Methods of using pyruvate kinase activators
Inventors
AGRESTA, Samuel V. • Chen, Yue • Cohen, Marvin B. • Dang, Lenny • Kung, Charles • Merica, Elizabeth A. • Silver, Bruce A. • Yang, Hua
Assignees
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Publication Number
US-11234976-B2
Publication Date
2022-02-01
Expiration Date
Abstract
Described herein are methods for using compounds that activate pyruvate kinase.
Core Innovation
The disclosure describes Compound 1, identified as N-(4-(4-(cyclopropylmethyl)piperazine-1-carbonyl)phenyl)quinoline-8-sulfonamide, as an allosteric activator of wild-type and mutant pyruvate kinase R (PKR). It presents methods for treating pyruvate kinase deficiency (PKD), a blood disorder, by orally administering Compound 1, a pharmaceutically acceptable salt or hydrate thereof, or a pharmaceutical composition containing it and a pharmaceutically acceptable carrier.
Preclinical evaluations and clinical-study data in healthy volunteers show increased PKR activity, PKR flux, and adenosine triphosphate (ATP), accompanied by decreased 2,3-diphosphoglycerate (2,3-DPG). The disclosure also reports pharmacokinetic, pharmacodynamic, and safety monitoring using these markers. It does not report clinical efficacy in people with PKD or provide specific details on uses beyond PKD and other blood disorders.
Claims Coverage
The relevant claims identify two independent claims, claims 1 and 7, which encompass two inventive features directed to methods for treating pyruvate kinase deficiency (PKD) using Compound 1 or a pharmaceutical composition containing it.
Oral treatment of PKD with Compound 1
Claim 1 recites treating PKD in a subject in need thereof by orally administering Compound 1, a pharmaceutically acceptable salt or hydrate thereof, or a pharmaceutical composition containing Compound 1 and a pharmaceutically acceptable carrier; dose and administration-schedule details are [procedural detail omitted for safety].
Oral treatment of PKD across a broader dose range
Claim 7 recites treating PKD in a subject in need thereof by orally administering Compound 1, a pharmaceutically acceptable salt or hydrate thereof, or a pharmaceutical composition containing Compound 1 and a pharmaceutically acceptable carrier across a broader dose range; dose and administration-schedule details are [procedural detail omitted for safety].
Both independent claims cover oral treatment of PKD using Compound 1 or a pharmaceutical composition containing it, differing primarily in their claimed dose ranges, while dependent claims further specify dosing options and administration schedules.
Stated Advantages
The claims state that the method treats PKD in the subject.
Documented Applications
Treatment of pyruvate kinase deficiency (PKD) in a subject in need thereof.
Proposed treatment of unspecified other blood disorders.
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