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Last Updated: April 25, 2024

Claims for Patent: 6,316,259


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Summary for Patent: 6,316,259
Title: Antisense inhibition of glycogen synthase kinase 3 alpha expression
Abstract:Antisense compounds, compositions and methods are provided for modulating the expression of glycogen synthase kinase 3 alpha. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding glycogen synthase kinase 3 alpha. Methods of using these compounds for modulation of glycogen synthase kinase 3 alpha expression and for treatment of diseases associated with expression of glycogen synthase kinase 3 alpha are provided.
Inventor(s): Monia; Brett P. (La Costa, CA), McKay; Robert (San Diego, CA), Butler; Madeline M. (Rancho Sante Fe, CA), Wyatt; Jacqueline (Encinitas, CA)
Assignee: Isis Pharmaceuticals, Inc. (Carlsbad, CA)
Application Number:09/488,856
Patent Claims:1. An antisense compound 8 to 30 nucleobases in length targeted to nucleotides 3 through 22 of a 5' untranslated region, nucleotides 84 through 110 of a start codon, nucleotides 230 through 249, nucleotides 307 through 326, nucleotides 353 through 394, nucleotides 410 through 464, nucleotides 491 through 510, nucleotides 518 through 537, nucleotides 565 through 592, nucleotides 617 through 651, nucleotides 665 through 684, nucleotides 706 through 725, nucleotides 782 through 801, nucleotides 840 through 878, nucleotides 887 through 909, nucleotides 960 through 985, nucleotides 1058 through 1077, nucleotides 1309 through 1328, or nucleotides 1491 through 1510 of a coding region, nucleotides 1708 through 1729, nucleotides 1747 through 1774, nucleotides 1936 through 1973, nucleotides 2064 through 2083, or nucleotides 2116 through 2135 of a 3' untranslated region of human glycogen synthase kinase 3 alpha (SEQ. ID. NO:3), or to nucleotides 1191 through 1210, nucleotides 1309 through 1328, nucleotides 2646 through 2665, nucleotides 2938 through 2957, nucleotides 3241 through 3260, nucleotides 3504 through 3523, nucleotides 4021 through 4040, nucleotides 5633 through 5652, nucleotides 5788 through 5807, nucleotides 6647 through 6666, nucleotides 7056 through 7075, nucleotides 7190 through 7209, nucleotides 7312 through 7331, nucleotides 7823 through 7842, nucleotides 8748 through 8767, nucleotides 8967 through 8986, nucleotides 9827 through 9846, nucleotides 10612 through 10631, nucleotides 10669 through 10688, or nucleotides 11332 through 11351 of an intron of human glycogen synthase kinase 3 alpha (SEQ. ID. NO:10), wherein said antisense compound specifically hybridizes with and inhibits the expression of human glycogen synthase kinase 3 alpha mRNA.

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. An antisense compound up to 30 nucleobases in length comprising at least an 8-nucleobase portion of SEQ ID NO:12, 14, 15, 16, 17, 19, 23, 24, 27, 28, 30, 31, 32, 33, 35, 36, 38, 39, 44, 45, 47, 52, 53, 54, 55, 56, 57, 58, 61, 66, 67, 69, 74, 75, 76, 77, 78, 82, 83 or 87 which inhibits the expression of human glycogen synthase kinase 3 alpha.

11. The antisense compound of claim 10 which is an antisense oligonucleotide.

12. The antisense compound of claim 11 wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.

13. The antisense compound of claim 12 wherein the modified internucleoside linkage is a phosphorothioate linkage.

14. The antisense compound of claim 11 wherein the antisense oligonucleotide comprises at least one modified sugar moiety.

15. The antisense compound of claim 14 wherein the modified sugar moiety is a 2'-O-methoxyethyl sugar moiety.

16. The antisense compound of claim 11 wherein the antisense oligonucleotide comprises at least one modified nucleobase.

17. The antisense compound of claim 16 wherein the modified nucleobase is a 5-methylcytosine.

18. The antisense compound of claim 11 wherein the antisense oligonucleotide is a chimeric oligonucleotide.

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

20. The composition of claim 19 further comprising a colloidal dispersion system.

21. The composition of claim 19 wherein the antisense compound is an antisense oligonucleotide.

22. A composition comprising the antisense compound of claim 10 and a pharmaceutically acceptable carrier or diluent.

23. The composition of claim 22 further comprising a colloidal dispersion system.

24. The composition of claim 22 wherein the antisense compound is an antisense oligonucleotide.

25. A method of inhibiting the expression of human glycogen synthase kinase 3 alpha 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 glycogen synthase kinase 3 alpha is inhibited.

26. A method of inhibiting the expression of human glycogen synthase kinase 3 alpha in human cells or tissues comprising contacting said cells or tissues in vitro with the antisense compound of claim 10 so that expression of human glycogen synthase kinase 3 alpha is inhibited.

Details for Patent 6,316,259

Applicant Tradename Biologic Ingredient Dosage Form BLA Approval Date Patent No. Expiredate
Merck Sharp & Dohme Corp. INTRON A interferon alfa-2b For Injection 103132 06/04/1986 ⤷  Try a Trial 2039-02-26
Merck Sharp & Dohme Corp. INTRON A interferon alfa-2b For Injection 103132 ⤷  Try a Trial 2039-02-26
Merck Sharp & Dohme Corp. INTRON A interferon alfa-2b Injection 103132 ⤷  Try a Trial 2039-02-26
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

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