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1. 发明授权

US5210040A Process for coupling antibodies or antibody fragments to liposomes 失效
标题翻译：将抗体或抗体片段与脂质体偶联的方法
公开(公告)号：US5210040A
公开(公告)日：1993-05-11
申请号：US485395
申请日：1990-02-22
申请人： Yi-Her Jou , Roger C. Hu , Peter A. Lagocki
发明人： Yi-Her Jou , Roger C. Hu , Peter A. Lagocki
IPC分类号： G01N33/543 , G01N33/58 , G01N33/68 , G01N33/76
CPC分类号： G01N33/6857 , G01N33/5432 , G01N33/586 , G01N33/76 , Y10S436/829
摘要： The present invention provides for novel homogeneous immunoassay systems involving complement-mediated lysis of marker-encapsulating lipid vesicles (liposomes) for detection of analyte in a fluid sample. These systems do not require the separation of unbound antigens and/or antibody conjugates yet provide highly sensitive procedures for analyte detection. Liposomes containing a marker, are coupled to antibody fragments in a way which confers the liposomes with immunological specificity yet avoids sensitizing the liposomes to complement mediated lysis in the absence of analyte. Antibody sensitized liposomes (the first reagent) are sequentially incubated with an analyte-containing sample, and optionally "dummy" liposomes, which do not contain encapsulated marker, a second antibody (the second reagent), and finally with a complement source such as plasma. Complement is activated by the liposome-antibody-antigen-second antibody complex causing liposome lysis and a concomitant release of marker. Also provided are methods for preparing antibody sensitized liposomes in the presence of a polysaccharide capable of forming a reversible gel and methods for preparing derivatized Fab' antibody fragments for coupling to lipid vesicles.
摘要翻译：本发明提供了用于检测流体样品中分析物的补体介导的用于标记包封的脂质囊泡（脂质体）的裂解的均相免疫测定系统。这些系统不需要分离未结合的抗原和/或抗体缀合物，同时为分析物检测提供高度敏感的程序。含有标记物的脂质体以使得脂质体具有免疫特异性的方式与抗体片段偶联，而避免在不存在分析物的情况下使脂质体对致敏介导的裂解进行敏化。将抗体致敏脂质体（第一试剂）与含分析物的样品和任选的“虚拟”脂质体（其不包含包封标记物），第二抗体（第二试剂），最后用补体来源例如血浆。补体由脂质体 - 抗体 - 抗原 - 第二抗体复合物激活，引起脂质体溶解和伴随释放标记物。还提供了在能够形成可逆凝胶的多糖存在下制备抗体致敏脂质体的方法以及用于制备用于偶联至脂质囊泡的衍生化Fab'抗体片段的方法。

2. 发明授权

US4971916A Liposome based homogeneous immunoassay for diagnostic tests 失效
标题翻译：基于脂质体的均质免疫测定用于诊断测试
公开(公告)号：US4971916A
公开(公告)日：1990-11-20
申请号：US312430
申请日：1989-02-17
申请人： Yi-Her Jou , Roger C. Hu , Peter A. Lagocki
发明人： Yi-Her Jou , Roger C. Hu , Peter A. Lagocki
IPC分类号： G01N33/543 , G01N33/58 , G01N33/68 , G01N33/76
CPC分类号： G01N33/76 , G01N33/5432 , G01N33/586 , G01N33/6857 , Y10S436/80 , Y10S436/818 , Y10S436/829
摘要： The present invention provides for novel homogeneous immunoassay systems involving complement-mediated lysis of marker-encapsulating lipid vesicles (liposomes) for detection of analyte in a fluid sample. These systems do not require the separation of unbound antigens and/or antibody conjugates yet provide highly sensitive procedures for analyte detection. Liposomes containing a marker, are coupled to antibody fragments in a way which confers the liposomes with immunological specificity yet avoids sensitizing the liposomes to complement mediated lysis in the absence of analyte. Antibody sensitized liposomes (the first reagent) are sequentially incubated with an analyte-containing sample, and optionally "dummy" liposomes, which do not contain encapsulated marker, a second antibody (the second reagent), and finally with a complement source such as plasma. Complement is activated by the liposome-antibody-antigen-second antibody complex causing liposome lysis and a concomitant release of marker. Also provided are methods for preparing antibody sensitized liposomes in the presence of a polysaccharide capable of forming a reversible gel and methods for preparing derivatized Fab' antibody fragments for coupling to lipid vesicles.
摘要翻译：本发明提供了用于检测流体样品中分析物的补体介导的用于标记包封的脂质囊泡（脂质体）的裂解的均相免疫测定系统。这些系统不需要分离未结合的抗原和/或抗体缀合物，同时为分析物检测提供高度敏感的程序。含有标记物的脂质体以使得脂质体具有免疫特异性的方式与抗体片段偶联，而避免在不存在分析物的情况下使脂质体对致敏介导的裂解进行敏化。将抗体致敏脂质体（第一试剂）与含分析物的样品和任选的“虚拟”脂质体（其不包含包封标记物），第二抗体（第二试剂），最后用补体来源例如血浆。补体由脂质体 - 抗体 - 抗原 - 第二抗体复合物激活，引起脂质体溶解和伴随释放标记物。还提供了在能够形成可逆凝胶的多糖存在下制备抗体致敏脂质体的方法以及用于制备用于偶联至脂质囊泡的衍生化Fab'抗体片段的方法。

