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.

公开(公告)号：US07411063B2

公开(公告)日：2008-08-12

申请号：US11594156

申请日：2006-11-08

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

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

IPC分类号： C07D491/12 ,  C07D498/06

CPC分类号： C07D498/14 ,  C07D491/14

摘要： The present invention describes the preparation of maytansinol by methods that minimize processing steps, and reduce solvent volumes, making the process more efficient, and scaleable. This process comprises a step of converting bridged acetals of maytansinol to maytansinol. The simplified processing also aids in lowering the potential for human exposure to chemicals. Also provided is an isolated C3 to C9 bridged acetal of maytansinol.

摘要翻译： 本发明描述了通过使加工步骤最小化并减少溶剂体积，使该方法更有效和可扩缩的方法制备美登素的方法。 该方法包括将美登醇的桥联缩醛转化为美登素。 简化的处理也有助于降低人类接触化学品的可能性。 还提供了美登醇的分离的C3至C9桥连缩醛。

公开(公告)号：US07008942B2

公开(公告)日：2006-03-07

申请号：US10684746

申请日：2003-10-15

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

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

IPC分类号： A61K31/337 ,  C07D305/14

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.

公开(公告)号：US08809320B2

公开(公告)日：2014-08-19

申请号：US13774059

申请日：2013-02-22

申请人： Wei Li ,  Nathan Elliott Fishkin ,  Robert Yongxin Zhao ,  Michael Louis Miller ,  Ravi V. J. Chari

发明人： Wei Li ,  Nathan Elliott Fishkin ,  Robert Yongxin Zhao ,  Michael Louis Miller ,  Ravi V. J. Chari

IPC分类号： C07D519/00 ,  A61K31/5517 ,  A61P35/00 ,  A61K47/48 ,  C07D487/04 ,  A61K38/07 ,  A61K45/06 ,  C07D498/04 ,  C07K5/103 ,  C07K16/28

CPC分类号： C07K16/2896 ,  A61K31/5517 ,  A61K38/07 ,  A61K45/06 ,  A61K47/60 ,  A61K47/6835 ,  A61K47/6849 ,  A61K47/6863 ,  A61P35/00 ,  C07D487/04 ,  C07D498/04 ,  C07D519/00 ,  C07K5/0202 ,  C07K5/1008 ,  C07K16/2803 ,  C07K16/46 ,  C07K19/00

摘要： The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepines of formula (I) and (II), in which the diazepine ring (B) is fused with a heterocyclic ring (CD), wherein the heterocyclic ring is bicyclic or a compound of formula (III), in which the diazepine ring (B) is fused with a heterocyclic ring (C), wherein the heterocyclic ring is monocyclic. The invention provides cytotoxic dimers of these compounds. The invention also provides conjugates of the monomers and the dimers. 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. The invention further relates to methods of using the compounds or conjugates for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

摘要翻译： 本发明涉及具有抗增殖活性的新型苯并二氮杂衍生物，更具体地涉及式（I）和（II）的新型苯并二氮杂，其中二氮杂环（B）与杂环（CD）稠合，其中杂环是双环的 或其中二氮杂环（B）与杂环（C）稠合的式（III）化合物，其中杂环是单环的。 本发明提供这些化合物的细胞毒二聚体。 本发明还提供了单体和二聚体的共轭物。 本发明还提供了使用本发明的化合物或缀合物来抑制哺乳动物异常细胞生长或治疗增殖性病症的组合物和方法。 本发明还涉及将化合物或缀合物用于体外，原位和体内诊断或治疗哺乳动物细胞或相关病理状况的方法。

公开(公告)号：US08802667B2

公开(公告)日：2014-08-12

申请号：US13826181

申请日：2013-03-14

申请人： Wei Li ,  Nathan Elliott Fishkin ,  Robert Yongxin Zhao ,  Michael Louis Miller ,  Ravi V. J. Chari

发明人： Wei Li ,  Nathan Elliott Fishkin ,  Robert Yongxin Zhao ,  Michael Louis Miller ,  Ravi V. J. Chari

IPC分类号： C07D519/00 ,  A61K31/5517 ,  A61K31/55 ,  A61P35/00 ,  A61K47/48 ,  C07K5/103 ,  C07D498/04 ,  A61K38/07 ,  A61K45/06 ,  C07D487/04 ,  C07K16/28

