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公开(公告)号：US08168655B2
公开(公告)日：2012-05-01
申请号：US11436906
申请日：2006-05-17
申请人： Thomas Gadek , John Burnier
发明人： Thomas Gadek , John Burnier
IPC分类号： A61K31/47
CPC分类号： A61K31/4725 , A61B3/101 , A61B3/145 , A61K9/0014 , A61K9/0019 , A61K9/0043 , A61K9/0048 , A61K9/0051 , A61K9/0053 , A61K31/197 , A61K31/198 , A61K31/275 , A61K31/341 , A61K31/352 , A61K31/381 , A61K31/40 , A61K31/404 , A61K31/405 , A61K31/4162 , A61K31/4184 , A61K31/4192 , A61K31/44 , A61K31/4709 , A61K31/472 , A61K31/4745 , A61K31/495 , A61K31/496 , A61K31/517 , A61K31/5377 , A61K31/54 , A61K31/541 , A61K33/00 , A61K33/06 , A61K38/07 , A61K38/08 , A61K38/12 , A61K38/1703 , A61K45/06 , C07C279/28 , C07C317/50 , C07D207/06 , C07D217/00 , C07D217/02 , C07D217/06 , C07D217/20 , C07D217/26 , C07D307/52 , C07D333/38 , C07D401/06 , C07D405/06 , C07D405/14 , C07D409/14 , C07D413/14 , C07D471/04 , G01N33/5011 , G01N33/5032 , G01N33/5047 , G01N33/566 , G01N33/6872 , G01N2333/705 , G01N2333/70525 , G01N2333/70546 , G01N2500/02 , G01N2500/04 , G01N2500/10 , G01N2500/20 , G01N2800/16 , Y10S514/912 , Y10S514/914
摘要： The present invention provides compounds and methods for the treatment of LFA-1 mediated diseases. In particular, LFA-1 antagonists are described herein and these antagonists are used in the treatment of LFA-1 mediated diseases. One aspect of the invention provides for diagnosis of an LFA-1 mediated disease and administration of a LFA-1 antagonist, after the patient is diagnosed with a LFA-1 mediated disease. In some embodiments, the LFA-1 mediated diseases treated are dry eye disorders. Also provided herein are methods for identifying compounds which are LFA-1 antagonists.
摘要翻译： 本发明提供了用于治疗LFA-1介导的疾病的化合物和方法。 特别地，本文描述了LFA-1拮抗剂，并且这些拮抗剂用于治疗LFA-1介导的疾病。 在患者被诊断患有LFA-1介导的疾病之后，本发明的一个方面提供LFA-1介导的疾病的诊断和LFA-1拮抗剂的施用。 在一些实施方案中，治疗的LFA-1介导的疾病是干眼症。 本文还提供了用于鉴定LFA-1拮抗剂的化合物的方法。
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公开(公告)号：US20120107404A1
公开(公告)日：2012-05-03
申请号：US13289172
申请日：2011-11-04
申请人： John Burnier , Thomas Gadek , Frederic Naud
发明人： John Burnier , Thomas Gadek , Frederic Naud
IPC分类号： A61K9/14 , A61K31/4725 , A61K31/56 , A61P29/00 , A61P27/02 , A61P27/14 , A61P11/02 , A61P11/06 , A61P17/00 , A61P17/06 , A61P17/08 , A61P17/02 , A61P17/14 , A61K9/00 , C07D405/10 , B82Y5/00
CPC分类号： C07D405/06 , A61K9/06 , A61K9/08 , A61K31/4709 , A61K31/4725 , A61K45/06 , A61K47/02 , A61K47/06 , A61K47/10 , A61K47/14 , A61K47/183 , A61K47/186 , A61K47/22 , A61K47/38 , C07C317/48 , C07D217/02 , C07D217/04 , C07D217/26 , C07D405/10
摘要： Novel crystalline polymorphic forms, Forms A, B, C, D, and E of a compound of Formula I, which has been found to be a potent inhibitor of LFA-1, are disclosed. Methods of preparation and uses thereof in the treatment of LFA-1 mediated diseases are also disclosed in this invention.
