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1. 发明申请

WO2013052484A1 DYE CONJUGATED PEPTIDES FOR FLUORESCENT IMAGING 审中-公开
标题翻译：用于荧光成像的DYE结合肽
公开(公告)号：WO2013052484A1
公开(公告)日：2013-04-11
申请号：PCT/US2012/058462
申请日：2012-10-02
申请人： IMMUNOMEDICS, INC. , REGINO, Celeste Aida S. , MCBRIDE, William J. , CHANG, Chien-Hsing , GOLDENBERG, David M.
发明人： REGINO, Celeste Aida S. , MCBRIDE, William J. , CHANG, Chien-Hsing , GOLDENBERG, David M.
IPC分类号： G01N33/533 , G01N21/76
CPC分类号： A61K51/088 , A61K51/1045 , A61K51/1078 , G01N21/6428 , G01N21/6456 , G01N33/542 , G01N33/57407 , G01N33/57484 , G01N33/582 , G01N33/6854 , G01N33/6872 , G01N2333/912 , Y02A50/57
摘要： The present application discloses compositions and methods of use of dye conjugated peptides for fluorescent detection, diagnosis and/or imaging. In preferred embodiments, the compositions comprise a DNL complex comprising an anti-hapten antibody or antigen-binding fragment thereof conjugated to an AD moiety and a DDD moiety conjugated to an antibody or antigen-binding fragment thereof that binds to the target antigen, wherein two copies of the DDD moiety form a dimer that binds to the AD moiety to form the DNL complex. More preferably, the compositions comprise a targetable construct comprising at least one hapten and a fluorescent probe. Binding of the DNL complex to the target antigen and of the hapten on the targetable construct to the DNL complex results in fluorescent labeling of the target antigen. Most preferably, fluorescent imaging is of use in intraoperative, intraperitoneal, laparoscopic, endoscopic or intravascular procedures for detection of diseased tissues.
摘要翻译：本申请公开了用于荧光检测，诊断和/或成像的染料缀合肽的组合物和方法。在优选的实施方案中，组合物包含DNL复合物，其包含与AD部分缀合的抗半抗原抗体或其抗原结合片段和与靶抗原结合的抗体或其抗原结合片段缀合的DDD部分，其中两个 DDD部分的拷贝形成与AD部分结合形成DNL复合物的二聚体。更优选地，组合物包含包含至少一个半抗原和荧光探针的可靶向构建体。将DNL复合物与目标抗原和可靶向构建体上的半抗原结合到DNL复合物上导致靶抗原的荧光标记。最优选地，荧光成像在术中，腹膜内，腹腔镜，内窥镜或血管内程序中用于检测患病组织。

2. 发明申请

WO2010022225A9 DOCK-AND-LOCK (DNL) VACCINES FOR CANCER THERAPY 审中-公开
公开(公告)号：WO2010022225A9
公开(公告)日：2010-02-25
申请号：PCT/US2009/054441
申请日：2009-08-20
申请人： IBC PHARMACEUTICALS, INC. , CHANG, Chien-Hsing , GOLDENBERG, David M.
发明人： CHANG, Chien-Hsing , GOLDENBERG, David M.
IPC分类号： A61K39/00
摘要： The present invention concerns methods and compositions for forming anti-cancer vaccine DNL complexes using dock-and-lock technology. In preferred embodiments, the anti-cancer vaccine DNL complex comprises an antibody moiety that binds to dendritic cells, such as an anti-CD74 antibody or antigen-binding fragment thereof, attached to an AD (anchoring domain) moiety and a xenoantigen, such as CD20, attached to a DDD (dimerization and docking domain) moiety, wherein two copies of the DDD moiety form a dimer that binds to the AD moiety, resulting in the formation of the DNL complex. The anti-cancer vaccine DNL complex is capable of inducing an immune response against xenoantigen expressing cancer cells, such as CD138 neg CD20 + MM stem cells, and inducing apoptosis of and inhibiting the growth of or eliminating the cancer cells.