CPC分类号： C07K16/2896 ,  A61K31/5517 ,  A61K38/07 ,  A61K45/06 ,  A61K47/60 ,  A61K47/6835 ,  A61K47/6849 ,  A61K47/6863 ,  A61P35/00 ,  C07D487/04 ,  C07D498/04 ,  C07D519/00 ,  C07K5/0202 ,  C07K5/1008 ,  C07K16/2803 ,  C07K16/46 ,  C07K19/00

摘要： The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepines of formula (I) and (II), in which the diazepine ring (B) is fused with a heterocyclic ring (CD), wherein the heterocyclic ring is bicyclic or a compound of formula (III), in which the diazepine ring (B) is fused with a heterocyclic ring (C), wherein the heterocyclic ring is monocyclic. The invention provides cytotoxic dimers of these compounds. The invention also provides conjugates of the monomers and the dimers. 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. The invention further relates to methods of using the compounds or conjugates for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

公开(公告)号：USRE44704E1

公开(公告)日：2014-01-14

申请号：US13613743

申请日：2012-09-13

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

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

IPC分类号： A61K39/395 ,  A61K31/21 ,  A61K31/33 ,  A61K31/40 ,  A61K31/44 ,  A61K31/337 ,  A61K31/075 ,  A61K31/09 ,  A61K31/165 ,  A61K31/166 ,  A61K31/167 ,  A61K31/122

CPC分类号： Y02A50/423 ,  Y02A50/486 ,  Y02A50/487 ,  Y02A50/491

摘要： The present invention is based on the discovery that the administration of at least one immunoconjugate and at least one chemotherapeutic agent provides an unexpectedly superior treatment for cancer. The present invention is directed to compositions comprising at least one immunoconjugate and at least one chemotherapeutic agent and to methods of treating cancer using at least one immunoconjugate and at least one chemotherapeutic agent. The present invention also provides methods of modulating the growth of selected cell populations, such as cancer cells, by administering a therapeutically effective amount of at least one chemotherapeutic agent and at least one immunoconjugate.

摘要翻译： 本发明基于这样的发现，即至少一种免疫缀合物和至少一种化学治疗剂的施用提供了对于癌症的意想不到的优异治疗。 本发明涉及包含至少一种免疫缀合物和至少一种化学治疗剂的组合物以及使用至少一种免疫缀合物和至少一种化学治疗剂治疗癌症的方法。 本发明还提供了通过施用治疗有效量的至少一种化学治疗剂和至少一种免疫缀合物来调节所选细胞群体如癌细胞的生长的方法。

公开(公告)号：US08404678B2

公开(公告)日：2013-03-26

申请号：US12689797

申请日：2010-01-19

申请人： Hervé Bouchard ,  Ravi V. J. Chari ,  Alain Commerçon ,  Yonghong Deng ,  Laurence Gauzy

发明人： Hervé Bouchard ,  Ravi V. J. Chari ,  Alain Commerçon ,  Yonghong Deng ,  Laurence Gauzy

IPC分类号： C07D487/00 ,  C07D519/00 ,  A61K31/5517

CPC分类号： C07D487/04 ,  C07D519/00

摘要： The invention relates to novel tomaymicine derivatives comprising a linker. It also relates to the conjugate molecules that comprise one or more of said tomaymicine derivatives covalently linked to a cell binding agent through a linking group that is present on the linker of the tomaymycin derivative. It also relates to the preparation of the tomaymicine derivatives and of the conjugate molecules.

摘要翻译： 本发明涉及包含连接体的新颖的甲氧基衍生物。 它还涉及包含一种或多种通过存在于茅屋霉素衍生物的接头上的连接基团与细胞结合剂共价连接的所述柚皮苷衍生物的缀合物分子。 它还涉及制备汤姆米明衍生物和共轭分子。

公开(公告)号：US08088387B2

公开(公告)日：2012-01-03

申请号：US10960602

申请日：2004-10-08

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

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

IPC分类号： A61K39/395

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：US07655660B2

公开(公告)日：2010-02-02

申请号：US11649822

申请日：2007-01-05

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

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

IPC分类号： A61K31/497 ,  C07D241/04

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。