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    Processes for Preparing a Polypeptide
    1.
    发明申请
    Processes for Preparing a Polypeptide 审中-公开
    制备多肽的方法

    公开(公告)号：US20100234566A1

    公开(公告)日：2010-09-16

    申请号：US12727653

    申请日：2010-03-19

    Applicant: Anup Kumar Ray ,  Hiren Kumar V. Patel ,  Johannes Ludescher ,  Mariappan Anbazhagan ,  Mahendra R. Patel ,  Ingolf Macher

    Inventor： Anup Kumar Ray ,  Hiren Kumar V. Patel ,  Johannes Ludescher ,  Mariappan Anbazhagan ,  Mahendra R. Patel ,  Ingolf Macher

    IPC: C07K1/08

    CPC classification number: C08G69/10 ,  A61K38/00 ,  C07K14/001

    Abstract: The present invention relates to an improved process for preparing a polypeptide or pharmaceutically acceptable salt thereof comprising L-tyrosine, L-alanine, L-glutamate, and L-lysine. The polypeptide or pharmaceutically acceptable salt thereof is preferably glatiramer acetate. The process comprises: (a) polymerizing a mixture of N-carboxyanhydride of L-tyrosine, N-carboxyanhydride of L-alanine, N-carboxyanhydride of a protected L-glutamate and N-carboxyanhydride of a protected L-lysine, in a polar aprotic solvent in the presence of an initiator, to form a protected polypeptide; (b) admixing an acid with the protected polypeptide formed in Step (a) and a solvent, to form a product; and (c) admixing a substance selected from the group consisting of an alkali or alkaline earth metal hydroxide, a carbonate, a hydrogencarbonate, and mixtures thereof, with the product formed in Step (b), and a solvent or a mixture of a solvent and water, to form a deprotected polypeptide or a pharmaceuticaly acceptable salt thereof.

    Abstract translation: 本发明涉及制备包含L-酪氨酸，L-丙氨酸，L-谷氨酸和L-赖氨酸的多肽或其药学上可接受的盐的改进方法。 多肽或其药学上可接受的盐优选为醋酸格拉司他。 该方法包括：（a）将L-酪氨酸的N-羧酸酐，L-丙氨酸的N-羧酸酐，受保护的L-谷氨酸的N-羧酸酐和受保护的L-赖氨酸的N-羧酸酐的极性 在引发剂存在下的非质子溶剂，以形成受保护的多肽; （b）将酸与步骤（a）中形成的被保护的多肽和溶剂混合以形成产物; 和（c）将选自碱金属或碱土金属氢氧化物，碳酸盐，碳酸氢盐及其混合物的物质与步骤（b）中形成的产物和溶剂或溶剂的混合物 和水，以形成去保护的多肽或其药学上可接受的盐。

    Process for the synthesis of bis-aryl diamidoxime compounds
    3.
    发明授权
    Process for the synthesis of bis-aryl diamidoxime compounds 失效
    双芳基二肟化合物的合成方法

    公开(公告)号：US07071338B2

    公开(公告)日：2006-07-04

    申请号：US10722085

    申请日：2003-11-25

    Applicant: David W. Boykin ,  Mariappan Anbazhagan ,  Richard R. Tidwell

    Inventor： David W. Boykin ,  Mariappan Anbazhagan ,  Richard R. Tidwell

    IPC: C07D207/335 ,  C07D307/52 ,  C07D333/22

    CPC classification number: C07D307/54

    Abstract: Bis-aryl diamidoxime compounds, such as 2,5-bis [4-hydroxy and 4-O-alkylamidinophenyl] furans, can be prepared from 2,5-bis tri-alkylstannanes via a one step palladium-catalyzed cross reaction. Bis-aryl diamidoxime compounds, such as 2,5-bis [4-hydroxy and 4-O-alkylamidinophenyl]furans, are useful as therapeutic compounds. The disclosed process is scalable, simpler, more economic and more feasible than other presently known methods of preparing 2,5-bis [4-hydroxy and 4-O-alkylamidinophenyl]furans and other bis-aryl diamidoxime compounds.

