Compositions and methods of treating liver disease

• US 10,668,108 B2
• Filed: 11/03/2017
• Issued: 06/02/2020
• Est. Priority Date: 11/04/2016
• Status: Active Grant

• Current Assignee: Children's Hospital & Medical Center
• Original Assignee: Children's Hospital & Medical Center
• Inventors: Takebe, Takanori, Ouchi, Rie
• Primary Examiner(s): Valenrod, Yevgeny
• Application Number:
  US16/343,157
• Publication Number:
  US 20190314387A1
• Time in Patent Office: 942 Days
• Field of Search: 514169
• CPC Class Codes: A61K 31/575 substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
• CPC Class Codes: A61K 35/407 Liver; Hepatocytes
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0029 Parenteral nutrition; Parenteral nutrition compositions as drug carriers
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: C12N 15/01 Preparation of mutants without inserting foreign genetic material therein; Screening processes therefor
• CPC Class Codes: C12N 2500/36 Lipids
• CPC Class Codes: C12N 2501/119 Other fibroblast growth factors, e.g. FGF-4, FGF-8, FGF-10
• CPC Class Codes: C12N 2506/45 from artificially induced pluripotent stem cells
• CPC Class Codes: C12N 5/0671 Three-dimensional culture, tissue culture or organ culture; Encapsulated cells
• CPC Class Codes: C12N 5/0672 Stem cells; Progenitor cells; Precursor cells; Oval cells
• CPC Class Codes: C12N 5/0696 Artificially induced pluripotent stem cells, e.g. iPS
• CPC Class Codes: C12N 5/0697 Artificial constructs associating cells of different lineages, e.g. tissue equivalents blood vessels C12N5/0691
• CPC Class Codes: G01N 33/5008 for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics

Abstract

Disclosed are methods of treating or reducing the occurrence of a steatohepatitis disorder. The disorder may include, for example, NASH, parenteral nutrition associated liver disease (PNALD), or genetic forms of liver disease. The method may comprise the step of administering a composition comprising obeticholic acid to an individual in need thereof.

Claims

1. A method of treating or reducing the occurrence of a steatohepatitis disorder selected from NASH, parenteral nutrition associated liver disease (PNALD), and a genetic liver disease, comprising the step of administering a composition comprising obeticholic acid and Fibroblast Growth Factor 19 (“

FGF19”

) to an individual in need thereof.

2. The method of claim 1, wherein said composition is administered in an amount sufficient to reduce the occurrence of liver cell fibrosis.

3. The method of claim 1 wherein said composition is administered prior to, following, or during administration of parenteral nutrition to said individual in need thereof.

4. The method of claim 1 wherein said composition comprises a buffer.

5. The method of claim 1 wherein said composition a carrier.

6. The method of claim 1 wherein said composition is administered parenterally or intravenously.

7. A composition comprising

a. total parenteral nutrition (TPN) or peripheral parenteral nutrition (PPN);

b. Fibroblast Growth Factor 19 (“

FGF19”

); and

c. obeticholic acid.

8. An article of manufacture comprising a container, a composition of claim 7 in a dosage form, and instructions for administering said dosage form to an individual diagnosed or suspected of having or developing PNALD.