# US 2021/0228545 A1 · Methods of treating conditions related to the s1p1 receptor

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2021/0228545 A1
- Document ID: US20210228545A1
- Status: Published application
- Kind: A1
- Application number: 15/734,920
- Filed: 2019-06-05
- Published: 2021-07-29
- Earliest claimed: 2018-06-06
- Assignees: Arena Pharmaceuticals, Inc.
- Applicants: Arena Pharmaceuticals, Inc.
- Inventors: Ronald J. Christopher; Abu J.M. Sadeque
- Web page: https://patentgrep.com/patent/US20210228545A1

## CPC

- A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates}
- A61K 31/403: condensed with carbocyclic rings, e.g. carbazole
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/48: Preparations in capsules, e.g. of gelatin, of chocolate {(A61K9/0004 takes precedence; bite capsules A61K9/0056)}
- A61K 31/195: having an amino group
- A61K 31/4196: 1,2,4-Triazoles
- A61K 31/49: Cinchonan derivatives, e.g. quinine
- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61K 31/565: not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K 31/566: having an oxo group in position 17, e.g. estrone
- A61K 31/7048: having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- G01N 33/6872: {Intracellular protein regulatory factors and their receptors, e.g. including ion channels}
- G01N 2800/065: Bowel diseases, e.g. Crohn, ulcerative colitis, IBS
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- 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

Provided are methods of treatment of a sphingosine 1-phosphate subtype 1 (S1PI) receptor-associated disorder comprising prescribing and/or administering to an individual in need thereof a standard dose of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indo1-3-yl)acetic acid (Compound 1), or a pharmaceutically acceptable salt, hydrate, or solvate thereof.

## Claims

### Claim 1

A method of treating an individual with a sphingosine 1-phosphate subtype 1 (S1P1) receptor-associated disorder comprising:
administering to the individual in need thereof a pharmaceutical dosage form comprising a therapeutically effective amount of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid (Compound 1), or a pharmaceutically acceptable salt, hydrate, or solvate thereof,
wherein the pharmaceutical dosage form has a mean fed/fasted ratio of the area under the plasma concentration versus time curve of from about 0.8 to about 1.25 and a mean fed/fasted ratio of the maximum plasma concentration (Cmax) from about 0.8 to about 1.25.

### Claim 2

A method of administering a sphingosine 1-phosphate subtype 1 (S1P1) receptor modulator chosen from (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid (Compound 1), or a pharmaceutically acceptable salt, hydrate, or solvate thereof, to a patient in need thereof wherein the patient is also being administered a cytochrome P450 (CYP) substrate, organic anion transporter (OAT) substrate, UDP-glucuronosyltransferase (UGT) substrate, cytochrome P450 2C8 (CYP2C8) inhibitor, cytochrome P450 2C9 (CYP2C9) inhibitor, CYP2C8 inducer, CYP2C9 inducer, UDP-glucuronosyltransferase (UGT) enzyme UGT1A1 inhibitor, or UDP-glucuronosyltransferase (UGT) enzyme UGT1A6 inhibitor, comprising:
administering to the patient a therapeutically effective amount of the S1P1 modulator,
wherein the therapeutically effective amount of the S1P1 modulator is less than the amount that would be administered to a patient who is not also being administered a CYP substrate, OAT substrate, UGT substrate, CYP2C8 inhibitor, CYP2C9 inhibitor, CYP2C8 inducer, CYP2C9 inducer, UGT1A1 inhibitor, or UGT1A6 inhibitor.

### Claim 3

(canceled)

### Claim 4

(canceled)

### Claim 5

(canceled)

### Claim 6

(canceled)

### Claim 7

(canceled)

### Claim 8

(canceled)

### Claim 9

(canceled)

### Claim 10

(canceled)

### Claim 11

(canceled)

### Claim 12

(canceled)

### Claim 13

(canceled)

### Claim 14

(canceled)

### Claim 15

(canceled)

### Claim 16

(canceled)

### Claim 17

(canceled)

### Claim 18

(canceled)

### Claim 19

(canceled)

### Claim 20

(canceled)

### Claim 21

(canceled)

### Claim 22

(canceled)

### Claim 23 (depends on 1)

The method of claim 1, wherein the dosage form is administered under fasted conditions.

