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    Double-acylated GLP-1 derivatives with a linker
    11.
    发明授权
    Double-acylated GLP-1 derivatives with a linker 有权
    具有接头的双酰化GLP-1衍生物

    公开(公告)号：US09006178B2

    公开(公告)日：2015-04-14

    申请号：US13883946

    申请日：2011-11-09

    申请人： Jacob Kofoed ,  Jesper Lau ,  Lars Linderoth ,  Patrick William Garibay ,  Thomas Kruse

    发明人： Jacob Kofoed ,  Jesper Lau ,  Lars Linderoth ,  Patrick William Garibay ,  Thomas Kruse

    IPC分类号： A61K38/26 ,  A61P3/10 ,  A61P7/12 ,  C07K14/605 ,  A61K38/28 ,  C07K5/00 ,  C07K7/00 ,  C07K16/00 ,  C07K17/00 ,  A61K47/48

    CPC分类号： C07K14/605 ,  A61K47/542

    摘要： The invention relates to a derivative of a GLP-1 analog, which analog comprises a first K residue at a position corresponding to position 18 of GLP-1(7-37) (SEQ ID NO: 1), a second K residue at another position, and a maximum of twelve amino acid changes as compared to GLP-1(7-37); which derivative comprises two protracting moieties attached to said first and second K residue, respectively, via a linker, wherein the protracting moiety is selected from Chem. 1: HOOC—(CH2)x—CO—*, and Chem. 2: HOOC—C6H4-0-(CH2)y—CO—*, in which x is an integer in the range of 6-18, and y is an integer in the range of 3-17; and the linker comprises Chem. 3: *—NH—(CH2)q—CH[(CH2)w—NH2]—CO—*, wherein q is an integer in the range of 0-5, and w is an integer in the range of 0-5; or a pharmaceutically acceptable salt, amide, or ester thereof. The invention also relates to the pharmaceutical use thereof, for example in the treatment and/or prevention of all forms of diabetes and related diseases, as well as to corresponding novel peptides and side chain intermediates. The derivatives are potent, protracted, and suitable for oral administration.

    摘要翻译： 本发明涉及GLP-1类似物的衍生物，其类似物包含在对应于GLP-1（7-37）（SEQ ID NO：1）的第18位的位置处的第一个K残基，另一个的第二个K残基 位置和与GLP-1（7-37）相比最多12个氨基酸变化; 该衍生物分别包含通过接头分别连接到所述第一和第二K残基的两个伸长部分，其中伸长部分选自Chem。 1：HOOC-（CH 2）x-CO- *，和Chem。 2：HOOC-C6H4-0-（CH2）y-CO- *，其中x是6-18的整数，y是3-17的整数; 连接体包括Chem。 3：* -NH-（CH 2）q-CH [（CH 2）w -NH 2] -CO- *，其中q是0-5的整数，w是0-5的整数 ; 或其药学上可接受的盐，酰胺或酯。 本发明还涉及其药物用途，例如用于治疗和/或预防所有形式的糖尿病和相关疾病，以及相应的新型肽和侧链中间体。 衍生物有效，延长，适合口服。

    Glucagon-Like Peptide-1 derivatives and their pharmaceutical use
    12.
    发明授权
    Glucagon-Like Peptide-1 derivatives and their pharmaceutical use 有权
    胰高血糖素样肽-1衍生物及其药物用途

    公开(公告)号：US08895694B2

    公开(公告)日：2014-11-25

    申请号：US12676451

    申请日：2008-09-05

    申请人： Jane Spetzler ,  Lauge Schäffer ,  Jesper Lau ,  Thomas Kruse ,  Patrick William Garibay ,  Steffen Reedtz-Runge ,  Henning Thøgersen ,  Ingrid Pettersson

    发明人： Jane Spetzler ,  Lauge Schäffer ,  Jesper Lau ,  Thomas Kruse ,  Patrick William Garibay ,  Steffen Reedtz-Runge ,  Henning Thøgersen ,  Ingrid Pettersson

    IPC分类号： A61K38/00 ,  A61K39/00 ,  C07K14/605

    CPC分类号： C07K14/605 ,  A61K38/26

    摘要： The invention relates to protracted Glucagon-Like Peptide-1 (GLP-1) derivatives and therapeutic uses thereof. The GLP-1 derivative of the invention comprises a modified GLP-1(7-37) sequence having a total of 2-12 amino acid modifications, including Glu22 and Arg26, and being derivatised with an albumin binding residue or pegylated in position 18, 20, 23, 30, 31, 34, 36, 37, or 39. These compounds are useful in the treatment or prevention of diabetes type 2 and related diseases. The compounds are potent, stable, have long half-lives, a high affinity of binding to albumin, and/or a high affinity of binding to the extracellular domain of the GLP-1 receptor (GLP-1R), all of which is of potential relevance for the overall aim of achieving long-acting, stable and active GLP-1 derivatives with a potential for once weekly administration.

