Antisense modulation of caspase 3 expression

• US 6,303,374 B1
• Filed: 01/18/2000
• Issued: 10/16/2001
• Est. Priority Date: 01/18/2000
• Status: Expired due to Term

• Current Assignee: Ionis Pharmaceuticals, Inc.
• Original Assignee: ISIS Pharmaceuticals Incorporated (Ionis Pharmaceuticals, Inc.)
• Inventors: Zhang, Hong, Cowsert, Lex M.
• Primary Examiner(s): McGarry, Sean
• Application Number:
  US09/484,617
• Time in Patent Office: 637 Days
• Field of Search: 435/6, 435/455, 435/458, 435/375, 536/23.1, 536/24.1, 536/24.5, 514/44
• 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 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• 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 2310/3341 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: C12Y 304/22056 Caspase-3 (3.4.22.56)
• 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 caspase 3. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding caspase 3. Methods of using these compounds for modulation of caspase 3 expression and for treatment of diseases associated with expression of caspase 3 are provided.

Claims

1. The antisense co pound up to 30 nucleobases in length targeted to a nucleic acid molecules encoding caspase 3, wherein said antisense compound comprises at least an 8 nucleobase portion of SEQ ID NO:

18, 19, 20, 23, 24, 25, 26, 27, 30, 31, 32, 33, 34, 35, 36, 38, 39, 40, 41, 42, 44, 46, 47, 48, 50, 51, 54, 55, 56, 57, 59, 61, 63, 64, 65, 67, 68, 71, 72, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 89, 91, 92, 94, 95,96, 97, 98, 101, 102, 103, 106, 107, 108, 113, 114, 116, 117, 118, 119, 120, 121, 122, 124, 126, 127, 129, 131, 133, 140, 142, 143, 146, 150, 151, 154, 159, 160, 164, 167 or 169 and wherein said antisense compound specifically hybridizes with and inhibits the expression of said nucleic acid molecule encoding caspase 3.

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

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

4. The antisense compound of claim 3 wherein the modified internucleoside linkage is a phosphorothioate linkage.

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

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

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

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

12. A method of inhibiting the expression of caspase 3 in cells or tissues in vitro comprising contacting said cells or tissues with the antisense compound of claim 1 so that expression of caspase 3 is inhibited.

5. The antisense compound of claim 5 wherein the modified sugar moiety is a 2′

-O-methoxyethyl sugar moiety.

7. The antisense compound of claim 7 wherein the modified nucleobase is a 5-methylcytosine.

10. The pharmaceutical composition of claim 10 further comprising a colloidal dispersion system.

11. The pharmaceutical composition of claim 10 wherein the antisense compound is an antisense oligonucleotide.