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Publication Number
US-11964948-B2
Publication Date
2024-04-23
Expiration Date
Abstract
Provided are new bifunctional chelators for use in the manufacture of radiolabeled targeting agents for therapeutic or diagnostic use. Also provided are conjugates of the new bifunctional chelators with various cancer antigen targeting agents.
Core Innovation
The invention relates to a bifunctional chelator compound comprising a formula R-L1-M, where R is a reactive group, L1 comprises a linking component, and M is a chelator moiety. The disclosure defines chelator, linker, and reactive-group variants through formulas and related sub-formulas, including specific example chelator moieties such as DOTA and derivatives including p-NH2-Bn-DOTA and DOTA-GA(tBu).
The invention further defines reactive-group options for the bifunctional chelator compound, including NHS or SCN reactive-group types, PODS or ethyl or propyl-sulfone analogs, and 4-pyridyl for Zincke-type chemistry. Linker components are also specified, including benzyl, amino-acid-derived linkers, and PEG spacers, together with detailed repeating units for the structural variants.
Additionally, the disclosure describes chelator-conjugated proteins and antibodies formed by conjugating the bifunctional chelator to molecules containing primary amine groups or free thiol groups and chelating an enumerated set of radionuclides with the chelator moiety. The described targets include CD38 targeting agents and TROP2 and 5T4 targets, with radionuclides explicitly listed across many elemental radioisotopes and including 225Ac and 227Th.
Claims Coverage
The partial content identifies two independent claims. Across these claims, inventive features are directed to a bifunctional chelator compound with a reactive group-linker-chelator architecture and selectable components, and manufacturing a chelator-conjugated molecule by reacting an amine-containing molecule with the bifunctional chelator, optionally including subsequent radionuclide chelation.
Bifunctional chelator compound architecture
A bifunctional chelator compound comprising a formula R-L1-M, wherein R is a reactive group, wherein L1 comprises a linking component, and wherein M is a chelator moiety.
Radionuclide-containing chelator conjugate
The conjugate further comprises a chelated radionuclide selected from an enumerated set of radionuclides.
Selectable chelator moiety formulas for M
M includes a formula selected from chemical structures IIIA, IIIB, and IIIC.
Selectable reactive-group formulas for R
R is selected from a group of specified structural formulas (IIID, IIIE, and IIIF) shown in the claim.
Amine-based manufacture of chelator-conjugated molecule
A method for manufacturing a chelator-conjugated molecule comprising reacting a molecule comprising at least one primary amine group with a bifunctional chelator compound comprising the structure recited in the claim.
Chelation of radionuclide to the chelator-conjugated molecule
The method further includes chelating a radionuclide to the chelator-conjugated molecule.
Radionuclide selected from an explicit enumerated set
The radionuclide is specified as a selected radionuclide from the listed radionuclides.
Overall, the claim coverage centers on a bifunctional chelator compound defined by a reactive group, linker, and chelator moiety, including selectable sub-formulas for M and R, and a manufacturing method that conjugates the bifunctional chelator to an amine-containing molecule, with optional chelation of an enumerated radionuclide to form a radionuclide-containing chelator conjugate.
Stated Advantages
Documented Applications
No documented applications found
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