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1. 发明申请

WO2009015491A1 UMPS ISOFORMS AS NOVEL PREDICTIVE MARKERS AND THERAPEUTIC TARGETS FOR CHEMOTHERAPEUTICS 审中-公开
标题翻译： UMPS ISOFORMS作为化学疗法的新型预测标记和治疗目标
公开(公告)号：WO2009015491A1
公开(公告)日：2009-02-05
申请号：PCT/CA2008/001427
申请日：2008-08-01
申请人： BC CANCER AGENCY , MARRA, Marco A. , TAI, Isabella T. , GRIFFITH, Malachi
发明人： MARRA, Marco A. , TAI, Isabella T. , GRIFFITH, Malachi
IPC分类号： C12N15/60 , A61K31/7105 , A61K48/00 , A61P35/00 , C12N9/88 , C12Q1/527 , C12Q1/68 , C40B30/00
CPC分类号： C12Q1/6886 , C12N9/1205 , C12N9/90 , C12Q2600/118 , C12Q2600/172 , C12Y207/01048 , G01N2800/52
摘要： a method of predicting a subject's response to a chemotherapeutic treatment comprising the steps of: obtaining a sample from the subject, detecting a target gene in the sample, and assessing sample to detect at least one isoform of the target gene. if an isoform is detected, then identifying and quantifying isoform. the quantified isoform is compared to a suitable control. a change in expression of the quantified isoform relative to the control indicates the subject's responsiveness to said chemotherapeutic treatment. one embodiment relates to assessing a subject's responsiveness to chemotherapeutic treatments comprising 5-fluorouracil, by detecting, assessing and quantifying selected isoforms of uridine 5'-monophosphate synthase gene. another embodiment relates to assessing a subject's responsiveness to chemotherapeutic treatments comprising 5-fluorouracil, by detecting, assessing and quantifying isoforms a and b, and determining the ratio of expression of isoforms a to b compared to the ratio of expression of a suitable control.
摘要翻译：预测受试者对化学治疗反应的方法，包括以下步骤：从受试者获得样品，检测样品中的靶基因，并评估样品以检测靶基因的至少一种同种型。如果检测到同种型，则鉴定和定量同种型。将量化的同种型与合适的对照进行比较。相对于对照，量化的同种型的表达变化表明受试者对所述化学治疗的反应性。一个实施方案涉及通过检测，评估和定量所选的尿苷5'-单磷酸合酶基因的同种型来评估受试者对包含5-氟尿嘧啶的化学治疗的反应性。另一个实施方案涉及通过检测，评估和定量同种型a和b来评估受试者对包含5-氟尿嘧啶的化学治疗的反应性，以及确定同种型a与b的表达的比率与适合的对照的表达比例。

2. 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。

3. 发明申请

WO2007085906A3 FUNCTIONAL MUTANT LOXP SEQUENCES AND USES THEREOF 审中-公开
标题翻译：功能性突变体LOXP序列及其用途
公开(公告)号：WO2007085906A3
公开(公告)日：2007-11-29
申请号：PCT/IB2006004132
申请日：2006-10-12
申请人： BC CANCER AGENCY , HOLT ROBERT A , MISSIRLIS PERSEUS I
发明人： HOLT ROBERT A , MISSIRLIS PERSEUS I
IPC分类号： C12N15/90 , C12N15/09 , C12N15/87
CPC分类号： C12N15/90 , C12N15/70 , C12N2800/30
摘要： Compositions comprising mutant loxP elements having a mutated spacer region In one specific embodiment, the loxP recombination elements also have one mutated inverted repeat (e.g. Iox66 right inverted repeat or Iox71 left inverted repeat) as well as a wild type inverted repeat Such elements are particularly useful for procedures requiring multiple site-specific recombination reactions, including deletions or insertions of multiple genes or other sequences in the same organism, staged insertions or deletions of genes of the same organism at different times, assembly of large polynucleotide constructs by serial site-specific recombination, and the like Pn one aspect, compositions of the invention include particular mutant spacer oligonucleotides of loxP recombination elements, the recombination elements themselves, and pairs of mutant loxP elements
摘要翻译：包含具有突变的间隔区的突变型loxP元件的组合物在一个具体实施方案中，loxP重组元件还具有一个突变的反向重复（例如，Iox66右反向重复或Iox71左反向重复）以及野生型反向重复。这些元件特别有用对于需要多个位点特异性重组反应的程序，包括相同生物体中多个基因或其他序列的缺失或插入，在不同时间分离相同生物体基因的分期插入或缺失，通过连续位点特异性重组装配大多核苷酸构建体等Pn一方面，本发明的组合物包括特异性的loxP重组元件的突变间隔寡核苷酸，重组元件本身和突变型loxP元件对

