Invention Grant
US07829664B2 Modified nucleotide sequence encoding glucagon-like peptide-1 (GLP-1), nucleic acid construct comprising same for production of glucagon-like peptide-1 (GLP-1), human cells comprising said construct and insulin-producing constructs, and methods of use thereof
有权
编码胰高血糖素样肽-1(GLP-1)的修饰的核苷酸序列,包含用于产生胰高血糖素样肽-1(GLP-1)的核酸构建体,包含所述构建体的人细胞和产生胰岛素的构建体的方法 使用它
- Patent Title: Modified nucleotide sequence encoding glucagon-like peptide-1 (GLP-1), nucleic acid construct comprising same for production of glucagon-like peptide-1 (GLP-1), human cells comprising said construct and insulin-producing constructs, and methods of use thereof
- Patent Title (中): 编码胰高血糖素样肽-1(GLP-1)的修饰的核苷酸序列,包含用于产生胰高血糖素样肽-1(GLP-1)的核酸构建体,包含所述构建体的人细胞和产生胰岛素的构建体的方法 使用它
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Application No.: US11756821Application Date: 2007-06-01
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Publication No.: US07829664B2Publication Date: 2010-11-09
- Inventor: Revati J. Tatake , Margaret M. O'Neill , Kelli-Ann Monaco
- Applicant: Revati J. Tatake , Margaret M. O'Neill , Kelli-Ann Monaco
- Applicant Address: DE
- Assignee: Boehringer Ingelheim International GmbH
- Current Assignee: Boehringer Ingelheim International GmbH
- Current Assignee Address: DE
- Agent Michael P. Morris; Edouard G. Lebel; Mary-Ellen M. Devlin
- Main IPC: A61K38/22
- IPC: A61K38/22 ; A61K31/711 ; A61K48/00 ; C12N15/00 ; C12N15/17

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.
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