Multi-Substituted Insulins
AssigneeNovo Nordisk A/S
InventorsThomas Hoeg-Jensen, Peter Madsen, Jane Spetzler, Tina Moeller Tagmose
Life of this patent
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Abstract
The present invention regards an insulin derivative comprising at least 2 albumin binding moieties, wherein said albumin binding moieties comprise fatty diacid substitutions and a method for preparing such an insulin derivative by acylation and/or reductive alkylation. The present invention also concern a pharmaceutical comprising such an insulin derivative.
Claims22
A soluble insulin derivative or a pharmaceutically acceptable salt thereof of the general formula
- wherein
- a. Ins represents an insulin comprising a B29 lysine or B29 arginine residue and/or a A22 lysine residue
- b. X, X1 and X2 is a fatty diacid substitution and X2 is optional, wherein said fatty diacid substitution comprises 14-20 carbon atoms
- c. Zn, Z1 and Z2 is a linker between Ins and X, X1 and X2, respectively wherein Z2 is absent when X2 is absent and
- d. n, m and p is zero or 1.
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A soluble insulin derivative or pharmaceutically acceptable salt hereof selected from the group consisting of A22Nε-hexadecandioyl-γ-L-glutamyl B29Nε-hexadecandioyl-γ-L-glutamyl A22K desB30 human insulin, A22Nε-octadecandioyl-γ-L-glutamyl-OEG-OEG B29Nε-octadecandioyl-γ-L-glutamyl-OEG-OEG A22K desB30 human insulin, A22Nε-tetradecandioyl-γ-L-glutamyl B29Nε-tetradecandioyl-γ-L-glutamyl A22K desB30 human insulin, A22Nε-octadecandioyl-γ-D-glutamyl B29Nε-octadecandioyl-γ-D-glutamyl A22K desB30 human insulin, A22Nε-hexadecandioyl-γ-L-glutamyl B29Nε-hexadecandioyl-γ-L-glutamyl A14E A22K B25H desB30 human insulin, A22Nε-octadecandioyl-γ-L-glutamyl-OEG-OEG B29Nε-octadecandioyl-γ-L-glutamyl-OEG-OEG A14E A22K B25H desB30 human insulin, A1Nα-hexadecandioyl-γ-L-glutamyl B29Nε-hexadecandioyl-γ-L-glutamyl A14E B25H desB30 human insulin, A1Nα-hexadecandioyl-γ-L-glutamyl B29Nε-hexadecandioyl-γ-L-glutamyl desB30 human insulin, A1Nα-octadecandioyl-γ-L-glutamyl-OEG-OEG B29Nε-octadecandioyl-γ-L-glutamyl-OEG-OEG A14E B25H desB30 human insulin, A1Nα-octadecandioyl-γ-L-glutamyl-OEG-OEG-aminomethyl-benzyl B1Nα-octadecandioyl-γ-L-glutamyl-OEG-OEG-4-aminomethyl-benzyl A14E B25H desB27 desB30 human insulin, A1Nα-octadecandioyl-γ-L-glutamyl-OEG-OEG-aminomethyl-benzyl B1Nα-octadecandioyl-γ-L-glutamyl-OEG-OEG-4-aminomethyl-benzyl A14E B25H desB30 human insulin, A1Nα-hexadecandioyl-γ-L-glutamyl-OEG-OEG-aminomethyl-benzyl B1Nα-hexadecandioyl-γ-L-glutamyl-OEG-OEG-4-aminomethyl-benzyl A14E B25H desB27 desB30 human insulin, A1Nα-tetradecandioyl-γ-L-glutamyl-OEG-OEG-aminomethyl-benzyl B1Nα-tetradecandioyl-γ-L-glutamyl-OEG-OEG-4-aminomethyl-benzyl A14E B25H desB27 desB30 human insulin, A1Nα-hexadecandioyl-γ-L-glutamyl-OEG-OEG4-aminomethyl-benzyl B1Nα-hexadecandioyl-γ-L-glutamyl-OEG-OEG-4-aminomethyl-benzyl A14E B25H desB30 human insulin, B1Nα-octadecandioyl-γ-L-glutamyl-OEG-OEG-aminomethyl-benzyl B29Nε-octadecandioyl-γ-L-glutamyl-OEG-OEG A14E B25H desB30 human insulin, A1Nα-octadecandioyl-γ-L-glutamyl-OEG-OEG-4-aminomethyl-benzyl B1Nα-octadecandioyl-γ-L-glutamyl-OEG-OEG-4-aminomethyl-benzyl B29Nεoctadecandioyl-γ-L-glutamyl-OEG-OEG A14E B25H desB30 human insulin, A1Nα-octadecandioyl-N-carboxymethyl-beta-alanyl B29Nε-octadecandioyl-N-carboxymethyl-beta-alanyl A14E B25H desB30 human insulin, A1Nαoctadecandioyl-N-2-carboxyethyl-glycyl B29Nε-octadecandioyl-N-2-carboxyethyl-glycyl A14E B25H desB30 human insulin, A1Nα-octadecandioyl-N-carboxymethyl-beta-alanyl A22Nε-N-octadecandioyl-N-carboxymethyl-beta-alanyl A22K B29R desB30 human insulin, A22Nε-hexadecandioyl-γ-L-glutamyl-OEG-OEG B29Nε-hexadecandioyl-γ-L-glutamyl-OEG-OEG A14E B25H desB30 human insulin, A1Nα-hexadecandioyl-γ-L-glutamyl-OEG-OEG B29Nε-hexadecandioyl-γ-L-glutamyl-OEG-OEG A14E B25H desB30 human insulin, A1Nα-hexadecandioyl-γ-L-glutamyl-OEG-OEG B29Nε-hexadecandioyl-γ-L-glutamyl-OEG-OEG A14E B16H B25H desB30 human insulin, A1Nα-octadecandioyl-γ-L-glutamyl-OEG-OEG B1Nα-octadecandioyl-γ-L-glutamyl-OEG-OEG A14E B25H B29R desB30 human, A22Nε-eicosandioyl-γ-L-glutamyl-OEG-OEG B29Nε-eicosandioyl-γ-L-glutamyl-OEG-OEG A14E A22K B25H desB30 human insulin, B1Nα-octadecandioyl-γ-L-glutamyl-OEG-OEG-4-aminomethyl-benzyl B29Nε-octadecandioyl-γ-L-glutamyl-OEG-OEG A14E B16H B25H desB30 human insulin, B1Nα-(octadecandioyl-γ-L-glutamyl-OEG-OEG-4-aminomethyl-benzyl A14E B25H B29Nε-octadecandioyl-γ-L-glutamyl-OEG-OEG desB30 human insulin, B1Nα-octadecandioyl-γ-L-glutamyl-OEG-OEG-aminomethyl-benzyl B29Nε-octadecandioyl-γ-L-glutamyl-OEG-OEG A14E B25H desB27 desB30 human insulin, A22Nε-4-carboxyphenoxy-decanoyl-γ-L-glutamyl-OEG-OEG B29Nε-4-carboxyphenoxy-decanoyl-γ-L-glutamyl-OEG-OEG A14E A22K B25H desB30 human insulin.
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Dependencies are inferred from the claim text.