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    Stably tethered structures of defined compositions with multiple functions or binding specificities
    1.
    发明授权
    Stably tethered structures of defined compositions with multiple functions or binding specificities 有权
    具有多种功能或结合特异性的定义组合物的稳定的束缚结构

    公开(公告)号：US07521056B2

    公开(公告)日：2009-04-21

    申请号：US11391584

    申请日：2006-03-28

    申请人： Chien Hsing Chang ,  David M. Goldenberg ,  William J. McBride ,  Edmund A. Rossi

    发明人： Chien Hsing Chang ,  David M. Goldenberg ,  William J. McBride ,  Edmund A. Rossi

    IPC分类号： A61K38/01 ,  A61K38/19 ,  A61K38/21 ,  A61K39/395 ,  C07K14/52 ,  C07K14/535 ,  C07K14/405 ,  C07K14/56

    CPC分类号： C07K16/18 ,  A61K39/395 ,  A61K47/65 ,  A61K47/6853 ,  A61K51/088 ,  A61K51/1048 ,  B82Y5/00 ,  B82Y10/00 ,  B82Y30/00 ,  C07K16/283 ,  C07K16/3007 ,  C07K16/468 ,  C07K2317/31 ,  C07K2317/55 ,  C07K2317/569 ,  C07K2319/00 ,  C07K2319/70

    摘要： The present invention concerns methods and compositions for stably tethered structures of defined compositions with multiple functionalities and/or binding specificities. Particular embodiments concern stably tethered structures comprising a homodimer of a first monomer, comprising a dimerization and docking domain attached to a first precursor, and a second monomer comprising an anchoring domain attached to a second precursor. The first and second precursors may be virtually any molecule or structure, such as antibodies, antibody fragments, antibody analogs or mimetics, aptamers, binding peptides, fragments of binding proteins, known ligands for proteins or other molecules, enzymes, detectable labels or tags, therapeutic agents, toxins, pharmaceuticals, cytokines, interleukins, interferons, radioisotopes, proteins, peptides, peptide mimetics, polynucleotides, RNAi, oligosaccharides, natural or synthetic polymeric substances, nanoparticles, quantum dots, organic or inorganic compounds, etc. The disclosed methods and compositions provide a simple, easy to purify way to obtain any binary compound attached to any monomeric compound, or any trinary compound.

    摘要翻译： 本发明涉及用于具有多种功能和/或结合特异性的限定组合物的稳定束缚结构的方法和组合物。 具体实施方案涉及稳定的包含第一单体的同二聚体的束缚结构，其包含连接到第一前体的二聚化和对接结构域，以及包含连接到第二前体的锚定结构域的第二单体。 第一和第二前体实际上可以是任何分子或结构，例如抗体，抗体片段，抗体类似物或模拟物，适体，结合肽，结合蛋白片段，蛋白质或其他分子的已知配体，酶，可检测标记或标签， 治疗剂，毒素，药物，细胞因子，白介素，干扰素，放射性同位素，蛋白质，肽，肽模拟物，多核苷酸，RNAi，寡糖，天然或合成聚合物质，纳米颗粒，量子点，有机或无机化合物等。 组合物提供了一种简单，易于纯化的方式来获得连接到任何单体化合物或任何三元化合物上的任何二元化合物。

    Methods for generating stably linked complexes composed of homodimers, homotetramers or dimers of dimers and uses
    2.
    发明授权
    Methods for generating stably linked complexes composed of homodimers, homotetramers or dimers of dimers and uses 有权
    用于产生由同型二聚体，同三聚体或二聚体二聚体和用途组成的稳定连接络合物的方法

    公开(公告)号：US07550143B2

    公开(公告)日：2009-06-23

    申请号：US11389358

    申请日：2006-03-24

    申请人： Chien Hsing Chang ,  David M. Goldenberg ,  William J. McBride ,  Edmund A. Rossi

    发明人： Chien Hsing Chang ,  David M. Goldenberg ,  William J. McBride ,  Edmund A. Rossi

    IPC分类号： C07K16/46 ,  C07K16/28 ,  C07K16/30 ,  A61K38/01 ,  A61K38/19 ,  A61K39/395

    CPC分类号： C12N9/12 ,  B82Y5/00 ,  B82Y10/00 ,  C07K16/18 ,  C07K16/2803 ,  C07K16/2887 ,  C07K16/3007 ,  C07K16/3092 ,  C07K2317/31 ,  C07K2317/55 ,  C07K2319/00 ,  C07K2319/70 ,  C12Y207/11011

