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1. 发明申请

WO2009022129A1 A 3' -BASED SEQUENCING APPROACH FOR MICROARRAY MANUFACTURE 审中-公开
标题翻译：一种用于微型制造的3'-BASED测序方法
公开(公告)号：WO2009022129A1
公开(公告)日：2009-02-19
申请号：PCT/GB2008/002735
申请日：2008-08-12
申请人： ALMAC DIAGNOSTICS LIMITED , HARKIN, Paul , MULLIGAN, Karl , TANNEY, Austin , OLIVER, Gavin , FULTON, Ciaran
发明人： HARKIN, Paul , MULLIGAN, Karl , TANNEY, Austin , OLIVER, Gavin , FULTON, Ciaran
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6809 , C12Q1/6837 , C12Q2525/185 , C12Q2565/501
摘要： Methods are described to derive design sequences for the production of nucleic acid microarrays. The present methods use high throughput 3 ' sequencing of transcripts in a tissue sample or diseased state to design probes for nucleic acid microarrays. Also described are nucleic acid microarrays that possess probes directed to the extreme 3' end of transcripts in a tissue. These microarrays preferably represent alternate polyadenylation sequences that are specific to the tissue from which the transcripts are derived. Also described are methods of using the microarrays directed to the extreme 3 ' end of the transcript for evaluating gene expression in a tissue where there are reduced false positive and false negative results.
摘要翻译：描述了用于衍生用于产生核酸微阵列的设计序列的方法。本方法使用组织样品或病态的转录物的高通量3'测序来设计核酸微阵列的探针。还描述了具有针对组织中转录物的极端3'末端的探针的核酸微阵列。这些微阵列优选代表对衍生转录物的组织特异性的替代聚腺苷酸化序列。还描述了使用指向转录物的极端3'末端的微阵列来评估组织中的基因表达的方法，其中减少了假阳性和假阴性结果。

2. 发明申请

WO2006048291A2 TRANSCRIPTOME MICROARRAY TECHNOLOGY AND METHODS OF USING THE SAME 审中-公开
标题翻译：转录微波技术及其使用方法
公开(公告)号：WO2006048291A2
公开(公告)日：2006-05-11
申请号：PCT/EP2005/011783
申请日：2005-11-03
申请人： ARRADX LIMITED , HARKIN, Paul , JOHNSTON, Patrick , MULLIGAN, Karl
发明人： HARKIN, Paul , JOHNSTON, Patrick , MULLIGAN, Karl
CPC分类号： C12Q1/6886 , C12Q1/6837 , C12Q2600/106 , C12Q2600/158
摘要： Arrays containing a transcriptome of a diseased tissue and methods of using the arrays for diagnosis, prognosis, screening, and identification of disease are provided herein. The transcriptome arrays from diseased tissue are useful for diagnosis of a disease by analysis of the genetic profile of a tissue sample specific to a disease state. The genetic profiles are then correlated with data on the effectiveness of specific therapeutic agents. Correlating expression profiles to the effectiveness of therapeutic agents provides a way to screen and select further patients predicted to respond to those therapeutic agents, thereby minimizing needless exposure to ineffective therapy.
摘要翻译：本文提供了包含患病组织的转录组的阵列和用于诊断，预后，筛选和鉴定疾病的阵列的方法。来自病变组织的转录组阵列可用于通过分析特定于疾病状态的组织样品的遗传图谱来诊断疾病。然后将遗传图谱与特定治疗剂的有效性数据相关联。将表达谱与治疗剂的有效性相关联提供了筛选和选择进一步预测对这些治疗剂作出反应的患者的方法，从而使不必要的暴露于无效治疗最小化。

3. 发明申请

WO2015033172A1 MOLECULAR DIAGNOSTIC TEST FOR OESOPHAGEAL CANCER 审中-公开
标题翻译：用于食管癌的分子诊断测试
公开(公告)号：WO2015033172A1
公开(公告)日：2015-03-12
申请号：PCT/GB2014/052727
申请日：2014-09-09
申请人： ALMAC DIAGNOSTICS LIMITED
发明人： KEATING, Karen , HILL, Laura , DEHARO, Steve , O'BRIEN, Eamonn , DAVISON, Tim , HARKIN, Paul , KENNEDY, Richard , O'DONNELL, Jude
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/158
摘要： Methods and compositions are provided for the identification of a molecular diagnostic test for oesophageal adenocarcinoma (OAC). The test defines a novel DNA damage repair deficient molecular subtype and enables classification of a patient within this subtype. The present invention can be used to determine whether patients with OAC are clinically responsive or non-responsive to a therapeutic regimen prior to administration of any chemotherapy. This test may be used with different drugs that directly or indirectly affect DNA damage or repair, such as many of the standard cytotoxic chemotherapeutic drugs currently in use. In particular, the present invention is directed to the use of certain combinations of predictive markers, wherein the expression of the predictive markers correlates with responsiveness or non-responsiveness to a therapeutic regimen.
摘要翻译：提供了用于鉴定食管腺癌（OAC）的分子诊断试验的方法和组合物。该测试定义了一种新的DNA损伤修复缺陷型分子亚型，并能够对该亚型中的患者进行分类。本发明可用于确定在给予任何化学疗法之前，OAC患者是否具有临床响应或对治疗方案无反应。该测试可以与直接或间接影响DNA损伤或修复的不同药物一起使用，例如目前使用的许多标准细胞毒性化学治疗药物。特别地，本发明涉及预测标记物的某些组合的用途，其中预测标记的表达与对治疗方案的反应性或非反应性相关。