3. 发明申请

WO2007047609A3 INHIBITION OF PLACENTA GROWTH FACTOR (PlGF) MEDICATED METASTASIS AND/OR ANGIOGENESIS 审中-公开
标题翻译：抑制PLACENTA生长因子（PlGF）药物化学和/或血管生成
公开(公告)号：WO2007047609A3
公开(公告)日：2009-03-19
申请号：PCT/US2006040431
申请日：2006-10-16
申请人： CT MOLECULAR MED & IMMUNOLOGY , IMMUNOMEDICS INC , GOLDENBERG DAVID M , CHANG CHIEN HSING
发明人： GOLDENBERG DAVID M , CHANG CHIEN HSING
IPC分类号： A61K38/17 , A61K39/395 , A61K48/00 , C07H21/02
CPC分类号： C07K16/22 , A61K38/00 , C07K14/515
摘要： The present invention concerns methods and compositions for inhibiting angiogenesis and/or tumor growth, survival and/or metastasis. In particular embodiments, the methods and compositions may concern ligands against placenta growth factor (PlGF), such as BP-1, BP-2, BP-3 or BP-4. Some methods may comprise administering one or more PlGF ligands, alone or in combination with one or more other agents, such as chemotherapeutic agents, other anti-angiogenic agents, immunotherapeutic agents or radioimmunotherapeutic agents to a subject. The PlGF ligands are effective to inhibit angiogenesis, tumor cell motility, tumor metastasis, tumor growth and/or tumor survival. In certain embodiments, PlGF ligands may be administered to subjects to ameliorate other angiogenesis related conditions, such as macular degeneration. In some embodiments, PlGF expression levels may be determined by any known method to select those patients most likely to respond to PlGF targeted therapies.
摘要翻译：本发明涉及用于抑制血管发生和/或肿瘤生长，存活和/或转移的方法和组合物。在具体实施方案中，所述方法和组合物可涉及针对胎盘生长因子（PlGF）的配体，例如BP-1，BP-2，BP-3或BP-4。一些方法可以包括单独或与一种或多种其它试剂（例如化学治疗剂，其它抗血管生成剂，免疫治疗剂或放射免疫治疗剂）组合施用一种或多种PlGF配体。 PlGF配体有效抑制血管生成，肿瘤细胞运动，肿瘤转移，肿瘤生长和/或肿瘤存活。在某些实施方案中，可将PlGF配体施用于受试者以改善其它血管生成相关病症，例如黄斑变性。在一些实施方案中，PlGF表达水平可以通过任何已知方法来确定，以选择那些最有可能对PlGF靶向治疗作出反应的患者。

4. 发明申请

WO2007015848A3 IMPROVED METHODS AND COMPOSITIONS FOR INCREASING LONGEVITY AND PROTEIN YIELD FROM A CELL CULTURE 审中-公开
标题翻译：用于增加细胞培养物的长寿和蛋白质产量的改进方法和组合物
公开(公告)号：WO2007015848A3
公开(公告)日：2007-10-04
申请号：PCT/US2006027820
申请日：2006-07-14
申请人： IMMUNOMEDICS INC , NORDSTROM DIANE , GOLDENBERG DAVID M , QU ZHENGXING , CHANG CHIEN HSING , ROSSI EDWARD A , YANG JENG-DAR
发明人： GOLDENBERG DAVID M , QU ZHENGXING , CHANG CHIEN HSING , ROSSI EDWARD A , YANG JENG-DAR
IPC分类号： C12N5/00 , C12N5/09 , C12N15/00
CPC分类号： C07K16/00 , A61K2039/505 , C07K14/4747 , C07K16/18 , C07K16/2803 , C07K16/3007 , C07K2317/24 , C07K2317/31 , C12N5/0694 , C12N2500/90 , C12N2501/48 , C12N2510/02 , C12P21/02
摘要： Disclosed are compositions and methods for increasing the longevity of a cell culture and permitting the increased production of proteins, preferably recombinant proteins, such as antibodies, peptides, enzymes, growth factors, interleukins, interferons, hormones, and vaccines. Cells transfected with an apoptosis-inhibiting gene or vector, such as a triple mutant Bcl-2 gene, can survive longer in culture, resulting in extension of the state and yield of protein biosynthesis. Such transfected cells exhibit maximal cell densities that equal or exceed the maximal density achieved by the parent cell lines. Transfected cells can also be pre-adapted for growth in serum-free medium, greatly decreasing the time required to obtain protein production in serum-free medium. In certain methods, the pre-adapted cells can be used for protein production following transformation under serum-free conditions. The method preferably involves eukaryotic cells, more preferably mammalian cells.
摘要翻译：公开了用于增加细胞培养物寿命并允许蛋白质（优选重组蛋白质，如抗体，肽，酶，生长因子，白细胞介素，干扰素，激素和疫苗）产量增加的组合物和方法。用凋亡抑制基因或载体例如三突变Bcl-2基因转染的细胞可以在培养中更长时间地存活，导致蛋白质生物合成的状态和产量的延长。这种转染的细胞表现出等于或超过亲代细胞系所达到的最大密度的最大细胞密度。转染的细胞也可以预先适应在无血清培养基中生长，大大减少了在无血清培养基中获得蛋白质产生所需的时间。在某些方法中，预适应细胞可以在无血清条件下转化后用于蛋白质生产。该方法优选涉及真核细胞，更优选涉及哺乳动物细胞。

