Antibody-drug conjugates through specific linker oligopeptides
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.
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