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1. 发明授权

US6120768A Dota-biotin derivatives 失效
标题翻译：多塔生物素衍生物
公开(公告)号：US6120768A
公开(公告)日：2000-09-19
申请号：US990843
申请日：1997-12-15
申请人： Gary L. Griffiths , Hans Hansen , Serengulam V. Govindan
发明人： Gary L. Griffiths , Hans Hansen , Serengulam V. Govindan
IPC分类号： A61K41/00 , A61K47/48 , A61K49/08 , A61K51/04 , A61K51/10 , G01N33/531 , G01N33/534 , G01N33/574 , G01N33/68 , A61K39/395
CPC分类号： A61K49/10 , A61K41/0095 , A61K47/48353 , A61K47/48753 , A61K49/085 , A61K51/0497 , A61K51/1048 , A61K51/1093 , B82Y5/00 , G01N33/531 , G01N33/534 , G01N33/574 , G01N33/686 , A61K2121/00 , A61K2123/00
摘要： A radionuclide-chelator conjugate composition for detecting and/or treating lesions in a patient in a pre-targeting protocol which comprises pre-targeting the target cell, tissue, or pathogen with a substrate, using a targeting protein that specifically binds a marker substance on the target cell, tissue, or pathogen and to which the substrate is directly or indirectly bound; parenterally injecting the detection or therapeutic composition of the invention which comprises a chelate conjugate of biotin, a chelator, and a chelatable detection or therapeutic agent, and allowing the composition to accrete at the targeted cell, tissue, or pathogen; wherein the chelate conjugate is purified by chromatography after chelate formation, or further comprises a blood transit-modifying linker or addend that is covalently bound within the chelate conjugate, or both; and using the detection or therapeutic agent to detect or treat the targeted cell, tissue, or pathogen.
摘要翻译： 1.一种放射性核素 - 螯合剂缀合物组合物，其用于在预靶向方案中检测和/或治疗患者的损伤，其包括使用特异性结合标记物质的靶向蛋白将靶标细胞，组织或病原体用靶基因靶细胞，组织或病原体，底物直接或间接结合在其上; 肠胃外注射本发明的检测或治疗组合物，其包含生物素的螯合物缀合物，螯合剂和可螯合的检测或治疗剂，并允许组合物在靶细胞，组织或病原体上进入; 其中所述螯合物缀合物在螯合形成之后通过色谱法纯化，或进一步包含共转运结合在螯合物缀合物内的血液转运修饰接头或加成物，或两者; 并使用检测或治疗剂来检测或治疗靶细胞，组织或病原体。

2. 发明授权

US06818742B1 Stable radioiodine conjugates and methods for their synthesis 有权
公开(公告)号：US06818742B1
公开(公告)日：2004-11-16
申请号：US09696740
申请日：2000-10-26
申请人： Serengulam V. Govindan , Gary L. Griffiths
发明人： Serengulam V. Govindan , Gary L. Griffiths
IPC分类号： A61K3800
CPC分类号： A61K51/0491 , A61K51/088 , A61K51/10 , A61K51/1093 , C07H3/04 , C07K1/1077 , G01N33/543
摘要： Methods are described for conjugating radioiodinated non-metabolizable peptides to proteins and antibodies with improved yields and qualities of conjugates. Radioiodinated residualizing antibody conjugates comprising any aminopolycarboxylate-appended peptide, or any carbohydrate-appended peptide, are also provided. Additionally, methods are described for conjugating radioiodinated aminopolycarboxylates to proteins and antibodies, as well as for conjugating radioiodinated non-metabolizable carbohydrates to proteins and antibodies by a variety of chemical approaches. The instant radioiodinated residualizing antibody conjugates are particularly stable in vivo and are suitable for radioimmunodetection and radioimmunotherapy.

