# US 11,998,526 B2 · Methods of improving renal function

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- Number: US 11,998,526 B2
- Document ID: US11998526B2
- Status: Granted
- Kind: B2
- Application number: 18/223,340
- Filed: 2023-07-18
- Published: 2023-11-09
- Granted: 2024-06-04
- Earliest claimed: 2019-12-17
- Assignees: Chinook Therapeutics, Inc.
- Applicants: Chinook Therapeutics, Inc.
- Inventors: Philip Thomas Frohlich; Andrew James King; Chidambaram Ramachandran; Sarah Beth Noonberg
- Web page: https://patentgrep.com/patent/US11998526B2

## CPC

- A61K 31/4025: not condensed and containing further heterocyclic rings, e.g. cromakalim
- A61K 31/70: Carbohydrates; Sugars; Derivatives thereof (sorbitol A61K31/047)
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 7/12: Antidiuretics, e.g. drugs for diabetes insipidus (ADH A61P5/10)
- A61P 13/12: of the kidneys
- C07D 405/04: directly linked by a ring-member-to-ring-member bond
- A61K 31/41: having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K 31/472: Non-condensed isoquinolines, e.g. papaverine
- A61K 31/7042: Compounds having saccharide radicals and heterocyclic rings
- 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
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Provided herein are methods of improving kidney function in a subject in need thereof.

## Claims

### Claim 1

A method of decreasing the occurrence of hematuria in a subject having biopsy-diagnosed IgA nephropathy, the method comprising administering to the subject from about 0.20 mg to about 1.5 mg of atrasentan, or an equivalent amount of a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein the hematuria is microhematuria, gross hematuria, symptomatic hematuria, or asymptomatic hematuria.

### Claim 3 (depends on 1)

The method of claim 1, comprising administering to the subject from about 0.40 mg to about 0.85 mg of atrasentan, or an equivalent amount of a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 3)

The method of claim 3, comprising administering to the subject about 0.75 mg of atrasentan, or an equivalent amount of a pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 1)

The method of claim 1, wherein atrasentan is administered as atrasentan mandelate or atrasentan hydrochloride.

### Claim 6 (depends on 1)

The method of claim 1, wherein the subject has not been previously diagnosed with one or more of diabetic nephropathy, HIV/AIDS, or acute kidney failure.

### Claim 7

A method of reducing IgA-immune complex deposition in a kidney of a subject in need thereof, comprising administering to the subject from about mg to about 1.5 mg of atrasentan, or an equivalent amount of a pharmaceutically acceptable salt thereof.

### Claim 8 (depends on 7)

The method of claim 7, comprising a reduction in IgA-immune complexes in serum or urine of the subject, or in a kidney biopsy sample from the subject.

### Claim 9 (depends on 7)

The method of claim 7, comprising a reduction in autoantibodies specific for galactose-deficient IgA in serum of the subject.

### Claim 10 (depends on 7)

The method of claim 7, comprising administering to the subject from about 0.40 mg to about 0.85 mg of atrasentan, or an equivalent amount of a pharmaceutically acceptable salt thereof.

### Claim 11 (depends on 10)

The method of claim 10, comprising administering to the subject about 0.75 mg of atrasentan, or an equivalent amount of a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 7)

The method of claim 7, wherein atrasentan is administered as atrasentan mandelate or atrasentan hydrochloride.

### Claim 13 (depends on 7)

The method of claim 7, wherein the subject has not been previously diagnosed with one or more of diabetic nephropathy, HIV/AIDS, or acute kidney failure.

### Claim 14 (depends on 1)

The method of claim 1, wherein the subject is concomitantly receiving a SGLT-2 inhibitor.

### Claim 15 (depends on 1)

The method of claim 1, wherein the subject is concomitantly receiving an angiotensin converting enzyme (ACE) inhibitor, an angiotensin II receptor blocker (ARB), or a combination thereof.

### Claim 16 (depends on 1)

The method of claim 1, wherein the subject has a proteinuria of at least about 1 g/day in at least two of three consecutive readings over the year prior to administering atrasentan, or a pharmaceutically acceptable salt thereof.

