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Patent Application
App. No. 13/003,740

Compositions And Methods For Inhibiting Expression Of GSK-3 Genes

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Patent No.
US None
App. No.
13/003,740
Abstract

The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting Glycogen Synthase Kinase-3 (GSK-3), and methods of using the dsRNA to inhibit expression of GSK-3.

Claims (34)

1 . A double-stranded ribonucleic acid (dsRNA), comprising a sense strand and an antisense strand, the sense strand comprising a first sequence and the antisense strand comprising a second sequence, the second sequence comprising a region complementary to an mRNA encoding a GSK-3, and wherein said region of complementarity is less than 30 nucleotides in length.

2 . (canceled)

3 . The dsRNA of claim 1 , the second sequence comprising a region complementary to at least 15 nucleotides of the sense strand of huGSKA-3 (SEQ ID NO:13075).

4 . The dsRNA of claim 1 , the second sequence comprising a region complementary to the sense strand of huGSKA-3 (SEQ ID NO:13075).

5 . The dsRNA of claim 1 , the antisense strand comprising at least 15 nucleotides of the antisense strand of huGSKA-3 (SEQ ID NO:13083).

6 . The dsRNA of claim 1 , the antisense strand comprising the antisense strand of huGSKA-3 (SEQ ID NO:13083).

7 . The dsRNA of claim 1 , the antisense strand consisting of the antisense strand of huGSKA-3 (SEQ ID NO:13083).

8 . The dsRNA of claim 1 , the sense strand comprising at least 15 nucleotides of the sense strand of huGSKA-3 (SEQ ID NO:13075).

9 . The dsRNA of claim 1 , the sense strand comprising the sense strand of huGSKA-3 (SEQ ID NO:13075).

10 . The dsRNA of claim 1 , the sense strand consisting of the sense strand of huGSKA-3 (SEQ ID NO:13075).

11 . The dsRNA of claim 1 , the sense strand consisting of the sense strand of huGSKA-3 (SEQ ID NO:13075) and the antisense strand consisting of the antisense strand of huGSKA-3 (SEQ ID NO:13083).

12 . (canceled)

13 . (canceled)

14 . (canceled)

15 . (canceled)

16 . The dsRNA of claim 1 , wherein said dsRNA comprises at least one modified nucleotide.

17 . The dsRNA of claim 16 , wherein at least one of said modified nucleotides is chosen from the group of: a 2′-O-methyl modified nucleotide, a nucleotide comprising a 5′-phosphorothioate group, and a terminal nucleotide linked to a cholesteryl derivative or dodecanoic acid bisdecylamide group.

18 . The dsRNA of claim 16 , wherein said modified nucleotide is chosen from the group of: a 2′-deoxy-2′-fluoro modified nucleotide, a 2′-deoxy-modified nucleotide, a locked nucleotide, an abasic nucleotide, 2′-amino-modified nucleotide, 2′-alkyl-modified nucleotide, morpholino nucleotide, a phosphoramidate, and a non-natural base comprising nucleotide.

19 . The dsRNA of claim 16 , comprising at least one 2′-O-methyl modified nucleotide and at least one nucleotide comprising a 5′-phosphorothioate group,

20 . The dsRNA of claim 1 , wherein the region of complementary is at least 15 nucleotides in length.

21 . The dsRNA of claim 1 , wherein the region of complementarity is between 19 and 21 nucleotides in length.

22 . The dsRNA of claim 1 , wherein the region of complementarity is 19 nucleotides in length.

23 . The dsRNA of claim 1 , wherein administration of the dsRNA inhibits expression of GSK3 by more than 40%.

24 . The dsRNA of claim 1 , wherein the dsRNA exhibits an 1050 of less than or equal to 10 nM in suppressing GSK3.

25 . The dsRNA of claim 1 , wherein the dsRNA exhibits an 1050 of less than or equal to 1.0 nM in suppressing GSK3.

26 . A cell comprising the dsRNA of claim 1 .

27 . A vector comprising at least one strand of the dsRNA of claim 1 .

28 . A cell comprising the vector of claim 27 .

29 . A pharmaceutical composition for inhibiting expression of an GSK-3 gene comprising the dsRNA of claim 1 .

30 . A method of inhibiting GSK-3 expression in a cell, the method comprising:

(a) introducing into the cell the dsRNA of claim 1 ; and

(b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of a GSK-3 gene, thereby inhibiting expression of a GSK-3 gene in the cell.

31 . A method of treating a disorder mediated by GSK-3 expression comprising administering to a human in need of such treatment a therapeutically effective amount of the dsRNA of claim 1 .

32 . (canceled)

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 23, 2011
From: SAH, DINAH WEN-YEE; HINKLE, GREGORY
To: ALNYLAM PHARMACEUTICALS, INC.
Reel/Frame 026006/0028 →