OLIGONUCLEOTIDES FOR REDUCING EXPRESSION OF PD-L1 Russian patent published in 2025 - IPC C12N15/113 A61K31/712 A61K47/50 C07H21/00 

FIELD: biotechnology.

SUBSTANCE: disclosed is an antisense oligonucleotide conjugate for reducing expression of PD-L1. Antisense oligonucleotide conjugate has the formula GN2- C6_oc_oa_oCCtatttaacatcAGAC, where C6 denotes an aminoalkyl group with 6 carbon atoms, capital letters denote beta-D-oxy nucleosides LNA, lowercase letters denote DNA nucleosides, all C LNA represent 5-methylcytosine, subscript o denotes a phosphodiester nucleoside bond and, unless otherwise specified, all internucleoside bonds are phosphorothioate internucleoside bonds and where GN2 denotes a trivalent N-acetylgalactosamine (GalNAc) cluster shown in Figure 3, wherein the wavy line in Figure 3 illustrates the conjugation site of said trivalent GalNAc cluster with the C6 aminoalkyl group. Also disclosed is a pharmaceutical composition for treating a disease or disorder which can be alleviated or cured by reducing the expression of PD-L1, such as viral hepatic infections, including HBV (hepatitis B virus), HCV (hepatitis C virus) and HDV (hepatitis D virus), or parasitic infections containing an antisense oligonucleotide conjugate and a pharmaceutically acceptable diluent, solvent, carrier, salt and/or adjuvant. Disclosed is a method for in vitro reduction of PD-L1 expression in a target cell which expresses PD-L1, wherein said method involves introducing an antisense oligonucleotide conjugate or a pharmaceutical composition into said cell in an effective amount. Disclosed is a method of treating or preventing a disease or disorder which can be relieved or cured by reducing the expression of PD-L1, such as viral hepatic infections such as HBV, HCV and HDV, or parasitic infections, involving administering a therapeutically or prophylactically effective amount of an antisense oligonucleotide conjugate or a pharmaceutical composition to a subject suffering or susceptible to said disease or disorder.

EFFECT: invention extends the range of agents which are able to reduce the expression of PD-L1 (programmed death ligand-1) in a target cell.

15 cl, 13 dwg, 24 tbl, 10 ex