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1. 发明申请

WO2006037229A1 FORMULATION OF MULTIVALENT ANTIBODY CONSTRUCTS AND USE OF SAME FOR CANCER THERAPY 审中-公开
标题翻译：多发性抗体构建物的配方及其用于癌症治疗的用途
公开(公告)号：WO2006037229A1
公开(公告)日：2006-04-13
申请号：PCT/CA2005/001535
申请日：2005-10-06
申请人： BC CANCER AGENCY , CHIU, Gigi , BALLY, Marcel
发明人： CHIU, Gigi , BALLY, Marcel
IPC分类号： A61K39/395 , G01N33/53 , A61K47/48 , A61K9/127
CPC分类号： G01N33/5011 , A61K9/1271 , A61K47/6849 , A61K47/6867 , A61K47/6913 , C07K16/2896 , C07K16/32 , G01N33/5047 , G01N33/6854
摘要： The invention relates to the formation of multivalent antibody constructs for testing and therapeutic purposes. In one embodiment the constructs consist of antibodies or antibody fragments conjugated to liposomes. The constructs are employed in a cell-based in vitro assay for comparing the therapeutic activity of antibodies or antibody fragments in multivalent form to the same antibodies or fragments in bivalent, free form. The assay is useful for identifying antibodies having potential in vivo activity. Selected antibodies may then be tested in an animal model of a disease state, such as cancer or an autoimmune disorder. Co-delivery of antibodies and chemotherapeutics may also be investigated. In accordance with the invention, a significant enhancement in the activity of antibodies such as trastuzumab and rituximab was observed when these antibodies were presented in the multivalent liposomal form. Key cell survival signaling molecules were down-regulated upon treatment with the multivalent liposomal antibody construct. The invention demonstrates the potential of liposome technology to enhance the therapeutic effect of antibodies via a mechanism that modulates cell survival, likely through clustering of target/antibody complex.
摘要翻译：本发明涉及用于测试和治疗目的的多价抗体构建体的形成。在一个实施方案中，构建体由与脂质体缀合的抗体或抗体片段组成。将构建体用于基于细胞的体外测定，用于将抗体或多价形式的抗体片段的治疗活性与二价，游离形式的相同抗体或片段进行比较。该测定可用于鉴定具有潜在的体内活性的抗体。然后可以在疾病状态的动物模型（例如癌症或自身免疫性疾病）中测试所选择的抗体。也可以研究抗体和化学治疗剂的共同递送。根据本发明，当以多价脂质体形式存在这些抗体时，观察到抗体如曲妥珠单抗和利妥昔单抗的活性显着增强。用多价脂质体抗体构建体治疗时，关键细胞存活信号分子被下调。本发明证明了脂质体技术通过调节细胞存活的机制来增强抗体的治疗效果，可能通过聚合目标/抗体复合物来增强抗体的治疗效果。

2. 发明申请

WO2006079216A1 LIPOSOMAL COMPOSITIONS FOR PARENTERAL DELIVERY OF AGENTS 审中-公开
标题翻译：用于家族代理的药物组合物
公开(公告)号：WO2006079216A1
公开(公告)日：2006-08-03
申请号：PCT/CA2006/000114
申请日：2006-01-30
申请人： BC CANCER AGENCY , UNIVERSITY HEALTH NETWORK , WASAN, Ellen , BALLY, Marcel , COGSWELL, Sebastian , BERGER, Stuart
发明人： WASAN, Ellen , BALLY, Marcel , COGSWELL, Sebastian , BERGER, Stuart
IPC分类号： A61K31/4174 , A61P35/00 , A61P31/10 , A61K9/127 , A61K47/48
CPC分类号： A61K9/1271 , A61K9/1278 , A61K31/4174
摘要： The invention provides methods and compositions for loading an agent, such as econazole, onto a liposome for parental delivery. The loading of the agent into a liposome comprises combining the agent with a micelle-forming compound to form a micelle including the agent, where the agent is releasable from the micelle-forming compound, and adding the micelle to the liposome, where the micelle combines with the liposome such that the agent is loaded into the liposome to form a loaded liposome. The methods are suitable for the loading of poorly soluble agents onto liposome.
摘要翻译：本发明提供了用于将药剂（例如益康唑）加载到用于亲代递送的脂质体上的方法和组合物。将试剂加载到脂质体中包括将试剂与胶束形成化合物组合以形成包含试剂的胶束，其中试剂可从胶束形成化合物释放，并将胶束加入脂质体中，其中胶束结合与脂质体一起使得试剂加载到脂质体中以形成负载的脂质体。该方法适用于将难溶性物质加载到脂质体上。

