公开(公告)号：EP2512449A1

公开(公告)日：2012-10-24

申请号：EP10838298.7

申请日：2010-12-17

申请人： The University of British Columbia ,  Alnylam Pharmaceuticals, Inc.

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

IPC分类号： A61K9/127 ,  A61K9/133

CPC分类号： A61K47/543 ,  A61K9/1272 ,  A61K47/6911 ,  C12N15/88

摘要： 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.

公开(公告)号：EP3100718B1

公开(公告)日：2019-11-27

申请号：EP16163003.3

申请日：2008-12-31

申请人： Arbutus Biopharma Corporation ,  The University of British Columbia ,  Alnylam Pharmaceuticals, Inc.

发明人： HOPE, Michael, J. ,  SEMPLE, Sean C. ,  CHEN, Jianxin ,  MADDEN, Thomas D. ,  MUI, Barbara ,  CULLIS, Pieter R. ,  CIUFOLINI, Marco A. ,  WONG, Kim F. ,  MANOHARAN, Muthiah ,  RAJEEV, Kallanthottathil G. ,  SRINIVASULU, Masunu

IPC分类号： A61K9/127 ,  A61K31/7088 ,  C07D317/28 ,  C07C229/30

公开(公告)号：EP3494963A1

公开(公告)日：2019-06-12

申请号：EP18203249.0

申请日：2010-12-17

申请人： The University of British Columbia ,  Arbutus Biopharma Corporation

发明人： HOPE, Michael, J. ,  MADDEN, Thomas, D. ,  CULLIS, Pieter ,  MAIER, Martin, A. ,  JAYARAMAN, Muthusamy ,  RAJEEV, Kallanthottathil, G. ,  AKINC, Akin ,  MANOHARAN, Muthiah ,  HAFEZ, Ismail Mahmoud

IPC分类号： A61K9/127 ,  A61K9/133 ,  C12N15/88 ,  A61K47/69 ,  A61K47/54

摘要： 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.

公开(公告)号：EP2224912A1

公开(公告)日：2010-09-08

申请号：EP08866209.3

申请日：2008-12-31

申请人： TEKMIRA Pharmaceuticals Corporation ,  THE UNIVERSITY OF BRITISH COLUMBIA ,  Alnylam Pharmaceuticals

发明人： HOPE, Michael, J. ,  SEMPLE, Sean, C. ,  CHEN, Jianxin ,  MADDEN, Thomas, D. ,  MUI, Barbara ,  CULLIS, Pieter, R. ,  CIUFOLINI, Marco, A. ,  WONG, Kim, F. ,  MANOHARAN, Muthiah ,  RAJEEV, Kallanthottathil, G. ,  SRINIVASULU, Masunu

IPC分类号： A61K9/127 ,  A61K31/7088

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

摘要： 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.

公开(公告)号：EP2512449B1

公开(公告)日：2019-08-07

申请号：EP10838298.7

申请日：2010-12-17

申请人： The University of British Columbia ,  Arbutus Biopharma Corporation

发明人： HOPE, Michael, J. ,  MADDEN, Thomas, D. ,  CULLIS, Pieter ,  MAIER, Martin, A. ,  JAYARAMAN, Muthusamy ,  RAJEEV, Kallanthottathil, G. ,  AKINC, Akin ,  MANOHARAN, Muthiah ,  HAFEZ, Ismail Mahmoud

IPC分类号： A61K9/127 ,  C12N15/88

公开(公告)号：EP2224912B1

公开(公告)日：2016-05-11

申请号：EP08866209.3

申请日：2008-12-31

申请人： TEKMIRA Pharmaceuticals Corporation ,  THE UNIVERSITY OF BRITISH COLUMBIA ,  Alnylam Pharmaceuticals

发明人： HOPE, Michael, J. ,  SEMPLE, Sean, C. ,  CHEN, Jianxin ,  MADDEN, Thomas, D. ,  MUI, Barbara ,  CULLIS, Pieter, R. ,  CIUFOLINI, Marco, A. ,  WONG, Kim, F. ,  MANOHARAN, Muthiah ,  RAJEEV, Kallanthottathil, G. ,  SRINIVASULU, Masunu

