current: 435/375
• 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 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• 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: 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 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• 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 2310/3525 MOE, methoxyethoxy
• CPC Class Codes: Y02P 20/582 Recycling of unreacted starting or intermediate materials

Abstract

Antisense compounds, compositions and methods are provided for modulating the expression of X-linked inhibitor of apoptosis. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding X-linked inhibitor of apoptosis. Methods of using these compounds for modulation of X-linked inhibitor of apoptosis expression and for treatment of diseases associated with expression of X-linked inhibitor of apoptosis are provided.

Claims

1. An antisense compound up to 30 nucleobases in length targeted to a nucleic acid molecule encoding human X-linked inhibitor of apoptosis comprising at least an 8 nucleobase portion of SEQ ID NO:

8, 12, 13, 14, 21, 23, 25, 26, 27, 28, 30, 31, 32, 33, 34, 35, 36, 37, 38, 40 41, 42, 43, 44, 9, 10, 11, 15, 16, 17, 18, 19, 20, 24, 29, 39 or 45 and which inhibits expression of human X-linked inhibitor of apoptosis.

2. The antisense compound of claim 1 which is an antisense oligonucleotide.

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

8, 12, 13, 14, 21, 23, 25, 26, 27, 28, 31, 32, 33, 34, 35, 36, 37, 38, 40, 41, 42, 43 or 44.

4. The antisense compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.

5. The antisense compound of claim 4 wherein the modified internucleoside linkage is a phosphorothioate linkage.

6. The antisense compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified sugar moiety.

7. The antisense compound of claim 6 wherein the modified sugar moiety is a 2'"'"'-O-methoxyethyl sugar moiety.

8. The antisense compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified nucleobase.

9. The antisense compound of claim 8 wherein the modified nucleobase is a 5-methylcytosine.

10. The antisense compound of claim 2 wherein the antisense oligonucleotide is a chimeric oligonucleotide.

11. A composition comprising the antisense compound of claim 1 and a pharmaceutically acceptable carrier or diluent.

12. The composition of claim 11 further comprising a colloidal dispersion system.

13. The composition of claim 11 wherein the antisense compound is an antisense oligonucleotide.

14. A method of inhibiting the expression of X-linked inhibitor of apoptosis in human cells or tissues in vitro comprising contacting said cells or tissues in vitro with the antisense compound of claim 1 so that expression of X-linked inhibitor of apoptosis is inhibited.