3. 发明申请

WO2006037230A1 LIPOSOMES WITH IMPROVED DRUG RETENTION FOR TREATMENT OF CANCER 审中-公开
标题翻译：具有改善药物治疗癌症的药物
公开(公告)号：WO2006037230A1
公开(公告)日：2006-04-13
申请号：PCT/CA2005/001536
申请日：2005-10-06
申请人： BC CANCER AGENCY , BALLY, Marcel , RAMSAY, Euan
发明人： BALLY, Marcel , RAMSAY, Euan
IPC分类号： A61K47/02
CPC分类号： A61K9/127 , A61K31/4745 , A61K47/02
摘要： The present invention relates to the use of copper ions to achieve enhanced retention of a therapeutic agent within a liposome. The invention may be employed to more effectively deliver a liposomally encapsulated therapeutic agent to a target site in vitro and in vivo for anti-cancer or other therapy. The liposome may comprise an interior buffer solution containing the therapeutic agent, the solution having a pH less than 6.5 and most preferably approximating pH 3.5. At least some of the copper ions are retained within the interior solution. In a particular embodiment the therapeutic agent may be a chemotherapeutic drug, such as irinotecan. The invention may also comprise an ionophore to facilitate loading of drug into the liposome. In one particular embodiment the combination of the ionophore A23187 and encapsulated divalent copper (Cu2+) resulted in an irinotecan formulation that exhibited surprisingly improved drug retention attributes.
摘要翻译：本发明涉及使用铜离子来实现治疗剂在脂质体内的保留。本发明可用于在体外和体内更有效地将脂质体包封的治疗剂递送至靶位点用于抗癌或其它治疗。脂质体可以包含含有治疗剂的内部缓冲溶液，该溶液的pH小于6.5，最优选接近pH 3.5。至少一些铜离子保留在内部溶液中。在一个具体实施方案中，治疗剂可以是化学治疗药物，例如伊立替康。本发明还可以包含离子载体以便于将药物负载到脂质体中。在一个具体实施方案中，离子载体A23187和包封的二价铜（Cu 2+）的组合导致伊立替康制剂显示惊人的改善的药物保留性质。

4. 发明公开

EP1796729A1 LIPOSOMES WITH IMPROVED DRUG RETENTION FOR TREATMENT OF CANCER 审中-公开
标题翻译：具有改进的药物保留用于治疗癌症的脂质体
公开(公告)号：EP1796729A1
公开(公告)日：2007-06-20
申请号：EP05791552.2
申请日：2005-10-06
申请人： BC Cancer Agency
发明人： BALLY, Marcel , RAMSAY, Euan
IPC分类号： A61K47/02 , A61K9/127 , A61K31/4745 , A61P35/00
CPC分类号： A61K9/127 , A61K31/4745 , A61K47/02
摘要： The present invention relates to the use of copper ions to achieve enhanced retention of a therapeutic agent within a liposome. The invention may be employed to more effectively deliver a liposomally encapsulated therapeutic agent to a target site in vitro and in vivo for anti-cancer or other therapy. The liposome may comprise an interior buffer solution containing the therapeutic agent, the solution having a pH less than 6.5 and most preferably approximating pH 3.5. At least some of the copper ions are retained within the interior solution. In a particular embodiment the therapeutic agent may be a chemotherapeutic drug, such as irinotecan. The invention may also comprise an ionophore to facilitate loading of drug into the liposome. In one particular embodiment the combination of the ionophore A23187 and encapsulated divalent copper (Cu2+) resulted in an irinotecan formulation that exhibited surprisingly improved drug retention attributes.

