# US 10,245,277 B2 · Compositions, methods of treatment and diagnostics for treatment of hepatic steatosis alone or in combination with a hepatitis C virus infection

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- Number: US 10,245,277 B2
- Document ID: US10245277B2
- Status: Granted
- Kind: B2
- Application number: 15/624,275
- Filed: 2017-06-15
- Published: 2018-05-10
- Granted: 2019-04-02
- Earliest claimed: 2010-03-03
- Assignees: Volant Holdings GmbH; Therabrake, Inc.
- Applicants: Volant Holdings GmbH
- Inventors: Joseph M. Fayad; Jerome Schentag
- Web page: https://patentgrep.com/patent/US10245277B2

## CPC

- A61K 31/7004: Monosaccharides having only carbon, hydrogen and oxygen atoms
- A61K 9/2009: {Inorganic compounds}
- A61K 9/2013: {Organic compounds, e.g. phospholipids, fats}
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/2059: {Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin}
- A61K 9/282: {Organic compounds, e.g. fats}
- A61K 9/2846: {Poly(meth)acrylates}
- A61K 9/2866: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/288: {Compounds of unknown constitution, e.g. material from plants or animals (oils, fats, waxes, shellac A61K9/282)}
- A61K 9/4891: {Coated capsules; Multilayered drug free capsule shells (with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004)}
- A61K 31/00: Medicinal preparations containing organic active ingredients
- A61K 31/555: containing heavy metals, e.g. hemin, hematin, melarsoprol
- A61K 31/70: Carbohydrates; Sugars; Derivatives thereof (sorbitol A61K31/047)
- A61K 31/7056: containing five-membered rings with nitrogen as a ring hetero atom
- A61K 31/7072: having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
- A61K 35/741: Probiotics (probiotic yeast, e.g. saccharomyces A61K36/06)
- A61K 36/05: Chlorophycota or chlorophyta (green algae), e.g. Chlorella
- A61K 36/48: Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K 36/8998: Hordeum (barley)
- A61K 38/21: Interferons {[IFN]}
- A61K 38/212: {IFN-alpha}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/12: Antivirals
- A61P 31/14: for RNA viruses
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- Y02A 90/10: Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation
- 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
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present invention is directed to pharmaceutical compositions and methods of treatment that relate to the inhibition, resolution and/or prevention of an array of the manifestations of metabolic syndromes, including Type 2 diabetes, hyperlipidemia, weight gain, obesity, insulin resistance, hypertension, atherosclerosis, fatty liver diseases and certain chronic inflammatory states that lead to these manifestations, among others. In additional aspects, the present invention relates to compositions and methods which may be used to treat, inhibit or reduce the likelihood of hepatitis viral infections, including Hepatitis B and Hepatitis C viral infections, as well as the secondary disease states and/or conditions which are often associated with such viral infections, including hepatic steatosis (steatohepatitis), cirrhosis, fatty liver and hepatocellular cancer, among other disease states or conditions.

## Claims

### Claim 1

A method of treating hepatic steatosis in a patient comprising orally administering an effective amount of an ileal brake composition in an oral dosage form comprising an ileal brake compound wherein at least 50% by weight of the ileal brake compound administered to said patient is released in the ileum of the patient.

### Claim 2 (depends on 1)

The method according to claim 1 wherein the ileal brake composition lowers one or more of; elevated insulin resistance; elevated liver enzymes ALT and AST; and triglycerides.

### Claim 3 (depends on 2)

The method according to claim 2 wherein the lowering one or more of; elevated insulin resistance; elevated liver enzymes ALT and AST; and triglycerides, mimics the effects of Roux-en-Y gastric bypass surgery (RYGB).

### Claim 4 (depends on 1)

The method according to claim 1 wherein said patient is infected with hepatitis B or C and said ileal brake compound is coadministered with an antiviral agent.

### Claim 5 (depends on 4)

The method according to claim 4 wherein said patient is infected with hepatitis C.

