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1. 发明授权

US07078013B2 Pretargeting methods and compounds 失效
公开(公告)号：US07078013B2
公开(公告)日：2006-07-18
申请号：US10775897
申请日：2004-02-10
申请人： Donald B Axworthy , Louis J Theodore , Linda M Gustavson , John M Reno
发明人： Donald B Axworthy , Louis J Theodore , Linda M Gustavson , John M Reno
IPC分类号： A61K39/00 , C07D257/02 , C07D495/04
CPC分类号： B82Y5/00 , A61K47/557 , A61K47/665 , A61K47/68 , A61K47/6887 , A61K47/6893 , A61K47/6898 , A61K51/0497 , A61K51/1268 , A61K2121/00 , A61K2123/00 , Y10S530/825
摘要： Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, methods for radiometal labeling of biotin and for improved radiohalogenation of biotin, as well as related compounds, are described. Also, clearing agents, anti-ligand-targeting moiety conjugates, target cell retention enhancing moieties and additional methods are discussed.

2. 发明授权

US06908903B1 Cluster clearing agents 失效
标题翻译：群集清理代理
公开(公告)号：US06908903B1
公开(公告)日：2005-06-21
申请号：US09687055
申请日：2000-10-12
申请人： Louis J. Theodore , Donald B. Axworthy
发明人： Louis J. Theodore , Donald B. Axworthy
IPC分类号： A61K47/48 , A61K51/12 , A01N43/04 , A61K31/70 , A61K39/395
CPC分类号： B82Y5/00 , A61K47/557 , A61K47/6893 , A61K47/6898 , A61K51/1268
摘要： Cluster clearing agents (CCAs) and the use thereof are discussed. CCAs are composed of a hepatic clearance directing moiety which directs the biodistribution of a CCA-containing construct to hepatic clearance; and a binding moiety which mediates binding of the CCA to a compound for which rapid hepatic clearance is desired.
摘要翻译：讨论了群集清除代理（CCAs）及其使用。 CCA由肝间隙导向部分组成，其指导含CCA构建体的生物分布为肝脏清除; 以及介导CCA与需要快速肝清除的化合物的结合的结合部分。

3. 发明授权

US06287536B1 Two-step pretargeting methods using improved bidtin-active agent conjugates 失效
标题翻译：使用改进的bidtin活性剂缀合物的两步预靶向方法
公开(公告)号：US06287536B1
公开(公告)日：2001-09-11
申请号：US08788339
申请日：1997-01-27
申请人： John M. Reno , Louis J. Theodore , Linda M. Gustavson
发明人： John M. Reno , Louis J. Theodore , Linda M. Gustavson
IPC分类号： A61K5100
CPC分类号： B82Y5/00 , A61K47/557 , A61K47/665 , A61K47/68 , A61K47/6887 , A61K47/6893 , A61K47/6898 , A61K51/0497 , A61K51/1268 , A61K2121/00 , A61K2123/00 , Y10S530/825
摘要： Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, methods for radiometal labeling of biotin and for improved radiohalogenation of biotin, as well as related compounds, are described. Also, clearing agents, anti-ligand-targeting moiety conjugates, target cell retention enhancing moieties and additional methods are discussed.
摘要翻译：公开了与诊断和治疗剂的预靶向递送相关的方法，化合物，组合物和试剂盒。特别地，描述了用于生物素的放射性金属标记和改善生物素的放射性卤化的方法以及相关化合物。此外，讨论了清除剂，抗配体靶向部分缀合物，靶细胞保留增强部分和另外的方法。

