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1. 发明授权

EP1049933B1 MEASUREMENT OF HYDRIDE USING CHEMILUMINESCENT ACRIDINIUM COMPOUNDS 有权
标题翻译：测量使用氢化物化学发光的吖啶
公开(公告)号：EP1049933B1
公开(公告)日：2005-09-14
申请号：EP99972738.1
申请日：1999-11-24
申请人： BAYER CORPORATION
发明人： SHARPE, David , NATRAJAN, Anand , JIANG, Qingping , PARSONS, George , LAW, Say-Jong
IPC分类号： G01N33/58 , C12Q1/00 , C12Q1/32 , C07D219/04 , C07D221/12 , C07D215/50
CPC分类号： C12Q1/008 , G01N33/581 , G01N33/582

2. 发明公开

EP1203091A1 CHEMILUMINESCENT SUBSTRATES OF HYDROLYTIC ENZYMES SUCH AS PHOSPHATASES 有权
标题翻译：水解酶如何磷酸酶的化学发光底物
公开(公告)号：EP1203091A1
公开(公告)日：2002-05-08
申请号：EP00950764.1
申请日：2000-07-27
申请人： Bayer Corporation
发明人： JIANG, Qingping , NATRAJAN, Anand , SHARPE, David, J. , WONG, Wen-Jee , LAW, Say-Jong
IPC分类号： C12Q1/42 , C07D219/06
CPC分类号： C07D491/10 , C07D219/04 , C07F9/64 , C12Q1/42 , C12Q2334/00
摘要： Chemiluminescent substrates of hydrolytic enzymes are disclosed having general Formula Lumi-M-P, where Lumi is a chemiluminescent moiety capable of producing light (a) by itself, (b) with MP attached and (c) with M attached, wherein the different properties of Lumi-M-P and Lumi-M allow them to be distinguished. Lumi includes, but is not limited to, acridinium compounds (e.g. acridinium esters, carboxyamides, thioesters and oxime esters), reduced forms thereof (e.g. acridans), and spiroacridan compounds. M is selected from oxygen, nitrogen and sulfur. P is a group that can be readily removed by hydrolytic enzymes to give Lumi-M and P. The hydrolytic enzyme can be phosphatase, glycosidase, peptidase, protease, esterase, sulfatase and guanidinobenzoatase.

3. 发明公开

EP0988551A2 CHEMILUMINESCENT ENERGY TRANSFER CONJUGATES AND THEIR USES AS LABELS IN BINDING ASSAYS 失效
标题翻译：化学发光能量转化偶联物及其作为MARKER结合剂在测试中
公开(公告)号：EP0988551A2
公开(公告)日：2000-03-29
申请号：EP98920688.3
申请日：1998-05-29
申请人： Bayer Corporation
发明人： JIANG, Qingping , XI, Jun , NATRAJAN, Anand , SHARPE, David , BAUMANN, Marcus , HILFIKER, Rolf , SCHMIDT, Erika , SENN, Paul , THOMMEN, Fritz , WALDNER, Adrian , ALDER, Alex , LAW, Say-Jong
IPC分类号： G01N33/58
CPC分类号： C09B15/00 , C09B11/04 , G01N33/533 , G01N33/542 , G01N33/582 , Y10S436/80 , Y10S436/816 , Y10S436/817
摘要： A new class of chemiluminescent acridinium or benzacridinium compounds is disclosed by virtue of forming an intramolecular energy transfer conjugate (ETC) between the acridinium or benzacridinium compound and a luminophore. A method of extending the emission wavelengths of acridinium or benzacridinium esters in order to further reduce or eliminate the emission spectral overlap between the parent polysubstituted aryl Acridinium Esters (DMAE) and Benzacridinium Esters (LEAE) is disclosed. The ETC's retain the unique desired properties of acridinium or benzacridinium compounds including complete light emission in very short period of time, monophasic emission spectrum, simplicity of triggering mechanism, ability of labeling the biological molecules of interest to form a tracer, and good stability. Additionally, the range of the emission spectrum of an acridinium or benzacridinium compound can now be shifted at will and at longer leap through the choice of a luminophore as the integral part of an ETC molecule. Disclosed are chemiluminescent labeled conjugates comprising an acridinium or benzacridinium moiety convalently attached to a luminophore via a spacer, said moiety further conjugated to a biological molecule of interest, wherein said spacer is of an appropriate length to allow the excited species generated from said moiety to transfer energy efficiently to said luminophore, resulting in the emission of light in the spectral region of said luminophore. Also disclosed are binding assays using said conjugates, test kits comprising said conjugates and methods of preparing the conjugates.