    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. Particular embodiments concern homodimers comprising monomers that contain a dimerization and docking domain attached to a precursor. The precursors may be virtually any molecule or structure, such as antibodies, antibody fragments, antibody analogs or mimetics, aptamers, binding peptides, fragments of binding proteins, known ligands for proteins or other molecules, enzymes, detectable labels or tags, therapeutic agents, toxins, pharmaceuticals, cytokines, interleukins, interferons, radioisotopes, proteins, peptides, peptide mimetics, polynucleotides, RNAi, oligosaccharides, natural or synthetic polymeric substances, nanoparticles, quantum dots, organic or inorganic compounds, etc. Other embodiments concern tetramers comprising a first and second homodimer, which may be identical or different. The disclosed methods and compositions provide a facile and general way to obtain homodimers, homotetramers and heterotetramers of virtually any functionality and/or binding specificity.

    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。 具体实施方案涉及包含单体的同型二聚体，其含有连接到前体的二聚化和对接结构域。 前体实际上可以是任何分子或结构，例如抗体，抗体片段，抗体类似物或模拟物，适体，结合肽，结合蛋白的片段，蛋白质或其他分子的已知配体，酶，可检测标记或标签，治疗剂， 毒素，药物，细胞因子，白细胞介素，干扰素，放射性同位素，蛋白质，肽，肽模拟物，多核苷酸，RNAi，寡糖，天然或合成聚合物质，纳米颗粒，量子点，有机或无机化合物等。其他实施方案涉及四聚体， 和第二同二聚体，其可以相同或不同。 所公开的方法和组合物提供了获得实质上任何功能性和/或结合特异性的同源二聚体，同源四聚体和异源四聚体的简便且一般的方式。

    Methods and compositions for treatment of human immunodeficiency virus infection with conjugated antibodies or antibody fragments
    3.
    发明授权
    Methods and compositions for treatment of human immunodeficiency virus infection with conjugated antibodies or antibody fragments 有权
    用共轭抗体或抗体片段治疗人类免疫缺陷病毒感染的方法和组合物

    公开(公告)号：US08333971B2

    公开(公告)日：2012-12-18

    申请号：US11745692

    申请日：2007-05-08

    申请人： David M. Goldenberg ,  Chien Hsing Chang ,  Edmund A. Rossi ,  William J. McBride

    发明人： David M. Goldenberg ,  Chien Hsing Chang ,  Edmund A. Rossi ,  William J. McBride

    IPC分类号： A61K39/00 ,  A61K39/395

    CPC分类号： A61K39/39583 ,  A61K31/4745 ,  A61K31/513 ,  A61K39/42 ,  A61K47/6809 ,  A61K47/6841 ,  A61K47/6879 ,  A61K2039/505 ,  C07K16/1045 ,  C07K16/1063 ,  C07K2317/732 ,  C07K2317/76

    摘要： The present invention concerns methods and compositions for treatment of HIV infection in a subject. The compositions may comprise a targeting molecule against an HIV antigen, such as an anti-HIV antibody or antibody fragment. The anti-HIV antibody or fragment may be conjugated to a variety of cytotoxic agents, such as doxorubicin. In a preferred embodiment, the antibody or fragment is P4/D10. Other embodiments may concern methods of imaging, detection or diagnosis of HIV infection in a subject using an anti-HIV antibody or fragment conjugated to a diagnostic agent. In alternative embodiments, a bispecific antibody with at least one binding site for an HIV antigen and at least one binding site for a carrier molecule may be administered, optionally followed by a clearing agent, followed by administration of a carrier molecule conjugated to a therapeutic agent.

    摘要翻译： 本发明涉及用于治疗受试者的HIV感染的方法和组合物。 组合物可以包含针对HIV抗原的靶向分子，例如抗HIV抗体或抗体片段。 抗HIV抗体或片段可以与多种细胞毒剂如多柔比星缀合。 在优选的实施方案中，抗体或片段是P4 / D10。 其他实施方案可涉及使用抗HIV抗体或缀合至诊断剂的片段在受试者中成像，检测或诊断HIV感染的方法。 在替代实施方案中，可以施用具有HIV抗原的至少一个结合位点和载体分子的至少一个结合位点的双特异性抗体，任选地随后是清除剂，然后施用与治疗剂缀合的载体分子 。

    Methods and compositions for increasing longevity and protein yield from a cell culture
    7.
    发明授权
    Methods and compositions for increasing longevity and protein yield from a cell culture 有权
    用于增加细胞培养物的寿命和蛋白质产量的方法和组合物

