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1. 发明申请

US20080051434A1 Hemiasterlin derivatives and uses thereof in the treatment of cancer 有权
标题翻译：半精球蛋白衍生物及其在癌症治疗中的应用
公开(公告)号：US20080051434A1
公开(公告)日：2008-02-28
申请号：US11701969
申请日：2007-02-02
申请人： James Kowalczyk , Galina Kuznetsov , Shawn Schiller , Boris Seletsky , Mark Spyvee , Hu Yang
发明人： James Kowalczyk , Galina Kuznetsov , Shawn Schiller , Boris Seletsky , Mark Spyvee , Hu Yang
IPC分类号： A61K31/445 , A61K31/164 , A61K31/195 , A61K31/221 , A61P43/00 , C07C233/00 , C07D221/00 , C07C229/00 , A61P35/00 , A61K31/40 , A61K31/426
CPC分类号： C07K7/06 , A61K38/05 , A61K38/06 , A61K38/07 , A61K38/08 , C07C237/22 , C07D207/08 , C07D207/16 , C07D211/60 , C07D295/185 , C07D401/14 , C07K5/06078 , C07K5/06156 , C07K5/06165 , C07K5/0808 , C07K5/0821 , C07K5/0823 , C07K5/1016
摘要： The present invention provides compounds having formula (I): and additionally provides methods for the synthesis thereof and methods for the use thereof in the treatment of cancer, wherein R1-R7, X1, X2, R, Q, and n are as defined herein.
摘要翻译：本发明提供具有式（I）的化合物：另外提供其合成方法及其用于治疗癌症的方法，其中R 1 -R 7 X 1，X 2，R 3，Q 3和n如本文所定义。

2. 发明申请

US20050239870A1 Hrmiasterlin derivatives and uses thereof 有权
标题翻译： Hrmiasterlin衍生物及其用途
公开(公告)号：US20050239870A1
公开(公告)日：2005-10-27
申请号：US10508607
申请日：2003-03-21
申请人： James Kowalczyk , Galina Kuznetsov , Shawn Schiller , Boris Seletsky , Mark Spyvee , Hu Yang
发明人： James Kowalczyk , Galina Kuznetsov , Shawn Schiller , Boris Seletsky , Mark Spyvee , Hu Yang
IPC分类号： C07D295/18 , A61K31/16 , A61K31/165 , A61K31/197 , A61K31/40 , A61K31/401 , A61K31/426 , A61K31/427 , A61K31/4465 , A61K31/454 , A61P1/00 , A61P9/00 , A61P11/00 , A61P13/00 , A61P35/00 , C07C237/12 , C07D207/08 , C07D207/16 , C07D211/60 , C07D277/20 , C07D277/56 , C07D295/185 , C07D401/12 , C07D401/14 , C07K5/062 , C07K5/065 , C07K5/078 , C07K5/083 , C07K5/087 , C07K5/097 , C07K5/107 , C07K7/02 , C07K7/06
CPC分类号： C07K7/06 , A61K38/05 , A61K38/06 , A61K38/07 , A61K38/08 , C07C237/22 , C07D207/08 , C07D207/16 , C07D211/60 , C07D295/185 , C07D401/14 , C07K5/06078 , C07K5/06156 , C07K5/06165 , C07K5/0808 , C07K5/0821 , C07K5/0823 , C07K5/1016
摘要： The present invention provides compounds having formula (I): and additionally provides methods for the synthesis thereof and methods for the use thereof in the treatment of cancer, wherein R1-R7, X1, X2, R, Q, and n are as defined herein.
摘要翻译：本发明提供具有式（I）的化合物：另外提供其合成方法及其用于治疗癌症的方法，其中R 1 -R 7 X 1，X 2，R 3，Q 3和n如本文所定义。

3. 发明授权

US08633224B2 Hemiasterlin derivatives and uses thereof in the treatment of cancer 失效
标题翻译：半精球蛋白衍生物及其在癌症治疗中的应用
公开(公告)号：US08633224B2
公开(公告)日：2014-01-21
申请号：US13365728
申请日：2012-02-03
申请人： James J. Kowalczyk , Galina Kuznetsov , Shawn Schiller , Boris M. Seletsky , Mark Spyvee , Hu Yang
发明人： James J. Kowalczyk , Galina Kuznetsov , Shawn Schiller , Boris M. Seletsky , Mark Spyvee , Hu Yang
IPC分类号： A61K31/454 , C07D401/12
CPC分类号： C07K7/06 , A61K38/05 , A61K38/06 , A61K38/07 , A61K38/08 , C07C237/22 , C07D207/08 , C07D207/16 , C07D211/60 , C07D295/185 , C07D401/14 , C07K5/06078 , C07K5/06156 , C07K5/06165 , C07K5/0808 , C07K5/0821 , C07K5/0823 , C07K5/1016
摘要： The present invention provides compounds having formula (I): and additionally provides methods for the synthesis thereof and methods for the use thereof in the treatment of cancer, wherein R1-R7, X1, X2, R, Q, and n are as defined herein.
摘要翻译：本发明提供具有式（I）的化合物：另外提供其合成方法及其用于治疗癌症的方法，其中R1-R7，X1，X2，R，Q和n如本文所定义。

