NOVEL INSULIN DERIVATIVES HAVING AN EXTREMELY DELAYED TIME-ACTION PROFILE

摘要

THE INVENTION RELATES TO NOVEL INSULIN ANALOGS HAVING A BASAL TIME-ACTION PROFILE, WHICH ARE CHARACTERIZED BY THE FOLLOWING FEATURES: A) THE B CHAIN END CONSISTS OF AN AMIDATED BASIC AMINO ACID RESIDUE SUCH AS LYSINE OR ARGININE AMIDE; B) THE N-TERMINAL AMINO ACID RESIDUE OF THE INSULIN A CHAIN IS A LYSINE OR ARGININE RADICAL; C) THE AMINO ACID POSITION A8 IS OCCUPIED BY A HISTIDINE RADICAL; D) THE AMINO ACID POSITION A21 IS OCCUPIED BY A GLYCINE RADICAL; AND E) ONE OR MORE SUBSTITUTIONS AND/OR ADDITIONS OF NEGATIVELY CHARGED AMINO ACID RESIDUES ARE CARRIED OUT IN THE POSITIONS A5, A15, A18, B-I, BO, BI, B2, B3 AND B4.