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21. 发明授权

US5635603A Preparation and use of immunoconjugates 失效
标题翻译：免疫缀合物的制备和使用
公开(公告)号：US5635603A
公开(公告)日：1997-06-03
申请号：US352715
申请日：1994-12-05
申请人： Hans J. Hansen , Shui-on Leung , Jerry Shevitz , Gary L. Griffiths , Seregulam V. Govindan
发明人： Hans J. Hansen , Shui-on Leung , Jerry Shevitz , Gary L. Griffiths , Seregulam V. Govindan
IPC分类号： G01N33/53 , A61K38/00 , A61K39/395 , A61K49/00 , A61K51/10 , C07H21/04 , C07K16/00 , C07K16/30 , C07K17/00 , C12N15/09 , C12P21/08 , C12R1/91 , G01N33/532 , G01N33/563 , G01N33/68
CPC分类号： G01N33/6857 , A61K51/1048 , A61K51/1069 , A61K51/1093 , C07K16/00 , C07K16/30 , C07K16/3007 , C07K16/3061 , G01N33/532 , A61K2121/00 , A61K2123/00 , A61K38/00
摘要： The present invention relates to immunoconjugates comprising an antibody fragment which is covalently bound to a diagnostic or therapeutic principle through a carbohydrate moiety in the light chain variable region of the antibody fragment. The invention also relates to immunoconjugates comprising an antibody moiety that is an intact antibody containing a glycosylation site in the light chain variable domain which has been introduced into the antibody by mutating the nucleotide sequence encoding the light chain. The resultant immunoconjugates retain the immunoreactivity of the antibody fragment or intact antibody, and target the diagnostic or therapeutic principle to a target tissue where the diagnostic or therapeutic effect is realized. Thus, the invention contemplates the use of such immunoconjugates for diagnosis and immunotherapy. The invention further relates to methods for preparing such immunoconjugates.
摘要翻译：本发明涉及包含通过抗体片段的轻链可变区中的碳水化合物部分与诊断或治疗原理共价结合的抗体片段的免疫缀合物。本发明还涉及包含抗体部分的免疫缀合物，所述抗体部分是通过突变编码轻链的核苷酸序列而被引入抗体的包含轻链可变结构域中的糖基化位点的完整抗体。所得的免疫偶联物保留抗体片段或完整抗体的免疫反应性，并将诊断或治疗原理靶向实现诊断或治疗效果的靶组织。因此，本发明考虑使用这种免疫缀合物进行诊断和免疫治疗。本发明还涉及制备这种免疫缀合物的方法。

22. 发明申请

US20090246131A1 Production and Use of Novel Peptide-Based Agents for Use with Bi-Specific Antibodies 有权
标题翻译：用于双特异性抗体的新型基于肽的试剂的生产和使用
公开(公告)号：US20090246131A1
公开(公告)日：2009-10-01
申请号：US12481233
申请日：2009-06-09
申请人： Hans J. Hansen , Gary L. Griffiths , Shui-on Leung , William J. McBride , Zhengxing Qu
发明人： Hans J. Hansen , Gary L. Griffiths , Shui-on Leung , William J. McBride , Zhengxing Qu
IPC分类号： A61K51/10 , A61K47/42
CPC分类号： C07K16/468 , A61K47/6863 , A61K47/6899 , A61K51/1048 , A61K51/1063 , A61K2039/505 , B82Y5/00 , C07K16/18 , C07K16/30 , C07K16/3007 , C07K16/3046 , C07K16/44 , C07K2317/12 , C07K2317/13 , C07K2317/24 , C07K2317/31 , C07K2317/55 , C07K2317/622 , C07K2319/00
摘要： The present invention relates to a bi-specific antibody or antibody fragment having at least one arm that is reactive against a targeted tissue and at least one other arm that is reactive against a targetable conjugate. The targetable conjugate encompasses a hapten to which antibodies have been prepared. In preferred embodiments, the hapten is histamine-succinyl-glycine (HSG). In more preferred embodiments, the at least one arm comprises the CDR sequences of the HSG-binding 679 antibody. The targetable conjugate is attached to one or more therapeutic and/or diagnostic agents. The invention provides constructs and methods for producing the bispecific antibodies or antibody fragments, as well as methods for using them and kits comprising them.
摘要翻译：本发明涉及一种双特异性抗体或抗体片段，该双特异性抗体或抗体片段具有至少一个对目标组织有反应性的臂和至少一种其它可靶向缀合物反应的其他臂。可靶向缀合物包含已制备抗体的半抗原。在优选的实施方案中，半抗原是组胺 - 琥珀酰甘氨酸（HSG）。在更优选的实施方案中，所述至少一个臂包含HSG结合679抗体的CDR序列。可靶向缀合物连接至一种或多种治疗和/或诊断剂。本发明提供了用于产生双特异性抗体或抗体片段的构建体和方法，以及使用它们的方法和包含它们的试剂盒。

