公开(公告)号：EP3218414A1

公开(公告)日：2017-09-20

申请号：EP15859337.6

申请日：2015-11-13

申请人： Angiochem Inc.

发明人： DEMEULE, Michel ,  CHE, Christian ,  DAS, Sanjoy ,  YANG, Gaoqiang

IPC分类号： C07K19/00 ,  A61K47/50 ,  A61P35/00 ,  C07K14/81 ,  C07K16/28

CPC分类号： A61K39/395 ,  A61K39/39558 ,  A61K47/6803 ,  A61K47/6855 ,  A61K47/6869 ,  A61K47/6883 ,  A61K47/6885 ,  C07K14/8117 ,  C07K16/32 ,  C07K2319/00

摘要： The present invention relates to antibody-polypeptide-cytotoxin conjugates and methods of making, packaging, and using the conjugates. The polypeptide can be a Kunitz-type protease inhibitor or a derivative thereof that facilitates transport of the conjugate across the blood-brain barrier and/or into cancer cells outside the CNS, and the antibody moiety selectively binds a target within the CNS or in peripheral tumors to direct the cytotoxic agent to that target (e.g., a tumor or cancer cell). The conjugates can be further defined by the inclusion of a linker between the antibody moiety and the polypeptide; by the number of polypeptides and cytotoxic agents conjugated thereto; by the positions at which the entities within the conjugates are bound to one another; and by the larger configuration of the conjugate. Modified polypeptides (e.g., polypeptides conjugated to cytotoxic agents but not to an anti-body moiety), pharmaceutical compositions, kits (e.g., including a modified polypeptide and an as-yet unconjugated antibody), and methods of making and using the conjugates are also features of the invention.

摘要翻译： 本发明涉及抗体 - 多肽 - 细胞毒素缀合物以及制造，包装和使用缀合物的方法。 多肽可以是Kunitz型蛋白酶抑制剂或其衍生物，其有助于缀合物穿过血脑屏障和/或进入CNS外的癌细胞，并且抗体部分选择性地结合CNS内或外周 肿瘤将细胞毒素剂引导至该靶标（例如肿瘤或癌细胞）。 缀合物可以通过包含抗体部分和多肽之间的接头进一步定义; 通过与其缀合的多肽和细胞毒性剂的数量; 由共轭物中的实体相互结合的位置决定; 并通过缀合物的较大配置。 经修饰的多肽（例如与细胞毒剂偶联但不与抗体部分缀合的多肽），药物组合物，试剂盒（例如，包括修饰的多肽和尚未偶联的抗体）以及制备和使用缀合物的方法也是 本发明。

公开(公告)号：EP2885318A1

公开(公告)日：2015-06-24

申请号：EP13829574.6

申请日：2013-08-14

申请人： Angiochem Inc.

发明人： DEMEULE, Michel ,  LAROCQUE, Alain ,  YANG, Gaoqiang ,  TRIPATHY, Sasmita

IPC分类号： C07K14/81 ,  A61K47/48 ,  A61K49/00 ,  C07K14/00

CPC分类号： A61K47/48253 ,  A61K38/10 ,  A61K47/593 ,  A61K47/595 ,  A61K47/64 ,  A61K47/641 ,  C07K14/8117

摘要： The invention relates to dendrimers conjugated to multiple targeting peptides and one or more therapeutic, diagnostic, or imaging agents for delivery of such agents across the blood-brain barrier and into certain cell types including, cells expressing the LRP-1 receptor. Also described are methods of making compounds that comprise dendrimers conjugated to targeting peptides and therapeutic, diagnostic, or imaging agents.

公开(公告)号：EP2346896A1

公开(公告)日：2011-07-27

申请号：EP09820163.5

申请日：2009-10-15

申请人： Angiochem Inc.

发明人： DEMEULE, Michel ,  CHE, Christian ,  GABATHULER, Reinhard ,  YANG, Gaoqiang

IPC分类号： C07K14/81 ,  A61K31/704 ,  A61K31/7048 ,  A61K47/42 ,  A61K47/48 ,  A61P35/00 ,  C07H15/252 ,  C07H17/04 ,  C07K14/00 ,  C07K7/08 ,  C07K14/705

CPC分类号： A61K47/48246 ,  A61K31/04 ,  A61K31/337 ,  A61K31/704 ,  A61K31/7048 ,  A61K38/10 ,  A61K39/39558 ,  A61K45/06 ,  A61K47/62 ,  A61K47/64 ,  C07H17/04 ,  C07K14/515 ,  A61K2300/00

摘要： The invention relates to improvements in the field of drug delivery. More particularly, the invention relates to polypeptides having a hydrolyzable covalent bond to a therapeutic agent that includes, etoposide, etoposide 4'- dimethylglycine or doxorubicin. These polypeptide conjugates can be used as vectors to transport the podophyllotoxin derivative across the blood brain barrier (BBB) or into particular cell types such as ovary, liver, lung, or kidney. The invention also relates to pharmaceutical compositions that include the compounds of the invention and to uses thereof in methods of treatment.

摘要翻译： 本发明涉及药物递送领域的改进。 更具体地说，本发明涉及具有包含依托泊苷，依托泊苷4'-二甲基甘氨酸或多柔比星的治疗剂的可水解共价键的多肽。 这些多肽缀合物可用作载体，以将鬼臼毒素衍生物跨越血脑屏障（BBB）或特定的细胞类型如卵巢，肝，肺或肾运送。 本发明还涉及包含本发明化合物及其在治疗方法中的用途的药物组合物。

公开(公告)号：EP2885321A1

公开(公告)日：2015-06-24

申请号：EP13829923.5

申请日：2013-08-14

申请人： Angiochem Inc.

发明人： CASTAIGNE, Jean-Paul ,  YANG, Gaoqiang ,  CHE, Christian ,  DEMEULE, Michel

IPC分类号： C07K19/00 ,  A61K47/48 ,  A61P35/00 ,  C07K14/81 ,  C07K16/18 ,  C07K16/28

CPC分类号： A61K47/48246 ,  A61K31/337 ,  A61K47/482 ,  A61K47/48384 ,  A61K47/48407 ,  A61K47/48561 ,  A61K47/48569 ,  A61K47/48584 ,  A61K47/48684 ,  A61K47/487 ,  A61K47/593 ,  A61K47/64 ,  A61K47/6803 ,  A61K47/6809 ,  A61K47/6849 ,  A61K47/6851 ,  A61K47/6855 ,  A61K47/6881 ,  A61K47/6885 ,  C07K14/8117 ,  C07K16/2863 ,  C07K16/3015 ,  C07K16/32 ,  C07K2317/24 ,  C07K2319/33

摘要： The present invention relates to antibody-polypeptide-cytotoxin conjugates and methods of making, packaging, and using the conjugates. The polypeptide can be a Kunitz-type protease inhibitor or a derivative thereof that facilitates transport of the conjugate across the blood-brain barrier and/or into cancer cells outside the CNS, and the antibody moiety selectively binds a target within the CNS or in peripheral tumors to direct the cytotoxic agent to that target (e.g., a tumor or cancer cell). The conjugates can be further defined by the inclusion of a linker between the antibody moiety and the polypeptide; by the number of polypeptides and cytotoxic agents conjugated thereto; by the positions at which the entities within the conjugates are bound to one another; and by the larger configuration of the conjugate. Modified polypeptides (e.g., polypeptides conjugated to cytotoxic agents but not to an antibody moiety), pharmaceutical compositions, kits (e.g., including a modified polypeptide and an as-yet unconjugated antibody), and methods of making and using the conjugates are also features of the invention.