### Claim 17 (depends on 1)

The method of claim 1, wherein the subject has an estimated glomerular filtration rate (eGFR) of at least 30 mL/min/1.73 m2 prior to administering atrasentan, or the pharmaceutically acceptable salt thereof.

### Claim 18 (depends on 1)

The method of claim 1, comprising administering to the subject a dose of about 0.75 mg of atrasentan, or an equivalent amount of a pharmaceutically acceptable salt thereof, once per day.

### Claim 19 (depends on 1)

The method of claim 1, comprising administering to the subject a dosage form comprising about 0.75 mg of atrasentan, or an equivalent amount of a pharmaceutically acceptable salt thereof, wherein the dosage form is a tablet.

### Claim 20 (depends on 1)

The method of claim 1, wherein atrasentan is administered as atrasentan monohydrochloride.

### Claim 21 (depends on 1)

The method of claim 1, wherein atrasentan, or a pharmaceutically acceptable salt thereof, is administered in one or more polymorphic forms characterized, when measured at about 25° C. with Cu-Kα radiation, by an X-ray powder diffraction pattern comprising:
(i) at least three peaks having respective values of about 8,3°, 9,7°, 10,0°, 13,0°, 17.2° or 19,5° and essentially without peaks having 20 values below about 6.2° and/or between about 6.6° and 8.0°; and/or
(ii) peaks having respective values of about 6.7° and 22.05° and at least one peak having a respective value of about 8.4°, 15.6°, 18.0°, 18.5°, 19.8° or 20.6°; and/or
(iii) peaks having respective values of about 6.7° and 21.95° and at least one peak having a respective 20 value of about 8.4°, 15.6°, 18.0°, 18.5°, 19.8° or 20.6°.

### Claim 22 (depends on 7)

The method of claim 7, wherein the subject is concomitantly receiving a SGLT-2 inhibitor.

### Claim 23 (depends on 7)

The method of claim 7, wherein the subject is concomitantly receiving an angiotensin converting enzyme (ACE) inhibitor, an angiotensin II receptor blocker (ARB), or a combination thereof.

### Claim 24 (depends on 7)

The method of claim 7, wherein the subject has a proteinuria of at least about 1 g/day in at least two of three consecutive readings over the year prior to administering atrasentan, or a pharmaceutically acceptable salt thereof.

### Claim 25 (depends on 7)

The method of claim 7, wherein the subject has an estimated glomerular filtration rate (eGFR) of at least 30 mL/min/1.73 m2 prior to administering atrasentan, or the pharmaceutically acceptable salt thereof.

### Claim 26 (depends on 7)

The method of claim 7, comprising administering to the subject a dose of about 0.75 mg of atrasentan, or an equivalent amount of a pharmaceutically acceptable salt thereof, once per day.

### Claim 27 (depends on 7)

The method of claim 7, comprising administering to the subject a dosage form comprising about 0.75 mg of atrasentan, or an equivalent amount of a pharmaceutically acceptable salt thereof, wherein the dosage form is a tablet.

### Claim 28 (depends on 7)

The method of claim 7, wherein atrasentan is administered as atrasentan monohydrochloride.

### Claim 29 (depends on 7)

The method of claim 7, wherein atrasentan, or a pharmaceutically acceptable salt thereof, is administered in one or more polymorphic forms characterized, when measured at about 25° C. with Cu-Kα radiation, by an X-ray powder diffraction pattern comprising:
(i) at least three peaks having respective 2-9, values of about 8,3°, 9.7°, 10,0°, 13,0°, 15,6°, 17.2° or 19,5° and essentially without peaks having 20 values below about 6,2° and/or between about 6.6° and 8.0°; and/or
(ii) peaks having respective 2, values of about 6.7° and 22.05° and at least one peak having a respective 2-9, value of about 8.4°, 15.6°, 18.0°, 18.5°, 19.8° or 20.6°; and/or
(iii) peaks having respective values of about 6.7° and 21.95° and at least one peak having a respective 20 value of about 8.4°, 15.6°, 18,0° 18.5°, 19,8° or 20.6°.