公开(公告)号：WO2010144740A1

公开(公告)日：2010-12-16

申请号：PCT/US2010/038224

申请日：2010-06-10

申请人： ALNYLAM PHARMACEUTICALS, INC. ,  CHEN, Jianxin ,  ANSELL, Steven ,  AKINC, Akin ,  DORKIN, Joseph, R. ,  QIN, Xiaojun ,  CANTLEY, William ,  MANOHARAN, Muthiah ,  RAJEEV, Kallanthottathil, G. ,  NARAYANANNAIR, Jayaprakash, K. ,  JAYARAMAN, Muthusamy

发明人： CHEN, Jianxin ,  ANSELL, Steven ,  AKINC, Akin ,  DORKIN, Joseph, R. ,  QIN, Xiaojun ,  CANTLEY, William ,  MANOHARAN, Muthiah ,  RAJEEV, Kallanthottathil, G. ,  NARAYANANNAIR, Jayaprakash, K. ,  JAYARAMAN, Muthusamy

IPC分类号： A61K9/127 ,  C07C211/00 ,  A61K31/20

CPC分类号： A61K9/1272 ,  A61K9/1278 ,  A61K31/22 ,  A61K31/7088 ,  A61K31/712 ,  A61K31/713 ,  A61K38/1709 ,  A61K38/4846 ,  A61K47/14 ,  A61K47/549 ,  A61K47/551 ,  A61K47/6911 ,  A61K48/0033 ,  C07C29/58 ,  C07C227/18 ,  C07C227/40 ,  C07C229/12 ,  C07D475/04 ,  C12N15/113 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/341 ,  C12N2310/346 ,  C12N2310/351 ,  C12N2310/3515 ,  C12N2320/32 ,  Y02A50/463 ,  A61K2300/00 ,  C12N2310/3521 ,  C12N2310/3533

摘要： The invention features a cationic lipid of formula (I), an improved lipid formulation comprising a cationic lipid of formula I and corresponding methods of use. Also disclosed are targeting lipids, and specific lipid formulations comprising such targeting lipids.

摘要翻译： 本发明的特征在于式（I）的阳离子脂质，包含式I的阳离子脂质和相应的使用方法的改进的脂质制剂。 还公开了靶向脂质和包含这种靶向脂质的特定脂质制剂。

公开(公告)号：WO2010088537A2

公开(公告)日：2010-08-05

申请号：PCT/US2010/022614

申请日：2010-01-29

申请人： ALNYLAM PHARMACEUTICALS, INC. ,  AKINC, Akin ,  QUERBES, William ,  WONG, Frances ,  DORKIN, Joseph, Robert ,  QIN, Xiaojun ,  CANTLEY, William ,  BORODOVSKY, Anna ,  DE, Soma ,  MANOHARAN, Muthiah ,  JAYARAMAN, Muthusamy ,  RAJEEV, Kallanthottathil, G.

发明人： AKINC, Akin ,  QUERBES, William ,  WONG, Frances ,  DORKIN, Joseph, Robert ,  QIN, Xiaojun ,  CANTLEY, William ,  BORODOVSKY, Anna ,  DE, Soma ,  MANOHARAN, Muthiah ,  JAYARAMAN, Muthusamy ,  RAJEEV, Kallanthottathil, G.

IPC分类号： A61K9/127

CPC分类号： A61K48/0008 ,  A61K9/1272

摘要： The invention features an improved lipid formulation comprising a cationic lipid of formula (A), a neutral lipid, a sterol and a PEG or PEG-modified lipid, where R 1 and R 2 are independently alkyl, alkenyl or alkynyl, each can be optionally substituted, and R 3 and R 4 are independently lower alkyl or R 3 and R 4 can be taken together to form an optionally subsituted heterocyclic ring. In one embodiment, R 1 and R 2 are independently selected from oleoyl, pamitoyl, steroyl, linoleyl and R 3 and R 4 are methyl. Also disclosed are targeting lipids, and specific lipid formulations comprising such targeting lipids.

