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1. 发明申请

WO2007014150A2 METHOD OF ADMINISTERING LIPOSOMES CONTAINING OLIGONUCLEOTIDES 审中-公开
标题翻译：含有寡核苷酸的脂质体的施用方法
公开(公告)号：WO2007014150A2
公开(公告)日：2007-02-01
申请号：PCT/US2006/028658
申请日：2006-07-24
申请人： NEOPHARM, INC. , SHERMAN, Jeffrey , PARKER, Kristen , AHMAD, Imran
发明人： SHERMAN, Jeffrey , PARKER, Kristen , AHMAD, Imran
IPC分类号： A61K48/00
CPC分类号： A61K48/0008 , A61K9/1272 , C12N15/1135 , C12N2310/11
摘要： The invention provides a method of treating a cellular proliferative disease, a method of inhibiting the growth of neoplastic cells and a method of reducing the expression of a raf sequence by administering an effective amount of a cationic liposomal composition. The cationic liposomal composition comprises c-raf Antisense Oligonucleotide (c-rafAON), a cationic cardiolipin analogue and, desirably, another lipid species. The preferred cationic cardiolipin analogue is l,3-Bis-(l,2-bis-tetradecyloxy-propyl-3- dimethylethoxyammoniumbromide)-propane-2-ol (PCL-2). The preferred lipids include cholesterol, dioleoylphosphatidylethanolamine (DOPE), 1,2 Dioleoyl-sn-glycero-3- phosphocholine (DOPC), alpha tocopheryl acid succinate and phosphatidylcholine. The effective amount of the cationic liposomal composition is about 60 mg/m 2 .
摘要翻译：本发明提供了治疗细胞增殖性疾病的方法，抑制肿瘤细胞生长的方法和通过施用有效量的阳离子脂质体组合物来降低raf序列的表达的方法。阳离子脂质体组合物包含c-raf反义寡核苷酸（c-rafAON），阳离子心磷脂类似物，并且理想地是另一种脂质物质。优选的阳离子心磷脂类似物是1,3-双 - （1,2-双 - 十四烷氧基 - 丙基-3-二甲基乙氧基溴化铵） - 丙-2-醇（PCL-2）。优选的脂质包括胆固醇，二油酰磷脂酰乙醇胺（DOPE），1,2-二油酰-sn-甘油-3-磷酸胆碱（DOPC），α-生育酚酸琥珀酸酯和磷脂酰胆碱。阳离子脂质体组合物的有效量为约60mg / m 2。

2. 发明公开

EP1811962A2 MANUFACTURING PROCESS FOR LIPOSOMAL PREPARATIONS 审中-公开
标题翻译： PROCESS FOR脂质体制剂
公开(公告)号：EP1811962A2
公开(公告)日：2007-08-01
申请号：EP05820001.5
申请日：2005-10-28
申请人： Neopharm, Inc. , Ahmad, Zafeer , Anyarambhatla, Gopal , Prem, Sushil , Ahmad, Imran
发明人： AHMAD, Zafeer , ANYARAMBHATLA, Gopal , PREM, Sushil , AHMAD, Imran
IPC分类号： A61K9/127
CPC分类号： A61K9/1277 , A61K9/19
摘要： The present invention provides a manufacturing process for liposomal preparations comprising water-insoluble or hydrophobic active principals. In accordance with one aspect of the inventive method, at least one active principal and lipid fraction are dissolved in an organic solvent. This solution is then subjected to reduced pressure (vacuum) in a container with or with out inert packing to remove the organic solvent, thereby forming a puffy cake comprising the active principal or principals and lipid fraction. This puffy cake is then mixed with an aqueous solution, under controlled conditions suitable to form a bulk liposomal preparation. Because the active principal is imbedded in the lipid bilayer, removal of the aqueous solution is optional.

3. 发明申请

WO2007100808A4 METHOD AND PROCESS FOR PREPARING CARDIOLIPIN 审中-公开
公开(公告)号：WO2007100808A4
公开(公告)日：2007-09-07
申请号：PCT/US2007/005038
申请日：2007-02-22
申请人： NEOPHARM, INC. , ALI, Shoukath, M. , AHMAD, Moghis, U. , AHMAD, Imran
发明人： ALI, Shoukath, M. , AHMAD, Moghis, U. , AHMAD, Imran
IPC分类号： A61K48/00 , C07F5/06
摘要： The invention provides novel methods for preparing cardiolipin and cardiolipin analogs having varying fatty acid chain lengths, particularly l,r,2,2'-tetramyristoyl cardiolipin. The methods comprise reacting a starting compound, such as a 1,2- O-sn - diacylglycerol and a 2-protected glycerol, with a phosphoramidite reagent to produce a protected cardiolipin, which is deprotected to prepare cardiolipin. The cardiolipin and cardiolipin analogs may be prepared in the presence of an activator, such as pyridiniuin trifluororacetate. The methods of the present invention are used to prepare cardiolipin and cardiolipin analogs in large quantities. The cardiolipin prepared by the present methods can be incorporated into liposomes which can also include active agents such as hydrophobic or hydrophilic drugs. Such liposomes can be used to treat diseases or in diagnostic and/or analytical assays.

