Abstract: The present invention relates to a method for producing an active form of a long-acting insulin analogue derivative, in which the amino acid at position 22 of the insulin B-chain is substituted from arginine (Arg) to lysine (Lys), so that the insulin analogue can be converted to an active form without cleavage of the B-chain even when it is reacted with clostripain. In a conventional method of converting pro-insulin to an active form by use of trypsin, an albumin binding domain is cleaved, making it difficult to convert the long-acting insulin analogue derivative to an active form. The production method according to the present invention overcomes this difficulty, and thus it can be effectively used for the production of a long-acting therapeutic agent for treatment of diabetes.

Abstract: The present invention relates to a method for producing an active form of a long-acting insulin analogue derivative, in which the amino acid at position 22 of the insulin B-chain is substituted from arginine (Arg) to lysine (Lys), so that the insulin analogue can be converted to an active form without cleavage of the B-chain even when it is reacted with clostripain. In a conventional method of converting pro-insulin to an active form by use of trypsin, an albumin binding domain is cleaved, making it difficult to convert the long-acting insulin analogue derivative to an active form. The production method according to the present invention overcomes this difficulty, and thus it can be effectively used for the production of a long-acting therapeutic agent for treatment of diabetes.