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 having a primary amine residue, said linker having the peptide structure (shown in N?C direction) (Aax)m-(Aax)(NH2)-(Aax)n-B-(Aax)o, or (Aax)m-B-(Aax)n-(Aax)(NH2)-(Aax)o, to a Gln residue comprised in the heavy or light chain of an antibody.

Abstract: The present invention relates to a peptide linker comprising (a) an amino acid residue comprising a primary amine; and (b) two or more payloads; wherein each of the two or more payloads can be independently attached to: (i) an N-terminal end of the peptide linker, (ii) a C-terminal end of the peptide linker, or (iii) a side chain of an amino acid residue comprised in the peptide linker. Further, the present invention relates to antibody-payload conjugates comprising the peptide linker of the invention, methods for generating said antibody-payload conjugates and uses thereof.

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 transglutaminase. The method comprises a step of conjugating a linker comprising the structure (shown in N?C direction) (Sp1)-K-(Sp2)-B-(Sp3) or (Sp1)-B-(Sp2)-K-(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; K is lysine or a lysine derivative or a lysine mimetic; B is a linking moiety or a payload; 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; and wherein the antibody is contacted with less than 80 molar equivalents of the linker. Further, the invention relates to antibody-linker conjugates, antibody-drug conjugates and linker constructs comprising a lysine residue.

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 having a primary amine residue, said linker having the peptide structure (shown in N->C direction) (Aax)m-(Aax)(NH2)-(Aax)n-B-(Aax)o, or (Aax)m-B-(Aax)n-(Aax)(NH2)-(Aax)o, to a Gln residue comprised in the heavy or light chain of an antibody. Aax(NH2) is an amino acid, amino acid derivative or amino acid mimetic comprising a side chain having a primary amine group.

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 having a primary amine residue, said linker having the peptide structure (shown in N->C direction) (Aax)m-(Aax)(NH2)-(Aax)n-B-(Aax)o, or (Aax)m-B-(Aax)n-(Aax)(NH2)-(Aax)o, to a Gln residue comprised in the heavy or light chain of an antibody.

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 or having the structure (shown in N—>C direction) Aax-(Sp1)-B1-(Sp2) via a primary amine in the N-terminal residue Aax to a glutamine (Gln) residue comprised in the heavy or light chain of an antibody, wherein Aax is an amino acid having the structure NH2—Y—COOH, wherein Y comprises a substituted or unsubstituted alkyl or heteroalkyl chain; (Sp1) is a chemical spacer or is absent; (Sp2) is a chemical spacer or is absent; and B1 is a linking moiety or a payload. Further the present invention relates to antibody-linker conjugates that have been generated with the method of the invention and uses thereof.

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 or having the peptide structure (shown in N->C direction) Gly-(Aax)m-B-(Aax)n via the N-terminal primary amine of the N-terminal glycine (Gly) residue to a glutamine (Gln) residue comprised in the heavy or light chain of an antibody.

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 having a primary amine residue, said linker having the peptide structure (shown in N->C direction) (Aax)m-(Aax)(NH2)-(Aax)n-B-(Aax)o, or (Aax)m-B-(Aax)n-(Aax)(NH2)-(Aax)o, to a Gln residue comprised in the heavy or light chain of an antibody. Aax(NH2) is an amino acid, amino acid derivative or amino acid mimetic comprising a side chain having a primary amine group.