Stable, concentrated radionuclide complex solutions
Inventors
Barbato, Donato • Brambati, Clementina • Chicco, Daniela • de Palo, Francesco • Fugazza, Lorenza • Mariani, Maurizio • Tesoriere, Giovanni
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12144873-B2
Publication Date
2024-11-19
Expiration Date
Abstract
The present invention relates to radionuclide complex solutions of high concentration and of high chemical stability, that allows their use as drug product for diagnostic and/or therapeutic purposes. The stability of the drug product is achieved by at least one stabilizer against radiolytic degradation. The use of two stabilizers introduced during the manufacturing process at different stages was found to be of particular advantage.
Core Innovation
The invention relates to a pharmaceutical aqueous solution for radionuclide complex drug products used in treating a tumor, including gastroenteropancreatic neuroendocrine tumors. The solution comprises a complex of the radionuclide 177Lu and a somatostatin receptor binding peptide linked to the chelating agent DOTA, together with at least one stabilizer against radiolytic degradation. The formulation is ethanol-free or low ethanol and is described as suitable for ready-to-use commercialization with defined solution volumes.
The core formulation constraint is that the at least one stabilizer against radiolytic degradation is present in a specified total concentration range, while the radionuclide provides a specified volumetric radioactivity range. The solution comprises less than 2% ethanol in general embodiments and less than 1% ethanol in gastroenteropancreatic neuroendocrine tumor embodiments. The document emphasizes stabilization against radiolytic degradation and maintenance of chemical and radiochemical purity over time.
The invention highlights maintenance of radiochemical purity of at least 95% over a defined storage period at 25°C, with radiochemical purity determined by HPLC. The document also describes that the formulation is suitable for treatment of neuroendocrine tumors, including gastroenteropancreatic neuroendocrine tumors, and specifically references Lu-177 DOTA-TATE (oxodotreotide) and Lu-177 DOTA-TOC formulations as stabilized aqueous radionuclide complex drug products.
Claims Coverage
The independent claims are clm-00001 and clm-00027. Across these claims, the coverage centers on administering a stabilized 177Lu-DOTA somatostatin receptor binding peptide aqueous solution with specified stabilizer concentration, specified volumetric radioactivity, and ethanol limits, to treat tumor types including gastroenteropancreatic neuroendocrine tumors. The independent claims each define the main inventive formulation constraints and the treatment context.
Stabilized 177Lu-DOTA somatostatin receptor binding peptide aqueous solution for tumor treatment
A method of treating a tumor in a patient in need thereof by administering a pharmaceutical aqueous solution comprising a complex of 177Lu and a somatostatin receptor binding peptide linked to DOTA, and at least one stabilizer against radiolytic degradation.
Radiolytic stabilizer concentration, volumetric radioactivity, and ethanol limit
The at least one stabilizer against radiolytic degradation is present in a total concentration of 0.5 mg/mL to 10.0 mg/mL; the radionuclide provides a volumetric radioactivity of 250 to 500 MBq/mL; and the pharmaceutical aqueous solution comprises less than 2% ethanol.
Stabilized 177Lu-DOTA somatostatin receptor binding peptide aqueous solution for gastroenteropancreatic neuroendocrine tumor treatment
A method of treating a gastroenteropancreatic neuroendocrine tumor in a patient in need thereof by administering a pharmaceutical aqueous solution comprising a complex of 177Lu and a somatostatin receptor binding peptide linked to DOTA, and at least one stabilizer against radiolytic degradation.
Radiolytic stabilizer concentration, volumetric radioactivity, and ethanol limit for gastroenteropancreatic neuroendocrine tumors
The at least one stabilizer against radiolytic degradation is present in a total concentration of 1.0 mg/mL to 5.0 mg/mL; the radionuclide provides a volumetric radioactivity of 250 to 500 MBq/mL; and the pharmaceutical aqueous solution comprises less than 1% ethanol.
Overall, clm-00001 and clm-00027 cover tumor treatment by administering a stabilized ethanol-free or low-ethanol pharmaceutical aqueous solution containing a 177Lu/DOTA-linked somatostatin receptor binding peptide complex, with stabilizer concentration and volumetric radioactivity constrained to specified ranges and with stricter ethanol limits for gastroenteropancreatic neuroendocrine tumors.
Stated Advantages
Stabilized against radiolytic degradation.
Maintenance of radiochemical purity at least 95% for at least 72 hours when stored at 25°C, with purity determined by HPLC.
Enables ready-to-use commercialization via ethanol-free or low ethanol pharmaceutical aqueous solution.
Documented Applications
Treating a tumor in a patient in need thereof using an aqueous pharmaceutical solution comprising 177Lu with a somatostatin receptor binding peptide linked to DOTA and stabilizers against radiolytic degradation.
Treating a gastroenteropancreatic neuroendocrine tumor in a patient in need thereof using an aqueous pharmaceutical solution comprising 177Lu with a somatostatin receptor binding peptide linked to DOTA and stabilizers against radiolytic degradation.
Interested in licensing this patent?