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1. 发明申请

WO1997027332A1 METHOD FOR DETECTION OF DRUG-INDUCED MUTATIONS IN THE REVERSE TRANSCRIPTASE GENE 审中-公开
标题翻译：用于检测逆转录酶基因中药物诱导突变的方法
公开(公告)号：WO1997027332A1
公开(公告)日：1997-07-31
申请号：PCT/EP1997000211
申请日：1997-01-17
申请人： INNOGENETICS N.V. , STUYVER, Lieven , LOUWAGIE, Joost , ROSSAU, Rudi
发明人： INNOGENETICS N.V.
IPC分类号： C12Q01/70
CPC分类号： C12Q1/703
摘要： The present invention relates to a method for the rapid and reliable detection of drug-induced mutations in the reverse transcriptase gene allowing the simultaneous characterization of a range of codons involved in drug resistance using specific sets of probes optimized to function together in a reverse-hybridization assay. More particularly, the present invention relates to a method for determining the susceptibility to antiviral drugs of HIV strains present in a biological sample, comprising: (i) if need be releasing, isolating or concentrating the polynucleic acids present in the sample; (ii) if need be amplifying the relevant part of the reverse transcriptase genes present in said sample with at least one suitable primer pair; (iii) hybridizing the polynucleic acids of step (i) or (ii) with at least two RT gene probes hybridizing specifically to one or more target sequences with said probes being applied to known locations on a solid support and with said probes being capable of simultaneously hybridizing to their respective target regions under appropriate hybridization and wash conditions allowing the detection of homologous targets, or said probes hybridizing specifically with a sequence complementary to any of said target sequences, or a sequence wherein T is replaced by U; (iv) detecting the hybrids formed in step (iii); (v) inferring the nucleotide sequence at the codons of interest and/or the amino acids of the codons of interest and/or antiviral drug resistance spectrum, and possibly the type of HIV isolates involved from the differential hybridization signal(s) obtained in step (iv).
摘要翻译：本发明涉及用于快速和可靠地检测逆转录酶基因中的药物诱发突变的方法，其允许使用经优化以在反向杂交中一起起作用的特定的探针组来同时表征涉及耐药性的一系列密码子检测。更具体地说，本发明涉及确定存在于生物样品中的HIV病毒抗病毒药物易感性的方法，其包括：（i）如果需要释放，分离或浓缩样品中存在的多核酸; （ii）如果需要用至少一个合适的引物对扩增所述样品中存在的逆转录酶基因的相关部分; （iii）将步骤（i）或（ii）中的多核苷酸与至少两个与一个或多个靶序列特异性杂交的RT基因探针杂交，所述探针被施加到固体支持物上的已知位置，并且所述探针能够在适当的杂交和洗涤条件下同时与其各自的靶区域杂交，允许检测同源靶标，或所述探针与与任何所述靶序列互补的序列特异性杂交，或其中T被U替代的序列; （iv）检测步骤（iii）中形成的杂交体; （v）推断感兴趣的密码子和/或感兴趣的密码子的氨基酸和/或抗病毒药物抗性谱的核苷酸序列，以及可能的步骤中获得的差异杂交信号所涉及的HIV分离物的类型（ⅳ）。

