Methods of treating kidney conditions using modified forms of trimetazidine
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Publication Number
US-12285428-B2
Publication Date
2025-04-29
Expiration Date
Abstract
The invention provides methods of treating kidney conditions using compositions that contain modified forms of trimetazidine, such as CV-8972. Providing such compositions increases energy production in the kidney. Therefore, methods of the invention are useful for treating a variety of kidney conditions, such as acute kidney disease, chronic kidney disease, chronic kidney insufficiency, diabetic kidney, or diabetic nephropathy.
Core Innovation
The invention relates to increasing ATP production in a kidney of a subject by providing a composition comprising a compound of formula (IX) or a pharmaceutically acceptable salt thereof. The composition is provided to a subject having a kidney condition, and the described approach links administration to a kidney condition and a mitochondrial-energy context.
The invention addresses a kidney condition by stimulating ATP synthesis through multiple mechanisms. The described mechanisms include shifting mitochondrial substrate use toward glucose oxidation and providing nicotinic acid to support NAD+ and mitochondrial respiration, with the overall effect presented as increased renal ATP production.
The document further describes a metabolic pathway of CV-8972 to CV-8814 and then to trimetazidine. It presents this pathway as rationale versus trimetazidine side effects and describes kidney conditions including acute kidney diseases such as AKI/ATN, chronic kidney conditions such as CKD and diabetic nephropathy, and conditions involving ischemia/reperfusion injury and inflammation-associated disorders.
The document also reports a Phase 1 first-in-human randomized placebo-controlled study of IMB-1018972 (CV-8972) and metabolites including IMB-1028814 (CV-8814) and trimetazidine. The study description includes safety/tolerability observations and pharmacokinetics, including food-effect and exposure/half-life and renal excretion observations for the metabolites, and states that IMB-1018972 has a positive risk/benefit and further development is warranted.
Claims Coverage
The independent claims are directed to increasing ATP production in a kidney and treating a kidney condition, each by providing a composition comprising a compound of formula (IX) or a pharmaceutically acceptable salt. Across the independent-claim scope and associated dependent refinements, the coverage centers on the formula (IX) composition and administration to kidney treatment/ATP production, with additional inventive features specifying formulation timing and type, administration route, dosing frequency, dosing amount range, and selected kidney conditions.
Providing a formula (IX) composition for increasing kidney ATP production
A method of increasing ATP production in a kidney of a subject by providing to a subject having a kidney condition a composition comprising a compound of formula (IX) or a pharmaceutically acceptable salt thereof.
Providing a formula (IX) composition for treating kidney conditions
A method of treating a kidney condition in a subject by providing to a subject having a kidney condition a composition comprising a compound of formula (IX) or a pharmaceutically acceptable salt thereof.
Selected kidney condition from a defined list
The kidney condition is selected from a defined group or list of kidney and related urologic diseases and pathological conditions.
Oral administration
The composition is administered orally.
One dose per day dosing schedule
The composition is provided as a single daily dose, one dose per day.
Daily dose range for a compound of formula (X)
The composition is administered as a daily dose containing about 25 mg to about 1000 mg of the compound of formula (X).
Immediate-release or modified-release formulation
The composition is formulated as an immediate-release formulation, including refinement to a modified-release formulation in the dependent coverage.
The claim coverage is anchored to administering a composition containing a compound of formula (IX) or a pharmaceutically acceptable salt for kidney-focused outcomes: increasing renal ATP production or treating a kidney condition. Dependent coverage narrows the approach by specifying selected kidney conditions, oral administration, one dose per day regimens, daily dose ranges tied to a compound of formula (X), and immediate-release or modified-release formulation.
Stated Advantages
Increased renal ATP production by stimulating ATP synthesis.
Stimulation of ATP synthesis through multiple mechanisms including shifting mitochondrial substrate use toward glucose oxidation and supporting NAD+ and mitochondrial respiration.
A metabolic pathway for CV-8972 to CV-8814 and then to trimetazidine, positioned as rationale versus trimetazidine side effects.
IMB-1018972 is stated to have positive risk/benefit and further development is warranted.
Documented Applications
Treating kidney conditions by providing a composition comprising a compound of formula (IX), with kidney conditions described to include AKI/ATN, CKD, diabetic nephropathy, ischemia/reperfusion injury, and inflammation-associated disorders.
Increasing ATP production in a kidney of a subject with a kidney condition by providing the formula (IX) composition.
First-in-human Phase 1 randomized placebo-controlled study use for IMB-1018972 (CV-8972), including safety/tolerability and pharmacokinetics and renal excretion observations for IMB-1018972 metabolites (IMB-1028814 and trimetazidine).
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