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101 条记录 (耗时 0.059 秒)

    Stably tethered structures of defined compositions with multiple functions or binding specificities
    91.
    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：US07871622B2

    公开(公告)日：2011-01-18

    申请号：US12396965

    申请日：2009-03-03

    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： C07K16/28 ,  C07K16/32 ,  C12P21/08 ,  A61K39/395 ,  A61K39/44

    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
    92.
    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

    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： A61K51/08 ,  A61K39/395 ,  A61P35/00 ,  A61P31/22 ,  A61P11/06 ,  A61P37/06 ,  A61P7/02 ,  A61P35/02 ,  A61P19/02 ,  A61P25/28 ,  A61K38/02 ,  A61K38/49 ,  A61K38/19 ,  A61K49/14 ,  A61K49/00 ,  A61K49/22

    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
    93.
    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

    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： A61K31/74 ,  A61K38/21 ,  A61K38/22 ,  A61K38/36 ,  A61K38/43 ,  C12N11/08 ,  C07K17/08 ,  C07K16/00 ,  C07K14/52 ,  C07K14/545 ,  C07K14/55 ,  C07K14/56

    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 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.

    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。

    Methods and Compositions for Improved F-18 Labeling of Proteins, Peptides and Other Molecules
    94.
    发明申请
    Methods and Compositions for Improved F-18 Labeling of Proteins, Peptides and Other Molecules 有权
    改进的蛋白质，肽和其他分子的F-18标记的方法和组合物

    公开(公告)号：US20100008858A1

    公开(公告)日：2010-01-14

    申请号：US12541527

    申请日：2009-08-14

    申请人： William J. McBride ,  David M. Goldenberg

    发明人： William J. McBride ,  David M. Goldenberg

    IPC分类号： A61K49/00 ,  A61K38/16 ,  A61K39/395 ,  A61K38/00

    CPC分类号： A61K51/08 ,  A61K51/088 ,  C07B59/008

    摘要： The present application discloses compositions and methods of synthesis and use of F-18 labeled molecules of use, for example, in PET imaging techniques. In particular embodiments, the labeled molecules may be peptides or proteins, although other types of molecules including but not limited to aptamers, oligonucleotides and nucleic acids may be labeled and utilized for such imaging studies. In preferred embodiments, the F-18 label may be conjugated to a targeting molecule by formation of a metal complex and binding of the F-18-metal complex to a chelating moiety, such as DOTA, NOTA, DTPA, TETA or NETA. In other embodiments, the metal may first be conjugated to the chelating group and subsequently the F-18 bound to the metal. In other preferred embodiments, the F-18 labeled moiety may comprise a targetable conjugate that may be used in combination with a bispecific or multi specific antibody to target the F-18 to an antigen expressed on a cell or tissue associated with a disease, medical condition, or pathogen. Exemplary results show that F-18 labeled targetable conjugate peptides are stable in human serum at 37° C. for several hours, sufficient time to perform PET imaging analysis.

    摘要翻译： 本申请公开了用于例如PET成像技术的F-18标记分子的合成和使用的组合物和方法。 在具体实施方案中，标记的分子可以是肽或蛋白质，尽管其他类型的分子包括但不限于适体，寡核苷酸和核酸可以被标记并用于这种成像研究。 在优选的实施方案中，F-18标记可以通过形成金属络合物和F-18-金属络合物与螯合部分如DOTA，NOTA，DTPA，TETA或NETA的结合而与靶向分子缀合。 在其它实施方案中，金属可以首先与螯合基团缀合，随后F-18与金属结合。 在其它优选的实施方案中，F-18标记的部分可以包含可靶向缀合物，其可以与双特异性或多特异性抗体组合使用，以将F-18靶向在与疾病相关的细胞或组织上表达的抗原，医学 病症或病原体。 示例性结果表明，F-18标记的可靶向缀合物肽在人血清中在37℃下稳定数小时，足够的时间进行PET成像分析。

    Methods and Compositions for F-18 Labeling of Proteins, Peptides and Other Molecules
    95.
    发明申请
    Methods and Compositions for F-18 Labeling of Proteins, Peptides and Other Molecules 有权
    蛋白质，肽和其他分子的F-18标记的方法和组合物