5. 发明公开

EP1855669A1 LIPOSOMAL COMPOSITIONS FOR PARENTERAL DELIVERY OF AGENTS 审中-公开
标题翻译：用于胃肠外给药AGENTS脂质体组合物
公开(公告)号：EP1855669A1
公开(公告)日：2007-11-21
申请号：EP06701601.4
申请日：2006-01-30
申请人： BC Cancer Agency , University Health Network
发明人： WASAN, Ellen , BALLY, Marcel , COGSWELL, Sebastian , BERGER, Stuart
IPC分类号： A61K31/4174 , A61P35/00 , A61P31/10 , A61K9/127 , A61K47/48
CPC分类号： A61K9/1271 , A61K9/1278 , A61K31/4174
摘要： The invention provides methods and compositions for loading an agent, such as econazole, onto a liposome for parental delivery. The loading of the agent into a liposome comprises combining the agent with a micelle-forming compound to form a micelle including the agent, where the agent is releasable from the micelle-forming compound, and adding the micelle to the liposome, where the micelle combines with the liposome such that the agent is loaded into the liposome to form a loaded liposome. The methods are suitable for the loading of poorly soluble agents onto liposome.

6. 发明申请

WO2006032136A1 FREE OR LIPOSOMAL GEMCITABINE ALONE OR IN COMBINATION WITH FREE OR LIPOSOMAL IDARUBICIN 审中-公开
标题翻译：免费或药物化疗药物或与免费或脂质代谢产物组合
公开(公告)号：WO2006032136A1
公开(公告)日：2006-03-30
申请号：PCT/CA2005/001434
申请日：2005-09-20
申请人： BRITISH COLUMBIA CANCER AGENCY BRANCH , BALLY, Marcel , DOS SANTOS, Nancy , RAMSAY, Euan
发明人： BALLY, Marcel , DOS SANTOS, Nancy , RAMSAY, Euan
IPC分类号： A61K31/7068
CPC分类号： A61K9/127 , A61K9/1271 , A61K31/00 , A61K31/4745 , A61K31/704 , A61K31/7068
摘要： The use of the maximum tolerated dose (MTD) of individual drugs to determine appropriate administration ratios of drugs for combination therapy, wherein the ratios of drugs are fixed based on the same percentage of the MTD for each drug. Furthemore, antineoplastic compositions comprising liposomal encapsulated gemcitabine alone or in combination with free or liposomal encapsulated antineoplastic agents, such as idarubicin, irinotecan, etopside, cisplatin, cyclophosphamide, doxorubicin, or vincristine are diclosed.
摘要翻译：使用单个药物的最大耐受剂量（MTD）来确定用于联合治疗的药物的适当施用比例，其中药物比例基于每种药物的相同百分比的MTD而固定。令人惊讶的是，包含单独的脂质体包封的吉西他滨或与游离或脂质体包封的抗肿瘤剂如伊达比星，伊立替康，依托泊苷，顺铂，环磷酰胺，多柔比星或长春新碱组合的抗肿瘤组合物被包围。