4. 发明申请

WO2017158358A1 GENE SIGNATURES FOR CANCER DETECTION AND TREATMENT 审中-公开
标题翻译：癌症检测和治疗的基因签名
公开(公告)号：WO2017158358A1
公开(公告)日：2017-09-21
申请号：PCT/GB2017/050712
申请日：2017-03-15
申请人： ALMAC DIAGNOSTICS LIMITED
发明人： EL-HELALI, Aya , MCGIVERN, Niamh , MCCAVIGAN, Andrena , PRICE, Bethanie , KNIGHT, Laura , MCCABE, Nuala , KENNEDY, Richard , HARKIN, Paul , GOURLEY, Charlie
IPC分类号： C12Q1/68
摘要： A molecular subgroup of cancer is characterised by misregulation of the MAPK signalling pathway and the epithelial-mesenchymal transition (EMT) pathway. Biomarker signatures can be used to identify cancers within the molecular subgroup. The signatures are also useful for identifying the treatment that is best suited for a given patient. A method for selecting a treatment for a subject having a cancer, comprises measuring the expression level(s)of at least biomarker selected from Table A or Table B in a sample from the subject. By assessing the expression level(s) of the at least 1 biomarker it can be determined whether the sample from the subject is positive or negative for a biomarker signature comprising the at least 1 biomarker. Based on the outcome of this assessment different treatments selected from MAPK pathway 10 inhibitors, EMT pathway inhibitors, SRC pathway inhibitors, taxanes and anti-angiogenic therapeutic agents may be indicated. Related treatment methods and products are also provided.
摘要翻译：癌症的分子亚型的特征在于MAPK信号传导途径和上皮 - 间质转化（EMT）途径的失调。生物标志物特征可用于识别分子亚群内的癌症。签名对于确定最适合给定患者的治疗也很有用。选择用于患有癌症的受试者的治疗的方法包括测量来自受试者的样品中至少选自表A或表B的生物标志物的表达水平。通过评估至少1种生物标志物的表达水平，可以确定来自受试者的样品对于包含至少1种生物标志物的生物标志物标志物是阳性还是阴性。基于该评估的结果，可以指出选自MAPK途径10抑制剂，EMT途径抑制剂，SRC途径抑制剂，紫杉烷和抗血管生成治疗剂的不同治疗。还提供了相关的治疗方法和产品。

5. 发明申请

WO2017216559A1 PREDICTING RESPONSIVENESS TO THERAPY IN PROSTATE CANCER 审中-公开
标题翻译：预测对前列腺癌的治疗反应
公开(公告)号：WO2017216559A1
公开(公告)日：2017-12-21
申请号：PCT/GB2017/051740
申请日：2017-06-14
申请人： ALMAC DIAGNOSTICS LIMITED
发明人： KNIGHT, Laura , WALKER, Steven , KENNEDY, Richard , HARKIN, Paul , DAVIDSON, Catherine
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/118 , C12Q2600/158
摘要： A method of predicting responsiveness of a subject having a prostate cancer to a mitotic inhibitor and/or a DNA damaging therapeutic agent comprises measuring expression levels of at least one gene selected from Table 1-45 in a sample from the subject. The measured expression levels are used to determine whether the prostate cancer has a deficiency in DNA damage repair and/or displays immune activation (to abnormal DNA). If the prostate cancer does not have a deficiency in DNA damage repair and/or does not display immune activation to abnormal DNA responsiveness to a mitotic inhibitor is predicted. If the prostate cancer has a deficiency in DNA damage repair and/or displays immune activation (to abnormal DNA) non-responsiveness to a mitotic inhibitor is predicted. If the prostate cancer has a deficiency in DNA damage repair and/or displays elevated immune signalling responsiveness to a DNA damaging therapeutic agent is predicted. If the prostate cancer does not have a deficiency in DNA damage repair and/or does not display immune activation (to abnormal DNA) non-responsiveness to a DNA damaging therapeutic agent is predicted. Corresponding products and methods of treatment are provided.
摘要翻译：预测患有前列腺癌的受试者对有丝分裂抑制剂和/或DNA损伤性治疗剂的反应性的方法包括测量样品中至少一种选自表1-45的基因的表达水平从主题。测量的表达水平用于确定前列腺癌是否具有DNA损伤修复缺陷和/或显示免疫激活（针对异常DNA）。如果前列腺癌不具有DNA损伤修复缺陷和/或不显示对异常DNA的免疫激活，则预测对有丝分裂抑制剂的反应性。如果前列腺癌具有DNA损伤修复缺陷和/或显示免疫激活（针对异常DNA），则预测对有丝分裂抑制剂无应答。如果前列腺癌具有DNA损伤修复缺陷和/或预示升高的免疫信号对DNA损伤治疗剂的应答性。如果前列腺癌不具有DNA损伤修复缺陷和/或不显示免疫激活（针对异常DNA），则预测对DNA损伤治疗剂的非响应性。提供了相应的产品和治疗方法。