2. 发明申请

WO1994012670A2 PROCESS FOR TYPING OF HCV ISOLATES 审中-公开
标题翻译：分离型HCV的方法
公开(公告)号：WO1994012670A2
公开(公告)日：1994-06-09
申请号：PCT/EP1993003325
申请日：1993-11-26
申请人： N.V. INNOGENETICS S.A. , MAERTENS, Geert , STUYVER, Lieven , ROSSAU, Rudi , VAN HEUVERSWYN, Hugo
发明人： N.V. INNOGENETICS S.A.
IPC分类号： C12Q01/70
CPC分类号： C12Q1/707 , C12Q1/6834 , C12Q2563/131 , C12Q2545/101 , C12Q2525/101 , C12Q2531/113
摘要： The invention relates to a process for genotyping any HCV isolate present in a biological sample, previously identified as being HCV positive, and for classifying said isolate according to the percentage of homology with other HCV isolates, comprising the steps of: contacting said sample in which the ribonucleotides or deoxyribonucleotides have been made accessible, if need be, under suitable denaturation, with at least one probe from about 10 to about 40 nucleotides, with said probe being liable to hybridize to a region being in the domain extending from nucleotide at position -291 to nucleotide at position -66 of the 5' untranslated region of one of the HCV isolates represented by their cDNA sequences, with said numbering of position beginning with the first ATG codon of the open reading frame encoding the HCV polyprotein, or with said probe being complementary to the above-defined probes; detecting the complexes possibly formed between said probe and the nucleotide sequence of the HCV isolate to be identified.
摘要翻译：本发明涉及用于对先前鉴定为HCV阳性的生物样品中存在的任何HCV分离物进行基因分型的方法，以及根据与其它HCV分离株的同源性百分比对所述分离物进行分类的方法，包括以下步骤：如果需要的话，核糖核苷酸或脱氧核糖核苷酸可以在合适的变性下与至少一个约10至约40个核苷酸的探针接触，所述探针易于与位置延伸的结构域延伸的区域杂交。 291到由其cDNA序列表示的HCV分离物之一的5'非翻译区的-66位的核苷酸，其中所述编号的位置开始于编码HCV多蛋白的开放阅读框的第一个ATG密码子，或与所述探针与上述探针互补; 检测可能形成在所述探针和待鉴定的HCV分离物的核苷酸序列之间的复合物。

3. 发明申请

WO0073499A3 NUCLEIC ACID PROBES AND METHODS FOR DETECTING CLINICALLY IMPORTANT FUNGAL PATHOGENS 审中-公开
标题翻译：用于检测临床重要真菌病原体的核酸探针和方法
公开(公告)号：WO0073499A3
公开(公告)日：2001-08-09
申请号：PCT/EP0004714
申请日：2000-05-24
申请人： INNOGENETICS NV , ENTPR IE TRD AS BIORESEARCH IE , SMITH TERRY , MAHER MAJELLA , MARTIN CARA , JANNES GEERT , ROSSAU RUDI , WEIDE MARJO V D
发明人： SMITH TERRY , MAHER MAJELLA , MARTIN CARA , JANNES GEERT , ROSSAU RUDI , VAN DER WEIDE MARJO
IPC分类号： C12N15/09 , C12Q1/68
CPC分类号： C12Q1/6895
摘要： The current invention relates to the field of detection and identification of clinically important fungi. More particularly, the present invention relates to species specific probes originating from the Internal Transcribed Spacer (ITS) region of rDNA for the detection of fungal species such as Candida albicans, Candida parapsilosis, Candida tropicalis, Candida kefyr, Candida krusei, Candida glabrata, Candida dubliniensis, Aspergillus flavus, Aspergillus versicolor, Aspergillus nidulans, Aspergillus fumigatus, Cryptococcus neoformans and Pneumocystis carinii in clinical samples, and methods using said probes.
摘要翻译：本发明涉及临床重要真菌的检测和鉴定领域。更具体地说，本发明涉及源自rDNA的内部转录间隔区（ITS）区域的物种特异性探针，用于检测真菌物种，例如白色念珠菌，披膜假丝酵母，热带假丝酵母，假丝酵母，假丝酵母，念珠菌玻璃假丝酵母（Candida dubliniensis），黄曲霉（Aspergillus flavus），白曲霉（Aspergillus versicolor），构巢曲霉（Aspergillus nodulans），烟曲霉（Aspergillus fumigatus），新型隐球酵母（Cryptococcus neoformans）和卡氏肺囊虫（Pneumocystis carinii），以及使用所述探针的方法。

