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1. 发明授权

US08901118B2 Compounds and methods for kinase modulation, and indications therefor 有权
标题翻译：用于激酶调节的化合物和方法及其适应症
公开(公告)号：US08901118B2
公开(公告)日：2014-12-02
申请号：US13090969
申请日：2011-04-20
申请人： Jiazhong Zhang , Prabha N. Ibrahim , Wayne Spevak , Jianming Tsai , Todd Ewing , Ying Zhang , Chao Zhang
发明人： Jiazhong Zhang , Prabha N. Ibrahim , Wayne Spevak , Jianming Tsai , Todd Ewing , Ying Zhang , Chao Zhang
IPC分类号： C07D487/04 , A61K31/519 , C07D471/04 , A61P19/02 , A61P19/10 , A61P25/28 , A61P29/00 , A61K31/437
CPC分类号： C07D487/04 , C07D471/04
摘要： Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described, wherein the compounds have formula I: In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof are active on one or more of Fms, Kit, Flt3, TrkA, TrkB and TrkC kinase protein. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of one or more of Fms, Kit, Flt3, TrkA, TrkB and TrkC, including rheumatoid arthiritis, osteoarthritis, osteoporosis, peri-prosthetic osteolysis, systemic sclerosis, demyelinating disorders, multiple sclerosis, Charcot Marie Tooth syndrome, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, global ischemia, ulcerative colitis, Crohn's disease, immune thrombocytopenic purpura, atherosclerosis, systemic lupus erythematosis, myelopreparation for autologous transplantation, transplant rejection, glomerulonephritis, interstitial nephritis, Lupus nephritis, tubular necrosis, diabetic nephropathy, renal hypertrophy, type I diabetes, acute pain, inflammatory pain, neuropathic pain, acute myeloid leukemia, melanoma, multiple myeloma, breast cancer, prostate cancer, pancreatic cancer, lung cancer, ovarian cancer, gliomas, glioblastoma, neurofibromatosis, osteolytic bone metastases, brain metasteses, gastrointestinal stromal tumors, and giant cell tumors.
摘要翻译：描述了其化合物和盐，其制剂，其缀合物，其衍生物，其形式及其用途，其中所述化合物具有式I：在某些方面和实施方案中，所述的化合物或其盐，其制剂，其缀合物，其衍生物其形式在Fms，Kit，Flt3，TrkA，TrkB和TrkC激酶蛋白中的一种或多种上是有活性的。还描述了其用于治疗疾病和病症的方法，包括与Fms，Kit，Flt3，TrkA，TrkB和TrkC中的一种或多种的活性相关的疾病和病症，包括类风湿性关节炎，骨关节炎，骨质疏松症，假体周围骨质溶解，系统性硬化症，脱髓鞘疾病，多发性硬化症，Charcot玛丽牙综合征，肌萎缩性侧索硬化症，阿尔茨海默氏病，帕金森病，全球缺血，溃疡性结肠炎，克罗恩病，免疫性血小板减少性紫癜，动脉粥样硬化，系统性红斑狼疮，自体移植骨髓移植，移植排斥肾小球肾炎，间质性肾炎，狼疮性肾炎，肾小管坏死，糖尿病性肾病，肾肥大，I型糖尿病，急性疼痛，炎性疼痛，神经性疼痛，急性骨髓性白血病，黑素瘤，多发性骨髓瘤，乳腺癌，前列腺癌，胰腺癌，肺癌癌症，卵巢癌，神经胶质瘤，成胶质细胞瘤，神经纤维瘤病，溶骨性骨转移，脑转移，胃肠道间质瘤和巨细胞瘤。

2. 发明授权

US5763198A Screening assays for compounds 失效
标题翻译：化合物的筛选试验
公开(公告)号：US5763198A
公开(公告)日：1998-06-09
申请号：US279321
申请日：1994-07-22
申请人： Klaus Peter Hirth , Harald App , Jianming Tsai
发明人： Klaus Peter Hirth , Harald App , Jianming Tsai
IPC分类号： G01N33/68 , G01N33/543
CPC分类号： G01N33/6842 , G01N33/68 , G01N2333/9121
摘要： The invention is directed to rapid and quantitative assay systems for screening test compounds for their ability to modulate tyrosine kinase or phosphatase activities involved in signal transduction by determining the tyrosine phosphorylation state of a protein substrate using an anti-phosphotyrosine antibody and an antibody specific for the protein substrate. These assays may be practiced in a whole cell or cell-free system. The assays can be used to identify test compounds for use in therapeutic applications to disease processes in which tyrosine kinase or phosphatase activity in a signal transduction pathway contributes to a pathological process.
摘要翻译：本发明涉及快速和定量的测定系统，用于通过使用抗磷酸酪氨酸抗体和特异于抗磷酸酪氨酸抗体测定蛋白质底物的酪氨酸磷酸化状态来筛选测试化合物的调节酪氨酸激酶或参与信号转导的磷酸酶活性的能力蛋白质底物。这些测定可以在整个细胞或无细胞系统中实施。该测定可用于鉴定用于治疗应用于疾病过程的测试化合物，其中信号转导途径中的酪氨酸激酶或磷酸酶活性有助于病理过程。

