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1. 发明专利

AU3764099A Polyanionic polymers which enhance fusogenicity 未知
公开(公告)号：AU3764099A
公开(公告)日：1999-11-16
申请号：AU3764099
申请日：1999-04-27
申请人： INEX PHARMACEUTICALS CORP , TAO CHEN , YUEHUA HE , PETER CULLIS , THOMAS MADDEN , PETER SCHERRER , JUNG SOO KIM , DAVID TIRRELL , PHALGUN JOSHI
发明人： CHEN TAO , HE YUEHUA , CULLIS PETER , MADDEN THOMAS , SCHERRER PETER , KIM JUNG SOO , TIRRELL DAVID , JOSHI PHALGUN
IPC分类号： A61K9/127 , C08F8/00 , C08F8/32 , C08F8/34

2. 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。

3. 发明授权

US5976567A Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer 失效
公开(公告)号：US5976567A
公开(公告)日：1999-11-02
申请号：US660025
申请日：1996-06-06
申请人： Jeffery J. Wheeler , Marcel B. Bally , Yuan-Peng Zhang , Dorothy L. Reimer , Michael Hope , Pieter R. Cullis , Peter Scherrer
发明人： Jeffery J. Wheeler , Marcel B. Bally , Yuan-Peng Zhang , Dorothy L. Reimer , Michael Hope , Pieter R. Cullis , Peter Scherrer
IPC分类号： C12N15/09 , A61K9/127 , A61K48/00 , C12N15/88 , A61K31/70
CPC分类号： A61K47/48815 , A61K9/1272 , C12N15/88
摘要： Novel lipid-nucleic acid particulate complexes which are useful for in vitro or in vivo gene transfer are described. The particles can be formed using either detergent dialysis methods or methods which utilize organic solvents. Upon removal of a solubilizing component (i.e., detergent or an organic solvent) the lipid-nucleic acid complexes form particles wherein the nucleic acid is serum-stable and is protected from degradation. The particles thus formed have access to extravascular sites and target cell populations and are suitable for the therapeutic delivery of nucleic acids.

4. 发明授权

US07341738B2 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：US07341738B2
公开(公告)日：2008-03-11
申请号：US10658947
申请日：2003-09-09
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 , 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。

5. 发明授权

US06986902B1 Polyanionic polymers which enhance fusogenicity 失效
标题翻译：增强融合性的聚阴离子聚合物
公开(公告)号：US06986902B1
公开(公告)日：2006-01-17
申请号：US09674191
申请日：1999-04-27
申请人： Tao Chen , Yuehua He , Peter Cullis , Thomas Madden , Peter Scherrer , David Tirrell , Phalgun Joshi , Jung Soo Kim
发明人： Tao Chen , Yuehua He , Peter Cullis , Thomas Madden , Peter Scherrer , David Tirrell , Phalgun Joshi , Jung Soo Kim
IPC分类号： A61K9/127 , C08G63/48 , C08G67/02 , C08F265/08
CPC分类号： A61K9/1273 , C08F8/12 , C08F8/30 , C08F8/32 , C08F120/06 , C08F297/026
摘要： The present invention relates generally to the amphiphilic polyelectrolyte, poly(2-ethylacrylic acid) and covalently bonded lipids to generate Lipo-PEAA. These Lipo-PEAA are then used to make pH-sensitive liposomes which become unstable, permeable or fusogenic with certain pH changes. In addition, this invention generally describes methods for delivering therapeutic compounds and drugs to target cells by administering to a host the pH-sensitive liposomes of the present invention.
摘要翻译：本发明一般涉及两亲性聚电解质，聚（2-乙基丙烯酸）和共价键合的脂质以产生Lipo-PEAA。然后将这些Lipo-PEAA用于制备pH敏感的脂质体，其在某些pH变化下变得不稳定，可渗透或融合。此外，本发明总体上描述了通过向宿主施用本发明的pH敏感脂质体来将治疗化合物和药物递送至靶细胞的方法。