4. 发明授权

US5985826A Methods of using hepatic-directed compounds in pretargeting strategies 失效
标题翻译：使用肝取向化合物预先靶向策略的方法
公开(公告)号：US5985826A
公开(公告)日：1999-11-16
申请号：US808024
申请日：1997-03-03
申请人： Louis J. Theodore , Donald B. Axworthy , John M. Reno
发明人： Louis J. Theodore , Donald B. Axworthy , John M. Reno
IPC分类号： A61K31/7028 , A61K47/48 , A61K51/08 , A61P1/16 , C07H15/04 , C07H15/14 , C07H15/26 , A61K31/70 , A61K31/715 , A61K31/73 , A61K38/14
CPC分类号： B82Y5/00 , A61K47/4873 , A61K51/0465 , C07H15/04 , C07H15/14 , A61K2121/00
摘要： Hepatic-directed compounds, reagents useful in making such compounds and associated methods and compositions are disclosed. Hepatic-directed compounds are processed by metabolic mechanisms, which generally differ in degree or in kind from the metabolic mechanisms encountered by compounds which are not so directed. Hepatic-directed compounds useful in the methods disclosed include a hexose cluster characterized by multiple hexose residues connected in an iteratively branched configuration. In one embodiment, the hexose cluster comprises at least four hexose residues with each branch of the configuration having two prongs. In another embodiment, the hexose cluster comprises at least nine hexose residues with each branch of the configuration having three prongs.
摘要翻译：公开了肝取向化合物，可用于制备这些化合物的试剂和相关方法和组合物。肝取向化合物通过代谢机制进行处理，其代谢机制通常在程度上或种类上不同于未被引导的化合物所遇到的代谢机制。可用于所公开方法的肝取向化合物包括以多个己糖残基以反复分支构型连接的特征的己糖簇。在一个实施方案中，己糖簇包含至少四个己糖残基，其中每个分支具有两个分支。在另一个实施方案中，己糖簇包含至少九个己糖残基，其中每个分支具有三个分支。

5. 发明授权

US5608060A Biotinidase-resistant biotin-DOTA conjugates 失效
标题翻译：生物素抗生物素 - DOTA共轭物
公开(公告)号：US5608060A
公开(公告)日：1997-03-04
申请号：US351469
申请日：1995-02-21
申请人： Donald B. Axworthy , Louis J. Theodore , Linda M. Gustavson , John M. Reno
发明人： Donald B. Axworthy , Louis J. Theodore , Linda M. Gustavson , John M. Reno
IPC分类号： A61K39/395 , A61K47/48 , A61K51/00 , A61K51/04 , A61K51/12 , A61P43/00 , C07D495/04 , C07D257/02 , A61K31/415 , C07H17/04
CPC分类号： C07D495/04 , A61K47/48023 , A61K47/48146 , A61K47/48353 , A61K47/48369 , A61K47/48707 , A61K47/4873 , A61K47/48753 , A61K51/0497 , A61K51/1268 , B82Y5/00 , A61K2121/00 , A61K2123/00
摘要： Biotinidase-resistant biotin-DOTA conjugates, and methods of use thereof in diagnostic and therapeutic pretargeting methods are provided. These conjugates are useful in diagnosis and treatment of cancer.
摘要翻译： PCT No.PCT / US93 / 05406 Sec。 371日期1995年2月21日 102（e）日期1995年2月21日PCT提交1993年6月7日PCT公布。公开号WO93 / 25240 日期：1993年12月23日提供了用于诊断和治疗预靶向方法中的抗生物素 - 生物素 - DOTA缀合物及其使用方法。这些缀合物可用于诊断和治疗癌症。

