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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
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.
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公开(公告)号：US20240115726A1
公开(公告)日：2024-04-11
申请号：US18012791
申请日：2021-06-22
Applicant: SAPREME TECHNOLOGIES B.V.
Inventor： Ruben POSTEL , Guy HERMANS
CPC classification number: A61K47/6851 , A61K47/542 , A61K47/545 , A61K47/549 , A61K47/6889
Abstract: The invention relates to a saponin derivative 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 AOC. 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. Furthermore, the invention relates to an in vitro or ex vivo method for transferring 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. The invention also relates to a saponin conjugate comprising a cell-surface molecule binding-molecule, capable of binding to a target cell, covalently bound to the saponin. The invention also relates to a pharmaceutical combination comprising a pharmaceutical composition comprising the saponin conjugate of the invention and a second pharmaceutical composition comprising an active pharmaceutical ingredient, or to a pharmaceutical composition comprising the saponin conjugate of the invention and an active pharmaceutical ingredient. In addition, the invention relates to said pharmaceutical combination of the invention or said pharmaceutical composition of the invention, for use as a medicament, or for use in the treatment or the prophylaxis of a cancer or an auto-immune disease.
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3.发明公开公开(公告)号：US20230270872A1
公开(公告)日：2023-08-31
申请号：US18012710
申请日：2020-07-09
Inventor： Ruben POSTEL , Guy HERMANS , Hendrik FUCHS
CPC classification number: A61K47/6807 , A61K45/06 , A61K47/6855 , A61K47/6849 , A61P35/00
Abstract: The invention relates to a conjugate for transferring a saponin of the monodesmosidic triterpene glycoside type or of the bidesmosidic triterpene glycoside type from outside a cell into said cell, the conjugate comprising a single-domain antibody, capable of binding to said cell, covalently bound to a saponin. The invention also relates to a pharmaceutical combination comprising a first pharmaceutical composition comprising the conjugate of the invention and a second pharmaceutical composition comprising an active pharmaceutical ingredient, or to a pharmaceutical composition comprising the conjugate of the invention and an active pharmaceutical ingredient. In addition, the invention relates to the pharmaceutical combination of the invention or the pharmaceutical composition of the invention, for use as a medicament, or for use in the treatment or the prophylaxis of a cancer, an auto-immune disease, an infection, an enzyme deficiency, a gene defect. Furthermore, the invention relates to an in vitro or ex vivo method for transferring a molecule from outside a cell to inside said cell, comprising the application of the conjugate of the invention. Finally, the invention relates to a kit of parts, comprising the pharmaceutical combination of the invention or the pharmaceutical composition of the invention, or the conjugate of the invention, and instructions for use thereof.
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公开(公告)号：US20240279684A1
公开(公告)日：2024-08-22
申请号：US18564885
申请日：2022-05-19
Applicant: SAPREME TECHNOLOGIES B.V.
Inventor： Ruben POSTEL , Alexander WENG , Matthias Friedrich MELZIG , Simko SAMA
CPC classification number: C12N15/87 , C12N9/22 , C12N15/11 , C12N15/88 , C12N15/907 , C12N2310/20 , C12N2800/80
Abstract: A first aspect of the invention relates to the use of a saponin in the in vitro delivery of a nucleic acid into a cell. Typically, the nucleic acid is plasmid DNA, e.g. with a relatively large size of at least 5.5 kbp. In embodiments, the nucleic acid is transfected into cells in the presence of saponin GE1741 and/or saponin SO1861. A second aspect of the invention relates to a method for delivering a nucleic acid encoding for a CRISPR/Cas construct into a cell in vitro. Typically, the nucleic acid is plasmid DNA, e.g. with a relatively large size of at least 5.5 kbp. In embodiments, the nucleic acid is transfected into cells in the presence of saponin GE1741 and/or saponin SO1861. In embodiments, the nucleic acid is combined with poly-lysine, forming nanoplexes for transfection of the nucleic acid into a In cell. A third aspect of the invention relates to a kit of parts for delivering a nucleic acid encoding for a CRISPR/Cas construct into a cell in vitro. In addition, the invention also relates to a nanoparticle suitable for in vitro delivery of a nucleic acid into a cell, the nanoparticle comprising or consisting of a nucleic acid encoding for a CRISPR/Cas construct, a poly-lysine peptide and optionally a saponin.
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公开(公告)号：US20230365617A1
公开(公告)日：2023-11-16
申请号：US18012698
申请日：2021-06-23
Applicant: SAPREME TECHNOLOGIES B.V.
Inventor： Ruben POSTEL , Guy HERMANS , Hendrik FUCHS
CPC classification number: C07J17/005 , A61K36/48 , A61K47/549 , A61K47/6807 , A61K47/6819 , A61P35/00
Abstract: The invention relates to a Quillaja saponaria 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 prophylaxis of a cancer, an infectious disease, viral infection, hypercholesterolemia, primary hyperoxaluria, haemophilia A, haemophilia B, alpha-1 antitrypsin related liver disease, acute hepatic porphyria, transthyretin-mediated amyloidosis, or an autoimmune disease. Furthermore, the invention relates to an in vitro or ex vivo method for transferring 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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Patent Agency Ranking
公开(公告)号：US20230302140A1
公开(公告)日：2023-09-28
申请号：US18012729
申请日：2021-06-22
Applicant: SAPREME TECHNOLOGIES B.V.