### Claim 6 (depends on 4)

The method according to claim 4 wherein viral counts in said patient are effectively lowered, and the health of steatotic cells in the liver of said patient, are improved.

### Claim 7 (depends on 4)

The method according to claim 4 wherein said antiviral agent is ribavirin, pegylated interferon, boceprevir, daclatasvir, asunapavir, INX-189, FV-100, NM 283, VX-950 (telaprevir), SCH 50304, TMC435, VX-500, BX-813, SCH503034, R1626, ITMN-191 (R7227), R7128, PF-868554, TT033, CGH-759, GI 5005, MK-7009, SIRNA-034, MK-0608, A-837093, GS 9190, GS 9256, GS 9451, GS 5885, GS 6620, GS 9620, GS9669, ACH-1095, ACH-2928, GSK625433, TG4040 (MVA-HCV), A-831, F351, NS5A, NS4B, ANA598, A-689, GNI-104, IDX102, ADX184, ALS-2200, ALS-2158, BI 201335, BI 207127, BIT-225, BIT-8020, GL59728, GL60667, PSI-938, PSI-7977, PSI-7851, SCY-635, TLR9 Agonist, PHX1766, SP-30 or a mixture thereof.

### Claim 8 (depends on 4)

The method according to claim 4, wherein the antiviral agent is an effective amount of pegylated interferon in combination with ribavirin.

### Claim 9 (depends on 4)

The method according to claim 4, wherein the antiviral agent is pegylated interferon and/or ribavirin, further combined with boceprevir in a dosage of at least 800 mg three times daily.

### Claim 10 (depends on 4)

The method according to claim 4, wherein the antiviral agent is pegylated interferon and/or ribavirin, further combined with telaprevir in a dosage of at least 750 mg three times daily.

### Claim 11 (depends on 4)

The method according to claim 4, wherein the antiviral agent is an effective amount of daclatasvir, asunaprevir or a mixture thereof, optionally in further combination with an effective amount of pegylated interferon and/or ribavirin.

### Claim 12 (depends on 4)

The method according to claim 4, wherein the antiviral agent is an effective amount of daclatasvir alone or in combination with an effective amount of pegylated interferon and/or ribavirin.

### Claim 13 (depends on 4)

The method according to claim 4, wherein the antiviral agent is an effective amount of asunaprevir alone or in combination with an effective amount of pegylated interferon and/or ribavirin.

### Claim 14 (depends on 4)

The method according to claim 4, wherein the antiviral agent is an effective amount of INX-189, alone or in combination with an effective amount of pegylated interferon and/or ribavirin.

### Claim 15 (depends on 4)

The method according to claim 4, wherein the antiviral agent is an effective amount of FV-100 alone or in combination with an effective amount of pegylated interferon and/or ribavirin.

### Claim 16

A method for producing an oral ileal brake compound composition which comprises the steps of:
1) coating the ileal brake compound with a material which has a pH dissolution or time delayed profile that delays the release in vivo of the majority of the ileal brake compound until the dosage form reaches the subject's ileum; and
2) coating the ileal brake compound inside a microparticle to form a population of microparticles, said microparticles releasing the compound at pH values specific to the coating within the range of about 7.0 to about 7.8.

### Claim 17 (depends on 1)

The method according to claim 1 wherein a majority of the ileal brake compound is released from the dosage form when the dosage form reaches the patient's ileum, whereupon the ileal brake composition may either activate or re-activate the L-cells of the ileum and thereby produce all of the chemical and physiological characteristics of an activated ileal brake in a manner similar to RYGB surgery.

### Claim 18 (depends on 17)

The method according to claim 17, wherein the ileal brake compound microparticles comprise a core which are coated by an enteric coating, wherein the coating thickness controls the dissolution of said ileal brake compound from said microparticles, thereby delaying release of the majority of the ileal brake compound until the microparticles reach the patient's ileum.