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1. 发明专利

JP2005118044A New sequence of hepatitis c virus genotype and its use as prophylactic, therapeutic and diagnostic agent 审中-公开
标题翻译：丙型肝炎病毒基因组的新序列及其用作预防，治疗和诊断代理
公开(公告)号：JP2005118044A
公开(公告)日：2005-05-12
申请号：JP2004305574
申请日：2004-10-20
申请人： Innogenetics Nv , イノジェネティックス・ナムローゼ・フェンノートシャップInnogenetics N.V.
发明人： MAERTENS GEERT , STUYVER LIEVEN
IPC分类号： G01N33/53 , A61K38/00 , A61K38/08 , A61K38/10 , A61K39/00 , A61K39/29 , A61K39/395 , A61K48/00 , A61P1/16 , A61P31/12 , A61P31/14 , A61P37/04 , C07H21/00 , C07K4/02 , C07K7/06 , C07K7/08 , C07K14/18 , C07K16/08 , C07K16/10 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/09 , C12N15/11 , C12N15/40 , C12N15/51 , C12P21/02 , C12Q1/68 , C12Q1/70 , G01N33/543 , G01N33/566 , G01N33/569 , G01N33/576 , G01N33/577
CPC分类号： C07K14/005 , A61K38/00 , A61K39/00 , A61K2039/525 , C12N2770/24222
摘要： PROBLEM TO BE SOLVED: To provide a new sequence of hepatitis C virus genotype and its use as prophylactic, therapeutic and diagnostic agents. SOLUTION: The invention relates to HCV polynucleic acid or a complement thereof having a nucleotide sequence which is unique to a theretofore unidentified HCV type or subtype different from HCV subtypes 1a, 1b, 1c, 2a, 2b, 2c, 2d, 3a, 3b, 3c, 3d, 3e, 3f, 4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i, 4j, 5a or 6a classified by comparison of a part of the NS5 gene nucleotide sequence and containing at least one nucleotide differing from said known HCV nucleotide sequence. COPYRIGHT: (C)2005,JPO&NCIPI
摘要翻译：要解决的问题：提供丙型肝炎病毒基因型的新序列及其作为预防，治疗和诊断剂的用途。解决方案：本发明涉及HCV多核酸或其互补物，其具有与之前未鉴定的HCV型或不同于HCV亚型1a，1b，1c，2a，2b，2c，2d，3a的亚型特有的核苷酸序列，3b，3c，3d，3e，3f，4a，4b，4c，4d，4e，4f，4g，4h，4i，4j，5a，6a分类为NS5基因核苷酸序列的一部分，一个核苷酸与所述已知的HCV核苷酸序列不同。版权所有（C）2005，JPO＆NCIPI

2. 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。

3. 发明申请

WO9425601A3 NEW SEQUENCES OF HEPATITIS C VIRUS GENOTYPES AND THEIR USE AS THERAPEUTIC AND DIAGNOSTIC AGENTS 审中-公开
标题翻译：丙型肝炎病毒基因组的新序列及其作为治疗和诊断试剂的使用
公开(公告)号：WO9425601A3
公开(公告)日：1995-03-02
申请号：PCT/EP9401323
申请日：1994-04-27
申请人： INNOGENETICS NV , MAERTENS GEERT , STUYVER LIEVEN
发明人： MAERTENS GEERT , STUYVER LIEVEN
IPC分类号： G01N33/50 , A61K31/711 , A61K31/713 , A61K35/76 , A61K38/00 , A61K39/00 , A61K39/395 , A61K48/00 , A61P1/16 , A61P31/12 , A61P31/14 , A61P31/20 , C07K14/02 , C07K14/10 , C07K14/18 , C07K16/00 , C07K16/08 , C07K16/10 , C12N15/09 , C12N15/40 , C12N15/41 , C12N15/51 , C12Q1/68 , C12Q1/70 , G01N33/15 , G01N33/53 , G01N33/566 , G01N33/576 , A61K39/29 , C07N14/18
CPC分类号： C07K14/005 , A61K38/00 , A61K39/00 , C12N2770/24222
摘要： The present invention relates to new polynucleic acid and amino acid sequences corresponding to new HCV type 5 sequences. The present invention also relates to the use of these polynucleic acids and amino acids in methods or processes for the detection of one or more HCV genotypes, or for the preparation of antibodies against new HCV type 5 polypeptides. The invention also includes compositions comprising said polynucleic acid and amino acid sequences. The present invention further relates to kits comprising polynucleic acid probes and/or primers defined by the invention, or comprising polypeptides according to the invention.