    公开(公告)号：US20090246130A1

    公开(公告)日：2009-10-01

    申请号：US12433212

    申请日：2009-04-30

    申请人： William J. McBride ,  Christopher A. D'Souza ,  David M. Goldenberg

    发明人： William J. McBride ,  Christopher A. D'Souza ,  David M. Goldenberg

    IPC分类号： A61K51/08 ,  A61P35/00 ,  A61P37/00 ,  A61P29/00 ,  A61K51/10 ,  C07D255/02

    CPC分类号： A61K51/082 ,  A61K47/6897 ,  A61K51/0406 ,  A61K51/0491 ,  A61K51/08 ,  A61K51/083 ,  A61K51/088 ,  A61K51/109 ,  B82Y5/00

    摘要： The present application discloses compositions and methods of synthesis and use of 18F or 19F labeled molecules of use in PET or MRI imaging. The labeled molecules may be peptides or proteins, although other types of molecules may be labeled. Preferably, the 18F or 19F is conjugated to a targeting molecule by formation of a metal complex and binding of the 18F- or 19F-metal complex to a chelating moiety. Alternatively, the metal may first be conjugated to the chelating group and subsequently the 18F or 19F bound to the metal. In other embodiments, the 18F or 19F labeled moiety may comprise a targetable construct used in combination with a bispecific antibody to target a disease-associated antigen. The 18F or 19F labeled targetable construct peptides are stable in serum at 37° C. for a sufficient time to perform PET or MRI imaging.

    摘要翻译： 本申请公开了合成和使用用于PET或MRI成像的18F或19F标记分子的组合物和方法。 标记的分子可以是肽或蛋白质，尽管其它类型的分子可以被标记。 优选地，18F或19F通过形成金属络合物和18F-或19F-金属络合物与螯合部分的结合而与靶向分子缀合。 或者，金属可以首先与螯合基团缀合，随后18F或19F与金属结合。 在其它实施方案中，18F或19F标记的部分可以包含与靶向疾病相关抗原的双特异性抗体组合使用的可靶向构建体。 18F或19F标记的可靶向构建体肽在血清中在37℃下稳定足够的时间进行PET或MRI成像。

    Methods and compositions for F-18 labeling of proteins, peptides and other molecules
    96.
    发明授权
    Methods and compositions for F-18 labeling of proteins, peptides and other molecules 有权
    用于蛋白质，肽和其他分子的F-18标记的方法和组合物

    公开(公告)号：US07563433B2

    公开(公告)日：2009-07-21

    申请号：US12112289

    申请日：2008-04-30

    申请人： William J. McBride ,  David M. Goldenberg

    发明人： William J. McBride ,  David M. Goldenberg

    IPC分类号： A61K51/00 ,  A61M36/14

    CPC分类号： A61K51/082 ,  A61K47/6897 ,  A61K51/0406 ,  A61K51/0491 ,  A61K51/08 ,  A61K51/088 ,  A61K51/109 ,  B82Y5/00 ,  C07B59/008

    摘要： The present application discloses compositions and methods of synthesis and use of F-18 labeled molecules of use, for example, in PET imaging techniques. In particular embodiments, the labeled molecules may be peptides or proteins, although other types of molecules including but not limited to aptamers, oligonucleotides and nucleic acids may be labeled and utilized for such imaging studies. In preferred embodiments, the F-18 label may be conjugated to a targeting molecule by formation of a metal complex and binding of the F-18-metal complex to a chelating moiety, such as DOTA, NOTA, DTPA, TETA or NETA. In other embodiments, the metal may first be conjugated to the chelating group and subsequently the F-18 bound to the metal. In other preferred embodiments, the F-18 labeled moiety may comprise a targetable conjugate that may be used in combination with a bispecific or multispecific antibody to target the F-18 to an antigen expressed on a cell or tissue associated with a disease, medical condition, or pathogen. Exemplary results show that F-18 labeled targetable conjugate peptides are stable in human serum at 37° C. for several hours, sufficient time to perform PET imaging analysis.