3. 发明授权

US5846741A Boron neutron capture therapy using pre-targeting methods 失效
标题翻译：硼中子捕获治疗使用预定位方法
公开(公告)号：US5846741A
公开(公告)日：1998-12-08
申请号：US687626
申请日：1996-07-26
申请人： Gary L. Griffiths , Serengulam V. Govindan
发明人： Gary L. Griffiths , Serengulam V. Govindan
IPC分类号： A61K33/22 , A61K39/395 , A61K41/00 , A61K47/48 , A61K51/10 , A61P35/00 , G01N33/534 , G01N33/574 , G01N33/53
CPC分类号： B82Y5/00 , A61K41/0095 , A61K47/48353 , A61K47/48753 , A61K51/1078 , G01N33/534 , G01N33/574
摘要： The present invention provides a method for targeting boron atoms to tumor cells in a patient. The method comprises the steps of: (A) administering a targeting composition comprising a conjugate of a first member of a binding pair and an antibody, wherein the antibody selectively binds to antigens produced by or associated with the tumor cells, and allowing the conjugate to localize at said tumor cells; (B) optionally, administering a clearing composition, and allowing the clearing composition to clear non-localized conjugate from circulation; (C) administering a boron-containing compound comprising a conjugate comprising a complementary member of said binding pair and boron atoms, and allowing the compound to localize at the tumor cells. The method may further comprise the step of irradiating the boron atoms of the boron compound, thereby effecting BNCT of the tumor cells. Compositions and kits for carrying out the method also are provided.
摘要翻译：本发明提供了一种将硼原子靶向患者肿瘤细胞的方法。该方法包括以下步骤：（A）施用包含结合对的第一个成员和抗体的缀合物的靶向组合物，其中所述抗体选择性地结合由肿瘤细胞产生或与肿瘤细胞相关的抗原，并且允许缀合物在所述肿瘤细胞上定位; （B）任选地，施用清除组合物，并使清除组合物从循环中清除非局部缀合物; （C）施用含有包含所述结合对的互补成员和硼原子的缀合物的含硼化合物，并使化合物定位于肿瘤细胞。该方法还可以包括照射硼化合物的硼原子，从而实现肿瘤细胞的BNCT的步骤。还提供了用于实施该方法的组合物和试剂盒。

4. 发明授权

US06558669B1 Stable radioiodine conjugates and methods for their synthesis 失效
标题翻译：稳定的放射性碘共轭物及其合成方法
公开(公告)号：US06558669B1
公开(公告)日：2003-05-06
申请号：US08919477
申请日：1997-08-28
申请人： Serengulam V. Govindan , Gary L. Griffiths
发明人： Serengulam V. Govindan , Gary L. Griffiths
IPC分类号： C07K506
CPC分类号： A61K51/0491 , A61K51/088 , A61K51/10 , A61K51/1093 , C07H3/04 , C07K1/1077 , G01N33/543
摘要： Methods are described for conjugating radioiodinated peptides or carbohydrate structures to proteins with improved yields and qualities of conjugates. In one method, specially designed radioiodinated bifunctional peptides containing nonmetabolizable amide bonds are coupled to antibodies. In a second method, radioiodinated nonmetabolizable bifunctional peptides, which also contain aminopolycarboxylates, are coupled to antibodies. In a third method, radioiodinated bifunctional aminopolycarboxylates are coupled to antibodies. In a fourth method, a hydrazide-appended antibody is coupled to a radioiodinated carbohydrate or a thiolated antibody is coupled to a hydrazide-appended and radioiodinated carbohydrate. In a fifth method a monoderivatized cyanuric chloride is used to conjugate thiolated antibody. Radioiodinated residualizing antibody conjugates made by these methods are particularly stable in vivo and are suitable for radioimmunodetection and radioimmunotherapy.
摘要翻译：描述了将放射性碘化肽或碳水化合物结构与缀合物的产率和质量提高的蛋白质缀合的方法。在一种方法中，将特异设计的含有非代谢性酰胺键的放射性碘化双功能肽与抗体偶联。在第二种方法中，也含有氨基多羧酸盐的放射性碘化的不可代谢的双功能肽与抗体偶联。在第三种方法中，放射性碘化双官能氨基多羧酸盐与抗体偶联。在第四种方法中，将酰肼附着的抗体与放射性碘化碳水化合物偶联，或硫醇化抗体与酰肼附着和放射性碘化碳水化合物偶联。在第五种方法中，使用monoderivatized氰尿酰氯来缀合硫醇化抗体。通过这些方法制备的放射性碘化残留抗体缀合物在体内特别稳定，适用于放射免疫检测和放射免疫治疗。