5. 发明申请

WO2007075270A2 MULTIVALENT IMMUNOGLOBULIN-BASED BIOACTIVE ASSEMBLIES 审中-公开
标题翻译：基于免疫球蛋白的生物活性成分
公开(公告)号：WO2007075270A2
公开(公告)日：2007-07-05
申请号：PCT/US2006/046367
申请日：2006-12-05
申请人： IBC PHARMACEUTICALS, INC. , CHANG, Chien-Hsing , GOLDENBERG, David , ROSSI, Edmund
发明人： CHANG, Chien-Hsing , GOLDENBERG, David , ROSSI, Edmund
IPC分类号： C12Q1/70 , G01N33/574 , A61K39/395 , C07K14/82 , C07K16/30 , C07K14/415 , A61K39/00 , C07K16/46
CPC分类号： C07K16/468 , A61K47/6853 , A61K47/6879 , A61K2039/505 , C07K16/00 , C07K16/3007 , C07K2317/55 , C07K2317/624 , C07K2317/732 , C07K2317/734 , C07K2319/00 , C07K2319/70
摘要： The present invention concerns methods and compositions for stably tethered structures of defined compositions, which may have multiple functionalities and/or binding specificities. Preferred embodiments concern hexameric stably tethered structures comprising one or more IgG antibody fragments and which may be monospecific or bispecific. The disclosed methods and compositions provide a facile and general way to obtain stably tethered structures of virtually any functionality and/or binding specificity. The stably tethered structures may be administered to subjects for diagnostic and/or therapeutic use, for example for treatment of cancer or autoimmune disease. The stably tethered structures may bind to and/or be conjugated to a variety of known effectors, such as drugs, enzymes, radionuclides, therapeutic agents and/or diagnostic agents.
摘要翻译：本发明涉及可以具有多种功能和/或结合特异性的限定组合物的稳定的束缚结构的方法和组合物。优选的实施方案涉及包含一种或多种IgG抗体片段并且可以是单特异性或双特异性的六聚体稳定的束缚结构。所公开的方法和组合物提供了实现任何功能和/或结合特异性的稳定的束缚结构的简便和一般的方法。稳定的束缚结构可以施用于受试者用于诊断和/或治疗用途，例如用于治疗癌症或自身免疫性疾病。稳定的束缚结构可以结合到各种已知的效应物上，和/或与其结合，例如药物，酶，放射性核素，治疗剂和/或诊断剂。

