Therapeutic targets involved in the progression of nonalcoholic steatohepatitis (NASH)

Patent metadata

Field	Value
Publication number	US-12285464-B2
Application number	US-201716094111-A
Country	US
Kind code	B2
Filing date	Apr 18, 2017
Priority date	Apr 18, 2016
Publication date	Apr 29, 2025
Grant date	Apr 29, 2025

Abstract

The present invention relates to methods and compositions for specifically modulating the Hippo pathway transcription factor TAZ (WWTR1), as a therapeutic target for inhibiting or preventing liver conditions including the progression of steatosis-to-NASH in a patient.

First claim

The invention claimed is:

1. A method for treating or preventing progression of steatosis to non-alcoholic steatohepatitis (NASH) in a patient in need thereof, the method comprising administering to the patient in need thereof a therapeutically effective amount of an inhibitor of TAZ, where the inhibitor of TAZ is a nucleic acid comprising a sequence complementary to a sequence encoding human TAZ.

2. The method of claim 1 , wherein the inhibitor of TAZ is administered to at least one hepatocyte of said patient.

3. The method of claim 1 , further comprising administering a therapeutically effective amount of an inhibitor of Indian hedgehog (Ihh), an inhibitor of YAP, an inhibitor of TEAD1, and inhibitor of TEAD2, an inhibitor of TEAD3, an inhibitor of TEAD4, or any combination thereof.

4. The method of claim 1 , wherein the nucleic acid is selected from the group consisting of antisense oligonucleotide, siRNA, shRNA, and combinations thereof.

5. The method of claim 1 , wherein the sequence complementary to the sequence encoding human TAZ is set forth by SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NOs: 55-72, or SEQ ID NO: 81.

6. The method of claim 4 , wherein the nucleic acid is formulated in a nanoparticle.

7. The method of claim 6 , wherein the nanoparticle comprises: 1) a hydrophobic inner core, 2) a hydrophilic outer shell and 3) a hepatocyte targeting ligand.

Assignees

• Univ Columbia
• Brigham & Womens Hospital Inc

Inventors

• Tabas Ira
• Wang Xiaobo
• Farokhzad Omid
• Xu Xiaoding

Classifications

• A61K9/5073

  having two or more different coatings optionally including drug-containing subcoatings · CPC title

• A61K31/4439

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title

• G01N33/50

  Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing (measuring or testing processes involving enzymes or microorganisms, compositions or test papers therefor; processes for forming such compositions, condition responsive control in microbiological or enzymological processes C12Q) · CPC title

• A61K31/4178

  not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin · CPC title

• C12N2310/14

  interfering nucleic acids [NA] · CPC title