摘要翻译： 公开了已被发现是LFA-1的有效抑制剂的式I化合物的新型结晶多晶型物形式A，B，C，D和E。 本发明还公开了其在治疗LFA-1介导的疾病中的制备方法及其用途。
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公开(公告)号：US08080562B2
公开(公告)日：2011-12-20
申请号：US12386361
申请日：2009-04-15
申请人： John Burnier , Thomas Gadek , Frederic Naud
发明人： John Burnier , Thomas Gadek , Frederic Naud
IPC分类号： A61K31/47 , C07D217/02
CPC分类号： C07D405/06 , A61K9/06 , A61K9/08 , A61K31/4709 , A61K31/4725 , A61K45/06 , A61K47/02 , A61K47/06 , A61K47/10 , A61K47/14 , A61K47/183 , A61K47/186 , A61K47/22 , A61K47/38 , C07C317/48 , C07D217/02 , C07D217/04 , C07D217/26 , C07D405/10
摘要： Novel crystalline polymorphic forms, Forms A, B, C, D, and E of a compound of Formula I, which has been found to be a potent inhibitor of LFA-1, are disclosed. Methods of preparation and uses thereof in the treatment of LFA-1 mediated diseases are also disclosed in this invention.
摘要翻译： 公开了已被发现是LFA-1的有效抑制剂的式I化合物的新型结晶多晶型物形式A，B，C，D和E。 本发明还公开了其在治疗LFA-1介导的疾病中的制备方法及其用途。
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公开(公告)号：US08367701B2
公开(公告)日：2013-02-05
申请号：US13289172
申请日：2011-11-04
申请人： John Burnier , Thomas Gadek , Frederic Naud
发明人： John Burnier , Thomas Gadek , Frederic Naud
IPC分类号： A61K31/47 , C07D217/00
CPC分类号： C07D405/06 , A61K9/06 , A61K9/08 , A61K31/4709 , A61K31/4725 , A61K45/06 , A61K47/02 , A61K47/06 , A61K47/10 , A61K47/14 , A61K47/183 , A61K47/186 , A61K47/22 , A61K47/38 , C07C317/48 , C07D217/02 , C07D217/04 , C07D217/26 , C07D405/10
摘要： Novel crystalline polymorphic forms, Forms A, B, C, D, and E of a compound of Formula I, which has been found to be a potent inhibitor of LFA-1, are disclosed. Methods of preparation and uses thereof in the treatment of LFA-1 mediated diseases are also disclosed in this invention.
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公开(公告)号：US20090258069A1
公开(公告)日：2009-10-15
申请号：US12386347
申请日：2009-04-15
申请人： John Burnier , Thomas Gadek
发明人： John Burnier , Thomas Gadek
IPC分类号： A61K9/14 , A61K39/395 , A61K33/30 , A61K33/06 , A61K33/00 , A61K31/56 , A61K31/437 , A61K31/47 , A61K31/165 , A61K31/4725
CPC分类号： A61K31/165 , A61K9/0014 , A61K9/0048 , A61K9/06 , A61K9/08 , A61K31/381 , A61K31/437 , A61K31/47 , A61K31/472 , A61K31/4725 , A61K31/56 , A61K45/06 , A61K2300/00
摘要： The present invention provides compositions and methods for treating disorders and diseases by delivery of LFA-1 antagonists to the gastrointestinal system. Methods include delivery of LFA-1 antagonists to effect localized treatment.