6. 发明申请

WO2007047609A2 INHIBITION OF PLACENTA GROWTH FACTOR (PlGF) MEDICATED METASTASIS AND/OR ANGIOGENESIS 审中-公开
标题翻译：抑制PLACENTA生长因子（PlGF）药物化学和/或血管生成
公开(公告)号：WO2007047609A2
公开(公告)日：2007-04-26
申请号：PCT/US2006/040431
申请日：2006-10-16
申请人： CENTER FOR MOLECULAR MEDICINE AND IMMUNOLOGY , IMMUNOMEDICS, INC. , GOLDENBERG, David M. , CHANG, Chien Hsing
发明人： GOLDENBERG, David M. , CHANG, Chien Hsing
IPC分类号： C07K16/46 , A61K39/395
CPC分类号： C07K16/22 , A61K38/00 , C07K14/515 , Y02A50/491
摘要： The present invention concerns methods and compositions for inhibiting angiogenesis and/or tumor growth, survival and/or metastasis. In particular embodiments, the methods and compositions may concern ligands against placenta growth factor (PlGF), such as BP-1, BP-2, BP-3 or BP-4. Some methods may comprise administering one or more PlGF ligands, alone or in combination with one or more other agents, such as chemotherapeutic agents, other anti-angiogenic agents, immunotherapeutic agents or radioimmunotherapeutic agents to a subject. The PlGF ligands are effective to inhibit angiogenesis, tumor cell motility, tumor metastasis, tumor growth and/or tumor survival. In certain embodiments, PlGF ligands may be administered to subjects to ameliorate other angiogenesis related conditions, such as macular degeneration. In some embodiments, PlGF expression levels may be determined by any known method to select those patients most likely to respond to PlGF targeted therapies.
摘要翻译：本发明涉及用于抑制血管发生和/或肿瘤生长，存活和/或转移的方法和组合物。在具体实施方案中，所述方法和组合物可涉及针对胎盘生长因子（PlGF）的配体，例如BP-1，BP-2，BP-3或BP-4。一些方法可以包括单独或与一种或多种其它试剂（例如化学治疗剂，其它抗血管生成剂，免疫治疗剂或放射免疫治疗剂）组合施用一种或多种PlGF配体。 PlGF配体有效抑制血管生成，肿瘤细胞运动，肿瘤转移，肿瘤生长和/或肿瘤存活。在某些实施方案中，可将PlGF配体施用于受试者以改善其它血管生成相关病症，例如黄斑变性。在一些实施方案中，PlGF表达水平可以通过任何已知方法来确定，以选择那些最有可能对PlGF靶向治疗作出反应的患者。

7. 发明申请

WO2007046893A2 METHODS AND COMPOSITIONS FOR GENERATING BIOACTIVE ASSEMBLIES OF INCREASED COMPLEXITY AND USES 审中-公开
标题翻译：用于产生增加复杂性和用途的生物组装的方法和组合物
公开(公告)号：WO2007046893A2
公开(公告)日：2007-04-26
申请号：PCT/US2006/025499
申请日：2006-06-29
申请人： IBC PHARMACEUTICALS, INC. , CHANG, Chien, Hsing , GOLDENBERG, David, M. , MCBRIDE, William, J. , ROSSI, Edmund, A.
发明人： CHANG, Chien, Hsing , GOLDENBERG, David, M. , MCBRIDE, William, J. , ROSSI, Edmund, A.
IPC分类号： C12Q1/70 , G01N33/574 , A61K39/395 , C07K14/82 , C07K16/30 , C07K14/415 , A61K39/00 , C07K16/46
CPC分类号： C07K16/2881 , A61K47/6849 , C07K2317/55 , C07K2319/00 , C07K2319/30
摘要： The present invention concerns methods and compositions for making and using bioactive assemblies of defined compositions, which may have multiple functionalities and/or binding specificities. In particular embodiments, the bioactive assembly is formed using dock-and-lock (DNL) methodology, which takes advantage of the specific binding interaction between dimerization and docking domains (DDD) and anchoring domains (AD) to form the assembly. In various embodiments, one or more effectors may be attached to a DDD or AD sequence. Complementary AD or DDD sequences may be attached to an adaptor module that forms the core of the bioactive assembly, allowing formation of the assembly through the specific DDD/AD binding interactions. Such assemblies may be attached to a wide variety of effector moieties for treatment, detection and/or diagnosis of a disease, pathogen infection or other medical or veterinary condition.
摘要翻译：本发明涉及用于制备和使用具有多种功能和/或结合特异性的限定组合物的生物活性组合物的方法和组合物。在特定的实施方案中，生物活性组件使用对接和锁定（DNL）方法形成，其利用二聚化和对接结构域（DDD）和锚定结构域（AD）之间的特异性结合相互作用形成组件。在各种实施方案中，一个或多个效应物可以连接到DDD或AD序列。互补AD或DDD序列可以连接到形成生物活性组件核心的适配器模块，从而允许通过特定的DDD / AD结合相互作用形成组装。这些组合物可以连接到各种各样的效应部分，用于治疗，检测和/或诊断疾病，病原体感染或其他医学或兽医病症。