6. 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。

7. 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。

8. 发明授权

US07422902B1 Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer 失效
标题翻译：通过疏水性脂质 - 核酸复合物中间体制备并用于基因转移的脂质 - 核酸颗粒
公开(公告)号：US07422902B1
公开(公告)日：2008-09-09
申请号：US09431594
申请日：1999-11-01
申请人： Jeffery J. Wheeler , Marcel B. Bally , Yuan-Peng Zhang , Dorothy L. Reimer , Michael Hope , Pieter R. Cullis , Peter Scherrer
发明人： Jeffery J. Wheeler , Marcel B. Bally , Yuan-Peng Zhang , Dorothy L. Reimer , Michael Hope , Pieter R. Cullis , Peter Scherrer
IPC分类号： C12N15/88 , C12Q1/68 , A61K9/127 , C07H21/04 , A01N43/04
CPC分类号： A61K9/1272 , A61K47/6911 , C12N15/88 , Y10S436/829
摘要： Novel lipid-nucleic acid particulate complexes which are useful for in vitro or in vivo gene transfer are described. The particles can be formed using either detergent dialysis methods or methods which utilize organic solvents. Upon removal of a solubilizing component (i.e., detergent or an organic solvent) the lipid-nucleic acid complexes form particles wherein the nucleic acid is serum-stable and is protected from degradation. The particles thus formed have access to extravascular sites and target cell populations and are suitable for the therapeutic delivery of nucleic acids.
摘要翻译：描述了可用于体外或体内基因转移的新型脂质 - 核酸颗粒复合物。可以使用洗涤剂透析方法或利用有机溶剂的方法形成颗粒。在除去增溶组分（即洗涤剂或有机溶剂）后，脂质 - 核酸复合物形成其中核酸是血清稳定的并且被保护免于降解的颗粒。由此形成的颗粒可以进入血管外部位和靶细胞群，并且适合于治疗性递送核酸。

9. 发明申请

US20050255153A1 High efficiency encapsulation of charged therapeutic agents in lipid vesicles 有权
标题翻译：电荷治疗剂在脂质囊泡中的高效包封
公开(公告)号：US20050255153A1
公开(公告)日：2005-11-17
申请号：US10658947
申请日：2003-09-09
申请人： Sean Semple , Sandra Klimuk , Troy Harasym , Michael Hope , Steven Ansell , Pieter Cullis , Peter Scherrer , Dan Debeyer
发明人： Sean Semple , Sandra Klimuk , Troy Harasym , Michael Hope , Steven 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
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。

10. 发明授权

US06734171B1 Methods for encapsulating nucleic acids in lipid bilayers 失效
标题翻译：将核酸包封在脂质双层中的方法
公开(公告)号：US06734171B1
公开(公告)日：2004-05-11
申请号：US09169573
申请日：1998-10-09
申请人： Edward George Saravolac , Yuan-Peng Zhang , Jeffery J. Wheeler , Pieter R. Cullis , Peter Scherrer , Ljiljana D. Kojic , Olga Ludkovski
发明人： Edward George Saravolac , Yuan-Peng Zhang , Jeffery J. Wheeler , Pieter R. Cullis , Peter Scherrer , Ljiljana D. Kojic , Olga Ludkovski
IPC分类号： A61K4800
CPC分类号： A61K48/0041 , A61K48/0008 , A61K48/0025
摘要： The present invention relates to lipid-based formulations for nucleic acid delivery to cells, methods for the preparation of such formulations and, in particular, to lipid encapsulated plasmids. The compositions are safe and practical for clinical use. In addition, the present invention provides methods for introducing nucleic acids into cells and for inhibiting tumor growth in cells using such lipid-nucleic acid formulations.
摘要翻译：本发明涉及用于核酸递送至细胞的基于脂质的制剂，用于制备这些制剂的方法，特别是脂质包封的质粒。组合物对于临床使用是安全和实用的。此外，本发明提供了使用这种脂质 - 核酸制剂将核酸引入细胞并抑制细胞中的肿瘤生长的方法。

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