US 12,576,158 B2 · Antibody drug conjugates with cleavable linkers

Abstract

The present invention relates to prodrugs comprising a linker comprising five- or six-membered cyclic acetals and an adjacent specific cleavage site, and to precursor compounds for the synthesis of said prodrugs. In one aspect the present invention relates to antibody-targeted amatoxin conjugates comprising said linkers, to methods for their synthesis, and to the use of said antibody-targeted amatoxin conjugates. In a further aspect, the invention relates to pharmaceutical compositions comprising said conjugates, and to the use of said conjugates or compositions for therapeutic purposes, in particular for tumor therapy and oncology.

Claims22

Dependent claims

A compound of Formula I or II comprising a cytotoxic drug moiety

wherein
D is a cytotoxic drug moiety comprising at least one 1,2- or 1,3-diol moiety upon release from the compound, wherein D is an amatoxin selected from the group consisting of α-amanitin, β-amanitin, amanin, amaninamide, analogues thereof, derivatives thereof, and salts thereof;
Z is CH2, CH2—CH2 or CHR3-CHR3, wherein each R3 is independently H or an alkyl group, optionally substituted by one or more heteroatoms;
R1 is H or a C1-C6 alkyl group;
A is an electron donating group;
E is a cleavage site;
and
each R2 is independently H, an electron withdrawing group, or an electron donating group.

5 more elements

Dependencies are inferred from the claim text.

Facts

Application

17/613,638Filed 22 May 2020

Priority

EP 1917627823 May 2019

Published

US 2023/0173087 A18 Jun 2023

Granted

17 Mar 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification14 codes

A61K 47/6831
Toxins: fungal toxins, e.g. alpha sarcine, mitogillin, zinniol or restrictocin
A61K 39/395
Medicinal preparations containing antigens or antibodies: antibodies ; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61K 47/6849
The modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site: the antibody targeting a receptor, a cell…
A61K 47/6851
The modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site: the antibody targeting a determinant of a…

Antibody drug conjugates with cleavable linkers

Life of this patent

Antibody drug conjugates with cleavable linkers

Life of this patent

Abstract

Claims22