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21. 发明公开

US20230248844A1 COMBINATION COMPRISING AN ADC OR AN AOC COMPRISING A VHH, AND A SAPONIN OR A LIGAND-SAPONIN CONJUGATE 审中-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
申请人： SAPREME TECHNOLOGIES B.V. , CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN
发明人： Ruben POSTEL , Guy HERMANS , Hendrik FUCHS
IPC分类号： A61K47/68 , A61K31/704 , A61K47/54 , A61P35/00
CPC分类号： A61K47/6849 , A61K31/704 , A61K47/549 , A61K47/6803 , A61P35/00
摘要： 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.

22. 发明申请

US20220313834A1 IMPROVED ANTIBODY-OLIGONUCLEOTIDE CONJUGATE 有权
公开(公告)号：US20220313834A1
公开(公告)日：2022-10-06
申请号：US17312019
申请日：2019-12-09
申请人： Sapreme Technologies B.V. , Charité - Universitätsmedizin Berlin
发明人： Ruben Postel , Hendrik Fuchs
IPC分类号： A61K47/68
摘要： The invention relates to a ligand-effector moiety provided with at least one saponin and antibody-effector moiety provided with at least one saponin. An aspect of the invention is a composition comprising the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin of the invention. The invention also relates to an antibody-drug conjugate comprising covalently linked saponin and to an antibody-oligonucleotide conjugate comprising covalently linked saponin. An aspect of the invention relates to a pharmaceutical composition comprising the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin of the invention, and optionally further comprising a pharmaceutically acceptable excipient. The invention also relates to the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin, for use as a medicament. The invention also relates to the ligand-effector moiety provided with at least one saponin or the antibody-effector moiety provided with at least one saponin of the invention for use in the treatment or prophylaxis of a cancer.

23. 发明申请

US20220249674A1 BIOACTIVE SAPONIN LINKED TO A FUNCTIONAL MOIETY 有权
公开(公告)号：US20220249674A1
公开(公告)日：2022-08-11
申请号：US17629598
申请日：2020-07-27
申请人： Sapreme Technologies B.V. , Charité - Universitätsmedizin Berlin
发明人： Hendrik Fuchs , Ruben Postel
IPC分类号： A61K47/54 , A61K47/55 , A61K47/60 , A61K47/68 , A61K47/64
摘要： The invention relates to an endosomal and/or lysosomal escape enhancing conjugate comprising a saponin optionally linked to a targeting molecule such as an antibody and optionally linked to an effector molecule such as a toxin or an oligonucleotide. The invention also relates to a therapeutic combination of such an endosomal and/or lysosomal escape enhancing conjugate of the invention and a functionalized binding molecule comprising an effector molecule, wherein the endosomal and/or lysosomal escape enhancing conjugate comprises an enhancer of said effector molecule, i.e. a saponin. In particular the invention relates to such a therapeutic combination for use as a medicament, in particular for use in the treatment of a tumour. The invention further relates to a method of treating cancer or an autoimmune disease by administering an effective dose of the therapeutic combination to a patient in need thereof or by administering an effective dose of the endosomal and/or lysosomal escape enhancing conjugate comprising a saponin complexed with a targeting molecule such as an immunoglobulin specific for a tumor-cell surface molecule and complexed with an effector molecule, to a patient in need thereof. The invention also relates to a functionalized saponin with endosomal/lysosomal escape enhancing activity.

24. 发明申请

US20220218837A1 DRUG CONJUGATE 有权
公开(公告)号：US20220218837A1
公开(公告)日：2022-07-14
申请号：US17415759
申请日：2019-12-09
申请人： Sapreme Technologies B.V. , Charité - Universitätsmedizin Berlin
发明人： Ruben Postel , Hendrik Fuchs
IPC分类号： A61K47/68 , A61K47/64 , A61K47/60 , A61K47/54 , A61P35/00
摘要： The invention relates to antibody-drug conjugates (ADC) that are potentiated by co-administration of the ADC with a moiety comprising covalently linked saponin. The invention also relates to antibody-oligonucleotide conjugates (AOC) that are potentiated by co-administration of the AOC with a moiety comprising covalently linked saponin. The invention also relates to ADCs and AOCs which are conjugated with a saponin via a covalent linker. The invention further relates to an effector moiety such as a toxin or an antisense oligonucleotide such as for example a BNA, conjugated with a saponin via a covalent linkage. The invention also relates to a BNA covalently conjugated with a targeting moiety such as an antibody. The invention also relates to therapeutic combinations comprising a first pharmaceutical composition comprising a conjugate of a cell-targeting moiety such as an antibody and an antisense oligonucleotide such as a BNA covalently bound thereto, and comprising a second pharmaceutical composition comprising either a free saponin, or a conjugate of a cell-targeting moiety such as an antibody with a saponin covalently linked thereto. Furthermore, the invention relates to any of these conjugates or therapeutic compositions or therapeutic combinations, for use as a medicament. The invention also relates to any of these conjugates or therapeutic compositions or therapeutic combinations, for use in a method for the treatment or the prophylaxis of a cancer. Finally, the invention relates to methods for producing any of these conjugates of the invention.