4. 发明公开

EP1049933A1 MEASUREMENT OF HYDRIDE USING CHEMILUMINESCENT ACRIDINIUM COMPOUNDS 有权
标题翻译：测量使用氢化物化学发光的吖啶
公开(公告)号：EP1049933A1
公开(公告)日：2000-11-08
申请号：EP99972738.1
申请日：1999-11-24
申请人： Bayer Corporation
发明人： SHARPE, David , NATRAJAN, Anand , JIANG, Qingping , PARSONS, George , LAW, Say-Jong
IPC分类号： G01N33/58 , C12Q1/00 , C12Q1/32 , C07D219/04 , C07D221/12 , C07D215/50
CPC分类号： C12Q1/008 , G01N33/581 , G01N33/582
摘要： The present invention discloses a method for the measurement of hydride using a chemiluminescent compound, such as an acridinium compound. The source of hydride for the reduction of acridinium compound may be of chemical or biochemical origin, or the result of enzymatic catalysis. The chemical source of hydride, might be NaBH4. A biochemical source of hydride might be that derived from NADH, or NADPH, while an enzymatic source would be the class of oxidoreductases termed dehydrogenases which convert NADH or NADPH from NAD or NADP. Among applications for acridinium compounds as chemiluminescent indicators of hydride are diagnostic assays using dehydrogenases as reagents, indicators, diagnostic markers or as labels. Ethanol, for example, might be detected with acridinium ester chemiluminescence through the reaction of alcohol dehydrogenase on ethanol, said reaction producing NADH. As a label, dehydrogenase might be used in an ELISA for the detection of a specific analyte with acridinium ester providing the signaling response.

5. 发明授权

EP0754178B1 NOVEL FUNCTIONALIZED HYDROPHILIC ACRIDINIUM ESTERS 失效
标题翻译：功能化的亲水性吖啶酯
公开(公告)号：EP0754178B1
公开(公告)日：2003-01-15
申请号：EP95913298.6
申请日：1995-04-06
申请人： Bayer Corporation
发明人： LAW, Say-Jong , SOTIRIOU-LEVENTIS, Chariklia , NATRAJAN, Anand , JIANG, Qingping , CONNOLLY, Peter, B. , KILROY, John, P. , MCCUDDEN, Constance, R. , TIRRELL, Stephen, M.
IPC分类号： C07D219/04 , G01N33/533 , G01N33/58 , C07J43/00
CPC分类号： C07D401/12 , C07D219/04 , C07F9/64 , C07J1/0011 , C07J1/0022 , C07J21/006 , C07J43/003 , C12Q1/6816 , G01N33/533 , G01N33/586 , C12Q2563/161 , C12Q2563/103
摘要： Novel acridinium esters that are useful, either alone or when incorporated into liposomes, as chemiluminescent agents in binding assays (e.g., immunoassays and gene probe assays) with improved sensitivity are disclosed. In addition, the synthesis of these esters and their use in assays for detecting an analyte is described. In particular, assays for testosterone and the Rubella virus are disclosed.

