# US 9,040,481 B2 · Methods for treating steatotic disease

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- Number: US 9,040,481 B2
- Document ID: US9040481B2
- Status: Granted
- Kind: B2
- Application number: 13/882,825
- Filed: 2011-11-02
- Published: 2013-10-31
- Granted: 2015-05-26
- Earliest claimed: 2010-11-02
- Assignees: The General Hospital Corporation
- Applicants: Joel F. Habener; Eva Tomas-Falco
- Inventors: Joel F. Habener; Eva Tomas-Falco
- Web page: https://patentgrep.com/patent/US9040481B2

## CPC

- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- A61K 38/08: Peptides having 5 to 11 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 38/10: Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 38/1709: {from mammals}
- A61K 38/26: Glucagons
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/06: Antihyperlipidemics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/12: Antidiuretics, e.g. drugs for diabetes insipidus (ADH A61P5/10)
- C07K 7/06: having 5 to 11 amino acids
- C07K 14/57563: {Vasoactive intestinal peptide [VIP]; Related peptides}
- C07K 14/605: Glucagons
- C07K 14/775: Apolipopeptides
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- 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

## Abstract

Methods for treating fatty liver disease, e.g., hepatic steatosis, using peptide fragments of the C-terminal end of glucagon-like peptide-1 (GLP-1), e.g., GLP-1(28-36).

## Claims

### Claim 1

A method of treating or preventing a dyslipidemia or a fatty liver disease (FLD) in a mammal, the method comprising administering to the mammal a therapeutically effective amount of a peptide consisting of (Phe/Tyr)-Ile-Ala-Trp-Leu-Val-(Lys/Arg)-Gly-Arg-Xaa (SEQ ID NO:9), wherein Xaa can be Gly, Gly-Arg, Gly-Arg-Gly, or absent, wherein one or more amino acid residues of SEQ ID NO:9 are modified by attachment of a fatty acid.

### Claim 2 (depends on 1)

The method of claim 1, wherein the peptide is amidated, acetylated, or both.

### Claim 3 (depends on 1)

The method of claim 1, wherein the fatty acid is selected from the group consisting of palmitate and oleate.

### Claim 4 (depends on 1)

The method of claim 1, wherein the peptide consists of SEQ ID NO:1.

### Claim 5 (depends on 4)

The method of claim 4, wherein the peptide is amidated, acetylated, or both.

### Claim 6 (depends on 4)

The method of claim 4, wherein the fatty acid is selected from the group consisting of palmitate and oleate.

### Claim 7 (depends on 1)

The method of claim 1, wherein the mammal has Nonalcoholic Steatohepatitis (NASH) or is at risk of developing NASH.

### Claim 8 (depends on 1)

The method of claim 1, wherein the mammal has Nonalcoholic Fatty Liver Disease (NAFLD) or is at risk of developing NAFLD.

### Claim 9 (depends on 1)

The method of claim 1, further comprising selecting the mammal on the basis that they have or are at risk of developing a FLD.

### Claim 10 (depends on 1)

The method of claim 1, further comprising evaluating fatty liver disease in the subject, before, during, or after administration of the peptide.

### Claim 11 (depends on 1)

The method of claim 1, wherein the subject has elevated levels of total cholesterol, high-density lipoprotein (HDL), or triglycerides compared to normal ranges of total cholesterol, HDL, or triglyceride level respectively in healthy subjects.

### Claim 12 (depends on 1)

The method of claim 1, wherein the peptide is administered orally.