5. 发明授权

US5965131A Delivery of diagnostic and therapeutic agents to a target site 失效
公开(公告)号：US5965131A
公开(公告)日：1999-10-12
申请号：US731107
申请日：1996-10-09
申请人： Gary L. Griffiths , Hans J. Hansen , Serengulam V. Govindan , Habibe Karacay
发明人： Gary L. Griffiths , Hans J. Hansen , Serengulam V. Govindan , Habibe Karacay
IPC分类号： A61K38/22 , A61K39/395 , A61K41/00 , A61K45/08 , A61K47/48 , A61K49/00 , A61K51/00 , A61K51/10 , G01N33/531 , G01N33/534 , G01N33/574 , G01N33/68 , A01N37/18 , G01N33/53
CPC分类号： B82Y5/00 , A61K41/0095 , A61K47/48353 , A61K47/4873 , A61K47/48746 , A61K47/48753 , A61K49/0017 , A61K51/1078 , A61K51/1093 , G01N33/531 , G01N33/534 , G01N33/574 , G01N33/686 , A61K2121/00 , A61K2123/00 , Y10S424/90
摘要： An improvement in in vivo pretargeting methods for delivering diagnostic or therapeutic agents to a target site in a mammal uses a clearing agent that binds to the target-binding site of the targeting species, whereby non-bound primary targeting species is cleared from circulation but the clearing agent does not remove the bound primary targeting species. Anti-idiotype antibodies and antibody fragments are preferred clearing agents. Fast clearance is achieved by glycosylating the clearing agent with sugar residues that bind to the hepatic asialoglycoprotein receptor.

6. 发明授权

US5746996A Thiolation of peptides for radionuclide-based radiodetection and radiotherapy 失效
标题翻译：基于放射性核素的放射性检测和放射治疗的肽的硫醇化
公开(公告)号：US5746996A
公开(公告)日：1998-05-05
申请号：US483095
申请日：1995-06-07
申请人： Serengulam V. Govindan , Gary L. Griffiths , Hans L. Hansen
发明人： Serengulam V. Govindan , Gary L. Griffiths , Hans L. Hansen
IPC分类号： A61K38/00 , A61K39/395 , A61K51/00 , A61K51/08 , A61K51/10 , A61P9/08 , A61P9/10 , A61P31/00 , A61P35/00 , A61P37/00 , C07B59/00 , C07K1/13 , C07K14/00 , C07K16/00 , C09K3/00 , A61M36/14
CPC分类号： A61K51/088 , A61K2121/00 , A61K2123/00
摘要： A method of radiolabeling a peptide, e.g., somatostatin or an analogue thereof or vasoactive intestinal peptide, with a radioisotope of technetium or rhenium, comprises the steps of: (a) reacting the peptide with an acetyl-protected t-thiol-containing, amine-reactive bifunctional chelating agent; (b) deprotecting the acetyl-t-thiol group to generate a free t-thiol group; and either (c) admixing the peptide-t-thiol-containing conjugate with a stannous salt; and (d) reacting the mixture of step (c) with pertechnetate or perrhenate, or (c') adding reduced pertechnetate or perrhenate to said peptide-t-thiol-containing conjugate, thereby forming a radiolabeled peptide. Kits for effecting the radiolabeling method, and methods of tumor detection/imaging or therapy are provided.
摘要翻译：使用锝或铼的放射性同位素将肽例如生长抑素或其类似物或血管活性肠肽放射标记的方法包括以下步骤：（a）使肽与含有乙酰基保护的含硫代硫醇的胺反应 - 反应双功能螯合剂; （b）使乙酰基-t-硫醇基团去保护以产生游离的t-硫醇基团; 并且（c）将含有肽-硫醇的缀合物与亚锡盐混合; 和（d）使步骤（c）的混合物与高锝酸盐或高铼酸盐反应，或（c'）向所述含肽-T-硫醇的缀合物加入降低的高锝酸盐或高铼酸盐，从而形成放射性标记的肽。提供用于实现放射性标记方法的试剂盒，以及肿瘤检测/成像或治疗方法。