4. 发明申请

WO1997021094A1 IMPEDIMETRIC DETECTION SYSTEM AND METHOD OF PRODUCTION THEREOF 审中-公开
标题翻译：预防性检测系统及其生产方法
公开(公告)号：WO1997021094A1
公开(公告)日：1997-06-12
申请号：PCT/EP1996005290
申请日：1996-11-29
申请人： INNOGENETICS N.V. , INTERUNIVERSITAIR MICRO-ELECTRONICA CENTRUM (IMEC) , VAN GERWEN, Peter , BAERT, Kris , ROSSAU, Rudi
发明人： INNOGENETICS N.V. , INTERUNIVERSITAIR MICRO-ELECTRONICA CENTRUM (IMEC)
IPC分类号： G01N27/22
CPC分类号： C12Q1/6816 , C12Q1/6825 , G01N27/3276 , G01N33/5438 , C12Q2565/607 , C12Q2565/501
摘要： A sensor for identifying molecular structures within a sample solution is disclosed. The sensor comprises an insulating layer with a plurality of interspaced channels therein having essentially the same direction. Said channels have a bottom and at least two opposite side-walls along said direction. The channels furthermore have submicron dimensions. A metal coating is applied on one of said two opposite side-walls of essentially each channel and on top of the dielectric layer inbetween said channels thereby forming an impedimetric device with said sample solution within and between adjacent channels. Probes for specifically binding to said molecular structures can be applied, said probes being applied to either the insulating part of the channels (said bottom and the other side-wall of said channels), or to the surface of the electrodes or both, the insulating part of the channels and the surface of the electrodes. Furthermore, means are provided for applying a voltage on the metal coatings; and means for measuring the impedance inbetween the electrodes. Furthermore, a method of fabricating a sensor for identifying molecular structures within a sample solution is disclosed. This method comprises the steps of forming a plurality of interspaced channels in an insulating layer, said channels having essentially the same direction, said channels having a bottom and at least two opposite side-walls along said direction; depositing a metal layer on said insulating layer while aligning said insulating layer with respect to the metal deposition source such that the bottom of said canals and the side-walls of said canals along the deposition direction are shadowed and not covered by metal to thereby form an impedimetric device with said sample solution within and between adjacent channels; and applying probes for binding to said molecular structures, said probes being applied to either the insulating part of the channels (said bottom and the other side-wall of said channels), or to the surface of the electrodes or both, the insulating part of the channels and the surface of the electrodes, facing the deposition direction.
摘要翻译：公开了一种用于识别样品溶液内的分子结构的传感器。传感器包括其中具有基本上相同方向的多个间隔通道的绝缘层。所述通道具有沿着所述方向的底部和至少两个相对的侧壁。通道还具有亚微米尺寸。金属涂层施加在基本上每个通道的所述两个相对的侧壁中的一个上，并且位于所述通道之间的电介质层的顶部上，从而形成具有所述样品溶液在相邻通道内和相邻通道之间的阻抗测量装置。可以应用用于特异性结合所述分子结构的探针，所述探针被施加到通道的绝缘部分（所述通道的所述底部和另一侧壁）或电极或两者的表面，绝缘通道的一部分和电极的表面。此外，提供了用于在金属涂层上施加电压的装置; 以及用于测量电极之间的阻抗的装置。此外，公开了一种制造用于识别样品溶液内的分子结构的传感器的方法。该方法包括以下步骤：在绝缘层中形成多个间隔通道，所述通道具有基本相同的方向，所述通道具有沿着所述方向的底部和至少两个相对的侧壁; 在所述绝缘层上沉积金属层，同时相对于金属沉积源对准所述绝缘层，使得沿着沉积方向的所述运河的底部和所述运河的侧壁被遮蔽并且不被金属覆盖，从而形成阻抗测量装置，其中所述样品溶液在相邻通道内和之间; 以及施加用于结合到所述分子结构的探针，所述探针被施加到通道的绝缘部分（所述通道的所述底部和另一侧壁）或电极或两者的表面，绝缘部分电极的通道和表面，面向沉积方向。