23. 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。

24. 发明授权

US07074405B1 Use of bi-specific antibodies for pre-targeting diagnosis and therapy 失效
标题翻译：使用双特异性抗体进行预定位诊断和治疗
公开(公告)号：US07074405B1
公开(公告)日：2006-07-11
申请号：US09337756
申请日：1999-06-22
申请人： Hans J. Hansen , Gary L. Griffiths , Shui-on Leung , William J. McBride , Zhengxing Qu
发明人： Hans J. Hansen , Gary L. Griffiths , Shui-on Leung , William J. McBride , Zhengxing Qu
IPC分类号： A61K39/395
CPC分类号： C07K16/468 , A61K47/67 , A61K47/6853 , A61K47/6863 , A61K47/6879 , A61K47/6893 , A61K47/6897 , A61K51/088 , A61K51/1048 , A61K51/1063 , A61K2039/505 , B82Y5/00 , C07K16/18 , C07K16/3007 , C07K16/4266 , C07K16/44 , C07K2317/12 , C07K2317/13 , C07K2317/24 , C07K2317/31 , C07K2317/55 , C07K2317/622 , C07K2319/00
摘要： The present invention relates to a bi-specific antibody or antibody fragment having at least one arm that specifically binds a targeted tissue and at least one other arm that specifically binds a targetable conjugate. The targetable conjugate comprises a carrier portion which comprises or bears at least one epitope recognizable by at least one arm of said bi-specific antibody or antibody fragment. The targetable conjugate further comprises one or more therapeutic or diagnostic agents or enzymes. The invention provides constructs and methods for producing the bi-specific antibodies or antibody fragments, as well as methods for using them.
摘要翻译：本发明涉及具有特异性结合目标组织的至少一个臂和特异性结合可靶向缀合物的至少一个其他臂的双特异性抗体或抗体片段。可靶向缀合物包含载体部分，其包含或携带至少一个可被所述双特异性抗体或抗体片段的至少一个臂识别的表位。可靶向缀合物还包含一种或多种治疗剂或诊断剂或酶。本发明提供用于产生双特异性抗体或抗体片段的构建体和方法，以及使用它们的方法。

25. 发明授权

US06962702B2 Production and use of novel peptide-based agents for use with bi-specific antibodies 失效
标题翻译：用于双特异性抗体的新型基于肽的试剂的生产和使用
公开(公告)号：US06962702B2
公开(公告)日：2005-11-08
申请号：US09823746
申请日：2001-04-03
申请人： Hans J. Hansen , Gary L. Griffiths , Shui-on Leung , William J. McBride , Zhengxing Qu
发明人： Hans J. Hansen , Gary L. Griffiths , Shui-on Leung , William J. McBride , Zhengxing Qu
IPC分类号： G01R33/28 , A61B5/055 , A61K39/395 , A61K49/00 , A61K51/00 , A61K51/08 , A61K51/10 , C07K5/107 , C07K5/11 , C07K16/18 , C07K16/28 , C07K16/30 , C07K16/44 , C07K16/46 , C07K19/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/09 , C12P21/08 , C12Q1/68 , G01N33/50 , G01N33/574 , G01N33/577
CPC分类号： C07K16/468 , A61K47/6863 , A61K47/6899 , A61K51/1048 , A61K51/1063 , A61K2039/505 , B82Y5/00 , C07K16/18 , C07K16/30 , C07K16/3007 , C07K16/3046 , C07K16/44 , C07K2317/12 , C07K2317/13 , C07K2317/24 , C07K2317/31 , C07K2317/55 , C07K2317/622 , C07K2319/00
摘要： The present invention relates to a bi-specific antibody or antibody fragment having at least one arm that is reactive against a targeted tissue and at least one other arm that is reactive against a linker moiety. The linker moiety encompasses a hapten to which antibodies have been prepared. The antigenic linker is conjugated to one or more therapeutic or diagnostic agents or enzymes. The invention provides constructs and methods for producing the bispecific antibodies or antibody fragments, as well as methods for using them.
摘要翻译：本发明涉及一种双特异性抗体或抗体片段，其具有至少一个对靶组织有反应性的臂，以及至少一个对接头部分具有反应性的其它臂。接头部分包括已经制备抗体的半抗原。抗原性接头与一种或多种治疗剂或诊断剂或酶缀合。本发明提供了用于产生双特异性抗体或抗体片段的构建体和方法，以及使用它们的方法。

