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US 2024/0197907 A1Published application
Dual-Cleavage Ester Linkers for Antibody-Drug Conjugates
OwnerStepan Chuprakov, Ayodele O. Ogunkoya +1inventors
InventorsStepan Chuprakov, Ayodele O. Ogunkoya, Penelope M. Drake
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Abstract
The present disclosure provides antibody-drug conjugate structures, where the antibody-drug conjugate includes a cleavable linker containing an ester group that links the antibody to the drug. The disclosure also encompasses compounds and methods for production of such conjugates. In addition, the disclosure also encompasses pharmaceutical compositions and methods of using the conjugates.
Claims23
A conjugate of formula (I):
- wherein:
- W1 is a drug;
- W2 is a polypeptide;
- A is an amino acid residue, where k is 0 or an integer from 1 to 5;
- L is a linker;
- G is a conjugation moiety;
- X1 is selected from:
- and —(CHR1)j(CHR2)—;
- R1 is selected from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl and R3, wherein R1 optionally substituted with R3;
- j is 0 or an integer from 1 to 5;
- R2 is R3;
- or R2 is selected from alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, and substituted heterocyclyl, wherein R2 is substituted with R3;
- X2 is —NH— or —C(O)—;
- each R3 is independently a glycoside or glycoside derivative.
11 more elements
A compound of formula (IV):
- wherein:
- W1 is a drug;
- A is an amino acid residue, where k is 0 or an integer from 1 to 5;
- L is a linker;
- G is a conjugation moiety;
- X1 is selected from:
- and —(CHR1)j(CHR2)—;
- R1 is selected from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl and R3, wherein R1 is optionally substituted with R3;
- j is 0 or an integer from 1 to 5;
- R2 is R3;
- or R2 is selected from alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocyclyl, and substituted heterocyclyl, wherein R2 is substituted with R3;
- X2 is —NH— or —C(O)—;
- each R3 is independently a glycoside or glycoside derivative.
10 more elements
-38. (canceled)
Dependencies are inferred from the claim text.