US 12,453,782 B2
Antibody-oligonucleotide conjugate
Ruben Postel, Utrecht (NL); and Hendrik Fuchs, Berlin (DE)
Assigned to Sapreme Technologies B.V., Bilthoven (NL)
Appl. No. 17/312,019
Filed by Sapreme Technologies B.V., Bilthoven (NL)
PCT Filed Dec. 9, 2019, PCT No. PCT/EP2019/084242
§ 371(c)(1), (2) Date Jun. 9, 2021,
PCT Pub. No. WO2020/126620, PCT Pub. Date Jun. 25, 2020.
Claims priority of application No. 2022283 (NL), filed on Dec. 21, 2018; application No. 2023468 (NL), filed on Jul. 10, 2019; and application No. 2023568 (NL), filed on Jul. 25, 2019.
Prior Publication US 2022/0313834 A1, Oct. 6, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 47/68 (2017.01); A61K 47/54 (2017.01); A61K 47/55 (2017.01); A61K 47/59 (2017.01); A61K 47/60 (2017.01); A61K 47/64 (2017.01); A61P 35/00 (2006.01); C12N 15/113 (2010.01)
CPC A61K 47/6885 (2017.08) [A61K 47/549 (2017.08); A61K 47/55 (2017.08); A61K 47/554 (2017.08); A61K 47/593 (2017.08); A61K 47/595 (2017.08); A61K 47/60 (2017.08); A61K 47/6415 (2017.08); A61K 47/642 (2017.08); A61K 47/643 (2017.08); A61K 47/6807 (2017.08); A61K 47/6817 (2017.08); A61K 47/6825 (2017.08); A61K 47/6845 (2017.08); A61K 47/6849 (2017.08); A61K 47/6851 (2017.08); A61K 47/6855 (2017.08); A61K 47/6857 (2017.08); A61K 47/6889 (2017.08); A61P 35/00 (2018.01); C12N 15/113 (2013.01); C12N 2310/11 (2013.01); C12N 2320/30 (2013.01)] 17 Claims
 
1. A conjugate comprising a cell-surface molecule targeting molecule and at least one effector moiety and further comprising at least one covalently bound saponin,
wherein the at least one saponin is a triterpenoid saponin and/or a bisdesmosidic triterpene saponin belonging to the type of a 12,13-dehydrooleanane with an aldehyde function in position C-23 and comprising a glucuronic acid function in a carbohydrate substituent at the C-3beta-OH group of the saponin, and
wherein the cell-surface molecule targeting molecule comprises or consists of an immunoglobulin, at least one binding domain of an immunoglobulin and/or at least one binding fragment of an immunoglobulin, an antibody, an IgG, a molecule comprising or consisting of a Vhh domain or Vh domain, a Fab, an scFv, an Fv, a dAb, an F(ab)2, Fcab fragment, which can bind to the cell-surface molecule, and
wherein the at least one effector moiety comprises or consists of any one or more of oligonucleotide, a nucleic acid and a xeno nucleic acid, or selected from any one or more of a vector, a gene, a cell suicide inducing transgene, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), anti-sense oligonucleotide (ASO, AON), short interfering RNA (siRNA), microRNA (miRNA), DNA aptamer, RNA aptamer, mRNA, mini-circle DNA, peptide nucleic acid (PNA), phosphoramidate morpholino oligomer (PMO), locked nucleic acid (LNA), bridged nucleic acid (BNA), 2′-deoxy-2′-fluoroarabino nucleic acid (FANA), 2′-O-methoxyethyl-RNA (MOE), 2′-O,4′-aminoethylene bridged nucleic acid, 3′-fluoro hexitol nucleic acid (FHNA), a plasmid, glycol nucleic acid (GNA) and threose nucleic acid (TNA).