4. 发明申请

WO02055741A3 METHOD FOR DETECTION OF DRUG-INDUCED MUTATIONS IN THE HIV REVERSE TRANSCRIPTASE GENE 审中-公开
标题翻译：用于检测HIV逆转录酶基因中的药物诱导突变的方法
公开(公告)号：WO02055741A3
公开(公告)日：2003-05-01
申请号：PCT/EP0200153
申请日：2002-01-09
申请人： INNOGENETICS NV , DE SMET KOENRAAD , STUYVER LIEVEN
发明人： DE SMET KOENRAAD , STUYVER LIEVEN
IPC分类号： C12Q1/68 , C12Q1/70 , C07K14/16
CPC分类号： C12Q1/703 , C12Q2600/156
摘要： The present invention relates to a method for the rapid, reliable and precise 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 the genetic detection of the following mutations in the HIV RT gene: K103N/R, V106A/I/L, Q151M/L, Y181C/I, M184V/I, Y188L, G190A/S/R and/or T215Y/F/D/S/A. The present invention also relates to probes and primers for such detection, to a diagnostic kit and a LiPA assay. The present invention further relates to HIV RT sequences comprising previously unknown polymorphisms.
摘要翻译：本发明涉及用于快速，可靠和精确地检测逆转录酶基因中的药物诱导突变的方法，其允许使用优化以反向一起共同作用的特定探针组同时表征涉及耐药性的一系列密码子杂交测定。更具体地，本发明涉及HIV RT基因中以下突变的遗传检测：K103N / R，V106A / I / L，Q151M / L，Y181C / I，M184V / I，Y188L，G190A / S / R 和/或T215Y / F / D / S / A。本发明还涉及用于这种检测的探针和引物，诊断试剂盒和LiPA测定。本发明还涉及包含先前未知多态性的HIV RT序列。

5. 发明申请

WO0138498A3 A NEW GENOTYPE OF HEPATITIS B VIRUS 审中-公开
标题翻译：一种新的乙型肝炎病毒基因组
公开(公告)号：WO0138498A3
公开(公告)日：2002-01-24
申请号：PCT/US0032108
申请日：2000-11-21
申请人： PHARMASSET LTD , INNOGENETICS NV , STUYVER LIEVEN , SCHINAZI RAYMOND , GENDT SIJA DE , GEYT CAROLINE VAN , ZOULIM FABIEN , FRIED MICHAEL , ROSSAU RUDI
发明人： STUYVER LIEVEN , SCHINAZI RAYMOND , DE GENDT SIJA , VAN GEYT CAROLINE , ZOULIM FABIEN , FRIED MICHAEL , ROSSAU RUDI
IPC分类号： A61K39/00 , C07K14/02 , C12N7/00 , C12Q1/70 , C07K16/08 , G01N33/569
CPC分类号： C07K14/005 , A61K39/00 , A61K2039/525 , A61K2039/53 , C12N7/00 , C12N2730/10122 , C12Q1/706
摘要： The present invention provides a purified hepatitis B virus, genotype G. Also provided are methods of detecting hepatitis B virus, genotype G in a sample, comprising: (a) contacting the sample with an antibody of this invention under conditions whereby an antigen/antibody complex can form; and (b) detecting the presence of the antigen/antibody complex, whereby the detection of the antigen/antibody complex indicates the presence of hepatitis B virus, genotype G in a sample. Further provided is a method of detecting hepatitis B virus, genotype G in a sample, comprising: (a) contacting the sample with a nucleic acid of this invention under conditions whereby the nucleic acid can hybridize with a nucleic acid sequence in the sample; and (b) detecting the presence of nucleic acid hybridization complexes, whereby the detection of the hybridization complexes indicates the presence of hepatitis B virus, genotype G in the sample. Additional methods related to HBV, genotype G are also provided.
摘要翻译：本发明提供纯化的乙型肝炎病毒，基因型G.还提供了检测样品中的乙型肝炎病毒，基因型G的方法，其包括：（a）将样品与本发明的抗体接触，其中抗原/抗体复杂可以形成; 和（b）检测抗原/抗体复合物的存在，由此抗原/抗体复合物的检测表明样品中存在乙型肝炎病毒，基因型G。进一步提供一种检测样品中乙型肝炎病毒基因型G的方法，包括：（a）使样品与本发明的核酸在待测样品中与核酸序列杂交的条件下接触; 和（b）检测核酸杂交复合物的存在，由此杂交复合物的检测表明样品中存在乙型肝炎病毒，基因型G。还提供了与HBV相关的其他方法，基因型G。

