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    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
    1.
    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

    申请人： Revati J. Tatake ,  Margaret M. O'Neill ,  Kelli-Ann Monaco

    发明人： Revati J. Tatake ,  Margaret M. O'Neill ,  Kelli-Ann Monaco

    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。

    Process for preparing human proinsulin
    5.
    发明授权
    Process for preparing human proinsulin 失效
    人胰岛素原的制备方法

    公开(公告)号：US5952461A

    公开(公告)日：1999-09-14

    申请号：US9145

    申请日：1998-01-20

    申请人： Chang-Kyu Kim ,  Yong-In Kim ,  Je-Nie Pheu ,  Jeong-Woo Shin ,  Sung-Jin Oh ,  Chung-Il Hong ,  Jung-Woo Kim ,  Wang-Sik Lee

    发明人： Chang-Kyu Kim ,  Yong-In Kim ,  Je-Nie Pheu ,  Jeong-Woo Shin ,  Sung-Jin Oh ,  Chung-Il Hong ,  Jung-Woo Kim ,  Wang-Sik Lee

    IPC分类号： C12N15/09 ,  A61K38/00 ,  C07K1/22 ,  C07K14/62 ,  C12N1/06 ,  C12N15/17 ,  C12N15/62 ,  C12P21/02 ,  C12R1/19 ,  A61K38/28

    CPC分类号： C07K14/62 ,  A61K38/00

    摘要： The present invention relates to a process for preparing human proinsulin which is represented as a following chemical formula(I): ##STR1## wherein, R is an amino acid residue or a peptide which is degradable enzymatically or chemically; and, X is a linkage of an amino group of A-1 in insulin A chain and a carboxyl group of B-30 in insulin B chain which can be separated from the A chain or the B chain enzymatically or chemically, provided that a region from A-1 to A-21 is the insulin A chain and a region from B-1 to B-30 is the insulin B chain. In accordance with the present invention, human recombinant insulin precursor can be simply manufactured with a good reproducibility, since dissolution, sulfonation, concentration, desalting and purification are remarkably simplified, while increasing the yield of refolding reaction.

    摘要翻译： 本发明涉及以下列化学式（I）表示的人胰岛素原的制备方法：其中，R为可酶促或化学降解的氨基酸残基或肽; 并且X是胰岛素A链中A-1的氨基与胰岛素B链中的B-30的羧基之间的连接，其可以通过酶学或化学方法与A链或B链分离，条件是一个区域 从A-1到A-21是胰岛素A链，并且从B-1到B-30的区域是胰岛素B链。 根据本发明，由于溶出，磺化，浓缩，脱盐和纯化显着简化，同时提高了再折叠反应的产率，因此可以简单地制备人重组胰岛素前体，具有良好的再现性。

    Method for manufacture of proinsulin with high export yield
    7.
    发明授权
    Method for manufacture of proinsulin with high export yield 失效
    具有高出口产量的胰岛素原的制造方法

    公开(公告)号：US5840542A

    公开(公告)日：1998-11-24

    申请号：US508664

    申请日：1995-07-28

    申请人： Yup Kang ,  Ji-Won Yoon

    发明人： Yup Kang ,  Ji-Won Yoon

    IPC分类号： C07K14/62 ,  C12N15/17

    CPC分类号： C07K14/62 ,  C07K2319/00

    摘要： The present invention provides a method for manufacture of proinsulin with high export yield, by modifying the connecting peptide region of the proinsulin. According to the method of the present invention, the highest export yield of proinsulin can be obtained, when its connecting peptide region is similar in size to that of human insulin-like growth factor I(hIGFI) or when most of the connecting peptide region of the proinsulin is deleted.

    摘要翻译： 本发明提供了通过改变胰岛素原的连接肽区域来制备具有高出口收率的胰岛素原的方法。 根据本发明的方法，当其连接肽区域的大小与人类胰岛素样生长因子I（hIGFI）的大小相似时，或当大部分连接肽区域的连接肽区域 胰岛素原被删除。

    Asp.sup.B1 insulin analogs
    9.
    发明授权
    Asp.sup.B1 insulin analogs 失效
    AspB1胰岛素类似物

    公开(公告)号：US5559094A

    公开(公告)日：1996-09-24

    申请号：US285661

    申请日：1994-08-02

    申请人： David N. Brems ,  Diane L. Bakaysa

    发明人： David N. Brems ,  Diane L. Bakaysa

    IPC分类号： C12N15/09 ,  A61K38/00 ,  A61K38/28 ,  A61P9/12 ,  C07K14/62 ,  C12P21/02 ,  C12N15/00 ,  C12N15/17

    CPC分类号： C07K14/62 ,  A61K38/00 ,  Y10S530/866

    摘要： Analogs of human insulin containing an aspartic acid at position 1 of the B chain (Asp.sup.B1), and optionally, having a gln modification at position 13 (Gln.sup.B13), display modified physico-chemical and pharmacokinetic properties which enable them to be long acting. These analogs are useful in the treatment of hyperglycemia because they are soluble and display an increased tendency to self-associate.

    摘要翻译： 在B链（AspB1）的1位含有天冬氨酸的人类胰岛素类似物，并且任选地，在第13位具有gln修饰（GlnB13），显示出改变的物理化学和药代动力学性质，使得它们能够长效。 这些类似物可用于治疗高血糖症，因为它们是可溶性的并显示出增加的自身联系倾向。