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1. 发明申请

WO2010125079A3 INSULINOTROPIC PEPTIDE SYNTHESIS USING SOLID AND SOLUTION PHASE COMBINATION TECHNIQUES 审中-公开
公开(公告)号：WO2010125079A3
公开(公告)日：2010-11-04
申请号：PCT/EP2010/055662
申请日：2010-04-28
申请人： F. HOFFMANN-LA ROCHE AG , CHEN, Lin , HAN, Yeun-Kwei , ROBERTS, Christopher, R.
发明人： CHEN, Lin , HAN, Yeun-Kwei , ROBERTS, Christopher, R.
IPC分类号： C07K14/605
摘要： The present invention relates to the preparation of insulino tropic peptides including the amino acid sequence of (SEQ ID NO. 9) Z-HX 8 EGTFTSDVSSYLEGQAAKEFIAWLVKX 35 R-NH 2 wherein Z is H-, and X 8 and X 35 are each independently achiral, optionally sterically hindered amino acid residues, by using a solid and solution phase ("hybrid") approach. Generally, the approach includes synthesizing three different peptide intermediate fragments using solid phase chemistry. Solution phase chemistry is then used to couple the second fragment and the first fragment. Alternatively, a different second fragment is coupled to a first fragment in the solid phase. Then, solution phase chemistry is used to add the third fragment, whereby the third fragment is coupled to the coupled first and second fragments in the solution phase.

2. 发明申请

WO2009074483A3 INSULINOTROPIC PEPTIDE SYNTHESIS USING SOLID AND SOLUTION PHASE COMBINATION TECHNIQUES 审中-公开
公开(公告)号：WO2009074483A3
公开(公告)日：2009-06-18
申请号：PCT/EP2008/066585
申请日：2008-12-02
申请人： F. HOFFMANN-LA ROCHE AG , CHEN, Lin , HAN, Yeun-Kwei , ROBERTS, Christopher, R.
发明人： CHEN, Lin , HAN, Yeun-Kwei , ROBERTS, Christopher, R.
IPC分类号： C07K14/605 , A61K38/26
摘要： The present invention relates to the preparation of insulinotropic peptides that are synthesized using a solid and solution phase ('hybrid') approach. Generally, the approach includes synthesizing three different peptide intermediate fragments using solid phase chemistry. Solution phase chemistry is then used to add additional amino acid material to the third fragment which is then coupled to the second fragment and then the first fragment in solution. Alternatively, a different second fragment is coupled to the first fragment in the solid phase. Then, solution phase chemistry is then used to add additional amino acid material to a different third fragment. Subsequently, this different third fragment is coupled to the coupled first and different second fragment in the solution phase. The use of a pseudoproline in one of the fragments eases solid phase synthesis of that fragment and also eases subsequent solution phase coupling of this fragment to the other fragments. The present invention is very useful for forming insulinotropic peptides such as GLP- 1(7-36) and its natural and non-natural counterparts.

3. 发明申请

WO2008080845A1 METHODS FOR THE SYNTHESIS OF CYCLIC PEPTIDES 审中-公开
标题翻译：周期肽合成方法
公开(公告)号：WO2008080845A1
公开(公告)日：2008-07-10
申请号：PCT/EP2007/064186
申请日：2007-12-19
申请人： F. HOFFMANN-LA ROCHE AG , CHEN, Lin , HAN, Yeun-Kwei , ROBERTS, Christopher R
发明人： CHEN, Lin , HAN, Yeun-Kwei , ROBERTS, Christopher R
IPC分类号： C07K1/04 , C07K5/06 , C07K7/06
CPC分类号： C07K1/04 , C07K5/06113 , C07K7/56 , C07K14/665
摘要： Methods for the synthesis of cyclic peptides are provided, as well as novel dipeptide compounds. The methods include the solid phase synthesis of a dipeptide, which is the coupled to a second peptide in a solid phase reaction. The peptide is then cyclized following the coupling reaction. The methods and dipeptides are particularly useful for the synthesis of MC-4 receptor agonist peptides.
摘要翻译：提供了合成环肽的方法，以及新型二肽化合物。所述方法包括在固相反应中与第二肽偶联的二肽的固相合成。然后在偶合反应后使肽环化。该方法和二肽特别可用于合成MC-4受体激动剂肽。