摘要翻译： 本发明提供了通过将LFA-1拮抗剂递送至胃肠系统来治疗疾病和疾病的组合物和方法。 方法包括递送LFA-1拮抗剂以实现局部治疗。
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公开(公告)号：US20120232019A1
公开(公告)日：2012-09-13
申请号：US13398542
申请日：2012-02-16
申请人： Thomas Gadek , John Burnier , Johan Oslob , Wang Shen , Kenneth Barr , Min Zhong
发明人： Thomas Gadek , John Burnier , Johan Oslob , Wang Shen , Kenneth Barr , Min Zhong
IPC分类号： A61K31/473 , A61K31/437 , A61K31/197 , A61K31/343 , C07D409/14 , A61K31/341 , C07D405/14 , C07D471/04 , C07D409/12 , A61K38/02 , A61K31/4015
CPC分类号： A61K31/4725 , A61B3/101 , A61B3/145 , A61K9/0014 , A61K9/0019 , A61K9/0043 , A61K9/0048 , A61K9/0051 , A61K9/0053 , A61K31/197 , A61K31/198 , A61K31/275 , A61K31/341 , A61K31/352 , A61K31/381 , A61K31/40 , A61K31/404 , A61K31/405 , A61K31/4162 , A61K31/4184 , A61K31/4192 , A61K31/44 , A61K31/4709 , A61K31/472 , A61K31/4745 , A61K31/495 , A61K31/496 , A61K31/517 , A61K31/5377 , A61K31/54 , A61K31/541 , A61K33/00 , A61K33/06 , A61K38/07 , A61K38/08 , A61K38/12 , A61K38/1703 , A61K45/06 , C07C279/28 , C07C317/50 , C07D207/06 , C07D217/00 , C07D217/02 , C07D217/06 , C07D217/20 , C07D217/26 , C07D307/52 , C07D333/38 , C07D401/06 , C07D405/06 , C07D405/14 , C07D409/14 , C07D413/14 , C07D471/04 , G01N33/5011 , G01N33/5032 , G01N33/5047 , G01N33/566 , G01N33/6872 , G01N2333/705 , G01N2333/70525 , G01N2333/70546 , G01N2500/02 , G01N2500/04 , G01N2500/10 , G01N2500/20 , G01N2800/16 , Y10S514/912 , Y10S514/914
摘要： The present invention provides compounds and methods for the treatment of LFA-1 mediated diseases. In particular, LFA-1 antagonists are described herein and these antagonists are used in the treatment of LFA-1 mediated diseases. One aspect of the invention provides for diagnosis of an LFA-1 mediated disease and administration of a LFA-1 antagonist, after the patient is diagnosed with a LFA-1 mediated disease. In some embodiments, the LFA-1 mediated diseases treated are dry eye disorders. Also provided herein are methods for identifying compounds which are LFA-1 antagonists.
摘要翻译： 本发明提供了用于治疗LFA-1介导的疾病的化合物和方法。 特别地，本文描述了LFA-1拮抗剂，并且这些拮抗剂用于治疗LFA-1介导的疾病。 在患者被诊断患有LFA-1介导的疾病之后，本发明的一个方面提供LFA-1介导的疾病的诊断和LFA-1拮抗剂的施用。 在一些实施方案中，治疗的LFA-1介导的疾病是干眼症。 本文还提供了用于鉴定LFA-1拮抗剂的化合物的方法。
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公开(公告)号：US20100092542A1
公开(公告)日：2010-04-15
申请号：US12508367
申请日：2009-07-23
申请人： John Burnier , Thomas Gadek , Wang Shen , Johan D. Oslob , Kenneth Barr
发明人： John Burnier , Thomas Gadek , Wang Shen , Johan D. Oslob , Kenneth Barr
IPC分类号： A61K9/00 , A61K9/127 , A61K9/12 , A61K31/4725 , C07D401/14 , A61P27/02
CPC分类号： A61K31/4725 , A61B3/101 , A61B3/145 , A61K9/0014 , A61K9/0019 , A61K9/0043 , A61K9/0048 , A61K9/0051 , A61K9/0053 , A61K31/197 , A61K31/198 , A61K31/275 , A61K31/341 , A61K31/352 , A61K31/381 , A61K31/40 , A61K31/404 , A61K31/405 , A61K31/4162 , A61K31/4184 , A61K31/4192 , A61K31/44 , A61K31/4709 , A61K31/472 , A61K31/4745 , A61K31/495 , A61K31/496 , A61K31/517 , A61K31/5377 , A61K31/54 , A61K31/541 , A61K33/00 , A61K33/06 , A61K38/07 , A61K38/08 , A61K38/12 , A61K38/1703 , A61K45/06 , C07C279/28 , C07C317/50 , C07D207/06 , C07D217/00 , C07D217/02 , C07D217/06 , C07D217/20 , C07D217/26 , C07D307/52 , C07D333/38 , C07D401/06 , C07D405/06 , C07D405/14 , C07D409/14 , C07D413/14 , C07D471/04 , G01N33/5011 , G01N33/5032 , G01N33/5047 , G01N33/566 , G01N33/6872 , G01N2333/705 , G01N2333/70525 , G01N2333/70546 , G01N2500/02 , G01N2500/04 , G01N2500/10 , G01N2500/20 , G01N2800/16 , Y10S514/912 , Y10S514/914
摘要： The present invention provides compounds and methods for the treatment of LFA-1 mediated diseases. In particular, LFA-1 antagonists are described herein and these antagonists are used in the treatment of LFA-1 mediated diseases. One aspect of the invention provides for diagnosis of an LFA-1 mediated disease and administration of a LFA-1 antagonist, after the patient is diagnosed with a LFA-1 mediated disease. In some embodiments, the LFA-1 mediated diseases treated are dry eye disorders. Also provided herein are methods for identifying compounds which are LFA-1 antagonists.
