Patent ID: 11944689
Assignee: SEAGEN INC.
Field: Pharmaceuticals (Chemistry)
Classification: CPC C  A | IPC A  C

Claim 3:
4. The Ligand Drug Conjugate compound of claim 2, wherein the compound is represented by the structure of:, , or pharmaceutically acceptable salt(s) thereof, wherein
Su is a carbohydrate moiety;
E′ is a heteroatom, optionally substituted, of a glycosidic bond cleavable by a glycosidase;
J′ represents a heteroatom, optionally substituted;
Y′ is absent or Y′ is —O—, —S—, —NH— or −O—C(═O)—, provided that Y′ is absent when D is a quaternized Drug Unit (D+) that is a tubulysin or auristatin;
V, Z1, Z2 and Z3 independently are ═N— or ═C(R24)—, wherein each R24 is independently selected from the group consisting of hydrogen and C1-C8 alkyl, C2-C8 alkenyl and C2-C8 alkynyl, optionally substituted, halogen, an electron withdrawing group, an electron donating group, —O′-Su, —C(R8)(R9)—Y′-D and —C(R8)(R9)-D+,
provided that one and only one of —C(R8)(R9)—Y′-D and —C(R8)(R9)-D+ moieties and one and only one —O′-Su moiety is present;
wherein one of V, Z1, Z2 and Z3 is ═C(R24)—, in which R24 is —C(R8)(R9)—Y′-D or —C(R8)(R9)-D+ and another of V, Z1, Z2 and Z3 is ═C(R24)—, in which R24 is —O′-Su, provided the —O′-Su and —C(R8)(R9)—Y′-D or —C(R8)(R9)-D+ moieties are ortho or para to each other;
R8 and R9 independently are hydrogen, C1-C8 alkyl, C2-C8 alkenyl and C2-C8 alkynyl, optionally substituted, or C5-C10 aryl or C5-C10 heteroaryl, optionally substituted or R8 and R9 together with the carbon atom to which both are attached define an optionally substituted C5-C6 carbocyclo; and
wherein glycosidase cleavage of the glycosidic bond within a Ligand Drug Conjugate compound initiates release of D/D+ as a biologically active compound or derivative thereof tubulysin or auristatin from that Ligand Drug Conjugate compound,, or, wherein the compound is represented by the structure of:, or pharmaceutically acceptable salt(s) thereof, wherein
J is a heteroatom, optionally substituted;
Y′ is absent or Y′ is —O—, —S—, —NH— or −O—C(═O)—, provided that —Y′— is absent when D is a quaternized Drug Unit (D+) that is a tubulysin or auristatin;
W is a Peptide Cleavable Unit;
V, Z1, Z2 and Z3 are independently ═N— or ═C(R24)—, wherein each R24 is independently selected from the group consisting of hydrogen and C1-C8 alkyl, C2-C8 alkenyl and C2-C8 alkynyl, optionally substituted, halogen, an electron withdrawing group, an electron donating group, —C(R8)(R9)—Y′-D and —C(R8)(R9)-D+, provided that one and only one of —C(R8)(R9)—Y′-D and —C(R8)(R9)-D+ moieties is present,
wherein one of V, Z1, Z2 and Z3 is ═C(R24)—, in which R24 is —C(R8)(R9)—Y′-D or —C(R8)(R9)-D+, provided the —C(R8)(R9)—Y′-D or —C(R8)(R9)-D+ moiety is ortho or para to J;
R8 and R9 independently are hydrogen, C1-C8 alkyl, C2-C8 alkenyl and C2-C8 alkynyl, optionally substituted, or C5-C10 aryl or C5-C10 heteroaryl, optionally substituted, or R8 and R9 together with the carbon atom to which both are attached define an optionally substituted C5-C6 carbocyclo;
wherein protease action on W results in cleavage of the W-J bond within a Ligand Drug Conjugate so as to initiate release of D/D+ as a tubulysin or auristatin from that Ligand Drug Conjugate compound.