3. 发明授权

US6001659A Assays using chemiluminescent electron-rich aryl-substituted 1,2-dioxetanes 失效
标题翻译：使用化学发光富电子的芳基取代的1,2-二氧杂环丁烷的测定
公开(公告)号：US6001659A
公开(公告)日：1999-12-14
申请号：US437342
申请日：1995-05-09
申请人： Nai-Yi Wang , Roger C. Hu
发明人： Nai-Yi Wang , Roger C. Hu
IPC分类号： C07D321/00 , C07D493/04 , C07F7/18 , C07F9/655 , C07F9/6561 , C12Q1/34 , C12Q1/42 , C12Q1/68 , C12Q1/70 , G01N33/533 , G01N33/58
CPC分类号： G01N33/582 , C07F7/1856 , C07F9/65512 , C12Q1/34 , C12Q1/42 , G01N33/533 , C12Q2334/00 , Y10S435/968
摘要： Chemiluminescent electron-rich aryl-substituted 1,2-dioxetane compounds are disclosed in which the aryl group is poly-substituted with suitable electron-donating groups such that the light-emitting pattern of the molecule results in a very high luminescent count, thus providing for a sensitive and precise assay for haptens, analytes, polynucleotides and the like. These substituted aryl-containing 1,2-dioxetane compounds can be used as direct labels in an immunoassay or when derivatized with an appropriate leaving group, can be used as a substrate for a enzyme immunoassay. The unusual chemiluminescence of the compounds allows the timing of the luminescent reaction to be exactly controlled.
摘要翻译：公开了化学发光富电子的芳基取代的1,2-二氧杂环丁烷化合物，其中芳基被合适的给电子基团多取代，使得分子的发光图案导致非常高的发光计数，从而提供对于半抗原，分析物，多核苷酸等的敏感和精确的测定。这些取代的含芳基的1,2-二氧杂环丁烷化合物可以在免疫测定中用作直接标记，或者当用合适的离去基团衍生化时，可用作酶免疫测定的底物。化合物的不寻常的化学发光使得准确控制发光反应的时间。

4. 发明授权

US6139781A Chemiluminescent electron-rich aryl-substituted 1,2-dioxetanes 失效
标题翻译：化学发光富电子的芳基取代的1,2-二氧杂环丁烷
公开(公告)号：US6139781A
公开(公告)日：2000-10-31
申请号：US885445
申请日：1997-06-30
申请人： Nai-Yi Wang , Roger C. Hu
发明人： Nai-Yi Wang , Roger C. Hu
IPC分类号： C07D321/00 , C07D493/04 , C07F7/18 , C07F9/655 , C07F9/6561 , C12Q1/34 , C12Q1/42 , C12Q1/68 , C12Q1/70 , G01N33/533 , G01N33/58 , C09K3/00 , C07D303/00
CPC分类号： G01N33/582 , C07F7/1856 , C07F9/65512 , C12Q1/34 , C12Q1/42 , G01N33/533 , C12Q2334/00 , Y10S435/968
摘要： Chemiluminescent electron-rich aryl-substituted 1,2-dioxetane compounds are disclosed in which the aryl group is poly-substituted with suitable electron-donating groups such that the light-emitting pattern of the molecule results in a very high luminescent count, thus providing for a sensitive and precise assay for haptens, analytes, polynucleotides and the like. These substituted aryl-containing 1,2-dioxetane compounds can be used as direct labels in an immunoassay or when derivatized with an appropriate leaving group, can be used as a substrate for a enzyme immunoassay. The unusual chemiluminescence of the compounds allows the timing of the luminescent reaction to be exactly controlled.
摘要翻译：公开了化学发光富电子的芳基取代的1,2-二氧杂环丁烷化合物，其中芳基被合适的给电子基团多取代，使得分子的发光图案导致非常高的发光计数，从而提供对于半抗原，分析物，多核苷酸等的敏感和精确的测定。这些取代的含芳基的1,2-二氧杂环丁烷化合物可以在免疫测定中用作直接标记，或者当用合适的离去基团衍生化时，可用作酶免疫测定的底物。化合物的不寻常的化学发光使得准确控制发光反应的时间。

