公开(公告)号：US06441163B1

公开(公告)日：2002-08-27

申请号：US09867598

申请日：2001-05-31

申请人： Ravi V. J. Chari ,  Wayne C. Widdison

发明人： Ravi V. J. Chari ,  Wayne C. Widdison

IPC分类号： C07D49112

CPC分类号： C07D498/18

摘要： The present invention discloses a one-step process for the production of cytotoxic conjugates of maytansinoids and cell binding agents. Maytansinoids having a disulfide linker that bears a reactive moiety are linked to cell binding agents, such as antibodies, without prior modification of the cell binding agent. These conjugates are useful as therapeutic agents which are delivered specifically to target cells and are cytotoxic.

摘要翻译： 本发明公开了一种用于生产美登木素生物碱和细胞结合剂的细胞毒性缀合物的一步法。 具有带有反应性部分的二硫键连接体的美登木素生物碱与细胞结合剂（例如抗体）连接，而无需先前修饰细胞结合剂。 这些缀合物可用作特异性递送至靶细胞并具有细胞毒性的治疗剂。

公开(公告)号：US08765740B2

公开(公告)日：2014-07-01

申请号：US13397195

申请日：2012-02-15

申请人： Wei Li ,  Michael Miller ,  Nathan Fishkin ,  Ravi V. J. Chari

发明人： Wei Li ,  Michael Miller ,  Nathan Fishkin ,  Ravi V. J. Chari

IPC分类号： C07D519/00 ,  A61K31/5517 ,  A61K31/55 ,  A61P35/00

CPC分类号： C07K16/30 ,  A61K31/5517 ,  A61K45/06 ,  A61K47/545 ,  A61K47/6803 ,  A61K47/6849 ,  A61K47/6851 ,  A61K47/6867 ,  A61K2039/505 ,  C07D487/04 ,  C07D519/00 ,  C07K2317/24 ,  C07K2317/92 ,  C07K2317/94

摘要： The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formula (I)-(VII). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.

公开(公告)号：US08388960B2

公开(公告)日：2013-03-05

申请号：US13229422

申请日：2011-09-09

申请人： Viktor S. Goldmakher ,  Robert J. Lutz ,  Ravi V. J. Chari ,  Yelena V. Kovtun ,  John M. Lambert ,  Rita Steeves ,  Hans K. Erickson ,  Wayne C. Widdison

发明人： Viktor S. Goldmakher ,  Robert J. Lutz ,  Ravi V. J. Chari ,  Yelena V. Kovtun ,  John M. Lambert ,  Rita Steeves ,  Hans K. Erickson ,  Wayne C. Widdison

IPC分类号： A61K39/00

CPC分类号： C07K16/3046 ,  A61K31/5383 ,  A61K31/58 ,  A61K47/6803 ,  A61K47/6849 ,  A61K2039/505 ,  C07D498/18 ,  C07K2317/24

摘要： Methods of killing or inhibiting tumors comprising of heterogeneous or mixed cell populations is described. The killing or inhibition of tumors is achieved by selectively targeting a unique ligand suspected of being expressed on a particular cell population to also kill a cell population lacking the unique ligand. These conjugates have therapeutic use as they are delivered to a specific cell population to kill these cells and the cytotoxic drug is released to kill non-targeted cells, thereby eliminating the tumor.

摘要翻译： 描述了杀死或抑制包含异源或混合细胞群的肿瘤的方法。 通过选择性地靶向疑似在特定细胞群体上表达的独特配体也杀死缺乏独特配体的细胞群体来实现肿瘤的杀伤或抑制。 这些缀合物具有治疗用途，因为它们被递送到特定细胞群以杀死这些细胞，并释放细胞毒性药物以杀死非靶向细胞，从而消除肿瘤。

公开(公告)号：US08236319B2

公开(公告)日：2012-08-07

申请号：US12433604

申请日：2009-04-30

申请人： Ravi V. J. Chari ,  Robert Yongxin Zhao ,  Yelena Kovtun ,  Rajeeva Singh ,  Wayne Charles Widdison

发明人： Ravi V. J. Chari ,  Robert Yongxin Zhao ,  Yelena Kovtun ,  Rajeeva Singh ,  Wayne Charles Widdison

IPC分类号： A61K39/00 ,  A61K38/04 ,  A61K38/06 ,  C07K16/08

CPC分类号： C07K16/28 ,  A61K31/5365 ,  A61K47/65 ,  A61K47/6809 ,  A61K47/6849 ,  C07D207/46 ,  C07K5/0202 ,  C07K5/06026 ,  C07K5/0806 ,  C07K5/0819 ,  Y02A50/423 ,  Y02A50/491

摘要： Charged or pro-charged cross-linking moieties and conjugates of cell binding agents and drugs comprising the charged or pro-charged cross-linking moieties and method of making the same.