6. 发明申请

WO0104358A3 DETECTION OF ANTI-HEPATITIS B DRUG RESISTANCE 审中-公开
标题翻译：检测抗乙型肝炎药物耐药性
公开(公告)号：WO0104358A3
公开(公告)日：2001-08-30
申请号：PCT/EP0006306
申请日：2000-07-05
申请人： INNOGENETICS NV , STUYVER LIEVEN , MAERTENS GEERT , GEYT CAROLINE VAN
发明人： STUYVER LIEVEN , MAERTENS GEERT , VAN GEYT CAROLINE
IPC分类号： C12N15/09 , C12Q20060101 , C12Q1/68 , C12Q1/70
CPC分类号： C12Q1/706
摘要： The present invention relates to a method for the monitoring of anti-HBV drug resistance in a patient by genetic detection of at least one of the mutations L528M, M552V/I and/or V/L/M555I in the DNA polymerase of the HBV strains present in a biological sample of said patient. The present invention provides new HBV DNA polymerase sequences to be used for the design of new probes allowing a very specific and sensitive detection of anti-HBV drug resistance.
摘要翻译：本发明涉及通过遗传检测HBV株DNA聚合酶中的至少一个突变L528M，M552V / I和/或V / L / M555I来监测患者抗HBV耐药性的方法存在于所述患者的生物样品中。本发明提供新的HBV DNA聚合酶序列，用于设计新的探针，允许对抗HBV耐药性的非常特异和灵敏的检测。