25. 发明申请

US20220111066A1 ANTIBODY-DRUG CONJUGATE WITH IMPROVED THERAPEUTIC WINDOW 有权
公开(公告)号：US20220111066A1
公开(公告)日：2022-04-14
申请号：US17312403
申请日：2019-12-09
申请人： Sapreme Technologies B.V. , Charité - Universitätsmedizin Berlin
发明人： Ruben Postel , Hendrik Fuchs
IPC分类号： A61K47/68 , A61P35/00 , A61K47/54 , A61K47/55 , A61K47/60 , A61K47/59
摘要： The invention relates to a therapeutic combination, comprising a first proteinaceous molecule comprising a first binding site for binding to a first epitope of a first cell-surface molecule, the first proteinaceous molecule provided with at least one saponin covalently bound to an amino-acid residue of said first proteinaceous molecule, and comprising a second pharmaceutical composition comprising a second proteinaceous molecule different from the first proteinaceous molecule, the second proteinaceous molecule comprising a second binding site for binding to a second epitope of a second cell-surface molecule different from the first cell-surface molecule, and comprising an effector moiety, wherein the second epitope is different from the first epitope. An aspect of the invention is a composition comprising the first proteinaceous molecule and the second proteinaceous molecule of the invention. The invention also relates to a composition or therapeutic combination comprising an antibody-drug conjugate or antibody-oligonucleotide conjugate and the first proteinaceous molecule of the invention. An aspect of the invention relates to a pharmaceutical composition comprising the composition or the antibody-drug conjugate of the invention, and optionally further comprising a pharmaceutically acceptable excipient. The invention also relates to the therapeutic combination or the composition or the antibody-drug conjugate or the pharmaceutical composition of the invention, for use as a medicament. The invention also relates to the therapeutic combination of the invention for use in the treatment or prophylaxis of a cancer.

26. 发明申请

US20220072149A1 BIOLOGICALLY ACTIVE CLUSTER OF MOLECULES 有权
公开(公告)号：US20220072149A1
公开(公告)日：2022-03-10
申请号：US17312476
申请日：2019-12-09
申请人： Sapreme Technologies B.V. , Charité - Universitätsmedizin Berlin
发明人： Ruben Postel , Hendrik Fuchs
IPC分类号： A61K47/68 , A61K47/54 , A61K47/55 , A61K47/59 , A61K47/60 , A61K47/64 , A61K47/69
摘要： The invention relates to a molecular scaffold suitable for covalently binding at least one biologically active molecule to a carrier molecule, the scaffold comprising a polymeric structure and the biologically active molecules covalently bound to said polymeric structure, and wherein the scaffold further comprises a chemical group for covalently coupling of the scaffold to the carrier molecule. The biologically active molecule has a molecular weight of 3.000 Dalton or less, such as 1.700 Dalton-1.950 Dalton. The biologically active molecule is an amphiphilic molecule in some embodiments. The biologically active molecule is a single specific molecule or is a mixture of different types of molecules, when more than one biologically active molecules are covalently bound to the polymeric (or oligomeric) structure. In particular, the invention relates to monoclonal antibody-based antibody-drug conjugates with improved therapeutic window of the drug due to covalent linkage of (a cluster of) potentiator molecules, e.g. a payload such as a protein toxin or oligonucleotide to the ADC, or alternatively, due to co-administration of an ADC and a cell-targeting conjugate comprising (a cluster of) potentiator molecules to a patient in need thereof. The invention also relates to a method for producing a scaffold suitable for covalently binding a biologically active molecule to a carrier molecule, providing a cluster of potentiator molecules. Furthermore, the invention relates to a method for producing a scaffold covalently bound to a carrier molecule, the scaffold comprising a covalently bound biologically active molecule, the carrier molecule comprising an antibody and a payload.

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