    摘要翻译： 本发明涉及长效的胰高血糖素样肽-1（GLP-1）衍生物及其治疗用途。 本发明的GLP-1衍生物包含具有总共2-12个氨基酸修饰的修饰的GLP-1（7-37）序列，包括Glu22和Arg26，并用白蛋白结合残基衍生或在18位聚乙二醇化， 20,23,30,31,34,36,37或39.这些化合物可用于治疗或预防2型糖尿病和相关疾病。 该化合物是有效的，稳定的，具有长的半衰期，与白蛋白结合的高亲和力，和/或与GLP-1受体（GLP-1R）细胞外结构域结合的高亲和力，所有这些都是 对于实现长效，稳定和活性的GLP-1衍生物的总体目标的潜在相关性，具有每周一次行政的潜力。

    Double-Acylated GLP-1 Derivatives
    14.
    发明申请
    Double-Acylated GLP-1 Derivatives 有权
    双酰化GLP-1衍生物

    公开(公告)号：US20130288960A1

    公开(公告)日：2013-10-31

    申请号：US13882947

    申请日：2011-11-09

    申请人： Alice Ravn Madsen ,  Birgit Wieczorek ,  Jacob Kofoed ,  Jesper Lau ,  Jane Spetzler ,  Janos Tibor Kodra ,  Lars Linderoth ,  Patrick William Garibay ,  Per Sauerberg ,  Thomas Kruse

    发明人： Alice Ravn Madsen ,  Birgit Wieczorek ,  Jacob Kofoed ,  Jesper Lau ,  Jane Spetzler ,  Janos Tibor Kodra ,  Lars Linderoth ,  Patrick William Garibay ,  Per Sauerberg ,  Thomas Kruse

    IPC分类号： C07K14/605

    CPC分类号： C07K14/605 ,  A61K47/542

    摘要： The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue at a position corresponding to position 18 of GLP-1 (7-37) (SEQ ID NO: 1), a second K residue at another position, and a maximum of twelve amino acid changes as compared to GLP-1 (7-37); which derivative comprises two protracting moieties attached to said first and second K residue, respectively, via a linker, wherein the protracting moiety is selected from Chem. 1, Chem. 2, and Chem. 3: Chem.: HOOC—(CH2)x—CO—* Chem. 2: HOOC—C6H4-0-(CH2)y—CO—* Chem. 3: R2—C6H4—(CH2)z—CO—*, in which x is an integer in the range of 6-18, y is an integer in the range of 3-17, z is an integer in the range of 1-5, and R2 is a group having a molar mass not higher than 150 Da; and the linker comprises Chem. 4: *—NH—(CH2)2-(0-(CH2)2)k-0-(CH2)n—CO—*. wherein k is an integer in the range of 1-5, and n is an integer in the range of 1-5; or a pharmaceutically acceptable salt, amide, or ester thereof. The invention also relates to the pharmaceutical use thereof, for example in the treatment and/or prevention of all forms of diabetes and related diseases, as well as to corresponding novel peptides and side chain intermediates. The derivatives are suitable for oral administration.

    摘要翻译： 本发明涉及GLP-1类似物的衍生物，其类似物包含在对应于GLP-1（7-37）（SEQ ID NO：1）的第18位的位置处的第一个K残基，另一个的第二个K残基 位置和与GLP-1（7-37）相比最多12个氨基酸变化; 该衍生物分别包含通过接头分别连接到所述第一和第二K残基的两个伸长部分，其中伸长部分选自Chem。 1，Chem。 2和Chem。 3：化学式：HOOC-（CH2）x-CO- * 2：HOOC-C6H4-0-（CH2）y-CO- * Chem。 3：R2-C6H4-（CH2）z-CO- *，其中x是6-18的整数，y是3-17的整数，z是1的整数 -5和R2是摩尔质量不高于150Da的基团; 连接体包括Chem。 4：* -NH-（CH 2）2 - （O-（CH 2）2）k -O-（CH 2）n -CO- *。 其中k是1-5的整数，n是1-5的整数; 或其药学上可接受的盐，酰胺或酯。 本发明还涉及其药物用途，例如用于治疗和/或预防所有形式的糖尿病和相关疾病，以及相应的新型肽和侧链中间体。 该衍生物适用于口服给药。

    DERIVATISED HYBRID PEPTIDES OF AMYLIN AND SALMON CALCITONIN
    17.
    发明申请
    DERIVATISED HYBRID PEPTIDES OF AMYLIN AND SALMON CALCITONIN 审中-公开
    氨基酸和沙门碱钙的衍生杂交肽

