IP Library › Granted Patent US 12,350,267
Granted Patent B2
US 12,350,267 · App. 17/730,737 · Granted Jul 8, 2025

Bile acid recycling inhibitors for treatment of pediatric cholestatic liver diseases

Inventors: Bronislava Gedulin (Del Mar, CA); Michael Grey (Rancho Sante Fe, CA); Niall O'Donnell (Encintas, CA)
Assignee: SHIRE HUMAN GENETIC THERAPIES, INC.
A61K31/4995A61K9/0053A61K9/0056A61K9/1611A61K9/1617A61K9/1623A61K9/1635A61K9/2009A61K9/2013A61K9/2018A61K9/2027A61K9/2054A61K9/2059A61K9/2081A61K31/155A61K31/38A61K31/41A61K31/495A61K31/4965A61K31/4985A61K31/5377A61K31/554A61K45/06A61P1/16C07D281/10C07D337/08C07D409/10C07D487/08C07H15/26A61K31/4436A61K31/7042
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Quick Facts
Patent No.
US 12,350,267
App. No.
17/730,737
Granted
Jul 8, 2025
Kind
B2
Abstract

Provided herein are methods of treating or ameliorating a pediatric cholestatic liver disease by non-systemically administering to an individual in need thereof a therapeutically effective amount of a pediatric formulation comprising an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) or a pharmaceutically acceptable salt thereof. Also provided are methods for treating or ameliorating a pediatric liver disease, decreasing the levels of serum bile acids or hepatic bile acids, treating or ameliorating pruritis, reducing liver enzymes, or reducing bilirubin comprising non-systemically administering to an individual in need thereof a therapeutically effective amount of a pediatric formulation comprising an ASBTI or a pharmaceutically acceptable salt thereof.

Claims (23)

1. A method for treating or ameliorating progressive familial intrahepatic cholestasis (PFIC) in a pediatric subject comprising administering to the pediatric subject an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI), wherein the ASBTI is

or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

2. A method for treating or ameliorating pruritus in a pediatric subject having progressive familial intrahepatic cholestasis (PFIC) comprising administering to the pediatric subject an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI), wherein the ASBTI is

or a pharmaceutically acceptable salt thereof.

3. The method of claim 1 , wherein the method comprises reducing serum lipoprotein X, liver enzymes, bilirubin, intraenterocyte bile acids/salts, or necrosis and/or damage to hepatocellular architecture.

4. The method of claim 1 comprising administering to the pediatric subject a pharmaceutical composition comprising the ASBTI, or the pharmaceutically acceptable salt thereof.

5. The method of claim 4 , wherein the composition is a pediatric dosage form.

6. The method of claim 5 , wherein the pediatric dosage form is selected from a solution, syrup, suspension, elixir, powder for reconstitution as suspension or solution, dispersible/effervescent tablet, chewable tablet, gummy candy, lollipop, freezer pops, troches, oral thin strips, orally disintegrating tablet, sachet, soft gelatin capsule, and sprinkle oral powder or granules.

7. The method of claim 6 , wherein the pediatric dosage form comprises between about 0.1 mg to about 100 mg of the ASBTI.

8. The method of claim 6 , wherein the pediatric dosage form comprises between about 0.001 mg/kg and about 50 mg/kg of the ASBTI.

9. The method of claim 8 , wherein the pediatric dosage form comprises between about 0.01 mg/kg and about 10 mg/kg of the ASBTI.

10. The method of claim 6 , wherein the pediatric dosage form of the ASBTI comprises between about 1 μg/kg/day to about 10 mg/kg/day.

11. The method of claim 1 , wherein the pediatric cholestatic liver disease is PFIC type 1, PFIC type 2, or PFIC type 3.

12. The method of claim 1 , wherein the PFIC is characterized by one or more symptoms selected from jaundice, pruritus, cirrhosis, hypercholemia, neonatal respiratory distress syndrome, lung pneumonia, increased serum concentration of bile acids, increased hepatic concentration of bile acids, increased serum concentration of bilirubin, hepatocellular injury, liver scarring, liver failure, hepatomegaly, malabsorption, splenomegaly, diarrhea, pancreatitis, hepatocellular necrosis, giant cell formation, hepatocellular carcinoma, gastrointestinal bleeding, portal hypertension, hearing loss, fatigue, loss of appetite, anorexia, peculiar smell, dark urine, light stools, steatorrhea, failure to thrive, and renal failure.