8. 发明申请

WO2007015848A2 IMPROVED METHODS AND COMPOSITIONS FOR INCREASING LONGEVITY AND PROTEIN YIELD FROM A CELL CULTURE 审中-公开
标题翻译：用于增加细胞培养物的长寿和蛋白质产量的改进方法和组合物
公开(公告)号：WO2007015848A2
公开(公告)日：2007-02-08
申请号：PCT/US2006/027820
申请日：2006-07-14
申请人： IMMUNOMEDICS, INC. , NORDSTROM, Diane , GOLDENBERG, David M. , QU, Zhengxing , CHANG, Chien Hsing , ROSSI, Edward A. , YANG, Jeng-Dar
发明人： GOLDENBERG, David M. , QU, Zhengxing , CHANG, Chien Hsing , ROSSI, Edward A. , YANG, Jeng-Dar
IPC分类号： C07H21/04 , C12P21/06 , C12N9/00 , C07K14/52 , C07K14/54 , C07K14/56 , C07K14/475 , C07K16/18 , C07K14/505
CPC分类号： C07K16/00 , A61K2039/505 , C07K14/4747 , C07K16/18 , C07K16/2803 , C07K16/3007 , C07K2317/24 , C07K2317/31 , C12N5/0694 , C12N2500/90 , C12N2501/48 , C12N2510/02 , C12P21/02
摘要： Disclosed are compositions and methods for increasing the longevity of a cell culture and permitting the increased production of proteins, preferably recombinant proteins, such as antibodies, peptides, enzymes, growth factors, interleukins, interferons, hormones, and vaccines. Cells transfected with an apoptosis-inhibiting gene or vector, such as a triple mutant Bcl-2 gene, can survive longer in culture, resulting in extension of the state and yield of protein biosynthesis. Such transfected cells exhibit maximal cell densities that equal or exceed the maximal density achieved by the parent cell lines. Transfected cells can also be pre-adapted for growth in serum-free medium, greatly decreasing the time required to obtain protein production in serum-free medium. In certain methods, the pre-adapted cells can be used for protein production following transformation under serum-free conditions. The method preferably involves eukaryotic cells, more preferably mammalian cells.
摘要翻译：公开了用于增加细胞培养物的寿命并允许增加蛋白质，优选重组蛋白质如抗体，肽，酶，生长因子，白细胞介素，干扰素，激素等的产生的组合物和方法。和疫苗。用凋亡抑制基因或载体例如三突变Bcl-2基因转染的细胞可以在培养中更长时间地存活，导致蛋白质生物合成的状态和产量的延长。这种转染的细胞表现出等于或超过亲代细胞系所达到的最大密度的最大细胞密度。转染的细胞也可以预先适应在无血清培养基中生长，大大减少了在无血清培养基中获得蛋白质产生所需的时间。在某些方法中，预适应细胞可以在无血清条件下转化后用于蛋白质生产。该方法优选涉及真核细胞，更优选涉及哺乳动物细胞。

