# US 9,872,866 B2 · Vitamin D receptor/SMAD genomic circuit gates fibrotic response

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- Number: US 9,872,866 B2
- Document ID: US9872866B2
- Status: Granted
- Kind: B2
- Application number: 14/921,230
- Filed: 2015-10-23
- Published: 2016-04-21
- Granted: 2018-01-23
- Earliest claimed: 2013-04-24
- Assignees: The Salk Institute for Biological Studies; The University of Sydney
- Applicants: Salk Institute for Biological Studies; The University of Sydney
- Inventors: Ning Ding; Michael Downes; Christopher Liddle; Ronald M. Evans
- Web page: https://patentgrep.com/patent/US9872866B2

## CPC

- A61K 31/592: 9,10-Secoergostane derivatives, e.g. ergocalciferol, i.e. vitamin D2
- A61K 9/167: {with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface (with further drug-free outer coating A61K9/5073)}
- A61K 31/07: Retinol compounds, e.g. vitamin A (retinoic acids A61K31/203)
- A61K 31/59: Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
- A61K 31/593: 9,10-Secocholestane derivatives, e.g. cholecalciferol, i.e. vitamin D3
- A61K 31/7068: having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/542: {Carboxylic acids, e.g. a fatty acid or an amino acid}
- A61K 47/62: the modifying agent being a protein, peptide or polyamino acid
- A61K 47/6929: {the form being a nanoparticle, e.g. an immuno-nanoparticle}
- A61K 47/6931: {the material constituting the nanoparticle being a polymer}
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 1/18: for pancreatic disorders, e.g. pancreatic enzymes
- A61P 3/02: Nutrients, e.g. vitamins, minerals
- A61P 13/12: of the kidneys
- A61P 31/12: Antivirals
- A61P 35/00: Antineoplastic agents
- A61P 39/02: Antidotes
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- G01N 33/5058: {Neurological cells}
- G01N 33/82: involving vitamins {or their receptors}
- G01N 2500/10: involving cells
- G01N 2800/085: Liver diseases, e.g. portal hypertension, fibrosis, cirrhosis, bilirubin
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present disclosure provides compositions that include a nanoparticle and a compound that increases the biological activity of the vitamin D receptor (VDR) (e.g., a VDR agonist), and methods of using such compounds to increase retention or storage of vitamin A, vitamin D, and/or lipids by a cell, such as an epithelial or stellate cell. Such methods can be used to treat or prevent fibrosis.

## Claims

### Claim 1

A method for treating pancreatic fibrosis in a subject, comprising:
administering to the subject a therapeutically effective amount of a composition comprising
a nanoparticle comprising retinyl palmitate on its surface, and
calcipotriol, which is in or attached to the nanoparticle,
thereby treating the pancreatic fibrosis in the subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein the administering comprises orally administering the therapeutically effective amount of the composition into the subject.

### Claim 3 (depends on 1)

The method of claim 1, wherein the administering comprises intravenously, intrathecally, intramuscularly, intraperitoneally, intra-articularly, intratumorally, or subcutaneously administering a therapeutically effective amount of the composition into the subject.

### Claim 4 (depends on 1)

The method of claim 1, wherein the subject is a human subject.

### Claim 5 (depends on 1)

The method of claim 1, wherein the subject is a mammalian subject.