4. 发明授权

US07528152B2 Hemiasterlin derivatives and uses thereof in the treatment of cancer 有权
标题翻译：半精球蛋白衍生物及其在癌症治疗中的应用
公开(公告)号：US07528152B2
公开(公告)日：2009-05-05
申请号：US11701969
申请日：2007-02-02
申请人： James J. Kowalczyk , Galina Kuznetsov , Shawn Schiller , Boris M. Seletsky , Mark Spyvee , Hu Yang
发明人： James J. Kowalczyk , Galina Kuznetsov , Shawn Schiller , Boris M. Seletsky , Mark Spyvee , Hu Yang
IPC分类号： A61K31/445 , C07D211/60
CPC分类号： C07K7/06 , A61K38/05 , A61K38/06 , A61K38/07 , A61K38/08 , C07C237/22 , C07D207/08 , C07D207/16 , C07D211/60 , C07D295/185 , C07D401/14 , C07K5/06078 , C07K5/06156 , C07K5/06165 , C07K5/0808 , C07K5/0821 , C07K5/0823 , C07K5/1016
摘要： The present invention provides compounds having formula (I): and additionally provides methods for the synthesis thereof and methods for the use thereof in the treatment of cancer, wherein R1-R7, X1, X2, R, Q, and n are as defined herein.
摘要翻译：本发明提供具有式（I）的化合物：另外提供其合成方法及其用于治疗癌症的方法，其中R1-R7，X1，X2，R，Q和n如本文所定义。

5. 发明授权

US08129407B2 Hemiasterlin derivatives and uses thereof in the treatment of cancer 有权
标题翻译：半精球蛋白衍生物及其在癌症治疗中的应用
公开(公告)号：US08129407B2
公开(公告)日：2012-03-06
申请号：US12394882
申请日：2009-02-27
申请人： James J. Kowalczyk , Galina Kuznetsov , Shawn Schiller , Boris M. Seletsky , Mark Spyvee , Hu Yang
发明人： James J. Kowalczyk , Galina Kuznetsov , Shawn Schiller , Boris M. Seletsky , Mark Spyvee , Hu Yang
IPC分类号： A61K31/445 , C07D211/32
CPC分类号： C07K7/06 , A61K38/05 , A61K38/06 , A61K38/07 , A61K38/08 , C07C237/22 , C07D207/08 , C07D207/16 , C07D211/60 , C07D295/185 , C07D401/14 , C07K5/06078 , C07K5/06156 , C07K5/06165 , C07K5/0808 , C07K5/0821 , C07K5/0823 , C07K5/1016
摘要： The present invention provides compounds having formula (I): and additionally provides methods for the synthesis thereof and methods for the use thereof in the treatment of cancer, wherein R1-R7, X1, X2, R, Q, and n are as defined herein.
摘要翻译：本发明提供具有式（I）的化合物：另外提供其合成方法及其用于治疗癌症的方法，其中R1-R7，X1，X2，R，Q和n如本文所定义。

6. 发明授权

US07192972B2 Hemiasterlin derivatives and uses thereof 有权
标题翻译：半精球蛋白衍生物及其用途
公开(公告)号：US07192972B2
公开(公告)日：2007-03-20
申请号：US10508607
申请日：2003-03-21
申请人： James J. Kowalczyk , Galina Kuznetsov , Shawn Schiller , Boris M. Seletsky , Mark Spyvee , Hu Yang
发明人： James J. Kowalczyk , Galina Kuznetsov , Shawn Schiller , Boris M. Seletsky , Mark Spyvee , Hu Yang
IPC分类号： C07D211/32 , A61K31/445
CPC分类号： C07K7/06 , A61K38/05 , A61K38/06 , A61K38/07 , A61K38/08 , C07C237/22 , C07D207/08 , C07D207/16 , C07D211/60 , C07D295/185 , C07D401/14 , C07K5/06078 , C07K5/06156 , C07K5/06165 , C07K5/0808 , C07K5/0821 , C07K5/0823 , C07K5/1016
摘要： The present invention provides compounds having formula (I): and additionally provides methods for the synthesis thereof and methods for the use thereof in the treatment of cancer, wherein R1–R7, X1, X2, R, Q, and n are as defined herein.
摘要翻译：本发明提供具有式（I）的化合物：另外提供其合成方法及其用于治疗癌症的方法，其中R 1 -R 7 X 1，X 2，R 3，Q 3和n如本文所定义。