    摘要翻译： 本申请公开了用于例如PET成像技术的F-18标记分子的合成和使用的组合物和方法。 在具体实施方案中，标记的分子可以是肽或蛋白质，尽管其他类型的分子包括但不限于适体，寡核苷酸和核酸可以被标记并用于这种成像研究。 在优选的实施方案中，F-18标记可以通过形成金属络合物和F-18-金属络合物与螯合部分如DOTA，NOTA，DTPA，TETA或NETA的结合而与靶向分子缀合。 在其它实施方案中，金属可以首先与螯合基团缀合，随后F-18与金属结合。 在其它优选的实施方案中，F-18标记的部分可以包含可靶向的缀合物，其可以与双特异性或多特异性抗体组合使用，以将F-18靶向在与疾病相关的细胞或组织上表达的抗原，医学病症 ，或病原体。 示例性结果表明，F-18标记的可靶向缀合物肽在人血清中在37℃下稳定数小时，足够的时间进行PET成像分析。

    Methods and Compositions for F-18 Labeling of Proteins, Peptides and Other Molecules
    97.
    发明申请
    Methods and Compositions for F-18 Labeling of Proteins, Peptides and Other Molecules 有权
    蛋白质，肽和其他分子的F-18标记的方法和组合物

    公开(公告)号：US20090155166A1

    公开(公告)日：2009-06-18

    申请号：US12343655

    申请日：2008-12-24

    申请人： William J. McBride ,  Christopher A. D'Souza ,  David M. Goldenberg

    发明人： William J. McBride ,  Christopher A. D'Souza ,  David M. Goldenberg

    IPC分类号： A61K51/10 ,  C07K14/00 ,  A61K51/08

    CPC分类号： A61K51/082 ,  A61K47/6897 ,  A61K51/0406 ,  A61K51/0491 ,  A61K51/08 ,  A61K51/083 ,  A61K51/088 ,  A61K51/109 ,  B82Y5/00 ,  C07K1/13

    摘要： The present application discloses compositions and methods of synthesis and use of F-18 labeled molecules of use, for example, in PET imaging techniques. The labeled molecules may be peptides or proteins, although other types of molecules may be labeled by the described methods. Preferably, the F-18 may be conjugated to a targeting molecule by formation of a metal complex and binding of the F-18-metal complex to a chelating moiety. Alternatively, the metal may first be conjugated to the chelating group and subsequently the F-18 bound to the metal. In other embodiments, the F-18 labeled moiety may comprise a targetable construct used in combination with a bispecific or multi specific antibody to target F-18 to a disease-associated antigen, such as a tumor-associated antigen. The F-18 labeled targetable construct peptides are stable in serum at 37° C. for a sufficient time to perform PET imaging analysis.

    摘要翻译： 本申请公开了用于例如PET成像技术的F-18标记分子的合成和使用的组合物和方法。 标记的分子可以是肽或蛋白质，尽管其它类型的分子可以通过所述方法进行标记。 优选地，F-18可以通过形成金属络合物和F-18-金属络合物与螯合部分的结合而与靶向分子缀合。 或者，金属可以首先与螯合基团缀合，随后F-18与金属结合。 在其它实施方案中，F-18标记的部分可以包含与靶向F-18的双特异性或多特异性抗体与疾病相关抗原如肿瘤相关抗原组合使用的可靶向构建体。 F-18标记的可靶向构建体肽在血清中在37℃下稳定足够的时间进行PET成像分析。

    Radiometal-binding peptide analogues
    100.
    发明授权
    Radiometal-binding peptide analogues 失效

    公开(公告)号：US07045503B1

    公开(公告)日：2006-05-16

    申请号：US09676783

    申请日：2000-10-02

    申请人： William J. McBride ,  Gary L. Griffiths

    发明人： William J. McBride ,  Gary L. Griffiths

    IPC分类号： A61K38/16

    CPC分类号： A61K51/088 ,  A61K51/083 ,  A61K2123/00

    摘要： Novel metal binding ligands are disclosed that may be coupled to peptides for use in methods of diagnosis and therapy. Peptides containing the ligands are produced using a method wherein ligand introduction or cyclization can be conducted at any point during the synthesis of the peptide. Such peptide derivatives are readily labeled with radiometals, such as isotopes of rhenium or technetium, while retaining their ability to tightly bind specific peptide receptors.