Patent ID: 8512707

Claim:
A method of treating refractory or drug-resistant cancer cells in a patient in need of such treatment, said method comprising: (a) evaluating whether the patient has a refractory or drug-resistant cancer, (b) administering to the patient having a refractory or drug-resistant cancer an effective amount of a Drug-Linker-Ligand conjugate of the following formula: L-(LU-D) p I or a pharmaceutically acceptable salt or solvate thereof wherein, L- is a Ligand unit; LU is a Linker unit; p is an integer from 1 to about 20; and -D is a Drug unit having the Formula D F : wherein, independently at each location: R 2 is selected from the group consisting of H and C 1 -C 10 alkyl; R 3 is selected from the group consisting of H, C 1 -C 10 alkyl, C 3 -C 8 carbocycle, aryl, C 1 -C 10 alkyl-aryl, C 1 -C 10 alkyl-(C 3 -C 8 carbocycle), C 3 -C 8 heterocycle and C 1 -C 10 alkyl-(C 3 -C 8 heterocycle); R 4 is selected from the group consisting of H, C 1 -C 10 alkyl, C 3 -C 8 carbocycle, aryl, C 1 -C 10 alkyl-aryl, C 1 -C 10 alkyl-(C 3 -C 8 carbocycle), C 3 -C 8 heterocycle and C 1 -C 10 alkyl-(C 3 -C 8 heterocycle); R 5 is selected from the group consisting of H and methyl; or R 4 and R 5 jointly form a carbocyclic ring and have the formula —(CR a R b ) n1 — wherein R a and R b are independently selected from the group consisting of H, C 1 -C 10 alkyl and C 3 -C 8 carbocycle and n1 is selected from the group consisting of 2, 3, 4, 5 and 6; R 6 is selected from the group consisting of H and C 1 -C 10 alkyl; R 7 is selected from the group consisting of H, C 1 -C 10 alkyl, C 3 -C 8 carbocycle, aryl, C 1 -C 10 alkyl-aryl, C 1 -C 10 alkyl-(C 3 -C 8 carbocycle), C 3 -C 8 heterocycle and C 1 -C 10 alkyl-(C 3 -C 8 heterocycle); each R 8 is independently selected from the group consisting of H, OH, C 1 -C 10 alkyl, C 3 -C 8 carbocycle and O—(C 1 -C 10 alkyl); R 9 is selected from the group consisting of H and C 1 -C 10 alkyl; R 10 is selected from the group consisting of aryl and C 3 -C 8 heterocycle; Z is O; R 11 is H or Me; and (c) monitoring the patient to determine the status of the cancer; wherein administration of the Drug-Linker-Ligand conjugate kills or inhibits the proliferation of the cancer cells.