Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12133844-B2
Publication Date
2024-11-05
Expiration Date
Abstract
The present invention provides methods and compositions for treating epithelioid cell tumors (such as a PEComa) by administering a composition comprising nanoparticles comprising an mTOR inhibitor and an albumin.
Core Innovation
The invention relates to treating a malignant perivascular epithelioid tumor (PEComa) in an individual using a nanoparticle composition comprising sirolimus and an albumin. The composition is administered intravenously as an effective amount of sirolimus, with dosing on days 1 and 8 of a 21-day cycle.
The nanoparticle composition comprises sirolimus and an albumin component, including human albumin and optionally recombinant albumin. The nanoparticles are described as having an average diameter of no greater than about 150 nm, with albumin:mTOR inhibitor weight ratios including about 1:1 to about 18:1 and Nab-sirolimus/ABI-009 HSA:sirolimus ratios such as about 8:1 to about 9:1.
The compositions are described as stable aqueous suspensions and as substantially free of Cremophor/surfactant, and may be provided as a dry (lyophilized) formulation or as a liquid suspended formulation. Treatment settings described include locally advanced, metastatic, recurrent, neoadjuvant, and adjuvant settings, with biomarker-driven patient selection using mTOR-pathway mutations and phosphorylation markers, including testing by immunohistochemistry and/or DNA sequencing, including circulating/cell-free DNA.
Claims Coverage
The provided independent claim coverage centers on intravenous treatment of malignant PEComa with a nanoparticle composition comprising sirolimus and albumin. The merged inventive features include the disease treatment context, the sirolimus effective amount range, the 21-day dosing schedule, and refinements to nanoparticle size and albumin identity.
Intravenous albumin/sirolimus nanoparticle treatment of malignant PEComa
A method of treating a malignant perivascular epithelioid tumor (PEComa) in an individual by intravenously administering an effective amount of a composition comprising nanoparticles comprising sirolimus and an albumin.
Sirolimus effective amount range in nanoparticle composition
The effective amount of sirolimus in the nanoparticle composition is about 10 mg/m2 to about 100 mg/m2.
Days 1 and 8 dosing on a 21-day cycle
The nanoparticle composition is administered on days 1 and 8 of a 21-day cycle.
Nanoparticles with average diameter no greater than 150 nm
The nanoparticle composition comprises nanoparticles having an average diameter of no greater than about 150 nm.
Human albumin
The albumin is human albumin.
Coverage is anchored in treating malignant PEComa with an intravenous sirolimus-and-albumin nanoparticle composition, using an effective sirolimus amount of about 10 mg/m2 to about 100 mg/m2 and dosing on days 1 and 8 of a 21-day cycle. Additional features refine the nanoparticle average diameter to no greater than about 150 nm and specify human albumin.
Stated Advantages
Tumor shrinkage.
Progression-free survival and/or survival extension.
Metastasis inhibition (metastasis/recurrent prevention).
Symptom alleviation.
Enables stable aqueous suspensions without toxic solvents/surfactants.
Compositions are substantially free of Cremophor/surfactant.
Achieves stabilization over defined time periods.
Provides options for dry (lyophilized) or liquid suspended formulations.
Albumin carrier role reduces side effects by avoiding toxic delivery vehicles.
Documented Applications
Treatment of locally advanced, metastatic, and recurrent malignant PEComa.
Neoadjuvant and adjuvant treatment settings for malignant PEComa.
Biomarker-driven patient selection and response-likelihood assessment using mTOR-pathway mutations and phosphorylation markers, including testing via immunohistochemistry and/or DNA sequencing, including circulating/cell-free DNA.
Treating a malignant perivascular epithelioid tumor (PEComa) in an individual by intravenous administration of a sirolimus-and-albumin nanoparticle composition on a 21-day cycle.
Interested in licensing this patent?