7. 发明授权

US07064211B2 Hemiasterlin derivatives and uses thereof 失效
标题翻译：半精球蛋白衍生物及其用途
公开(公告)号：US07064211B2
公开(公告)日：2006-06-20
申请号：US10667864
申请日：2003-09-22
申请人： James J. Kowalczyk , Galina Kuznetsov , Shawn Schiller , Boris M. Seletsky , Mark Spyvee , Hu Yang
发明人： James J. Kowalczyk , Galina Kuznetsov , Shawn Schiller , Boris M. Seletsky , Mark Spyvee , Hu Yang
IPC分类号： C07D211/30 , A61K31/445
CPC分类号： C07D207/04 , C07D207/12 , C07D207/16 , C07D207/42 , C07D209/20 , C07D211/60 , C07D217/26 , C07D223/06 , C07D233/84 , C07D237/04 , C07D241/04 , C07D265/30 , C07D277/06 , C07D279/12 , C07D401/06 , C07D401/12 , C07D401/14 , C07D403/06 , C07D405/12 , C07D471/04 , C07K5/0205 , C07K5/0207 , C07K5/0821
摘要： The present invention provides compounds having formula (I): and additionally provides methods for the synthesis thereof and methods for the use thereof in the treatment of cancer, wherein R1–R7, X1, X2, R, Q, and n are as defined herein.
摘要翻译：本发明提供具有式（I）的化合物：另外提供其合成方法及其用于治疗癌症的方法，其中R 1 -R 7 X 1，X 2，R 3，Q 3和n如本文所定义。

8. 发明申请

US20060154312A1 Tubulin isotype screening in cancer therapy using halichondrin B analogs 审中-公开
标题翻译：使用软骨素B类似物的癌症治疗中的微管蛋白同种型筛选
公开(公告)号：US20060154312A1
公开(公告)日：2006-07-13
申请号：US11299260
申请日：2005-12-07
申请人： Sergei Agoulnik , Galina Kuznetsov , Bruce Littlefield
发明人： Sergei Agoulnik , Galina Kuznetsov , Bruce Littlefield
IPC分类号： G01N33/574 , A61K31/353
CPC分类号： A61K31/353 , G01N33/5091 , G01N33/574 , G01N33/57407 , G01N33/57496 , G01N2500/00 , Y10T436/143333
摘要： Chemotherapeutic agents that interfere with microtubule assembly or disassembly in the cell are potent inhibitors of cell replication. Examples of such agents include halichondrin B analogs. It has been shown that the susceptibility of certain cancers to analogs of halichondrin B correlates with the expression of particular tubulin isotypes or other microtubule-associated proteins such as MAP-4 and stathmin. Correlations such as these may be used in identifying patients suitable for treatment using a particular chemotherapeutic agent. Such a system avoids treating patients with cytotoxic compounds where there is a minimal or no effect on the cancer. The invention also provides a system of establishing these correlations for different compounds and cancer types. The system will be particularly useful in establishing correlations between anti-microtubule agents and cancers such as lung, breast, and ovarian cancer. Kits and reagents useful in practicing the invention are also provided.
摘要翻译：影响细胞中微管组装或分解的化学治疗剂是细胞复制的有效抑制剂。这些试剂的实例包括软骨素B类似物。已经显示某些癌症对软骨素B类似物的易感性与特定的微管蛋白同种型或其它微管相关蛋白如MAP-4和stathmin的表达相关。诸如这些的相关性可以用于鉴定适合于使用特定化学治疗剂的治疗的患者。这样的系统避免了治疗患有细胞毒性化合物的患者，其中对癌症最小或没有影响。本发明还提供了一种为不同化合物和癌症类型建立这些相关性的系统。该系统将特别有用于建立抗微管剂和肺癌，乳腺癌和卵巢癌等癌症之间的相关性。还提供了可用于实践本发明的试剂盒和试剂。

