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    • 51. 发明授权
    • Fluorescence quenching with immunological pairs in immunoassays
    • 荧光猝灭与免疫对免疫测定
    • US4174384A
    • 1979-11-13
    • US731255
    • 1976-10-12
    • Edwin F. UllmanMoshe Schwarzberg
    • Edwin F. UllmanMoshe Schwarzberg
    • G01N33/542G01N21/38C07G7/00G01N31/00G01N33/16
    • G01N33/542Y10S435/968Y10S436/80Y10S436/816Y10S530/806
    • Immunoassays are provided employing antibodies and a fluorescer-quencher (F-Q) chromophoric pair, wherein one or both of the chromophoric pair are bonded to antibodies. Depending on the particular ligand of interest, various reagent combinations can be employed, where the amount of quenching is directly related to the amount of ligand present in the assay medium.In carrying out the assay, the unknown and antibody specific for the ligand of interest to which is bound one of the F-Q pair, are combined in an aqueous buffered medium. Depending on the protocol, different assay reagents are employed in the aqueous buffered medium: (1) ligand analog bonded to the other of the F-Q pair; (2) antibodies specific for the ligand to which is bound the other of the F-Q pair or; finally, (3) a combination of a plurality of ligands bonded together through linking groups to a hub molecule, usually a polymer, in combination with antibody bound to the other of the F-Q pair. The composition is irradiated with light at a wavelength, absorbed by the fluorescing molecule and the amount of fluorescence determined. By employing appropriate standards, the presence and amount of the ligand can be determined.
    • 使用抗体和荧光猝灭剂(F-Q)发色对提供免疫测定,其中发色对中的一个或两个与抗体结合。 根据感兴趣的具体配体,可以使用各种试剂组合,其中猝灭量与测定培养基中存在的配体的量直接相关。 在进行测定时,将结合F-Q对之一的目的配体的未知和抗体结合在含水缓冲介质中。 根据方案,在水性缓冲介质中使用不同的测定试剂:(1)与F-Q对中的另一个键合的配体类似物; (2)对与F-Q对中的另一个结合的配体特异的抗体; 最后,(3)通过连接基团连接在一起的多个配体与轮毂分子(通常为聚合物)结合的F-Q对另一个结合的抗体的组合。 用波长的光照射组合物,由荧光分子吸收并测定荧光量。 通过采用适当的标准,可以确定配体的存在和量。
    • 53. 发明授权
    • Fluorescence quenching with immunological pairs in immunoassays
    • 荧光猝灭与免疫对免疫测定
    • US3996345A
    • 1976-12-07
    • US591386
    • 1975-06-30
    • Edwin F. UllmanMoshe Schwarzberg
    • Edwin F. UllmanMoshe Schwarzberg
    • G01N33/18G01N33/542G01N21/00G01N33/16
    • G01N33/542G01N33/1833Y10S435/968Y10S436/80Y10S436/815Y10S436/816Y10S436/817
    • Immunoassays employing antibodies and a fluorescer-quencher (F-Q) chromophoric pair, wherein one or both of the chromophoric pair are bonded to antibodies. Depending on the particular ligand of interest, various reagent combinations can be employed, where the amount of quenching is directly related to the amount of ligand present in the assay medium. In carrying out the assay, the unknown and antibody specific for the ligand of interest to which is bound one of the F-Q pair, are combined in an aqueous buffered medium. Depending on the protocol, different assay reagents are employed in the aqueous buffered medium: (1) ligand analog bonded to the other of the F-Q pair; (2) antibodies specific for the ligand to which is bound the other of the F-Q pair or; finally, (3) a combination of a plurality of ligands bonded together through linking groups to a hub molecule, usually a polymer, in combination with antibody bound to the other of the F-Q pair. The composition is irradiated with light at a wavelength, absorbed by the fluorescing molecule and the amount of fluorescence determined. By employing appropriate standards, the presence and amount of the ligand can be determined.
