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Publication Number
US-11975081-B2
Publication Date
2024-05-07
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 new bifunctional chelator compounds for preparing radiolabeled targeting agents. The bifunctional chelator compounds include a chelator moiety and a reactive group linked through a linker in which the linker includes an integer parameter n, expressed in the form R-L-M or R-L1-M, where n is 1 or an integer greater than 1.
The reactive group is conjugatable and is described as selected from NHS, SCN, PODS, and a 4-pyridyl reactive group option based on the Zincke reaction. Linker families include benzyl, amino-acid or amino-acid derivatives, PEG spacers with PEGn, cyclic or linear hydrocarbons, ethyleneamine, and thiourea, together with spacer or auxiliary components such as PEGn and benzyl.
The chelator moiety is described with specific chelator types and variants, including DOTA, DOTA-GA, p-NH2-Bn-DOTA, DOTA-GA(tBu)4, and DOTA-methylamine variants. The disclosure also recites chelator conjugates formed by reacting bifunctional chelator compounds with molecules that provide primary amine groups or free thiol groups, including optional disulfide bond reduction, and conjugation to antibody and antibody fragment formats including heavy and light chain formats, Fab, Fab2, scFv, and nanobodies.
The disclosure further enumerates chelatable radionuclide isotopes including Ce-134, Sc-43/44/47, Co-55, Cu-60/61/62/64/67, Ga-66/67/68, Rb-82, Y-86/87/90, Ho-166, Zr-89, Ru-97, Rh-105, Pd-109, In-111 and 117mSn, Pm-149, Tb-149, Sm-153, Lu-177, Tl-201 and 203Pb, Pb-212, Bi-212/213, Ac-225, and Th-227. The partial content also links the chelator compounds to downstream conjugate and composition contexts for radiolabeled targeting agents, including proteins, antibodies, scFv, CD38, TROP2, and 5T4.
Claims Coverage
The partial claim set includes two independent claims. Across these independent claims, the core inventive subject matter is bifunctional chelator compounds having a reactive group linked to a chelator moiety through a linker with n defined, and a method that reacts a molecule with at least one primary amine group with such a bifunctional chelator compound.
Bifunctional chelator compound with R-L1-M structure including n
A bifunctional chelator compound comprising a formula R-L1-M, where R is a reactive group, L1 comprises n where n is 1 or an integer greater than 1, and M is a chelator moiety.
Manufacturing chelator-conjugated molecule by reacting primary-amine molecule with bifunctional chelator compound
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 in which n is 1 or an integer greater than 1.
The claims coverage is centered on the structural definition of bifunctional chelator compounds and a corresponding manufacturing method reacting primary-amine-containing molecules with these bifunctional chelator compounds to form chelator-conjugated molecules. Dependent claims further specify conjugation and reactive-group chemistry, selected chelator-moiety structures, optional radionuclide chelation, and enumerated radionuclide isotope lists.
Stated Advantages
Documented Applications
No documented applications found
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