Peptide derivatives of exendin-4

• US 8,268,781 B2
• Filed: 03/02/2007
• Issued: 09/18/2012
• Est. Priority Date: 09/03/2004
• Status: Expired due to Fees

• Current Assignee: Philipps-Universität Marburg
• Original Assignee: Philipps-Universität Marburg
• Inventors: Gotthardt, Martin, Behr, Thomas, Béhé, Martin, Göke, Burkhard J.
• Primary Examiner(s): Gupta, Anish
• Application Number:
  US11/712,978
• Publication Number:
  US 20090180953A1
• Time in Patent Office: 2,027 Days
• Field of Search: None
• US Class Current: 514/11.7
• CPC Class Codes: A61K 51/08 Peptides, e.g. proteins , carriers being peptides, polyamino acids, proteins
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 14/57563 Vasoactive intestinal peptide [VIP]; Related peptides
• CPC Class Codes: C07K 14/605 Glucagons
• CPC Class Codes: G01N 33/74 involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors

Abstract

In the current invention peptides, which are derived from GLP-1 (glucagon-like peptide-1) and exendin-3 and/or exendin-4, are provided which bond to the GLP-receptor and can be used, labeled or unlabeled, for the production of an agent for diagnostic and therapy of benign and malignant diseases, in which GLP-1 receptor expression plays a role.

Claims

1. Peptide derivatives of exendin-4, wherein their C-terminus is modified by an amine and wherein their N-terminus binds to the GLP-1 receptor, of the formula exendin-4 (1-39)-A, wherein exendin 4 (1-39) corresponds to a sequence identity of over 90% to the amino acid sequence of

2. Peptide derivatives from exendin-4 according to the claim 1, wherein the chelator is N,N-Bis(2-[bis(carboxymethyl)amino]-ethyl)glycine), DOTA (1,4,7,10-Tetraazacyclodo-decane-1,4,7,10-tetra-acetic acid), HYNIC (6-Hydrazinopyridin-3-carbonic acid), MAG3 (mercaptoacetyl-glycylglycylglycine), N4 (1,4,8,11-tetraazaundecane).

3. Peptide derivatives from exendin-4 according to the claim 1, wherein the chosen radionuclide is in particular from the group F-18, Cu-64, Cu-67, Ga-67, Ga-68, Y-86, Y-90, Tc-99m, In-111, I-123, I-124, I-131, Lu-177, Re-186, Re-188, Pt-193m, Pt-195m, Ac-225, At-211, Bi-213, Sm-153 or Er-169.

4. Agent for the diagnostic and therapy of benign and malignant diseases, in which GLP-1 receptor expression plays a role, wherein it contains labeled peptide derivatives of exendin-4 according to claim 1.

5. Agent according to claim 4 wherein the labeled peptide derivatives contain a radionuclide.

6. Agent according to the claim 5, wherein after labeling with radionuclides for in vitro applications, free bonding sites are saturated with ^natInCL₃.

7. Peptide derivatives from extendin-4 according to claim 2, wherein the chelator is DTPA (Diethylenetriaminepentaacetic acid).