6. 发明授权

US5346670A Phthalocyanine and tetrabenztriazaporphyrin reagents 失效
标题翻译：酞菁和四苯并三氮杂卟啉试剂
公开(公告)号：US5346670A
公开(公告)日：1994-09-13
申请号：US895601
申请日：1992-06-08
申请人： George E. Renzoni , Deborah C. Schindele , Louis J. Theodore , Clifford C. Leznoff , Karen L. Fearon , Barry V. Pepich
发明人： George E. Renzoni , Deborah C. Schindele , Louis J. Theodore , Clifford C. Leznoff , Karen L. Fearon , Barry V. Pepich
IPC分类号： A61K41/00 , C07H21/00 , C12Q1/68 , G01N33/533 , G01N21/76
CPC分类号： G01N33/533 , A61K41/0071 , C07H21/00 , Y10S435/808 , Y10S435/968 , Y10S436/808 , Y10T436/13
摘要： Red-shifted, water-soluble, fluorescent, monomerically-tetherable derivatives having the formula: ##STR1##wherein, M represents either H.sub.2 or is selected from among the following metals: aluminum, silicon, phosphorus, gallium, germanium, cadmium, scandium, magnesium, tin, and zinc. Each R.sub.1 is independently selected from --XYW, --YW, and --W. X represents either a carbon, or heteroatom selected from among oxygen, nitrogen, sulfur, phosphorus, silicon, and selenium; Y represents a linking group; and W represents a water solubilizing group. The substituent R.sub.2 is selected from among --A, --Y'A, --XA, and --XY'A, where A denotes a biological entity such as an antibody, antibody fragment, nucleotide, nucleic acid probe, antigen, oligonucleotide, deoxynucleotide, dideoxynucleotide, avidin, streptavidin or membrane probe, or R.sub.2 is a reactive or activatable group suitable for conjugating to a biological entity. Y' is a linking group that tethers the biological entity to the phthalocyanine or tetrabenztriazaporphyrin macrocycle. Z is either a nitrogen atom or a carbon substituted with hydrogen, alkyl, aryl, or aralkyl groups. Z may also be attached to R.sub.2. Also disclosed are derivatives of the compounds of the above Formula in which 1-4 of the benzo ring(s) contain 1 or 2 N atoms. Methods of sequencing DNA and detecting analytes, including cells, using these derivatives are disclosed, as are kits for carrying out assays for the analytes and flow cytometry. Methods of detecting DNA using cationic compounds of the above Formula, wherein R.sub.2 =R.sub.1 and W=-N.sup.+ D.sub.1 D.sub.2 D.sub.3 are also disclosed. Further, compounds containing Tc, Gd, etc. as the metal in the above Formula may be used for imaging or therapy.
摘要翻译：具有下式的红移，水溶性，荧光，单体 - 可连接的衍生物：选自以下金属：铝，硅，磷，镓，锗，镉，钪，镁，锡和锌。每个R1独立地选自-XYW，-YW和-W。 X表示选自氧，氮，硫，磷，硅和硒中的碳或杂原子; Y表示连接基团; W表示水溶性基团。取代基R2选自-A，-Y'A，-XA和-XY'A，其中A表示生物实体，例如抗体，抗体片段，核苷酸，核酸探针，抗原，寡核苷酸，脱氧核苷酸，双脱氧核苷酸，抗生物素蛋白，链霉抗生物素蛋白或膜探针，或R2是适于与生物实体缀合的反应性或活化性基团。 Y'是将生物实体连接到酞菁或四苯并三氮杂卟啉大环的连接基团。 Z是氮原子或被氢，烷基，芳基或芳烷基取代的碳。 Z也可以连接到R2。还公开了上述式的化合物的衍生物，其中1-4个苯并环含有1或2个N原子。公开了使用这些衍生物测序DNA和检测分析物（包括细胞）的方法，以及用于进行分析物和流式细胞术的测定的试剂盒。还公开了使用上述式的阳离子化合物（其中R2 = R1和W = -N + D1D2D3）检测DNA的方法。此外，可以使用含有上述式中的金属的Tc，Gd等的化合物进行成像或治疗。

7. 发明授权

US06358490B2 Three-step pretargeting methods and compounds 失效
标题翻译：三步预靶向方法和化合物
公开(公告)号：US06358490B2
公开(公告)日：2002-03-19
申请号：US09316452
申请日：1999-05-21
申请人： Louis J. Theodore , John M. Reno , Linda M. Gustavson
发明人： Louis J. Theodore , John M. Reno , Linda M. Gustavson
IPC分类号： A61K5110
CPC分类号： B82Y5/00 , A61K47/557 , A61K47/665 , A61K47/68 , A61K47/6887 , A61K47/6893 , A61K47/6897 , A61K47/6898 , A61K51/0497 , A61K51/1268 , A61K2121/00 , A61K2123/00
摘要： Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, three-step pretargeting methods are described.
摘要翻译：公开了与诊断和治疗剂的预靶向递送相关的方法，化合物，组合物和试剂盒。特别地，描述了三步预定靶方法。

