Insulin derivative
AssigneeGan & Lee Pharmaceuticals
InventorsZhongru Gan, Wei Chen, Yining Zhang, Fangkai Xue, Lingyu Cai, Jianghong Niu, Bin Mu
Life of this patent
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Abstract
Disclosed is an acylated insulin, a pharmaceutical formulation thereof, a pharmaceutical composition thereof with a long-acting GLP-1 compound, and a medical use of the acylated insulin, the pharmaceutical formulation and the pharmaceutical composition. Compared with insulin degludec or other insulin derivatives, the acylated insulin has an unexpected, significantly increased drug effect, a longer duration of action, a longer in vivo half-life, an excellent bioavailability, as well as better physical and chemical stabilities.
Claims43
An insulin derivative comprising an insulin parent and an acyl moiety, wherein the insulin parent is A14E, B16H, B25H, desB30 human insulin, and the acyl moiety is linked to an amino group of a lysine residue or an N-terminal amino acid residue of the insulin parent, wherein the acyl moiety is shown as formula (D):
- W1-(W2)m2-(W3)n2- (D),
- wherein,
- m2 is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, and n2 is 11, 12, 13, 14, 15, 16, 17, or 18;
- W3 is a neutral and alkylene glycol-containing amino acid residue;
- W2 is an acidic amino acid residue;
- W1 is a fatty diacid containing 20-24 carbon atoms, wherein formally, a hydroxyl group has been removed from one of the carboxyl groups in the fatty diacid;
- W1, W2 and W3 are linked by amide bonds;
- and
- the order of W2 and W3 presented in the formula (D) is optionally interchanged independently.
An insulin derivative comprising an A14E, B16H, B25H, desB30 human insulin having an A-chain of SEQ ID NO:
- 3 and a B-chain of SEQ ID NO:
- 4, and an acyl moiety, wherein the acyl moiety has the formula (A):
- III-(II)m-(I)n- (A)
- wherein,
- I is —HN—(CH2)2—O—(CH2)2—O—CH2—CO—;
- II is the amino acid residue of γGlu;
- III is HOOC—(CH2)18—CO—, HOOC—(CH2)19—CO—, or HOOC—(CH2)20—CO—;
- m is an integer of 1, and
- n is 12,
- wherein,
- I, II, III are linked together by amide bonds in the acyl moiety, and
- the acyl moiety is linked to the ε amino group of the lysine residue at position B29 of the B-chain via the C-terminal of I.
An insulin derivative, having the following structure:
Dependencies are inferred from the claim text.