4. 发明申请

WO2006102533A3 PHARMACEUTICALLY ACTIVE LIPID-BASED FORMULATION OF NUCLEOSIDE-LIPID CONJUGATES 审中-公开
公开(公告)号：WO2006102533A3
公开(公告)日：2006-09-28
申请号：PCT/US2006/010638
申请日：2006-03-23
申请人： NEOPHARM, INC. , ZHANG, Jia-Ai , UGWU, Sydney , MA, Lan , AHMAD, Moghis, U. , ALI, Shoukath, M. , KHAN, Abdul, R. , AHMAD, Imran
发明人： ZHANG, Jia-Ai , UGWU, Sydney , MA, Lan , AHMAD, Moghis, U. , ALI, Shoukath, M. , KHAN, Abdul, R. , AHMAD, Imran
IPC分类号： A01N43/04 , A61K31/70
摘要： Novel formulations of nucleoside-lipid conjugates, the methods of preparing them and the methods for administering them are provided. More particularly, methods for making liposomal formulations of nucleoside-cardiolipin and analogues thereof are provided. By encapsulating nucleoside prodrugs, drugs are protected from degradation, thereby extending the drugs' plasma half-life and intracellular release. In addition, compositions that demonstrate greater efficacy and higher cytotoxicity are produced. Accordingly, nucleoside-lipid conjugates that demonstrate greater in-vitro and in-vivo activity are produced.

5. 发明申请

WO2005000318A2 METHOD OF INDUCING APOPTOSIS AND INHIBITING CARDIOLIPIN SYNTHESIS 审中-公开
标题翻译：诱导细胞凋亡和抑制心肌肽合成的方法
公开(公告)号：WO2005000318A2
公开(公告)日：2005-01-06
申请号：PCT/US2004/020104
申请日：2004-06-23
申请人： NEOPHARM, INC. , JAMIL, Haris , AHMAD, Moghis, U. , AHMAD, Imran
发明人： JAMIL, Haris , AHMAD, Moghis, U. , AHMAD, Imran
IPC分类号： A61K31/661
CPC分类号： C12N15/1137 , A61K31/00 , A61K31/661 , A61K31/683 , A61K31/70 , A61K45/06 , A61K48/00 , A61K2300/00
摘要： The present invention provides a method for inducing apoptosis within a cell by exposing the cell to an inhibitor of cardiolipin synthesis under conditions sufficient to induce apoptosis within the cell. The method can be used to investigate or treat disorders such as cancer, obesity, and cardiovascular disorders. The invention also provides a pharmaceutical composition including an inhibitor of cardiolipin synthesis and a liposomal carrier.
摘要翻译：本发明提供了通过在足以诱导细胞内凋亡的条件下将细胞暴露于心磷脂合成抑制剂而诱导细胞内细胞凋亡的方法。该方法可用于调查或治疗诸如癌症，肥胖症和心血管疾病等疾病。本发明还提供了包含心磷脂合成抑制剂和脂质体载体的药物组合物。

6. 发明申请

WO2004035523A1 CATIONIC CARDIOLIPIN ANALOGS AND USE THEREOF 审中-公开
标题翻译：阳离子卡泊醇类似物及其用途
公开(公告)号：WO2004035523A1
公开(公告)日：2004-04-29
申请号：PCT/US2003/033099
申请日：2003-10-16
申请人： NEOPHARM, INC. , AHMAD, Moghis, U. , KASIREDDY, Krishnudu , AHMAD, Imran
发明人： AHMAD, Moghis, U. , KASIREDDY, Krishnudu , AHMAD, Imran
IPC分类号： C07C217/04
CPC分类号： C07F9/10 , A61K9/1271 , A61K9/1272 , A61K31/522 , A61K31/7068 , A61K31/7072 , A61K47/18 , A61K47/24
摘要： The invention provides cationic cardiolipin compounds, and methods for synthesizing and using them in liposomal formulation, gene transfection, etc. In particular, the invention provides liposomes comprising cationic cardiolipin analog, pharmaceutical compositions comprising cationic cardiolipin analogs, and methods of using such liposomes and compositions, in delivering active pharmaceutical agents to treat human and animal diseases and/or in diagnostic assays.
摘要翻译：本发明提供阳离子心磷脂化合物，以及在脂质体制剂，基因转染等中合成和使用它们的方法。特别地，本发明提供了包含阳离子心磷脂类似物的脂质体，包含阳离子心磷脂类似物的药物组合物，以及使用这种脂质体和组合物的方法在递送活性药剂以治疗人和动物疾病和/或诊断测定中。