摘要翻译： 带电或带电荷的交联部分和细胞结合剂的缀合物和包含带电荷或带正电荷的交联部分的药物及其制备方法。

公开(公告)号：US08163888B2

公开(公告)日：2012-04-24

申请号：US11927217

申请日：2007-10-29

申请人： Rita M. Steeves ,  Ravi V. J. Chari ,  Walter A. Blattler

发明人： Rita M. Steeves ,  Ravi V. J. Chari ,  Walter A. Blattler

IPC分类号： C07K16/00

CPC分类号： C07K16/3092 ,  A61K47/6803 ,  A61K47/6851 ,  A61K47/6855 ,  A61K47/6889 ,  A61K2039/505 ,  C07K16/18 ,  C07K16/32 ,  C07K2317/24 ,  C07K2317/92

摘要： The present invention discloses a method for targeting maytansinoids to a selected cell population, the method comprising contacting a cell population or tissue suspected of containing the selected cell population with a cell-binding agent maytansinoid conjugate, wherein one or more maytansinoids is covalently linked to the cell-binding agent via a non-cleavable linker and the cell-binding agent binds to cells of the selected cell population.

公开(公告)号：US07989598B2

公开(公告)日：2011-08-02

申请号：US11927251

申请日：2007-10-29

申请人： Rita M. Steeves ,  Ravi V. J. Chari ,  Walter A. Blattler

发明人： Rita M. Steeves ,  Ravi V. J. Chari ,  Walter A. Blattler

IPC分类号： C07K16/00

CPC分类号： C07K16/3092 ,  A61K47/6803 ,  A61K47/6851 ,  A61K47/6855 ,  A61K47/6889 ,  A61K2039/505 ,  C07K16/18 ,  C07K16/32 ,  C07K2317/24 ,  C07K2317/92

摘要： The present invention discloses a method for targeting maytansinoids to a selected cell population, the method comprising contacting a cell population or tissue suspected of containing the selected cell population with a cell-binding agent maytansinoid conjugate, wherein one or more maytansinoids is covalently linked to the cell-binding agent via a non-cleavable linker and the cell-binding agent binds to cells of the selected cell population.

摘要翻译： 本发明公开了一种将美登木素生物素靶向选定的细胞群体的方法，所述方法包括将怀疑含有所选细胞群的细胞群体或组织与细胞粘附剂美登木素生物碱缀合物接触，其中一种或多种美登木素生物碱共价连接到 细胞结合剂通过不可切割的接头和细胞结合剂结合所选细胞群的细胞。

公开(公告)号：US07906545B2

公开(公告)日：2011-03-15

申请号：US12505175

申请日：2009-07-17

申请人： Robert Yongxin Zhao ,  Ravi V. J. Chari

发明人： Robert Yongxin Zhao ,  Ravi V. J. Chari

IPC分类号： A61K31/40 ,  C07D209/56

CPC分类号： C07D307/85 ,  A61K31/407 ,  A61K31/4545 ,  A61K31/495 ,  A61K31/496 ,  A61K31/675 ,  A61K47/545 ,  A61K47/548 ,  A61K47/60 ,  C07D209/42 ,  C07D209/60 ,  C07D403/14 ,  C07D405/12 ,  C07F9/5728 ,  C07F9/65583 ,  Y02A50/423 ,  Y02A50/491 ,  Y02P20/55

摘要： Prodrugs of analogs of the anti-tumor antibiotic CC-1065 having a cleavable protective group such as a piperazino carbamate, a 4-piperidino-piperidino carbamate or a phosphate, in which the protecting group confers enhanced water solubility and stability upon the prodrug, and in which the prodrug also has a moiety, such as a disulfide, that can conjugate to a cell binding reagent such as an antibody. The therapeutic use of such prodrug conjugates is also described; such prodrugs of cytotoxic agents have therapeutic use because they can deliver cytotoxic prodrugs to a specific cell population for enzymatic conversion to cytoxic drugs in a targeted fashion.