摘要翻译： 本发明的特征在于改进的脂质制剂，其包含式（A）的阳离子脂质，中性脂质，固醇和PEG或PEG修饰的脂质，其中R 1和R 2独立地为烷基，烯基或炔基，各自可任选被取代， 并且R 3和R 4独立地为低级烷基或R 3和R 4可以一起形成任选取代的杂环。 在一个实施方案中，R 1和R 2独立地选自油酰基，苯甲酰基，甾烷基，亚油酰基，并且R 3和R 4是甲基。 还公开了靶向脂质和包含这种靶向脂质的特定脂质制剂。

公开(公告)号：WO2009132131A1

公开(公告)日：2009-10-29

申请号：PCT/US2009/041442

申请日：2009-04-22

申请人： ALNYLAM PHARMACEUTICALS, INC. ,  MANOHARAN, Muthiah ,  RAJEEV, Kallanthottathil, G. ,  JAYARAMAN, Muthusamy ,  BUTLER, David ,  WONG, Frances ,  AKINC, Akin ,  DORKIN, Joseph, R. ,  QIN, Xiaojun

发明人： MANOHARAN, Muthiah ,  RAJEEV, Kallanthottathil, G. ,  JAYARAMAN, Muthusamy ,  BUTLER, David ,  WONG, Frances ,  AKINC, Akin ,  DORKIN, Joseph, R. ,  QIN, Xiaojun

IPC分类号： C07D317/28 ,  A61K9/127 ,  A61K47/48

CPC分类号： C07D317/28 ,  A61K9/1272 ,  A61K47/543 ,  A61K47/6911

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 aicd 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. Formulae (I), (II), (III), (IV).

摘要翻译： 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，并将包封的核酸在体内有效递送到细胞。 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。 式（I），（II），（III），（IV）。

公开(公告)号：WO2010088537A3

公开(公告)日：2010-09-23

申请号：PCT/US2010022614

申请日：2010-01-29

申请人： ALNYLAM PHARMACEUTICALS INC ,  AKINC AKIN ,  QUERBES WILLIAM ,  WONG FRANCES ,  DORKIN JOSEPH ROBERT ,  QIN XIAOJUN ,  CANTLEY WILLIAM ,  BORODOVSKY ANNA ,  DE SOMA ,  MANOHARAN MUTHIAH ,  JAYARAMAN MUTHUSAMY ,  RAJEEV KALLANTHOTTATHIL G

发明人： AKINC AKIN ,  QUERBES WILLIAM ,  WONG FRANCES ,  DORKIN JOSEPH ROBERT ,  QIN XIAOJUN ,  CANTLEY WILLIAM ,  BORODOVSKY ANNA ,  DE SOMA ,  MANOHARAN MUTHIAH ,  JAYARAMAN MUTHUSAMY ,  RAJEEV KALLANTHOTTATHIL G

IPC分类号： A61K9/127 ,  A61K48/00

CPC分类号： A61K48/0008 ,  A61K9/1272

摘要： The invention features an improved lipid formulation comprising a cationic lipid of formula (A), a neutral lipid, a sterol and a PEG or PEG-modified lipid, where R1 and R2 are independently alkyl, alkenyl or alkynyl, each can be optionally substituted, and R3 and R4 are independently lower alkyl or R3 and R4 can be taken together to form an optionally subsituted heterocyclic ring. In one embodiment, R1 and R2 are independently selected from oleoyl, pamitoyl, steroyl, linoleyl and R3 and R4 are methyl. Also disclosed are targeting lipids, and specific lipid formulations comprising such targeting lipids.

摘要翻译： 本发明的特征在于改进的脂质制剂，其包含式（A）的阳离子脂质，中性脂质，固醇和PEG或PEG修饰的脂质，其中R 1和R 2独立地为烷基，烯基或炔基，各自可任选被取代， 并且R 3和R 4独立地为低级烷基或R 3和R 4可以一起形成任选取代的杂环。 在一个实施方案中，R 1和R 2独立地选自油酰基，苯甲酰基，甾烷基，亚油酰基，并且R 3和R 4是甲基。 还公开了靶向脂质和包含这种靶向脂质的特定脂质制剂。