9. 发明申请

WO2007015691A2 METHODS AND COMPOSITIONS FOR INCREASING LONGEVITY AND PROTEIN YIELD FROM A CELL CULTURE 审中-公开
标题翻译：从细胞培养物中增加长度和蛋白质含量的方法和组合物
公开(公告)号：WO2007015691A2
公开(公告)日：2007-02-08
申请号：PCT/US2005026224
申请日：2005-07-25
申请人： IMMUNOMEDICS INC , GOLDENBERG DAVID M , QU ZHENGXING , HORAK EVA , HORAK IVAN D , CHANG CHIEN-HSING KEN , ROSSI EDMUND A , YANG JENG-DAR
发明人： GOLDENBERG DAVID M , QU ZHENGXING , HORAK EVA , HORAK IVAN D , CHANG CHIEN-HSING KEN , ROSSI EDMUND A , YANG JENG-DAR
IPC分类号： C07H21/04 , C07K14/475 , C07K14/505 , C07K14/52 , C07K14/54 , C07K14/56 , C07K16/18 , C12N9/00 , C12P21/06
CPC分类号： C12P21/02 , C07K14/4747 , C07K16/00
摘要： Disclosed herein are compositions and methods for increasing the longevity of a cell culture and permitting the increased production of proteins, preferably recombinant proteins, such as antibodies, peptides, enzymes, growth factors, interleukins, interferons, hormones, and vaccines. By transfecting cells in culture with an apoptosis-inhibiting gene or vector, cells in culture can survive longer, resulting in extension of the state and yield of protein biosynthesis. Expression of the apoptosis-inhibitor within the cells, because it does not kill the cells, allows the cells, or an increased fraction thereof, to be maintained in culture for longer periods. This invention then allows for controlled, enhanced protein production of cell lines for commercial and research uses, particularly the enhanced production of growth factors, interferons, interleukins, hormones, enzymes, and monoclonal antibodies, and the like. The method preferentially involves eukaryotic cells in culture, and more advantageously mammalian cells in culture.
摘要翻译：本文公开了用于增加细胞培养物的寿命并允许增加蛋白质生产的组合物和方法，优选重组蛋白，例如抗体，肽，酶，生长因子，白细胞介素，干扰素，激素和疫苗。通过用细胞凋亡抑制基因或载体转染培养细胞，培养中的细胞可以长时间存活，导致蛋白质生物合成的状态和产量的延长。凋亡抑制剂在细胞内的表达，因为它不杀死细胞，允许细胞或其增加的部分在培养物中保持较长时间。本发明然后允许用于商业和研究用途的细胞系的受控增强的蛋白质生产，特别是生长因子，干扰素，白细胞介素，激素，酶和单克隆抗体的增强生产等。该方法优先涉及培养中的真核细胞，更有利于培养中的哺乳动物细胞。

10. 发明申请

WO2005014618A2 BISPECIFIC ANTIBODIES FOR INDUCING APOPTOSIS OF TUMOR AND DISEASED CELLS 审中-公开
标题翻译：诱导肿瘤和疾病细胞凋亡的双重抗体
公开(公告)号：WO2005014618A2
公开(公告)日：2005-02-17
申请号：PCT/US2004/025840
申请日：2004-08-09
申请人： IMMUNOMEDICS, INC. , CHANG, Chien-Hsing , GOLDENBERG, David, M. , HANSEN, Hans, J. , HORAK, Eva , HORAK, Ivan
发明人： CHANG, Chien-Hsing , GOLDENBERG, David, M. , HANSEN, Hans, J. , HORAK, Eva , HORAK, Ivan
IPC分类号： C07K
CPC分类号： C07K16/2887 , C07K16/2803 , C07K2317/31 , C07K2317/55 , C07K2317/73 , C07K2317/75
摘要： The bispecific antibodies of the present invention are in the form of a heteroconjugate that inhibits growth and induces apoptosis of a diseased cell and that does not require the recruitment of effector cells. The heteroconjugate has at least two binding arms wherein each of the binding arms possesses a different specificity and need not have apoptotic activity when not conjugated to each other. Also provided are methods of treating and diagnosing a diseased cell using the bispecfic antibodies of the present invention.
摘要翻译：本发明的双特异性抗体是异源结合物的形式，其抑制生长并诱导病变细胞的凋亡，并且不需要募集效应细胞。杂合物具有至少两个结合臂，其中每个结合臂具有不同的特异性，并且当不彼此结合时不需要具有凋亡活性。还提供了使用本发明的双特异性抗体治疗和诊断患病细胞的方法。

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