6. 发明公开

EP1104405A1 NEAR INFRARED CHEMILUMINESCENT ACRIDINIUM COMPOUNDS AND USES THEREOF 有权
标题翻译：中红外化学发光吖啶衍生物及其
公开(公告)号：EP1104405A1
公开(公告)日：2001-06-06
申请号：EP99941005.3
申请日：1999-08-10
申请人： Bayer Corporation
发明人： NATRAJAN, Anand , JIANG, Qingping , SHARPE, David , LAW, Say-Jong
IPC分类号： C07D219/04 , G01N33/58 , G01N33/533
CPC分类号： G01N33/582 , C07D219/04 , Y10S436/80 , Y10S436/815 , Y10S436/817 , Y10S530/812 , Y10T436/13
摘要： Our results thus identify two sets of necessary and sufficient criteria for observing long-wavelength emission from acridinium compounds: Set A: (a) the creation of an extended conjugation system by the attachment of appropriate functional groups on the acridinium nucleus (electronic requirement). (b) Coplanarity of the attached functional group and the acridone moiety during light emission (geometry requirement). (c) Said functional group must consist of at least one aromatic ring and one electron-donating atom or group with an extra pair of electrons which can readily delocalize into the extended π system to which the heteroatom is directly attached or built into, and establish stable extended resonance with the electron-withdrawing carbonyl moiety of the light emitting acridone. Such electron-donating atom or group that exists in the form of an anion has particularly strong effect to further the bathochromic shift of the emission wavelength. Set B: (a) A direct attachment at one or more of positions C-2, C-4, C-5, or C-7 of the acridinium nucleus, of electron-donating atoms or groups having extra pair(s) of electrons. The electron-donating entities can be the same or different if more than one electron-donating entity is used. Such electron-donating atom or group that exists in the form of an anion has particularly strong effect to further the bathochromic shift of the emission wavelenth. For molecules for which the above criteria are met such as LEAE, 3-HS-DMAE, and 2-hydroxy-DMAE long wavelength-emission exceeding 500 nm and reaching into NIR region is expected and observed. Preferably, the utility of an NIR-AC of comparable quantum yield as the conventional acridinium compounds goes hand-in-hand with the employment of a luminescence detector of good to excellent detection efficiency. To achieve efficient NIR signal detection and facilitate the performing of diagnostic assays, a further objective of the present invention is the advance of a concept and the realization of substituting a state-of-the-art charge-coupled device (CCD) detector for the red-insensitive photomultiplier tube (PMT) in a conventional fully or semi-automatic analyzer such as MLA-II of Chiron Diagnostics, Walpole, MA.

7. 发明授权

EP1203091B1 CHEMILUMINESCENT SUBSTRATES OF HYDROLYTIC ENZYMES SUCH AS PHOSPHATASES 有权
标题翻译：水解酶如何磷酸酶的化学发光底物
公开(公告)号：EP1203091B1
公开(公告)日：2005-03-16
申请号：EP00950764.1
申请日：2000-07-27
申请人： Bayer Corporation
发明人： JIANG, Qingping , NATRAJAN, Anand , SHARPE, David, J. , WONG, Wen-Jee , LAW, Say-Jong
IPC分类号： C12Q1/42 , C07D219/06
CPC分类号： C07D491/10 , C07D219/04 , C07F9/64 , C12Q1/42 , C12Q2334/00

8. 发明授权

EP0988551B1 CHEMILUMINESCENT ENERGY TRANSFER CONJUGATES AND THEIR USES AS LABELS IN BINDING ASSAYS 失效
标题翻译：化学发光能量转化偶联物及其作为MARKER结合剂在测试中
公开(公告)号：EP0988551B1
公开(公告)日：2003-09-10
申请号：EP98920688.3
申请日：1998-05-29
申请人： Bayer Corporation
发明人： JIANG, Qingping , XI, Jun , NATRAJAN, Anand , SHARPE, David , BAUMANN, Marcus , HILFIKER, Rolf , SCHMIDT, Erika , SENN, Paul , THOMMEN, Fritz , WALDNER, Adrian , ALDER, Alex , LAW, Say-Jong
IPC分类号： G01N33/58
CPC分类号： C09B15/00 , C09B11/04 , G01N33/533 , G01N33/542 , G01N33/582 , Y10S436/80 , Y10S436/816 , Y10S436/817
摘要： A new class of chemiluminescent acridinium or benzacridinium compounds is disclosed by virtue of forming an intramolecular energy transfer conjugate (ETC) between the acridinium or benzacridinium compound and a luminophore. A method of extending the emission wavelengths of acridinium or benzacridinium esters in order to further reduce or eliminate the emission spectral overlap between the parent polysubstituted aryl Acridinium Esters (DMAE) and Benzacridinium Esters (LEAE) is disclosed. The ETC's retain the unique desired properties of acridinium or benzacridinium compounds including complete light emission in very short period of time, monophasic emission spectrum, simplicity of triggering mechanism, ability of labeling the biological molecules of interest to form a tracer, and good stability. Additionally, the range of the emission spectrum of an acridinium or benzacridinium compound can now be shifted at will and at longer leap through the choice of a luminophore as the integral part of an ETC molecule. Disclosed are chemiluminescent labeled conjugates comprising an acridinium or benzacridinium moiety convalently attached to a luminophore via a spacer, said moiety further conjugated to a biological molecule of interest, wherein said spacer is of an appropriate length to allow the excited species generated from said moiety to transfer energy efficiently to said luminophore, resulting in the emission of light in the spectral region of said luminophore. Also disclosed are binding assays using said conjugates, test kits comprising said conjugates and methods of preparing the conjugates.

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