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21. 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.

22. 发明授权

US5780054A Methods for increasing the circulation half-life of protein-based therapeutics 失效
标题翻译：增加蛋白质治疗剂循环半衰期的方法
公开(公告)号：US5780054A
公开(公告)日：1998-07-14
申请号：US588014
申请日：1996-01-17
申请人： Paul G. Tardi , Erik Swartz , Marcel B. Bally , Pieter R. Cullis
发明人： Paul G. Tardi , Erik Swartz , Marcel B. Bally , Pieter R. Cullis
IPC分类号： A61K9/127
CPC分类号： A61K9/1271 , Y10S436/829
摘要： Methods of increasing the circulation half-life of protein-based therapeutics in a host, the methods comprising: (a) administering to the host an amount of a first liposome formulation comprising liposomes and an antineoplastic agent; and (b) administering to the host a second formulation comprising the protein-based therapeutic, wherein the amount of the first liposome formulation is sufficient to suppress an immune response to the protein-based therapeutic of the second formulation, thereby increasing the circulation half-life of the protein-based therapeutic.
摘要翻译：增加宿主中基于蛋白质的治疗剂的循环半衰期的方法，所述方法包括：（a）向宿主施用一定量的包含脂质体和抗肿瘤剂的第一脂质体制剂; 并且（b）向宿主施用包含基于蛋白质的治疗剂的第二制剂，其中第一脂质体制剂的量足以抑制对第二制剂的基于蛋白质的治疗的免疫应答，从而增加循环半衰期，基于蛋白质的治疗的生命。

23. 发明授权

US5380531A Accumulations of amino acids and peptides into liposomes 失效
标题翻译：将氨基酸和肽累积到脂质体中
公开(公告)号：US5380531A
公开(公告)日：1995-01-10
申请号：US896509
申请日：1992-06-02
申请人： Ajoy Chakrabarti , Ian Clark-Lewis , Pieter R. Cullis
发明人： Ajoy Chakrabarti , Ian Clark-Lewis , Pieter R. Cullis
IPC分类号： A61K9/127 , A61K31/223 , A61K38/00 , A61K38/10 , A61K38/22 , A61K38/25
CPC分类号： A61K9/1278 , A61K31/00 , A61K38/105 , A61K38/2207 , A61K38/25 , Y10S436/829 , Y10T428/2984
摘要： The present invention relates to liposomal compositions having a concentration gradient which load amino acids and peptides exhibiting weak acid or base characteristics into liposomes. Specifically loaded into liposomes by the methods of the present invention are C-terminal substituted amino acids or peptides. The liposomes are preferably large unilamellar vesicles. The concentration gradient is formed by encapsulating a first medium in the liposomes, said medium having a first concentration of the one or more charged species, and suspending the liposomes in a second medium having a second concentration of the one or more charged species, such as for example a pH gradient. Also disclosed are pharmaceutical preparations comprising such C-terminal substituted amino acids or peptides which have been loaded into the liposomes by the method of the invention.
摘要翻译：本发明涉及脂质体组合物，其具有将氨基酸和显示出弱酸或碱特征的肽加载到脂质体中的浓度梯度。通过本发明的方法特异性加载到脂质体中是C-末端取代的氨基酸或肽。脂质体优选是大的单层囊泡。浓缩梯度通过将脂质体中的第一培养基包封而形成，所述培养基具有一种或多种带电物质的第一浓度，并将脂质体悬浮在第二培养基中，所述第二培养基具有一种或多种带电物质的第二浓度，例如例如pH梯度。还公开了包含通过本发明的方法加载到脂质体中的这种C末端取代的氨基酸或肽的药物制剂。

24. 发明授权

US5204112A Induction of asymmetry in vesicles 失效
公开(公告)号：US5204112A
公开(公告)日：1993-04-20
申请号：US61837
申请日：1987-06-12
申请人： Michael J. Hope , Pieter R. Cullis
发明人： Michael J. Hope , Pieter R. Cullis
IPC分类号： A61K9/127 , A61K9/133
CPC分类号： A61K9/1277 , A61K9/1278 , Y10S436/829 , Y10T428/2984
摘要： Methods are described for controlling the transbilayer distribution of ionizable lipids and proteins in vesicles. Control of the ion gradient of the exterior bathing medium in relation to that of the interior entrapped aqueous compartment of the vesicles induces migration of ionizable lipids or proteins to one or the other of the monolayers comprising the bilayer. This can result in an asymmetric distribution of the ionizable lipid or ionizable protein. The basic ionizable lipids, such as stearylamine and sphingosine, are sequestered into the inner monolayer when the liposome interior is acidic relative to the liposome exterior. Conversely, acidic ionizable lipids such as oleic acid and stearic acid are sequestered into the inner monolayer when the liposome interior is basic relative to the liposome exterior bathing solution. Likewise, phospholipids such as phosphatidylglycerol, phosphatidylinositol, and cardiolipin may also be sequestered into the inner monolayer in response to a relatively acidic exterior medium. Such vesicles may contain bioactive agents and may be administered to mammals including humans.

