公开(公告)号：US20240115712A1

公开(公告)日：2024-04-11

申请号：US18262994

申请日：2022-01-26

Applicant: SAPREME TECHNOLOGIES B.V.

Inventor： Guy HERMANS ,  Ruben POSTEL ,  Helmus VAN DE LANGEMHEEN ,  Mazdak ASADIAN BIRJAND

IPC: A61K47/55 ,  A61K47/54

CPC classification number: A61K47/55 ,  A61K47/554

Abstract: The invention relates to a saponin conjugate comprising a saponin derivative based on a saponin comprising a triterpene aglycone and at least one of a first saccharide chain and a second saccharide chain linked to the aglycone core structure, wherein the saponin derivative comprises an aglycone core structure comprising an aldehyde functional group which aldehyde functional group has been transformed to a semicarbazone functional group, the saponin conjugate further comprising a proteinaceous molecule capable of binding to a cell-surface molecule. The invention also relates to a composition comprising the saponin conjugate. In addition, the invention relates to a pharmaceutical combination comprising said composition comprising the saponin conjugate and a pharmaceutical composition comprising for example an ADC or an antibody-oligonucleotide conjugate (AOC). The invention also relates to a pharmaceutical composition comprising the saponin conjugate and comprising for example an ADC or an AOC. The invention also relates to the pharmaceutical combination or pharmaceutical composition, for use as a medicament. The invention also relates to the saponin conjugate comprising the saponin derivative, a proteinaceous molecule capable of binding to a cell surface molecule (endocytic receptor), and further comprising an effector moiety such as an oligonucleotide. The invention also relates to an in vitro or ex vivo method for transferring a molecule from outside a cell to inside said cell.

公开(公告)号：US20240066045A1

公开(公告)日：2024-02-29

申请号：US18044950

申请日：2021-09-09

Applicant: SAPREME TECHNOLOGIES B.V.

Inventor： Guy HERMANS ,  Ruben POSTEL ,  Helmus VAN DE LANGEMHEEN ,  Mazdak ASADIAN BIRJAND

IPC: A61K31/7034 ,  A61K47/68 ,  A61P3/06 ,  A61P35/00

CPC classification number: A61K31/7034 ,  A61K47/6803 ,  A61P3/06 ,  A61P35/00 ,  A61K2121/00

Abstract: The invention relates to a saponin derivative based on a saponin comprising a triterpene aglycone and at least one of a first saccharide chain and a second saccharide chain linked to the aglycone core structure, wherein the saponin derivative comprises an aglycone core structure comprising an aldehyde functional group which has been transformed to a semicarbazone functional group. The invention also relates to a first pharmaceutical composition comprising the saponin derivative of the invention. In addition, the invention relates to a pharmaceutical combination comprising the first pharmaceutical composition of the invention and a second pharmaceutical composition comprising for example an ADC or a GalNAc-oligonucleotide conjugate. The invention also relates to the first pharmaceutical composition or the pharmaceutical combination of the invention, for use as a medicament, or use in the treatment or prophylaxis of a cancer or an auto-immune disease, a cardiovascular disease or hypercholesterolemia, or in a method for lowering LDL-cholesterol in the circulation of a subject. The invention also relates to a saponin conjugate comprising a proteinaceous molecule, capable of binding to a cell, and optionally comprising an effector moiety such as an oligonucleotide. The invention also relates to a saponin conjugate comprising GalNAc and an oligonucleotide.

公开(公告)号：US20240327829A1

公开(公告)日：2024-10-03

申请号：US18044945

申请日：2021-09-09

Applicant: SAPREME TECHNOLOGIES B.V.

Inventor： Guy HERMANS ,  Ruben POSTEL ,  Helmus VAN DE LANGEMHEEN ,  Mazdak ASADIAN BIRJAND

IPC: C12N15/113

CPC classification number: C12N15/113 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/351 ,  C12N2310/53

Abstract: The invention relates to a conjugate comprising a saponin covalently linked to a ligand for ASGPR, the ligand comprising at least one GalNAc moiety, and comprising an oligonucleotide covalently linked to the saponin and the ligand for ASGPR. In addition, the invention relates to a pharmaceutical composition comprising the conjugate of the invention. Furthermore, the invention relates to a pharmaceutical composition of the invention, for use as a medicament. The invention also relates to a pharmaceutical composition of the invention, for use in the treatment or prophylaxis of a disease or health problem in which an expression product is involved of for example genes: apoB, HSP17, TTR, PCSK9, ALAS1, AT3, GO, CC5, X gene of HBV, S gene of HBV, AAT and LDH, and for use in the treatment or prophylaxis of for example a cancer, an infectious disease, a viral infection, hypercholesterolemia, primary hyperoxaluria, haemophilia A, haemophilia B, AAT related liver disease, acute hepatic porphyria, TTR amyloidosis, complement-mediated disease, hepatitis B infection, or an auto-immune disease. The invention also relates to a method for producing an oligonucleotide conjugate of the invention. Finally, the invention relates to an in vitro or ex vivo method for transferring the conjugate of the invention from outside a cell to inside said cell.

公开(公告)号：US20240307545A1

公开(公告)日：2024-09-19

申请号：US18571599

申请日：2022-03-08

Applicant: SAPREME TECHNOLOGIES B.V.

Inventor： Ruben POSTEL ,  Guy HERMANS ,  Helmus VAN DE LANGEMHEEN ,  Mazdak ASADIAN BIRJAND

IPC: A61K47/54 ,  A61K31/713 ,  A61K47/55

CPC classification number: A61K47/549 ,  A61K31/713 ,  A61K47/55

Abstract: The invention relates to a conjugate comprising a saponin covalently linked to a ligand for ASGPR, the ligand comprising at least one GalNAc moiety, and comprising an oligonucleotide covalently linked to the saponin and the ligand for ASGPR. In addition, the invention relates to a pharmaceutical composition comprising the conjugate of the invention. Furthermore, the invention relates to a pharmaceutical composition of the invention for use as a medicament. The invention also relates to a pharmaceutical composition of the invention for use in the treatment or prophylaxis of a disease or health problem in which an expression product is involved of for example genes: apoB, HSP17, TTR, PCSK9, ALASI, AT3, GO, CC5, X gene of HBV, S gene of HBV, AAT and LDH, and for use in the treatment or prophylaxis of for example a cancer, an infectious disease, a viral infection, hypercholesterolemia, primary hyperoxaluria, haemophilia A, haemophilia B, AAT related liver disease, acute hepatic porphyria, TTR amyloidosis, complement-mediated disease, hepatitis B infection, or an auto-immune disease. The invention also relates to an in vitro or ex vivo method for transferring the oligonucleotide conjugate of the invention from outside a cell to inside said cell.