IP Library Granted Patent US 8,642,544
Granted Patent B2
US 8,642,544 · App. 13/260,702 · Granted Feb 4, 2014

N-terminus conformationally constrained GLP-1 receptor agonist compounds

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Quick Facts
Patent No.
US 8,642,544
App. No.
13/260,702
Granted
Feb 4, 2014
Kind
B2
Abstract

The disclosure provides N-terminus conformationally constrained compounds, which may comprise peptide mimetics and/or amino acid substitutions, which may be used in peptides, such as GLP-1 receptor agonist compounds, to induce a β-turn secondary structure at the N-terminus. The N-terminus conformationally constrained compounds may be used for research purposes; to produce GLP-1 receptor agonist compounds having improved GLP-1 receptor binding activity, enzymatic stability, or in vivo glucose lowering activity; and to develop GLP-1 receptor agonist compounds which have fewer amino acid residues. The disclosure also provides GLP-1 receptor agonist compounds, such as exendins, exendin analogs, GLP-1 (7-37), GLP-1 (7-37) analogs, comprising the N-terminus conformationally constrained compounds. The compounds are useful for treating various diseases, such as diabetes and obesity. The disclosure also provides methods for chemically synthesizing the N-terminus conformationally constrained compounds.

Claims (13)

1. A peptide comprising the amino acid sequence as set forth in Formula (D):

Xaa 1 Xaa 2 Xaa 3 Xaa 4 TFTSDLSKQXaa 14 EEEAVRLFIEXaa 25 LKNGGPSSGAPPPS-Z (SEQ ID No:3);

wherein:

Xaa 1 is His;

Xaa 2 is Gly or dAla;

Xaa 3 is Pro;

Xaa 4 is Gly;

Xaa 14 is Leu or Met;

Xaa 25 is Phe or Trp;

and

Z is OH or NH 2 .

2. The peptide of claim 1 , wherein the peptide comprises the amino sequence as set forth in SEQ ID NO:40, 41, or 42.

3. A method for lowering blood glucose levels in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of the peptide of claim 1 to lower blood glucose levels in the patient.

Assignments (3)
AMYLIN PHARMACEUTICALS, LLC ASSIGNS AN EQUAL AND UNDIVIDED ONE-HALF OF ITS ENTIRE RIGHT, TITLE AND INTEREST TO ASTRAZENECA PHARMACEUTICALS LP Recorded Oct 26, 2012
From: AMYLIN PHARMACEUTICALS, LLC
To: ASTRAZENECA PHARMACEUTICALS LP
Reel/Frame 029195/0555 →
CHANGE OF NAME Recorded Oct 25, 2012
From: AMYLIN PHARMACEUTICALS, INC.
To: AMYLIN PHARMACEUTICALS, LLC
Reel/Frame 029198/0396 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 7, 2011
From: ALFARO-LOPEZ, JOSUE; SHARMA, ABHINANDINI; GHOSH, SOUMITRA S.
To: AMYLIN PHARMACEUTICALS, INC.
Reel/Frame 027031/0017 →