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公开(公告)号：US20080248052A1
公开(公告)日：2008-10-09
申请号：US12064191
申请日：2006-08-18
IPC分类号： A61K39/395 , A61P43/00
CPC分类号： A61K47/48338 , A61K47/551 , A61K47/64 , A61K47/65
摘要： Described herein are compounds, pharmaceutical compositions and methods for treating pathogenic cell populations in a patient. The compounds described herein include conjugates of a plurality of cytotoxic drugs and vitamin receptor binding ligands. The plurality of drugs may be the same or different. Similarly, the vitamin receptor binding ligands may be the same or different. The conjugates also include a linker that is formed from one or more spacer linkers, heteroatom linkers, and releasable linkers.
摘要翻译： 本文描述了用于治疗患者中病原体细胞群体的化合物，药物组合物和方法。 本文所述的化合物包括多种细胞毒性药物和维生素受体结合配体的缀合物。 多种药物可以相同或不同。 类似地，维生素受体结合配体可以相同或不同。 缀合物还包括由一个或多个间隔基连接体，杂原子接头和可释放接头形成的接头。
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公开(公告)号：US20120270791A1
公开(公告)日：2012-10-25
申请号：US13440641
申请日：2012-04-05
CPC分类号： A61K51/04 , A61K47/551 , A61K47/552 , A61K49/0002 , A61K51/00 , C07D475/04 , C07D519/00 , C07K7/02
摘要： The invention relates to a method for diagnosing a kidney disease state. The method comprises the steps of administering to a patient a composition comprising a conjugate or complex of the general formula V-L-D where the group V comprises a vitamin receptor binding ligand that binds to kidney proximal tubule cells and the group D comprises a diagnostic marker, and diagnosing the kidney disease state. The invention also relates to a method for treating a kidney disease state. The method comprises the steps of administering to a patient suffering from the disease state an effective amount of a composition comprising a conjugate or complex of the general formula V-L-D where the group V comprises a vitamin receptor binding ligand that binds to kidney proximal tubule cells and the group D comprises an antigen, a cytotoxin, or a cell growth inhibitor, and eliminating the disease state.
摘要翻译： 本发明涉及诊断肾脏疾病状态的方法。 该方法包括以下步骤：向患者施用包含通式VLD的缀合物或复合物的组合物，其中组V包含结合肾近端小管细胞的维生素受体结合配体，D组包括诊断标记物，并诊断 肾脏疾病状态。 本发明还涉及治疗肾脏疾病状态的方法。 该方法包括以下步骤：向患有疾病状态的患者施用有效量的包含通式VLD的缀合物或复合物的组合物，其中组V包含结合肾近端小管细胞的维生素受体结合配体， D组包含抗原，细胞毒素或细胞生长抑制剂，并消除疾病状态。
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公开(公告)号：US20110172254A1
公开(公告)日：2011-07-14
申请号：US13063889
申请日：2009-09-17
IPC分类号： A61K31/519 , A61K31/517 , C07D471/04 , C07D239/72 , A61P35/00
CPC分类号： A61K47/48338 , A61K31/475 , A61K31/517 , A61K47/55 , A61K47/551 , C07D487/04
摘要： Conjugates of antifolates, releasable linkers, and drugs, and pharmaceutical compositions containing them are described. The conjugates are useful for treating diseases arising from pathogenic cell populations. Methods for treating such diseases are also described.
摘要翻译： 描述了抗叶酸剂，可释放接头和药物的结合物，以及含有它们的药物组合物。 缀合物可用于治疗由致病细胞群体引起的疾病。 还描述了治疗这些疾病的方法。
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公开(公告)号：US08546425B2
公开(公告)日：2013-10-01
申请号：US13063889
申请日：2009-09-17
IPC分类号： A01N43/90 , A61K31/44 , C07D239/72
CPC分类号： A61K47/48338 , A61K31/475 , A61K31/517 , A61K47/55 , A61K47/551 , C07D487/04
摘要： Conjugates of antifolates, releasable linkers, and drugs, and pharmaceutical compositions containing them are described. The conjugates are useful for treating diseases arising from pathogenic cell populations. Methods for treating such diseases are also described.
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公开(公告)号：US20130065841A1
公开(公告)日：2013-03-14
申请号：US13698215
申请日：2011-05-19
CPC分类号： C07K7/02 , A61K47/551
摘要： The invention described herein pertains to an improved process for preparing the folate-targeted conjugate EC 145 and to the conjugate EC 145 prepared using the improved process, as well as to a pharmaceutical composition comprising the conjugate EC 145 prepared using the improved process.
