Dosing Regimen

Patent metadata

Field	Value
Publication number	US-2016296602-A1
Application number	US-201414777789-A
Country	US
Kind code	A1
Filing date	Mar 19, 2014
Priority date	Mar 20, 2013
Publication date	Oct 13, 2016
Grant date	—

Abstract

The present invention relates to a long acting insulin analogue for use in reducing the risk of hypoglycaemia in a patient suffering from diabetes and requiring high amounts of delivered insulin, wherein the long acting insulin analogue is administered to said patient and in an amount of greater than 80 U/administration.

First claim

1 . A long acting insulin analogue for use in reducing the risk of hypoglycaemia in a patient suffering from diabetes and requiring amounts of delivered insulin of greater than 80 U/administration, wherein the long acting insulin analogue is administered to said patient in an amount of greater than 80 U/administration and in the form of a pharmaceutical composition comprising said insulin at a concentration of greater than 100 U/ml,
and wherein the long acting insulin analogue is a naturally occurring insulin or an insulin analogue having a side chain attached either to the α-amino group of the N-terminal amino acid residue of the B chain or to the ε-amino group of a Lys residue present in the B chain of the parent insulin, the side chain being of the general formula (I):
—W—X—Y—Z

wherein W is:
an α-amino acid residue having a carboxylic acid group in the side chain which residue forms, with one of its carboxylic acid groups, an amide group together with the α-amino group of the N-terminal amino acid residue of the B chain or together with the ε-amino group of a Lys residue present in the B chain of the parent insulin;
a chain composed of two, three or four α-amino acid residues linked together via amide bonds, which chain—via an amide bond—is linked to the α-amino group of the N-terminal amino acid residue of the B chain or to the ε-amino group of a Lys residue present in the B chain of the parent insulin, the amino acid residues of W being selected from the group of amino acid residues having a neutral side chain and amino acid residues having a carboxylic acid group in the side chain so that W has at least one amino acid residue which has a carboxylic acid group in the side chain; or
a covalent bond from X to the α-amino group of the N-terminal amino acid residue of the B chain or to the ε-amino group of a Lys residue present in the B chain of the parent insulin;
wherein X is:
—CO—;
—COCH(COOH) C O—;
—CON(CH 2 COOH)CH 2 C O—;
—CON(CH 2 COOH)CH 2 CON(CH 2 COOH)CH 2 C O—;
—CON(CH 2 CH 2 COOH)CH 2 CH 2 C O—;
—CON(CH 2 CH 2 COOH)CH 2 CH 2 CON(CH 2 CH 2 COOH)CH 2 CH 2 C O—;
—CONHCH(COOH)(CH 2 ) 4 NH C O—;
—CON(CH 2 CH 2 COOH)CH 2 C O—; or
—CON(CH 2 COOH)CH 2 CH 2 C O—,
that a) when W is an amino acid residue or a chain of amino acid residues, via a bond from the underscored carbonyl carbon forms an amide bond with an amino group in W, or b) when W is a covalent bond, via a bond from the underscored carbonyl carbon forms an amide bond with the N-terminal α-amino group in the B chain or with the g-amino group of a Lys residue present in the B chain of the parent insulin; wherein Y is:
—(CH 2 ) m — where m is an integer in the range of 6 to 32;
a divalent hydrocarbon chain comprising 1, 2 or 3 —CH═CH— groups and a number of —CH 2 — groups sufficient to give a total number of carbon atoms in the chain in the range of 10 to 32;
a divalent hydrocarbon chain of the formula —(CH 2 ) v C 6 H 4 (CH 2 ) W — wherein v and w are integers or one of them is zero so that the sum of v and w is in the range of 6 to 30; and

wherein Z is:
—COOH;
—CO-Asp;
—CO-Glu;
—CO-Gly;
—CO-Sar;
—CH(COOH) 2 ;
—N(CH 2 COOH) 2 ;
—SO 3 H; or
—PO 3 H;
and any Zn 2+ complexes thereof, provided that when W is a covalent bond and X is —CO—, then Z is different from —COOH.