    • 使用抗体和荧光猝灭剂(F-Q)发色对的免疫测定法,其中发色对中的一个或两个与抗体结合。 根据感兴趣的具体配体,可以使用各种试剂组合,其中猝灭量与测定培养基中存在的配体的量直接相关。 在进行测定时,将结合F-Q对之一的目的配体的未知和抗体结合在含水缓冲介质中。 根据方案,在水性缓冲介质中使用不同的测定试剂:(1)与F-Q对中的另一个键合的配体类似物; (2)对与F-Q对中的另一个结合的配体特异的抗体; 最后,(3)通过连接基团连接在一起的多个配体与轮毂分子(通常为聚合物)结合的F-Q对另一个结合的抗体的组合。 用波长的光照射组合物,由荧光分子吸收并测定荧光量。 通过采用适当的标准,可以确定配体的存在和量。
    • 54. 发明授权
    • Methods for single nucleotide polymorphism detection
    • 单核苷酸多态性检测方法
    • US06632606B1
    • 2003-10-14
    • US09592053
    • 2000-06-12
    • Edwin F. UllmanSharat Singh
    • Edwin F. UllmanSharat Singh
    • C12Q168
    • C12Q1/6827C12Q1/6834C12Q2565/519C12Q2535/125C12Q2563/179C12Q2563/131
    • Methods and compositions are provided for determining large numbers of single nucleotide polymorphisms in target DNA employing particles having (1) primers complementary to sequences in the target DNA where the next succeeding 3′-nucleotide is a potential single nucleotide polymorphism and coding composition members, where the members are unique for each primer, and (2) differentially labeled terminating nucleotides, where the label permits separation of the terminating nucleotides. Desirably the particles are separated into groups having a common prevalent next succeeding nucleotide. The particles and target DNA are combined under nucleotide extending conditions, the particles separated into groups in accordance with the terminating nucleotide and the coding members identified, so that one knows the sequence and the single nucleotide polymorphism. Various protocols are provided for the determination.
    • 提供了用于使用具有(1)与目标DNA中的序列互补的引物,其中下一个后续的3'-核苷酸是潜在的单核苷酸多态性和编码组成成员的粒子来确定靶DNA中大量单核苷酸多态性的方法和组合物,其中 成员对于每个引物是独特的,和(2)差异标记的终止核苷酸,其中标记允许分离终止的核苷酸。 理想地,将颗粒分离成具有普通的下一个后续核苷酸的基团。 颗粒和靶DNA在核苷酸延伸条件下合并,根据终止的核苷酸和鉴定的编码成员将颗粒分成组,以便知道序列和单核苷酸多态性。 提供各种协议用于确定。
    • 56. 发明授权
    • Receptors for immune complexes
    • 免疫复合物受体
    • US06326159B1
    • 2001-12-04
    • US08300572
    • 1994-09-02
    • Edwin F. UllmanJohn JeleskoMarcel R. PirioThomas D. Kempe
    • Edwin F. UllmanJohn JeleskoMarcel R. PirioThomas D. Kempe
    • C07K1600
    • C07K16/42G01N33/564G01N33/948Y10S435/975Y10S436/80Y10S436/804Y10S436/805Y10S436/808Y10S436/815Y10S436/817Y10S530/808
    • Receptors are disclosed that are antibodies that exhibit a binding affinity for an immune complex of a monoepitopic antigen and an antibody for such antigen that is substantially greater than the binding affinity for the monoepitopic antigen or the antibody for the monoepitopic antigen apart from the immune complex. Normally, the monoepitopic antigen has a molecular weight less than 1500 and is an organic compound. The antibodies of the present invention find use in a method for determining a monoepitopic antigen in a sample suspected of containing such antigen. The method comprises forming an immune sandwich complex comprising the monoepitopic antigen or an analog thereof, a first monoclonal antibody that binds to the monoepitopic antigen, and a second monoclonal antibody that is an antibody of the present invention and detecting the immune sandwich complex. Compositions of matter and kits for use in conducting an assay in accordance with the invention as well as methods for producing the above receptors are also disclosed.
