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    Methods for Generating Stably Linked Complexes Composed of Homodimers, Homotetramers or Dimers of Dimers and Uses
    4.
    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：US20120196346A1

    公开(公告)日：2012-08-02

    申请号：US13419614

    申请日：2012-03-14

    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： C07K19/00 ,  C12N9/96

    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 for generating stably linked complexes composed of homodimers, homotetramers or dimers of dimers and uses
    5.
    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：US08163291B2

    公开(公告)日：2012-04-24

    申请号：US12468589

    申请日：2009-05-19

    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： A61K39/385 ,  A61K39/44 ,  A61K39/00 ,  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。

    Dimeric Alpha Interferon PEGylated Site-Specifically Shows Enhanced and Prolonged Efficacy in Vivo
    7.
    发明申请
    Dimeric Alpha Interferon PEGylated Site-Specifically Shows Enhanced and Prolonged Efficacy in Vivo 有权
    二聚体阿尔法干扰素聚乙二醇化位点 - 具体显示体内增强和延长功效

    公开(公告)号：US20110300105A1

    公开(公告)日：2011-12-08

    申请号：US13178092

    申请日：2011-07-07

    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： A61K38/21 ,  A61P35/00 ,  A61P37/06 ,  A61P31/12

    CPC分类号： C12N9/1205 ,  A61K39/395 ,  A61K47/60 ,  A61K47/64 ,  B82Y10/00 ,  B82Y30/00 ,  C07K16/00 ,  C07K16/005 ,  C07K16/283 ,  C07K16/3007 ,  C07K16/468 ,  C07K2317/31 ,  C07K2317/55 ,  C07K2317/73 ,  C07K2319/00 ,  C07K2319/70 ,  Y02A50/386

    摘要： 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 therapeutic agents and one PEG moiety. In alternative embodiments, the therapeutic 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 therapeutic agent. In more preferred embodiments, the therapeutic agent may comprise any peptide or protein of physiologic or therapeutic activity, preferably a cytokine, more preferably interferon-α2b. 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.

    摘要翻译： 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，以形成具有两个治疗剂和一个PEG部分的PEG化复合物。 在替代实施方案中，治疗剂可以连接到AD序列，并将PEG连接到DDD序列以与两个PEG部分和一种治疗剂形成聚乙二醇化复合物。 在更优选的实施方案中，治疗剂可以包含生理或治疗活性的任何肽或蛋白质，优选细胞因子，更优选干扰素-α2b。 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。

    Methods for generating stably linked complexes composed of homodimers, homotetramers or dimers of dimers and uses
    8.
    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。

    PEGylation by the Dock and Lock (DNL) Technique
    9.
    发明申请
    PEGylation by the Dock and Lock (DNL) Technique 有权
    通过Dock和Lock（DNL）技术进行PEG化

    公开(公告)号：US20090060862A1

    公开(公告)日：2009-03-05

    申请号：US11925408

    申请日：2007-10-26

    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： A61K38/20 ,  C07K14/00 ,  C12N9/00 ,  C07K14/805 ,  C07K16/00 ,  C07K14/54 ,  A61K38/28 ,  A61K38/18 ,  C07K14/555 ,  C07K14/62 ,  C07K14/505 ,  A61K38/16 ,  A61K38/21

    CPC分类号： A61K47/6835 ,  A61K38/1816 ,  A61K38/193 ,  A61K38/212 ,  A61K47/60 ,  A61K47/65 ,  A61K47/6853 ,  A61K51/1048 ,  B82Y5/00 ,  B82Y10/00 ,  C07K2319/00 ,  C07K2319/70

    摘要： 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 target 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.

    摘要翻译： 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，通过将目标试剂连接到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。