# US 9,517,241 B2 · Amelioration of intestinal fibrosis and treatment of Crohn's disease

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- Number: US 9,517,241 B2
- Document ID: US9517241B2
- Status: Granted
- Kind: B2
- Application number: 15/051,850
- Filed: 2016-02-24
- Published: 2016-06-16
- Granted: 2016-12-13
- Earliest claimed: 2013-12-19
- Assignees: The Regents of the University of Michigan
- Applicants: The Regents of the University of Michigan
- Inventors: Robert U. Simpson; Peter D. R. Higgins; Laura A. Johnson
- Web page: https://patentgrep.com/patent/US9517241B2

## CPC

- A61K 31/59: Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 31/592: 9,10-Secoergostane derivatives, e.g. ergocalciferol, i.e. vitamin D2
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- 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)

## Abstract

Methods of treating patients with inflammatory bowel disease, intestinal fibrosis, or Crohn's disease involve administering a therapeutic amount of CARD-024 or related compound.

## Claims

### Claim 1

A method of ameliorating intestinal fibrosis in a subject, the method comprising administering to the subject a composition comprising a compound of Formula (I)
wherein Et is ethyl,
wherein the dashed line indicates a single bond or a double bond in the E configuration between carbon 22 and carbon 23, and
wherein the configuration at carbon 24 to which Et is attached is in the R configuration or the S configuration.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the compound has a single bond between carbon 22 and carbon 23.

### Claim 3 (depends on 2)

The method according to claim 2, wherein carbon 24 is in the S configuration.

### Claim 4 (depends on 1)

The method according to claim 1, wherein carbon 24 is in the R configuration.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the compound has a double bond in the E configuration between carbon 22 and carbon 23.

### Claim 6 (depends on 5)

The method according to claim 5, wherein carbon 24 is in the S configuration.

### Claim 7 (depends on 5)

The method according to claim 5, wherein carbon 24 is in the R configuration.

### Claim 8 (depends on 1)

The method according to claim 1, wherein the subject is diagnosed with Crohn's disease.

### Claim 9 (depends on 1)

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

### Claim 10 (depends on 1)

The method according to claim 1, comprising administering 5 mcg to 500 mcg of the compound.

### Claim 11 (depends on 1)

The method according to claim 1, comprising administering 1 to 4 doses per day of the composition.

### Claim 12 (depends on 1)

The method according to claim 1, comprising administering 20 mcg to 1000 mcg of the compound in a delayed release composition.

### Claim 13 (depends on 12)

The method according to claim 12, comprising administering the delayed release composition once per day.

### Claim 14 (depends on 2)

The method according to claim 2, comprising administering the effective dose orally.

### Claim 15 (depends on 1)

The method of claim 1, further comprising administering to the patient a compound selected from infliximab, adelimumab, certolizumab (CDP-870), interleukin-10, interleukin-4,6-[(Aminocarbonyl)(2,6-difluorophenyl)amino]-2-(2,4-difluorophenyl)-3-pyridinecarboxamide (VX 702), 6-Chloro-5-[[(2R,5S)-4-[(4-fluorophenyl)methyl]-2,5-dimethyl-1-piperazinyl]carbonyl]-N,N,1-trimethyl-α-oxo-1H-Indole-3-acetamide (SCIO 469), doramapimod, ((2R)-2-((3R)-3-amino-3{4-[2-methyl-4-quinolinyl) methoxy] phenyl}-2-oxopyrrolidinyl)-N-hydroxy-4-methylpentanamide)) (DPC 333), pranalcasan, mycophenolate, merimepodib, cyclosporine, tacrolimus, pimecrolimus, 6-[(2S,3R,4R,6E)-3-hydroxy-4-methyl-2-(methylamino)-6,8-nonadienoic acid]-Cyclosporin A (ISAtx247), 5-aminosalicylic acid, mesalamine, sulfasalazine, balsalazide disodium, olsalazine sodium, methotrexate, azathioprine, SCIO 323 and alosetron.