    Abstract translation: 双芳基二肟化合物，如2,5-双[4-羟基和4-O-烷基脒基苯基]呋喃，可以通过一步钯催化的交叉反应由2,5-双三烷基锡烷制备。 双芳基二肟化合物，例如2,5-双[4-羟基和4-O-烷基脒基苯基]呋喃，可用作治疗化合物。 所公开的方法比其它目前已知的制备2,5-双[4-羟基和4-O-烷基脒基苯基]呋喃和其它双芳基二肟基化合物的方法是可扩展的，更简单的，更经济的和更可行的。

    Processes for preparing a polypeptide
    4.
    发明授权
    Processes for preparing a polypeptide 失效
    制备多肽的方法

    公开(公告)号：US08536305B2

    公开(公告)日：2013-09-17

    申请号：US11904422

    申请日：2007-09-27

    Applicant: Anup K Ray ,  Hiren V Patel ,  Johannes Ludescher ,  Mariappan Anbazhagan ,  Mahendra R Patel ,  Ingolf Macher

    Inventor： Anup K Ray ,  Hiren V Patel ,  Johannes Ludescher ,  Mariappan Anbazhagan ,  Mahendra R Patel ,  Ingolf Macher

    IPC: A61K38/00 ,  C07K1/00 ,  C07K2/00

    CPC classification number: C08G69/10 ,  A61K38/00 ,  C07K14/001

    Abstract: The present invention relates to an improved process for preparing a polypeptide or pharmaceutically acceptable salt thereof comprising L-tyrosine, L-alanine, L-glutamate, and L-lysine. The polypeptide or pharmaceutically acceptable salt thereof is preferably glatiramer acetate. The process comprises: (a) polymerizing a mixture of N-carboxyanhydride of L-tyrosine, N-carboxyanhydride of L-alanine, N-carboxyanhydride of a protected L-glutamate and N-carboxyanhydride of a protected L-lysine, in a polar aprotic solvent in the presence of an initiator, to form a protected polypeptide; (b) admixing an acid with the protected polypeptide formed in Step (a) and a solvent, to form a product; and (c) admixing a substance selected from the group consisting of an alkali or alkaline earth metal hydroxide, a carbonate, a hydrogencarbonate, and mixtures thereof, with the product formed in Step (b), and a solvent or a mixture of a solvent and water, to form a deprotected polypeptide or a pharmaceutically acceptable salt thereof.

    Abstract translation: 本发明涉及制备包含L-酪氨酸，L-丙氨酸，L-谷氨酸和L-赖氨酸的多肽或其药学上可接受的盐的改进方法。 多肽或其药学上可接受的盐优选为醋酸格拉司他。 该方法包括：（a）将L-酪氨酸的N-羧酸酐，L-丙氨酸的N-羧酸酐，受保护的L-谷氨酸的N-羧酸酐和受保护的L-赖氨酸的N-羧基酐的极性 在引发剂存在下的非质子溶剂，以形成受保护的多肽; （b）将酸与步骤（a）中形成的被保护的多肽和溶剂混合以形成产物; 和（c）将选自碱金属或碱土金属氢氧化物，碳酸盐，碳酸氢盐及其混合物的物质与步骤（b）中形成的产物和溶剂或溶剂的混合物 和水，以形成去保护的多肽或其药学上可接受的盐。

    Processes for preparing a polypeptide
    5.
    发明申请
    Processes for preparing a polypeptide 失效
    制备多肽的方法

    公开(公告)号：US20080021200A1

    公开(公告)日：2008-01-24

    申请号：US11904422

    申请日：2007-09-27

    Applicant: Anup Ray ,  Hiren Patel ,  Johannes Ludescher ,  Mariappan Anbazhagan ,  Mahendra Patel ,  Ingolf Macher

    Inventor： Anup Ray ,  Hiren Patel ,  Johannes Ludescher ,  Mariappan Anbazhagan ,  Mahendra Patel ,  Ingolf Macher

    IPC: C07K16/00

    CPC classification number: C08G69/10 ,  A61K38/00 ,  C07K14/001

    Abstract: The present invention relates to an improved process for preparing a polypeptide or pharmaceutically acceptable salt thereof comprising L-tyrosine, L-alanine, L-glutamate, and L-lysine. The polypeptide or pharmaceutically acceptable salt thereof is preferably glatiramer acetate. The process comprises: (a) polymerizing a mixture of N-carboxyanhydride of L-tyrosine, N-carboxyanhydride of L-alanine, N-carboxyanhydride of a protected L-glutamate and N-carboxyanhydride of a protected L-lysine, in a polar aprotic solvent in the presence of an initiator, to form a protected polypeptide; (b) admixing an acid with the protected polypeptide formed in Step (a) and a solvent, to form a product; and (c) admixing a substance selected from the group consisting of an alkali or alkaline earth metal hydroxide, a carbonate, a hydrogencarbonate, and mixtures thereof, with the product formed in Step (b), and a solvent or a mixture of a solvent and water, to form a deprotected polypeptide or a pharmaceutically acceptable salt thereof.