    公开(公告)号：US20110152183A1

    公开(公告)日：2011-06-23

    申请号：US13000225

    申请日：2009-06-25

    申请人： Lauge Schäffer ,  Thomas Kruse

    发明人： Lauge Schäffer ,  Thomas Kruse

    IPC分类号： A61K38/23 ,  C07K14/585 ,  A61P3/10 ,  A61P3/04 ,  A61P25/28

    CPC分类号： C07K14/575 ,  A61K38/00 ,  C07K14/461 ,  C07K14/585 ,  C07K2319/00

    摘要： Described are derivatives of hybrid peptides and pharmaceutical compositions comprising such, wherein said hybrid peptides comprise the C-terminal end of the human amylin peptide sequence, the middle portion of the salmon calcitonin peptide sequence and the N-terminal end of the human amylin peptide sequence, and wherein an albumin binding moiety is attached to the hybrid peptide, optionally via a linker.

    摘要翻译： 描述了杂交肽的衍生物和包含其的药物组合物，其中所述杂合肽包含人胰岛淀粉样多肽肽序列的C末端，鲑鱼降钙素肽序列的中间部分和人胰岛淀粉样多肽肽序列的N-末端 ，并且其中白蛋白结合部分任选地经由接头连接到杂交肽上。

    Method for optimizing characteristics map
    19.
    发明授权
    Method for optimizing characteristics map 有权
    优化特征图的方法

    公开(公告)号：US07177758B2

    公开(公告)日：2007-02-13

    申请号：US11133749

    申请日：2005-05-19

    申请人： Thomas Kruse ,  Volker Imhof ,  Ernst Kloppenburg ,  Harald Stuhler

    发明人： Thomas Kruse ,  Volker Imhof ,  Ernst Kloppenburg ,  Harald Stuhler

    IPC分类号： G06F19/00 ,  G01L3/26

    CPC分类号： F02D41/2422 ,  F02D41/1406 ,  F02D41/2416 ,  F02D2041/1433 ,  G01M15/05

    摘要： A method for optimizing characteristics maps for the control of an internal combustion engine in which a model of the internal combustion engine is first formed by measurements on the internal combustion engine. In the process, a dependency of output variables of the internal combustion engine on the characteristics maps is illustrated. In the optimization, the dependency of the output variables of the internal combustion engine on the characteristics maps and the smoothing of the characteristics maps are optimized simultaneously.

    摘要翻译： 一种用于优化用于内燃机控制的特性图的方法，其中内燃机的型号首先通过在内燃机上的测量形成。 在此过程中，说明内燃机输出变量对特征图的依赖性。 在优化中，内燃机的输出变量对特征图的依赖性和特征图的平滑同时优化。

    Wheelchair lift
    20.
    发明授权
    Wheelchair lift 失效
    轮椅电梯

    公开(公告)号：US06007289A

    公开(公告)日：1999-12-28

    申请号：US100389

    申请日：1998-06-19

    申请人： Thomas Kruse ,  Jeffrey Moone

    发明人： Thomas Kruse ,  Jeffrey Moone

    IPC分类号： A61G3/02 ,  B60P1/54 ,  B60R9/042 ,  B60R9/06 ,  B66C23/44

    CPC分类号： B60R9/06 ,  A61G3/0209 ,  B60P1/5495 ,  B60R9/0426 ,  B66C23/44 ,  Y10S414/134

    摘要： A self propelled personal mobility vehicle lift operable in a stored configuration and a deployed configuration operatively mounted to the rear portion of a vehicle to selectively lift and remove a self propelled personal mobility vehicle into and from the rear portion of the vehicle, the self propelled personal mobility vehicle lift includes a stanchion or tower assembly pivotally mounted to a lift mounting assembly secured to the vehicle, a boom assembly to support a hoist assembly and a lift support assembly to support the self propelled personal mobility vehicle lift when deployed telescopingly coupled to the upper and lower portions of the stanchion or tower assembly respectively, the hoist assembly includes a hoist mechanism having a flexible hoist element to couple the self propelled personal mobility vehicle lift to the self propelled personal mobility vehicle when the self propelled personal mobility vehicle lift is in the deployed configuration to selectively lift or lower the self propelled personal mobility vehicle into or from the rear portion of the vehicle.

    摘要翻译： 可自行推进的个人行动车辆升降机，其可操作于存储结构和可操作地安装到车辆后部的展开构型，以选择性地将自行推进的个人行动性车辆从车辆的后部提升和移出，该自推进的个人 移动式车辆升降机包括枢转地安装到固定到车辆的升降机安装组件的支柱或塔架组件，支撑起重机组件的起重臂组件和升降支撑组件，以在展开时可伸缩地联接到上部 并且分支的下部分分别包括一个提升机构，该起重机构具有一个柔性起重机构，用于将自行推进的个人行动车辆升降机连接到自推进式个人行动车辆上， 部署配置以选择升降 将自行车个人行动车辆从车辆的后部进入或离开。