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    Insulin precursors
    1.
    发明授权
    Insulin precursors 失效
    胰岛素前列腺素

    公开(公告)号：US5202415A

    公开(公告)日：1993-04-13

    申请号：US623739

    申请日：1990-12-13

    申请人： Ib Jonassen ,  Ib G. Clausen ,  Einer B. Jensen ,  Allan Svendsen

    发明人： Ib Jonassen ,  Ib G. Clausen ,  Einer B. Jensen ,  Allan Svendsen

    IPC分类号： C12N15/09 ,  A61K38/00 ,  C07K14/575 ,  C07K14/62 ,  C12N15/17 ,  C12P21/02 ,  C12R1/865

    CPC分类号： C07K14/62 ,  A61K38/00

    摘要： Insulin precursors characterized by the amino acid sequence B(1-29)-X.sub.1 -X.sub.2 -Y.sub.2 -Y.sub.1 -A(1-21), wherein B(1-29) are the 29 first amino acid residues of the B chain of human insulin starting from the N-terminus, A(1-21) are the 21 amino acid residues of the A chain of human insulin, X.sub.1 represents a peptide bond or one or more arbitrary amino acid residues, X.sub.2 represents Glu or Asp, and Y.sub.1 and Y.sub.2 each represents Lys or Arg, the positions A6 and A11, A7 and B7 and A20 and B19, respectively, are connected through sulphur bridges, and, if desired, one or more of the amino acid residues of the chains B(1-29) and A(1-21) are substituted by another amino acid residue, are provided. The insulin precursors are prepared by culturing a yeast strain transformed with a replicable expression vehicle comprising a DNA sequence encoding an insulin precursor of the above formula in a suitable medium and isolating the insulin precursor thus formed from the culture medium. The insulin precursors can be converted into human insulin or insulin analogues by enzymatic treatment in a manner known per se.

    DNA sequences encoding insulin precursors and methods of production
    2.
    发明授权
    DNA sequences encoding insulin precursors and methods of production 失效
    编码胰岛素前体的DNA序列和生产方法

    公开(公告)号：US5324641A

    公开(公告)日：1994-06-28

    申请号：US952696

    申请日：1992-09-23

    申请人： Ib Jonassen ,  Ib G. Clausen ,  Ejner B. Jensen ,  Allan Svendsen

    发明人： Ib Jonassen ,  Ib G. Clausen ,  Ejner B. Jensen ,  Allan Svendsen

    IPC分类号： C12N15/09 ,  A61K38/00 ,  C07K14/575 ,  C07K14/62 ,  C12N15/17 ,  C12P21/02 ,  C12R1/865 ,  C12N15/00 ,  C12N1/08 ,  C12P21/06

    CPC分类号： C07K14/62 ,  A61K38/00

    摘要： DNA molecule and process for producing insulin precursors having the formula B(1-29) -H.sub.1 --X.sub.2 --Y.sub.2 --Y.sub.1 --A(1-21), wherein B(1-29) are the 29 first amino acid residues of the B chain of human insulin starting from the N-terminus, A(1-21) are the 21 amino acid residues of the A chain of human insulin, X.sub.1 represents a peptide bond or one naturally-occurring alpha-amino acid acid residues, X.sub.2 represents Glu or Asp, and Y.sub.1 and Y.sub.2 each represent Lys or Arg, the positions A6 and A11, A7 and B7 and A20 and B19, respectively, are connected through sulphur bridges, and, if desired, one or more of the glutamic acid residues in positions A4, A17, B13 and B21 are substituted by another naturally-occurring alpha-amino acid residue having an uncharged side chain, are provided. The insulin precursors are prepared by culturing a yeast strain transformed with a replicable plasmid comprising a DNA sequence encoding an insulin precursor of the above formula in a suitable medium and isolating the insulin precursor thus formed from the culture medium. The insulin precursor can be converted into human insulin or insulin analogues by enzymatic treatment in a manner known per se.

    摘要翻译： DNA分子和具有式B（1-29）-H1-X2-Y2-Y1-A（1-21）的胰岛素前体的制备方法，其中B（1-29）是B的第一个氨基酸残基 A（1-21）是人胰岛素A链的21个氨基酸残基，X1表示肽键或一个天然存在的α-氨基酸酸残基，X2表示 Glu或Asp，Y1和Y2各自表示Lys或Arg，位置A6和A11，A7和B7和A20和B19分别通过硫桥连接，如果需要，一个或多个谷氨酸残基在 位置A4，A17，B13和B21被另一个具有不带电侧链的天然存在的α-氨基酸残基所取代。 通过在合适的培养基中培养用包含编码上式胰岛素前体的DNA序列的可复制质粒转化的酵母菌株并分离由培养基形成的胰岛素前体来制备胰岛素前体。 胰岛素前体可以通过本身已知的方式通过酶处理转化为人胰岛素或胰岛素类似物。

    Insulin derivatives
    3.
    发明申请
    Insulin derivatives 有权
    胰岛素衍生物

    公开(公告)号：US20120208749A1

    公开(公告)日：2012-08-16

    申请号：US13506292

    申请日：2012-04-09

    申请人： Patrick William Garibay ,  Thomas Hoeg-Jensen ,  Ib Jonassen ,  Svend Havelund ,  Peter Madsen ,  Palle Jakobsen

