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

Claim 0:
1. A Ligand Drug Conjugate (LDC) compound, wherein the compound is represented by the structure of Formula 1 or Formula 2:, , or a pharmaceutically acceptable salt thereof, wherein
L is a Ligand Unit, wherein the Ligand Unit is an antibody or an antigen binding fragment thereof;
S is a sulfur atom of the Ligand Unit, which in Formula 2 is bonded to the carbon atom α or β to the carboxylic acid functional group of the indicated succinic acid amide (M3) moiety;
RM is hydrogen or an optionally substituted C1-C6 alkyl, which in Formula 2 is bonded to the saturated carbon atom adjacent to the carbon substituted by L-S—;
subscript w is 0 or 1;
subscript n is 1, 2, 3 or 4;
subscript a is 0 or 1;
subscript b is 0 or 1,
provided that subscript b is 1 when subscript n is 2, 3 or 4 and subscript b is 0 when subscript n is 1;
A is a first optional Stretcher Unit comprising an α-amino acid, a β-amino acid or other amine-containing acid residue;
AO is —C(═O)—;
B is an optional Branching Unit comprising a natural or un-natural amino acid or other amine-containing acid residue having a functionalized side chain; and
wherein each of A, AO and B is an independently selected single unit or is optionally comprised or consists of two, three or four independently selected subunits;
Y is optionally present as an optionally substituted heteroatom, an optionally substituted functional group or a Spacer Unit, independently selected when subscript y is 2 so that Yy is —Y—Y′—, wherein Y and Y′ are, respectively, a first and second optionally substituted heteroatom, optionally substituted functional group or Spacer Unit;
subscript w is 0 or 1, wherein W is absent when subscript w is 0, or when subscript w is 1 then
W is a Peptide Cleavable Unit, or
W is a Glucuronide Unit of formula —Y(W′)—, wherein W′ represents a carbohydrate moiety with glycosidic bonding to Y through a optionally substituted heteroatom;
provided that Y bonded to W′ is a self-immolative Spacer Unit;
subscript y is 0, 1 or 2,
provided that subscript y is 1 or 2, when W is a Glucuronide Unit, in which instance subscript y is inclusive of the self-immolative Spacer Unit bonded to W′, except that subscript y is 1 and Y of the Glucuronide Unit is bonded to D when D is a quaternized Drug Unit (D+) that is a tubulysin or auristatin, and
provided that subscript y is 1 and Y is a self-immolative Spacer Unit bonded to D and W when W is a Peptide Cleavable Unit and D is a quaternized Drug Unit (D+) that is a tubulysin or auristatin;, subscript P is 1 and subscript Q is 1, 2 or 3, or subscript P is 2 and Q is 1 or 2;, and
wherein Ra3 is —H, C1-C6 alkyl, —C1-C4 alkylene-(C6-C10 aryl), or —RPEG1—O—(CH2CH2O)n′—RPEG2, wherein RPEG1 is C1-C4 alkylene, RPEG2 is —H or C1-C4 alkyl, and subscript n′ ranges from 1 to 36;
wherein the basic nitrogen bonded to Ra3 is optionally protonated;
D is a Drug Unit that is a tubulysin or auristatin, or
D is a quaternized Drug Unit that is a tubulysin or auristatin represented as D+ so that D+ replaces D in Formula 1 and Formula 2 provided that subscript w is 1;
wherein if subscript w is 1, activation of the Glucuronide Unit by a glycosidase or activation of the Peptide Cleavable Unit by a protease within a Ligand Drug Conjugate compound initiates release of the Drug Unit or quaternized Drug Unit as a tubulysin or auristatin from that Ligand Drug Conjugate compound,
or if subscript w is 0, a tubulysin or auristatin is released from a Ligand Drug Conjugate compound on enzymatic or non-enzymatic cleavage of a bond within a drug linker moiety of the Conjugate compound that attaches Yy-D to the indicated LSS or LS structure of that drug linker moiety; and
wherein subscript p′ is an integer ranging from 1 to 24.