7. 发明申请

WO2003070221A1 CHEMOSENSITIZING WITH LIPOSOMES CONTAINING OLIGONUCLEOTIDES 审中-公开
标题翻译：含有寡核苷酸的脂质体的化学物质
公开(公告)号：WO2003070221A1
公开(公告)日：2003-08-28
申请号：PCT/US2003/004681
申请日：2003-02-14
申请人： GEORGETOWN UNIVERSITY , NEOPHARM, INC. , KASID, Usha , GOKHALE, Prafulla , PEI, Jin , MEWANI, Rajshree , AHMAD, Imran , DRISCHILO, Anatoly , RAHMAN, Aquilur
发明人： KASID, Usha , GOKHALE, Prafulla , PEI, Jin , MEWANI, Rajshree , AHMAD, Imran , DRISCHILO, Anatoly , RAHMAN, Aquilur
IPC分类号： A61K9/127
CPC分类号： C12N15/1135 , A61K9/1272 , A61K31/7088 , A61K31/7125 , A61K38/00 , A61K41/00 , A61K45/06 , C07H21/00 , C12N2310/315 , C12N2310/341 , C12N2310/345 , A61K2300/00
摘要： The invention relates to the use of oliognucleotide containing cationic liposomal formulations to enhance the efficacy of chemotherapy and/or radiotherapy, particularly as a means to chemosensitize cancer are tumor tissues to the efficiencies of chemotherapy. This is particularly advantageous in the context of treatment of ras expressing tumors such as breast, lung, pancreatic and prostate cancer.
摘要翻译：本发明涉及含有核苷酸的阳离子脂质体制剂用于增强化学疗法和/或放射疗法的功效的用途，特别是作为化学敏感化癌症的手段是肿瘤组织以达到化学疗效的效果。这在治疗表达诸如乳腺癌，肺癌，胰腺癌和前列腺癌的肿瘤的ras的情况下特别有利。

8. 发明申请

WO2002081642A3 GENE BRCC-3 AND DIAGNOSTIC AND THERAPEUTIC USES THEREOF 审中-公开
公开(公告)号：WO2002081642A3
公开(公告)日：2002-10-17
申请号：PCT/US2002/010855
申请日：2002-04-08
申请人： GEORGETOWN UNIVERSITY , NEOPHARM, INC. , KASID, Usha , GOKHALE, Prafulla , KUMAR, Deepak , BOUDREAU, Howard, E. , AHMAD, Imran , DRITSCHILO, Anatoly , RAHMAN, Aquilur
发明人： KASID, Usha , GOKHALE, Prafulla , KUMAR, Deepak , BOUDREAU, Howard, E. , AHMAD, Imran , DRITSCHILO, Anatoly , RAHMAN, Aquilur
IPC分类号： C12Q1/68
摘要： A gene that is a modulator of tumor growth and metastasis in certain cancer types is provided. This gene and corresponding polypeptide have diagnostic and therapeutic application for detecting and treating cancers that involve expression of BRCC-3 such as breast cancer and lung cancer.

