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41. 发明申请

US20120309045A1 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：US20120309045A1
公开(公告)日：2012-12-06
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： C07K7/06 , C12N13/00 , B29C59/16 , G01N21/21 , G01N21/59 , G01N21/64 , F21V9/16
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。

42. 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。

43. 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。

44. 发明授权

US06576746B2 Site-specific labeling of disulfide-containing targeting vectors 有权
标题翻译：二硫化物靶向载体的位点特异性标记
公开(公告)号：US06576746B2
公开(公告)日：2003-06-10
申请号：US09417109
申请日：1999-10-13
申请人： William J. McBride , Gary L. Griffiths
发明人： William J. McBride , Gary L. Griffiths
IPC分类号： C07K1600
CPC分类号： G01N33/531 , A61K47/6889 , A61K51/1093 , Y10S435/81
摘要： A method of producing a diagnostic or therapeutic conjugate of a protein, polypeptide or peptide containing at least one disulfide bond which is necessary to maintain its biological activity, and bearing at least one thiol-containing moiety linked thereto through a hydrazone or hydrazine linkage, is effected by contacting said protein, polypeptide or peptide with a thiol-reactive diagnostic or therapeutic agent, either preformed or generated in situ, to form a stable diagnostic or therapeutic conjugate of the protein, polypeptide or peptide without substantial cleavage of the disulfide bond. Diagnostic and therapeutic conjugates produced using the foregoing method, as well as kits for carrying out the method are provided.
摘要翻译：产生含有维持其生物学活性所必需的至少一个二硫键的蛋白质，多肽或肽的诊断或治疗性缀合物的方法，以及通过腙或肼键连接至少一个含硫醇的部分，通过将所述蛋白质，多肽或肽与硫醇反应性诊断或治疗剂接触，其通过预先形成或原位产生，以形成蛋白质，多肽或肽的稳定的诊断或治疗缀合物，而不显着切割二硫键。提供了使用上述方法制备的诊断和治疗缀合物，以及用于实施该方法的试剂盒。

45. 发明授权

US06358489B1 Fluorination of proteins and peptides for F-18 positron emission tomography 有权
公开(公告)号：US06358489B1
公开(公告)日：2002-03-19
申请号：US09644706
申请日：2000-08-24
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 (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.

46. 发明授权

US5753206A Radiometal-binding analogues of luteinizing hormone releasing hormone 失效
标题翻译：促黄体激素释放激素的放射性结合类似物
公开(公告)号：US5753206A
公开(公告)日：1998-05-19
申请号：US474555
申请日：1995-06-07
申请人： William J. McBride , Habibe Karacay , Gary L. Griffiths
发明人： William J. McBride , Habibe Karacay , Gary L. Griffiths
IPC分类号： A61K38/00 , A61K51/00 , A61K51/08 , C07K7/23 , C07K14/575 , A61M36/14
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。

47. 发明授权

US07213552B1 Variable geometry camshaft 失效
标题翻译：可变几何凸轮轴
公开(公告)号：US07213552B1
公开(公告)日：2007-05-08
申请号：US10871984
申请日：2004-06-18
申请人： Gary L. Griffiths
发明人： Gary L. Griffiths
IPC分类号： F01L1/34
CPC分类号： F01L13/0015 , F01L1/026 , F01L13/0063
摘要： The invention improves volumetric efficiency of the internal combustion engine. A suspended cam, 1, follows a limited arc of rotation about the axis of a drive gear, 3. A change in engine speed (r.p.m.) activates the hydraulic piston 8, and alters the cam heel position along this arc that is tangent to a cam follower, 9. The separation distance, between the cam follower and cam heel, determines the duration of valve opening. The separation distance and the rocker arm ratio control the amount of valve lift. As the cam axis sweeps across the cam follower, there is coordinated movement of the cam follower fulcrum, 11. This tempers the otherwise excessive change in rocker arm ratio as the cam contact point on the cam follower moves in the “x” direction with rotation of the suspension assembly, 2. The rotation of the cam axis and gear reduction assembly, 4, 5, & 6, about the drive gear, shifts the timing of cam contact. This timing shift creates a desirable asymmetrical expansion or contraction in the duration period of valve opening.
摘要翻译：本发明提高了内燃机的体积效率。悬挂的凸轮1围绕驱动齿轮3的轴线旋转有限的弧。发动机转速（r.p.m.）的变化激活液压活塞8，并且改变沿着与凸轮从动件9相切的弧的凸轮跟随位置。凸轮从动件和凸轮脚跟之间的间隔距离决定了阀打开的持续时间。分离距离和摇臂比控制气门升程量。当凸轮轴线扫过凸轮从动件时，凸轮从动件支点11的协调运动。随着凸轮从动件上的凸轮接触点随着悬架组件的旋转而沿“x”方向移动，这样会缓和摇摆臂比例的过大变化。凸轮轴和齿轮减速组件4,5和6围绕驱动齿轮的转动会改变凸轮接触时间。该定时偏移在阀开启的持续时间段中产生期望的不对称膨胀或收缩。