    公开(公告)号：US07531327B2

    公开(公告)日：2009-05-12

    申请号：US11187863

    申请日：2005-07-25

    申请人： David M. Goldenberg ,  Zhengxing Qu ,  Eva Horak ,  Ivan D. Horak ,  Chien Hsing Chang ,  Edmund A. Rossi ,  Jeng-Dar Yang

    发明人： David M. Goldenberg ,  Zhengxing Qu ,  Eva Horak ,  Ivan D. Horak ,  Chien Hsing Chang ,  Edmund A. Rossi ,  Jeng-Dar Yang

    IPC分类号： C12N5/10 ,  C12N5/16

    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 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。

    Nucleic acids encoding polyvalent protein complexes
    8.
    发明授权
    Nucleic acids encoding polyvalent protein complexes 有权
    编码多价蛋白复合物的核酸

    公开(公告)号：US08829175B2

    公开(公告)日：2014-09-09

    申请号：US11830413

    申请日：2007-07-30

    申请人： Edmund A. Rossi ,  Chien Hsing Chang ,  William John McBride

    发明人： Edmund A. Rossi ,  Chien Hsing Chang ,  William John McBride

    IPC分类号： C07H21/04

    CPC分类号： C07K16/44 ,  A61K2039/505 ,  C07K16/3007 ,  C07K16/468 ,  C07K2317/24 ,  C07K2317/626 ,  C07K2318/20 ,  C07K2319/00

    摘要： The invention provides for a polyvalent protein complex (PPC) comprising two polypeptide chains generally arranged laterally to one another. Each polypeptide chain typically comprises 3 or 4 “v-regions”, which comprise amino acid sequences capable of forming an antigen binding site when matched with a corresponding v-region on the opposite polypeptide chain. Up to about 6 “v-regions” can be used on each polypeptide chain. The v-regions of each polypeptide chain are connected linearly to one another and may be connected by interspersed linking regions. When arranged in the form of the PPC, the v-regions on each polypeptide chain form individual antigen binding sites.

    摘要翻译： 本发明提供了包含两条多肽链的多价蛋白质复合物（PPC），其通常彼此横向排列。 每个多肽链通常包含3或4个“v区”，其包含当与相对的多肽链上的相应v-区域匹配时能够形成抗原结合位点的氨基酸序列。 每个多肽链可以使用多达约6个“v区”。 每个多肽链的v-区域彼此线性连接并且可以通过散在的连接区域连接。 当以PPC的形式排列时，每个多肽链上的v-区域形成单独的抗原结合位点。

    Inhibition of Placenta Growth Factor (PLGF) Mediated Metastasis and/or Angiogenesis
    9.
    发明申请
    Inhibition of Placenta Growth Factor (PLGF) Mediated Metastasis and/or Angiogenesis 有权
    抑制胎盘生长因子（PLGF）介导的转移和/或血管发生

    公开(公告)号：US20100216662A1

    公开(公告)日：2010-08-26

    申请号：US12620013

    申请日：2009-11-17

    申请人： Alice P. Taylor ,  David M. Goldenberg ,  Chien Hsing Chang

    发明人： Alice P. Taylor ,  David M. Goldenberg ,  Chien Hsing Chang

    IPC分类号： C40B30/04

    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 (P1GF), such as BP-1, BP-2, BP-3 or BP-4. Some methods may comprise administering one or more P1GF 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 P1GF ligands are effective to inhibit angiogenesis, tumor cell motility, tumor metastasis, tumor growth and/or tumor survival. In certain embodiments, P1GF ligands may be administered to subjects to ameliorate other angiogenesis related conditions, such as macular degeneration. In some embodiments, P1GF expression levels may be determined by any known method to select those patients most likely to respond to P1GF 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以涉及针对胎盘生长因子（P1GF）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P1GF配体。 P1GF配体有效抑制血管发生，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，P1GF配体可以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，P1GF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P1GF靶向治疗作出反应的患者。

    Inhibition of placenta growth factor (PLGF) mediated metastasis and/or angiogenesis
    10.
    发明授权
    Inhibition of placenta growth factor (PLGF) mediated metastasis and/or angiogenesis 有权
    抑制胎盘生长因子（PLGF）介导的转移和/或血管发生

    公开(公告)号：US07642239B2

    公开(公告)日：2010-01-05

    申请号：US11581287

    申请日：2006-10-16

    申请人： Alice P. Taylor ,  David M. Goldenberg ,  Chien Hsing Chang

    发明人： Alice P. Taylor ,  David M. Goldenberg ,  Chien Hsing Chang

    IPC分类号： A61K38/04

    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。