Methods for Generating Stably Linked Complexes Composed of Homodimers, Homotetramers or Dimers of Dimers and Uses
    71.
    发明申请
    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,同分子或二聚体和用途的二聚体组成的稳定连接的复合物的方法

    公开(公告)号:US20110008251A1

    公开(公告)日:2011-01-13

    申请号:US12468589

    申请日:2009-05-19

    Abstract: 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.

    Abstract translation: 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。

    Inhibition of Placenta Growth Factor (PLGF) Mediated Metastasis and/or Angiogenesis
    73.
    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

    CPC classification number: C07K16/22 A61K38/00 C07K14/515 Y02A50/491

    Abstract: 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.

    Abstract translation: 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。

    PEGylation by the dock and lock (DNL) technique
    74.
    发明授权
    PEGylation by the dock and lock (DNL) technique 有权
    通过码头和锁定(DNL)技术进行PEG化

    公开(公告)号:US07666400B2

    公开(公告)日:2010-02-23

    申请号:US11925408

    申请日:2007-10-26

    Abstract: The present invention concerns methods and compositions for forming PEGylated complexes of defined stoichiometry and structure. In preferred embodiments, the PEGylated complex is formed using dock-and-lock technology, by attaching a therapeutic agent to a DDD sequence and attaching a PEG moiety to an AD sequence and allowing the DDD sequence to bind to the AD sequence in a 2:1 stoichiometry, to form PEGylated complexes with two target agents and one PEG moiety. In alternative embodiments, the target agent may be attached to the AD sequence and the PEG to the DDD sequence to form PEGylated complexes with two PEG moieties and one target agent. In more preferred embodiments, the target agent may comprise any peptide or protein of physiologic or therapeutic activity. The PEGylated complexes exhibit a significantly slower rate of clearance when injected into a subject and are of use for treatment of a wide variety of diseases.

    Abstract translation: 本发明涉及用于形成定义化学计量和结构的聚乙二醇化配合物的方法和组合物。 在优选的实施方案中,使用对接和锁定技术形成聚乙二醇化复合物,通过将治疗剂连接到DDD序列并将PEG部分连接到AD序列并允许DDD序列以2: 1化学计量,以形成与两个靶剂和一个PEG部分的聚乙二醇化复合物。 在替代实施方案中,靶物质可以连接到AD序列,并将PEG连接到DDD序列以形成具有两个PEG部分和一个目标试剂的PEG化复合物。 在更优选的实施方案中,靶剂可以包含生理或治疗活性的任何肽或蛋白质。 当注射到受试者中时,聚乙二醇化复合物表现出明显较慢的清除率,并且可用于治疗各种各样的疾病。

    Structural Variants of Antibodies for Improved Therapeutic Characteristics
    75.
    发明申请
    Structural Variants of Antibodies for Improved Therapeutic Characteristics 有权
    用于改善治疗特征的抗体的结构变体

    公开(公告)号:US20100034738A1

    公开(公告)日:2010-02-11

    申请号:US12506992

    申请日:2009-07-21

    Abstract: The present invention provides substituted humanized, chimeric or human anti-CD20 antibodies or antigen binding fragments thereof and bispecific antibodies or fusion proteins comprising the substituted antibodies or antigen binding fragments thereof. The antibodies, fusion proteins or fragments are useful for treatment of B-cell disorders, such as B-cell malignancies and autoimmune diseases, as well as GVHD, organ transplant rejection, and hemolytic anemia and cryoglobulinemia. Amino acid substitutions, particularly substitution of an aspartate residue at Kabat position 101 of CDR3 VH (CDRH3), result in improved therapeutic properties, such as decreased dissociation rates, improved CDC activity, improved apoptosis, improved B-cell depletion and improved therapeutic efficacy at very low dosages. Veltuzumab, a humanized anti-CD20 antibody that incorporates such sequence variations, exhibits improved therapeutic efficacy compared to similar antibodies of different CDRH3 sequence, allowing therapeutic effect at dosages as low as 200 mg or less, more preferably 100 mg or less, more preferably 80 mg or less, more preferably 50 mg or less, most preferably 30 mg or less of naked antibody when administered i.v. or s.c.

    Abstract translation: 本发明提供取代的人源化,嵌合或人抗CD20抗体或其抗原结合片段和包含取代的抗体或其抗原结合片段的双特异性抗体或融合蛋白。 抗体,融合蛋白或片段可用于治疗B细胞病变,如B细胞恶性肿瘤和自身免疫性疾病,以及GVHD,器官移植排斥,溶血性贫血和冷球蛋白血症。 氨基酸取代,特别是取代CDR3 VH(CDRH3)Kabat 101位天冬氨酸残基导致改善的治疗性质,例如降低的解离速率,改善的CDC活性,改善的细胞凋亡,改善的B细胞消耗和改善的治疗功效 非常低的剂量 Veltuzumab是与不同CDRH3序列的相似抗体相比具有改善的治疗效果的,具有这种序列变异性的人源化抗-CD20抗体,其能够以低至200mg或更低,更优选为100mg或更少,更优选为80mg mg或更少,更优选50mg或更少,最优选30mg或更少的裸抗体 或s.c.

    Inhibition of placenta growth factor (PLGF) mediated metastasis and/or angiogenesis
    76.
    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

    CPC classification number: C07K16/22 A61K38/00 C07K14/515 Y02A50/491

    Abstract: 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.

    Abstract translation: 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。

    Methods and compositions for increasing longevity and protein yield from a cell culture
    79.
    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

    Abstract: 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.

    Abstract translation: 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。

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