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1. 发明授权

US08021686B2 Lipid-encapsulated polyanionic nucleic acid 有权
标题翻译：脂质包封的聚阴离子核酸
公开(公告)号：US08021686B2
公开(公告)日：2011-09-20
申请号：US12028696
申请日：2008-02-08
申请人： Sean C. Semple , Sandra K. Klimuk , Troy Harasym , Michael J. Hope , Steven M. Ansell , Pieter R. Cullis , Peter Scherrer , Dan Debeyer
发明人： Sean C. Semple , Sandra K. Klimuk , Troy Harasym , Michael J. Hope , Steven M. Ansell , Pieter R. Cullis , Peter Scherrer , Dan Debeyer
IPC分类号： A61K9/127 , A61K31/70 , C12N11/02 , C12N15/88 , C07H21/00
CPC分类号： A61K9/1277 , A61K9/1272 , Y10T428/2984
摘要： Methods for the preparation of a lipid-nucleic acid composition are provided. According to the methods, a mixture of lipids containing a protonatable or deprotonatable lipid, for example an amino lipid and a lipid such as a PEG- or Polyamide oligomer-modified lipid is combined with a buffered aqueous solution of a charged therapeutic agent, for example polyanionic nucleic acids, to produce particles in which the therapeutic agent is encapsulated in a lipid vesicle. Surface charges on the lipid particles are at least partially neutralized to provide surface-neutralized lipid-encapsulated compositions of the therapeutic agents. The method permits the preparation of compositions with high ratios of therapeutic agent to lipid and with encapsulation efficiencies in excess of 50%.
摘要翻译：提供了制备脂质 - 核酸组合物的方法。根据该方法，将包含可质子化或不可质令排泄的脂质，例如氨基脂质和脂质如PEG-或聚酰胺低聚物修饰的脂质的脂质混合物与带电疗法的缓冲水溶液组合，例如聚阴离子核酸，以产生其中治疗剂包封在脂质囊泡中的颗粒。脂质颗粒上的表面电荷至少部分被中和，以提供治疗剂的表面中和的脂质包封的组合物。该方法允许制备具有高比例的治疗剂与脂质并且包封效率超过50％的组合物。

2. 发明申请

US20110117125A1 COMPOSITIONS AND METHODS FOR THE DELIVERY OF NUCLEIC ACIDS 审中-公开
标题翻译：用于提供核酸的组合物和方法
公开(公告)号：US20110117125A1
公开(公告)日：2011-05-19
申请号：US12811195
申请日：2008-12-31
申请人： Michael J. Hope , Sean C. Semple , Jianxin Chen , Thomas D. Madden , Barbara Mui , Pieter R. Cullis , Marco A. Ciufolini , Kim F. Wong , Muthiah Manoharan , Rajeev G. Kallanthottathil
发明人： Michael J. Hope , Sean C. Semple , Jianxin Chen , Thomas D. Madden , Barbara Mui , Pieter R. Cullis , Marco A. Ciufolini , Kim F. Wong , Muthiah Manoharan , Rajeev G. Kallanthottathil
IPC分类号： A61K39/12 , A61K39/00 , A61K39/02 , C12N5/02 , A61K31/7088 , A61P37/00 , C07D295/12 , C07D241/04 , C07D317/00 , C11C3/00 , C07C229/00 , C07C229/30 , C07C321/00
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.
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。

3. 发明授权

US07811602B2 Liposomal formulations comprising dihydrosphingomyelin and methods of use thereof 有权
标题翻译：包含二氢鞘磷脂的脂质体制剂及其使用方法
公开(公告)号：US07811602B2
公开(公告)日：2010-10-12
申请号：US11131436
申请日：2005-05-16
申请人： Pieter R Cullis , Thomas D Madden , Michael J Hope , Steven M Ansell , Barbara L S Mui , Sean C Semple , Norbert Maurer
发明人： Pieter R Cullis , Thomas D Madden , Michael J Hope , Steven M Ansell , Barbara L S Mui , Sean C Semple , Norbert Maurer
IPC分类号： A61K9/127
CPC分类号： A61K31/4745 , A61K9/1272 , A61K9/1278 , A61K33/32 , A61K2300/00
摘要： 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.
摘要翻译：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。

4. 发明授权

US07311924B2 Compositions and methods for treating cancer 有权
标题翻译：用于治疗癌症的组合物和方法
公开(公告)号：US07311924B2
公开(公告)日：2007-12-25
申请号：US10407864
申请日：2003-04-03
申请人： Andreas H Sarris , Fernando Cabanillas , Patricia M Logan , Clive T R Burge , James H Goldie , Murray S Webb , Thomas D Madden , Sean C Semple , Quet F Ahkong , Sandra K Klimuk
发明人： Andreas H Sarris , Fernando Cabanillas , Patricia M Logan , Clive T R Burge , James H Goldie , Murray S Webb , Thomas D Madden , Sean C Semple , Quet F Ahkong , Sandra K Klimuk
IPC分类号： A61K9/127
CPC分类号： A61K45/06 , A61K9/127 , A61K9/1272 , A61K9/1278 , A61K31/4745 , A61K31/475 , A61K31/704 , A61K2300/00
摘要： This invention provides compositions and methods for treating neoplasias in a mammal. In particular, the invention provides liposome-encapsulated vinca alkaloids, e.g., vinorelbine, and methods of treating a mammal using such compositions.
摘要翻译：本发明提供用于治疗哺乳动物的肿瘤的组合物和方法。特别地，本发明提供脂质体包封的长春花生物碱，例如长春瑞滨，以及使用这种组合物治疗哺乳动物的方法。

