# US 12,599,648 B2 · Pharmaceutical composition comprising a combination of a guanylate cyclase C (GUCY2C) agonist and a short-chain fatty acid or prodrug thereof

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- Number: US 12,599,648 B2
- Document ID: US12599648B2
- Status: Granted
- Kind: B2
- Application number: 18/011,718
- Filed: 2020-06-30
- Published: 2023-07-20
- Granted: 2026-04-14
- Earliest claimed: 2020-06-30
- Applicants: Sören Ocvirk
- Inventors: Sören Ocvirk
- Web page: https://patentgrep.com/patent/US12599648B2

## CPC

- A61K 38/12: Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)}
- A61K 31/19: Carboxylic acids, e.g. valproic acid (salicylic acid A61K31/60)
- A61K 31/575: substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
- A61K 38/10: Peptides having 12 to 20 amino acids {(A61K38/043 - A61K38/046 take precedence)}
- A61K 38/164: {from bacteria}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 35/00: Antineoplastic agents
- A61K 9/0031: {Rectum, anus}
- 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

A pharmaceutical composition includes a combination of a guanylate cyclase C (GUCY2C) agonist and a short-chain C2 to C5 fatty acid and/or a salt and/or a prodrug thereof in a therapeutically effective amount and one or more pharmaceutically acceptable excipients as well as to a method of preventing and/or treating colorectal tumorigenesis and/or carcinogenesis and/or chronic intestinal inflammation and/or cystic fibrosis related gastrointestinal manifestations by administering to a patient, who has developed or is at risk to develop colorectal tumorigenesis and/or carcinogenesis and/or chronic intestinal inflammation and/or cystic fibrosis related gastrointestinal manifestations, a therapeutically effective amount of a combination of a GUCY2C agonist and a short-chain C2 to C5 fatty acid or a salt or a prodrug thereof.

## Claims

### Claim 1

A pharmaceutical composition comprising a combination of a guanylate cyclase C (GUCY2C) agonist and a short-chain fatty acid and/or a salt and/or a prodrug thereof in a therapeutically effective amount and one or more pharmaceutically acceptable excipients, wherein the short-chain fatty acid is selected from the group consisting of butyric acid or a salt or ester thereof.

### Claim 2 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the short-chain fatty acid comprises sodium butyrate or tributyrin.

### Claim 3 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the composition comprises one or more GUCY2C agonists, which is/are selected from the group consisting of linaclotide, plecanatide, dolcanatide and STa toxin.

### Claim 4 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition further comprises one or more farnesoid X receptor (FXR) agonists, one or more bile acids and/or one or more bile acid derivatives.

### Claim 5 (depends on 4)

The pharmaceutical composition according to claim 4, wherein the composition wherein the one or more farnesoid X receptor (FXR) agonists are selected from the group consisting of chenodeoxycholic acid (IUPAC: (R)-((3R,5S,7R,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[α]phenanthren-17-yl)pentanoic acid), cholic acid (IUPAC: R)-4-((3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-3,7,12-Trihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[α]phenanthren-17-yl)pentanoic acid), deoxycholic acid (IUPAC: (3α,5β,12α,20R)-3,12-Dihydroxycholan-24-oic acid), lithocholic acid (IUPAC: (4R)-4-[(3R,5R,8R,9S, OS,13R,14S,17R)-3-Hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-11-cyclopenta[α]phenanthren-17-yl]pentanoic acid), taurocholic acid (IUPAC: 2-{[(3α,5μ,7α,12α)-3,7,12-trihydroxy-24-oxocholan-24-yl]amino}ethanesulfonic acid), ursodeoxycholic acid (IUPAC: (R)-4-((3R,5S,7S,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-10,13-dimethylhexadecahydro-1H-cyclopenta[α]phenanthren-17-yl)pentanoic acid), semi-synthetic obeticholic acid (IUPAC: 6α-ethyl-chenodeoxycholic acid), AND synthetic GW 4064 (IUPAC: 3-[2-[2-Chloro-4-[[3(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methoxy]phenyl]ethenyl]benzoic acid).

### Claim 6 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is an oral formulation.

### Claim 7 (depends on 6)

The pharmaceutical composition according to claim 6, wherein the oral composition is an enteric-coated oral formulation, selected from the group consisting of a tablet, a capsule, a powder and a granulate.

### Claim 8 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is a rectal formulation.

### Claim 9 (depends on 8)

The pharmaceutical composition according to claim 8, wherein the rectal formulation is selected from the group consisting of a suppository, a rectal gel and a rectal foam.

### Claim 10 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the composition comprises the GUCY2C agonist linaclotide in an amount of 0.1 to 1,000 mg per dose unit.

### Claim 11 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the composition comprises the short chain fatty acid or a salt or a prodrug thereof in an amount of 0.1 to 5,000 mg per dose unit.

### Claim 12 (depends on 11)

The pharmaceutical composition according to claim 11, wherein the short chain fatty acid comprises butyrate or tributyrin.

### Claim 13 (depends on 1)

A method of preventing and/or treating colorectal tumorigenesis and/or carcinogenesis and/or chronic intestinal inflammation and/or cystic fibrosis related gastrointestinal manifestations, which the method comprises administering to a patient, who has or is at risk to develop colorectal tumorigenesis and/or carcinogenesis and/or chronic intestinal inflammation and/or cystic fibrosis related gastrointestinal manifestations, a pharmaceutical composition according to claim 1.

### Claim 14 (depends on 13)

The method according to claim 13, wherein the colorectal tumorigenesis and/or carcinogenesis is selected from the group consisting of colorectal cancer (CRC), early stage preceding CRC, as crypt dysplasia, crypt hyperplasia, colorectal adenoma, colorectal adenomatous polyps, and colorectal carcinoma; inflammatory bowel diseases (IBD), Crohn's disease, and ulcerative colitis; or wherein the cystic fibrosis related gastrointestinal manifestations is selected from the group consisting of intestinal mucus inspissation, intestinal dysmotility, and distal intestinal obstruction syndrome.

### Claim 15 (depends on 13)

The method according to claim 13, wherein the composition comprises the GUCY2C agonist linaclotide in an amount of 0.1 to 1,000 mg per dose unit.

### Claim 16 (depends on 13)

The method according to claim 13, wherein the composition comprises the short chain fatty acid or a salt or a prodrug thereof, preferably butyrate or tributyrin in an amount of 0.1 to 5,000 mg per dose unit.