公开(公告)号：WO9640964A3

公开(公告)日：1997-04-24

申请号：PCT/US9609949

申请日：1996-06-06

Applicant: INEX PHARMACEUTICALS CORP ,  WHEELER JEFFERY J ,  BALLY MARCEL B ,  ZHANG YUANG-PENG ,  REIMER DOROTHY L ,  HOPE MICHAEL ,  CULLIS PIETER R ,  SCHERRER PETER

Inventor： WHEELER JEFFREY J ,  BALLY MARCEL B ,  ZHANG YUANG-PENG ,  REIMER DOROTHY L ,  HOPE MICHAEL ,  CULLIS PIETER R ,  SCHERRER PETER

IPC: C12N15/09 ,  A61K9/127 ,  A61K48/00 ,  C12N15/88 ,  C12N15/87

CPC classification number: C12N15/88 ,  A61K9/1272 ,  A61K47/6911

Abstract: 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.

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

Applicant: BC CANCER AGENCY ,  CHIU, Gigi ,  BALLY, Marcel

Inventor： CHIU, Gigi ,  BALLY, Marcel

IPC: A61K39/395 ,  G01N33/53 ,  A61K47/48 ,  A61K9/127

CPC classification number: G01N33/5011 ,  A61K9/1271 ,  A61K47/6849 ,  A61K47/6867 ,  A61K47/6913 ,  C07K16/2896 ,  C07K16/32 ,  G01N33/5047 ,  G01N33/6854

Abstract: 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.

Abstract translation: 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。

公开(公告)号：WO2004087105A8

公开(公告)日：2005-03-10

申请号：PCT/CA2004000508

申请日：2004-04-02

Applicant: CELATOR TECHNOLOGIES INC ,  MAYER LAWRENCE ,  BALLY MARCEL ,  WEBB MURRAY ,  TARDI PAUL ,  SHEW CLIFFORD

Inventor： MAYER LAWRENCE ,  BALLY MARCEL ,  WEBB MURRAY ,  TARDI PAUL ,  SHEW CLIFFORD

IPC: A61K9/127 ,  A61K33/24 ,  A61K45/06 ,  A61K31/282 ,  A61K31/513 ,  A61K31/7068 ,  A61K31/7072

CPC classification number: A61K9/127 ,  A61K9/1271 ,  A61K33/24 ,  A61K45/06 ,  A61K2300/00

Abstract: Compositions which comprise liposomes having stably associated therewith a platinum agent and an antimetabolite are useful in achieving enhanced therapeutic effects when combinations of these drugs are administered.

Abstract translation: 包含与铂剂和抗代谢物稳定相关的脂质体的组合物在施用这些药物的组合时可用于获得增强的治疗效果。

公开(公告)号：WO2004078677A3

公开(公告)日：2004-11-04

申请号：PCT/CA2004000344

申请日：2004-03-08

Applicant: CELATOR TECHNOLOGIES INC ,  MAYER LAWRENCE ,  SHABBITS JENNIFER ,  BALLY MARCEL

Inventor： MAYER LAWRENCE ,  SHABBITS JENNIFER ,  BALLY MARCEL

IPC: A61K9/127 ,  A61P35/00

CPC classification number: A61K31/56 ,  A61K9/1272 ,  A61K31/685 ,  A61K31/739

Abstract: Compositions which comprise delivery vehicles having stably associated therewith at least one organic acid derivative of a sterol are useful in achieving enhanced cellular delivery of physiologically relevant sphingolipids when the compositions are administered.

Abstract translation: 包含与其稳定缔合的至少一种甾醇的有机酸衍生物的递送载体的组合物可用于当组合物被施用时实现生理相关的鞘脂的增强的细胞递送。

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

Applicant: CELATOR TECHNOLOGIES INC. ,  MAYER, Lawrence ,  BALLY, Marcel ,  WEBB, Murray ,  TARDI, Paul ,  JOHNSTONE, Sharon

Inventor： MAYER, Lawrence ,  BALLY, Marcel ,  WEBB, Murray ,  TARDI, Paul ,  JOHNSTONE, Sharon

IPC: A61K9/127

Abstract: 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.

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

Applicant: CELATOR TECHNOLOGIES INC. ,  DOS SANTOS, Nancy ,  BALLY, Marcel ,  MAYER, Lawrence

Inventor： DOS SANTOS, Nancy ,  BALLY, Marcel ,  MAYER, Lawrence

IPC: A61K9/133

CPC classification number: A61K9/1271

Abstract: 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.