5. 发明授权

US5780249A Competitive assays using chemiluminescent electron-rich aryl-substituted 1,2-dioxetanes 失效
标题翻译：使用化学发光富电子的芳基取代的1,2-二氧杂环丁烷的竞争性测定
公开(公告)号：US5780249A
公开(公告)日：1998-07-14
申请号：US437343
申请日：1995-05-09
申请人： Nai-Yi Wang , Roger C. Hu
发明人： Nai-Yi Wang , Roger C. Hu
IPC分类号： C07D321/00 , C07D493/04 , C07F7/18 , C07F9/655 , C07F9/6561 , C12Q1/34 , C12Q1/42 , C12Q1/68 , C12Q1/70 , G01N33/533 , G01N33/58 , G01N33/53 , G01N33/543
CPC分类号： G01N33/582 , C07F7/1856 , C07F9/65512 , C12Q1/34 , C12Q1/42 , G01N33/533 , C12Q2334/00 , Y10S435/968
摘要： Chemiluminescent electron-rich aryl-substituted 1,2-dioxetane compounds are disclosed in which the aryl group is poly-substituted with suitable electron-donating groups such that the light-emitting pattern of the molecule results in a very high luminescent count, thus providing for a sensitive and precise assay for haptens, analytes, polynucleotides and the like. These substituted aryl-containing 1,2-dioxetane compounds can be used as direct labels in an immunoassay or when derivatized with an appropriate leaving group, can be used as a substrate for a enzyme immunoassay. The unusual chemiluminescence of the compounds allows the timing of the luminescent reaction to be exactly controlled.
摘要翻译：公开了化学发光富电子的芳基取代的1,2-二氧杂环丁烷化合物，其中芳基被合适的给电子基团多取代，使得分子的发光图案导致非常高的发光计数，从而提供对于半抗原，分析物，多核苷酸等的敏感和精确的测定。这些取代的含芳基的1,2-二氧杂环丁烷化合物可以在免疫测定中用作直接标记，或者当用合适的离去基团衍生化时，可用作酶免疫测定的底物。化合物的不寻常的化学发光使得准确控制发光反应的时间。

6. 发明授权

US5603868A Chemiluminescent electron-rich aryl-substituted 1,2-dioxetanes 失效
公开(公告)号：US5603868A
公开(公告)日：1997-02-18
申请号：US968911
申请日：1992-10-30
申请人： Nai-Yi Wang , Roger C. Hu
发明人： Nai-Yi Wang , Roger C. Hu
IPC分类号： C07D321/00 , C07D493/04 , C07F7/18 , C07F9/655 , C07F9/6561 , C12Q1/34 , C12Q1/42 , C12Q1/68 , C12Q1/70 , G01N33/533 , G01N33/58 , C09K3/00 , C07F9/06
CPC分类号： G01N33/582 , C07F7/1856 , C07F9/65512 , C12Q1/34 , C12Q1/42 , G01N33/533 , C12Q2334/00 , Y10S435/968
摘要： Chemiluminescent electron-rich aryl-substituted 1,2-dioxetane compounds are disclosed in which the aryl group is poly-substituted with suitable electron-donating groups such that the light-emitting pattern of the molecule results in a very high luminescent count, thus providing for a sensitive and precise assay for haptens, analytes, polynucleotides and the like. These substituted aryl-containing 1,2-dioxetane compounds can be used as direct labels in an immunoassay or when derivatized with an appropriate leaving group, can be used as a substrate for a enzyme immunoassay. The unusual chemiluminescence of the compounds allows the timing of the luminescent reaction to be exactly controlled.