9. 发明申请

US20100190843A1 Tubulin Isotype Screening in Cancer Therapy Using Halichondrin B Analogs 审中-公开
标题翻译：使用Halichondrin B类似物的癌症治疗中的微管蛋白同种型筛选
公开(公告)号：US20100190843A1
公开(公告)日：2010-07-29
申请号：US12534277
申请日：2009-08-03
申请人： Sergei Agoulnik , Galina Kuznetsov , Bruce A. Littlefield
发明人： Sergei Agoulnik , Galina Kuznetsov , Bruce A. Littlefield
IPC分类号： A61K31/335 , C07H21/04 , G01N33/68 , C12Q1/02 , G01N33/48 , C12Q1/68 , C40B30/04 , G01N33/53 , A61P35/00
CPC分类号： A61K31/353 , G01N33/5091 , G01N33/574 , G01N33/57407 , G01N33/57496 , G01N2500/00 , Y10T436/143333
摘要： Chemotherapeutic agents that interfere with microtubule assembly or disassembly in the cell are potent inhibitors of cell replication. Examples of such agents include halichondrin B analogs. It has been shown that the susceptibility of certain cancers to analogs of halichondrin B correlates with the expression of particular tubulin isotypes or other microtubule-associated proteins such as MAP-4 and stathmin. Correlations such as these may be used in identifying patients suitable for treatment using a particular chemotherapeutic agent. Such a system avoids treating patients with cytotoxic compounds where there is a minimal or no effect on the cancer. The invention also provides a system of establishing these correlations for different compounds and cancer types. The system will be particularly useful in establishing correlations between anti-microtubule agents and cancers such as lung, breast, and ovarian cancer. Kits and reagents useful in practicing the invention are also provided.
摘要翻译：影响细胞中微管组装或分解的化学治疗剂是细胞复制的有效抑制剂。这些试剂的实例包括软骨素B类似物。已经显示某些癌症对软骨素B类似物的易感性与特定的微管蛋白同种型或其它微管相关蛋白如MAP-4和stathmin的表达相关。诸如这些的相关性可以用于鉴定适合于使用特定化学治疗剂的治疗的患者。这样的系统避免了治疗患有细胞毒性化合物的患者，其中对癌症最小或没有影响。本发明还提供了一种为不同化合物和癌症类型建立这些相关性的系统。该系统将特别有用于建立抗微管剂和肺癌，乳腺癌和卵巢癌等癌症之间的相关性。还提供了可用于实践本发明的试剂盒和试剂。

10. 发明申请

US20060148014A1 Tubulin isotype screening in cancer therapy using hemiasterlin analogs 审中-公开
标题翻译：使用半球蛋白类似物的癌症治疗中的微管蛋白同种型筛选
公开(公告)号：US20060148014A1
公开(公告)日：2006-07-06
申请号：US11296920
申请日：2005-12-07
申请人： Sergei Agoulnik , Galina Kuznetsov , Bruce Littlefield
发明人： Sergei Agoulnik , Galina Kuznetsov , Bruce Littlefield
IPC分类号： G01N33/574 , A61K31/44 , A61K31/18 , A61K38/04
CPC分类号： G01N33/57415 , A61K9/06 , A61K31/18 , A61K31/44 , A61K38/04 , G01N33/574 , G01N33/57423 , G01N33/57449 , G01N2333/4703 , G01N2800/44
摘要： Chemotherapeutic agents that interfere with microtubule assembly or disassembly in the cell are potent inhibitors of cell replication. Examples of such agents include hemiasterlin analogs. It has been shown that the susceptibility of certain cancers to analogs of hemiasterlin correlates with the expression of particular tubulin isotypes or other microtubule-associated proteins such as MAP-4 and stathmin. Correlations such as these may be used in identifying patients suitable for treatment using a particular chemotherapeutic agent. Such a system avoids treating patients with cytotoxic compounds where there is a minimal or no effect on the cancer. The invention also provides a system of establishing these correlations for different compounds and cancer types. The system will be particularly useful in establishing correlations between anti-microtubule agents and cancers such as lung, breast, and ovarian cancer. Kits and reagents useful in practicing the invention are also provided.
摘要翻译：影响细胞中微管组装或分解的化学治疗剂是细胞复制的有效抑制剂。这些药剂的实例包括半球蛋白类似物。已经表明，某些癌症对半细胞因子类似物的易感性与特定的微管蛋白同种型或其它微管相关蛋白如MAP-4和stathmin的表达相关。诸如这些的相关性可以用于鉴定适合于使用特定化学治疗剂的治疗的患者。这样的系统避免了治疗患有细胞毒性化合物的患者，其中对癌症最小或没有影响。本发明还提供了一种为不同化合物和癌症类型建立这些相关性的系统。该系统将特别有用于建立抗微管剂和肺癌，乳腺癌和卵巢癌等癌症之间的相关性。还提供了可用于实践本发明的试剂盒和试剂。

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