STABILITY-MODULATING LINKERS FOR USE WITH ANTIBODY DRUG CONJUGATES Russian patent published in 2019 - IPC A61K47/68 C07K16/30 A61P35/00 

FIELD: chemistry; medicine.

SUBSTANCE: group of inventions relates to biotechnology and medicine, in particular to stability-modulated antibody-drug conjugates (ADC), stability-modulating linker components used to make these ADC, method for treating a cancer using said conjugates and method of making the conjugates. Antibody-drug conjugate has structure (I):

(I) or structure (II), and the linker component has structure (III), as defined in the claims. Antibody-drug conjugate is obtained by transglutaminase mediated conjugation. Method of treating a cancer in a subject in need comprises administering an effective amount of ADC to the subject. Linkers (III) used in conjugates ADC are able to up- and down-modulate the extracellular and/or intracellular stability of antibody-drug conjugates, so that more or less relative amount of the payload of ADCs is released at the desired site.

EFFECT: inventions permit the fine-tuning of ADC stability in vivo and permit the optimization of the therapeutic index of ADCs.

19 cl, 3 dwg, 9 tbl, 72 ex