# US 12,178,818 B2 · Methods for treating immune thrombocytopenia by administering (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile

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- Number: US 12,178,818 B2
- Document ID: US12178818B2
- Status: Granted
- Kind: B2
- Application number: 17/946,585
- Filed: 2022-09-16
- Published: 2023-04-20
- Granted: 2024-12-31
- Earliest claimed: 2019-10-14
- Assignees: Principia Biopharma Inc.
- Applicants: Principia Biopharma Inc.
- Inventors: Steven Gourlay; Ann Neale; Philip Nunn; Claire Langrish; Olga Bandman; Dolca Thomas
- Web page: https://patentgrep.com/patent/US12178818B2

## CPC

- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/28: Dragees; Coated pills or tablets {, e.g. with film or compression coating (A61K9/2072 takes precedence, e.g. partially coated tablets A61K9/2072, coated multilayer tablets A61K9/2086, tablets with drug-coated core A61K9/209)}
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Methods for treating immune thrombocytopenia comprising administering at least one compound chosen from (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile (PRN1008) and pharmaceutically acceptable salts thereof are disclosed. Pharmaceutical compositions comprising at least one compound chosen from PRN1008 and pharmaceutically acceptable salts thereof are also disclosed.

## Claims

### Claim 1

A method for achieving a platelet count of at least 50,000/μL in a human patient with immune thrombocytopenia (ITP) in need thereof comprising administering to the human patient a therapeutically effective amount of at least one compound chosen from (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile and pharmaceutically acceptable salts thereof, once a day or twice a day for a treatment period, wherein the human patient has been identified as having a platelet count of less than 30,000/μL for two or more consecutive platelet counts prior to the start of the treatment period, wherein two of the two or more platelet counts were measured no sooner than 7 days apart in the 15 days prior to the start of the treatment period, and wherein the human patient has been identified as having at least one characteristic chosen from:
a history of taking at least one prior ITP therapy prior to the start of the treatment period; and
splenectomy prior to the start of the treatment period.

### Claim 2 (depends on 1)

The method of claim 1, wherein achieving a platelet count comprises achieving at least two platelet counts of at least 50,000/μL.

### Claim 3 (depends on 1)

The method of claim 1, wherein achieving a platelet count comprises achieving at least two consecutive platelet counts of at least 50,000/μL.

### Claim 4 (depends on 1)

The method of claim 1, wherein achieving a platelet count comprises achieving a platelet count of at least 50,000/μL in at least 50% of platelet counts measured during the treatment period.

### Claim 5 (depends on 1)

The method of claim 1, wherein the human patient has been identified as having a history of taking at least two prior ITP therapies prior to the start of the treatment period.

### Claim 6 (depends on 1)

The method of claim 1, wherein the human patient had a splenectomy prior to the start of the treatment period.

### Claim 7 (depends on 1)

The method of claim 1, wherein the human patient has chronic ITP.

### Claim 8 (depends on 1)

The method of claim 1, wherein the human patient has relapsing ITP.

### Claim 9 (depends on 1)

The method of claim 1, wherein the human patient has refractory ITP.

### Claim 10 (depends on 1)

The method of claim 1, wherein the treatment period is at least 28 days.

### Claim 11 (depends on 1)

The method of claim 1, comprising administering to the human patient 400 mg of at least one compound chosen from (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile and pharmaceutically acceptable salts thereof, once a day or twice a day.

### Claim 12 (depends on 1)

The method of claim 1, comprising administering to the human patient 400 mg of at least one compound chosen from (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile and pharmaceutically acceptable salts thereof, once a day.

### Claim 13 (depends on 1)

The method of claim 1, comprising administering to the human patient 400 mg of at least one compound chosen from (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile and pharmaceutically acceptable salts thereof, twice a day.

### Claim 14 (depends on 1)

The method of claim 1, comprising administering to the human patient 300 mg of at least one compound chosen from (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile and pharmaceutically acceptable salts thereof, twice a day.

### Claim 15 (depends on 1)

The method of claim 1, wherein the at least one compound is administered as a monotherapy.

### Claim 16 (depends on 1)

The method of claim 1, wherein the at least one compound is further administered in combination with at least one concomitant ITP therapy.

### Claim 17 (depends on 16)

The method of claim 16, wherein the at least one concomitant ITP therapy is chosen from corticosteroids and thrombopoietin receptor agonists.

### Claim 18 (depends on 16)

The method of claim 16, wherein the at least one concomitant ITP therapy is chosen from corticosteroids, eltrombopag, and romiplostim.

### Claim 19 (depends on 1)

The method of claim 1, wherein the at least one compound comprises at least one compound chosen from the (E) isomer of (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile and pharmaceutically acceptable salts thereof.

### Claim 20 (depends on 1)

The method of claim 1, wherein the at least one compound comprises at least one compound chosen from the (Z) isomer of (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile and pharmaceutically acceptable salts thereof.

### Claim 21 (depends on 1)

The method of claim 1, wherein the at least one compound comprises a mixture of (E) and (Z) isomers of (R)-2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile or a pharmaceutically acceptable salt of the foregoing.

### Claim 22 (depends on 1)

The method of claim 1, wherein the at least one compound is orally administered to the human patient.