5. 发明申请

WO1996000298A1 SIMULTANEOUS DETECTION, IDENTIFICATION AND DIFFERENTIATION OF EUBACTERIAL TAXA USING A HYBRIDIZATION ASSAY 审中-公开
标题翻译：使用杂交测定法同时检测，鉴定和鉴定非特异性TAXA
公开(公告)号：WO1996000298A1
公开(公告)日：1996-01-04
申请号：PCT/EP1995002452
申请日：1995-06-23
申请人： INNOGENETICS N.V. , JANNES, Geert , ROSSAU, Rudi , VAN HEUVERSWYN, Hugo
发明人： INNOGENETICS N.V.
IPC分类号： C12Q01/68
CPC分类号： C12Q1/689 , C12Q1/6888 , C12Q2600/16
摘要： The present invention relates to a method for detection and identification of at least one microorganism, or for the simultaneous detection of several microorganisms in a sample, comprising the steps of: (i) if need be releasing, isolating or concentrating the polynucleic acids present in the sample; (ii) if need be amplifying the 16S-23S rRNA spacer region, or a part of it, with at least one suitable primer pair; (iii) hybridizing the polynucleic acids of step (i) or (ii) with at least one and preferably more than one of the spacer probes as mentioned in table 1a or equivalents of thereof, under the appropriate hybridization and wash conditions, and/or with a taxon-specific probe derived from any of the spacer sequences as represented in figs. 1-103 under the same hybridization and wash conditions; (iv) detecting the hybrids formed in step (iii) with each of the probes used under appropriate hybridization and wash conditions; (v) identification of the microorganism(s) present in the sample from the differential hybridization signals obtained in step (iv).
摘要翻译：本发明涉及用于检测和鉴定至少一种微生物或同时检测样品中几种微生物的方法，包括以下步骤：（i）如果需要释放，分离或浓缩存在于例子; （ii）如果需要用至少一个合适的引物对扩增16S-23S rRNA间隔区或其一部分; （iii）在合适的杂交和洗涤条件下，将步骤（i）或（ii）的多核酸与表1a或其等同物中所提及的至少一种并优选多于一种的间隔探针杂交，和/或具有从图中所示的任何间隔序列衍生的分类群特异性探针。 1-103在相同的杂交和洗涤条件下; （iv）在适当的杂交和洗涤条件下使用每种探针检测在步骤（iii）中形成的杂交体; （v）从步骤（iv）中获得的差异杂交信号鉴定样品中存在的微生物。

6. 发明申请

WO2004053148A1 METHOD FOR THE DETECTION OF PATHOGENIC GRAM POSITIVE BACTERIA FROM THE GENERA STAPHYLOCOCCUS, ENTEROCOCCUS AND STREPTOCOCCUS 审中-公开
标题翻译：用于从致病菌，肠杆菌和结肠癌中检测病原性阳性细菌的方法
公开(公告)号：WO2004053148A1
公开(公告)日：2004-06-24
申请号：PCT/EP2003/013545
申请日：2003-12-02
申请人： ROCHE DIAGNOSTICS GMBH , F. HOFFMANN-LA ROCHE AG , INNOGENETICS N.V. , HABERHAUSEN, Gerd , EMRICH, Thomas , ROSSAU, Rudi , JANNES, Geert , DE VOS, Daniel
发明人： HABERHAUSEN, Gerd , EMRICH, Thomas , ROSSAU, Rudi , JANNES, Geert , DE VOS, Daniel
IPC分类号： C12Q1/14
CPC分类号： C12Q1/689 , C12Q1/04 , C12Q1/14 , C12Q1/6851 , G01N2333/31 , G01N2333/315
摘要： The present invention is directed to a method for identification of a Gram positive pathogenic bacterium comprising (a) an amplification step with at least a first set of amplification primers capable of amplifying a preselected nucleic acid sequence region from a first predetermined sub-group of pathogenic Gram positive bacteria, (ab) a detection step with at least a first hybridization reagent capable of specifically detecting a preselected nucleic acid sequence region from said first predetermined sub-group of pathogenic Gram positive bacteria, said detection step comprising steps (aba) monitoring, whether hybridization has occurred at a preselected temperature, said occurrence of hybridization being indicative for at least the genus of the pathogenic organism present in the sample, and (abb) monitoring temperature dependence of hybridization, said temperature dependence being indicative for at least the species of said pathogenic Gram positive bacterium.
摘要翻译：本发明涉及用于鉴定革兰氏阳性致病菌的方法，其包括（a）扩增步骤，所述扩增步骤具有至少第一组扩增引物，所述第一组扩增引物能够从病原体的第一预定亚组扩增预选的核酸序列区革兰氏阳性菌，（ab）具有至少第一杂交试剂的检测步骤，所述第一杂交试剂能够特异性检测来自所述第一预定的病原性革兰氏阳性细菌亚组的预选核酸序列区，所述检测步骤包括步骤（aba）是否在预选温度下进行杂交，所述杂交的发生指示至少存在于样品中的病原生物的属，以及（abb）监测杂交的温度依赖性，所述温度依赖性至少指示所述致病性革兰氏阳性菌。