4. 发明申请

WO2006069443A1 SURFACE ROUGHNESS MEASUREMENT METHODS AND APPARATUS 审中-公开
标题翻译：表面粗糙度测量方法和设备
公开(公告)号：WO2006069443A1
公开(公告)日：2006-07-06
申请号：PCT/CA2005/001967
申请日：2005-12-23
申请人： BC CANCER AGENCY , ZENG, Haishan , TCHVIALEVA, Lioudmila , LEE, Tim K. , MCLEAN, David I. , LUI, Harvey
发明人： ZENG, Haishan , TCHVIALEVA, Lioudmila , LEE, Tim K. , MCLEAN, David I. , LUI, Harvey
IPC分类号： A61B5/107 , G01J9/02 , G01J9/00 , G01B11/30
CPC分类号： A61B5/0066 , A61B5/444 , A61B5/445 , G01B11/303 , G01J9/02 , G01N21/47 , G01N2021/479
摘要： Surface roughness measurements are made by illuminating a surface with coherent light to generate a speckle pattern and studying characteristics of the speckle pattern. The disclosed techniques may be applied to measuring the surface roughness of skin or other biological surfaces. Skin roughness information may be used in the diagnosis of conditions such as malignant melanoma. Methods and apparatus for measuring the coherence length of optical sources involve extracting information about speckle patterns resulting when light from the optical sources interacts with a surface having a known roughness.
摘要翻译：通过用相干光照射表面以产生斑点图案并研究斑点图案的特征来进行表面粗糙度测量。所公开的技术可以用于测量皮肤或其他生物表面的表面粗糙度。皮肤粗糙度信息可用于诊断恶性黑色素瘤等病症。用于测量光源的相干长度的方法和装置包括提取关于来自光源的光与具有已知粗糙度的表面相互作用的斑点图案的信息。

5. 发明申请

WO2005119295A1 METHOD AND APPARATUS FOR VERIFYING RADIATION DOSE DISTRIBUTIONS 审中-公开
标题翻译：用于验证辐射剂量分布的方法和装置
公开(公告)号：WO2005119295A1
公开(公告)日：2005-12-15
申请号：PCT/CA2005/000857
申请日：2005-06-03
申请人： BC CANCER AGENCY , PETRIC, Martin Peter , ROBAR, James L. , CLARK, Brenda G.
发明人： PETRIC, Martin Peter , ROBAR, James L. , CLARK, Brenda G.
IPC分类号： G01T1/164
CPC分类号： G01T1/02 , A61N5/1042 , A61N5/1048 , G01T1/20
摘要： Apparatus for verifying radiation dose distributions may be used to verify a radiation dose distribution produced by a radiation beam from a medical radiation source, such as a linear accelerator. The apparatus has a tissue-equivalent scintillator located to intersect the radiation beam and an optical element that redirects light from the scintillator to a camera. A layer of transparent tissue-equivalent material adjacent to the scintillator generates backscattered radiation.
摘要翻译：用于验证辐射剂量分布的装置可用于验证由诸如线性加速器的医疗辐射源的辐射束产生的辐射剂量分布。该装置具有定位成与辐射束相交的组织等效闪烁体和将闪烁体的光重定向到相机的光学元件。与闪烁体相邻的透明组织等效材料层产生反向散射辐射。

