RNA INTERFERENCE MEDIATED INHIBITION OF CATENIN (CADHERIN-ASSOCIATED PROTEIN), BETA 1 (CTNNB1) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (SINA)

• US 20190330639A1
• Filed: 02/08/2019
• Published: 10/31/2019
• Est. Priority Date: 08/02/2010
• Status: Abandoned Application

• Current Assignee: Sirna Therapeutics, Inc. (Alnylam Pharmaceuticals Incorporated)
• Original Assignee: Sirna Therapeutics, Inc. (Alnylam Pharmaceuticals Incorporated)
• Inventors: Brown, Duncan, Cunningham, James J., Gindy, Marian, Pickering, Victoria, Stanton, Matthew G., Stirdivant, Steven M., Strapps, Walter R.
• Application Number:
  US16/270,663
• Publication Number:
  US 20190330639A1
• Time in Patent Office: Days
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 15/1138 against receptors or cell surface proteins
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/332 Abasic residue
• CPC Class Codes: C12N 2310/346 having a combination of backbone and sugar modifications
• CPC Class Codes: C12N 2310/3521 Methyl
• CPC Class Codes: C12N 2320/32 Special delivery means, e.g. tissue-specific

Abstract

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of CTNNB1 gene expression and/or activity, and/or modulate a beta-catenin gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against CTNNB1 gene expression.

Claims

1. An isolated double-stranded short interfering nucleic acid (siNA) molecule that inhibits the expression of cadherin-associated protein, beta 1 (CTNNB1), wherein

(a) the siNA comprises a sense strand and an antisense strand;

(b) each strand is independently 15 to 30 nucleotides in length; and

(c) at least one strand comprises at least a 15 nucleotide sequence of any one of the nucleotide sequences selected from the group consisting of SEQ ID NO;

1-6374.

6. The double-stranded short interfering nucleic acid (siNA) molecule according to claim 1, wherein at least one nucleotide is a chemically modified nucleotide.

7. The double-stranded short interfering nucleic acid (siNA) molecule according to claim 1 further comprising at least one non-nucleotide.

8. The double-stranded short interfering nucleic acid (siNA) molecule according to claim 1, wherein at least one nucleotide comprises a universal base.

9. The double-stranded short interfering nucleic acid (siNA) molecule according to claim 1, having at least one phosphorothioate internucleotide linkage.

10. The double-stranded short interfering nucleic acid (siNA) molecule according to claim 1, comprising a cap on the 3′

-end, 5′

-end or both 3′ and

5′

ends of at least one strand.

11. The double-stranded short interfering nucleic acid (siNA) molecule according to claim 1, comprising one or more 3′

-overhang nucleotides on one or both strands.

13. The double-stranded short interfering nucleic acid (siNA) molecule of claim 11, wherein the 3′

-overhang nucleotides on at least one strand are 2′

-O-methyl nucleotides.

14. The double-stranded short interfering nucleic acid (siNA) molecule of claim 13, wherein the 2′

-O-methyl nucleotides are linked with a phosphorothioate internucleotide linkage

15. The double-stranded short interfering nucleic acid (siNA) molecule of claim 6, wherein the chemically modified nucleotide is a 2′

-deoxy-2′

-fluoro nucleotide.

16. The double-stranded short interfering nucleic acid (siNA) molecule of claim 6, wherein the chemically modified nucleotide is a 2′

-deoxy nucleotide.

17. The double-stranded short interfering nucleic acid (siNA) molecule of claim 6, wherein the chemically modified nucleotide is a 2′

-0-alkyl nucleotide.

30. A composition comprising the double-stranded short interfering nucleic acid (siNA) according to claim 1 in a pharmaceutically acceptable carrier or diluent.

38. A method of treating a human subject suffering from a condition which is mediated by the action, or by loss of action, of CTNNB1, which comprises administering to said subject an effective amount of the double-stranded short interfering nucleic acid (siNA) molecule of claim 1 or the composition of claim 30.

2-5. -5. (canceled)

12. (canceled)

18-29. -29. (canceled)

31-37. -37. (canceled)

39. The method according to claim 39, wherein the condition is cancer.