8. 发明授权

US6075010A Small molecular weight ligand-hexose containing clearing agents 失效
标题翻译：小分子量配体 - 己糖含清除剂
公开(公告)号：US6075010A
公开(公告)日：2000-06-13
申请号：US350551
申请日：1994-12-07
申请人： Louis J. Theodore , Donald B. Axworthy , John M. Reno
发明人： Louis J. Theodore , Donald B. Axworthy , John M. Reno
IPC分类号： A61K47/48 , A61K51/04 , A61K51/12 , C07D495/04 , A01N43/04 , A61K31/70
CPC分类号： C07D495/04 , A61K47/48146 , A61K47/48353 , A61K47/48369 , A61K47/48707 , A61K47/4873 , A61K47/48746 , A61K47/48753 , A61K51/0497 , A61K51/1268 , B82Y5/00 , A61K2121/00 , A61K2123/00
摘要： Small molecule weight clearing agents containing ligands such as biotin or biotin analogs and hexose residue, in particular galactose or N-acetyl galactosamine residues are taught. These clearing agents effectively clear anti-ligand containing conjugates in vivo via hepatocyte receptor mediated clearance mechanisms.
摘要翻译：教导了含有配体例如生物素或生物素类似物和己糖残基，特别是半乳糖或N-乙酰半乳糖胺残基的小分子量清除剂。这些清除剂通过肝细胞受体介导的清除机制在体内有效地清除含有配体的缀合物。

9. 发明授权

US5955605A Biotinidase resistant biotin-DOTA conjugates 失效
标题翻译：生物素抗生物素 - DOTA共轭物
公开(公告)号：US5955605A
公开(公告)日：1999-09-21
申请号：US695940
申请日：1996-08-12
申请人： Donald B. Axworthy , Louis J. Theodore , Linda M. Gustavson , John M. Reno
发明人： Donald B. Axworthy , Louis J. Theodore , Linda M. Gustavson , John M. Reno
IPC分类号： A61K51/04 , C07D495/04 , C07H7/033 , C07D257/02 , A61K31/415 , C07H17/04
CPC分类号： C07D495/04 , A61K51/0497 , C07H7/033
摘要： Biotinidase-resistant biotin-DOTA conjugates, and methods of use thereof in diagnostic and therapeutic pretargeting methods are provided. These conjugates are useful in diagnosis and treatment of cancer.
摘要翻译：提供了生物素抗性生物素-DTOTA缀合物及其在诊断和治疗预靶向方法中的应用方法。这些缀合物可用于诊断和治疗癌症。

10. 发明授权

US5578287A Three-step pretargeting methods using improved biotin-active agent 失效
标题翻译：使用改进的生物素活性剂的三步预靶向方法
公开(公告)号：US5578287A
公开(公告)日：1996-11-26
申请号：US156614
申请日：1993-11-23
申请人： Louis J. Theodore , John M. Reno , Linda M. Gustavson
发明人： Louis J. Theodore , John M. Reno , Linda M. Gustavson
IPC分类号： C07H13/06 , A61K31/70 , A61K31/7024 , A61K38/00 , A61K39/395 , A61K45/00 , A61K47/48 , A61K48/00 , A61K51/00 , A61K51/04 , A61K51/12 , A61P35/00 , A61K51/10 , A61K31/415 , C07D257/02 , C07K16/30
CPC分类号： B82Y5/00 , A61K47/48023 , A61K47/48146 , A61K47/48353 , A61K47/48707 , A61K47/4873 , A61K47/48746 , A61K47/48753 , A61K51/0497 , A61K51/1268 , A61K2121/00 , A61K2123/00
摘要： Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed. In particular, three-step pretargeting methods are described.
摘要翻译：公开了与诊断和治疗剂的预靶向递送相关的方法，化合物，组合物和试剂盒。特别地，描述了三步预定靶方法。

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