6. 发明申请

WO2004029673A3 IMPROVED DIAGNOSTIC FLUORESCENCE AND REFLECTANCE 审中-公开
标题翻译：改进的诊断荧光和反射
公开(公告)号：WO2004029673A3
公开(公告)日：2005-03-10
申请号：PCT/US0331036
申请日：2003-09-30
申请人： UNIV TEXAS , CHANG SUNG K , MIRABAL YVETTE , FOLLEN MICHELE , MALPICA ANAIS , UTZINGER URS , STAERKEL GREGG , COX DENNIS , ATKINSON E NEELY , MACAULAY CALUM , RICHARDS-KORTUM REBECCA , BC CANCER AGENCY
发明人： CHANG SUNG K , MIRABAL YVETTE , FOLLEN MICHELE , MALPICA ANAIS , UTZINGER URS , STAERKEL GREGG , COX DENNIS , ATKINSON E NEELY , MACAULAY CALUM , RICHARDS-KORTUM REBECCA
IPC分类号： A61B5/00 , G01N21/47 , G01N21/64
CPC分类号： G01N21/6486 , A61B5/0071 , A61B5/0075 , A61B5/0084 , A61B5/4331 , G01N21/474 , G01N2021/1734 , G01N2021/174 , G01N2021/4745 , G01N2021/6419 , G01N2021/6423 , G01N2021/6484
摘要： Systems and methods are described for improved diagnostic fluorescence and reflectance. A method of detecting tissue abnormality in a tissue sample in vivo detects a set of reflectance spectra emitted from a tissue sample as a result of illumination with an excitation light from a fiber optic probe that has at least one collection fiber positioned at a source-detector separation, and determining if the tissue sample is normal or abnormal based on the resulting reflectance spectra. Another method of detecting tissue abnormality in a tissue sample in vivo includes illuminating the tissue sample in vivo with at least one electromagnetic radiation wavelength selected to cause the tissue sample to produce a set of fluorescence intensity spectra indicative of tissue abnormality, detecting the resulting fluorescence intensity spectra, and determining if the tissue sample is normal or abnormal based on the resulting fluorescence intensity spectra. Yet another method of detecting tissue abnormality in a tissue sample in vivo includes combining the two methods described above.
摘要翻译：系统和方法被描述用于改进诊断荧光和反射。检测体内组织样品中的组织异常的方法检测作为使用来自光纤光学探头的激发光照射的组织样品的一组反射光谱，该光纤光学探头具有至少一个位于源 - 检测器的收集光纤分离，并且基于所得到的反射光谱来确定组织样本是正常的还是异常的。检测体内组织样品中组织异常的另一种方法包括用至少一种电磁辐射波长体内照射组织样品，所述电磁辐射波长选择成使组织样品产生指示组织异常的一组荧光强度谱，检测产生的荧光强度光谱，并基于所得到的荧光强度光谱确定组织样品是否正常或异常。在体内检测组织样品中的组织异常的另一种方法包括组合上述两种方法。