    发明人： Patrick William Garibay ,  Thomas Hoeg-Jensen ,  Ib Jonassen ,  Svend Havelund ,  Peter Madsen ,  Palle Jakobsen

    IPC分类号： A61K38/28 ,  A61P3/10 ,  C07K14/62

    CPC分类号： A61K47/48215 ,  A61K38/00 ,  A61K47/60 ,  C07K14/62

    摘要： The present invention is related to insulin derivatives having a side chain attached either to the α-amino group of the N-terminal amino acid residue of B chain or to an ε-amino group of a Lys residue present in the B chain of the parent insulin molecule via an amide bond which side chain comprises one or more residues of ethyleneglycol, propyleneglycol and/or butyleneglycol containing independently at each termini a group selected from —NH2 and —COOH; a fatty diacid moiety with 4 to 22 carbon atoms, at least one free carboxylic acid group or a group which is negatively charged at neutral pH; and possible linkers which link the individual components in the side chain together via amide or ether bonds, said linkers optionally comprising a free carboxylic acid group.

    摘要翻译： 本发明涉及具有侧链连接到B链的N末端氨基酸残基的α-氨基或存在于B链的B链中的Lys残基的亚氨基的胰岛素衍生物 母体胰岛素分子通过酰胺键，该侧链包含在每个末端独立地含有选自-NH 2和-COOH的一个或多个乙二醇，丙二醇和/或丁二醇残基; 具有4至22个碳原子的脂肪二酸部分，至少一个游离羧酸基团或在中性pH下带负电荷的基团; 以及通过酰胺或醚键将侧链中各个组分连接在一起的可能接头，所述接头任选地包含游离羧酸基团。

    Insulin derivatives
    4.
    发明申请
    Insulin derivatives 有权
    胰岛素衍生物

    公开(公告)号：US20120035104A1

    公开(公告)日：2012-02-09

    申请号：US13273659

    申请日：2011-10-14

    申请人： Janos Tibor Kodra ,  Patrick William Garibay ,  Thomas Hoeg-Jensen ,  Ib Jonassen ,  Peter Madsen ,  Tina Moeller Tagmose

    发明人： Janos Tibor Kodra ,  Patrick William Garibay ,  Thomas Hoeg-Jensen ,  Ib Jonassen ,  Peter Madsen ,  Tina Moeller Tagmose

    IPC分类号： A61K38/28 ,  A61P3/10 ,  C07K14/62

    CPC分类号： A61K38/28 ,  C07K14/62

    摘要： The present invention relates to insulin derivatives having a side chain attached either to the α-amino group of the N-terminal amino acid residue of the B chain or to the ε-amino group of a Lys residue present in the B chain of the parent insulin via an amide bond which side chain comprises at least one aromatic group; at least one free carboxylic acid group or a group which is negatively charged at neutral pH, a fatty acid moiety with 4 to 22 carbon atoms in the carbon chain; and possible linkers which link the individual components in the side chain together via amide bonds.

    摘要翻译： 本发明涉及具有侧链连接到B链的N末端氨基酸残基的α-氨基或存在于B链的B链中的Lys残基的' - 氨基的胰岛素衍生物 通过酰胺键的母体胰岛素，该侧链包含至少一个芳族基团; 至少一个游离羧酸基团或在中性pH下带负电荷的基团，碳链中具有4-22个碳原子的脂肪酸部分; 以及通过酰胺键将侧链中各个组分连接在一起的可能接头。

    Method for Making Acylated Polypeptides
    8.
    发明申请
    Method for Making Acylated Polypeptides 有权
    制备酰化多肽的方法

    公开(公告)号：US20100055738A1

    公开(公告)日：2010-03-04

    申请号：US12543027

    申请日：2009-08-18

    申请人： Ib Jonassen ,  Michi Egel- Mitani ,  Per Balschmidt ,  Jan Markussen ,  Ivan Diers ,  Thomas Borglum Kjeldsen

    发明人： Ib Jonassen ,  Michi Egel- Mitani ,  Per Balschmidt ,  Jan Markussen ,  Ivan Diers ,  Thomas Borglum Kjeldsen

    IPC分类号： C12P21/06 ,  C07K4/00

    CPC分类号： C07K1/006 ,  C07K1/1077

    摘要： The present invention related to a method of producing polypeptides in transformed host cells by expressing a precursor molecule of the desired polypeptide which are to be acylated in a subsequent in vitro step. The invention is also related to DNA-sequences, vectors and transformed host cells for use in the claimed method. Further, the present invention is related to certain precursors of the desired polypeptides and certain acylation methods. The invention provides a method for making polypeptides being preferentially acylated in certain lysine ε-amino groups.

    摘要翻译： 本发明涉及通过在随后的体外步骤中表达待酰化的所需多肽的前体分子，在转化的宿主细胞中产生多肽的方法。 本发明还涉及用于所要求保护的方法的DNA序列，载体和转化的宿主细胞。 此外，本发明涉及所需多肽的某些前体和某些酰化方法。 本发明提供了在某些赖氨酸和氨基中优先酰化多肽的方法。