IPC分类号： A61K9/127 ,  A61K31/7088 ,  C07D317/28 ,  C07C229/30

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

公开(公告)号：EP3100718A1

公开(公告)日：2016-12-07

申请号：EP16163003.3

申请日：2008-12-31

申请人： Arbutus Biopharma Corporation ,  The University of British Columbia ,  Alnylam Pharmaceuticals

发明人： HOPE, Michael, J. ,  SEMPLE, Sean C. ,  CHEN, Jianxin ,  MADDEN, Thomas D. ,  MUI, Barbara ,  CULLIS, Pieter R. ,  CIUFOLINI, Marco A. ,  WONG, Kim F. ,  MANOHARAN, Muthiah ,  RAJEEV, Kallanthottathil G. ,  SRINIVASULU, Masunu

IPC分类号： A61K9/127 ,  A61K31/7088 ,  C07D317/28 ,  C07C229/30

摘要： 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.

摘要翻译： 本发明提供了用于将治疗剂递送至细胞的组合物和方法。 具体而言，这些包括新型脂质和核酸 - 脂质颗粒，其提供有效的核酸包封和将包封的核酸有效递送至体内细胞。 本发明的组合物非常有效，从而允许以相对低的剂量有效敲减特定靶蛋白。 另外，本发明的组合物和方法毒性较低，并且与本领域先前已知的组合物和方法相比提供了更大的治疗指数。

公开(公告)号：EP4419536A1

公开(公告)日：2024-08-28

申请号：EP22884399.1

申请日：2022-10-19

申请人： Alnylam Pharmaceuticals, Inc.

发明人： MANOHARAN, Muthiah ,  MATSUDA, Shigeo ,  DATTA, Dhrubajyoti

IPC分类号： C07H21/04 ,  C07H19/20 ,  C12N15/113

CPC分类号： C12N15/113 ,  C12N2310/1420130101 ,  C12N2310/32220130101 ,  C12N2310/34420130101 ,  C12N15/111 ,  C12N2310/32120130101 ,  C12N2310/31520130101 ,  C12N2310/35120130101 ,  C12N2310/31220130101 ,  C07H19/06 ,  C07H23/00 ,  C07H19/16 ,  C07H21/00 ,  C07H21/02 ,  C07H19/04

公开(公告)号：EP4370132A2

公开(公告)日：2024-05-22

申请号：EP22842918.9

申请日：2022-07-15

申请人： Alnylam Pharmaceuticals, Inc.

发明人： MANOHARAN, Muthiah ,  DATTA, Dhrubajyoti

IPC分类号： A61K31/7008 ,  A61K31/7052 ,  A61K31/7056 ,  C07H19/056 ,  C08K5/28

CPC分类号： C07H19/056

公开(公告)号：EP4141116A1

公开(公告)日：2023-03-01

申请号：EP22169938.2

申请日：2012-11-16

申请人： Alnylam Pharmaceuticals, Inc.

发明人： RAJEEV, Kallanthottathil, G. ,  ZIMMERMANN, Tracy ,  MANOHARAN, Muthiah ,  MAIER, Martin ,  KUCHIMANCHI, Satyanarayana ,  CHARISSE, Klaus

IPC分类号： C12N15/113 ,  A61K31/7125

摘要： The present invention relates to a double-stranded RNAi agent capable of inhibiting the expression of a target gene, comprising a sense strand and an antisense strand, each strand having 14 to 30 nucleotides, wherein the sense strand sequence is represented by formula (I):

        5' n p -N a -(X X X ) i -N b -Y Y Y-N b -(Z Z Z ) j -N a -n q 3'     (I)

wherein: i and j are each independently 0 or 1; p and q are each independently 0-6; each N a independently represents an oligonucleotide sequence comprising 2-10 modified nucleotides, each sequence comprising at least two differently modified nucleotides; each Nb independently represents an oligonucleotide sequence comprising 0, 1, 2, 3, 4, 5, or 6 modified nucleotides, preferably 2'-O-methyl modified nucleotides; each n p and n q independently represent an overhang nucleotide; wherein N b and Y do not have the same modification; wherein XXX, YYY and ZZZ each independently represent one motif of three identical modifications on three consecutive nucleotides; and wherein the antisense strand of the dsRNA comprises two blocks of two phosphorothioate or methylphosphonate internucleotide linkages separated by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 phosphate internucleotide linkages.