13. The method of claim 1 , wherein the pediatric subject is between 2 months to 12 years old.

14. The method of claim 1 , wherein less than 10% of the ASBTI is systemically absorbed.

15. The method of claim 1 , wherein the ASBTI is effective for decreasing at least 20% of serum and/or hepatic bile acid levels in the pediatric subject as compared to bile acid levels prior to administration of the ASBTI.

16. The method of claim 1 , wherein the ASBTI is effective for decreasing at least 30% of serum and/or hepatic bile acid levels in the pediatric subject as compared to bile acid levels prior to administration of the ASBTI.

17. The method of claim 1 , wherein the ASBTI is effective for decreasing at least 40% of serum and/or hepatic bile acid levels in the pediatric subject as compared to bile acid levels prior to administration of the ASBTI.

18. The method of claim 1 , wherein the ASBTI is effective for decreasing at least 50% of serum and/or hepatic bile acid levels in the pediatric subject as compared to bile acid levels prior to administration of the ASBTI.

19. The method of claim 4 , wherein the composition further comprises a bile acid sequestrant or binder.

20. A method for treating or ameliorating progressive familial intrahepatic cholestasis (PFIC) comprising administering to a pediatric subject a pharmaceutical composition comprising an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI), wherein the ASBTI is

or a pharmaceutically acceptable salt, solvate, or prodrug thereof.

Assignments (6)
CORRECTIVE ASSIGNMENT TO CORRECT THE RECEIVING PARTY DATA PREVIOUSLY RECORDED ON REEL 59809 FRAME 491. ASSIGNOR(S) HEREBY CONFIRMS THE CHANGE OF NAME. Recorded Apr 15, 2025
From: LUMENA PHARMACEUTICALS, INC.
To: LUMENA PHARMACEUTICALS LLC
Reel/Frame 070849/0951 →
CORRECTIVE ASSIGNMENT TO CORRECT THE CONVEYING PARTY DATA AND RECEIVING PARTY ADDRESS PREVIOUSLY RECORDED ON REEL 59808 FRAME 186. ASSIGNOR(S) HEREBY CONFIRMS THE CHANGE OF ADDRESS. Recorded Apr 15, 2025
From: LUMENA PHARMACEUTICALS LLC
To: LUMENA PHARMACEUTICALS LLC
Reel/Frame 071079/0597 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 27, 2022
From: GEDULIN, BRONISLAVA; GREY, MICHAEL; O'DONNELL, NIALL
To: LUMENA PHARMACEUTICALS, INC.
Reel/Frame 059740/0996 →
MERGER AND CHANGE OF NAME Recorded Apr 27, 2022
From: LUMENA PHARMACEUTICALS LLC; SHIRE HUMAN GENETIC THERAPIES, INC.
To: SHIRE HUMAN GENETIC THERAPIES, INC.
Reel/Frame 059742/0836 →
CHANGE OF ADDRESS Recorded Apr 27, 2022
From: LUMENA PHARMACEUTICAL LLC
To: LUMENA PHARMACEUTICALS LLC
Reel/Frame 059808/0186 →
CHANGE OF NAME Recorded Apr 27, 2022
From: LUMENA PHARMACEUTICALS, INC.
To: LUMENA PHARMACEUTICAL LLC
Reel/Frame 059809/0491 →
Continuity (9)
Continuation 17498586 · Oct 11, 2021
Continuation 16679864 · Nov 11, 2019
Continuation 15137323 · Apr 25, 2016
Continuation 13866906 · Apr 19, 2013
Continuation 13662387 · Oct 26, 2012
Provisional Application 61607487 · Mar 6, 2012
Provisional Application 61607503 · Mar 6, 2012
Provisional Application 61553094 · Oct 28, 2011
Related Publication 20220265649A1 · Aug 25, 2022
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