摘要翻译： 具有可切割保护基的抗肿瘤抗生素CC-1065类似物的前药，例如哌嗪基氨基甲酸酯，4-哌啶子基 - 哌啶子基氨基甲酸酯或磷酸酯，其中保护基团赋予增强的水溶性和在前药上的稳定性， 其中前药还具有可与细胞结合试剂例如抗体缀合的部分，例如二硫化物。 还描述了这种前药缀合物的治疗用途; 这种细胞毒性药物的前药具有治疗用途，因为它们可以将细胞毒性前体药物递送至特定细胞群体，以靶向方式酶促转化为细胞毒性药物。

公开(公告)号：US20110003969A1

公开(公告)日：2011-01-06

申请号：US12793175

申请日：2010-06-03

申请人： Brenda A. Kellogg ,  Rajeeva Singh ,  Ravi V. J. Chari

发明人： Brenda A. Kellogg ,  Rajeeva Singh ,  Ravi V. J. Chari

IPC分类号： C07K14/62 ,  C07D498/18 ,  C07K14/555 ,  C07K14/54 ,  C07K14/55 ,  C07K14/485 ,  C07K14/495 ,  C07K14/50 ,  C07K14/475 ,  C07K14/535 ,  C07K14/79 ,  C07K16/18 ,  C07K16/46

CPC分类号： C07K16/46 ,  A61K47/60 ,  A61K47/6803 ,  A61K47/6849 ,  A61K47/6851 ,  A61K47/6855 ,  A61K47/6863 ,  A61K47/6891 ,  C07D213/71 ,  C07K2317/21 ,  C07K2317/24

摘要： This invention describes a method of conjugating a cell binding agent such as an antibody with an effector group (e.g., a cytotoxic agent) or a reporter group (e.g., a radionuclide), whereby the reporter or effector group is first reacted with a bifunctional linker and the mixture is then used without purification for the conjugation reaction with the cell binding agent. The method described in this invention is advantageous for preparation of stably-linked conjugates of cell binding agents, such as antibodies with effector or reporter groups. This conjugation method provides in high yields conjugates of high purity and homogeneity that are without inter-chain cross-linking and inactivated linker residues

摘要翻译： 本发明描述了将细胞结合剂如抗体与效应基团（例如，细胞毒性剂）或报告基团（例如，放射性核素）缀合的方法，由此报告物或效应基团首先与双官能接头 然后将混合物不经纯化用于与细胞结合剂的缀合反应。 本发明描述的方法有利于制备稳定连接的细胞结合剂的缀合物，例如具有效应物或报道基团的抗体。 这种共轭方法提供了高产率和高度均一性的缀合物，其不具有链间交联和失活的接头残基

公开(公告)号：US07816543B2

公开(公告)日：2010-10-19

申请号：US12276568

申请日：2008-11-24

申请人： Herve Bouchard ,  Alain Commercon ,  Ravi V. J. Chari

发明人： Herve Bouchard ,  Alain Commercon ,  Ravi V. J. Chari

IPC分类号： C07D309/30

CPC分类号： A61K47/6863 ,  A61K47/6803

摘要： Leptomycin derivatives having a moiety, such as a sulfide or a disulfide, that can conjugate to a cell binding reagent such as an antibody are disclosed. The therapeutic use of such leptomycin derivative conjugates is also described; such conjugates have therapeutic use because they can deliver cytotoxic leptomycin derivatives to a specific cell population in a targeted fashion.

摘要翻译： 公开了具有可与细胞结合试剂如抗体缀合的具有部分例如硫化物或二硫化物的紫霉素衍生物。 还描述了这种灵霉素衍生物缀合物的治疗用途; 这样的缀合物具有治疗用途，因为它们可以以靶向的方式将细胞毒性的曲霉素衍生物递送到特定细胞群体。

公开(公告)号：US07550609B2

公开(公告)日：2009-06-23

申请号：US11785483

申请日：2007-04-18

申请人： Ravi V. J. Chari ,  Walter A. Blättler

发明人： Ravi V. J. Chari ,  Walter A. Blättler

IPC分类号： C07D305/14 ,  A61K31/337

CPC分类号： C07D305/14 ,  A61K31/337 ,  A61K47/6803 ,  A61K47/6849 ,  A61K47/6851 ,  A61K47/6881 ,  A61K2039/505 ,  C07K16/2863 ,  C07K16/32 ,  Y02A50/423 ,  Y02A50/491

摘要： A cytotoxic agent comprising one or more taxanes linked to a cell binding agent. A therapeutic composition for killing selected cell populations comprising: (A) a cytotoxic amount of one or more taxanes covalently bonded to a cell binding agent through a linking group, and (B) a pharmaceutically acceptable carrier, diluent or excipient. A method for killing selected cell populations comprising contacting target cells or tissue containing target cells with an effective amount of a cytotoxic agent comprising one or more taxanes linked to a cell binding agent. Novel sulfur-containing taxanes.