25. 发明申请

US20140199374A1 METHODS FOR PREPARATION OF LIPID-ENCAPSULATED THERAPEUTIC AGENTS 审中-公开
标题翻译：用于制备脂质体包封治疗剂的方法
公开(公告)号：US20140199374A1
公开(公告)日：2014-07-17
申请号：US14140273
申请日：2013-12-24
申请人： Norbert Maurer , Pieter R. Cullis , Kim F. Wong
发明人： Norbert Maurer , Pieter R. Cullis , Kim F. Wong
IPC分类号： A61K9/127 , A61K31/7105 , A61K31/711
CPC分类号： A61K9/1278 , A61K9/127 , A61K9/1272 , A61K9/5089 , A61K31/7088 , A61K31/7105 , A61K31/711
摘要： Fully lipid-encapsulated therapeutic agent particles of a charged therapeutic agent are prepared by combining a lipid composition containing preformed lipid vesicles, a charged therapeutic agent, and a destabilizing agent to form a mixture of preformed vesicles and therapeutic agent in a destabilizing solvent. The destabilizing solvent is effective to destabilize the membrane of the preformed lipid vesicles without disrupting the vesicles. The resulting mixture is incubated for a period of time sufficient to allow the encapsulation of the therapeutic agent within the preformed lipid vesicles. The destabilizing agent is then removed to yield fully lipid-encapsulated therapeutic agent particles. The preformed lipid vesicles comprise a charged lipid which has a charge which is opposite to the charge of the charged therapeutic agent and a modified lipid having a steric barrier moiety for control of aggregation.
摘要翻译：通过将含有预先形成的脂质囊泡的脂质组合物，带电的治疗剂和去稳定剂混合以在去稳定的溶剂中形成预先形成的囊泡和治疗剂的混合物来制备带电药物的完全脂质包封的治疗剂颗粒。不稳定溶剂有效地使预先形成的脂质囊泡的膜不稳定而不破坏囊泡。将所得混合物温育足以允许将预处理的脂质囊泡中的治疗剂包封的时间。然后去除去稳定剂以产生完全脂质包封的治疗剂颗粒。预先形成的脂质囊泡包含带电荷的脂质，其具有与带电的治疗剂的电荷相反的电荷和具有用于控制聚集的空间屏障部分的修饰的脂质。

26. 发明申请

US20130273146A1 METHODS FOR PREPARATION OF LIPID-ENCAPSULATED THERAPEUTIC AGENTS 审中-公开
标题翻译：用于制备脂质体包封治疗剂的方法
公开(公告)号：US20130273146A1
公开(公告)日：2013-10-17
申请号：US13789360
申请日：2013-03-07
申请人： Norbert Maurer , Pieter R. Cullis , Kim F. Wong
发明人： Norbert Maurer , Pieter R. Cullis , Kim F. Wong
IPC分类号： A61K9/50 , A61K9/127 , A61K31/7088
CPC分类号： A61K9/1278 , A61K9/127 , A61K9/1272 , A61K9/5089 , A61K31/7088 , A61K31/7105 , A61K31/711
摘要： Fully lipid-encapsulated therapeutic agent particles of a charged therapeutic agent are prepared by combining a lipid composition containing preformed lipid vesicles, a charged therapeutic agent, and a destabilizing agent to form a mixture of preformed vesicles and therapeutic agent in a destabilizing solvent. The destabilizing solvent is effective to destabilize the membrane of the preformed lipid vesicles without disrupting the vesicles. The resulting mixture is incubated for a period of time sufficient to allow the encapsulation of the therapeutic agent within the preformed lipid vesicles. The destabilizing agent is then removed to yield fully lipid-encapsulated therapeutic agent particles. The preformed lipid vesicles comprise a charged lipid which has a charge which is opposite to the charge of the charged therapeutic agent and a modified lipid having a steric barrier moiety for control of aggregation.
摘要翻译：通过将含有预先形成的脂质囊泡的脂质组合物，带电的治疗剂和去稳定剂混合以在去稳定的溶剂中形成预先形成的囊泡和治疗剂的混合物来制备带电药物的完全脂质包封的治疗剂颗粒。不稳定溶剂有效地使预先形成的脂质囊泡的膜不稳定而不破坏囊泡。将所得混合物温育足以允许将预处理的脂质囊泡中的治疗剂包封的时间。然后去除去稳定剂以产生完全脂质包封的治疗剂颗粒。预先形成的脂质囊泡包含带电荷的脂质，其具有与带电的治疗剂的电荷相反的电荷和具有用于控制聚集的空间屏障部分的修饰的脂质。