### Claim 16 (depends on 1)

The method of claim 1, comprising administering to the patient a composition comprising CARD-024 and a compound selected from infliximab, adelimumab, certolizumab (CDP-870), interleukin-10, interleukin-4,6-[(Aminocarbonyl)(2,6-difluorophenyl)amino]-2-(2,4-difluorophenyl)-3-pyridinecarboxamide (VX 702), 6-Chloro-5-[[(2R,5S)-4-[(4-fluorophenyl)methyl]-2,5-dimethyl-1-piperazinyl]carbonyl]-N,N,1-trimethyl-α-oxo-1H-Indole-3-acetamide (SCIO 469), doramapimod, ((2R)-2-((3R)-3-amino-3{4-[2-methyl-4-quinolinyl) methoxy] phenyl}-2-oxopyrrolidinyl)-N-hydroxy-4-methylpentanamide)) (DPC 333), pranalcasan, mycophenolate, merimepodib, cyclosporine, tacrolimus, pimecrolimus, 6-[(2S,3R,4R,6E)-3-hydroxy-4-methyl-2-(methylamino)-6,8-nonadienoic acid]-Cyclosporin A (ISAtx247), 5-aminosalicylic acid, mesalamine, sulfasalazine, balsalazide disodium, olsalazine sodium, methotrexate, azathioprine, SCIO 323, and alosetron.

### Claim 17 (depends on 8)

The method of claim 8, comprising administering to the patient a compound selected from infliximab, adelimumab, certolizumab (CDP-870), interleukin-10, interleukin-4, 6-[(Aminocarbonyl)(2,6-difluorophenyl)amino]-2-(2,4-difluorophenyl)-3-pyridinecarboxamide (VX 702), 6-Chloro-5-[[(2R5S)-4-[(4-fluorophenyl)methyl]-2,5-dimethyl-1-piperazinyl]carbonyl]-N,N,1-trimethyl-α-oxo-1H-Indole-3-acetamide (SCIO 469), doramapimod, ((2R)-2-((3R)-3-amino-3{4-[2-methyl-4-quinolinyl) methoxy] phenyl}-2-oxopyrrolidinyl)-N-hydroxy-4-methylpentanamide)) (DPC 333), pranalcasan, mycophenolate, merimepodib, cyclosporine, tacrolimus, pimecrolimus, 6-[(2S,3R,4R,6E)-3-hydroxy-4-methyl-2-(methylamino)-6,8-nonadienoic acid]-Cyclosporin A (ISAtx247), 5-aminosalicylic acid, mesalamine, sulfasalazine, balsalazide disodium, olsalazine sodium, methotrexate, azathioprine, SCIO 323 and alosetron.

### Claim 18 (depends on 8)

The method of claim 8, comprising administering to the patient a composition comprising CARD-024 and a compound selected from infliximab, adelimumab, certolizumab (CDP-870), interleukin-10, interleukin-4,6-[(Aminocarbonyl)(2,6-difluorophenyl)amino]-2-(2,4-difluorophenyl)-3-pyridinecarboxamide (VX 702), 6-Chloro-5-[[(2R,5S)-4-[(4-fluorophenyl)methyl]-2,5-dimethyl-1-piperazinyl]carbonyl]-N,N,1-trimethyl-α-oxo-1H-1-Indole-3-acetamide (SCIO 469), doramapimod, ((2R)-2-((3R)-3-amino-3{4-[2-methyl-4-quinolinyl) methoxy] phenyl}-2-oxopyrrolidinyl)-N-hydroxy-4-methylpentanamide)) (DPC 333), pranalcasan, mycophenolate, merimepodib, cyclosporine, tacrolimus, pimecrolimus, 6-[(2S,3R,4R,6E)-3-hydroxy-4-methyl-2-(methylamino)-6,8-nonadienoic acid]-Cyclosporin A (ISAtx247), 5-aminosalicylic acid, mesalamine, sulfasalazine, balsalazide disodium, olsalazine sodium, methotrexate, azathioprine, SCIO 323 and alosetron.