7. 发明申请

WO2004029673A2 IMPROVED DIAGNOSTIC FLUORESCENCE AND REFLECTANCE 审中-公开
标题翻译：改进的诊断荧光和反射
公开(公告)号：WO2004029673A2
公开(公告)日：2004-04-08
申请号：PCT/US2003/031036
申请日：2003-09-30
申请人： BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEM , BC CANCER AGENCY , CHANG, Sung, K. , MIRABAL, Yvette , FOLLEN, Michele , MALPICA, Anais , UTZINGER, Urs , STAERKEL, Gregg , COX, Dennis , ATKINSON, Neely, N. , MACAULAY, Calum , RICHARDS-KORTUM, Rebecca
发明人： CHANG, Sung, K. , MIRABAL, Yvette , FOLLEN, Michele , MALPICA, Anais , UTZINGER, Urs , STAERKEL, Gregg , COX, Dennis , ATKINSON, Neely, N. , MACAULAY, Calum , RICHARDS-KORTUM, Rebecca
IPC分类号： G02B
CPC分类号： G01N21/6486 , A61B5/0071 , A61B5/0075 , A61B5/0084 , A61B5/4331 , G01N21/474 , G01N2021/1734 , G01N2021/174 , G01N2021/4745 , G01N2021/6419 , G01N2021/6423 , G01N2021/6484
摘要： Systems and methods are described for improved diagnostic fluorescence and reflectance. A method of detecting tissue abnormality in a tissue sample in vivo detects a set of reflectance spectra emitted from a tissue sample as a result of illumination with an excitation light from a fiber optic probe that has at least one collection fiber positioned at a source-detector separation, and determining if the tissue sample is normal or abnormal based on the resulting reflectance spectra. Another method of detecting tissue abnormality in a tissue sample in vivo includes illuminating the tissue sample in vivo with at least one electromagnetic radiation wavelength selected to cause the tissue sample to produce a set of fluorescence intensity spectra indicative of tissue abnormality, detecting the resulting fluorescence intensity spectra, and determining if the tissue sample is normal or abnormal based on the resulting fluorescence intensity spectra. Yet another method of detecting tissue abnormality in a tissue sample in vivo includes combining the two methods described above.
摘要翻译：描述了用于改善诊断荧光和反射率的系统和方法。一种在体内检测组织样本中的组织异常的方法，检测由组织样本发射的一组反射光谱，该组由来自光纤探针的激发光照射而成，该光纤探针具有至少一个收集光纤位于源检测器分离，并根据所得的反射光谱确定组织样本是正常还是异常。在体内检测组织样本中的组织异常的另一种方法包括以选择的至少一个电磁辐射波长在体内照射组织样本，以使组织样品产生指示组织异常的一组荧光强度光谱，检测所得到的荧光强度光谱，并且基于所得荧光强度光谱确定组织样品是正常还是异常。在体内检测组织样本中的组织异常的另一种方法包括组合上述两种方法。

8. 发明申请

WO2007110695A3 MODULAR GENOMES FOR SYNTHETIC BIOLOGY AND METABOLIC ENGINEERING 审中-公开
标题翻译：用于合成生物学和代谢工程的模块化基因
公开(公告)号：WO2007110695A3
公开(公告)日：2008-03-13
申请号：PCT/IB2006003706
申请日：2006-10-12
申请人： BC CANCER AGENCY , HOLT ROBERT A
发明人： HOLT ROBERT A
IPC分类号： C12N15/63 , C12N1/21 , C12N15/64 , C12N15/87
CPC分类号： C12N15/90 , C12N15/70 , C12N2800/30
摘要： The invention provides methods and compositions for assembling a modular replacement genome in a host microorganism. After such assembly, the host organism's genome is inactivated or ablated to permit full control of host cellular functions by the replacement genome. A modular replacement genome comprises an assembly of nucleic acid fragments, or segments, derived from one or more natural organisms or from synthetic polynucleotides or from a combination of both. Such an assembly, or set, of segments making up a replacement genome comprises a substantially complete set of genes and regulatory elements for carrying out minimal life functions under predefined culture conditions. The invention provides modular genomes having modules that are amenable to facile replacement, deletion, and/or additions. Such modules may be synthetic polynucleotides and may be designed for controlling gene content, excluding of genes that encode inhibitors or otherwise undesirable competing enzymes that divert a host cell from desired metabolic/synthetic processes; modifying codon usage to maximize or minimize protein production; modifying regulatory elements, including promoters, enhancers , repressors, activator, or the like, to modulate gene expression; balancing enzymatic and transport activities to optimize fluxes of substrates, intermediates, and products in metabolic pathways, and like objectives.
摘要翻译：本发明提供了用于在宿主微生物中组装模块替代基因组的方法和组合物。在这种装配之后，宿主生物体的基因组被灭活或消融以允许通过置换基因组完全控制宿主细胞功能。模块化替代基因组包含衍生自一种或多种天然生物体或来自合成多核苷酸或两者的组合的核酸片段或片段组合。构成替代基因组的片段或组合的组合包括用于在预定培养条件下进行最小寿命功能的基本完整的基因和调节元件。本发明提供了模块化基因组，其具有易于更换，删除和/或添加的模块。这样的模块可以是合成多核苷酸，并且可以设计用于控制基因含量，排除编码抑制剂的基因或以其它方式将宿主细胞从期望的代谢/合成过程转移的不希望的竞争性酶; 修改密码子使用以最大化或最小化蛋白质生产; 修饰调节元件，包括启动子，增强子，阻遏物，活化剂等，以调节基因表达; 平衡酶和运输活动以优化底物，中间体和代谢途径中的产物的通量以及类似目标。

