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.

The present invention provides Ligand-Drug Conjugates comprising a PEG Unit in a parallel orientation to the Drug Unit. The invention provides inter alia. Ligand-Drug Conjugates (LDCs), methods of preparing and using them, and intermediates thereof. The Ligand-Drug Conjugates are stable in circulation, yet capable of inflicting cell death on targeted cells or inhibiting proliferation of targeted cells once its drug cargo is released in the vicinity or within targeted cells. In principle embodiments, an LDC of the present invention is represented by the structure of Formula I.

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.

The present disclosure provides nucleic acid carriers comprising targeting agents, pharmaceutical compositions comprising the same, and methods of making and using the same.

Provided in the present invention is a linker and a preparation method thereof, wherein one end of the linker may covalently link a small molecule compound and the like and the other end may specifically and covalently link a targeting substance site under the action of Sortase enzyme. The linker of the present invention can be used to prepare a targeting drug conjugate.

The present disclosure provides nucleic acid carriers comprising one or more layers comprising multiple monomers, wherein each monomer comprises: a first and a second oligonucleotide; wherein a central portion of each of the first and second oligonucleotides is complementary to each other, forming a double-stranded region, wherein the two terminal portions of the first oligonucleotide are not complementary to the two terminal portions of the second oligonucleotide, forming four terminal arms; and at least one targeting agent conjugated to at least one peripheral terminal arm, wherein when the at least one targeting agent is an miRNA. The present disclosure also provides pharmaceutical composition comprising any of the nucleic acid carriers described herein, and a pharmaceutically acceptable vehicle. The present disclosure also provides methods of inducing an immune response in an animal comprising administering to the animal any of the nucleic acid carriers described herein.

A macromolecule includes i) a dendrimer comprising a core and at least one generation of building units, the outermost generation of building units having surface amino groups wherein at least two different terminal groups are covalently attached to the surface amino groups of the dendrimer, ii) a first terminal group which is a residue of a pharmaceutically active agent comprising a hydroxyl group, and iii) a second terminal group which is a pharmacokinetic modifying agent. The pharmaceutically active agent is cabazitaxel. The first terminal group is covalently attached to the surface amino group of the dendrimer through a diacid linker, the diacid linker comprising an alkyl chain interrupted by one or more oxygen, sulfur or nitrogen atoms, or a pharmaceutically acceptable salt thereof.

The disclosure relates to a bioactive molecule conjugate, preparation methods and use thereof, particularly relates to a novel bioactive molecule conjugate obtained by improving coupling of the drug and the targeting moiety in an ADC or SMDC, as well as its preparation method and use in the manufacture of a medicament for the treatment of a disease associated with an abnormal cell activity.

The disclosure relates to a bioactive molecule conjugate, preparation methods and use thereof, particularly relates to a novel bioactive molecule conjugate obtained by improving coupling of the drug and the targeting moiety in an ADC or SMDC, as well as its preparation method and use in the manufacture of a medicament for the treatment of a disease associated with an abnormal cell activity.

An immune conjugate according to the present invention provides a pharmaceutical composition, which can be used in the target-oriented drug treatment by conjugating a dendron allowing a plurality of drugs to be bound to a surface thereof and a target-directed antibody, and especially, can deliver high concentrations of drugs in a tumor-specific manner to exhibit a strong anticancer effect by conjugating a hydrophilic dendron, to which a plurality of anticancer drugs are bound, to an antibody.