4. 发明申请

WO2007147816A1 INSULINOTROPIC PEPTIDE SYNTHESIS 审中-公开
标题翻译：胰岛素肽合成
公开(公告)号：WO2007147816A1
公开(公告)日：2007-12-27
申请号：PCT/EP2007/056052
申请日：2007-06-19
申请人： F. HOFFMANN-LA ROCHE AG , CHEN, Lin , HAN, Yeun-Kwei , ROBERTS, Christopher R.
发明人： CHEN, Lin , HAN, Yeun-Kwei , ROBERTS, Christopher R.
IPC分类号： C07K14/605 , A61K38/26
CPC分类号： C07K14/605 , A61K38/00
摘要： The present invention relates to the preparation of insulinotropic peptides that are synthesized using a solid and solution phase ("hybrid") approach. Generally, the approach includes synthesizing three different peptide intermediate fragments using solid phase chemistry. Solution phase chemistry is then used to add additional amino acid material to one of the fragments. The fragments are then coupled together in the solid solution phase. The use of a pseudoproline in one of the fragments eases solid phase synthesis of that fragment and also eases subsequent solution phase coupling of this fragment to other fragments. The present invention is very useful for forming insulinotropic peptides such as GLP-1(7-36) and its natural and non-natural counterparts.
摘要翻译：本发明涉及使用固相和溶液相（“混合”）方法合成的促胰岛素肽的制备。通常，该方法包括使用固相化学合成三种不同的肽中间体片段。然后使用溶液相化学为其中一个片段添加另外的氨基酸材料。然后将片段在固溶相中偶联在一起。在其中一个片段中使用假脯氨酸使得该片段的固相合成减轻了该片段随后与其它片段的溶液相偶联。本发明对于形成促胰岛素肽如GLP-1（7-36）及其天然和非天然对应物非常有用。

5. 发明申请

WO2006069729A1 SYNTHESIS OF PEPTIDE T-1249 USING PEPTIDE INTERMEDIATE FRAGMENTS 审中-公开
标题翻译：使用肽中间体片段合成P-T-1249
公开(公告)号：WO2006069729A1
公开(公告)日：2006-07-06
申请号：PCT/EP2005/013854
申请日：2005-12-22
申请人： F. HOFFMANN-LA ROCHE AG , HAN, Yeun-Kwei , HODGES, L., Mark , JOHNSTON, David, A. , KHATRI, Hiralal, N.
发明人： HAN, Yeun-Kwei , HODGES, L., Mark , JOHNSTON, David, A. , KHATRI, Hiralal, N.
IPC分类号： C07K14/16
CPC分类号： C07K14/005 , A61K38/00 , C12N2740/16122
摘要： Methods for the solid phase synthesis of T-1249 peptides and peptide intermediates, in particular methods involving synthesizing T-1249 peptide intermediates at low loading factors to produce products having excellent purity and yield.
摘要翻译： T-1249肽和肽中间体的固相合成方法，特别是涉及在低负载因子下合成T-1249肽中间体以产生具有优异纯度和产率的产物的方法。

6. 发明申请

WO2005063793A1 PROCESS AND SYSTEMS FOR RECOVERY OF PEPTIDES 审中-公开
标题翻译：用于恢复肽的方法和系统
公开(公告)号：WO2005063793A1
公开(公告)日：2005-07-14
申请号：PCT/EP2004/014600
申请日：2004-12-22
申请人： F. HOFFMANN-LA ROCHE AG , HAN, Yeun-Kwei , KHATRI, Hiralal, N. , TOPPING, Robert, J.
发明人： HAN, Yeun-Kwei , KHATRI, Hiralal, N. , TOPPING, Robert, J.
IPC分类号： C07K1/30
CPC分类号： C07K14/005 , C07K1/30 , C12N2740/16122 , Y02P20/55
摘要： The invention provides methods of obtaining a peptide that include steps of synthesizing a peptide intermediate having one or more side chain protecting groups; providing a solvent to the peptide intermediate to form a peptide intermediate composition; and providing a precipitating agent in an amount sufficient to precipitate the peptide intermediate from the peptide intermediate composition, wherein the precipitating agent is an alcohol having three or more carbon atoms. Also provided are methods for precipitating peptides, methods for concentration peptides, and methods for filtering peptides.
摘要翻译：本发明提供了获得肽的方法，其包括合成具有一个或多个侧链保护基团的肽中间体的步骤; 向所述肽中间体提供溶剂以形成肽中间体组合物; 并提供足以使肽中间体从肽中间体组合物沉淀的沉淀剂，其中沉淀剂是具有三个或更多个碳原子的醇。还提供了沉淀肽的方法，浓缩肽的方法和肽过滤方法。

7. 发明申请

WO2006069728A1 SYNTHESIS OF PEPTIDE T-20 USING PEPTIDE INTERMEDIATE FRAGMENTS 审中-公开
标题翻译：使用肽中间体片段合成肽-T-20
公开(公告)号：WO2006069728A1
公开(公告)日：2006-07-06
申请号：PCT/EP2005/013853
申请日：2005-12-22
申请人： F. HOFFMANN-LA ROCHE AG , HAN, Yeun-Kwei , JOHNSTON, David, A. , KHATRI, Hiralal, N.
发明人： HAN, Yeun-Kwei , JOHNSTON, David, A. , KHATRI, Hiralal, N.
IPC分类号： C07K14/16
CPC分类号： C07K14/005 , C12N2740/16122
摘要： Methods for the solid phase synthesis of T-20 peptides and peptide intermediates, in particular methods involving synthesizing T-20 peptide intermediates at low loading factors to produce products having excellent purity and yield.
摘要翻译：用于固相合成T-20肽和肽中间体的方法，特别是涉及以低负载因子合成T-20肽中间体以产生具有优异纯度和产率的产物的方法。

