Granted Patent B2

US 12,440,466 · App. 18/418,901 · Granted Oct 14, 2025

Inventors: Hilde Steineger (Oslo, NO); David Alan Fraser (Blommenholm, NO); Tore Skjæret (Oslo, NO)

Assignee: BASF AS

A61K31/202A61K9/0053A61K45/06A61P1/16

Abstract

Claims (19)

1. A method of inhibiting the progression of hepatic fibrosis in a subject with non-alcoholic steatohepatitis, comprising administering to the subject a pharmaceutically effective amount of a compound of 2-(((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)oxy)butanoic acid (Compound A), or a pharmaceutically acceptable salt or ester thereof, having the structure:

wherein the subject has hepatic fibrosis and the hepatic fibrosis does not progress as compared to an untreated individual,

wherein the method further therapeutically treats non-alcoholic steatohepatitis.

2. The method of claim 1 , wherein the subject has type 2 diabetes.

3. The method of claim 1 , wherein the compound is present in the form of an enantiomer, a diastereomer, or a mixture thereof.

4. The method of claim 1 , wherein the compound is present in its R form, in its S form, or in racemic form.

5. The method of claim 1 , wherein the compound is administered in a dose ranging from about 5 mg to about 4 g per dose.

6. The method of claim 1 , wherein the compound is administered at a dosage of 300 mg daily or 600 mg daily.

7. The method of claim 1 , wherein the compound is administered once daily.

8. The method of claim 1 , wherein the method reverses non-alcoholic steatohepatitis.

9. The method of claim 1 , wherein the method provides a reduction of hepatic inflammation, hepatocellular ballooning, steatohepatitis, fibrosis, and/or a reduction in steatohepatitis.

10. The method of claim 1 , wherein the compound is formulated as a pharmaceutical composition, wherein the pharmaceutical composition further comprises at least one binder, excipient, diluent, or antioxidant, or a combination thereof.

11. The method of claim 10 , wherein the pharmaceutical composition is formulated for oral administration.

12. The method of claim 1 , wherein the compound is administered as a monotherapy.

13. The method of claim 1 , further comprising co-administering one or more additional active agent(s).

14. The method of claim 13 , wherein the one or more additional active agent(s) are independently chosen from allosteric acetyl-CoA carboxylase (ACC) inhibitors, angiotensin II receptor antagonists, angiotensin converting enzyme (ACE) inhibitors, apoptosis signal-regulating kinase-1 (ASK1) inhibitors, caspase inhibitors, cathepsin B inhibitors, CCR2 chemokine antagonists, CCR5 chemokine antagonists, chloride channel stimulators, cholesterol solubilizers, diacyl glycerol O-acyltransferase 1 (DGAT1) inhibitors, dipeptidyl peptidase IV (DPP IV) inhibitors, fibroblast-growth factor (FGF)-21 agonists, farnesoid X receptor (FXR) agonists, anti-CD3 mAb, galectin-3 inhibitors, glucagon-like peptide 1 (GLP1) receptor agonists, glutathione precursors, hepatitis C virus NS3 protease inhibitors, HMG CoA reductase inhibitors, 17β-hydroxysteroid dehydrogenase (17β-HSDI) inhibitors, heat shock protein (Hsp) 47 inhibitors, IL-1β antagonists, IL-6 antagonists, IL-10 agonists, IL-17 antagonists, ileal sodium bile acid co-transporter inhibitors, leptin analogs, 5-lipoxygenase inhibitors, LPL gene stimulators, lysyl oxidase homolog 2 (LOXL2) inhibitors, lysophosphatidic acid 1 (LPA1) receptor antagonists, omega-3 fatty acids, PDE3 inhibitors, PDE4 inhibitors, phospholipase C (PLC) inhibitors, PPARα agonists, PPARγ agonists, PPARβ/δ agonists, recombinant human pentraxin-2 protein (PRF-1), Rho associated protein kinase 2 (ROCK2) inhibitors, semicarbazide-sensitive amine oxidase (SSAO) inhibitors, sodium glucose transporter-2 (SGLT2) inhibitors, stearoyl CoA desaturase-1 inhibitors, thyroid hormone receptor β agonists, tumor necrosis factor a (TNFα) ligand inhibitors, transglutaminase inhibitors, transglutaminase inhibitor precursors, and small activating RNA (saRNA).

15. The method of claim 13 , wherein the one or more additional active agents are independently chosen from a Glucagon-like peptide 1 (GLP-1) receptor agonist; a dipeptidyl peptidase (DPP IV) inhibitor; and omega-3 fatty acids (n-3 PUFA).

16. The method of claim 13 , wherein the one or more additional active agents are independently chosen from acetylsalicylic acid, alipogene tiparvovec, aramchol, atorvastatin, BI 1467335, BLX-1002, BMS-986036, BMS-986020, cenicriviroc, cobiprostone, colesevelam, emricasan, enalapril, foramulab, GFT-505, GR-MD-02, GS-0976, GS-9674, hydrochlorothiazide, icosapent ethyl ester (ethyl eicosapentaenoic acid), IMM-124E, IVA337, K-877, KD-025, linagliptin, liraglutide, mercaptamine, MGL-3196, ND-L02-s0201, obeticholic acid, olesoxime, peg-ilodecakin, pioglitazone, PRM-151, PX-102, remogliflozin etabonate, selonsertib, simtuzumab, SHP-626, solithromycin, tipelukast, TRX-318, ursodeoxycholic acid, and VBY-376.

17. The method of claim 13 , wherein the co-administration is by simultaneous administration, sequential administration, overlapping administration, interval administration, continuous administration, or a combination thereof.

Assignments (2)

Priority Claims (2)

Continuity (3)

References Cited (293)