    Abstract translation: 本发明涉及制备包含L-酪氨酸，L-丙氨酸，L-谷氨酸和L-赖氨酸的多肽或其药学上可接受的盐的改进方法。 多肽或其药学上可接受的盐优选为醋酸格拉司他。 该方法包括：（a）将L-酪氨酸的N-羧酸酐，L-丙氨酸的N-羧酸酐，受保护的L-谷氨酸的N-羧酸酐和受保护的L-赖氨酸的N-羧酸酐的极性 在引发剂存在下的非质子溶剂，以形成受保护的多肽; （b）将酸与步骤（a）中形成的被保护的多肽和溶剂混合以形成产物; 和（c）将选自碱金属或碱土金属氢氧化物，碳酸盐，碳酸氢盐及其混合物的物质与步骤（b）中形成的产物和溶剂或溶剂的混合物 和水，以形成去保护的多肽或其药学上可接受的盐。

    Processes for Preparing a Polypeptide
    7.
    发明申请
    Processes for Preparing a Polypeptide 审中-公开
    制备多肽的方法

    公开(公告)号：US20100174048A1

    公开(公告)日：2010-07-08

    申请号：US12727758

    申请日：2010-03-19

    Applicant: Anup Kumar Ray ,  Hiren Kumar V. Patel ,  Johannes Ludescher ,  Mariappan Anbazhagan ,  Mahendra R. Patel ,  Ingolf Macher

    Inventor： Anup Kumar Ray ,  Hiren Kumar V. Patel ,  Johannes Ludescher ,  Mariappan Anbazhagan ,  Mahendra R. Patel ,  Ingolf Macher

    IPC: C07K1/06 ,  C07K2/00

    CPC classification number: C08G69/10 ,  A61K38/00 ,  C07K14/001

    Abstract: The present invention relates to an improved process for preparing a polypeptide or pharmaceutically acceptable salt thereof comprising L-tyrosine, L-alanine, L-glutamate, and L-lysine. The polypeptide or pharmaceutically acceptable salt thereof is preferably glatiramer acetate. The process comprises: (a) polymerizing a mixture of N-carboxyanhydride of L-tyrosine, N-carboxyanhydride of L-alanine, N-carboxyanhydride of a protected L-glutamate and N-carboxyanhydride of a protected L-lysine, in a polar aprotic solvent in the presence of an initiator, to form a protected polypeptide; (b) admixing an acid with the protected polypeptide formed in Step (a) and a solvent, to form a product; and (c) admixing a substance selected from the group consisting of an alkali or alkaline earth metal hydroxide, a carbonate, a hydrogencarbonate, and mixtures thereof, with the product formed in Step (b), and a solvent or a mixture of a solvent and water, to form a deprotected polypeptide or a pharmaceutically acceptable salt thereof.

    Abstract translation: 本发明涉及制备包含L-酪氨酸，L-丙氨酸，L-谷氨酸和L-赖氨酸的多肽或其药学上可接受的盐的改进方法。 多肽或其药学上可接受的盐优选为醋酸格拉司他。 该方法包括：（a）将L-酪氨酸的N-羧酸酐，L-丙氨酸的N-羧酸酐，受保护的L-谷氨酸的N-羧酸酐和受保护的L-赖氨酸的N-羧酸酐的极性 在引发剂存在下的非质子溶剂，以形成受保护的多肽; （b）将酸与步骤（a）中形成的被保护的多肽和溶剂混合以形成产物; 和（c）将选自碱金属或碱土金属氢氧化物，碳酸盐，碳酸氢盐及其混合物的物质与步骤（b）中形成的产物和溶剂或溶剂的混合物 和水，以形成去保护的多肽或其药学上可接受的盐。

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