6. 发明申请

WO2015087088A2 PROSTATE CANCER CLASSIFICATION 审中-公开
标题翻译：前列腺癌分类
公开(公告)号：WO2015087088A2
公开(公告)日：2015-06-18
申请号：PCT/GB2014/053694
申请日：2014-12-12
申请人： ALMAC DIAGNOSTICS LIMITED
发明人： WALKER, Steven , MCCAVIGAN, Andrena , DAVISON, Timothy , KENNEDY, Richard , HARKIN, Paul , HILL, Laura
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , A61K31/337 , C07K16/18 , C07K16/40 , C12Q2600/112 , C12Q2600/118 , C12Q2600/158
摘要： A method is provided for characterising and/or prognosing prostate cancer in a subject comprising determining the expression level of at least one of CREM, ERRFI1, SRSF5, PDK4, HJURP, PDRG1, TRPM3, PDE4D, F12, ADAMTS1, ADAMTS9, B3GNT5, CD38, CEBPD, CENPF, DKK1, EMP1, F3, IL1 R1, IL8, JUNB, KLF10, KLF4, LDLR, LGALS3, LPAR1, MALAT1, MTUS1, MYBPC1, NFIL3, NR4A3, OAT, PI15, PTGS2, RHOBTB3, RIN2, RNFT2, SELE, SLC15A2, SOCS2, SOCS3, SSTR1, ST6GAL1, TSC22D1, XBP1 and ZFP36 in a sample from the subject. The method may be used to predict the likelihood of metastasis. Also disclosed are methods for diagnosing and selecting treatment for prostate cancer, together with corresponding methods of treatment. Systems, kits and computer programs for performing the methods are also provided.
摘要翻译：提供了在受试者中表征和/或预测前列腺癌的方法，其包括测定CREM，ERRFI1，SRSF5，PDK4，HJURP，PDRG1，TRPM3，PDE4D，F12中的至少一种的表达水平，ADAMTS1，ADAMTS9，B3GNT5，CD38，CEBPD，CENPF，DKK1，EMP1，F3，IL1R1，IL8，JUNB，KLF10，KLF4，LDLR，LGALS3，LPAR1，MALAT1，MTUS1，MYBPC1，NFIL3，NR4A3，OAT， PTGS2，RHOBTB3，RIN2，RNFT2，SELE，SLC15A2，SOCS2，SOCS3，SSTR1，ST6GAL1，TSC22D1，XBP1和ZFP36。该方法可用于预测转移的可能性。还公开了诊断和选择前列腺癌治疗的方法以及相应的治疗方法。还提供了执行这些方法的系统，工具包和计算机程序。

7. 发明申请

WO2015033173A1 MOLECULAR DIAGNOSTIC TEST FOR LUNG CANCER 审中-公开
标题翻译：肺癌分子诊断测试
公开(公告)号：WO2015033173A1
公开(公告)日：2015-03-12
申请号：PCT/GB2014/052728
申请日：2014-09-09
申请人： ALMAC DIAGNOSTICS LIMITED
发明人： KEATING, Karen , HILL, Laura , DEHARO, Steve , O'BRIEN, Eamonn , DAVISON, Tim , HARKIN, Paul , KENNEDY, Richard , O'DONNELL, Jude
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/158
摘要： Methods and compositions are provided for the identification of a molecular diagnostic test for lung cancer. The test defines a novel DNA damage repair deficient molecular subtype and enables classification of a patient within this subtype. The present invention can be used to determine whether patients with NSCLC are clinically responsive or non-responsive to a therapeutic regimen prior to administration of any chemotherapy. This test may be used with different drugs that directly or indirectly affect DNA damage or repair, such as many of the standard cytotoxic chemotherapeutic drugs currently in use. In particular, the present invention is directed to the use of certain combinations of predictive markers, wherein the expression of the predictive markers correlates with responsiveness or non- responsiveness to a therapeutic regimen.
摘要翻译：提供了用于鉴定肺癌分子诊断试验的方法和组合物。该测试定义了一种新的DNA损伤修复缺陷型分子亚型，并能够对该亚型中的患者进行分类。本发明可用于确定在给予任何化学疗法之前，NSCLC患者是否具有临床响应或对治疗方案无反应。该测试可以与直接或间接影响DNA损伤或修复的不同药物一起使用，例如目前使用的许多标准细胞毒性化学治疗药物。特别地，本发明涉及预测标记物的某些组合的用途，其中预测标记物的表达与对治疗方案的反应性或非反应性相关。

