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1.发明申请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 有权修饰的核苷酸序列编码含有类糖蛋白-1（GLP-1），包含糖蛋白结构和胰岛素生产结构的人细胞的含有类胡萝卜素-1（GLP-1），含有胰蛋白酶的GLP-1（GLP-1），核酸结构， 使用它公开(公告)号：US20080299096A1
公开(公告)日：2008-12-04
申请号：US11756821
申请日：2007-06-01
CPC分类号： C07K14/605 , A61K38/00 , A61K48/00 , C07K14/495 , C07K14/62 , C07K2319/35 , C07K2319/50 , C12N15/85 , C12N2830/002
摘要： 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.
摘要翻译： 提供了编码人前胰岛素前导序列，胰高血糖素样肽-1（GLP-1）和人前胰岛素前导序列与GLP-1之间的弗林蛋白酶切割位点的分离的嵌合GLP-1核酸序列 。 还提供了编码人前胰岛素前导序列，胰高血糖素样肽-1（GLP-1）和人前胰岛素前导序列与GLP之间的弗林蛋白酶切割位点的分离的修饰嵌合GLP-1核酸序列 -1。 提供了包含组成型产生GLP-1的嵌合GLP-1核酸序列的重组表达载体，以及用这种表达载体转染的人细胞与包含胰岛素原核酸序列和表达载体的表达载体组合的人细胞 弗林蛋白酶和葡萄糖可调节的TGF-α启动子。 提供生产人GLP-1的方法，如制备GLP-1和胰岛素的方法或使用这种转染细胞以葡萄糖依赖性方式提供。 提供了治疗患有II型糖尿病的受试者的方法和治疗容易发生高血糖或患有高血糖症的受试者的方法，其中转染的细胞以葡萄糖依赖性方式产生人GLP-1和胰岛素。 还提供了通过植入到以葡萄糖依赖的方式产生人GLP-1和胰岛素的受试者转染细胞中来减轻受试者体重的方法。
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2.发明授权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 使用它公开(公告)号：US07829664B2
公开(公告)日：2010-11-09
申请号：US11756821
申请日：2007-06-01
IPC分类号： A61K38/22 , A61K31/711 , A61K48/00 , C12N15/00 , C12N15/17
CPC分类号： C07K14/605 , A61K38/00 , A61K48/00 , C07K14/495 , C07K14/62 , C07K2319/35 , C07K2319/50 , C12N15/85 , C12N2830/002
摘要： 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.
摘要翻译： 提供了编码人前胰岛素前导序列，胰高血糖素样肽-1（GLP-1）和人前胰岛素前导序列与GLP-1之间的弗林蛋白酶切割位点的分离的嵌合GLP-1核酸序列 。 还提供了编码人前胰岛素前导序列，胰高血糖素样肽-1（GLP-1）和人前胰岛素前导序列与GLP之间的弗林蛋白酶切割位点的分离的修饰嵌合GLP-1核酸序列 -1。 提供了包含组成型产生GLP-1的嵌合GLP-1核酸序列的重组表达载体，以及用这种表达载体转染的人细胞与包含胰岛素原核酸序列和表达载体的表达载体组合的人细胞 弗林蛋白酶和葡萄糖可调节的TGF-α启动子。 提供生产人GLP-1的方法，如制备GLP-1和胰岛素的方法或使用这种转染细胞以葡萄糖依赖性方式提供。 提供了治疗患有II型糖尿病的受试者的方法和治疗容易发生高血糖或患有高血糖症的受试者的方法，其中转染的细胞以葡萄糖依赖性方式产生人GLP-1和胰岛素。 还提供了通过植入到以葡萄糖依赖的方式产生人GLP-1和胰岛素的受试者转染细胞中来减轻受试者体重的方法。
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