Antisense inhibition of PI3K p85 expression

• US 6,100,090 A
• Filed: 06/25/1999
• Issued: 08/08/2000
• Est. Priority Date: 06/25/1999
• Status: Expired due to Term

• Current Assignee: Ionis Pharmaceuticals, Inc.
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Monia, Brett P., Cowsert, Lex M.
• Primary Examiner(s): Elliott, George C.
• Assistant Examiner(s): ZARA, JANE J
• Application Number:
  US09/344,521
• Time in Patent Office: 410 Days
• Field of Search: 435/6, 435/91.31, 435/325, 435/366, 435/91.1, 435/320.1, 435/375, 435/440, 435/443, 435/455, 514/44, 536/23.1, 536/23.2, 536/24.3, 536/24.31, 536/24.33, 536/25.3, 536/25.6, 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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 207/01137 Phosphatidylinositol 3-kinase (2.7.1.137)
• 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 PI3K p85. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding PI3K p85. Methods of using these compounds for modulation of PI3K p85 expression and for treatment of diseases associated with expression of PI3K p85 are provided.

Claims

1. An antisense compound 8 to 30 nucleobases in length targeted to nucleobases 88-3314 of the coding region of human pI3K p85 (SEQ ID NO:

1), wherein said antisense compound specifically hybridizes with and inhibits the expression of human pI3K p85.

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 5 wherein the modified sugar moiety is a 2'"'"'-O-methoxyethyl sugar moiety.

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

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

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

10. The antisense compound of claim 1 which is targeted to a nucleic acid molecule encoding a truncated form of human PI3K p85.

20. A method of inhibiting the expression of human pI3K p85 in human cells or tissues comprising contacting said cells or tissues in vitro with the antisense compound of claim 1 so that expression of human pI3K p85 is inhibited.

21. A method of inhibiting the expression of human pI3K p85 in human cells or tissues comprising contacting said cells or tissues in vitro with the antisense compound of claim 3 so that expression of human pI3K p85 is inhibited.

11. An antisense compound up to 30 nucleobases in length comprising at least an 8-nucleobase portion of SEQ ID NO:

21, 22, 27, 28, 30, 33, 40, 41, 8, 9, 12, 13, 14, 15, 17, 18, 20, 23, 24, 32, 37, 42 or 43 which inhibits the expression of human pI3K p85.

12. The antisense compound of claim 11 which is an antisense oligonucleotide.

13. The antisense compound of claim 12 wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.

14. The antisense compound of claim 13 wherein the modified internucleoside linkage is a phosphorothioate linkage.

15. The antisense compound of claim 12 wherein the antisense oligonucleotide comprises at least one modified sugar moiety.

16. The antisense compound of claim 15 wherein the modified sugar moiety is a 2'"'"'-O-methoxyethyl sugar moiety.

17. The antisense compound of claim 12 wherein the antisense oligonucleotide comprises at least one modified nucleobase.

18. The antisense compound of claim 17 wherein the modified nucleobase is a 5-methylcytosine.

19. The antisense compound of claim 12 wherein the antisense oligonucleotide is a chimeric oligonucleotide.