8. 发明申请

WO2006069727A2 SYNTHESIS USING PEPTIDE INTERMEDIATE FRAGMENTS III 审中-公开
标题翻译：使用肽中间片合成三
公开(公告)号：WO2006069727A2
公开(公告)日：2006-07-06
申请号：PCT/EP2005/013852
申请日：2005-12-22
申请人： F. HOFFMANN-LA ROCHE AG , HAN, Yeun-Kwei , JOHNSTON, David, A. , KHATRI, Hiralal, N.
发明人： HAN, Yeun-Kwei , JOHNSTON, David, A. , KHATRI, Hiralal, N.
IPC分类号： C07K14/16
CPC分类号： C07K14/005 , C12N2740/16122
摘要： Methods for the solid phase synthesis of T-20 peptides and peptide intermediates, in particular methods involving synthesizing T-20 peptide intermediates at low loading factors to produce products having excellent purity and yield.
摘要翻译：用于固相合成T-20肽和肽中间体的方法，特别是涉及在低负载因子下合成T-20肽中间体以产生具有优异纯度和产率的产物的方法。

9. 发明公开

EP2222695A2 INSULINOTROPIC PEPTIDE SYNTHESIS USING SOLID AND SOLUTION PHASE COMBINATION TECHNIQUES 审中-公开
标题翻译：利用固相和溶液相组合技术合成胰岛素肽
公开(公告)号：EP2222695A2
公开(公告)日：2010-09-01
申请号：EP08860359.2
申请日：2008-12-02
申请人： F. Hoffmann-La Roche AG
发明人： CHEN, Lin , HAN, Yeun-Kwei , ROBERTS, Christopher, R.
IPC分类号： C07K14/43
CPC分类号： C07K14/605
摘要： The present invention relates to the preparation of insulinotropic peptides that are synthesized using a solid and solution phase ('hybrid') approach. Generally, the approach includes synthesizing three different peptide intermediate fragments using solid phase chemistry. Solution phase chemistry is then used to add additional amino acid material to the third fragment which is then coupled to the second fragment and then the first fragment in solution. Alternatively, a different second fragment is coupled to the first fragment in the solid phase. Then, solution phase chemistry is then used to add additional amino acid material to a different third fragment. Subsequently, this different third fragment is coupled to the coupled first and different second fragment in the solution phase. The use of a pseudoproline in one of the fragments eases solid phase synthesis of that fragment and also eases subsequent solution phase coupling of this fragment to the other fragments. The present invention is very useful for forming insulinotropic peptides such as GLP- 1(7-36) and its natural and non-natural counterparts.
摘要翻译：本发明涉及使用固相和溶液相（“混合”）方法合成的促胰岛素肽的制备。通常，该方法包括使用固相化学合成三种不同的肽中间体片段。然后使用溶液相化学将另外的氨基酸物质添加至第三片段，然后将其与第二片段连接，然后与溶液中的第一片段连接。或者，不同的第二片段在固相中与第一片段偶联。然后，使用溶液相化学将另外的氨基酸物质添加至不同的第三片段。随后，该不同的第三片段在溶液阶段与偶联的第一不同第二片段偶联。在片段之一中使用假脯氨酸可以使该片段的固相合成变得容易，并且还使该片段随后的溶液相偶联到其他片段上。本发明对于形成促胰岛素肽诸如GLP-1（7-36）及其天然和非天然对应物非常有用。

10. 发明公开

EP2125862A1 METHODS FOR THE SYNTHESIS OF CYCLIC PEPTIDES 审中-公开
标题翻译：方法合成环肽
公开(公告)号：EP2125862A1
公开(公告)日：2009-12-02
申请号：EP07857809.3
申请日：2007-12-19
申请人： F. Hoffmann-La Roche AG
发明人： CHEN, Lin , HAN, Yeun-Kwei , ROBERTS, Christopher R
IPC分类号： C07K1/04 , C07K5/06 , C07K7/06
CPC分类号： C07K1/04 , C07K5/06113 , C07K7/56 , C07K14/665
摘要： Methods for the synthesis of cyclic peptides are provided, as well as novel dipeptide compounds. The methods include the solid phase synthesis of a dipeptide, which is the coupled to a second peptide in a solid phase reaction. The peptide is then cyclized following the coupling reaction. The methods and dipeptides are particularly useful for the synthesis of MC-4 receptor agonist peptides.

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