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41.发明授权
公开(公告)号：US5753206A
公开(公告)日：1998-05-19
申请号：US474555
申请日：1995-06-07
CPC分类号： C07K7/23 , A61K51/088 , A61K38/00
摘要： Peptide derivatives of leutenizing hormone releasing hormone that are capable of binding radionuclides are provided. The peptide derivatives are readily labeled with isotopes of rhenium or technetium, while retaining their ability to tightly bind LHRH receptors. Methods for preparing the labeled peptides and their use in methods of radiodiagnosis and radiotherapy are described.
摘要翻译： 提供了能够结合放射性核素的促黄体激素释放激素的肽衍生物。 肽衍生物容易用铼或锝的同位素标记，同时保持其紧密结合LHRH受体的能力。 描述了制备标记肽的方法及其在放射诊断和放射治疗方法中的应用。
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42.发明授权Hydrocarbylphenyl diaminodithiol radionuclide complexes and their use in imaging 失效烃基苯基二氨基二硫代放射性核素复合物及其在成像中的应用
公开(公告)号：US5080884A
公开(公告)日：1992-01-14
申请号：US660403
申请日：1991-02-22
申请人： William J. McBride , Ronald M. Baldwin , Janice M. Kerr , Lisa M. Schultze , Nilda Salazar , James M. Chinitz
发明人： William J. McBride , Ronald M. Baldwin , Janice M. Kerr , Lisa M. Schultze , Nilda Salazar , James M. Chinitz
IPC分类号： A61K51/04 , C07C323/25 , C07C323/60 , C07D285/00 , C07F13/00
CPC分类号： C07F13/005 , A61K51/0478 , C07C323/25 , C07C323/60 , C07D285/00
摘要： An agent for imaging organs using a radioactive complex of a radioactive metal with a benzene ring having two 2-mercapto-2-methylpropylamino substituents where one of these mercapto substituents is substituted with a hydrocarbyl group.
摘要翻译： 使用放射性金属的放射性复合物与具有两个巯基-2-甲基丙基氨基取代基的苯环成像器官成像器官的试剂，其中这些巯基取代基之一被烃基取代。
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43.发明申请公开(公告)号：US20130164816A1
公开(公告)日：2013-06-27
申请号：US13549906
申请日：2012-07-16
IPC分类号： C12N9/96
CPC分类号： A61K47/48438 , A61K31/00 , A61K38/00 , A61K47/48415 , A61K47/48484 , A61K47/485 , A61K47/48538 , A61K47/48546 , A61K47/48561 , A61K47/48569 , A61K47/6811 , A61K47/6817 , A61K47/6829 , A61K47/6833 , A61K47/6843 , A61K47/6845 , A61K47/6849 , A61K47/6851 , A61K2039/505 , B82Y5/00 , B82Y10/00 , B82Y15/00 , C07K14/475 , C07K16/18 , C07K16/22 , C07K16/28 , C07K16/2803 , C07K16/2833 , C07K16/2851 , C07K16/2863 , C07K16/2881 , C07K16/2887 , C07K16/2896 , C07K16/3007 , C07K16/3092 , C07K16/32 , C07K2317/31 , C07K2317/55 , C07K2317/76 , C07K2319/30 , C07K2319/35 , C07K2319/70 , C07K2319/74 , C12N9/12 , C12N9/22 , C12N9/96 , C12Y207/11001 , G01N33/54353 , G01N33/588 , Y02A50/491
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.
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44.发明授权公开(公告)号：US08435539B2
公开(公告)日：2013-05-07
申请号：US12964132
申请日：2010-12-09
IPC分类号： A61K39/385 , A61K51/08 , A61K38/04 , C08G59/00 , C07B41/08
CPC分类号： A61K45/06 , A61K31/4745 , A61K38/00 , A61K47/60 , A61K47/6885 , A61K47/6897 , A61K51/088 , B82Y5/00 , A61K2300/00
摘要： The present invention relates to methods and compositions for pretargeting delivery of therapeutic agents. In preferred embodiments, the pretargeting method comprises: a) administering a bispecific antibody with a first binding site for a disease-associated antigen and a hapten on a targetable construct; b) administering a targetable construct comprising at least one therapeutic agent. In preferred embodiments, the bispecific antibody is made by the dock-and-lock (DNL) technique. In a more preferred embodiment, the targetable construct comprises one or more SN-38 moieties.