### Claim 24 (depends on 1)

The method of claim 1, wherein the dosage form is administered under fed conditions.

### Claim 25 (depends on 1)

The method of claim 1, wherein the method is non-gender specific.

### Claim 26 (depends on 1)

The method of claim 1, wherein the therapeutically effective amount is equivalent to about 0.5 to about 5.0 mg of Compound 1.

### Claim 27

(canceled)

### Claim 28

(canceled)

### Claim 29

(canceled)

### Claim 30 (depends on 1)

The method of claim 1, further comprising monitoring the individual for an active infection.

### Claim 31 (depends on 30)

The method of claim 30, further comprising discontinuing administration if the individual develops an active infection.

### Claim 32 (depends on 1)

The method of claim 1, wherein treating comprises inducing and/or maintaining clinical response; improving endoscopic appearance of the mucosa; and/or inducing and/or maintaining clinical remission.

### Claim 33 (depends on 1)

The method of claim 1, wherein the Compound 1 is administered without titration.

### Claim 34 (depends on 1)

The method of claim 1, wherein said administering results in no serious adverse events.

### Claim 35 (depends on 1)

The method of claim 1, wherein the Compound 1 is administered without substantially inducing an acute heart rate reduction or heart block in the individual.

### Claim 36 (depends on 1)

The method of claim 1, wherein the S1P1 receptor-associated disorder is inflammatory bowel disease.

### Claim 37 (depends on 36)

The method of claim 36, wherein the inflammatory bowel disease is ulcerative colitis.

### Claim 38 (depends on 37)

The method of claim 37, wherein the inflammatory bowel disease is moderately to severely active ulcerative colitis.

### Claim 39 (depends on 36)

The method of claim 36, wherein the inflammatory bowel disease is Crohn's disease.

### Claim 40 (depends on 36)

The method of claim 36, wherein prior to said administering the individual has a 3-component Mayo Clinic Score of at least 6.

### Claim 41 (depends on 36)

The method of claim 36, wherein said administering results in an improvement of the individual's 3-component Mayo Clinic Score.

### Claim 42 (depends on 36)

The method of claim 36, wherein said administering results in an improvement of the individual's 2-component Mayo Clinic Score.

### Claim 43 (depends on 36)

The method of claim 36, wherein said administering results in an improvement of the individual's Total Mayo Clinic Score.

### Claim 44

(canceled)

### Claim 45

(canceled)

### Claim 46

(canceled)

### Claim 47

(canceled)

### Claim 48

(canceled)

### Claim 49

(canceled)

### Claim 50

(canceled)

### Claim 51

(canceled)

### Claim 52 (depends on 1)

The method of claim 1, wherein the therapeutically effective amount is in an amount equivalent to 1 mg of Compound 1, 2 mg of Compound 1 or 3 mg of Compound 1.

### Claim 53

(canceled)

### Claim 54

(canceled)

### Claim 55

(canceled)

### Claim 56

(canceled)

### Claim 57

(canceled)

### Claim 58

(canceled)

### Claim 59

(canceled)

### Claim 60 (depends on 1)

The method of claim 1, wherein the Compound 1, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, is an L-arginine salt of Compound 1.

### Claim 61

(canceled)

### Claim 62

(canceled)

### Claim 63

(canceled)

### Claim 64

(canceled)

### Claim 65

(canceled)

### Claim 66

(canceled)

### Claim 67

(canceled)

### Claim 68

(canceled)

### Claim 69

(canceled)

### Claim 70

(canceled)

### Claim 71

(canceled)

### Claim 72

(canceled)

### Claim 73

(canceled)

### Claim 74

(canceled)

### Claim 75

(canceled)

### Claim 76

(canceled)

### Claim 77

(canceled)

### Claim 78

(canceled)

### Claim 79

(canceled)

### Claim 80

(canceled)

### Claim 81 (depends on 1)

The method claim 1, wherein the patient is also being administered a substrate of a membrane transporter selected from P-glycoprotein (Pgp), BCRP (breast cancer resistance protein), and OATP1B1, wherein the substrate of OATP1B1 is rifampin and the daily dose of the S1P1 modulator is selected from: 1.0, 1.25, 1.5, and 1.75 mg of the S1P1 modulator.