Abstract: The present invention relates to an antibody-drug conjugate (ADC) comprising as a first payload a cytotoxic molecule and as a second payload a tumor-targeting small molecule for use in the treatment of cancer, wherein the cancer is characterized by the presence of a cancer cell comprising a first antigen that is specifically bound by an antibody portion of the ADC and a second antigen that specifically interacts with the tumor-targeting small molecule.

Abstract: Described is an antibody-drug conjugate (ADC) having the formula A-L, wherein A is an antibody or an antibody fragment and wherein L is a linker, said linker comprising: as a first payload a topoisomerase I inhibitor which is cell-permeable, preferably a camptothecin cytotoxic molecule which is cell-permeable; and as a second payload a topoisomerase I inhibitor which is not cell-permeable, preferably a camptothecin cytotoxic molecule which is not cell-permeable. Moreover, described is a pharmaceutical composition comprising said ADC and at least one pharmaceutically acceptable ingredient. Further, described is an ADC for use in a method of treating a patient suffering from, being at risk of developing, and/or being diagnosed for a neoplastic disease.

Abstract: Described is an antibody-drug conjugate (ADC) having the formula A-L, wherein A is an antibody or an antibody fragment and wherein L is a linker, said linker comprising: as a first payload a topoisomerase I inhibitor which is cell-permeable, e.g., a camptothecin cytotoxic molecule which is cell-permeable; as a second payload a topoisomerase I inhibitor which is not cell-permeable, e.g., a camptothecin cytotoxic molecule which is not cell-permeable; and as a as a third payload a toxin or a cytotoxin, e.g., an auristatin such as MMAE (Monomethyl auristatin E). Moreover, described is a pharmaceutical composition comprising said ADC and at least one pharmaceutically acceptable ingredient. Further, described method of treating a patient suffering from, being at risk of developing, and/or being diagnosed for a neoplastic disease.

Abstract: The present invention relates to a method for generating an antibody-payload conjugate by means of a microbial transglutaminase (MTG). The method comprises a step of conjugating a linker comprising the structure (shown in N->C direction) (Sp1)-RK-(Sp2)-B-(Sp3) or (Sp1)-B-(Sp2)-RK-(Sp3) to a Gln residue comprised in an antibody, wherein (Sp1) is a chemical spacer or is absent; (Sp2) is a chemical spacer or is absent; (Sp3) is a chemical spacer or is absent; R is arginine or an arginine derivative or an arginine mimetic; K is lysine or a lysine derivative or a lysine mimetic; B is a linking moiety or a payload; and wherein the linker is conjugated to the Gln residue comprised in the antibody via a primary amine comprised in the side chain of the lysine residue, the lysine derivative or the lysine mimetic. Further, the invention relates to antibody-linker conjugates, antibody-drug conjugates and linker constructs comprising an RK motif.

Abstract: The present invention relates to a method for generating an antibody-payload conjugate by means of a microbial transglutaminase (MTG). The method comprises a step of conjugating a linker comprising the structure (shown in N->C direction) (Sp1)-RK-(Sp2)-B-(Sp3) or (Sp1)-B-(Sp2)-RK-(Sp3) to a Gln residue comprised in an antibody, wherein (Sp1) is a chemical spacer or is absent; (Sp2) is a chemical spacer or is absent; (Sp3) is a chemical spacer or is absent; R is arginine or an arginine derivative or an arginine mimetic; K is lysine or a lysine derivative or a lysine mimetic; B is a linking moiety or a payload; and wherein the linker is conjugated to the Gln residue comprised in the antibody via a primary amine comprised in the side chain of the lysine residue, the lysine derivative or the lysine mimetic. Further, the invention relates to antibody-linker conjugates, antibody-drug conjugates and linker constructs comprising an RK motif.

Abstract: The present invention relates to a method for generating an antibody-payload conjugate by means of a microbial transglutaminase (MTG). The method comprises a step of conjugating a linker comprising the structure (shown in N?C direction) (Sp1)-RK-(Sp2)-B-(Sp3) or (Sp1)-B-(Sp2)-RK-(Sp3) to a Gln residue comprised in an antibody, wherein (Sp1) is a chemical spacer or is absent; (Sp2) is a chemical spacer or is absent; (Sp3) is a chemical spacer or is absent; R is arginine or an arginine derivative or an arginine mimetic; K is lysine or a lysine derivative or a lysine mimetic; B is a linking moiety or a payload; and wherein the linker is conjugated to the Gin residue comprised in the antibody via a primary amine comprised in the side chain of the lysine residue, the lysine derivative or the lysine mimetic. Further, the invention relates to antibody-linker conjugates, antibody-drug conjugates and linker constructs comprising an RK motif.

Abstract: The present invention relates to a method for generating an antibody-payload conjugate by means of a microbial transglutaminase (MTG). The method comprises a step of conjugating a linker comprising the structure (shown in N->C direction) (Sp1)-RK-(Sp2)-B-(Sp3) or (Sp1)-B-(Sp2)-RK-(Sp3) to a Gln residue comprised in an antibody, wherein (Sp1) is a chemical spacer or is absent; (Sp2) is a chemical spacer or is absent; (Sp3) is a chemical spacer or is absent; R is arginine or an arginine derivative or an arginine mimetic; K is lysine or a lysine derivative or a lysine mimetic; B is a linking moiety or a payload; and wherein the linker is conjugated to the Gin residue comprised in the antibody via a primary amine comprised in the side chain of the lysine residue, the lysine derivative or the lysine mimetic. Further, the invention relates to antibody-linker conjugates, antibody-drug conjugates and linker constructs comprising an RK motif.