8. 发明申请

WO2004042080A1 CANCER THERAPY DETERMINATION 审中-公开
标题翻译：癌症治疗决定
公开(公告)号：WO2004042080A1
公开(公告)日：2004-05-21
申请号：PCT/EP2003/012245
申请日：2003-11-03
申请人： THE QUEEN'S UNIVERSITY OF BELFAST , HARKIN, Paul , QUINN, Jennifer , KENNEDY, Richard
发明人： HARKIN, Paul , QUINN, Jennifer , KENNEDY, Richard
IPC分类号： C12Q1/68
CPC分类号： A61K31/475 , A61K31/335 , A61K31/337 , A61K31/357 , A61K31/65 , A61K31/665 , A61K31/7064 , A61K33/24 , C12Q1/6886 , C12Q2600/106 , C12Q2600/158
摘要： A method of determining a suitable chemotherapeutic agent for an individual comprises the steps of assaying a biological sample from the individual for BRCA1 activity. When the activity is greater than or equal to a normal level, an antimicrotubule chemotherapeutic agent is recommended. When the activity is below a normal level, a DNA damaging chemotherapeutic agent is recommended. BRCA1 activity is determined by assaying for BRCA1 mutation, BRCA1 expression levels, or both. A kit for carrying out the method of the invention is also disclosed.
摘要翻译：确定个体合适的化学治疗剂的方法包括从个体中检测BRCA1活性的生物样品的步骤。当活性大于或等于正常水平时，建议使用抗微管化学治疗剂。当活性低于正常水平时，建议使用DNA损伤化学治疗剂。通过测定BRCA1突变，BRCA1表达水平或两者来确定BRCA1活性。还公开了用于实施本发明的方法的套件。

9. 发明申请

WO2014006422A3 ADJUSTABLE STRUCTURES 审中-公开
公开(公告)号：WO2014006422A3
公开(公告)日：2014-01-09
申请号：PCT/GB2013/051792
申请日：2013-07-05
申请人： HARKIN, Paul
发明人： HARKIN, Paul
IPC分类号： E04B1/19 , A47C1/00 , B64C3/48 , E04B1/344
摘要： An adjustable structure (1) comprising a first structural layer (10) defined by a first array of extendable and/or retractable rods or beams (11, 11a, 11b) pivotally connected to each other at their ends and a second structural layer (20) connected to the first structural layer (10) and defined by a second array of extendable and/or retractable rods or beams (21, 21a, 21b) pivotally connected to each other at their ends, wherein at least a portion of the second layer (20) is outside the volume defined by the first structural layer (10) and the extendable and/or retractable rods or beams in the second arrayare more densely packed than the extendable and/or retractable rods or beams in the first array.

10. 发明申请

WO2005121786A2 BRCA1 MARKERS 审中-公开
标题翻译： BRCA1标记
公开(公告)号：WO2005121786A2
公开(公告)日：2005-12-22
申请号：PCT/GB2005/002227
申请日：2005-06-06
申请人： THE QUEEN'S UNIVERSITY OF BELFAST , HARKIN, Paul
发明人： HARKIN, Paul
IPC分类号： G01N33/50
CPC分类号： G01N33/5011 , G01N33/57415 , G01N33/57449 , G01N2800/52
摘要： A method of predicting the presence of a non-functional BRCA1 gene in a biological sample, comprises the step of assaying the sample for expression of at least one specific member of the S100 family of genes. The invention also describes a kit for predicting the presence of non-functional BRCA1, comprising means for assaying a sample for expression of at least one specific member of the S100 gene family. A method of detecting a genetic predisposition to cancer is also described, comprising the step of assaying a biological sample for expression of a specific member of the S100 family of genes. Also described is a method of determining a suitable chemotherapeutic agent for an individual.
摘要翻译：预测生物样品中无功能BRCA1基因的存在的方法包括测定样品以表达S100家族基因的至少一个特定成员的步骤。本发明还描述了一种用于预测非功能性BRCA1的存在的试剂盒，其包括用于测定样品以表达S100基因家族的至少一个特定成员的方法。还描述了检测癌症的遗传易感性的方法，其包括测定生物样品以表达S100家族基因的特定成员的步骤。还描述了确定个体的合适的化学治疗剂的方法。

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