# US 12,109,193 B2 · Spray-dried dispersions, formulations, and polymorphs of (s)-5-amino-3-(4-((5-fluoro-2-methoxybenzamido)methyl)phenyl)-1-(1,1,1-trifluoropropan-2-yl)-1H-pyrazole-4-carboxamide

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

- Number: US 12,109,193 B2
- Document ID: US12109193B2
- Status: Granted
- Kind: B2
- Application number: 17/260,745
- Filed: 2019-07-29
- Published: 2021-10-28
- Granted: 2024-10-08
- Earliest claimed: 2018-07-31
- Assignees: Loxo Oncology, Inc.
- Applicants: Loxo Oncology, Inc.
- Inventors: Barbara J. Brandhuber; Lauren T. Brent; Charles Todd Eary; Andrew Kenna; Firas Khan; Vivian F. H. Renshaw; Stacey Renee Spencer
- Web page: https://patentgrep.com/patent/US12109193B2

## CPC

- A61K 9/1652: {Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin (homeopathic globules A61K9/1623)}
- A61K 31/415: 1,2-Diazoles
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 9/2009: {Inorganic compounds}
- A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates}
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/2059: {Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin}
- A61K 31/635: having a heterocyclic ring, e.g. sulfadiazine
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 35/04: specific for metastasis
- C07K 16/2887: {against CD20}
- A61K 9/146: {with organic macromolecular compounds}
- C07B 2200/13: Crystalline forms, e.g. polymorphs
- 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
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

A spray-dried dispersions and pharmaceutical composition of (S)-5-amino-3-(4-((5-fluoro-2-methoxybenzamido)methyl)phenyl)-1-(1,1,1-trifluoropropan-2-yl)-1H-pyrazole-4-carboxamide, pharmaceutically acceptable salts thereof, or a combination thereof and the use of the spray-dried dispersion and pharmaceutical composition in the treatment of cancer and autoimmune and inflammatory diseases are disclosed. Also provided are crystalline forms of (S)-5-amino-3-(4-((5-fluoro-2-methoxy-benzamido)methyl)phenyl)-1-(1,1,1-trifluoropropan-2-yl)-1H-pyrazole-4-carboxamide also useful in the treatment of cancer and autoimmune and inflammatory diseases.

## Claims

### Claim 1

A pharmaceutical composition comprising a spray-dried dispersion comprising a compound of Formula I:
or a pharmaceutically acceptable salt thereof and one or more polymers selected from the group consisting of an HPMCAS polymer, an HPMC polymer, a vinylpyrrolidone-vinyl acetate copolymer, and a polyvinylpyrrolidone (PVP) polymer and a pharmaceutically acceptable excipient.

### Claim 2 (depends on 1)

The pharmaceutical composition of claim 1, wherein the compound of Formula I or a pharmaceutically acceptable salt thereof and the HPMCAS polymer are present in a ratio of about 1:1;
microcrystalline cellulose is present in an amount between about 30% w/w and about 60% w/w;
lactose monohydrate is present in an amount between about 10% w/w and about 60% w/w;
croscarmellose sodium is present in an amount between about 0.5% w/w and about 5% w/w;
magnesium stearate is present in an amount between about 0.05% w/w and about 2% w/w; and
silicon dioxide in an amount between about 0.3% w/w and about 0.6% w/w, when present, and
wherein the spray-dried dispersion is present in the pharmaceutical tablet composition in an amount between about 40% w/w and about 50% w/w.

### Claim 3 (depends on 1)

The pharmaceutical composition according to claim 1, wherein the one or more polymers is an HPMCAS polymer.

### Claim 4 (depends on 1, 3)

The pharmaceutical composition according to claim 1 or 3, wherein the HPMCAS polymer is one or more of HPMCAS-MG, HPMCAS-LF, HPMCAS-LG, HPMCAS-MF, HPMCAS-HF, or HPMCAS-HG.

### Claim 5 (depends on 4)

The pharmaceutical composition according to claim 4, wherein the HPMCAS polymer is HPMCAS-MG.

### Claim 6 (depends on 4)

The pharmaceutical composition according to claim 4, further comprising a coating.