Pharmaceutical combinations for the treatment of cancer
Inventors
Klinghoffer, Richard • DEY, Joyoti
Assignees
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Publication Number
US-11135198-B2
Publication Date
2021-10-05
Expiration Date
Abstract
The disclosure herein provides combination therapies for the treatment of cancers such as Leukemia, lymphoma and triple negative breast cancer. The disclosure provides combination therapies of CDK inhibitors, e.g., a CDK inhibitor represented by Formula (I): or a pharmaceutically acceptable salt thereof together with a BCL-2 inhibitor or proteasome inhibitor for the treatment of cancer.
Core Innovation
The invention provides a method of treating a blood cancer by administering to a subject in need thereof a therapeutically effective amount of a CDK inhibitor represented by Formula Ib, or a pharmaceutically acceptable salt thereof, together with a therapeutically effective amount of venetoclax, or a pharmaceutically acceptable salt thereof. The blood cancer is selected from a defined group of hematologic malignancies, including acute myeloid leukemia (AML), multiple lymphoma and leukemia subtypes, chronic lymphocytic leukemia, DLBCL, and triple-negative breast cancer (TNBC).
The disclosure characterizes the treatment through suppression of MCL-1 and induction of apoptosis, and it describes biomarker readouts such as cleaved PARP, cleaved caspase-3, MCL-1, XIAP, cMYC, p53, and the ER stress marker XBP1. It further references IRE1α and tunicamycin-related pathways, and reports kinase selectivity for CDK9 potency.
The document reports synergistic anti-tumor effects when combining the Formula Ib CDK inhibitor with venetoclax across in vitro and xenograft tumor models. It also describes synergy with venetoclax-family BCL-2 family inhibitors and with proteasome inhibitors, and compares voruciclib with other CDK inhibitors such as palbociclib.
Claims Coverage
The claim coverage centers on a combination treatment comprising a CDK inhibitor represented by Formula Ib and venetoclax, each in a therapeutically effective amount, for treating a selected blood cancer. The claim package includes 6 inventive features, refining the therapy by administration timing, co-formulation, and blood-cancer selection.
Combination of Formula Ib CDK inhibitor with venetoclax for treating a selected blood cancer
A method of treating a blood cancer by administering to a subject in need thereof a therapeutically effective amount of a CDK inhibitor represented by Formula Ib, or a pharmaceutically acceptable salt thereof, together with a therapeutically effective amount of venetoclax, or a pharmaceutically acceptable salt thereof, where the blood cancer is selected from the listed hematologic malignancies.
Concurrent administration of Formula Ib CDK inhibitor and venetoclax
The method wherein the CDK inhibitor and venetoclax are administered concurrently.
Sequential administration within about 12 hours
The method wherein the CDK inhibitor and venetoclax are administered sequentially within about 12 hours of each other.
Sequential administration within about 5 hours
The method wherein the CDK inhibitor and venetoclax are administered sequentially within about 5 hours of each other.
Co-formulation in a pharmaceutical composition
The method wherein the CDK inhibitor and venetoclax, or a pharmaceutically acceptable salt of either, are co-formulated together in a pharmaceutical composition.
Chronic lymphocytic leukemia indication
The method wherein the blood cancer is chronic lymphocytic leukemia.
Overall, the claim coverage is anchored on combining a Formula Ib CDK inhibitor with venetoclax to treat a selected blood cancer, with further refinements specifying concurrent or sequential administration, co-formulation, and chronic lymphocytic leukemia.
Stated Advantages
Documented Applications
No documented applications found
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