Organic compositions to treat beta-catenin-related diseases

Patent metadata

Field	Value
Publication number	US-10023862-B2
Application number	US-201314371131-A
Country	US
Kind code	B2
Filing date	Jan 8, 2013
Priority date	Jan 9, 2012
Publication date	Jul 17, 2018
Grant date	Jul 17, 2018

Abstract

The present disclosure relates to RNAi agents useful in methods of treating Beta-Catenin-related diseases such as adenomatous polyposis of the colon, colorectal cancer, basal cell carcinoma, breast cancer, kidney cancer, Wilms tumors, medulloblastoma, ovarian cancer, adrenocortical tumors, gastric cancer, liver cancer, melanoma, pancreatic cancers, prostate cancer, renal cancer, ectopic teeth and taste papillae, skin cancer, pilomatrixoma, anaplastic thyroid carcinoma, and uterine carcinosarcoma, oligodontia, osteoporosis, ageing, degenerative diseases, bedsores, chronic wounds and impaired wound healing, and similar and related diseases, using a therapeutically effective amount of a RNAi agent to Beta-Catenin.

First claim

We claim:

1. A composition comprising a RNAi agent comprising a sense strand and an antisense strand, wherein the antisense strand is 19-40 nucleotides in length and comprises the sequence AAAAGAACGAUAGCUAGGA (SEQ ID NO: 6121) (5′→3′), wherein SEQ ID NO: 6121 is nucleotides 1-19 from the 5′ terminal end of the antisense strand, and wherein SEQ ID NO: 6121 comprises at least one modified backbone and/or at least one 2′-modified nucleotide.

2. The composition of claim 1 , wherein the composition further comprises a second RNAi agent to Beta-Catenin.

3. The composition of claim 1 , wherein the sense strand of the RNAi agent comprises at least one modified backbone and/or at least one 2′-modified nucleotide.

4. The composition of claim 1 , wherein the RNAi agent is ligated to one or more agent selected from: diagnostic compound, reporter group, cross-linking agent, nuclease-resistance conferring moiety, natural or unusual nucleobase, lipophilic molecule, cholesterol, lipid, lectin, steroid, uvaol, hecigenin, diosgenin, terpene, triterpene, sarsasapogenin, Friedelin, epifriedelanol-derivatized lithocholic acid, vitamin, carbohydrate, dextran, pullulan, chitin, chitosan, synthetic carbohydrate, oligo lactate 15-mer, natural polymer, low- or medium-molecular weight polymer, inulin, cyclodextrin, hyaluronic acid, protein, protein-binding agent, integrin-targeting molecule, polycationic, peptide, polyamine, peptide mimic, and/or transferrin.

5. The composition of claim 1 , wherein the RNAi agent comprises a phosphorothioate linkage and/or a 2′-O-methyl modified nucleotide.

6. The composition of claim 4 , wherein the RNAi agent is ligated to one or more agents, the agent selected from cholesterol, carbohydrate, synthetic carbohydrate, natural polymer, low- or medium-molecular weight polymer, integrin-targeting molecule, peptide, polyamine, peptide mimic, and/or transferrin.

7. The composition of claim 1 , further comprising a pharmaceutically effective excipient.

8. The composition of claim 1 , wherein all the pyrimidines are 2′ O-methyl-modified nucleotides.

9. The composition of claim 4 , wherein all the pyrimidines are 2′ O-methyl-modified nucleotides.

Assignees

• Huesken Dieter
• Bettencourt Brian
• Bumcrot David
• Kuchimanchi Satyanarayana
• Milstein Stuart
• Schlabach Jr Michael
• Stegmeier Frank P
• Warmuth Markus
• Weiler Jan
• Novartis Ag
• Arrowhead Pharmaceuticals Inc

Inventors

• Bettencourt Brian Richard
• Bumcrot David Anton
• Huesken Dieter
• Kuchimanchi Satyanarayana
• Milstein Stuart
• Schlabach Jr Michael Ray
• Stegmeier Frank Peter
• Warmuth Markus
• Weiler Jan

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P19/10

  for osteoporosis · CPC title

• A61P17/02

  for treating wounds, ulcers, burns, scars, keloids, or the like · CPC title

• C12N2310/344

  Position-specific modifications, e.g. on every purine, at the 3'-end · CPC title

• C12N2310/321

  2'-O-R Modification · CPC title