公开(公告)号：WO2010042877A1

公开(公告)日：2010-04-15

申请号：PCT/US2009/060251

申请日：2009-10-09

Applicant: TEKMIRA PHARMACEUTICALS CORPORATION ,  THE UNIVERSITY OF BRITISH COLUMBIA ,  HOPE, Michael, J. ,  SEMPLE, Sean, C. ,  CHEN, Jianxin ,  MADDEN, Thomas, D. ,  CULLIS, Pieter, R. ,  CIUFOLINI, Marco, A. ,  LAHERTY, Carol, D. ,  MUI, Barbara

Inventor： HOPE, Michael, J. ,  SEMPLE, Sean, C. ,  CHEN, Jianxin ,  MADDEN, Thomas, D. ,  CULLIS, Pieter, R. ,  CIUFOLINI, Marco, A. ,  MUI, Barbara

IPC: C07D345/00 ,  C07D517/00 ,  A61K9/127

CPC classification number: A61K47/22 ,  A61K9/1271 ,  A61K31/713 ,  A61K39/39 ,  A61K2039/55511 ,  C07D317/28 ,  C07D319/06

Abstract: The present invention provides superior compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of specific target proteins at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.

Abstract translation: 本发明提供优异的用于将治疗剂递送至细胞的组合物和方法。 特别地，这些包括提供核酸的有效包封的新型脂质和核酸 - 脂质颗粒，并将包封的核酸有效地递送到细胞体内。 本发明的组合物是高度有效的，从而允许在相对低的剂量下有效击倒特异性靶蛋白。 此外，与本领域已知的组合物和方法相比，本发明的组合物和方法毒性低，并提供更大的治疗指数。

公开(公告)号：WO2009086558A1

公开(公告)日：2009-07-09

申请号：PCT/US2008/088676

申请日：2008-12-31

Applicant: TEKMIRA PHARMACEUTICALS CORPORATION ,  THE UNIVERSITY OF BRITISH COLUMBIA ,  ALNYLAM PHARMACEUTICALS ,  HOPE, Michael, J. ,  SEMPLE, Sean, C. ,  CHEN, Jianxin ,  MADDEN, Thomas, D. ,  MUI, Barbara ,  CULLIS, Pieter, R. ,  CIUFOLINI, Marco, A. ,  WONG, Kim, F. ,  MANOHARAN, Muthiah ,  KALLANTHOTTATHIL, Rajeev, G.

Inventor： HOPE, Michael, J. ,  SEMPLE, Sean, C. ,  CHEN, Jianxin ,  MADDEN, Thomas, D. ,  MUI, Barbara ,  CULLIS, Pieter, R. ,  CIUFOLINI, Marco, A. ,  WONG, Kim, F. ,  MANOHARAN, Muthiah ,  KALLANTHOTTATHIL, Rajeev, G.

IPC: A61K9/127 ,  A61K31/7088

CPC classification number: A61K31/7088 ,  A61K9/127 ,  A61K9/1275 ,  C07C215/10 ,  C07C217/08 ,  C07C217/28 ,  C07C219/08 ,  C07C229/12 ,  C07C271/12 ,  C07C323/25 ,  C07D317/28

Abstract: The present invention provides compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of specific target protein at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.

Abstract translation: 本发明提供了将治疗剂递送至细胞的组合物和方法。 特别地，这些包括提供核酸的有效包封的新型脂质和核酸 - 脂质颗粒，并将包封的核酸有效地递送到细胞体内。 本发明的组合物是高度有效的，从而允许以相对低的剂量有效击倒特异性靶蛋白。 此外，与本领域已知的组合物和方法相比，本发明的组合物和方法毒性低，并提供更大的治疗指数。

公开(公告)号：WO0202077A3

公开(公告)日：2002-12-12

申请号：PCT/CA0100925

申请日：2001-06-29

Applicant: INEX PHARMACEUTICALS CORP ,  MADDEN THOMAS D ,  SEMPLE SEAN C ,  AHKONG QUET F

Inventor： MADDEN THOMAS D ,  SEMPLE SEAN C ,  AHKONG QUET F

IPC: A61K9/127 ,  A61K31/4745 ,  A61K31/475 ,  A61K45/06 ,  A61K47/24 ,  A61K47/28 ,  A61P35/00

CPC classification number: A61K9/127 ,  A61K9/1272 ,  A61K9/1278 ,  A61K31/4745 ,  A61K45/06 ,  A61K2300/00

Abstract: This invention relates to liposomal antineoplastic agents ( e.g ., camptothecin) compositions and methods of using such compositions for treating neoplasia and for inhibiting angiogenesis. The compositions and methods are useful for modulating the plasma circulation half-life of an active agent.