5. 发明授权

US06287591B1 Charged therapeutic agents encapsulated in lipid particles containing four lipid components 失效
标题翻译：包含在含有四种脂质组分的脂质颗粒中的带电治疗剂
公开(公告)号：US06287591B1
公开(公告)日：2001-09-11
申请号：US09078954
申请日：1998-05-14
申请人： Sean C. Semple , Sandra K. Klimuk , Troy Harasym , Michael J. Hope , Steven M. Ansell , Pieter Cullis , Peter Scherrer , Dan Debeyer
发明人： Sean C. Semple , Sandra K. Klimuk , Troy Harasym , Michael J. Hope , Steven M. Ansell , Pieter Cullis , Peter Scherrer , Dan Debeyer
IPC分类号： A61K9127
CPC分类号： A61K9/1277 , A61K9/1272 , Y10T428/2984
摘要： Lipid-therapeutic agent particles are prepared containing a charged therapeutic agent encapsulated in lipid portion containing at least two lipid components including a protonatable or deprotonatable lipid such as an amino lipid and a lipid that prevents particle aggregation during lipid-therapeutic agent particle formation such as a PEG-modified or polyamide oligomer-modified lipid. Other lipid components may also be present and these include a neutral lipid such as DSPC, POPC, DOPE or SM, and a sterol such as Chol. The therapeutic agent is encapsulated by combining a mixture of the lipids with a buffered aqueous solution of a charged therapeutic agent to form an intermediate mixture containing lipid-encapsulated therapeutic agent particles, and changing the pH of the intermediate mixture to neutralize at least some surface charges on the particles. The method permits high ratios of therapeutic agent to lipid and encapsulation efficiencies in excess of 50%. The method is particularly useful for preparing lipid-encapsulated nucleic acids such as an antisense polyanionic nucleic acid having exclusively phosphodiester linkages. The encapsulated nucleic acid can be contacted with a cell to introduce the nucleic acid into the cell such as for treatment or prevention of a disease characterized by aberrant expression of a gene. A pharmaceutical composition may be prepared containing the lipid-encapsulated therapeutic agent particles and a carrier.
摘要翻译：制备包含含有至少两种脂质组分的脂质部分的带电治疗剂的脂质治疗剂颗粒，所述脂质组分包括可质子化或可去质子化的脂质如氨基脂质和防止脂质治疗剂颗粒形成期间的颗粒聚集的脂质，例如 PEG修饰或聚酰胺低聚物修饰的脂质。其他脂质组分也可以存在，它们包括中性脂质如DSPC，POPC，DOPE或SM，以及甾醇如Chol。通过将所述脂质的混合物与带电治疗剂的缓冲水溶液组合以形成含有脂质包封的治疗剂颗粒的中间体混合物并改变中间体混合物的pH以中和至少一些表面电荷来封装治疗剂在颗粒上。该方法允许高比例的治疗剂与脂质和包封效率超过50％。该方法特别可用于制备脂质包封的核酸，例如仅具有磷酸二酯键的反义聚阴离子核酸。封装的核酸可以与细胞接触以将核酸引入细胞，例如用于治疗或预防以基因异常表达为特征的疾病。可以制备含有脂质包封的治疗剂颗粒和载体的药物组合物。

6. 发明授权

US07244448B2 Liposomal antineoplastic drugs and uses thereof 有权
标题翻译：脂质体抗肿瘤药物及其用途
公开(公告)号：US07244448B2
公开(公告)日：2007-07-17
申请号：US09896812
申请日：2001-06-29
申请人： Thomas D. Madden , Sean C. Semple , Quet F. Ahkong
发明人： Thomas D. Madden , Sean C. Semple , Quet F. Ahkong
IPC分类号： A61K9/127
CPC分类号： A61K9/127 , A61K9/1272 , A61K9/1278 , A61K31/4745 , A61K45/06 , A61K2300/00
摘要： 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.
摘要翻译：本发明涉及脂质体抗肿瘤剂（例如喜树碱）组合物和使用这些组合物治疗瘤形成和抑制血管生成的方法。组合物和方法可用于调节活性剂的血浆循环半衰期。