7. 发明授权

US07259249B2 Method for preparing conjugates of proteins and chelating agents 有权
标题翻译：制备蛋白质和螯合剂缀合物的方法
公开(公告)号：US07259249B2
公开(公告)日：2007-08-21
申请号：US11000500
申请日：2004-12-01
申请人： Gary L. Griffiths , Serengulam V. Govindan
发明人： Gary L. Griffiths , Serengulam V. Govindan
IPC分类号： C07K1/00
CPC分类号： A61K51/1027 , A61K51/0482 , A61K51/1045
摘要： Improved synthesis methods are provided for preparing conjugates of proteins and chelating agents. In the synthesis methods, non-stable bonds are hydrolyzed after the conjugate is synthesized, for example by treating the conjugate with a quenching agent. The synthesis method provides conjugates that are substantially free of non-stable bonds between the protein and the chelating agent, such that the chelating agent is less likely to dissociate with the conjugate after the conjugate has been stored for extended periods. The conjugate may be useful for therapeutic or diagnostic methods.
摘要翻译：提供改进的合成方法用于制备蛋白质和螯合剂的缀合物。在合成方法中，在合成共轭物后，例如通过用猝灭剂处理缀合物，非稳定键被水解。合成方法提供基本上不含蛋白质和螯合剂之间的非稳定键的缀合物，使得螯合剂在缀合物长时间储存后不太可能与缀合物解离。缀合物可用于治疗或诊断方法。

8. 发明授权

US07230085B2 Anti-DOTA antibody 有权
标题翻译：抗DOTA抗体
公开(公告)号：US07230085B2
公开(公告)日：2007-06-12
申请号：US10305268
申请日：2002-11-27
申请人： Gary L. Griffiths , Hans J. Hansen , Serengulam V. Govindan , Michelle Losman , Zhengxing Qu
发明人： Gary L. Griffiths , Hans J. Hansen , Serengulam V. Govindan , Michelle Losman , Zhengxing Qu
IPC分类号： C12P21/08 , C07K16/44 , G01N33/534 , A61K51/10
CPC分类号： C07K16/2803 , A61K47/6849 , A61K2039/505 , C07K16/44
摘要： The present invention relates to an antibody or antibody fragment that binds to 1,4,7,10-tetrazacyclododecane-N,N′,N″,N′″-tetraacetic acid (DOTA),which is bound to an alkyl-amino group through one of its pendant carb.oxyl groups.
摘要翻译：本发明涉及与1,4,7,10-四氮环十二烷-N，N'，N“，N'-四乙酸（DOTA）结合的抗体或抗体片段，其结合于烷基 - 氨基通过其一个侧链碳氧基。