7. 发明申请

WO9954496A3 METHOD FOR TYPING OF HLA ALLELES 审中-公开
标题翻译： HLA ALLELES型方法
公开(公告)号：WO9954496A3
公开(公告)日：2000-03-02
申请号：PCT/EP9902614
申请日：1999-04-19
申请人： INNOGENETICS NV , CANCK ILSE DE , MERSCH GUY , ROSSAU RUDI
发明人： DE CANCK ILSE , MERSCH GUY , ROSSAU RUDI
IPC分类号： C07K14/705 , C07K14/74 , C12Q1/68
CPC分类号： C12Q1/6881 , C07K14/70539 , C12Q2600/156 , C12Q2600/16
摘要： The present invention relates to the typing of HLA alleles. The sequence of exon 2 and exon 3 of the alleles HLA-B*3913, HLA-B*1406 and HLA-B*51 new and of exon 2 of the alleles HLA-DRB1*0820, HLA-DRB1*04 new and HLA-DRB4*01 new are disclosed. The present invention relates to methods for typing of said alleles. According to a preferred embodiment, said typing comprises the following steps: i) amplifying a relevant fragment of said alleles using at least one suitable pair of primers; ii) hybridizing the amplification product of step i) to at least one probe that specifically hybridizes to a target region comprising one or more polymorphic nucleotides in said relevant fragment; iii) determining from the result of step ii) the absence or presence of said alleles in the sample. The present invention further provides primers and probes to be used in said methods for typing. A diagnostic kit comprising said primers and probes is also part of the present invention.
摘要翻译：本发明涉及HLA等位基因的分型。等位基因HLA-DRB1 * 0820，HLA-DRB1 * 04新和HLA的等位基因HLA-B * 3913，HLA-B * 1406和HLA-B * 51新和外显子2的外显子2和外显子3的序列 -DRB4 * 01新发布。本发明涉及所述等位基因的分型方法。根据优选实施方案，所述分型包括以下步骤：i）使用至少一对合适的引物扩增所述等位基因的相关片段; ii）将步骤i）的扩增产物杂交至至少一种与所述相关片段中包含一个或多个多核苷酸的靶区域特异性杂交的探针; iii）从步骤ii）的结果确定样品中不存在或存在所述等位基因。本发明还提供了用于所述打字方法的引物和探针。包括所述引物和探针的诊断试剂盒也是本发明的一部分。

8. 发明申请

WO1997040193A3 METHOD FOR TYPING AND DETECTING HBV 审中-公开
公开(公告)号：WO1997040193A3
公开(公告)日：1997-10-30
申请号：PCT/EP1997002002
申请日：1997-04-21
申请人： INNOGENETICS N.V. , STUYVER, Lieven , ROSSAU, Rudi , MAERTENS, Geert
发明人： INNOGENETICS N.V.
IPC分类号： C12Q01/70