7. 发明授权

US06858225B2 Lipid-encapsulated polyanionic nucleic acid 有权
标题翻译：脂质包封的聚阴离子核酸
公开(公告)号：US06858225B2
公开(公告)日：2005-02-22
申请号：US09895480
申请日：2001-06-29
申请人： Sean C. Semple , Sandra K. Klimuk , Troy Harasym , Michael J. Hope , Steven M. Ansell , Pieter Cullis , Peter Scherrer , Dan Debeyer
发明人： Sean C. Semple , Sandra K. Klimuk , Troy Harasym , Michael J. Hope , Steven M. Ansell , Pieter Cullis , Peter Scherrer , Dan Debeyer
IPC分类号： A61K9/127 , A61K9/50 , A61K31/7105 , A61K31/711 , A61K47/28 , A61K47/44 , A61K48/00 , A61K31/70 , C07H21/00 , C12N11/02 , C12N15/88
CPC分类号： A61K9/1277 , A61K9/1272 , Y10T428/2984
摘要： Methods for the preparation of a lipid-nucleic acid composition are provided. According to the methods, a mixture of lipids containing a protonatable or deprotonatable lipid, for example an amino lipid and a lipid such as a PEG- or Polyamide oligomer-modified lipid is combined with a buffered aqueous solution of a charged therapeutic agent, for example polyanionic nucleic acids, to produce particles in which the therapeutic agent is encapsulated in a lipid vesicle. Surface charges on the lipid particles are at least partially neutralized to provide surface-neutralized lipid-encapsulated compositions of the therapeutic agents. The method permits the preparation of compositions with high ratios of therapeutic agent to lipid and with encapsulation efficiencies in excess of 50%.
摘要翻译：提供了制备脂质 - 核酸组合物的方法。根据该方法，将包含可质子化或不可质令排泄的脂质，例如氨基脂质和脂质如PEG-或聚酰胺低聚物修饰的脂质的脂质混合物与带电疗法的缓冲水溶液组合，例如聚阴离子核酸，以产生其中治疗剂包封在脂质囊泡中的颗粒。脂质颗粒上的表面电荷至少部分被中和，以提供治疗剂的表面中和的脂质包封的组合物。该方法允许制备具有高比例的治疗剂与脂质并且包封效率超过50％的组合物。

8. 发明申请

US20130136787A1 Liposomal Camptothecins and Uses Thereof 审中-公开
标题翻译：脂质体营养素及其用途
公开(公告)号：US20130136787A1
公开(公告)日：2013-05-30
申请号：US13536325
申请日：2012-06-28
申请人： Thomas D. Madden , Sean C. Semple
发明人： Thomas D. Madden , Sean C. Semple
IPC分类号： A61K9/127
CPC分类号： A61K9/127 , A61K9/1272 , A61K9/1278 , A61K31/4745 , A61K45/06 , A61K2300/00
摘要： This invention relates to improved liposomal camptothecin compositions and methods of manufacturing and using such compositions for treating neoplasia and for inhibiting angiogenesis.
摘要翻译：本发明涉及改进的脂质体喜树碱组合物以及制备和使用这些组合物治疗瘤形成和抑制血管生成的方法。

9. 发明申请

US20110256175A1 AMINO LIPIDS AND METHODS FOR THE DELIVERY OF NUCLEIC ACIDS 有权
标题翻译：氨基酸和提供核酸的方法
公开(公告)号：US20110256175A1
公开(公告)日：2011-10-20
申请号：US13123307
申请日：2009-10-09
申请人： Michael J. Hope , Sean C. Semple , Jianxin Chen , Thomas D. Madden , Pieter R. Cullis , Marco A. Ciufolini , Barbara Low Shoud Mui
发明人： Michael J. Hope , Sean C. Semple , Jianxin Chen , Thomas D. Madden , Pieter R. Cullis , Marco A. Ciufolini , Barbara Low Shoud Mui
IPC分类号： A61K39/12 , C07D319/06 , C07D405/06 , C07D413/06 , A61K47/44 , A61K31/7088 , A61K48/00 , A61K31/713 , C12N5/071 , C12N15/63 , A61K39/02 , A61K39/00 , A61P37/04 , A61P35/00 , A61P31/12 , A61P31/04 , A61P33/00 , C07D317/28
CPC分类号： A61K47/22 , A61K9/1271 , A61K31/713 , A61K39/39 , A61K2039/55511 , C07D317/28 , C07D319/06
摘要： 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.
摘要翻译：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。

10. 发明授权

US07452550B2 Liposomal antineoplastic drugs and uses thereof 有权
标题翻译：脂质体抗肿瘤药物及其用途
公开(公告)号：US07452550B2
公开(公告)日：2008-11-18
申请号：US11430522
申请日：2006-05-09
申请人： Thomas D. Madden , Sean C. Semple , Quet F. Ahkong
发明人： Thomas D. Madden , Sean C. Semple , Quet F. Ahkong
IPC分类号： A61K9/127
CPC分类号： A61K9/127 , A61K9/0019 , A61K31/4745 , A61K31/496
摘要： 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.
摘要翻译：本发明涉及脂质体抗肿瘤剂（例如喜树碱）组合物和使用这些组合物治疗瘤形成和抑制血管生成的方法。组合物和方法可用于调节活性剂的血浆循环半衰期。

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