Means and methods for producing antibody-linker conjugates

A linker construct comprising the structure:

• (Sp1)-RK-(Sp2)-B-(Sp3)
• or
• (Sp1)-B-(Sp2)-RK-(Sp3);
• 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.

A method of treating a neoplastic disease, a neurological disease, an autoimmune disease, an inflammatory disease or an infectious disease, said method comprising administering to a patient in need thereof an antibody-drug conjugate comprising:

• a) an IgG antibody;
• and
• b) a linker comprising a drug moiety B, wherein the drug moiety B is covalently linked to an amino acid sequence selected from the group consisting of:
• RKAA (SEQ ID NO:1), RKA (SEQ ID NO:2), ARK (SEQ ID NO:3), RKR (SEQ ID NO:4) or RK-Val-Cit (SEQ ID NO:54);
• wherein the linker is conjugated to the IgG antibody via an isopeptide bond formed between the γ-carboxamide group of glutamine residue Q295 (EU numbering) of the CH2 domain of the antibody and the primary amine comprised in the side chain of the lysine residue comprised in the linker.

A method of treating a neoplastic disease, a neurological disease, an autoimmune disease, an inflammatory disease or an infectious disease, said method comprising administering to a patient in need thereof an antibody-linker conjugate comprising:

• a) an antibody;
• and
• b) a linker comprising the structure:
• (Sp1)-RK-(Sp2)-B-(Sp3)
• or
• (Sp1)-B-(Sp2)-RK-(Sp3);
• 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;
• wherein the linker is conjugated to the antibody via an isopeptide bond formed between a γ-carboxamide group of a glutamine residue comprised in the antibody and a primary amine comprised in the side chain of the lysine residue, the lysine derivative or the lysine mimetic comprised in the RK motif comprised in the linker.