26. 发明授权

US5976492A Radioactive phosphorus labeled proteins for targeted radiotherapy 失效
标题翻译：放射性磷标记的蛋白质用于靶向放射治疗
公开(公告)号：US5976492A
公开(公告)日：1999-11-02
申请号：US979932
申请日：1997-11-26
申请人： Gary L. Griffiths , Hans J. Hansen , Habibe Karacay
发明人： Gary L. Griffiths , Hans J. Hansen , Habibe Karacay
IPC分类号： A61K39/395 , A61K38/00 , A61K51/08 , A61K51/10 , A61P31/00 , A61P35/00 , C07K1/13 , C07K16/18 , A61K51/00 , C07K16/00
CPC分类号： A61K51/1045 , A61K51/08 , A61K51/088 , A61K2121/00 , A61K38/00
摘要： .sup.32 P- and .sup.33 P-labeled proteins which are useful for radiotherapy are prepared by stably linking .sup.32 P- or .sup.33 P-containing molecules to targeting proteins in such a way that the targeting protein retains the ability to bind to a cellular target. Methods for preparing the labeled proteins and their use in methods of radiotherapy are described.
摘要翻译：可用于放射治疗的32P和33P标记的蛋白质通过将靶向蛋白质以靶向蛋白质保持结合细胞靶标的方式稳定地连接32P或33P的分子与靶向蛋白质而制备。描述了制备标记蛋白的方法及其在放射疗法中的应用。

27. 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。

28. 发明授权

US5772981A Thiolation of proteins for radionuclide-based radioimmunodetection and radioimmunotherapy 失效
标题翻译：基于放射性核素的放射免疫检测和放射免疫治疗的蛋白质硫酸化
公开(公告)号：US5772981A
公开(公告)日：1998-06-30
申请号：US779556
申请日：1997-01-08
申请人： Seregulam V. Govindan , Ruth Grebenau , Gary L. Griffiths , Hans J. Hansen
发明人： Seregulam V. Govindan , Ruth Grebenau , Gary L. Griffiths , Hans J. 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： A61K51/1093 , A61K51/1048 , A61K2121/00 , A61K2123/00
摘要： A method of radiolabeling a protein with a radionuclide including contacting the protein with a protected tertiary thiol-containing bifunctional chelating agent that is capable of reacting with the protein at one end of the agent and is capable of complexing with a radionuclide at the other end of the agent, to form a protein-acetyl-t-thiol-containing conjugate. The protein-acetyl-t- thiol-containing conjugate then is deprotected and admixed with a reducing agent for the radionuclide, where the radionuclide is added in a subsequent step, to form a mixture of reducing agent and protein-t-thiol-containing conjugate. This mixture then is reacted with a radionuclide whereby the radionuclide reacts with pendant sulfhydryl groups present on the protein-t-thiol-containing conjugate. Methods of radioimmunotherapy and diagnostic kits suitable for forming a composition to be administered to a human patient also are disclosed.
摘要翻译：一种用放射性核素放射性标记蛋白质的方法，包括使蛋白质与受保护的含叔硫醇的双功能螯合剂接触，所述双功能螯合剂能够在所述试剂的一端与所述蛋白质反应，并且能够与另一端的放射性核素络合形成蛋白质 - 乙酰基-E，不含t + EE-硫醇的缀合物。然后将蛋白质 - 乙酰基 - + E，非t + EE-含硫醇的缀合物脱保护并与用于放射性核素的还原剂混合，其中在随后的步骤中加入放射性核素，以形成还原剂和蛋白质 - + E，uns t + EE-含硫醇的缀合物。然后将该混合物与放射性核素反应，由此放射性核素与存在于蛋白质+ E，非t + EE-硫醇的缀合物上的侧链巯基反应。还公开了放射免疫治疗方法和适合于形成待给予人类患者的组合物的诊断试剂盒。

