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51. 发明授权

US06953567B2 Fluorination of proteins and peptides for F-18 positron emission tomography 有权
标题翻译：用于F-18正电子发射断层扫描的蛋白质和肽的氟化
公开(公告)号：US06953567B2
公开(公告)日：2005-10-11
申请号：US10071247
申请日：2002-02-11
申请人： Gary L. Griffiths
发明人： Gary L. Griffiths
IPC分类号： A61K51/00 , A61K51/08 , A61K51/10 , C07B39/00 , C07B59/00 , C07K1/107 , C07K1/13 , C07K7/06 , C07K16/30 , C07K16/46 , A61K101/02 , A61K49/14 , A61K49/16 , C07K16/00 , G01N33/534
CPC分类号： C07K16/3007 , A61K51/08 , A61K51/083 , A61K51/088 , A61K51/10 , A61K2123/00 , C07B59/008 , C07K1/1077 , C07K1/13 , C07K16/468
摘要： Thiol-containing peptides can be radiolabeled with fluorine-18 (F-18) by reacting a peptide comprising a free thiol group with an F-18-bound labelling reagent which also has a group that is reactive with thiols. The resulting F-18-labeled peptides may be targeted to a tissue of interest using bispecific antibodies or bispecific antibody fragments having one arm specific for the F-18-labeled peptide or a low molecular weight hapten conjugated to the F-18-labeled peptide, and another arm specific to the targeted tissue. The targeted tissue is subsequently visualized by clinical positron emission tomography.
摘要翻译：含有硫醇的肽可以通过使包含游离巯基的肽与也与硫醇反应的基团的F-18键合的标记试剂反应，用氟-18（F-18）进行放射性标记。所得到的F-18标记的肽可以使用双特异性抗体或具有一个对F-18标记的肽特异性的臂或与F-18标记的肽缀合的低分子量半抗原的双特异性抗体片段靶向感兴趣的组织，另一只针对靶组织的手臂。目标组织随后通过临床正电子发射断层扫描显像。

52. 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.

53. 发明授权

US06187284B1 Fluorination of proteins and peptides for F-18 positron emission tomography 有权
标题翻译：用于F-18正电子发射断层扫描的蛋白质和肽的氟化
公开(公告)号：US06187284B1
公开(公告)日：2001-02-13
申请号：US09146318
申请日：1998-09-03
申请人： Gary L. Griffiths
发明人： Gary L. Griffiths
IPC分类号： A61K5100
CPC分类号： C07K16/3007 , A61K51/08 , A61K51/083 , A61K51/088 , A61K51/10 , A61K2123/00 , C07B59/008 , C07K1/1077 , C07K1/13 , C07K16/468
摘要： Thiol-containing peptides can be radiolabeled with fluorine-18 (18F) by reacting a peptide comprising a free thiol group with an 18F-bound labelling reagent which also has a group that is reactive with thiols. The resulting 18F-labeled peptides may be targeted to a tissue of interest using bispecific antibodies or bispecific antibody fragments having one arm specific for the 18F-labeled peptide or a low molecular weight hapten conjugated to the 18F-labeled peptide, and another arm specific to the targeted tissue. The targeted tissue is subsequently visualized by clinical positron emission tomography.
摘要翻译：含有硫醇的肽可以通过使包含游离硫醇基团的肽与也与具有与硫醇反应的基团的18F结合的标记试剂反应，用氟-18（18F）进行放射性标记。所得到的18F标记的肽可以使用双特异性抗体或具有一个对18F标记的肽特异性的臂或与18F标记的肽缀合的低分子量半抗原的双特异性抗体片段靶向感兴趣的组织，目标组织。目标组织随后通过临床正电子发射断层扫描显像。