Abstract translation: 本发明涉及脂质体抗肿瘤剂（例如喜树碱）组合物和使用这种组合物治疗瘤形成和抑制血管生成的方法。 该组合物和方法可用于调节活性剂的血浆循环半衰期。

公开(公告)号：WO2009088891A8

公开(公告)日：2009-07-16

申请号：PCT/US2008/088587

申请日：2008-12-31

Applicant: ALNYLAM PHARMACEUTICALS, INC. ,  CIUFOLINI, Marco ,  MADDEN, Thomas, D. ,  HOME, Michael, J. ,  MUI, Barbara ,  DE FOUGEROLLES, Antonin ,  NOVOBRANTSEVA, Tatiana ,  BORODOVSKY, Anna ,  AKINC, Akin ,  TRACY, Mark ,  CULLIS, Pieter, Rutter

Inventor： CIUFOLINI, Marco ,  MADDEN, Thomas, D. ,  HOME, Michael, J. ,  MUI, Barbara ,  DE FOUGEROLLES, Antonin ,  NOVOBRANTSEVA, Tatiana ,  BORODOVSKY, Anna ,  AKINC, Akin ,  TRACY, Mark ,  CULLIS, Pieter, Rutter

IPC: A61K9/127 ,  G01N33/50

Abstract: The invention features a method of identifying therapeutically relevant compositions which include a therapeutic agent and 2,2-Dilinoley 1-4- dimethylaminomethyl-[l,3]-dioxolane by screening for an effect of the agent on the liver of a model subject.

公开(公告)号：WO2006052767A3

公开(公告)日：2006-05-18

申请号：PCT/US2005/040061

申请日：2005-11-04

Applicant: INEX PHARMACEUTICALS CORPORATION ,  HERMANNS, Karl, R. ,  HOPE, Michael, J. ,  MUI, Barbara ,  MADDEN, Thomas, D.

Inventor： HOPE, Michael, J. ,  MUI, Barbara ,  MADDEN, Thomas, D.

IPC: A61K9/127 ,  A61K31/47 ,  A61K31/4745 ,  A61P35/00

Abstract: The present invention is directed to liposomal compositions comprising a camptothecin, which are optimized to reduce camptothecin degradation and/or precipitation of camptothecin degradation products in the external medium. The invention further provides improved methods of formulating liposomal camptothecins, kits comprising liposome-encapsulated camptothecins, and methods of using the same to treat a variety of diseases and disorders, including cancer.

公开(公告)号：WO2011075656A1

公开(公告)日：2011-06-23

申请号：PCT/US2010/061058

申请日：2010-12-17

Applicant: THE UNIVERSITY OF BRITISH COLUMBIA ,  ALNYLAM PHARMACEUTICALS, INC. ,  HOPE, Michael, J. ,  MADDEN, Thomas, D. ,  CULLIS, Pieter ,  MAIER, Martin, A. ,  JAYARAMAN, Muthusamy ,  RAJEEV, Kallanthottathil, G. ,  AKINC, Akin ,  MANOHARAN, Muthiah

Inventor： HOPE, Michael, J. ,  MADDEN, Thomas, D. ,  CULLIS, Pieter ,  MAIER, Martin, A. ,  JAYARAMAN, Muthusamy ,  RAJEEV, Kallanthottathil, G. ,  AKINC, Akin ,  MANOHARAN, Muthiah

IPC: A61K9/127 ,  A61K9/133

CPC classification number: A61K47/48815 ,  A61K9/1272 ,  A61K47/543 ,  A61K47/6911 ,  C12N15/88

Abstract: A lipid particle can include a plurality of cationic lipids, such as a first cationic lipid and a second cationic lipid. The first cationic lipid can be selected on the basis of a first property and the second cationic can be selected on the basis of a second property. The first and second properties are complementary. The attributes of the lipid particle can reflect the selected properties of the cationic lipids, and the complementary nature of those properties.

Abstract translation: 脂质颗粒可以包括多个阳离子脂质，例如第一阳离子脂质和第二阳离子脂质。 可以基于第一性质选择第一阳离子脂质，并且可以基于第二性质选择第二阳离子脂质。 第一和第二属性是互补的。 脂质颗粒的属性可以反映阳离子脂质的选择性质，以及这些性质的互补性质。

公开(公告)号：WO2006052767A2

公开(公告)日：2006-05-18

申请号：PCT/US2005040061

申请日：2005-11-04

Applicant: INEX PHARMACEUTICALS CORP ,  HERMANNS KARL R ,  HOPE MICHAEL J ,  MUI BARBARA ,  MADDEN THOMAS D

Inventor： HOPE MICHAEL J ,  MUI BARBARA ,  MADDEN THOMAS D

IPC: A61K9/127 ,  A61K31/47

CPC classification number: A61K31/4745 ,  A61K9/127 ,  A61K31/47

Abstract: The present invention is directed to liposomal compositions comprising a camptothecin, which are optimized to reduce camptothecin degradation and/or precipitation of camptothecin degradation products in the external medium. The invention further provides improved methods of formulating liposomal camptothecins, kits comprising liposome-encapsulated camptothecins, and methods of using the same to treat a variety of diseases and disorders, including cancer.

