MODIFIED ANTIBODY IN WHICH MOTIF COMPRISING CYSTEINE RESIDUE IS BOUND, MODIFIED ANTIBODY-DRUG CONJUGATE COMPRISING THE MODIFIED ANTIBODY, AND PRODUCTION METHOD FOR SAME

摘要

The present invention relates to an antibody in which a motif composed of an amino acid or peptide sequence including one or more cysteine residues is bound to the terminus of a parent antibody, particularly the terminus of the heavy chain of the parent antibody. Also, the present invention relates to a modified antibody-drug conjugate (mADC) comprising a drug bound to the antibody, and a method for producing the antibody or the modified antibody-drug conjugate. The modified antibody-drug conjugate according to the invention can accurately deliver the drug to a target cell due its high specificity to antigen, and thus can increase the therapeutic effect of the drug. Also, it can increase the usability of drugs, particularly anticancer drugs, the use of which is restricted due to their toxicity, despite their high efficacy. Moreover, the invention relates to a composition for treatment of diseases, particularly cancers, which comprise the modified antibody-drug conjugate.

主权项

1. An antibody-drug conjugate comprising a modified antibody comprising a cysteine-containing motif at the terminus of a parent antibody, with a formula 1:
Xa-[(MCys)n-Xbn]n  Formula (1)wherein (MCys)n is a metal ion binding motif that contains a cysteine residue; Xa and Xbn each independently is a peptide comprising 0 to 20 amino acid residues other than cysteine; and n is an integer ranging from 1 to 20,
the metal ion binding motif that contains a cysteine residue is any one or more selected from the group consisting of:
(A) a zinc finger motif that contains C2H2 group (Cys2His2 class: Cys-X2-4-Cys-X12-His-X3-5-His), C4 group (C4 class: Cys-X2-Cys-Xm-Cys-X2-Cys-Xm-Cys-X2-Cys-Xm-Cys-X2-Cys) or C6 group (C6 class: Cys-X2-Cys-X6-Cys-X5-12-Cys-X2-Cys-X6-8-Cys) of zinc finger protein, wherein each X is independently an amino acid residue other than Cys; m is an integer ranging from 1 to 10; and Xm or Xm-q of X2-4, X3-5, X5-12 or X6-8 in the C2H2 group, C4 group, or C6 group, is m or m to q amino acid residues other than Cys;(B) a metal ion binding motif artificially designed based on a zinc finger motif or a metal ion binding protein motif;(C) a Cys-Xm-Cys motif, a Met-X-Cys-X-X-Cys motif, or a C-Q-C-Q-C-A-C motif of transcription regulatory proteins, metal chaperone proteins, metal ion transporters, or superoxide dismutase; wherein each X is independently an amino acid residue other than Cys; m is an integer ranging from 1 to 10;(D) a Ser-Pro-Cys motif of membrane protein ATPase; and(E) a metal ion binding peptide motif having a circular structure; and the drug is conjugated to the thiol group of the cysteine residue in the metal ion binding motif.