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8.发明申请Aerosolized LFA-1 antagonists for use in localized treatment of immune related disorders 审中-公开用于局部治疗免疫相关疾病的气雾剂LFA-1拮抗剂公开(公告)号：US20090257957A1
公开(公告)日：2009-10-15
申请号：US12386363
申请日：2009-04-15
申请人： John Burnier , Thomas Gadek
发明人： John Burnier , Thomas Gadek
CPC分类号： C07D409/14 , A61K9/0014 , A61K9/0031 , A61K9/0048 , A61K9/008 , A61K9/12 , A61K31/00 , A61K31/381 , A61K31/472 , A61K31/4725 , A61K45/06 , C07D217/04 , C07D333/38 , C07D401/06 , C07D405/06 , C07D409/12
摘要： This invention provides specifically formulated LFA-1 antagonists or pharmaceutically acceptable salts thereof that are suitable for aerosolized delivery. In particular, the LFA-1 antagonists are particularly well suited for localized treatment by having a rapid systemic clearance rate. The invention also encompasses methods of treatment and prevention of immune related disorders using the LFA-1 aerosolized formulations of the present invention.
摘要翻译： 本发明提供了适用于雾化递送的特异性配制的LFA-1拮抗剂或其药学上可接受的盐。 特别地，LFA-1拮抗剂特别适用于通过具有快速的全身清除率的局部治疗。 本发明还包括使用本发明的LFA-1雾化制剂治疗和预防免疫相关疾病的方法。
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公开(公告)号：US08592450B2
公开(公告)日：2013-11-26
申请号：US13398542
申请日：2012-02-16
申请人： Thomas Gadek , John Burnier
发明人： Thomas Gadek , John Burnier
IPC分类号： A61K31/47
CPC分类号： A61K31/4725 , A61B3/101 , A61B3/145 , A61K9/0014 , A61K9/0019 , A61K9/0043 , A61K9/0048 , A61K9/0051 , A61K9/0053 , A61K31/197 , A61K31/198 , A61K31/275 , A61K31/341 , A61K31/352 , A61K31/381 , A61K31/40 , A61K31/404 , A61K31/405 , A61K31/4162 , A61K31/4184 , A61K31/4192 , A61K31/44 , A61K31/4709 , A61K31/472 , A61K31/4745 , A61K31/495 , A61K31/496 , A61K31/517 , A61K31/5377 , A61K31/54 , A61K31/541 , A61K33/00 , A61K33/06 , A61K38/07 , A61K38/08 , A61K38/12 , A61K38/1703 , A61K45/06 , C07C279/28 , C07C317/50 , C07D207/06 , C07D217/00 , C07D217/02 , C07D217/06 , C07D217/20 , C07D217/26 , C07D307/52 , C07D333/38 , C07D401/06 , C07D405/06 , C07D405/14 , C07D409/14 , C07D413/14 , C07D471/04 , G01N33/5011 , G01N33/5032 , G01N33/5047 , G01N33/566 , G01N33/6872 , G01N2333/705 , G01N2333/70525 , G01N2333/70546 , G01N2500/02 , G01N2500/04 , G01N2500/10 , G01N2500/20 , G01N2800/16 , Y10S514/912 , Y10S514/914
摘要： The present invention provides compounds and methods for the treatment of LFA-1 mediated diseases. In particular, LFA-1 antagonists are described herein and these antagonists are used in the treatment of LFA-1 mediated diseases. One aspect of the invention provides for diagnosis of an LFA-1 mediated disease and administration of a LFA-1 antagonist, after the patient is diagnosed with a LFA-1 mediated disease. In some embodiments, the LFA-1 mediated diseases treated are dry eye disorders. Also provided herein are methods for identifying compounds which are LFA-1 antagonists.