3. 发明授权

US5789427A Methods and compositions for inhibiting cell proliferative disorders 失效
公开(公告)号：US5789427A
公开(公告)日：1998-08-04
申请号：US399967
申请日：1995-03-07
申请人： Hui Chen , Aviv Gazit , Klaus Peter Hirth , Elaina Mann , Laura K. Shawver , Jianming Tsai , Peng Cho Tang
发明人： Hui Chen , Aviv Gazit , Klaus Peter Hirth , Elaina Mann , Laura K. Shawver , Jianming Tsai , Peng Cho Tang
IPC分类号： A61K31/245 , A61K31/277 , A61K31/415 , A61K31/4184 , A61K31/4402 , A61K31/498 , A61K31/517 , C07C229/60 , C07C255/36 , C07C255/37 , C07C255/41 , C07C255/42 , C07C255/66 , C07C311/27 , C07C317/46 , C07C327/44 , C07D241/52 , A01N43/40 , C07D211/72
CPC分类号： C07D241/52 , A61K31/245 , A61K31/277 , A61K31/415 , A61K31/4184 , A61K31/4402 , A61K31/498 , A61K31/517 , C07C229/60 , C07C255/36 , C07C255/37 , C07C255/41 , C07C255/42 , C07C255/66 , C07C311/27 , C07C317/46 , C07C327/44
摘要： The present invention concerns compounds and their use to inhibit the activity of a receptor tyrosine kinase. The invention is preferably used to treat cell proliferative disorders such as cancers characterized by over-activity or inappropriate activity HER2 or EGFR.

4. 发明授权

US5773476A Methods and compositions for inhibiting cell proliferative disorders 失效
公开(公告)号：US5773476A
公开(公告)日：1998-06-30
申请号：US486775
申请日：1995-06-07
申请人： Hui Chen , Aviv Gazit , Alexander Levitzki , Klaus Peter Hirth , Elaina Mann , Laura K. Shawver , Jianming Tsai , Peng Cho Tang
发明人： Hui Chen , Aviv Gazit , Alexander Levitzki , Klaus Peter Hirth , Elaina Mann , Laura K. Shawver , Jianming Tsai , Peng Cho Tang
IPC分类号： A61K31/245 , A61K31/277 , A61K31/415 , A61K31/4184 , A61K31/4402 , A61K31/498 , A61K31/517 , C07C229/60 , C07C255/36 , C07C255/37 , C07C255/41 , C07C255/42 , C07C255/66 , C07C311/27 , C07C317/46 , C07C327/44 , C07D241/52 , A01N37/18
CPC分类号： C07D241/52 , A61K31/245 , A61K31/277 , A61K31/415 , A61K31/4184 , A61K31/4402 , A61K31/498 , A61K31/517 , C07C229/60 , C07C255/36 , C07C255/37 , C07C255/41 , C07C255/42 , C07C255/66 , C07C311/27 , C07C317/46 , C07C327/44
摘要： The present invention concerns compounds and their use to inhibit the activity of a receptor tyrosine kinase. The invention is preferably used to treat cell proliferative disorders such as cancers charcterized by over-activity or inappropriate activity HER2 or EGFR.