2 . A long acting insulin analogue for use in treating a patient suffering from diabetes and requiring amounts of delivered insulin of greater than 80 U/administration, wherein the long acting insulin analogue is administered to said patient in an amount of greater than 80 U/administration and in the form of a pharmaceutical composition comprising said insulin at a concentration of greater than 100 U/mL,
and wherein the long acting insulin analogue is as defined in claim 1 .

3 . A long acting insulin analogue for use in providing beneficial glycaemic control in a patient suffering from diabetes and requiring amounts of delivered insulin of greater than 80 U/administration, wherein the long acting insulin analogue is administered to said patient in an amount of greater than 80 U/administration and in the form of a pharmaceutical composition comprising said insulin at a concentration of greater than 100 U/mL and wherein the long acting insulin analogue is as defined in claim 1 .

4 . A long acting insulin analogue for use according to claim 1 , wherein the long acting insulin analogue is administered in the form of a pharmaceutical composition comprising said insulin at a concentration of 200 U/mL or greater.

5 . The long acting insulin analogue for the use according to claim 1 , wherein the long acting insulin analogue is administered once daily.

6 . The long acting insulin analogue for the use according to claim 1 , wherein the long acting insulin analogue is administered by injection in an amount of greater than 80U/injection.

7 . The long acting insulin analogue for the use according to claim 1 , wherein the side chain —W—X—Y—Z is attached to the ε-amino group of a Lys residue present in position 29 of the B chain,
W is selected from the group consisting of α-Asp, β-Asp, α-Glu, γ-Glu, α-hGlu and δ-hGlu; preferably γ-Glu,
X is — C O
Y is a group of the formula —(CH 2 ) m — where m is an integer in the range of from 6 to 32, from 8 to 20, from 12 to 20, or from 12-16 and/or
Z is —COOH.

8 . The long acting insulin analogue for the use according to claim 1 , wherein the amino acid residue at position B30 has been deleted from the parent insulin analogue or wherein the parent insulin is des(30) human insulin.

9 . The long acting insulin analogue for the use according to claim 1 , wherein the long acting insulin analogue is insulin degludec.

10 . The long acting insulin analogue for the use according to claim 1 , wherein the patient is suffering from type-2 diabetes.

11 . The long acting insulin analogue for the use according to claim 1 , wherein the hypoglycaemia is nocturnal hypoglycaemia.

12 . The long acting insulin analogue for the use according to claim 1 , wherein the risk of hypoglycaemia is reduced to a rate of hypoglycaemic episodes of less than 2 episodes/exposure in a year, of less than 1.5 episodes/exposure in a year, of less than 1 episodes/exposure in a year or of less than 0.5 episodes/exposure in a year.

13 . The long acting insulin analogue for the use according to claim 1 , wherein the long actin insulin analogue has an insulin action for at least 24 hours.

14 . The long acting insulin analogue for the use according to claim 12 wherein the long actin insulin analogue has an insulin action for at least 30 hours, at least 36 hours, at least 42 hours, at least 48 hours, between 24 and 48 hours after administration, between 30 and 48 hours after administration, between 36 and 48 hours after administration, between 24 and 42 hours after administration, between 24 and 36 hours after administration, between 30 and 42 hours after administration, or between 30 and 36 hours after administration.

15 . A method for
reducing the risk of hypoglycaemia in a patient suffering from diabetes and requiring amounts of delivered insulin of greater than 80 U/administration; treating a patient suffering from diabetes and requiring amounts of delivered insulin of greater than 80 U/administration; or providing beneficial glycaemic control in a patient suffering from diabetes and requiring amounts of delivered insulin of greater than 80 U/administration,
wherein a long acting insulin analogue is administered to said patient in an amount of greater than 80 U/administration and in the form of a pharmaceuti

Assignees

• Novo Nordisk As

Inventors

• Johansen Thue

Classifications

• A61K38/28 Primary

  Insulins · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title