27. 发明申请

US20120276209A1 NUCLEIC ACID-CONTAINING LIPID PARTICLES AND RELATED METHODS 有权
标题翻译：含有核酸的脂质和相关方法
公开(公告)号：US20120276209A1
公开(公告)日：2012-11-01
申请号：US13464690
申请日：2012-05-04
申请人： Pieter R. Cullis , Nathan M. Belliveau , Carl Lars Genghis Hansen , Jens Huft , James Taylor , Andre Wild , Stuart Malcolm , Ismail Hafez , Alex Leung , David Walker
发明人： Pieter R. Cullis , Nathan M. Belliveau , Carl Lars Genghis Hansen , Jens Huft , James Taylor , Andre Wild , Stuart Malcolm , Ismail Hafez , Alex Leung , David Walker
IPC分类号： A61K31/7088 , A61K9/50 , C12N5/071
CPC分类号： C12N15/88 , A61K9/1272 , A61K9/145 , A61K9/146 , A61K31/7088 , A61K47/22 , C12N15/111 , C12N15/113 , C12N2310/14 , C12N2320/32
摘要： Lipid particles containing a nucleic acid, devices and methods for making the lipid particles, and methods for using the lipid particles.
摘要翻译：含有核酸的脂质颗粒，用于制备脂质颗粒的装置和方法，以及使用脂质颗粒的方法。

28. 发明申请

US20110177130A1 METHODS FOR PREPARATION OF LIPID-ENCAPSULATED THERAPEUTIC AGENTS 审中-公开
标题翻译：用于制备脂质体包封治疗剂的方法
公开(公告)号：US20110177130A1
公开(公告)日：2011-07-21
申请号：US12871537
申请日：2010-08-30
申请人： Norbert Maurer , Kim F. Wong , Pieter R. Cullis
发明人： Norbert Maurer , Kim F. Wong , Pieter R. Cullis
IPC分类号： A61K9/00 , A61K48/00 , A61P43/00
CPC分类号： A61K9/1278 , A61K9/127 , A61K9/1272 , A61K9/5089 , A61K31/7088 , A61K31/7105 , A61K31/711
摘要： Fully lipid-encapsulated therapeutic agent particles of a charged therapeutic agent are prepared by combining a lipid composition containing preformed lipid vesicles, a charged therapeutic agent, and a destabilizing agent to form a mixture of preformed vesicles and therapeutic agent in a destabilizing solvent. The destabilizing solvent is effective to destabilize the membrane of the preformed lipid vesicles without disrupting the vesicles. The resulting mixture is incubated for a period of time sufficient to allow the encapsulation of the therapeutic agent within the preformed lipid vesicles. The destabilizing agent is then removed to yield fully lipid-encapsulated therapeutic agent particles. The preformed lipid vesicles comprise a charged lipid which has a charge which is opposite to the charge of the charged therapeutic agent and a modified lipid having a steric barrier moiety for control of aggregation.
摘要翻译：通过将含有预先形成的脂质囊泡的脂质组合物，带电的治疗剂和去稳定剂混合以在去稳定的溶剂中形成预先形成的囊泡和治疗剂的混合物来制备带电药物的完全脂质包封的治疗剂颗粒。不稳定溶剂有效地使预先形成的脂质囊泡的膜不稳定而不破坏囊泡。将所得混合物温育足以允许将预处理的脂质囊泡中的治疗剂包封的时间。然后去除去稳定剂以产生完全脂质包封的治疗剂颗粒。预先形成的脂质囊泡包含带电荷的脂质，其具有与带电的治疗剂的电荷相反的电荷和具有用于控制聚集的空间屏障部分的修饰的脂质。

29. 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。

30. 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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