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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

WO0141738A3 LIPID CARRIER COMPOSITIONS WITH PROTECTED SURFACE REACTIVE FUNCTIONS 审中-公开
标题翻译：具有保护表面反应功能的脂质载体组合物
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
申请人： CELATOR TECHNOLOGIES INC , MAYER LAWRENCE D , CHIU GIGI , BALLY MARCEL B
发明人： MAYER LAWRENCE D , CHIU GIGI , BALLY MARCEL B
IPC分类号： A61K9/127
CPC分类号： A61K9/1271
摘要： 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.
摘要翻译：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。

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