9. 发明申请

WO9740193A2 METHOD FOR TYPING AND DETECTING HBV 审中-公开
标题翻译： HBV的筛选和检测方法
公开(公告)号：WO9740193A2
公开(公告)日：1997-10-30
申请号：PCT/EP9702002
申请日：1997-04-21
申请人： INNOGENETICS NV , STUYVER LIEVEN , ROSSAU RUDI , MAERTENS GEERT
发明人： STUYVER LIEVEN , ROSSAU RUDI , MAERTENS GEERT
IPC分类号： C12N15/36 , C12Q1/70
CPC分类号： C12Q1/706
摘要： The present invention relates to a method for detection and/or genetic analysis of HBV in a biological sample, comprising hybridizing the polynucleic acids of the sample with a combination of at least two nucleotide probes, with said combination hybridizing specifically to a mutant target sequence chosen from the HBV RT pol gene region and/or to a mutant target sequence chosen from the HBV preCore region and/or to a mutant target sequence chosen from the HBsAg region of HBV and/or to a HBV genotype-specific target sequence, with said target sequences being chosen from Figure 1, and with said probes being applied to known locations on a solid support and with said probes being capable of hybridizing to the polynucleic acids of the sample under the same hybridization and wash conditions, or with said probes hybridizing specifically with a sequence complementary to any of said target sequences, or a sequence wherein T of said target sequence is replaced by U; and detecting the hybrids formed; and inferring the HBV genotype and/or mutants present in said sample from the differential hybridization signal(s) obtained. The invention further relates to sets of nucleotide probes and possibly primers useful in said methods as well as to their use in a method for typing and/or detecting HBV and to assay kits using the same.
摘要翻译：本发明涉及用于生物样品中HBV的检测和/或遗传分析的方法，包括将所述样品的多核酸与至少两个核苷酸探针的组合杂交，所述组合特异性与选择的突变靶序列杂交从HBV RT pol基因区和/或选自HBV preCore区的突变靶序列和/或选自HBV的HBsAg区和/或HBV基因型特异性靶序列的突变靶序列，其中所述靶序列选自图1，并且将所述探针应用于固体支持物上的已知位置，并且所述探针能够在相同的杂交和洗涤条件下与样品的多核酸杂交，或者与所述探针特异性杂交具有与任何所述靶序列互补的序列，或其中所述靶序列的T被U替代的序列; 并检测形成的杂种; 并从所获得的差异杂交信号中推断存在于所述样品中的HBV基因型和/或突变体。本发明还涉及可用于所述方法的核苷酸探针和可能的引物的集合，以及它们在用于分型和/或检测HBV的方法中的用途以及使用其的测定试剂盒。

10. 发明申请

WO1994021818A1 PROCESS FOR TYPING HLA-B USING SPECIFIC PRIMERS AND PROBES SETS 审中-公开
标题翻译：使用特定的PRIMES和PROBES SETS设置HLA-B的方法
公开(公告)号：WO1994021818A1
公开(公告)日：1994-09-29
申请号：PCT/EP1994000654
申请日：1994-03-07
申请人： N.V. INNOGENETICS S.A. , ANDRIEN, Marc , DUPONT, Etienne , ROSSAU, Rudi , DE CANCK, Ilse
发明人： N.V. INNOGENETICS S.A.
IPC分类号： C12Q01/68
CPC分类号： C12Q1/6881 , C12Q2600/156
摘要： The invention relates to a method for typing or subtyping one or more HLA-B alleles characterized by the sequence GCCA at position 30 to 33 of exon 2 (with said numbering being according to Zemmour and Parham, 1992), liable to be present in a sample, with said method comprising at least the following steps: (i) amplifying HLA-B alleles with at least one 5' end amplification primer selected from the following list: 5' -AGGTATTTCTACCCGCCA-3' (B25P) or sequence variants thereof, in combination with an appropriate 3' end primer being chosen from the same alleles as the above defined 5' end primers, with said 5' and 3' end primers being possibly labelled; and, (ii) hybridizing the amplified product, being labelled during or after amplification, at appropriate conditions with one or more suitable probes selected from region 15 to 261 of the HLA-B exon 2 region, with said numbering being according to Zemmour and Parham, 1992, (iii) washing at appropriate washing conditions, (iv) detecting the hybrids formed; and, (v) inferring the allele present from the observed hybridization pattern.
摘要翻译：本发明涉及一种用于对一个或多个HLA-B等位基因进行分型或分类的方法，其特征在于外显子2的位置30至33的序列GCCA（所述编号根据Zemmour和Parham，1992），易于存在于所述方法包括至少以下步骤：（i）用选自以下列表的至少一个5'末端扩增引物扩增HLA-B等位基因：5'-AGGTATTTCTACCCGCCA-3'（B25P）或其序列变体，与适当的3'末端引物组合，其选自与上述定义的5'末端引物相同的等位基因，所述5'和3'末端引物可能被标记; 和（ii）将扩增产物杂交，在适当的条件下用一种或多种选自HLA-B外显子2区域的区域15至261的合适探针进行标记，其中所述编号根据Zemmour和Parham ，1992，（iii）在适当的洗涤条件下洗涤，（iv）检测所形成的杂交体; 和（v）从观察到的杂交模式推断存在的等位基因。

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