5. 发明授权

US07217737B2 Method and compositions for inhibiting cell proliferative disorders 失效
标题翻译：用于抑制细胞增殖性疾病的方法和组合物
公开(公告)号：US07217737B2
公开(公告)日：2007-05-15
申请号：US10602617
申请日：2003-06-25
申请人： Hui Chen , Aviv Gazit , Alexander Levitzki , Klaus Peter Hirth , Elaina Mann , Peng Cho Tang , Laura K. Shawver , Jianming Tsai
发明人： Hui Chen , Aviv Gazit , Alexander Levitzki , Klaus Peter Hirth , Elaina Mann , Peng Cho Tang , Laura K. Shawver , Jianming Tsai
IPC分类号： A61K31/275
CPC分类号： C07D241/52 , A61K31/245 , A61K31/277 , A61K31/415 , A61K31/4184 , A61K31/4402 , A61K31/498 , A61K31/517 , C07C229/60 , C07C255/36 , C07C255/37 , C07C255/41 , C07C255/42 , C07C255/66 , C07C311/27 , C07C317/46 , C07C327/44
摘要： The present invention concerns compounds and their use to inhibit the activity of a receptor tyrosine kinase. The invention is preferably used to treat cell proliferative disorders such as cancers characterized by over-activity or inappropriate activity HER2 or EGFR.
摘要翻译：本发明涉及化合物及其抑制受体酪氨酸激酶活性的用途。本发明优选用于治疗细胞增殖性疾病，例如以过度活动或不适当活性HER2或EGFR为特征的癌症。

6. 发明授权

US06596878B2 Methods and compositions for inhibiting cell proliferative disorders 失效
标题翻译：用于抑制细胞增殖性疾病的方法和组合物
公开(公告)号：US06596878B2
公开(公告)日：2003-07-22
申请号：US09953933
申请日：2001-09-18
申请人： Hui Chen , Aviv Gazit , Alexander Levitzki , Klaus Peter Hirth , Elaina Mann , Laura K. Shawver , Jianming Tsai , Peng Cho Tang
发明人： Hui Chen , Aviv Gazit , Alexander Levitzki , Klaus Peter Hirth , Elaina Mann , Laura K. Shawver , Jianming Tsai , Peng Cho Tang
IPC分类号： C07D23138
CPC分类号： C07D241/52 , A61K31/245 , A61K31/277 , A61K31/415 , A61K31/4184 , A61K31/4402 , A61K31/498 , A61K31/517 , C07C229/60 , C07C255/36 , C07C255/37 , C07C255/41 , C07C255/42 , C07C255/66 , C07C311/27 , C07C317/46 , C07C327/44
摘要： The present invention concerns compounds and their use to inhibit the activity of a receptor tyrosine kinase. The invention is preferably used to treat cell proliferative disorders such as cancers characterized by over-activity or inappropriate activity HER2 or EGFR.
摘要翻译：本发明涉及化合物及其抑制受体酪氨酸激酶活性的用途。本发明优选用于治疗细胞增殖性疾病，例如以过度活动或不适当活性HER2或EGFR为特征的癌症。

7. 发明授权

US08470818B2 Compounds and methods for kinase modulation, and indications therefor 有权
标题翻译：用于激酶调节的化合物和方法及其适应症
公开(公告)号：US08470818B2
公开(公告)日：2013-06-25
申请号：US12906980
申请日：2010-10-18
申请人： Prabha N. Ibrahim , Dean R. Artis , Ryan Bremer , Shumeye Mamo , Chao Zhang , Jiazhong Zhang , Jianming Tsai , Klaus-Peter Hirth , Gideon Bollag , Wayne Spevak , Hanna Cho , Samuel J. Gillette , Shenghua Shi
发明人： Prabha N. Ibrahim , Dean R. Artis , Ryan Bremer , Shumeye Mamo , Chao Zhang , Jiazhong Zhang , Jianming Tsai , Klaus-Peter Hirth , Gideon Bollag , Wayne Spevak , Hanna Cho , Samuel J. Gillette , Shenghua Shi
IPC分类号： A61K31/535
CPC分类号： C07D471/04 , A61K31/437 , A61K31/496 , A61K31/5377 , C07C37/62 , C07C39/27 , C07C45/00 , C07C45/673 , C07C45/71 , C07C47/565 , C07C47/575 , C07D209/08
摘要： Compounds active on protein kinases are described, as well as methods of using such compounds to treat diseases and conditions associated with aberrant activity of protein kinases.
摘要翻译：描述了对蛋白激酶有活性的化合物，以及使用这些化合物治疗与蛋白激酶异常活性相关的疾病和病症的方法。