48. 再颁专利

USRE37710E1 Radiometal-binding analogues of luteinizing hormone releasing hormone 有权
标题翻译：促黄体激素释放激素的放射性结合类似物
公开(公告)号：USRE37710E1
公开(公告)日：2002-05-21
申请号：US09572339
申请日：2000-05-18
申请人： William J. McBride , Habibe Karacay , Gary L. Griffiths
发明人： William J. McBride , Habibe Karacay , Gary L. Griffiths
IPC分类号： A61K5100
CPC分类号： C07K7/23 , A61K38/00 , A61K51/088
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肽，其中可以结合放射性核素的兴奋剂释放激素的衍生物。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。

49. 发明授权

US6071490A Position emission tomography using gallium-68 chelates 有权
标题翻译：使用镓-68螯合物进行位置发射断层扫描
公开(公告)号：US6071490A
公开(公告)日：2000-06-06
申请号：US306789
申请日：1999-05-07
申请人： Gary L. Griffiths , William J. McBride
发明人： Gary L. Griffiths , William J. McBride
IPC分类号： A61K51/10 , A61K51/00 , A61M36/14
CPC分类号： A61K51/109
摘要： A method of delivering Ga-68 to a target site is effected by administering a bi-specific antibody which specifically binds via a primary binding site to a substance produced by or associated with the target site and which specifically binds via a secondary binding site to a subsequently administered chelate-Ga-68 complex, and allowing the antibody to localize at the target site; optionally administering a clearing agent to clear non-localized bi-specific antibody rapidly from circulation; and administering a chelate-Ga-68 complex comprising Ga-68 chelated to Ac-Phe-Lys(DTPA)-Tyr-Lys(DTPA)-NH.sub.2 and allowing the chelate-Ga-68 complex to localize at the target site via specific binding by the secondary binding site of the bi-specific antibody. The targeted complex then can be used for PET imaging to give highly resolved images. Alternatively, the Ac-Phe-Lys(DTPA)-Tyr-Lys(DTPA)-NH.sub.2 can be conjugated to a targeting antibody fragment and used to elute Ga-68 from a generator, after which it is infused into a patient for direct targeting of the Ga-68 for PET imaging. Reagents and methods of making and using them also are provided.
摘要翻译：将Ga-68递送到靶位点的方法是通过施用特异性抗体，其通过主要结合位点特异性结合到由靶位点产生或与靶位点相关并通过二级结合位点特异性结合的双特异性抗体随后施用螯合物-Ga-68复合物，并允许抗体在靶位点定位; 任选地施用清除剂以快速从循环中清除非局部双特异性抗体; 并给予螯合-Ac-Phe-Lys（DTPA）-Tyr-Lys（DTPA）-NH2螯合的Ga-68螯合物-Ga-68复合物，并使螯合物-Ga-68复合物通过特异性结合在靶位点定位通过双特异性抗体的二级结合位点。然后，靶向复合物可用于PET成像以提供高度分辨的图像。或者，可以将Ac-Phe-Lys（DTPA）-Tyr-Lys（DTPA）-NH 2与靶向抗体片段缀合并用于从发生器洗脱Ga-68，之后将其输入到患者中用于直接靶向的Ga-68用于PET成像。还提供了试剂和制造和使用它们的方法。

50. 发明授权

US5128119A Methods for technetium/rhenium labeling of f(ab.sup.1).sub.2 fragments 失效
标题翻译： f（ab1）2片段的锝/铼标记方法
公开(公告)号：US5128119A
公开(公告)日：1992-07-07
申请号：US392280
申请日：1989-08-10
申请人： Gary L. Griffiths
发明人： Gary L. Griffiths
IPC分类号： A61K39/395 , A61K51/00 , A61K51/10 , A61P31/00 , A61P35/00 , C07B59/00 , C07K1/13 , C07K16/00
CPC分类号： A61K51/1018 , A61K51/1048 , A61K2123/00 , Y10S435/975 , Y10S436/804
摘要： A method for radiolabeling a protein with a radioisotope of technetium of rhenium comprises the steps of contacting a solution of a protein containing a plurality of adjacent free sulfhydryl groups, or in particular cases, intact protein containing at least one disulfide group, with stannous ions, and then with radiopertechnetate or radioperrhenate, the amount of stannous ion being sufficient to substantially completely reduce the radiopertechnetate or radioperrhenate, and recovering radiolabeled protein.
摘要翻译：用铼锝的放射性同位素放射性标记蛋白质的方法包括以下步骤：使含有多个相邻游离巯基的蛋白质溶液或特别是含有至少一个二硫键的完整蛋白质与亚锡离子接触，然后用高铁酸钠或无铼酸盐处理，亚锡离子的量足以基本上完全降低放射性高铁酸盐或无机化合物，并回收放射性标记的蛋白质。

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