Crystalline forms of n-(4-(4-(cyclopropylmethyl)piperazine-1-carbonyl)phenyl)quinoline-8-sulfonamide
Inventors
Rios Lizarraga, Jose Luis • Simone, Eric • Sizemore, Jacob P. • Zhang, Shijie • Wilson, Jeffrey D. • GUO, Liting • Mirmehrabi, Mahmoud • Su, Yeqing
Assignees
Solid State Pharma Inc • Crystal Pharmatech Co Ltd • Agios Pharmaceuticals Inc
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Publication Number
US-12612381-B2
Publication Date
2026-04-28
Expiration Date
Abstract
Provided herein are amorphous and crystalline hemisulfate salt forms of the formula.Also provided are pharmaceutical compositions comprising the amorphous and crystalline hemisulfate salt forms, methods for their manufacture, and uses thereof for treating conditions associated with pyruvate kinase such as e.g., pyruvate kinase deficiency.
Core Innovation
Compound 1 is an allosteric red-cell pyruvate kinase activator, featuring an amorphous form and multiple crystalline hemisulfate forms, including crystalline Form A identified as a sesquihydrate. The independent claim covers an amorphous form of the compound having the recited formula. Disclosed solid-state characterizations include powder X-ray diffraction, moisture sorption and desorption, and thermal-analysis profiles demonstrating a thermogravimetric weight loss of about 2.7 percent.
The disclosure describes pharmaceutical compositions comprising the amorphous form with pharmaceutically acceptable carriers. Therapeutic methods address blood disorders including pyruvate kinase deficiency, sickle cell disease, thalassemia, and hemolytic anemia, referencing red-cell and hemoglobin endpoints and combination with folic acid. Because background details are absent from the supplied content, the technical problem being solved is not explicitly described in patent.
Claims Coverage
The claims identify one independent claim directed to an amorphous form of the recited compound. Four inventive features are represented across the independent claim and associated dependent claims.
Amorphous form of the compound
The independent claim covers an amorphous form of a compound having the recited formula.
Treatment of specified blood disorders
Dependent claims describe administering an effective amount of the amorphous form to treat pyruvate kinase deficiency, sickle cell disease, thalassemia (including beta-thalassemia, non-transfusion-dependent thalassemia, and transfusion-dependent thalassemia), or hemolytic anemia.
Pharmaceutical composition with a carrier
Dependent claims cover a pharmaceutical composition comprising the amorphous form and a pharmaceutically acceptable carrier, including microcrystalline cellulose, mannitol, croscarmellose sodium, and sodium stearyl fumarate, alone or in combination.
Thermal-analysis characteristic
A dependent claim characterizes the amorphous form by a thermogravimetric-analysis weight-loss feature.
The claim coverage centers on the amorphous form of the compound and extends to pharmaceutical compositions with carriers, thermal-analysis characteristics, and methods for treating specified blood disorders.
Stated Advantages
Crystalline Form A is reported to have favorable crystallinity, humidity stability, particle size, and pharmacokinetic properties.
Documented Applications
The disclosed forms are described for pharmaceutical compositions and for the treatment of pyruvate kinase deficiency (PKD), sickle cell disease (SCD), thalassemia (including beta-thalassemia, non-transfusion-dependent thalassemia, and transfusion-dependent thalassemia), or hemolytic anemia by administering an effective amount of the amorphous form to a subject in need thereof.
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