Claims for Patent: 10,512,657

Summary for Patent: 10,512,657

Title:	Bile acid recycling inhibitors for treatment of pediatric cholestatic liver diseases
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.
Inventor(s):	Gedulin Bronislava, Grey Michael, "ODonnell Niall"
Assignee:	LUMENA PHARMACEUTIALS LLC
Application Number:	US15137323
Patent Claims:	4. The method of claim 1 , wherein the method comprises reducing xanthoma claim 1 , serum lipoprotein X claim 1 , liver enzymes claim 1 , bilirubin claim 1 , intraenterocyte bile acids/salts claim 1 , or necrosis and/or damage to hepatocellular architecture.5. The method of claim 3 , wherein the composition is a pediatric dosage form.6. The method of claim 5 , wherein the pediatric dosage form is selected from a solution claim 5 , syrup claim 5 , suspension claim 5 , elixir claim 5 , powder for reconstitution as suspension or solution claim 5 , dispersible/effervescent tablet claim 5 , chewable tablet claim 5 , gummy candy claim 5 , lollipop claim 5 , freezer pops claim 5 , troches claim 5 , oral thin strips claim 5 , orally disintegrating tablet claim 5 , sachet claim 5 , soft gelatin capsule claim 5 , and sprinkle oral powder or granules.7. The method of claim 1 , wherein the ASBTI is administered in an amount between about 10 μg/kg/day and about 300 μg/kg/day.8. The method of claim 1 , wherein the ASBTI is administered in an amount between about 14 μg/kg/day to about 280 μg/kg/day.9. The method of claim 1 , wherein the ASBTI is administered in an amount between about 14 μg/kg/day to about 140 μg/kg/day.10. The method of claim 5 , wherein the pediatric dosage form comprises between 0.1 to 20 mg of the ASBTI.11. The method of claim 1 , wherein the progressive familial intrahepatic cholestasis type 2 (PFIC2) is characterized by one or more symptoms selected from jaundice claim 1 , pruritis claim 1 , cirrhosis claim 1 , hypercholemia claim 1 , neonatal respiratory distress syndrome claim 1 , lung pneumonia claim 1 , increased serum concentration of bile acids claim 1 , increased hepatic concentration of bile acids claim 1 , increased serum concentration of bilirubin claim 1 , hepatocellular injury claim 1 , liver scarring claim 1 , liver failure claim 1 , hepatomegaly claim 1 , xanthomas claim 1 , malabsorption claim 1 , splenomegaly claim 1 , diarrhea claim 1 , pancreatitis claim 1 , hepatocellular necrosis claim 1 , giant cell formation claim 1 , hepatocellular carcinoma claim 1 , gastrointestinal bleeding claim 1 , portal hypertension claim 1 , hearing loss claim 1 , fatigue claim 1 , loss of appetite claim 1 , anorexia claim 1 , peculiar smell claim 1 , dark urine claim 1 , light stools claim 1 , steatorrhea claim 1 , failure to thrive claim 1 , and renal failure.12. The method of claim 1 , wherein the pediatric patient is between 6 months to 12 years old.13. The method of claim 1 , wherein less than 10% of the ASBTI is systemically absorbed.14. The method of claim 3 , wherein the composition further comprises a bile acid sequestrant or binder.15. 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.16. 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.17. 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.