7. 发明申请

WO9967428A3 METHOD FOR DETECTION OF DRUG-SELECTED MUTATIONS IN THE HIV PROTEASE GENE 审中-公开
标题翻译：用于检测HIV蛋白酶基因中的药物选择突变的方法
公开(公告)号：WO9967428A3
公开(公告)日：2000-04-13
申请号：PCT/EP9904317
申请日：1999-06-22
申请人： INNOGENETICS NV , STUYVER LIEVEN
发明人： STUYVER LIEVEN
IPC分类号： C12N15/09 , C12Q1/68 , C12Q1/70
CPC分类号： C12Q1/703
摘要： The present invention relates to a method for the rapid and reliable detection of drug-selected mutations in the HIV protease 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 viruses in a biological sample, with said method comprising: a) if need be, releasing, isolating or concentrating the polynucleic acids present in the sample; b) if need be amplifying the relevant part of the protease gene of HIV with at least one suitable primer pair; c) hybrydizing the polynucleic acids of step a) or b) with at least one of the following probes: probes specifically hybridizing to a target sequence comprising codon 30; probes specifically hybridizing to a target sequence comprising codon 46 and/or 48; probes specifically hybridizing to a target sequence comprising codon 50; probes specifically hybridizing to a target sequence comprising codon 54; probes specifically hybridizing to a target sequence comprising codon 82 and/or 84; probes specifically hybridizing to a target sequence comprising codon 90; or the complement of said probes ; further characterized in that said probes specifically hybridize to any of the target sequences presented in figure (1), or the complement of said target sequences ; d) inferring from the result of step c) whether or not a mutation giving rise to drug resistance is present in any of said target sequences.
摘要翻译：本发明涉及一种用于快速可靠地检测HIV蛋白酶基因中的药物选择突变的方法，其允许使用优化以在反向杂交中一起起作用的特定组探针同时表征涉及耐药性的一系列密码子检测。更具体地说，本发明涉及一种用于测定生物样品中HIV病毒抗病毒药物易感性的方法，所述方法包括：a）如果需要，释放，分离或浓缩样品中存在的多核酸; b）如果需要用至少一个合适的引物对扩增HIV的蛋白酶基因的相关部分; c）将步骤a）或b）中的多核酸与至少一种以下探针杂交：与包含密码子30的靶序列特异性杂交的探针; 与包含密码子46和/或48的靶序列特异性杂交的探针; 与包含密码子50的靶序列特异性杂交的探针; 与包含密码子54的靶序列特异性杂交的探针; 与包含密码子82和/或84的靶序列特异性杂交的探针; 与包含密码子90的靶序列特异性杂交的探针; u或所述探针的互补物; 其特征还在于所述探针与图（1）所示的任何目标序列或所述靶序列的互补体特异性杂交; d）从步骤c）的结果推测，是否存在任何所述靶序列中产生耐药性的突变。

8. 发明申请

WO9412670A3 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：WO9412670A3
公开(公告)日：1994-07-21
申请号：PCT/EP9303325
申请日：1993-11-26
申请人： INNOGENETICS NV , MAERTENS GEERT , STUYVER LIEVEN , ROSSAU RUDI , HEUVERSWYN HUGO VAN
发明人： MAERTENS GEERT , STUYVER LIEVEN , ROSSAU RUDI , VAN HEUVERSWYN HUGO
IPC分类号： C12N15/09 , C07H21/04 , C12N15/40 , C12Q1/02 , C12Q1/68 , C12Q1/70 , C12M9/34
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.

9. 发明申请

WO0140279A2 NEW HBV SEQUENCES 审中-公开
标题翻译：新的HBV序列
公开(公告)号：WO0140279A2
公开(公告)日：2001-06-07
申请号：PCT/EP0011526
申请日：2000-11-20
申请人： INNOGENETICS NV , STUYVER LIEVEN , GEYT CAROLINE VAN , GENDT SIJA DE
发明人： STUYVER LIEVEN , VAN GEYT CAROLINE , DE GENDT SIJA
IPC分类号： G01N33/50 , A61K38/00 , A61K39/00 , A61K39/395 , A61K45/00 , A61K48/00 , A61P31/20 , C07K14/02 , C07K16/08 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/09 , C12P21/02 , C12Q1/68 , G01N33/15 , G01N33/53 , G01N33/576 , G01N37/00
CPC分类号： C07K14/005 , A61K39/00 , C12N2730/10122
摘要： The complete nucleic acid sequence of a new human hepatitis B virus genotype, provisionally named genotype G, is reported. This genotype was found with a high prevalence in patients chronically infected with HBV and residing in Europe and the USA. The present invention further relates to polypeptides encoded by said nucleic acid sequence and to antibodies recognizing said polypeptides. The present invention also relates to the use of said nucleic acid, polypeptides and antibodies in HBV diagnosis, prophylaxis and therapy.
摘要翻译：报道了临时命名为基因型G的新型人乙型肝炎病毒基因型的完整核酸序列。发现这种基因型在长期感染HBV并居住在欧洲和美国的患者中患病率高。本发明还涉及由所述核酸序列编码的多肽和识别所述多肽的抗体。本发明还涉及所述核酸，多肽和抗体在HBV诊断，预防和治疗中的用途。