7. 发明申请

WO2003028697A2 LIPOSOME LOADING WITH METAL IONS 审中-公开
标题翻译： LIPOSOME加载金属离子
公开(公告)号：WO2003028697A2
公开(公告)日：2003-04-10
申请号：PCT/CA2002/001501
申请日：2002-10-03
申请人： CELATOR TECHNOLOGIES INC. , TARDI, Paul , JOHNSTONE, Sharon , WEBB, Murray , BALLY, Marcel , ABRAHAM, Sheela
发明人： TARDI, Paul , JOHNSTONE, Sharon , WEBB, Murray , BALLY, Marcel , ABRAHAM, Sheela
IPC分类号： A61K9/00
CPC分类号： A61K31/7072 , A61K9/127 , A61K9/1271 , A61K9/1272 , A61K31/00 , A61K31/4745 , A61K31/704 , A61K31/7048 , A61K31/7076 , A61K33/24 , A61K45/06 , A61K2300/00
摘要： This invention relates to encapsulation of drugs and other agents into liposomes.
摘要翻译：本发明涉及药物和其它试剂在脂质体中的包封。

8. 发明申请

WO2004087115A3 COMBINATION COMPOSITIONS OF CAMPTOTHECINS AND FLUOROPYRIMIDINES 审中-公开
公开(公告)号：WO2004087115A3
公开(公告)日：2004-10-14
申请号：PCT/CA2004/000507
申请日：2004-04-02
申请人： CELATOR TECHNOLOGIES INC. , MAYER, Lawrence , BALLY, Marcel , WEBB, Murray , TARDI, Paul , JOHNSTONE, Sharon
发明人： MAYER, Lawrence , BALLY, Marcel , WEBB, Murray , TARDI, Paul , JOHNSTONE, Sharon
IPC分类号： A61K9/127
摘要： Compositions which comprise liposomes having stably associated therewith a camptothecin and a fluoropyrimidine are useful in achieving enhanced therapeutic effects when combinations of these drugs are administered.

9. 发明申请

WO2003022250A2 VESICLES STABILIZED WITH SHORT CHAIN HYDROPHILIC POLYMERS 审中-公开
标题翻译：稳定短链羟基聚合物的VESICLES
公开(公告)号：WO2003022250A2
公开(公告)日：2003-03-20
申请号：PCT/CA2002/001365
申请日：2002-09-10
申请人： CELATOR TECHNOLOGIES INC. , DOS SANTOS, Nancy , BALLY, Marcel , MAYER, Lawrence
发明人： DOS SANTOS, Nancy , BALLY, Marcel , MAYER, Lawrence
IPC分类号： A61K9/133
CPC分类号： A61K9/1271
摘要： Short chain hydrophilic polymers impart enhanced circulation longevity to unilamellar vesicles made without cholesterol, when the hydrophilic polymer is incorporated into the vesicles at low densities.
摘要翻译：当亲水性聚合物以低密度掺入囊泡时，短链亲水性聚合物赋予不含胆固醇的单层囊泡增强的循环寿命。

10. 发明申请

WO2009141738A3 MODIFIED DRUGS FOR USE IN LIPOSOMAL NANOPARTICLES 审中-公开
公开(公告)号：WO2009141738A3
公开(公告)日：2009-11-26
申请号：PCT/IB2009/006532
申请日：2009-05-26
申请人： THE UNIVERSITY OF BRITISH COLUMBIA , CULLIS, Pieter , BALLY, Marcel , CIUFOLINI, Marco , MAURER, Norbert , JIGALTSEV, Igor
发明人： CULLIS, Pieter , BALLY, Marcel , CIUFOLINI, Marco , MAURER, Norbert , JIGALTSEV, Igor
IPC分类号： A61K9/127 , A61K31/337 , A61K45/00
摘要： Drag derivatives are provided herein which are suitable for loading into liposomal nanoparticle carriers. In some preferred aspects, the derivatives comprise a poorly water-soluble drag derivatized with a weak-base moiety that facilitates active loading of the drag through a LN transmembrane pH or ion gradient into the aqueous interior of the LN. The weak-base moiety can optionally comprise a lipophilic domain that facilitates active loading of the drag to the inner monolayer of the liposomal membrane. Advantageously, LN formulations of the drag derivatives exhibit improved solubility, reduced toxicity, enhanced efficacy, and/or other benefits relative to the corresponding free drags.

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