Organic compositions to treat HSF1-related diseases

Patent metadata

Field	Value
Publication number	US-10329563-B2
Application number	US-201715587538-A
Country	US
Kind code	B2
Filing date	May 5, 2017
Priority date	Sep 2, 2011
Publication date	Jun 25, 2019
Grant date	Jun 25, 2019

Abstract

The present disclosure relates to methods of treating heat stock factor 1 (HSF1)-related diseases such as cancer, autoimmune and viral diseases, using a therapeutically effective amount of a RNAi agent to HSF.

First claim

We claim:

1. A composition comprising a RNAi agent for inhibiting the expression of HSF1, the RNAi agent comprising a sense strand and an antisense strand, wherein the antisense strand comprises at least 19 contiguous nucleotides differing by 0 or 1 nucleotides from:
(i) the antisense strand sequence UUAGCAUAGAGCCUGUCUG (SEQ ID NO: 178); or
(ii) the antisense strand sequence UUUAGCAUAGAGCCUGUCU (SEQ ID NO: 179);

wherein the antisense strand comprises at least one modified backbone and/or at least one 2′-modified nucleotide, and wherein the sense strand is at least substantially complementary to the antisense strand.

2. The composition of claim 1 , wherein the composition further comprises a second RNAi agent to HSF1.

3. The composition of claim 1 , wherein the RNAi agent comprises at least one phosphorothioate linkage.

4. The composition of claim 1 , wherein the RNAi agent is ligated to one or more agent selected from: one or more 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 transferrin.

5. The composition of claim 1 , wherein the composition is a pharmaceutically effective formulation.

6. The composition of claim 2 , wherein the composition is a pharmaceutically effective formulation.

7. The composition of claim 1 , wherein all the pyrimidine nucleotides of the RNAi agent are 2′-O-methyl modified nucleotides.

8. The composition of claim 1 , wherein the antisense strand of the RNAi agent comprises:
(i) the sequence UUAGCAUAGAGCCUGUCUG (SEQ ID NO: 178); or
(ii) the sequence UUUAGCAUAGAGCCUGUCU (SEQ ID NO: 179).

9. The composition of claim 1 , wherein the sense strand of the RNAi agent comprises at least 19 contiguous nucleotides differing by 0, 1, 2, or 3 nucleotides from:
(i) the sequence CAGACAGGCUCUAUGCUAA (SEQ ID NO: 262); or
(ii) the sequence AGACAGGCUCUAUGCUAAA (SEQ ID NO: 263).

10. The composition of claim 9 , wherein the sense strand of the RNAi agent comprises at least 19 contiguous nucleotides differing by 0 or 1 nucleotides from:
(i) the sequence CAGACAGGCUCUAUGCUAA (SEQ ID NO: 262); or
(ii) the sequence AGACAGGCUCUAUGCUAAA (SEQ ID NO: 263).

11. The composition of claim 1 , wherein the RNAi agent comprises:
(i) an antisense strand that comprises the sequence UUAGCAUAGAGCCUGUCUG (SEQ ID NO: 178) and the sense strand comprises the sequence CAGACAGGCUCUAUGCUAA (SEQ ID NO: 262); or
(ii) an antisense strand that comprises the sequence UUUAGCAUAGAGCCUGUCU (SEQ ID NO: 179) and the sense strand comprises the sequence AGACAGGCUCUAUGCUAAA (SEQ ID NO: 263).

12. The composition of claim 11 , wherein the RNAi agent comprises:
(i) 2153_A22_S26 (SEQ ID Pair NOs: 346/430);
(ii) 2153_A25_S27 (SEQ ID Pair NOs: 358/442);
(iii) 2153_A81_S26 (SEQ ID Pair NOs: 370/454);
(iv) 2153_A48_S26 (SEQ ID Pair NOs: 382/466);
(v) 2153_A82_S36 (SEQ ID Pair NOs: 394/478);
(vi) 2153_A83_S36 (SEQ ID Pair NOs: 406/490); or
(vii) 2153_A84_S36 (SEQ ID Pair NOs: 418/502).

13. The composition of claim 11 , wherein the RNAi agent comprises:
(i) 2154_A22_S26 (SEQ ID Pair NOs: 347/431);
(ii) 2154_A25_S27 (SEQ ID Pair NOs: 359/443);
(iii) 2154_A81_S26 (SEQ ID Pair NOs: 371/455);
(iv) 2154_A48_S26 (SEQ ID Pair NOs: 383/467);
(v) 2154_A82_S36 (SEQ ID Pair NOs: 395/479);
(vi) 2154_A83_S36 (SEQ ID Pair NOs: 407/491); or
(vii) 2154_A84_S36 (SEQ ID Pair NOs: 419/503).

Assignees

• Arrowhead Pharmaceuticals Inc

Inventors

• Chen Jinyun
• Gampa Kalyani
• Huesken Dieter
• Stegmeier Frank
• Stump Mark
• Vargeese Chandra
• Weiler Jan
• Zhou Wenlai

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title