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1. 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。

2. 发明申请

US20050008689A1 High efficiency encapsulation of charged therapeutic agents in lipid vesicles 审中-公开
公开(公告)号：US20050008689A1
公开(公告)日：2005-01-13
申请号：US10925734
申请日：2004-08-24
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 , 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%.

3. 发明申请

US20050249794A1 Compositions for stimulating cytokine secretion and inducing an immune response 审中-公开
标题翻译：用于刺激细胞因子分泌和诱导免疫应答的组合物
公开(公告)号：US20050249794A1
公开(公告)日：2005-11-10
申请号：US10788028
申请日：2004-02-26
申请人： Sean Semple , Troy Harasym , Sandra Klimuk , Ljiljiana Kojic , Jonathan Bramson , Barbara Mui , Michael Hope
发明人： Sean Semple , Troy Harasym , Sandra Klimuk , Ljiljiana Kojic , Jonathan Bramson , Barbara Mui , Michael Hope
IPC分类号： A61K9/127 , A61K39/00 , A61K39/39 , A61K48/00
CPC分类号： A61K39/39 , A61K9/1272 , A61K39/0011
摘要： Lipid-nucleic acid particles can provide therapeutic benefits, even when the nucleic acid is not complementary to coding sequences in target cells. It has been found that lipid-nucleic acid particles, including those containing non-sequence specific oligodeoxynucleotides, can be used to stimulate cytokine secretion, thus enhancing the overall immune response of a treated mammal. Further, immune response to specific target antigens can be induced by administration of a antigenic molecule in association with lipid particles containing non-sequence specific oligodeoxynucleotides. The nucleic acid which is included in the lipid-nucleic acid particle can be a phosphodiester (i.e., an oligodeoxynucleotide consisting of nucleotide residues joined by phosphodiester linkages) or a modified nucleic acid which includes phosphorothioate or other modified linkages, and may suitably be one which is non-complementary to the human genome, such that it acts to provide immunostimulation in a manner which is independent of conventional base-pairing interactions between the nucleic acid and nucleic acids of the treated mammal. In particular, the nucleic acid may suitably contain an immune-stimulating motif such as a CpG motif, or an immune stimulating palindromic sequence. The cationic lipid included in the nucleic acid particles may be suitably selected from among DODAP, DODMA, DMDMA, DOTAP, DC-Chol, DDAB, DODAC, DMRIE, DOSPA and DOGS. In addition, the lipid particle may suitably contain an modified aggregation-limiting lipid such as a PEG-lipid, a PAO-lipid or a ganglioside.
摘要翻译：即使当核酸与靶细胞中的编码序列不互补时，脂质 - 核酸颗粒也可提供治疗益处。已经发现，包括含有非序列特异性寡脱氧核苷酸的脂质核酸颗粒可用于刺激细胞因子分泌，从而增强被治疗哺乳动物的总体免疫应答。此外，可以通过与含有非序列特异性寡脱氧核苷酸的脂质颗粒结合施用抗原分子来诱导对特异性靶抗原的免疫应答。包含在脂质 - 核酸颗粒中的核酸可以是磷酸二酯（即，由通过磷酸二酯键连接的核苷酸残基组成的寡脱氧核苷酸）或包括硫代磷酸酯或其它修饰的连接基的修饰的核酸，并且可以适当地是与人类基因组不互补，使得其以不依赖于经处理的哺乳动物的核酸和核酸之间的常规碱基配对相互作用的方式提供免疫刺激。特别地，核酸可以适当地含有免疫刺激基序，例如CpG基序或免疫刺激回文序列。包含在核酸颗粒中的阳离子脂质可以适当地选自DODAP，DODMA，DMDMA，DOTAP，DC-Chol，DDAB，DODAC，DMRIE，DOSPA和DOGS。此外，脂质颗粒可以适当地含有修饰的聚集限制性脂质，例如PEG-脂质，PAO-脂质或神经节苷脂。

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