GLP-1 gene delivery for the treatment of type 2 diabetes

• US 20090227660A1
• Filed: 03/05/2008
• Published: 09/10/2009
• Est. Priority Date: 05/21/2002
• Status: Abandoned Application

• Current Assignee: CLSN Laboratories, Inc. (Imunon, Inc.)
• Original Assignee: CLSN Laboratories, Inc. (Imunon, Inc.)
• Inventors: Lee, Minhyung, Ko, Kyungsoo, Oh, Seungjoon
• Application Number:
  US12/074,865
• Publication Number:
  US 20090227660A1
• Time in Patent Office: Days
• US Class Current: 514/44.R
• 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: A61K 47/59 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
• CPC Class Codes: A61K 47/593 Polyesters, e.g. PLGA or polylactide-co-glycolide
• CPC Class Codes: A61K 47/645 Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C07K 14/605 Glucagons

Abstract

This patent discloses compositions and methods of use thereof to normalize the blood glucose levels of patients with type 2 diabetes. It relates particularly to a plasmid comprising a chicken β actin promoter and enhancer; a modified GLP-1 (7-37) cDNA (pβGLP1), carrying a furin cleavage site, which is constructed and delivered into a cell for the expression of active GLP-1.

Claims

1. A method of normalizing blood glucose levels of a warm blooded animal having type 2 diabetes, comprising:

providing a transfection formulation comprising a cationic polymeric gene carrier complexed with a selected plasmid consisting essentially of;

an expression facilitating sequence derived from chicken β

-actin promoter and enhancer;

an expression sequence comprising ATG (start codon) followed by a sequence SEQ ID NO;

5 (CGTCAACGTCGT) coding for a furin cleavage site (FCS) and a sequence coding for the active form of GLP-1 (7-37) or derivatives thereof that are operably linked to said expression facilitating sequence in a proper charge ratio (positive charge of the copolymer/negative charge of the nucleic acid) that is optimally effective for both in vivo and in vitro transfection; and

administering to the animal to be treated an effective amount of the composition such that the cell internalizes the GLP-1 gene.

2. The method of claim 1, wherein the cationic polymeric gene carrier is PAGA.

3. The method of claim 2, wherein the weight ratio of DNA to PAGA is preferably within a range of 1:

0.82 to 1;

2.46.

4. The method of claim 2, wherein plasmid comprising an nucleotide sequence represented by the SEQ ID NO:

1 or having the nucleotide sequence represented by the SEQ ID NO;

2.

5. The method of claim 2, wherein the cationic polymeric gene carrier further comprises a targeting moiety.