Amanitin conjugates
AssigneeHeidelberg Pharma Research GmbH
InventorsChristian Lutz, Jan Anderl, Christoph Müller, Werner Simon, Susanne Werner-Simon, Torsten Hechler, Michael Kulke
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Abstract
The invention relates to a conjugate comprising (a) an amatoxin comprising (i) an amino acid 4 with a 6′-deoxy position; and (ii) an amino acid 8 with an S-deoxy position; (b) a target-binding moiety; and (c) optionally a linker linking said amatoxin and said target-binding moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate.
Claims6
A conjugate comprising (a) an amatoxin comprising (i) an amino acid 4 with a 6′-deoxy position;
- and (ii) an amino acid 8 with an S-deoxy position;
- (b) a target-binding moiety;
- and (c) a cleavable linker linking said amatoxin and said target-binding moiety, wherein said target-binding moiety is an antibody or antigen-binding fragment thereof, and wherein said cleavable linker is an enzymatically cleavable linker comprising the structure
- wherein L1 is a part of the linker that connects L* to the amatoxin, and L2 is a part of the linker that connects L* to the target-binding moiety, and wherein the conjugate has the structure I
- wherein:
- R2 is S;
- R3 is selected from —NHR5, —NH—OR5, and —OR5;
- R4 is H;
- and
- wherein one of R5 is -Ln-X, wherein L is said cleavable linker, n is 1, and X is said antibody or antigen-binding fragment thereof, and wherein the remaining R5 are H.
A construct comprising (a) an amatoxin comprising (i) an amino acid 4 with a 6′-deoxy position;
- and (ii) an amino acid 8 with an S-deoxy position;
- and (c) a cleavable linker moiety carrying a reactive group Y for linking said amatoxin to a target-binding moiety, wherein said target-binding moiety is an antibody or antigen-binding fragment thereof, and wherein said cleavable linker is an enzymatically cleavable linker comprising the structure
- wherein L1 is a part of the linker that connects L* to the amatoxin, and L2 is a part of the linker that connects L* to said reactive group Y, and wherein the construct has the structure II
- wherein:
- R2 is S;
- R3 is selected from NHR5, —NH—OR5, and OR5;
- R4 is H;
- and
- wherein one of R5 is -L-Y, wherein L is said cleavable linker, and Y is a reactive group for linking said construct to a target-binding moiety.
Dependencies are inferred from the claim text.