54. 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。

55. 发明授权

US5482698A Detection and therapy of lesions with biotin/avidin polymer conjugates 失效
标题翻译：用生物素/抗生物素蛋白聚合物缀合物检测和治疗病变
公开(公告)号：US5482698A
公开(公告)日：1996-01-09
申请号：US51144
申请日：1993-04-22
申请人： Gary L. Griffiths
发明人： Gary L. Griffiths
IPC分类号： A61K39/385 , A61K39/44 , A61K47/48 , A61K49/00 , A61K49/04 , A61K51/00 , A61K51/06 , A61K41/00 , A61K31/415 , A61K31/74 , A61K51/10
CPC分类号： B82Y5/00 , A61K47/48353 , A61K47/48753 , A61K51/065 , A61K2123/00
摘要： Methods of detecting and/or treating lesions in a patient are provided. The methods are an improvement over known methods comprising the steps of (a) parenterally injecting a subject with a targeting composition comprised of a biotin-protein conjugate or an avidin-protein conjugate, wherein the protein preferentially binds to a marker substance produced or associated with the targeted lesion, and allowing the protein conjugate to preferentially accrete at the targeted lesion; (b) then parenterally injecting a clearing composition comprised of (i) avidin, when the targeting composition is a biotin-protein conjugate, or (ii) biotin, when the targeting composition is a avidin-protein conjugate, and allowing the clearing composition to substantially clear the targeting composition from non-targeted sites and to bind to the targeting composition accreted at the targeted lesion; and (c) parenterally injecting a detection or therapeutic composition comprised of a conjugate of (i) avidin and detection or therapeutic agent when the clearing composition is biotin, or (ii) biotin and detection or therapeutic agent when the clearing agent is avidin, and allowing the composition to accrete at the targeted lesion. The improvement is having at least one of the compositions of step (a) or (b) further comprise a polymer to which multiple moieties of avidin or biotin can conjugate, thereby providing an increased number of binding sites to which a subsequently administrated composition can bind thereby amplifying the amount of detection or therapeutic agent at the targeted site.
摘要翻译：提供了检测和/或治疗患者病变的方法。所述方法是对已知方法的改进，其包括以下步骤：（a）用包含生物素 - 蛋白质缀合物或抗生物素蛋白 - 蛋白质缀合物的靶向组合物肠胃外注射受试者，其中所述蛋白质优先结合产生或与靶向病变，并允许蛋白质缀合物优先在目标病变处分泌; （b）然后当靶向组合物为抗生物素蛋白 - 蛋白质缀合物时，肠胃外注射由（i）抗生物素蛋白组成的清除组合物，当靶向组合物为生物素 - 蛋白质缀合物或（ii）生物素时），并使清除组合物从非靶向位点基本上清除靶向组合物，并结合靶向组合物在靶向病变处产生; 和（c）当清除组合物为生物素时，肠胃外注射由（i）抗生物素蛋白和检测或治疗剂的缀合物组成的检测或治疗组合物，或（ii）当所述清除剂为抗生物素蛋白时的生物素和检测或治疗剂，以及允许组合物在目标病变处进行扩散。改进之处在于步骤（a）或（b）的组合物中的至少一种还包含聚合物，其中多个部分的抗生物素蛋白或生物素可与其结合，从而提供随后施用的组合物可以结合的更多数量的结合位点从而扩大靶位点的检测量或治疗剂量。

