Methods of treating myeloproliferative neoplasms
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Publication Number
US-12268681-B2
Publication Date
2025-04-08
Expiration Date
Abstract
Therapeutic methods and pharmaceutical compositions for treating a myeloproliferative neoplasm (MPN), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis, are described. In certain embodiments, the invention includes therapeutic methods of treating a MPN using a combination of a compound of Formula (I) or Formula (II) with a therapeutic agent selected from the group consisting of a JAK inhibitor, an IDH inhibitor, a PD-1 inhibitor, a PD-L1 inhibitor, a PD-L2 inhibitor, an interferon, a PI3K inhibitor, an AKT inhibitor, an mTOR inhibitor, a nucleoside analog, and combinations thereof.
Core Innovation
The invention relates to a method of treating a myeloproliferative neoplasm (MPN) by administering to a human in need thereof therapeutically effective amounts of a MDM2 inhibitor in combination with a JAK inhibitor. The MDM2 inhibitor is a compound of Formula (I) or a pharmaceutically acceptable salt thereof.
The method is directed to treatment of an MPN in a human subject using a combination of an MDM2 inhibitor and a JAK inhibitor. The document refines patient and disease context through specific MPN forms, including polycythemia vera, essential thrombocythemia, and myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis.
Additional embodiments include JAK2V617F mutation status and the use of named JAK inhibitors in combination with the MDM2 inhibitor for treating MPNs. The document also specifies treatment refinements for the MDM2 inhibitor compound of Formula (I), including once-daily administration and administration on days 1 through 7 of each 28-day treatment cycle.
Claims Coverage
The independent claim covers combination therapy for treating an MPN using an MDM2 inhibitor of Formula (I) together with a JAK inhibitor. The claim family adds refinements for MPN subtype, JAK2V617F mutation status, enumerated JAK inhibitor choices, and dosing/cycle constraints for the Formula (I) compound, totaling five inventive feature groupings.
Mdm2 inhibitor of formula (I) with a JAK inhibitor for MPN treatment
Administering to a human in need thereof therapeutically effective amounts of an MDM2 inhibitor in combination with a JAK inhibitor, wherein the MDM2 inhibitor is a compound of Formula (I) or a pharmaceutically acceptable salt thereof.
Once-daily administration of the Formula (I) MDM2 inhibitor
The compound of Formula (I), or a pharmaceutically acceptable salt thereof, is administered once daily at a dose of 240 mg.
Cycle dosing on days 1 through 7 of a 28-day cycle
The compound of Formula (I), or a pharmaceutically acceptable salt thereof, is administered on days 1 through 7 of each 28-day treatment cycle.
Patient selection by JAK2V617F mutation status
The method is for a human subject whose MPN includes a JAK2V617F mutation.
Choice of JAK inhibitor from a specified set of inhibitors
The method uses a JAK inhibitor chosen from a specified group of named JAK inhibitors or their pharmaceutically acceptable salts.
Overall, the claim coverage centers on combination therapy for MPNs using an MDM2 inhibitor defined as a compound of Formula (I) or a pharmaceutically acceptable salt thereof together with a JAK inhibitor. Dependent coverage further specifies dosing and cycle timing for the Formula (I) compound, optional selection based on JAK2V617F mutation status, and a defined set of JAK inhibitor choices.
Stated Advantages
Documented Applications
Treating a myeloproliferative neoplasm (MPN) in a human using a therapeutically effective combination of an MDM2 inhibitor (Formula (I) or a pharmaceutically acceptable salt) and a JAK inhibitor.
Treating an MPN in a human subject whose MPN includes a JAK2V617F mutation using the MDM2 inhibitor and a JAK inhibitor combination.
Treating myelofibrosis selected from primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (post-PV MF), and post-essential thrombocythemia myelofibrosis (post-ET MF) using the method of the claims.
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