Modulation of endothelial lipase expression

• US 7,507,808 B2
• Filed: 12/12/2002
• Issued: 03/24/2009
• Est. Priority Date: 12/12/2002
• Status: Expired due to Fees

• Current Assignee: ISIS Pharmaceuticals Incorporated (Ionis Pharmaceuticals, Inc.)
• Original Assignee: ISIS Pharmaceuticals Incorporated (Ionis Pharmaceuticals, Inc.)
• Inventors: Dobie, Kenneth W.
• Primary Examiner(s): BOWMAN, AMY HUDSON
• Application Number:
  US10/319,915
• Publication Number:
  US 20040115653A1
• Time in Patent Office: 2,294 Days
• Field of Search: 536/24.5, 536/23.1, 514/44, 435/6, 435/325, 435/375
• US Class Current: 536/24.5
• 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: C07H 21/04 with deoxyribosyl as saccharide radical
• CPC Class Codes: C12N 15/1137 against enzymes viral enzymes C12N15/1131; receptors C12N15/1138
• CPC Class Codes: C12N 2310/11 Antisense
• 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 301/01003 Triacylglycerol lipase (3.1.1.3)

Abstract

Compounds, compositions and methods are provided for modulating the expression of endothelial lipase. The compositions comprise oligonucleotides, targeted to nucleic acid encoding endothelial lipase. Methods of using these compounds for modulation of endothelial lipase expression and for diagnosis and treatment of disease associated with expression of endothelial lipase are provided.

Claims

1. A composition comprising a single-stranded antisense compound or a salt form thereof, wherein the single-stranded antisense compound is 15 to 30 nucleobases in length and is at least 90% complementary within nucleobases 1099 to 1143 of SEQ ID NO:

4, and a pharmaceutically acceptable carrier or diluent.

2. The composition of claim 1, wherein the antisense compound comprises a DNA oligonucleotide.

3. The composition of claim 1, wherein the antisense compound comprises an RNA oligonucleotide.

4. The composition of claim 1, wherein the antisense compound comprises a chimeric antisense oligonucleotide.

5. The composition of claim 1, wherein the antisense compound comprises at least one modified internucleoside linkage, sugar moiety, or nucleobase.

6. The composition of claim 1, wherein the antisense compound comprises at least one 2′

-O-methoxyethyl sugar moiety.

7. The composition of claim 1, wherein the antisense compound comprises at least one phosphorothioate internucleoside linkage.

8. The composition of claim 1, wherein the antisense compound comprises at least one 5-methylcytosine.

9. The composition of claim 4, wherein the chimeric antisense oligonucleotide comprises a plurality of 2′

-deoxynucleotides flanked on each side by at least one 2′

-O-methoxyethyl nucleotide.

16. The composition of claim 1, wherein the antisense compound is at least 95% complementary within nucleobases 1099 to 1143 of SEQ ID NO:

4.

17. The composition of claim 1, wherein the antisense compound is fully complementary within nucleobases 1099 to 1143 of SEQ ID NO:

4.

10. A composition comprising a single-stranded antisense compound or a salt form thereof, wherein the single-stranded antisense compound is 15 to 30 nucleobases in length and is at least 90% complementary to at least 8 consecutive nucleobases within nucleobases 1104-1123 of SEQ ID NO:

4, wherein the single-stranded antisense compound is a chimeric antisense oligonucleotide, and a pharmaceutically acceptable carrier or diluent.

11. The composition of claim 10, wherein the antisense compound comprises at least one modified internucleoside linkage, sugar moiety, or nucleobase.

12. The composition of claim 11, wherein the modified internucleoside linkage is a phosphorothioate linkage.

13. The composition of claim 11, wherein the modified sugar moiety is a 2′

-O-methoxyethyl sugar moiety.

14. The composition of claim 11, wherein the modified nucleobase is a 5-methylcytidine.

15. The composition of claim 10, wherein the antisense compound comprises a plurality of 2′

-deoxynucleotides flanked on each side by at least one 2′

-O-methoxyethyl nucleotide.

18. The composition of claim 10, wherein the antisense compound is at least 95% complementary to at least 8 consecutive nucleobases within nucleobases 1104-1123 of SEQ ID NO:

4.

19. The composition of claim 10, wherein the antisense compound is fully complementary to at least 8 consecutive nucleobases within nucleobases 1104-1123 of SEQ ID NO:

4.

20. The composition of claim 15, wherein the antisense compound comprises ten 2′

-deoxynucleotides flanked on each side by five 2′

-O-methoxyethyl nucleotides.

21. The composition of claim 20, wherein the antisense compound is 20 nucleobases in length.