Amanitin antibody conjugates
AssigneeHeidelberg Pharma Research GmbH
InventorsTorsten Hechler, Michael Kulke, Christian Lutz, Andreas Pahl, Christoph Müller, Werner Simon, Anikó Pálfi
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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 BCMA-binding moiety comprising (i) the variable domains of humanized antibody J22.9-ISY, and (ii) a heavy chain constant region comprising a D265C mutation; and (c) a protease-cleavable linker linking said amatoxin and said target-binding moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate, particularly for use in the treatment of multiple myeloma.
Claims3
A conjugate according to Formula I comprising (a) an amatoxin;
- (b) a BCMA-binding moiety comprising the antibody heavy chain according to SEQ ID NO:
- 1 and the antibody light chain according to SEQ ID NO:
- 2, wherein the, heavy chain constant region of the antibody heavy chain sequence comprises a D265C mutation (J22.9-ISY-D265C);
- and (c) a protease-cleavable linker, wherein said BCMA-binding moiety is attached to said linker via the thiol group of the cysteine residue at position 265 in the antibody heavy chain, wherein said amatoxin is characterized by comprising (i) an amino acid 4 with a 6′-deoxy position;
- and (ii) an amino acid 8 with an S-deoxyposition
Dependencies are inferred from the claim text.