Abstract translation: 本发明涉及包含喜树碱的脂质体组合物，其被优化以降低喜树碱降解和/或在外部培养基中的喜树碱降解产物的沉淀。 本发明进一步提供了制备脂质体喜树碱的改进方法，包含脂质体包封的喜树碱的试剂盒及其使用方法来治疗各种疾病和病症，包括癌症。

公开(公告)号：WO2005120461A3

公开(公告)日：2006-03-16

申请号：PCT/US2005017054

申请日：2005-05-16

Applicant: INEX PHARMACEUTICALS CORP ,  HERMANNS KARL R ,  CULLIS PIETER R ,  MADDEN THOMAS D ,  HOPE MICHAEL J ,  ANSELL STEVEN M ,  MUI BARBARA L S ,  SEMPLE SEAN C ,  MAURER NORBERT

Inventor： CULLIS PIETER R ,  MADDEN THOMAS D ,  HOPE MICHAEL J ,  ANSELL STEVEN M ,  MUI BARBARA L S ,  SEMPLE SEAN C ,  MAURER NORBERT

IPC: A61K9/127

CPC classification number: A61K31/4745 ,  A61K9/1272 ,  A61K9/1278 ,  A61K33/32 ,  A61K2300/00

Abstract: The present invention includes novel liposomes comprising dihydrosphingomyelin. The invention also includes compositions comprising these liposomes and a therapeutic agent, in addition to methods and kits for delivering a therapeutic agent or treating a disease, e.g., a cancer, using these compositions.

Abstract translation: 本发明包括含有二氢鞘磷脂的新型脂质体。 除了使用这些组合物递送治疗剂或治疗疾病例如癌症的方法和试剂盒外，本发明还包括包含这些脂质体和治疗剂的组合物。

公开(公告)号：WO2002036767A3

公开(公告)日：2002-05-10

申请号：PCT/CA2001/001540

申请日：2001-10-31

Applicant: INEX PHARMACEUTICALS CORPORATION ,  MADDEN, Thomas, D. ,  WEBB, Murray, S.

Inventor： MADDEN, Thomas, D. ,  WEBB, Murray, S.

IPC: A61K31/7125

Abstract: It has now been discovered that oligonucleotides which tend to form multimeric aggregates have greater toxicity in the aggregate form than in monomeric form. Thus, the present invention provides therapeutic oligonucleotide compositions of reduced in vivo toxicity, and a method for making such compositions, as well as a method for administration of the therapeutic oligonucleotide, where the therapeutic oligonucleotide in one that tends to form multimeric aggregates. Compositions containing such aggregate-forming oligonucleotides are treated by heating, preferably no more than 24 hours prior to administration, or using chemical species such as mannitol which disrupt aggregates.

公开(公告)号：WO0236767A2

公开(公告)日：2002-05-10

申请号：PCT/CA0101540

申请日：2001-10-31

Applicant: INEX PHARMACEUTICALS CORP ,  MADDEN THOMAS D ,  WEBB MURRAY S

Inventor： MADDEN THOMAS D ,  WEBB MURRAY S

IPC: C12N15/09 ,  A61K9/00 ,  A61K9/19 ,  A61K31/7088 ,  A61K38/00 ,  A61K47/26 ,  A61K48/00 ,  A61P43/00 ,  C12N15/113 ,  C12N15/11 ,  A61K31/7125

CPC classification number: C12N15/113 ,  A61K9/0019 ,  A61K38/00 ,  A61K47/26 ,  C12N2310/315

Abstract: It has now been discovered that oligonucleotides which tend to form multimeric aggregates have greater toxicity in the aggregate form than in monomeric form. Thus, the present invention provides therapeutic oligonucleotide compositions of reduced in vivo toxicity, and a method for making such compositions, as well as a method for administration of the therapeutic oligonucleotide, where the therapeutic oligonucleotide in one that tends to form multimeric aggregates. Compositions containing such aggregate-forming oligonucleotides are treated by heating, preferably no more than 24 hours prior to administration, or using chemical species such as mannitol which disrupt aggregates.

Abstract translation: 现在已经发现，倾向于形成多聚体聚集体的寡核苷酸在聚集体形式中具有比单体形式更大的毒性。 因此，本发明提供了降低体内毒性的治疗性寡核苷酸组合物，以及制备该组合物的方法，以及治疗性寡核苷酸的施用方法，其中倾向于形成多聚体聚集体的治疗性寡核苷酸。 含有这种聚集形成寡核苷酸的组合物通过加热处理，优选不超过施用前24小时，或者使用破坏聚集体的化学物质例如甘露糖醇。