9. 发明申请

WO2005067632A2 LIPID COMPOSITIONS AND USE THEREOF 审中-公开
标题翻译：脂肪组合物及其用途
公开(公告)号：WO2005067632A2
公开(公告)日：2005-07-28
申请号：PCT/US2005/000418
申请日：2005-01-07
申请人： NEOPHARM, INC. , AHMAD, Moghis U. , SHEIKH, Saifuddin , ALI, Shoukath , CHIEN, Pei-Yu , JAMIL, Haris , ZHANG, Jia-Ai , UGWU, Sydney , ZHANG, Zhi-Yi , WANG, Jinkang , BHAMIDIPATI, Shastri , AHMAD, Zafeer , AHMAD, Imran
发明人： AHMAD, Moghis U. , SHEIKH, Saifuddin , ALI, Shoukath , CHIEN, Pei-Yu , JAMIL, Haris , ZHANG, Jia-Ai , UGWU, Sydney , ZHANG, Zhi-Yi , WANG, Jinkang , BHAMIDIPATI, Shastri , AHMAD, Zafeer , AHMAD, Imran
IPC分类号： A61K9/127 , A61K31/14 , A61K31/355 , A61K31/575 , A61K31/685 , A61K31/7088 , A61K31/7105 , A61K31/711 , A61K45/06 , A61K48/00 , C12N15/11 , C12N15/113
CPC分类号： A61K31/14 , A61K9/1272 , A61K31/355 , A61K31/575 , A61K31/685 , A61K31/7088 , A61K31/7105 , A61K31/711 , A61K45/06 , A61K48/0025 , A61K48/0041 , C12N15/111 , C12N15/1135 , C12N2310/11 , C12N2310/14 , C12N2320/32 , A61K2300/00
摘要： The invention provides a composition suitable for use as a transfection agent, comprising a cationic cardiolipin analogue and, another lipid species. The composition of the present invention can facilitate transfection of a wide variety of polynucleotide species (e.g., oligodeoxyribonucleotides, plasmids, RNAi species, etc.). Moreover, the transfection agent of the present invention is effective in promoting transfection of primary cell cultures as well as transformed cells. Also, the inventive transfection agent is suitable for use both in vitro and in vivo . The inventive composition has additional uses as well, such as delivery of a variety of active agents, dermatological and cosmetic uses, and uses in agriculture. The invention further provides a method of introducing an active agent into a cell by contacting the cell with the inventive composition. The invention further provides a method of inhibiting the growth of neoplastic cells and a method of treating a patient suffering from a neoplastic disease by employing the inventive composition, wherein an active agent is an antineoplastic agent. The invention further provides a method for validating a genetic target, comprising (a) administering to a cell a composition comprising a cationic liposome and a siRNA, whereby the siRNA enters the cell inhibits the expression of a gene within the cell and (b) assaying for the inhibition of the gene. The method also provides a fluorescent/ luminescent cationic cardiolipin analogue and compositions including such analogues. Using a cationic cardiolipin analogue, the invention provides a method of tracking the migration of a lipid substance within an animal.
摘要翻译：本发明提供适合用作转染剂的组合物，其包含阳离子心磷脂类似物和另一种脂质物质。本发明的组合物可以促进多种多样性物质（例如，寡脱氧核糖核苷酸，质粒，RNAi物种等）的转染。此外，本发明的转染剂有效促进原代细胞培养物以及转化细胞的转染。此外，本发明的转染剂适用于体外和体内。本发明的组合物也具有额外的用途，例如递送各种活性剂，皮肤病学和美容用途以及农业中的用途。本发明还提供了通过使细胞与本发明组合物接触将活性剂引入细胞的方法。本发明进一步提供抑制肿瘤细胞生长的方法和通过使用本发明组合物治疗患有肿瘤疾病的患者的方法，其中活性剂是抗肿瘤剂。本发明还提供了一种用于验证遗传靶标的方法，包括（a）向细胞施用包含阳离子脂质体和siRNA的组合物，由此siRNA进入细胞抑制细胞内基因的表达，（b）测定用于抑制基因。该方法还提供荧光/发光阳离子心磷脂类似物和包含这些类似物的组合物。使用阳离子心磷脂类似物，本发明提供了跟踪动物体内脂质的迁移的方法。

10. 发明申请

WO2004017944A1 LIPOSOMAL GEMCITABINE COMPOSITIONS FOR BETTER DRUG DELIVERY 审中-公开
标题翻译：用于更好的药物递送的组织化学药物组合物
公开(公告)号：WO2004017944A1
公开(公告)日：2004-03-04
申请号：PCT/US2003/025293
申请日：2003-08-13
申请人： NEOPHARM, INC. , ZHANG, Jia-Ai , AHMAD, Imran
发明人： ZHANG, Jia-Ai , AHMAD, Imran
IPC分类号： A61K9/127
CPC分类号： A61K45/06 , A61K9/127 , A61K9/1272 , A61K31/66 , A61K31/7068 , A61K31/7072 , A61K2300/00
摘要： The present invention is for novel compositions and methods for treating cancer, particularly, for treating cancer in mammals and more particularly in humans. The therapeutic compositions of the present invention include liposome entrapped gemcitabine in which the liposome can contain any of a variety of neutral or charged liposome-forming compounds including cardiolipin.
摘要翻译：本发明是用于治疗癌症的新型组合物和方法，特别是用于治疗哺乳动物，特别是人类的癌症。本发明的治疗组合物包括脂质体包埋的吉西他滨，其中脂质体可以含有多种中性或带电荷的脂质体形成化合物，包括心磷脂。

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