Biomarkers of METAP2 inhibitors and applications thereof
Inventors
Cornelius, Peter • Shanahan, James
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11612577-B2
Publication Date
2023-03-28
Expiration Date
Abstract
The present disclosure relates to small molecule or polymer conjugated MetAP2 inhibitors. The present disclosure also relates to methods of treating, or ameliorating at least one symptom of metabolic dysfunction associated with a treatment in a subject having a disease, such as cancer. The present disclosure also relates to methods of treating, or ameliorating at least one symptom of cancer comprising administering a combination of a polymer conjugated MetAP2 inhibitors and at least one second agent wherein the second agent may induce metabolic dysfunction.
Core Innovation
The invention relates to a method for treating, or ameliorating at least one symptom of, cancer in a subject in need thereof by administering a therapeutically effective amount of at least one compound of a Formula, or a pharmaceutically acceptable salt thereof, in combination with a therapeutically effective amount of alpelisib (BYL-719). The subject is pre-treated by administering at least one therapeutically effective amount of the at least one compound at least 10 days prior to the administration of alpelisib. The pre-treatment attenuates alpelisib-induced hyperglycemia.
The disclosed compounds are defined by variable ranges for x, y, and n, and generalized structures such as Z-Q-X—Y—C(O)—W. The description includes substituted compounds, stereodefined core motifs, pharmaceutically acceptable salts, prodrugs, metabolites, analogs, derivatives, polymer-conjugated embodiments, and amino-acid-derived linkers including glycine, leucine, valine, and phenylalanine.
The disclosure further describes compound embodiments with steroid-like or polycyclic cores, methoxy substitution, heterocycle substituents, tertiary amine/heteroatom functionalities, and fluorinated groups in representative examples. The combined regimen can include sequential or substantially simultaneous administration after pre-treatment, and the stated therapeutic context includes cancer treatment together with measurable metabolic and tumor-related outcomes.
Claims Coverage
The claim coverage centers on one primary inventive feature set: a cancer treatment method using at least one compound of a specified Formula with alpelisib (BYL-719), where the subject is pre-treated with the compound at least 10 days before alpelisib and the pre-treatment attenuates alpelisib-induced hyperglycemia. Dependent claims further refine dosage, timing, route, dosing schedule, sequencing, and cancer indication.
Pre-treatment with formula compound to attenuate alpelisib-induced hyperglycemia
A method for treating, or ameliorating at least one symptom of, cancer in a subject in need thereof comprising administering a therapeutically effective amount of at least one compound of a Formula, or a pharmaceutically acceptable salt thereof, in combination with a therapeutically effective amount of alpelisib (BYL-719), wherein the subject is pre-treated by administering at least one therapeutically effective amount of the at least one compound at least 10 days prior to the administration of alpelisib, wherein administration of the at least one compound attenuates alpelisib-induced hyperglycemia.
Compound parameter ranges
The Formula defines x in the range of 1 to about 450, y in the range of 1 to about 30, and n in the range of 1 to about 100, or a pharmaceutically acceptable salt thereof.
Daily dosage range
Administering the at least one compound at a daily dosage ranging from about 0.0001 mg/kg to about 5 mg/kg of body weight.
Sequencing with alpelisib
Administering alpelisib (BYL-719) together with at least one compound either sequentially or in substantially simultaneous manner after pre-treatment with the at least one compound.
q4d dosing schedule
Administering at least one compound on a q4d dosing schedule.
Parenteral or subcutaneous administration route
Administering at least one compound parenterally or subcutaneously.
Post-menopausal HR+/Her2− breast cancer indication
The method is for treating post-menopausal HR+/Her2− breast cancer.
Overall claim coverage centers on combining alpelisib with at least one compound of the specified Formula, using pre-treatment at least 10 days before alpelisib to attenuate alpelisib-induced hyperglycemia, with dependent claims adding dosage, sequencing, schedule, route, and post-menopausal HR+/Her2− breast cancer limitations.
Stated Advantages
Attenuates alpelisib-induced hyperglycemia.
Treats, or ameliorates at least one symptom of, cancer in a subject in need thereof.
Documented Applications
Treating, or ameliorating at least one symptom of, cancer in a subject in need thereof using a Formula compound with alpelisib (BYL-719) and pre-treatment that attenuates alpelisib-induced hyperglycemia.
Treating post-menopausal HR+/Her2− breast cancer.
Pre-treatment to reduce or attenuate alpelisib-induced hyperglycemia in a subject receiving alpelisib for cancer treatment.
Interested in licensing this patent?