    • 公开了受体,其是对单表皮抗原和这种抗原的抗体的免疫复合物具有结合亲和力的抗体,其显着大于除了免疫复合物之外的单表位抗原或单表位抗原的抗体的结合亲和力。 通常,单表位抗原的分子量小于1500,是有机化合物。 本发明的抗体用于确定疑似含有该抗原的样品中的单表位抗原的方法。 该方法包括形成包含单表皮抗原或其类似物的免疫三明治复合物,与单表位抗原结合的第一单克隆抗体和作为本发明抗体的第二单克隆抗体,并检测免疫三明治复合物。 还公开了用于进行根据本发明的测定的物质和试剂盒的组合物以及用于产生上述受体的方法。
    • 59. 发明授权
    • Detection of nucleic acids by target-catalyzed product formation
    • 通过靶催化产物形成检测核酸
    • US6121001A
    • 2000-09-19
    • US440363
    • 1999-11-15
    • Linda M. WesternSamuel J. RoseEdwin F. Ullman
    • Linda M. WesternSamuel J. RoseEdwin F. Ullman
    • C12Q1/68C12P19/34C12Q1/44
    • C12Q1/689C12Q1/682C12Q1/6823
    • A method is disclosed for modifying an oligonucleotide, which method has application to the detection of a polynucleotide analyte. An oligonucleotide is reversibly hybridized with a polynucleotide, for example, a polynucleotide analyte, in the presence of a 5'-nuclease under isothermal conditions. The polynucleotide analyte serves as a recognition element to enable a 5'-nuclease to cleave the oligonucleotide to provide (i) a first fragment that is substantially non-hybridizable to the polynucleotide analyte and (ii) a second fragment that lies 3' of the first fragment (in the intact oligonucleotide) and is substantially hybridizable to the polynucleotide analyte. At least a 100-fold molar excess of the first fragment and/or the second fragment are obtained relative to the molar amount of the polynucleotide analyte. The presence of the first fragment and/or the second fragment is detected, the presence thereof indicating the presence of the polynucleotide analyte. The method has particular application to the detection of a polynucleotide analyte such as DNA. Kits for conducting methods in accordance with the present invention are also disclosed.
    • 公开了一种修饰寡核苷酸的方法,该方法可用于检测多核苷酸分析物。 在等温条件下,在5'-核酸酶的存在下,寡核苷酸与多核苷酸例如多核苷酸分析物可逆地杂交。 多核苷酸分析物用作识别元件,使得5'-核酸酶能够切割寡核苷酸,以提供(i)与多核苷酸分析物基本上不可杂交的第一片段和(ii)位于3'末端的第3个片段 第一片段(在完整寡核苷酸中)并且与多核苷酸分析物基本上可杂交。 相对于多核苷酸分析物的摩尔量,获得至少100倍摩尔过量的第一片段和/或第二片段。 检测到第一片段和/或第二片段的存在,其存在表明多核苷酸分析物的存在。 该方法特别适用于多核苷酸分析物如DNA的检测。 还公开了用于根据本发明的方法的套件。
    • 60. 发明授权
    • Oligonucleotide modification, signal amplification, and nucleic acid
detection by target-catalyzed product formation
    • 通过靶催化产物形成的寡核苷酸修饰,信号扩增和核酸检测
    • US6110677A
    • 2000-08-29
    • US15949
    • 1998-01-30
    • Linda M. WesternSamuel J. RoseEdwin F. Ullman
    • Linda M. WesternSamuel J. RoseEdwin F. Ullman
    • C12Q1/68C12P19/34C12Q1/44C12Q1/48
    • C12Q1/689C12Q1/682C12Q1/6823
    • A method is disclosed for modifying an oligonucleotide, which method has application to the detection of a polynucleotide analyte. An oligonucleotide is reversibly hybridized with a polynucleotide, for example, a polynucleotide analyte, in the presence of a 5'-nuclease under isothermal conditions. The polynucleotide analyte serves as a recognition element to enable a 5'-nuclease to cleave the oligonucleotide to provide (i) a first fragment that is substantially non-hybridizable to the polynucleotide analyte and (ii) a second fragment that lies 3' of the first fragment (in the intact oligonucleotide) and is substantially hybridizable to the polynucleotide analyte. At least a 100-fold molar excess of the first fragment and/or the second fragment are obtained relative to the molar amount of the polynucleotide analyte. The presence of the first fragment and/or the second fragment is detected, the presence thereof indicating the presence of the polynucleotide analyte. The method has particular application to the detection of a polynucleotide analyte such as DNA. Kits for conducting methods in accordance with the present invention are also disclosed.
    • 公开了一种修饰寡核苷酸的方法,该方法可用于检测多核苷酸分析物。 在等温条件下,在5'-核酸酶的存在下,寡核苷酸与多核苷酸例如多核苷酸分析物可逆地杂交。 多核苷酸分析物用作识别元件,使得5'-核酸酶能够切割寡核苷酸,以提供(i)与多核苷酸分析物基本上不可杂交的第一片段和(ii)位于3'末端的第3个片段 第一片段(在完整寡核苷酸中)并且与多核苷酸分析物基本上可杂交。 相对于多核苷酸分析物的摩尔量,获得至少100倍摩尔过量的第一片段和/或第二片段。 检测到第一片段和/或第二片段的存在,其存在表明多核苷酸分析物的存在。 该方法特别适用于多核苷酸分析物如DNA的检测。 还公开了用于根据本发明的方法的套件。