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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.
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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.
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公开(公告)号：US20230277680A1
公开(公告)日：2023-09-07
申请号：US18012723
申请日：2020-07-09
Applicant: SAPREME TECHNOLOGIES B.V.
Inventor： Ruben POSTEL , Guy HERMANS , Hendrik FUCHS
CPC classification number: A61K47/6807 , A61K47/549 , A61K47/55 , A61K47/6825 , A61K47/6855
Abstract: The invention relates to a conjugate for transferring an effector molecule from outside a cell into said cell, the conjugate comprising at least one effector molecule to be transferred into the cell, at least one saponin of the mono-desmosidic triterpene glycoside type or the bi-desmosidic triterpene glycoside type, and at least one single-domain antibody (sdAb), covalently bound to each other, wherein the sdAb is capable of binding to a cell-surface molecule of said cell. The invention also 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. In addition, the invention relates to a pharmaceutical composition of the invention, for use in the treatment or the prophylaxis of any one or more of: a cancer, an auto-immune disease such as rheumatoid arthritis, an enzyme deficiency, a disease related to an enzyme deficiency, a gene defect, a disease relating to a gene defect, an infection such as a viral infection, hypercholesterolemia, primary hyperoxaluria, haemophilia A, haemophilia B, alpha-1 antitrypsin related liver disease, acute hepatic porphyria, an amyloidosis and transthyretin- mediated amyloidosis. The invention also relates to an in vitro or ex vivo method for transferring the conjugate from outside a cell to inside said cell or for transferring the effector molecule comprised by the conjugate of the invention from outside a cell to inside said cell, preferably to the cytosol of said cell.
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14.发明公开公开(公告)号：US20230256111A1
公开(公告)日：2023-08-17
申请号：US18012741
申请日：2020-07-09
Inventor： Ruben POSTEL , Guy HERMANS , Hendrik FUCHS
CPC classification number: A61K47/6849 , A61K47/6807 , A61K47/6815 , A61K47/6811 , A61K47/6809 , A61K47/6817 , A61K47/6829 , A61K47/26 , A61P35/00
Abstract: The invention relates to a pharmaceutical combination comprising: a first conjugate comprising at least one effector molecule and a single-domain antibody (sdAb) for binding to a first cell-surface molecule; and comprising a saponin, a derivative thereof, or a second conjugate comprising a binding molecule for binding to a second cell-surface molecule and the saponin and/or the derivative thereof, wherein the saponin or the derivative thereof is a monodesmosidic or bidesmosidic triterpene glycoside. The invention also relates to a composition comprising the first conjugate and the saponin (derivative) or the second conjugate comprising the saponin (derivative). In addition, the invention relates to a pharmaceutical combination or composition of the invention, for use as a medicament, and for use in the treatment or the prophylaxis of a cancer, an auto-immune disease such as rheumatoid arthritis, an enzyme deficiency, a gene defect, a disease relating to a gene defect, an amyloidosis, a disease related to an enzyme deficiency, an infection such as a viral infection, hypercholesterolemia, primary hyperoxaluria, haemophilia A, haemophilia B, alpha-1 antitrypsin related liver disease, acute hepatic porphyria, transthyretin-mediated amyloidosis. Furthermore, the invention relates to an in vitro or ex vivo method for transferring the first conjugate of the invention from outside a cell to inside said cell, preferably to the cytosol of said cell.
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Patent Agency Ranking
公开(公告)号：US20250057971A1
公开(公告)日：2025-02-20
申请号：US18723157
申请日：2022-12-20
Applicant: SAPREME TECHNOLOGIES B.V.
Inventor： Miriam Verena BUJNY , Ruben POSTEL , Guy HERMANS
Abstract: The invention lies in the field of treatment and prophylaxis of muscle wasting disorders, in particular the ones involving a genetic factor that can be targeted by a delivery of a therapeutic nucleic acid into the muscle cells. In line with the latter aspect, disclosed herein are pharmaceutical compositions and advantageous components thereof that substantially enhance the effective delivery and release of a therapeutic nucleic acid into the correct internal compartment of the muscle cell, such as the cytosol and/or the nucleus, in which compartment it can reach and act upon its genetic target. As disclosed herein, this substantially enhanced delivery and release is achieved by a provision of an endosomal-escape-enhancing saponin in the disclosed herein pharmaceutical compositions comprising therapeutic nucleic acids and muscle cell-targeting ligands. As for the first time demonstrated herein, these saponin types surprisingly not only appear to retain their endosomal-escape-enhancing properties in fully differentiated muscle cells, but also successfully reach and enter muscle cells in vivo through endothelial transcytosis route followed by endocytic capture at the sarcolemma.