56. 发明授权

US08547533B2 Composite probes and use thereof in super resolution methods 有权
标题翻译：复合探针及其在超分辨率方法中的应用
公开(公告)号：US08547533B2
公开(公告)日：2013-10-01
申请号：US13519737
申请日：2010-12-28
申请人： Jay R. Knutson , Gary L. Griffiths
发明人： Jay R. Knutson , Gary L. Griffiths
IPC分类号： G01C3/12
CPC分类号： C07K2/00 , C09B11/24 , C09B23/086 , G01N21/6428 , G01N21/6458 , G01N2021/6432 , G01N2021/6441 , Y10T436/21
摘要： Composite probes for super resolution optical techniques using super resolution via transiently activated quenchers (STAQ) include a donor moiety and an acceptor moiety joined by a linker, wherein the acceptor moiety, when excited by incident radiation, is excited to a state which, for example, absorbs in the donor emission region, such that the acceptor moiety in its excited state quenches at least a portion of the donor moiety emission. Other transiently activated quenching mechanisms and moieties could accomplish the same task by reducing donor population. Also disclosed are methods for irradiating a selected region of a target material including the composite probe, wherein the composite probe enables improved resolution by point spread function modification and/or nanoscale chemical reactions.
摘要翻译：用于通过瞬时激活猝灭剂（STAQ）使用超分辨率的超分辨率光学技术的复合探针包括通过接头连接的供体部分和受体部分，其中受体部分在被入射辐射激发时被激发到例如，在受体发射区吸收，使得其激发态的受体部分猝灭供体部分发射的至少一部分。其他瞬时激活的猝灭机制和部分可以通过减少供体群体来完成相同的任务。还公开了用于照射包括复合探针的靶材料的选定区域的方法，其中复合探针通过点扩散功能修饰和/或纳米级化学反应提高了分辨率。

57. 发明授权

US07045503B1 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.

58. 发明授权

US07011816B2 Labeling targeting agents with gallium-68 and gallium-67 有权
公开(公告)号：US07011816B2
公开(公告)日：2006-03-14
申请号：US10318401
申请日：2002-12-13
申请人： Gary L. Griffiths , William J. McBride
发明人： Gary L. Griffiths , William J. McBride
IPC分类号： A61K49/04
CPC分类号： A61K51/088 , A61K51/1093
摘要： A method and compositions are described for labeling a targeting agent with Ga-68, in which eluate from an acid-eluted Ge-68/Ga-68 generator is combined with a macrocycle-containing targetable agent. The labeling method and compositions disclosed ensure that a simple elution of gallium-68, taken directly from a generator, can be used without further manipulation to quantitatively label a macrocycle-containing targetable agent. The Ga-68 labeled targeting agent so produced is useful with specific targeting agents, and is most especially useful in a pretargeting method for positron emission tomographic detection.

59. 发明授权

US06228362B1 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：US06228362B1
公开(公告)日：2001-05-08
申请号：US09205243
申请日：1998-12-04
申请人： Gary L. Griffiths , Serengulam Govindan
发明人： Gary L. Griffiths , Serengulam Govindan
IPC分类号： A61K39395
CPC分类号： G01N33/686 , A61K41/0095 , A61K47/665 , A61K47/6893 , A61K47/6897 , A61K47/6898 , A61K51/1078 , A61K51/1093 , A61K2039/505 , A61K2121/00 , A61K2123/00 , B82Y5/00 , C07K16/18 , C07K16/3007 , C07K16/44 , C07K16/468 , C07K2317/12 , C07K2317/13 , C07K2317/31 , C07K2317/55 , C07K2317/622 , C07K2319/00 , G01N33/531 , G01N33/534 , G01N33/574
摘要： The present invention provides a method for targeting boron atoms to tumor cells in a patient. The method includes the steps of (A) administering a targeting composition comprising a conjugate of (i) at least one first antibody or antigen-binding antibody fragment which selectively binds to an antigen produced by or associated with the tumor cells and present at the tumor cells, and (ii) at least one second antibody or antibody fragment which specifically binds to a hapten on a boron compound; (B) optionally, a clearing composition; (C) said boron compound; and (D) optionally, a second clearing composition. 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）施用靶向组合物，所述靶组合物包含（i）至少一种第一抗体或抗原结合抗体片段的缀合物，所述第一抗体或抗原结合抗体片段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存在于肿瘤细胞，和（ii）与硼化合物上的半抗原特异性结合的至少一种第二抗体或抗体片段; （B）任选地，清除组合物; （C）所述硼化合物; 和（D）任选地，第二清除组合物。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。

60. 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。

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