초록 ▼

Targeting protein-diagnostic/therapeutic agent conjugates joined by stabilized Schiff base linkages are disclosed. Schiff base linkage of targeting protein and agent is accomplished without exposure of the targeting protein to harsh oxidizing or reducing conditions. The cleavable, heterobifunctional

Targeting protein-diagnostic/therapeutic agent conjugates joined by stabilized Schiff base linkages are disclosed. Schiff base linkage of targeting protein and agent is accomplished without exposure of the targeting protein to harsh oxidizing or reducing conditions. The cleavable, heterobifunctional linkers that are described provide certain advantages relating to in vivo administration of targeting protein conjugates, including controlled release of active agent at a target site.

대표청구항 ▼

A targeting protein conjugated to a radionuclide by a Schiff base linker and having the formula: [Figure] wherein etc. “Ar”is a substituted or unsubstituted aryl group; “N”is a nitrogen atom; “C”is a carbon atom; “R”is H or an alkyl, aryl or heteroaryl substituent; and “Z”comprises a radionuclide se

A targeting protein conjugated to a radionuclide by a Schiff base linker and having the formula: [Figure] wherein etc. “Ar”is a substituted or unsubstituted aryl group; “N”is a nitrogen atom; “C”is a carbon atom; “R”is H or an alkyl, aryl or heteroaryl substituent; and “Z”comprises a radionuclide selected from the group consisting of 123I, 125I, 130I, 131I, 133I, 135I, 47Sc, 72Se, 90Y, 88Y, 97Ru, 119Sb, 197Hg, 211At, 212Bi, 212Pb, 111In, 67Ga, 68Ga, 67Cu, 75Br, 76Br, 99mTc, 18F, 188Re, 186Re, 203Pb, 64Cu, 105Rh, 198Au and 199Au, and wherein the substituent of Ar, if present, is an electron-withdrawing group or an electron-donating group capable of modifying unreduced imine bond stability of the Schiff base linker, and wherein the Schiff base is formed by a process which comprises: reacting a non-oxidized and native amine-bearing or amine-derivatized targeting protein with aromatic aldehyde or ketone, wherein the aromatic aldehyde or ketone is directly conjugated to Z or indirectly conjugated to Z via a chelating ligand, to form a stabilized Schiff base linker, absent a subsequent stabilizing step with respect to the C=N bond, wherein antibody antigen binding antibody fragment carbohydrate content is not determinative of maximum possible aromatic aldehyde or ketone conjugation to the antibody or antigen binding antibody fragment.