Modified nucleotide sequence encoding glucagon-like...

Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – Insulin; related peptides

Reexamination Certificate

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C424S093100, C424S093210, C435S069400, C435S069700, C435S071100, C435S320100, C514S002600, C514S04400A, C530S324000, C530S399000, C536S023100, C536S023510

Reexamination Certificate

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07829664

ABSTRACT:
An isolated chimeric GLP-1 nucleic acid sequence encoding a human pro-insulin leader, a glucagon-like peptide-1 (GLP-1), and a furin cleavable site between the human pro-insulin leader sequence and the GLP-1 is provided. Also provided is an isolated modified chimeric GLP-1 nucleic acid sequence encoding a human pro-insulin leader, a glucagon-like peptide-1 (GLP-1), and a furin cleavable site between the human pro-insulin leader sequence and the GLP-1. Recombinant expression vectors comprising the chimeric GLP-1 nucleic acid sequences, which produce GLP-1 constitutively are provided, as are human cells transfected with such an expression vector in combination with an expression vector comprising a proinsulin nucleic acid sequence and an expression vector comprising a furin and a glucose-regulatable TGF-alpha promoter. Methods of producing human GLP-1 constitutively are provided as are method of producing GLP-1 and insulin or in a glucose-dependent manner using such transfected cells. Methods of treating a subject having Type II diabetes and methods of treating a subject prone to hyperglycemia or suffering from hyperglycemia are provided in which transfected cells produce human GLP-1 and insulin in a glucose-dependent manner. Also provided are methods of reducing weight in a subject by implanting into the subject transfected cells which produce human GLP-1 and insulin in a glucose-dependent manner.

REFERENCES:
patent: WO0136643 (2001-05-01), None
patent: WO03014318 (2003-02-01), None
patent: WO03030946 (2003-04-01), None
Sures et al, Science 208(4439):57-59, 1980.
International Search Report and Written Opinion of the International Application No. PCT/US2008/065015.
M. Kumar, Y. Hunag, Y. Glinka, GJ Prud'Homme, Q. Wang, Gene therapy of diabetes Using a novel GLP-1/1gG1-Fc fusion construct normalizes glucose levels in db/db mice, Gene Therapy (2007) 14, 162-172 XP-002499114.
GB Parsons, DW Souza, H. Wu, D. Yu, SG Wadsworth, RJ Gregory, D. Armentano, Ectopic expression of glucagon-like peptide 1 gene therapy of type II diabetes, Gene Therapy (2007) 14, 38-48 XP-002499115.

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