Insulins with an acyl moiety comprising repeating units of alkylene glycol containing amino acids

• US 8,962,794 B2
• Filed: 08/15/2008
• Issued: 02/24/2015
• Est. Priority Date: 08/15/2007
• Status: Active Grant

• Current Assignee: Novo Nordisk A/S
• Original Assignee: Novo Nordisk A/S
• Inventors: Madsen, Peter, Kjeldsen, Thomas Boerglum, Kodra, Janos Tibor
• Primary Examiner(s): Wax, Robert A
• Assistant Examiner(s): WORSHAM, JESSICA N
• Application Number:
  US12/673,337
• Publication Number:
  US 20110098439A1
• Time in Patent Office: 2,384 Days
• Field of Search: None
• US Class Current: 530/303
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 14/62 Insulins

Abstract

Acylated insulins wherein an acyl moiety is attached to the parent insulin and wherein said acyl moiety comprises repeating units of alkylene glycol containing amino acids and wherein there is only one lysine residue (K & Lys) in the parent insulin have satisfactory properties when administered pulmonary.

Claims

1. An acylated human insulin, wherein an acyl moiety is attached to the epsilon amino group of B29K of the parent insulin and wherein said acyl moiety comprises repeating units of alkylene glycol containing amino acids and wherein there is only one lysine residue in the parent insulin, wherein the acyl moiety is a group of formula (I):

Acy-AA1_n-AA2_m-AA3_p- 

 

(I),

wherein

n is an integer in the range 1-3,

m is 0 or an integer in the range 1-6,

p is an integer in the range 2-30

Acy is a fatty acid or a fatty diacid comprising 8 to 24 carbon atoms from which a hydroxy group has been removed from the fatty acid and a hydroxy group has been removed from one of the carboxy groups in the fatty diacid,

AA1 is a neutral cyclic amino acid from which a hydroxy group has been removed from the carboxy group and a hydrogen atom has been removed from the amino group, wherein AA1 is selected from

2. An acylated insulin, according to claim 1, wherein AA1 is

3. An acylated insulin, according to claim 2, wherein AA2 is Glu (α

or γ

, L or D), Asp (α

or β

, L or D),

4. An acylated insulin according to claim 1, which is selected from the group consisting of

B29K(N^ε

[2-(2-[2-(2-[2-(4-[(octadecandioylamino)methyl]-trans-cyclohexanecarboxyl)amino]-ethoxy)ethoxy]acetylamino)ethoxy]ethoxy)acetyl], desB30 human insulin; and

B29K(N^ε

[2-(2-[2-(2-[2-(4-[(eicosanedioylamino)methyl]-trans-cyclohexanecarboxyl)amino]-ethoxy)ethoxy]acetylamino)ethoxy]ethoxy)acetyl]), desB30 human insulin.