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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.
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公开(公告)号：US20230277612A1
公开(公告)日：2023-09-07
申请号：US18012694
申请日：2021-06-23
Inventor： Ruben POSTEL , Guy HERMANS , Hendrik FUCHS
IPC: A61K36/185 , A61K47/68
CPC classification number: A61K36/185 , A61K47/6807 , A61K47/6819 , A61K47/6849
Abstract: The invention relates to a saponin derivative based on a saponin comprising a triterpene aglycone and a first saccharide chain and/or a second saccharide chain, and comprising: an aglycone core structure comprising an aldehyde group which has been derivatised; and/or the first saccharide chain wherein the first saccharide chain comprises a carboxyl group, which has been derivatised; and/or the second saccharide chain wherein the second saccharide chain comprises at least one acetoxy group which has been derivatised. 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 any one or more of an antibody-toxin conjugate, a receptor-ligand-toxin conjugate, an antibody-drug conjugate, a receptor-ligand-drug conjugate, an antibody-oligonucleotide conjugate or a receptor-ligand-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 prophy laxis of a cancer, an infectious disease, viral infection, hypercholesterolemia, primary hyperoxalmia, haemophilia A. haemophilia B, alpha-1 antitrypsin related liver disease, acute hepatic porphyria, transthy retin-mediated amyloidosis, or an auto-immune disease. Furthermore, the invention relates to an in vitro or ex vivo method for trasferring a molecule from outside a cell to inside said cell, comprising contacting said cell with the molecule and with a saponin derivative of the invention.
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18.发明公开公开(公告)号：US20230263897A1
公开(公告)日：2023-08-24
申请号：US18012769
申请日：2021-06-18
Applicant: SAPREME TECHNOLOGIES B.V.
Inventor： Ruben POSTEL , Guy HERMANS
CPC classification number: A61K47/549 , A61K47/554 , A61K47/6801 , A61P35/00
Abstract: The invention relates to a saponin conjugate comprising a saponin covalently linked to a ligand for ASGPR, the ligand comprising at least one GalNAc. The invention also relates to a pharmaceutical combination comprising a first pharmaceutical composition comprising the saponin conjugate of the invention and a second pharmaceutical composition comprising a second conjugate of an effector molecule and a ligand for ASGPR, or a third conjugate of an effector molecule and a binding molecule for binding to a cell-surface molecule. In addition, the invention relates to a pharmaceutical composition comprising the saponin conjugate of the invention and the second conjugate or the third conjugate. Furthermore, the invention relates to a pharmaceutical combination or pharmaceutical composition of the invention, for use as a medicament. The invention also relates to a pharmaceutical combination or 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 genes: apoB, 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 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. Finally, the invention relates to an in vitro or ex vivo method for transferring the second conjugate or the third conjugate of the invention from outside a cell to inside said cell.
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19.发明公开公开(公告)号：US20230248844A1
公开(公告)日：2023-08-10
申请号：US18012754
申请日：2021-06-22
Inventor： Ruben POSTEL , Guy HERMANS , Hendrik FUCHS
IPC: A61K47/68 , A61K31/704 , A61K47/54 , A61P35/00
CPC classification number: A61K47/6849 , A61K31/704 , A61K47/549 , A61K47/6803 , A61P35/00
Abstract: The invention relates to a pharmaceutical combination comprising: a first conjugate comprising at least one effector molecule and a single-domain antibody (sdAb) for binding to a first cell-surface molecule; and comprising a saponin, a derivative thereof, or a second conjugate comprising a binding molecule for binding to a second cell-surface molecule on the same cell surface as the first cell-surface molecule and the saponin and/or the derivative thereof, wherein the saponin or the derivative thereof is a monodesmosidic or bidesmosidic triterpene glycoside. The invention also relates to a composition comprising the first conjugate and the saponin (derivative) or the second conjugate comprising the saponin (derivative). In addition, the invention relates to a pharmaceutical combination or composition of the invention, for use as a medicament, and for use in the treatment or the prophylaxis of a cancer, an auto-immune disease such as rheumatoid arthritis, an enzyme deficiency, a gene defect, a disease relating to a gene defect, an amyloidosis, a disease related to an enzyme deficiency, an infection such as a viral infection, hypercholesterolemia, primary hyperoxaluria, haemophilia A, haemophilia B, alpha-1 antitrypsin related liver disease, acute hepatic porphyria, transthyretin-mediated amyloidosis. Furthermore, the invention relates to an in vitro or ex vivo method for transferring the first conjugate of the invention from outside a cell to inside said cell, preferably to the cytosol of said cell.
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