公开(公告)号：US20030036053A1

公开(公告)日：2003-02-20

申请号：US09899044

申请日：2001-07-06

申请人： Innogenetics N.V.

发明人： Geert Maertens ,  Lieven Stuyver ,  Rudi Rossau ,  Hugo Van Heuverswyn

IPC分类号： C12Q001/70 ,  C12Q001/68

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 null291 to nucleotide at position null66 of the 5null 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 与上述定义的探针互补，检测可能形成在所述探针与H的核苷酸序列之间的复合物 CV分离鉴定。

公开(公告)号：US20020168626A1

公开(公告)日：2002-11-14

申请号：US09899302

申请日：2001-07-06

申请人： Innogenetics N.V.

发明人： Geert Maertens ,  Lieven Stuyver ,  Rudi Rossau ,  Hugo Van Heuverswyn

IPC分类号： C12Q001/70 ,  C12Q001/68 ,  C07H021/04

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 null291 to nucleotide at position null66 of the 5null 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.

公开(公告)号：US20020183508A1

公开(公告)日：2002-12-05

申请号：US09851138

申请日：2001-05-09

申请人： Innogenetics N.V.

发明人： Geert Maertens ,  Lieven Stuyver

IPC分类号： C12Q001/70 ,  C07H021/04 ,  C12N007/00

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. 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 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。 本发明涉及不同于已知HCV类型和亚型的新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型，1型和1型的HCV型1型序列; 亚型2e，2f，2g，2h，2I，2k和21l的新HCV 2型序列; 亚型3g的新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在诊断，预防和治疗中的应用。 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型和/ 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。

公开(公告)号：US20020106638A1

公开(公告)日：2002-08-08

申请号：US09899082

申请日：2001-07-06

申请人： Innogenetics N.V.

发明人： Geert Maertens ,  Lieven Stuyver ,  Rudi Rossau ,  Hugo Van Heuverswyn

IPC分类号： C12Q001/70 ,  C12Q001/68

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 null291 to nucleotide at position null66 of the 5null 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 与上述定义的探针互补，检测可能形成在所述探针与H的核苷酸序列之间的复合物 CV分离鉴定。

公开(公告)号：US20040029110A1

公开(公告)日：2004-02-12

申请号：US10453792

申请日：2003-06-04

申请人： INNOGENETICS N.V.

发明人： Lieven Stuyver ,  Rudi Rossau ,  Geert Maertens

IPC分类号： C12Q001/70 ,  C12Q001/68

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 FIG. 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基因区域和/或选自HBV preCore区域的突变靶序列和/或选自HBV的HBsAg区域和/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。 并且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。

公开(公告)号：US20030077575A1

公开(公告)日：2003-04-24

申请号：US09943983

申请日：2001-08-31

申请人： INNOGENETICS N.V.

发明人： Lieven Stuyver ,  Joost Louwagie ,  Rudi Rossau

IPC分类号： C12Q001/70 ,  C12Q001/68

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导突变的方法，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 测定。 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）。