8. 发明授权

US08415469B2 Compounds and methods for kinase modulation, and indications therefor 有权
公开(公告)号：US08415469B2
公开(公告)日：2013-04-09
申请号：US12616079
申请日：2009-11-10
申请人： Prabha N. Ibrahim , Dean R. Artis , Ryan Bremer , Gaston Habets , Shumeye Mamo , Marika Nespi , Chao Zhang , Jiazhong Zhang , Yong-Liang Zhu , Rebecca Zuckerman , Brian West , Yoshisa Suzuki , Jianming Tsai , Klaus-Peter Hirth , Gideon Bollag , Wayne Spevak , Hanna Cho , Samuel J. Gillette , Guoxian Wu , Hongyao Zhu , Shenghua Shi
发明人： Prabha N. Ibrahim , Dean R. Artis , Ryan Bremer , Gaston Habets , Shumeye Mamo , Marika Nespi , Chao Zhang , Jiazhong Zhang , Yong-Liang Zhu , Rebecca Zuckerman , Brian West , Yoshisa Suzuki , Jianming Tsai , Klaus-Peter Hirth , Gideon Bollag , Wayne Spevak , Hanna Cho , Samuel J. Gillette , Guoxian Wu , Hongyao Zhu , Shenghua Shi
IPC分类号： C07D413/14 , C07D401/14 , C07D471/04 , C07F7/02
CPC分类号： C07D471/04 , A61K31/437 , A61K31/496 , A61K31/5377 , C07C37/62 , C07C39/27 , C07C45/00 , C07C45/673 , C07C45/71 , C07C47/565 , C07C47/575 , C07D209/08
摘要： Compounds active on protein kinases are described, as well as methods of using such compounds to treat diseases and conditions associated with aberrant activity of protein kinases.

9. 发明授权

US5980034A Cross flow nozzle system for an ink jet printer 失效
标题翻译：用于喷墨打印机的横流喷嘴系统
公开(公告)号：US5980034A
公开(公告)日：1999-11-09
申请号：US613838
申请日：1996-03-11
申请人： Jianming Tsai , Pietro Lostumbo
发明人： Jianming Tsai , Pietro Lostumbo
IPC分类号： B41J2/175 , B41J2/165 , B41J2/17 , B41J2/18
CPC分类号： B41J2/1707 , B41J2/1652
摘要： An anti-clogging nozzle system for a continuous jet ink jet printer is disclosed. A printing nozzle has both an ink inlet and an ink outlet permitting constant ink flow behind the nozzle orifice during printing. A pressure sensor monitors the ink flow and signals clogs to an automatic unclogging system. The unclogging system includes a control circuit to initiate an unclogging operating cycle when necessary. One of two unclogging modes is employed, both of which require the control system to operate an unclogging valve to vary pressure in the ink return line.
摘要翻译：公开了一种用于连续喷墨打印机的防堵塞喷嘴系统。印刷喷嘴具有墨水入口和墨水出口，允许在打印期间喷嘴孔后方持续的墨水流动。压力传感器监测墨水流量，并将信号发送到自动停止系统。防盗系统包括一个控制电路，用于在必要时启动一个停止运行循环。采用两种不结冰模式之一，两者都要求控制系统操作一个不堵塞阀，以改变油墨返回管路中的压力。

10. 发明授权

US5646663A Method and apparatus for continuous ink jet printing with a non-sinusoidal driving waveform 失效
标题翻译：具有非正弦驱动波形的连续喷墨打印的方法和装置
公开(公告)号：US5646663A
公开(公告)日：1997-07-08
申请号：US307193
申请日：1994-09-16
申请人： James E. Clark , Mairi C. MacLean , Jianming Tsai
发明人： James E. Clark , Mairi C. MacLean , Jianming Tsai
IPC分类号： B41J2/025 , B41J2/02 , B41J2/07
CPC分类号： B41J2/025
摘要： An apparatus and method for producing a stream of ink drops in a continuous ink jet printer having a maximum allowable number of fast satellite drops. An ink, which may be a hot-melt ink in its liquid phase, is pressurized for continuous flow to a nozzle and a rectangular or triangular waveform is generated at a fixed frequency. The waveform is applied to a transducer coupled to the nozzle such that nozzle vibrates and the ink flow is perturbed and discharged from the nozzle as primary drops with satellite drops formed therewith. The harmonic content of the rectangular or triangular waveform is adjusted until the desired number of fast satellite drops suitable for desired image formation are formed in the stream of primary drops. In a preferred embodiment, the desired number of fast satellites is a maximum of three.
摘要翻译：一种用于在具有最大容许数量的快速卫星滴的连续喷墨打印机中产生墨滴流的装置和方法。可以是其液相中的热熔油墨的油墨被加压以连续流向喷嘴，并且以固定频率产生矩形或三角波形。该波形被施加到耦合到喷嘴的传感器，使得喷嘴振动并且墨水流被扰动并从喷嘴排出，因为与其形成的卫星滴一起滴下。调整矩形或三角波形的谐波含量，直到在初级液滴流中形成适合于期望的图像形成的所需数量的快速卫星下落。在优选实施例中，所需数量的快速卫星最多为三个。

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