摘要翻译： 本发明涉及用于预定靶递送治疗剂的方法和组合物。 在优选的实施方案中，预靶向方法包括：a）给予双特异性抗体与疾病相关抗原的第一结合位点和可靶向构建体上的半抗原; b）施用包含至少一种治疗剂的可靶向构建体。 在优选的实施方案中，双特异性抗体通过对接和锁定（DNL）技术制备。 在更优选的实施方案中，可靶向构建体包含一个或多个SN-38部分。
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45.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
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。
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46.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：US20120134920A1
公开(公告)日：2012-05-31
申请号：US13323139
申请日：2011-12-12
CPC分类号： A61K51/08 , A61B5/055 , A61K47/48746 , A61K47/6897 , A61K49/06 , A61K51/0406 , A61K51/041 , A61K51/044 , A61K51/0482 , A61K51/0491 , A61K51/082 , A61K51/083 , A61K51/088 , A61K51/109 , B82Y5/00 , C07D225/00 , C07F13/005
摘要： The present application discloses compositions and methods of synthesis and use of 18F or 19F-labeled molecules of use in PET, SPECT and/or MR imaging. Preferably, the 18F or 19F is conjugated to a targeting molecule by formation of a complex with a group IIIA metal and binding of the complex to a bifunctional chelating agent, which may be directly or indirectly attached to the targeting molecule. 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 disclosed methods and compositions allow the simple and reproducible labeling of molecules at very high efficiency and specific activity in 30 minutes or less. In preferred embodiments, the labeled molecule may be used for imaging in a subject without purification after labeling.
摘要翻译： 本申请公开了在PET，SPECT和/或MR成像中合成和使用18F或19F标记的分子的组合物和方法。 优选地，18F或19F通过与IIIA族金属形成络合物并将该复合物与双功能螯合剂结合（其可以直接或间接连接到靶向分子）而与靶向分子缀合。 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。 所公开的方法和组合物允许在30分钟或更短时间内非常高的效率和比活性的分子的简单且可重现的标记。 在优选的实施方案中，标记的分子可以在标记后不经纯化用于受试者的成像。
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47.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
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。
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48.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：US08147800B2
公开(公告)日：2012-04-03
申请号：US13163145
申请日：2011-06-17
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 multispecific 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。
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49.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
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。
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公开(公告)号：US07776311B1
公开(公告)日：2010-08-17
申请号：US11640790
申请日：2006-12-18
CPC分类号： C07K5/0815 , A61K38/00 , A61K47/6897 , A61K49/0002 , A61K51/109 , B82Y5/00 , C07K5/1008 , C07K5/1016 , C07K5/1019 , C07K5/1021 , C07K7/06 , Y02A50/411
摘要： The present invention provides compounds of the formula X—R1-D-[Dpr, Orn or Lys](A)-R2(Z)-D-[Dpr, Orn or Lys](B)—R3(Y)—NR4R5; or R1(X)-D-[Dpr, Orn or Lys](A)-R2(Z)-D-[Dpr, Orn or Lys](B)—R3(Y)—NR4R5, in which X is a hard acid cation chelator, a soft acid cation chelator or Ac-, R1, R2 and R3 are independently selected from a covalent bond or one or more D-amino acids that can be the same or different, Y is a hard acid cation chelator, a soft acid cation chelator or absent, Z is a hard acid cation chelator, a soft acid cation chelator or absent, and A and B are haptens or hard acid cation chelators and can be the same or different, and R4 and R5 are independently selected from the group consisting of hard acid cation chelators, soft acid cation chelators, enzymes, therapeutic agents, diagnostic agents and H. The present invention also provides methods of using these compounds and kits containing the compounds.
摘要翻译： 本发明提供式X-R1-D- [Dpr，Orn或Lys]（A）-R2（Z）-D- [Dpr，Orn或Lys]（B）-R3（Y）-NR4R5的化合物; 或R 1（X）-D- [Dpr，Orn或Lys]（A）-R2（Z）-D- [Dpr，Orn或Lys]（B）-R3（Y）-NR4R5，其中X为硬 酸阳离子螯合剂，软酸阳离子螯合剂或Ac-，R1，R2和R3独立地选自共价键或一个或多个可以相同或不同的D-氨基酸，Y是硬酸阳离子螯合剂， 软酸阳离子螯合剂或不存在，Z是硬酸阳离子螯合剂，软酸阳离子螯合剂或不存在，A和B是半抗原或硬酸阳离子螯合剂，可以相同或不同，并且R 4和R 5独立地选自 由硬酸阳离子螯合剂，软酸阳离子螯合剂，酶，治疗剂，诊断剂和H组成的组。本发明还提供使用这些化合物和含有该化合物的试剂盒的方法。
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