摘要翻译： 本发明提供了用于治疗LFA-1介导的疾病的化合物和方法。 特别地，本文描述了LFA-1拮抗剂，并且这些拮抗剂用于治疗LFA-1介导的疾病。 在患者被诊断患有LFA-1介导的疾病之后，本发明的一个方面提供LFA-1介导的疾病的诊断和LFA-1拮抗剂的施用。 在一些实施方案中，治疗的LFA-1介导的疾病是干眼症。 本文还提供了用于鉴定LFA-1拮抗剂的化合物的方法。
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公开(公告)号：US20100092541A1
公开(公告)日：2010-04-15
申请号：US12508311
申请日：2009-07-23
申请人： John Burnier , Thomas Gadek , Min Zhong
发明人： John Burnier , Thomas Gadek , Min Zhong
IPC分类号： A61K9/00 , C07D405/06 , A61K31/4725 , A61K9/127 , A61K9/12
CPC分类号： A61K31/4725 , A61B3/101 , A61B3/145 , A61K9/0014 , A61K9/0019 , A61K9/0043 , A61K9/0048 , A61K9/0051 , A61K9/0053 , A61K31/197 , A61K31/198 , A61K31/275 , A61K31/341 , A61K31/352 , A61K31/381 , A61K31/40 , A61K31/404 , A61K31/405 , A61K31/4162 , A61K31/4184 , A61K31/4192 , A61K31/44 , A61K31/4709 , A61K31/472 , A61K31/4745 , A61K31/495 , A61K31/496 , A61K31/517 , A61K31/5377 , A61K31/54 , A61K31/541 , A61K33/00 , A61K33/06 , A61K38/07 , A61K38/08 , A61K38/12 , A61K38/1703 , A61K45/06 , C07C279/28 , C07C317/50 , C07D207/06 , C07D217/00 , C07D217/02 , C07D217/06 , C07D217/20 , C07D217/26 , C07D307/52 , C07D333/38 , C07D401/06 , C07D405/06 , C07D405/14 , C07D409/14 , C07D413/14 , C07D471/04 , G01N33/5011 , G01N33/5032 , G01N33/5047 , G01N33/566 , G01N33/6872 , G01N2333/705 , G01N2333/70525 , G01N2333/70546 , G01N2500/02 , G01N2500/04 , G01N2500/10 , G01N2500/20 , G01N2800/16 , Y10S514/912 , Y10S514/914
摘要： The present invention provides compounds and methods for the treatment of LFA-1 mediated diseases. In particular, LFA-1 antagonists are described herein and these antagonists are used in the treatment of LFA-1 mediated diseases. One aspect of the invention provides for diagnosis of an LFA-1 mediated disease and administration of a LFA-1 antagonist, after the patient is diagnosed with a LFA-1 mediated disease. In some embodiments, the LFA-1 mediated diseases treated are dry eye disorders. Also provided herein are methods for identifying compounds which are LFA-1 antagonists.
摘要翻译： 本发明提供了用于治疗LFA-1介导的疾病的化合物和方法。 特别地，本文描述了LFA-1拮抗剂，并且这些拮抗剂用于治疗LFA-1介导的疾病。 在患者被诊断患有LFA-1介导的疾病之后，本发明的一个方面提供LFA-1介导的疾病的诊断和LFA-1拮抗剂的施用。 在一些实施方案中，治疗的LFA-1介导的疾病是干眼症。 本文还提供了用于鉴定LFA-1拮抗剂的化合物的方法。
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