9. 发明申请

WO2007059629A1 APPARATUS AND METHODS FOR AUTOMATED ASSESSMENT OF TISSUE PATHOLOGY 审中-公开
标题翻译：装置和方法对组织病理学进行自动评估
公开(公告)号：WO2007059629A1
公开(公告)日：2007-05-31
申请号：PCT/CA2006/001933
申请日：2006-11-27
申请人： BC CANCER AGENCY , MACAULAY, Calum, E. , GUILLAUD, Martial, Daniel , ROSIN, Miriam, Pearl
发明人： MACAULAY, Calum, E. , GUILLAUD, Martial, Daniel , ROSIN, Miriam, Pearl
IPC分类号： G01N15/00 , C12M1/34 , C12Q1/00 , G01N15/02 , G01N21/84 , G01N33/483 , G06F19/00 , G06T7/40 , G01N1/30
CPC分类号： G06T7/0012 , G01N1/30 , G01N15/1475 , G01N33/5091 , G01N33/574 , G06K9/00147 , G06T2207/30024
摘要： Methods and apparatus for assessing tissue pathology involve computing an index having a value based upon measures of a plurality of morphological features of cell nuclei in the tissue. The methods may be performed completely automatically or semi-automatically. The index value can be predictive of outcome. The index value may be determined by computing discriminant scores for the cell nuclei based upon values of the measures of morphological features and classifying the nuclei into bins based upon the discriminant score values. The index may be based upon proportions of the nuclei classified in different ones of the bins.
摘要翻译：用于评估组织病理学的方法和装置包括计算具有基于组织中细胞核的多个形态特征的测量的值的指数。这些方法可以完全自动或半自动进行。指标值可以预测结果。可以通过基于形态学特征的测量值来计算细胞核的判别分数并基于判别分数值将细胞核分类成分组来确定指数值。该指数可以基于分类在不同箱体中的核的比例。

10. 发明申请

WO2006005153A1 NUP98-HOX FUSIONS FOR EXPANSION OF HEMOPOIETIC STEM CELLS 审中-公开
标题翻译： NUP98-HOX融合用于扩增干细胞干细胞
公开(公告)号：WO2006005153A1
公开(公告)日：2006-01-19
申请号：PCT/CA2005/000755
申请日：2005-05-16
申请人： BC CANCER AGENCY , UNIVERSITE DE MONTREAL , HUMPHRIES, R. Keith , SAUVAGEAU, Guy
发明人： HUMPHRIES, R. Keith , SAUVAGEAU, Guy
IPC分类号： C12N15/62
CPC分类号： C12N5/0647 , C12N2501/40 , C12N2510/00
摘要： Nucleic acid constructs encoding homeobox-nucleoporin fusions are disclosed, compositions comprising same, and methods which provide enhanced expansion of stem cells. In particular, an isolated nucleic acid construct encoding a NUP98-HOX fusion is provided, which when introduced into hemopoietic stem cells provides enhanced expansion of these cells. Methods of expanding stem cells in vivo or ex vivo and methods of treatment using the stem cells are also described.
摘要翻译：公开了编码同源盒 - 核蛋白融合物的核酸构建体，包含其的组合物以及提供增强的干细胞扩增的方法。特别地，提供了编码NUP98-HOX融合物的分离的核酸构建体，其在引入造血干细胞时提供这些细胞的增强的扩增。还描述了使用干细胞在体内扩增干细胞的方法（I />或离体I I）和治疗方法。

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