10. 发明申请

WO9613590A2 NEW SEQUENCES OF HEPATITIS C VIRUS GENOTYPES AND THEIR USE AS PROPHYLACTIC, THERAPEUTIC AND DIAGNOSTIC AGENTS 审中-公开
标题翻译：丙型肝炎病毒基因组的新序列及其作为预防，治疗和诊断代理的用途
公开(公告)号：WO9613590A2
公开(公告)日：1996-05-09
申请号：PCT/EP9504155
申请日：1995-10-23
申请人： INNOGENETICS NV , MAERTENS GEERT , STUYVER LIEVEN
发明人： MAERTENS GEERT , STUYVER LIEVEN
IPC分类号： G01N33/53 , A61K38/00 , A61K38/08 , A61K38/10 , A61K39/00 , A61K39/29 , A61K39/395 , A61K48/00 , A61P1/16 , A61P31/12 , A61P31/14 , A61P37/04 , C07H21/00 , C07K4/02 , C07K7/06 , C07K7/08 , C07K14/18 , C07K16/08 , C07K16/10 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/09 , C12N15/11 , C12N15/40 , C12N15/51 , C12P21/02 , C12Q1/68 , C12Q1/70 , G01N33/543 , G01N33/566 , G01N33/569 , G01N33/576 , G01N33/577
CPC分类号： C07K14/005 , A61K38/00 , A61K39/00 , A61K2039/525 , C12N2770/24222
摘要： The present invention relates to new genomic nucleotide sequences and amino acid sequences corresponding to the coding region of these genomes. The invention relates to new HCV types and subtypes sequences which are different from the known HCV types and subtypes sequences. More particularly, the present invention relates to new HCV type 7 sequences, new HCV type 9 sequences, new HCV type 10 and new HCV type 11 sequences. Also, the present invention relates to new HCV type 1 sequences of subtypes 1d, 1e, 1f and 1g; new HCV type 2 sequences of subtypes 2e, 2f, 2g, 2h, 2i, 2k and 2l; new HCV type 3 sequences of subtype 3g, new HCV type 4 sequences of subtypes 4k, 4l and 4m; a process for preparing them, and their use for diagnosis, prophylaxis and therapy. More particularly, the present invention provides new type-specific sequences of the Core, the E1 and the NS5 regions of new HCV types 7, 9, 10 and 11, as well as of new variants (subtypes) of HCV types 1, 2, 3 and 4. These new HCV sequences are useful to diagnose the presence of HCV type 1, and/or type 2, and/or type 3, and/or type 4, and/or type 7, and/or type 9, and/or type 10, and/or type 11 genotypes or serotypes in a biological sample. Moreover, the availability of these new type-specific sequences can increase the overall sensitivity of HCV detection and should also prove to be useful for prophylactic and therapeutic purposes.
摘要翻译：本发明涉及对应于这些基因组的编码区的新的基因组核苷酸序列和氨基酸序列。本发明涉及与已知的HCV类型和亚型序列不同的新的HCV类型和亚型序列。更具体地，本发明涉及新的HCV 7型序列，新型HCV 9型序列，新型HCV 10型和新型HCV 11型序列。此外，本发明涉及新型的1型，1e，1f和1g型新型HCV 1型序列; 亚型2e，2f，2g，2h，2i，2k和2l的新HCV 2型序列; 亚型3g的新型HCV 3型序列，亚型4k，4l和4m的新型HCV 4型序列; 它们的制备过程及其用于诊断，预防和治疗。更具体地，本发明提供新型HCV 7型，9型，10型和11型的核心，E1和NS5区域的新型特异性序列，以及HCV类型1,2和2的新变体（亚型）这些新的HCV序列可用于诊断HCV 1型和/或2型和/或3型和/或4型和/或7型和/或9型的存在，以及 /或10型，和/或11型基因型或血清型。此外，这些新型特异性序列的可用性可以增加HCV检测的总体灵敏度，并且还应证明可用于预防和治疗目的。

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