9. 发明授权

US06858705B2 Stable radioiodine conjugates and methods for their synthesis 失效
标题翻译：稳定的放射性碘共轭物及其合成方法
公开(公告)号：US06858705B2
公开(公告)日：2005-02-22
申请号：US10686436
申请日：2003-10-16
申请人： Serengulam V. Govindan , Gary L. Griffiths
发明人： Serengulam V. Govindan , Gary L. Griffiths
IPC分类号： G01N33/534 , A61K49/00 , A61K51/00 , A61K51/04 , A61K51/08 , A61K51/10 , C07H3/04 , C07K1/107 , C07K1/13 , G01N33/543 , G01N33/60 , A61K38/00
CPC分类号： A61K51/0491 , A61K51/088 , A61K51/10 , A61K51/1093 , C07H3/04 , C07K1/1077 , G01N33/543
摘要： Methods are described for conjugating radioiodinated non-metabolizable peptides to proteins and antibodies with improved yields and qualities of conjugates. Radioiodinated residualizing antibody conjugates comprising any aminopolycarboxylate-appended peptide, or any carbohydrate-appended peptide, are also provided. Additionally, methods are described for conjugating radioiodinated aminopolycarboxylates to proteins and antibodies, as well as for conjugating radioiodinated non-metabolizable carbohydrates to proteins and antibodies by a variety of chemical approaches. The instant radioiodinated residualizing antibody conjugates are particularly stable in vivo and are suitable for radioimmunodetection and radioimmunotherapy.
摘要翻译：描述了将放射性碘化的不可代谢的肽与蛋白质和抗体结合的方法，其具有改进的缀合物的产率和质量。还提供了包含任何氨基多羧酸盐附着肽或任何碳水化合物附加肽的放射性碘化残留抗体缀合物。另外，描述了将放射性碘化氨基多羧酸盐与蛋白质和抗体结合的方法，以及通过各种化学方法将放射性碘化的不可代谢的碳水化合物与蛋白质和抗体缀合。瞬时放射性碘化残留抗体缀合物在体内特别稳定，适用于放射免疫检测和放射免疫治疗。

10. 发明授权

US5958408A Delivery of diagnostic and therapeutic agents to a target site 失效
标题翻译：将诊断和治疗剂递送到目标部位
公开(公告)号：US5958408A
公开(公告)日：1999-09-28
申请号：US972037
申请日：1997-11-17
申请人： Gary L. Griffiths , Hans J. Hansen , Serengulam V. Govindan , Habibe Karacay
发明人： Gary L. Griffiths , Hans J. Hansen , Serengulam V. Govindan , Habibe Karacay
IPC分类号： A61K38/22 , A61K39/395 , A61K41/00 , A61K45/08 , A61K47/48 , A61K49/00 , A61K51/00 , A61K51/10 , G01N33/531 , G01N33/534 , G01N33/574 , G01N33/68 , C07K16/00 , C12N15/11 , C07M21/00
CPC分类号： B82Y5/00 , A61K41/0095 , A61K47/48353 , A61K47/4873 , A61K47/48746 , A61K47/48753 , A61K49/0017 , A61K51/1078 , A61K51/1093 , G01N33/531 , G01N33/534 , G01N33/574 , G01N33/686 , A61K2121/00 , A61K2123/00 , Y10S424/90
摘要： An improvement in in vivo pretargeting methods for delivering diagnostic or therapeutic agents to a target site in a mammal uses a clearing agent that binds to the target-binding site of the targeting species, whereby non-bound primary targeting species is cleared from circulation but the clearing agent does not remove the bound primary targeting species. Anti-idiotype antibodies and antibody fragments are preferred clearing agents. Fast clearance is achieved by glycosylating the clearing agent with sugar residues that bind to the hepatic asialoglycoprotein receptor.
摘要翻译：用于将诊断或治疗剂递送到哺乳动物的靶位点的体内预靶向方法的改进使用结合靶向物种的靶结合位点的清除剂，由此未结合的初级靶向物质从循环中清除，但是清除代理不会删除绑定的主要目标物种。抗独特型抗体和抗体片段是优选的清除剂。通过用结合肝脏脱唾液酸糖蛋白受体的糖残基糖基化清除剂来实现快速清除。

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