Abstract translation: 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。

公开(公告)号：WO2002098465A2

公开(公告)日：2002-12-12

申请号：PCT/CA2002/000853

申请日：2002-06-07

Applicant: CELATOR TECHNOLOGIES, INC. ,  BALLY, Marcel, B. ,  SCHUTZE-REDELMEIER, Marie-Paul ,  CHIKH, Ghania

Inventor： BALLY, Marcel, B. ,  SCHUTZE-REDELMEIER, Marie-Paul ,  CHIKH, Ghania

IPC: A61K47/48

CPC classification number: A61K47/6911 ,  A61K47/62 ,  A61K47/646

Abstract: Compositions are provided for delivery of a biologically active agent to a cell, comprising a vehicle having the formula: A - (BC) wherein: A is a lipid-based vehicle; B is a moiety comprising an internalizing peptide; C is a moiety comprising a biologically active agent; (BC) is a complex comprising B and C in which B is conjugated to C; and A is conjugated to (BC).

Abstract translation: 提供用于将生物活性剂递送至细胞的组合物，其包含具有下式的载体：A - （BC）其中：A是基于脂质的载体; B是包含内化肽的部分; C是包含生物活性剂的部分; （BC）是包含B和C的络合物，其中B与C结合; 并且A与（BC）缀合。

公开(公告)号：WO0141738A3

公开(公告)日：2001-11-29

申请号：PCT/CA0001494

申请日：2000-12-11

Applicant: CELATOR TECHNOLOGIES INC ,  MAYER LAWRENCE D ,  CHIU GIGI ,  BALLY MARCEL B

Inventor： MAYER LAWRENCE D ,  CHIU GIGI ,  BALLY MARCEL B

IPC: A61K9/127

CPC classification number: A61K9/1271

Abstract: The liposomes of the invention have a reactive surface that demonstrates reduced interaction with macromolecules and increased blood circulation time. The reactive surface may comprise phosphatidylserine. The liposomes are protected by the presence of high levels of a hydrophilic polymer conjugated to a lipid. The invention further provides means for adjusting the appropriate ratio of hydrophilic polymer to a reactive lipid by a) determining the reactivity of the lipid; b) determining the time required for the carrier to reach its desired target location; c) determining the affinity of desired interactions with the reactive surface; and d) incorporating in the liposome or lipid carrier the amount of polyethylene glycol required to protect the reactive surface.

Abstract translation: 本发明的脂质体具有反应性表面，其表现出与大分子减少的相互作用和增加的血液循环时间。 反应性表面可以包含磷脂酰丝氨酸。 通过存在高水平的与脂质缀合的亲水性聚合物来保护脂质体。 本发明还提供了通过以下方法来调节亲水性聚合物与活性脂质的适当比例：a）确定脂质的反应性; b）确定承运人达到其所需目标位置所需的时间; c）确定与反应性表面的所需相互作用的亲和力; 和d）在脂质体或脂质载体中掺入保护反应性表面所需的聚乙二醇的量。

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

Applicant: BRITISH COLUMBIA CANCER AGENCY BRANCH ,  BALLY, Marcel ,  DOS SANTOS, Nancy ,  RAMSAY, Euan

Inventor： BALLY, Marcel ,  DOS SANTOS, Nancy ,  RAMSAY, Euan

IPC: A61K31/7068

CPC classification number: A61K9/127 ,  A61K9/1271 ,  A61K31/00 ,  A61K31/4745 ,  A61K31/704 ,  A61K31/7068

Abstract: 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.

Abstract translation: 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。

公开(公告)号：WO02098465B1

公开(公告)日：2003-09-12

申请号：PCT/CA0200853

申请日：2002-06-07

Applicant: CELATOR TECHNOLOGIES INC ,  BALLY MARCEL B ,  SCHUTZE-REDELMEIER MARIE-PAUL ,  CHIKH GHANIA

Inventor： BALLY MARCEL B ,  SCHUTZE-REDELMEIER MARIE-PAUL ,  CHIKH GHANIA

IPC: A61K47/48

CPC classification number: A61K47/6911 ,  A61K47/62 ,  A61K47/646

Abstract: Compositions are provided for delivery of a biologically active agent to a cell, comprising a vehicle having the formula: A - (BC) wherein: A is a lipid-based vehicle; B is a moiety comprising an internalizing peptide; C is a moiety comprising a biologically active agent; (BC) is a complex comprising B and C in which B is conjugated to C; and A is conjugated to (BC).

Abstract translation: 提供组合物用于将生物活性剂递送至细胞，其包含具有下式的媒介物：A-（BC）其中：A是基于脂质的媒介物; B是包含内化肽的部分; C是包含生物活性剂的部分; （BC）是包含B和C的复合物，其中B与C缀合; 并且A与（BC）缀合。