# US 10,118,897 B2 · Crystalline forms of a prolyl hydroxylase inhibitor

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- Number: US 10,118,897 B2
- Document ID: US10118897B2
- Status: Granted
- Kind: B2
- Application number: 15/462,688
- Filed: 2017-03-17
- Published: 2017-07-06
- Granted: 2018-11-06
- Earliest claimed: 2012-07-16
- Assignees: FibroGen, Inc.
- Applicants: FibroGen, Inc.
- Inventors: Claudia Witschi; Jung Min Park; Michael D. Thompson; Michael John Martinelli; David A. Yeowell; Michael P. Arend
- Web page: https://patentgrep.com/patent/US10118897B2

## CPC

- C07D 217/26: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/06: Antianaemics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 9/12: Antihypertensives
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 13/12: of the kidneys
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/08: Antiepileptics; Anticonvulsants
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 27/02: Ophthalmic agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/04: Antibacterial agents
- A61P 31/18: for HIV
- A61P 33/00: Antiparasitic agents
- A61P 35/00: Antineoplastic agents
- A61P 39/00: General protective or antinoxious agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K 31/47: Quinolines; Isoquinolines
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

The present disclosure relates to crystalline solid forms of [(4-hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid, the process of preparing the forms, and pharmaceutical compositions and methods of use thereof.

## Claims

### Claim 1

A process for preparing crystalline [(4-hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid (Compound A), comprising contacting Compound A, or a salt thereof, with acetic acid for a time sufficient to provide a crystalline Compound A wherein at least about 95% of the crystalline Compound A is Form A.

### Claim 2 (depends on 1)

The process of claim 1, wherein the process further comprises, following said contacting step, isolating the crystalline Compound A Form A.

### Claim 3 (depends on 2)

The process of claim 2, wherein the isolating comprises the steps of filtering, washing and drying the crystalline Compound A Form A.

### Claim 4 (depends on 1)

The process of claim 1, wherein the contacting comprises adding the acetic acid to Compound A at a temperature of from about 10° C. to about 90° C.

### Claim 5 (depends on 4)

The process of claim 4, wherein the acetic acid is added to the Compound A as an aqueous solution, slowly with stirring.

### Claim 6 (depends on 1)

The process of claim 1, wherein prior to contacting Compound A with the acetic acid, an aqueous solution of sodium hydroxide is added slowly to a stirred suspension of Compound A in water at temperature of from about 10° C. to about 90° C.

### Claim 7 (depends on 1)

The process of claim 1, wherein the Compound A Form A is characterized by a differential scanning calorimetry (DSC) curve that comprises an endotherm at about 223° C.

### Claim 8 (depends on 7)

The process of claim 7, wherein the DSC curve is substantially as shown in FIG. 2.

### Claim 9 (depends on 1)

The process of claim 1, wherein the Compound A Form A is characterized by an X-ray powder diffractogram comprising a peak at 8.5 ° 2θ±0.2 ° 2θ.

### Claim 10 (depends on 1)

The process of claim 1, wherein the Compound A Form A is characterized by an X-ray powder diffractogram comprising a peak at 16.2 ° 2θ±0.2 ° 2θ.

### Claim 11 (depends on 1)

The process of claim 1, wherein the Compound A Form A is characterized by an X-ray powder diffractogram comprising a peak at 27.4 ° 2θ±0.2 ° 2θ.

### Claim 12 (depends on 1)

The process of claim 1, wherein the Compound A Form A is characterized by an X-ray powder diffractogram comprising peaks at 8.5, 16.2, and 27.4 ° 2θ±0.2° 2θ.

### Claim 13 (depends on 12)

The process of claim 12, wherein the X-ray powder diffractogram further comprises peaks at 12.8, 21.6, and 22.9 ° 2θ±0.2 ° 2θ.

### Claim 14 (depends on 1)

The process of claim 1, wherein the Compound A Form A is characterized by an X-ray powder diffractogram substantially as shown in FIG. 1.

### Claim 15 (depends on 1)

The process of claim 1, wherein at least about 99% of the crystalline Compound A produced by the process is Compound A Form A.

### Claim 16 (depends on 1)

The process of claim 1, wherein at least about 99.5% of the crystalline Compound A produced by the process is Compound A Form A.

### Claim 17 (depends on 1)

The process of claim 1, wherein at least about 99.9% of the crystalline Compound A produced by the process is Compound A Form A.

### Claim 18 (depends on 1)

The process of claim 1, wherein at least about 99.99% of the crystalline Compound A produced by the process is Compound A Form A.