摘要翻译： 本文描述的本发明涉及用于制备叶酸靶向缀合物EC 145和使用改进方法制备的缀合物EC 145的改进方法，以及包含使用改进方法制备的缀合物EC 145的药物组合物。
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公开(公告)号：US07910594B2
公开(公告)日：2011-03-22
申请号：US10513372
申请日：2003-05-13
IPC分类号： A61K31/40 , A61K51/00 , A61P35/00 , A61M36/14 , C07D487/14
CPC分类号： C07D475/04 , A61K47/551
摘要： This invention relates to vitamin-mitomycin conjugates, to a method of using the conjugates to selectively eliminate a population of pathogenic cells in a host animal harboring the pathogenic cells, and to a method of preparation of the conjugates. The conjugate is of the general formula B-L-X wherein the group B is a vitamin, or an analog or a derivative thereof, that binds to a surface accessible vitamin receptor that is uniquely expressed, overexpressed, or preferentially expressed by a population of pathogenic cells, wherein the group L comprises a cleavable linker, and wherein the group X comprises a mitomycin compound, or an analog or a derivative thereof. An additional therapeutic agent, such as a chemotherapeutic agent, can be administered in combination with the conjugate.
摘要翻译： 本发明涉及维生素丝裂霉素缀合物，涉及一种使用该缀合物选择性地消除携带致病细胞的宿主动物中的病原细胞群的方法，以及该缀合物的制备方法。 缀合物是通式BLX，其中B组是维生素或其类似物或衍生物，其结合表达可获得的维生素受体，所述维生素受体是唯一表达，过表达或优先由病原细胞群体表达的，其中 组L包含可切割的接头，并且其中组X包含丝裂霉素化合物或其类似物或衍生物。 可以与缀合物组合施用另外的治疗剂，例如化学治疗剂。
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公开(公告)号：US09187521B2
公开(公告)日：2015-11-17
申请号：US12739579
申请日：2008-10-23
IPC分类号： A61K31/445 , C07K5/02
CPC分类号： C07K5/021 , C07K5/06139
摘要： Processes are described for the preparation of tubulysins. The processes are useful for preparing predetermined mixtures of tubulysins, preparing single tubulysins from mixtures of tubulysins, and for converting one tubulysin into a different tubulysin. The tubulysins described herein are useful in treating diseases and disease states that include pathogenic cell populations.
摘要翻译： 描述了制备肾上腺素的方法。 这些方法可用于制备预混合的肾上腺素的混合物，由tubulininins混合物制备单一的tubulinins，并将一种tubulyin转化成不同的tubulysin。 本文所述的管状体素可用于治疗包括致病细胞群体的疾病和疾病状态。
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公开(公告)号：US20130116195A1
公开(公告)日：2013-05-09
申请号：US13507076
申请日：2012-06-01
IPC分类号： A61K38/08
CPC分类号： A61K38/08 , A61K47/551 , A61K47/595
摘要： Described herein are compounds, pharmaceutical compositions, and methods for treating pathogenic cell populations. Kits including the compounds or pharmaceutical compositions are described. The compounds described herein include conjugates of tubulysins and folates. The conjugates also include a releasable bivalent linker.
摘要翻译： 本文描述了用于治疗致病细胞群体的化合物，药物组合物和方法。 描述了包括化合物或药物组合物的试剂盒。 本文所述的化合物包括肾上腺素和叶酸盐的缀合物。 缀合物还包括可释放的二价连接体。
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公开(公告)号：US08288557B2
公开(公告)日：2012-10-16
申请号：US11632895
申请日：2005-07-22
IPC分类号： C07D213/64 , C07D249/18
CPC分类号： C07D213/71 , A61K47/551 , A61K47/6803 , A61K49/0002 , C07D401/12 , C07D475/04
摘要： Bivalent linkers derived from compounds of formulae (V), (VI), and (VII), where X1 and X2 are leaving groups and the other variables are as defined in the claims, to be included in or for preparing vitamin, drug, diagnostic agent, and/or imaging agent conjugates are described.
摘要翻译： 衍生自式（V），（VI）和（VII）的化合物的二价连接体，其中X1和X2是离去基团，其它变量如权利要求中所定义，被包括在维生素，药物，诊断中 试剂和/或成像剂共轭物。
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公开(公告)号：US20100323973A1
公开(公告)日：2010-12-23
申请号：US12666712
申请日：2008-06-25
申请人： Christopher Paul Leamon , Iontcho Radoslavov Vlahov , Hari Krishna R. Santhapuram , Paul Joseph Kleindl , Yu Wang , Fei You
发明人： Christopher Paul Leamon , Iontcho Radoslavov Vlahov , Hari Krishna R. Santhapuram , Paul Joseph Kleindl , Yu Wang , Fei You
IPC分类号： A61K38/14 , C07K5/093 , A61K38/06 , A61K38/08 , A61P35/00 , C07K7/06 , C07K7/64 , A61K38/12 , C07K9/00 , A61P31/04 , A61P31/12 , A61P31/10 , A61P33/10 , A61P33/04 , A61P33/02
CPC分类号： C07K9/003 , A61K47/555 , A61K47/60 , A61K47/65 , C07H15/24
摘要： Described herein are compositions and methods for use in targeted drug delivery using cell receptor binding drug delivery conjugates containing hydrophilic spacer linkers for use in imaging, diagnosing, and/or treating diseases and disease states caused by pathogenic cell populations.
摘要翻译： 本文描述了使用含有用于成像，诊断和/或治疗由致病细胞群体引起的疾病和疾病状态的亲水性间隔物接头的细胞受体结合药物递送缀合物用于靶向药物递送的组合物和方法。
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