7. 发明授权

US6001561A Indicator reagents for assays using chemiluminescent electron-rich aryl substituted 1,2-dioxetanes 失效
标题翻译：使用化学发光富电子的芳基取代的1,2-二氧杂环丁烷的测定指示剂
公开(公告)号：US6001561A
公开(公告)日：1999-12-14
申请号：US437347
申请日：1995-05-09
申请人： Nai-Yi Wang , Roger C. Hu
发明人： Nai-Yi Wang , Roger C. Hu
IPC分类号： C07D321/00 , C07D493/04 , C07F7/18 , C07F9/655 , C07F9/6561 , C12Q1/34 , C12Q1/42 , C12Q1/68 , C12Q1/70 , G01N33/533 , G01N33/58 , C09K3/00
CPC分类号： G01N33/582 , C07F7/1856 , C07F9/65512 , C12Q1/34 , C12Q1/42 , G01N33/533 , C12Q2334/00 , Y10S435/968
摘要： Chemiluminescent electron-rich aryl-substituted 1,2-dioxetane compounds are disclosed in which the aryl group is poly-substituted with suitable electron-donating groups such that the light-emitting pattern of the molecule results in a very high luminescent count, thus providing for a sensitive and precise assay for haptens, analytes, polynucleotides and the like. These substituted aryl-containing 1,2-dioxetane compounds can be used as direct labels in an immunoassay or when derivatized with an appropriate leaving group, can be used as a substrate for a enzyme immunoassay. The unusual chemiluminescence of the compounds allows the timing of the luminescent reaction to be exactly controlled.
摘要翻译：公开了化学发光富电子的芳基取代的1,2-二氧杂环丁烷化合物，其中芳基被合适的给电子基团多取代，使得分子的发光图案导致非常高的发光计数，从而提供对于半抗原，分析物，多核苷酸等的敏感和精确的测定。这些取代的含芳基的1,2-二氧杂环丁烷化合物可以在免疫测定中用作直接标记，或者当用合适的离去基团衍生化时，可用作酶免疫测定的底物。化合物的不寻常的化学发光使得准确控制发光反应的时间。

8. 发明授权

US5607625A Chemiluminescent electron-rich aryl-substituted 1,2-dioxetanes 失效
标题翻译：化学发光富电子的芳基取代的1,2-二氧杂环丁烷
公开(公告)号：US5607625A
公开(公告)日：1997-03-04
申请号：US437728
申请日：1995-05-09
申请人： Nai-Yi Wang , Roger C. Hu
发明人： Nai-Yi Wang , Roger C. Hu
IPC分类号： C07D321/00 , C07D493/04 , C07F7/18 , C07F9/655 , C07F9/6561 , C12Q1/34 , C12Q1/42 , C12Q1/68 , C12Q1/70 , G01N33/533 , G01N33/58 , C09K3/00 , G01N21/76
CPC分类号： G01N33/582 , C07F7/1856 , C07F9/65512 , C12Q1/34 , C12Q1/42 , G01N33/533 , C12Q2334/00 , Y10S435/968
摘要： Chemiluminescent electron-rich aryl-substituted 1,2-dioxetane compounds are disclosed in which the aryl group is poly-substituted with suitable electron-donating groups such that the light-emitting pattern of the molecule results in a very high luminescent count, thus providing for a sensitive and precise assay for haptens, analytes, polynucleotides and the like. These substituted aryl-containing 1,2-dioxetane compounds can be used as direct labels in an immunoassay or when derivatized with an appropriate leaving group, can be used as a substrate for a enzyme immunoassay. The unusual chemiluminescence of the compounds allows the timing of the luminescent reaction to be exactly controlled.
摘要翻译：公开了化学发光富电子的芳基取代的1,2-二氧杂环丁烷化合物，其中芳基被合适的给电子基团多取代，使得分子的发光图案导致非常高的发光计数，从而提供对于半抗原，分析物，多核苷酸等的敏感和精确的测定。这些取代的含芳基的1,2-二氧杂环丁烷化合物可以在免疫测定中用作直接标记，或者当用合适的离去基团衍生化时，可用作酶免疫测定的底物。化合物的不寻常的化学发光使得准确控制发光反应的时间。

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