Insulin Derivatives
AssigneeNovo Nordisk
InventorsJanos Kodra, Patrick Garibay, Thomas Hoeg-Jensen, Ib Jonassen, Peter Madsen, Tina Tagmose
Life of this patent
Estimating the term…
Abstract
The present invention relates to insulin derivatives having a side chain attached either to the -amino group of the N-terminal amino acid residue of the B chain or to the amino group of a Lys residue present in the B chain of the parent insulin via an amide bond which side chain comprises at least one aromatic group; at least one free carboxylic acid group or a group which is negatively charged at neutral pH, a fatty acid moiety with 4 to 22 carbon atoms in the carbon chain; and possible linkers which link the individual components in the side chain together via amide bonds.
Claims23
An insulin derivative, said insulin derivative comprising a side chain attached either to the α-amino group of the N-terminal amino acid residue of the B chain or to an ε-amino group of a Lys residue present in the A or the B chain of the parent insulin moiety via an amid bond, which side chain comprises at least one aromatic group;
- at least one free carboxylic acid group or a group which is negatively charged at neutral pH, a fatty acid moiety with from 4 to 22 carbon atoms in the carbon chain;
- and possible one or more linkers linking the individual components in the side chain together via amide bonds, provided that the fatty acid moiety is not a divalent hydrocarbon chain of the formula —(CH2)v4C6H4(CH2)W1— wherein v and w are integers or one of them is zero so that the sum of v4 and w1 is in the range of 6 to 30.
A pharmaceutical composition for the treatment of diabetes in a patient in need of such treatment, comprising a therapeutically effective amount of an insulin derivative, said insulin derivative comprising a side chain attached either to the α-amino group of the N-terminal amino acid residue of the B chain or to an ε-amino group of a Lys residue present in the A or the B chain of the parent insulin moiety via an amid bond, which side chain comprises at least one aromatic group;
- at least one free carboxylic acid group or a group which is negatively charged at neutral pH, a fatty acid moiety with from 4 to 22 carbon atoms in the carbon chain;
- and possible one or more linkers linking the individual components in the side chain together via amide bonds, provided that the fatty acid moiety is not a divalent hydrocarbon chain of the formula —(CH2)v4C6H4(CH2)W1— wherein v and w are integers or one of them is zero so that the sum of v4 and w1 is in the range of 6 to 30 together with a pharmaceutically acceptable carrier.
A pharmaceutical composition for the treatment of diabetes in a patient in need of such treatment, comprising a therapeutically effective amount of an insulin derivative, said insulin derivative comprising a side chain attached either to the α-amino group of the N-terminal amino acid residue of the B chain or to an ε-amino group of a Lys residue present in the A or the B chain of the parent insulin moiety via an amid bond, which side chain comprises at least one aromatic group;
- at least one free carboxylic acid group or a group which is negatively charged at neutral pH, a fatty acid moiety with from 4 to 22 carbon atoms in the carbon chain;
- and possible one or more linkers linking the individual components in the side chain together via amide bonds, provided that the fatty acid moiety is not a divalent hydrocarbon chain of the formula —(CH2)v4C6H4(CH2)W1— wherein v and w are integers or one of them is zero so that the sum of v4 and w1 is in the range of 6 to 30 in mixture with an insulin or an insulin analogue which has a rapid onset of action, together with a pharmaceutically acceptable carrier.
A method of treating diabetes in a patient in need of such a treatment, comprising administering to the patient a therapeutically effective amount of an insulin derivative, said insulin derivative comprising a side chain attached either to the α-amino group of the N-terminal amino acid residue of the B chain or to an ε-amino group of a Lys residue present in the A or the B chain of the parent insulin moiety via an amid bond, which side chain comprises at least one aromatic group;
- at least one free carboxylic acid group or a group which is negatively charged at neutral pH, a fatty acid moiety with from 4 to 22 carbon atoms in the carbon chain;
- and possible one or more linkers linking the individual components in the side chain together via amide bonds, provided that the fatty acid moiety is not a divalent hydrocarbon chain of the formula —(CH2)v4C6H4(CH2)W1— wherein v and w are integers or one of them is zero so that the sum of v4 and w1 is in the range of 6 to 30 together with a pharmaceutically acceptable carrier.
A method of treating diabetes in a patient in need of such a treatment, comprising administering to the patient a therapeutically effective amount of an insulin derivative, said insulin derivative comprising a side chain attached either to the α-amino group of the N-terminal amino acid residue of the B chain or to an ε-amino group of a Lys residue present in the A or the B chain of the parent insulin moiety via an amid bond, which side chain comprises at least one aromatic group;
- at least one free carboxylic acid group or a group which is negatively charged at neutral pH, a fatty acid moiety with from 4 to 22 carbon atoms in the carbon chain;
- and possible one or more linkers linking the individual components in the side chain together via amide bonds, provided that the fatty acid moiety is not a divalent hydrocarbon chain of the formula —(CH2)v4C6H4(CH2)W1— wherein v and w are integers or one of them is zero so that the sum of v4 and w1 is in the range of 6 to 30 in mixture with an insulin or an insulin analogue which has a rapid onset of action, together with a pharmaceutically acceptable carrier.
(canceled)
Dependencies are inferred from the claim text.