Inventor： Ruben POSTEL , Guy HERMANS , Hendrik FUCHS
CPC classification number: A61K47/549 , A61K47/6415 , A61K47/6807 , 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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7.发明公开公开(公告)号：US20230293708A1
公开(公告)日：2023-09-21
申请号：US18012715
申请日：2021-06-22
Inventor： Ruben POSTEL , Guy HERMANS , Hendrik FUCHS
CPC classification number: A61K47/6809 , A61K47/6889 , A61K47/6851 , A61K47/6849 , A61K45/06 , A61P35/00
Abstract: The invention relates to a conjugate for transferring a saponin of the monodesmosidic triterpene glycoside type or of the bidesmosidic triterpene glycoside type from outside a cell into said cell, the conjugate comprising a single-domain antibody, capable of binding to said cell, covalently bound to a saponin. The invention also relates to a pharmaceutical combination comprising a first pharmaceutical composition comprising the conjugate of the invention and a second pharmaceutical composition comprising an active pharmaceutical ingredient, or to a pharmaceutical composition comprising the conjugate of the invention and an active pharmaceutical ingredient. In addition, the invention relates to the pharmaceutical combination of the invention or the pharmaceutical composition of the invention, for use as a medicament, or for use in the treatment or the prophylaxis of a cancer, an auto-immune disease, an infection, an enzyme deficiency, a gene defect. Furthermore, the invention relates to an in vitro or ex vivo method for transferring a molecule from outside a cell to inside said cell, comprising the application of the conjugate of the invention. Finally, the invention relates to a kit of parts, comprising the pharmaceutical combination of the invention or the pharmaceutical composition of the invention, or the conjugate of the invention, and instructions for use thereof.
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8.发明公开公开(公告)号：US20230293562A1
公开(公告)日：2023-09-21
申请号：US18012778
申请日：2021-06-23
Applicant: SAPREME TECHNOLOGIES B.V.
Inventor： Ruben POSTEL , Guy HERMANS
IPC: A61K31/704 , A61K47/54
CPC classification number: A61K31/704 , A61K47/549
Abstract: The invention relates to a pharmaceutical combination comprising: a conjugate of an effector molecule and a ligand for ASGPR, wherein the ligand for ASGPR comprises at least one GalNAc moiety; and a saponin of the monodesmosidic or bidesmosidic triterpene glycoside type. The invention also relates to a pharmaceutical composition comprising the conjugate and the saponin. In addition, the invention relates to a pharmaceutical combination or composition of the invention, for use as a medicament, or for use in the treatment or prophylaxis of a disease or health problem in which an expression product is involved of any one or more of genes: apoB, TTR, PCSK9, ALAS 1, ATS, GO, CCS, X gene of HBV, S gene of HBV, AAT and LDH, and/or 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-mediated amyloidosis, hereditary TTR amyloidosis (hATTR), complement-mediated disease, hepatitis B infection, or an auto-immune disease. Furthermore, the invention relates to an in vitro or ex vivo method for transferring an effector molecule of the invention from outside a cell to inside said cell, preferably into the cytosol of said cell. The invention also 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：US20230248845A1
公开(公告)日：2023-08-10
申请号：US18012760
申请日：2021-06-22
Applicant: SAPREME TECHNOLOGIES B.V.
Inventor： Ruben POSTEL , Guy HERMANS
CPC classification number: A61K47/6851 , A61K47/549 , A61K47/542 , A61K47/6815 , A61K47/6827 , A61K47/6817 , A61K47/6829 , A61K47/6809 , A61K47/6889 , A61P35/00
Abstract: The invention relates to a therapeutic combination comprising: (a) a first pharmaceutical composition comprising a conjugate comprising a first binding molecule for binding to a first binding site of a cell-surface molecule and the conjugate comprising a saponin bound to said first binding molecule, wherein the saponin is a triterpene glycoside; and (b) a second pharmaceutical composition comprising a conjugate comprising a second binding molecule different from the first binding molecule, the second binding molecule comprising a second binding region different from the first binding region, for binding to a second binding site of said cell-surface molecule different from the first binding site of said cell-surface molecule, and the conjugate comprising an effector molecule covalently bound to said second binding molecule. The invention also relates to a pharmaceutical composition comprising said two conjugates. In addition, the invention relates to the pharmaceutical combination or the pharmaceutical composition of the invention for use as a medicament. Furthermore, the invention relates to the pharmaceutical combination or the pharmaceutical composition of the invention, for use in the treatment or prevention of a cancer, an autoimmune disease, a disease relating to (over)expression of a protein, a disease relating to an aberrant cell such as a tumor cell or a diseased liver cell, a disease relating to a mutant gene, a disease relating to a gene defect, a disease relating to a mutant protein, a disease relating to absence of a (functional) protein, a disease relating to a (functional) protein deficiency.
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10.发明申请公开(公告)号：US20250051770A1
公开(公告)日：2025-02-13
申请号：US18723163
申请日：2022-12-20
Applicant: SAPREME TECHNOLOGIES B.V.
Inventor： Miriam Verena BUJNY , Ruben POSTEL , Guy HERMANS
IPC: C12N15/113 , A61K31/704 , A61K36/185 , A61K47/54 , A61K47/61 , A61K47/64 , A61K47/68 , A61P21/00
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 right 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, optionally, muscle cell-targeting ligands conjugated therewith. As for the first time demonstrated herein, these saponin types not only surprisingly retain their endosomal-escape-enhancing properties in fully differentiated muscle cells but also can in an unconjugated state successfully be delivered thereto together with the therapeutic nucleic acids.
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