29. 发明授权

US07470429B2 Methods and compositions for increasing the target-specific toxicity of a chemotherapy drug 有权
标题翻译：用于增加化疗药物靶标特异性毒性的方法和组合物
公开(公告)号：US07470429B2
公开(公告)日：2008-12-30
申请号：US10066782
申请日：2002-02-06
申请人： Gary L. Griffiths , Hans J. Hansen
发明人： Gary L. Griffiths , Hans J. Hansen
IPC分类号： A61K39/00
CPC分类号： B82Y5/00 , A61K47/6815 , A61K47/6863 , A61K47/6867 , A61K47/6879 , A61K47/6895 , A61K47/6899
摘要： A method for increasing the target-specific toxicity of a drug is effected by pretargeting an enzyme to a mammalian target site, and then administering a cytotoxic drug known to act at the target site, or a prodrug form thereof which is converted to the drug in situ, which drug is also detoxified to form an intermediate of lower toxicity using said mammal's ordinary metabolic processes, whereby the detoxified intermediate is reconverted to its more toxic form by the pretargeted enzyme and thus has enhanced cytotoxicity at the target site. Further enhancement can be achieved by pretargeting an enzyme which converts the prodrug to the cytotoxic drug at the target site. Kits for use with the method also are provided. The method and kits permit lower doses of cytotoxic agents, maximize target site activity and minimize systemic side effects.
摘要翻译：通过将酶靶向到哺乳动物靶位点，然后施用已知在靶位点起作用的细胞毒性药物或其转化为药物的前药形式，来实现增加药物的靶特异性毒性的方法使用所述哺乳动物的普通代谢过程，所述药物也被解毒以形成具有较低毒性的中间体，由此所述解毒中间体被所述预靶向酶再转化为其更具毒性的形式，因此在靶位点具有增强的细胞毒性。可以通过预靶向在靶位点将前药转化为细胞毒性药物的酶来实现进一步增强。还提供了与该方法一起使用的套件。该方法和试剂盒允许较低剂量的细胞毒剂，最大限度地提高目标部位活性并最大程度减少全身副作用。

30. 发明申请

US20080293921A1 Production and Use of Novel Peptide-Based Agents for Use with Bi-Specific Antibodies 有权
标题翻译：用于双特异性抗体的新型基于肽的试剂的生产和使用
公开(公告)号：US20080293921A1
公开(公告)日：2008-11-27
申请号：US11923279
申请日：2007-10-24
申请人： Hans J. Hansen , Gary L. Griffiths , Shui-on Leung , William J. McBride , Zhengxing Qu
发明人： Hans J. Hansen , Gary L. Griffiths , Shui-on Leung , William J. McBride , Zhengxing Qu
IPC分类号： C07K16/18
CPC分类号： C07K16/468 , A61K47/6863 , A61K47/6899 , A61K51/1048 , A61K51/1063 , A61K2039/505 , B82Y5/00 , C07K16/18 , C07K16/30 , C07K16/3007 , C07K16/3046 , C07K16/44 , C07K2317/12 , C07K2317/13 , C07K2317/24 , C07K2317/31 , C07K2317/55 , C07K2317/622 , C07K2319/00
摘要： The present invention relates to a bi-specific antibody or antibody fragment having at least one arm that is reactive against a targeted tissue and at least one other arm that is reactive against a linker moiety. The linker moiety encompasses a hapten to which antibodies have been prepared. In preferred embodiments, the hapten is histamine-succinyl-glycine (HSG). In more preferred embodiments, the at least one arm comprises the CDR sequences of the HSG-binding 679 antibody. The antigenic linker is conjugated to one or more therapeutic or diagnostic agents or enzymes. In one embodiment, the invention provides constructs and methods for producing the bispecific antibodies or antibody fragments, as well as methods for using them.
摘要翻译：本发明涉及一种双特异性抗体或抗体片段，其具有至少一个对靶组织有反应性的臂，以及至少一个对接头部分具有反应性的其它臂。接头部分包括已经制备抗体的半抗原。在优选的实施方案中，半抗原是组胺 - 琥珀酰甘氨酸（HSG）。在更优选的实施方案中，所述至少一个臂包含HSG结合679抗体的CDR序列。抗原性接头与一种或多种治疗剂或诊断剂或酶缀合。在一个实施方案中，本发明提供了用于产生双特异性抗体或抗体片段的构建体和方法，以及使用它们的方法。

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