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1. 发明申请

US20150232933A1 METHODS FOR EVALUATING PATHOLOGIC CONDITIONS USING EXTRACELLULAR RNA 审中-公开
标题翻译：使用细胞外RNA评估病态的方法
公开(公告)号：US20150232933A1
公开(公告)日：2015-08-20
申请号：US14511950
申请日：2014-10-10
申请人： Michael S. Kopreski
发明人： Michael S. Kopreski
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6883 , C12Q2600/118 , C12Q2600/158
摘要： This invention provides methods for the detection, diagnosing, monitoring, or predicting of non-neoplastic diseases, pathologic conditions, and injury. The methods of the invention detect extracellular non-neoplastic mammalian RNA in the blood, blood plasma, serum, cerebrospinal fluid or other bodily fluid of an animal, most preferably a human, having or predisposed to having a non-neoplastic disease, pathologic condition, or injury.
摘要翻译：本发明提供了检测，诊断，监测或预测非肿瘤性疾病，病理状况和损伤的方法。本发明的方法检测动物，最优选人类的血液，血浆，血清，脑脊液或其他体液中的细胞外非肿瘤哺乳动物RNA，其具有或易于具有非肿瘤性疾病，病理状况，或伤害。

2. 发明授权

US08163524B2 Comparative analysis of extracellular RNA species 有权
标题翻译：细胞外RNA物种的比较分析
公开(公告)号：US08163524B2
公开(公告)日：2012-04-24
申请号：US11857414
申请日：2007-09-18
申请人： Michael S. Kopreski
发明人： Michael S. Kopreski
IPC分类号： C12P19/34 , C12Q1/68 , C07H21/02 , C07H21/04 , C07H21/00
CPC分类号： C12Q1/6806 , C12Q1/6809 , C12Q2527/127 , C12Q2521/307 , C12Q2545/114
摘要： The invention provides methods for detecting tumor-associated RNA in plasma, serum, and other bodily fluids. In particular, the invention provides methods for detecting translocated gene RNA, including fusion gene RNA, in plasma or serum or other bodily fluids.
摘要翻译：本发明提供了检测血浆，血清和其他体液中肿瘤相关RNA的方法。特别地，本发明提供了在血浆或血清或其他体液中检测易位基因RNA（包括融合基因RNA）的方法。

3. 发明授权

US07968317B2 Detection of 5T4 RNA in plasma and serum 有权
标题翻译：血浆和血清中5T4 RNA的检测
公开(公告)号：US07968317B2
公开(公告)日：2011-06-28
申请号：US11415968
申请日：2006-05-02
申请人： Michael S. Kopreski , Christopher D. Gocke
发明人： Michael S. Kopreski , Christopher D. Gocke
IPC分类号： C12P19/34 , C12Q1/68 , C07H21/02 , C07H21/04 , C07H21/00
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/158
摘要： This invention provides methods for detecting the presence of malignant or premalignant cells, or trophoblastic cells in a human wherein the malignant, premalignant or trophoblastic cells express 5T4. The methods of the invention detect 5T4 RNA in blood, blood plasma, serum, and other bodily fluids. The inventive methods are useful for detection, diagnosis, monitoring, treatment, or evaluation of neoplastic disease, and for the detection and evaluation of placental tissue in pregnant women.
摘要翻译：本发明提供了用于检测人类恶性或癌前细胞或滋养细胞的存在的方法，其中恶性，恶化前或滋养细胞表达5T4。本发明的方法检测血液，血浆，血清和其他体液中的5T4 RNA。本发明的方法可用于检测，诊断，监测，治疗或评估肿瘤疾病，以及孕妇胎盘组织的检测和评价。

4. 发明授权

US07767422B2 Detection of 5T4 RNA in plasma and serum 有权
标题翻译：血浆和血清中5T4 RNA的检测
公开(公告)号：US07767422B2
公开(公告)日：2010-08-03
申请号：US10363023
申请日：2001-08-21
申请人： Michael S. Kopreski , Christopher D. Gocke
发明人： Michael S. Kopreski , Christopher D. Gocke
IPC分类号： C12P19/34 , C12Q1/68 , C07H21/02 , C07H21/04 , C07H21/00
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/158
摘要： This invention provides methods for detecting the presence of malignant or premalignant cells, or trophoblastic cells in a human wherein the malignant, premalignant or trophoblastic cells express 5T4. The methods of the invention detect 5T4 RNA in blood, blood plasma, serum, and other bodily fluids. The inventive methods are useful for detection, diagnosis, monitoring, treatment, or evaluation of neoplastic disease, and for the detection and evaluation of placental tissue in pregnant women.
摘要翻译：本发明提供了用于检测人类恶性或癌前细胞或滋养细胞的存在的方法，其中恶性，恶化前或滋养细胞表达5T4。本发明的方法检测血液，血浆，血清和其他体液中的5T4 RNA。本发明的方法可用于检测，诊断，监测，治疗或评估肿瘤疾病，以及孕妇胎盘组织的检测和评价。

5. 发明申请

US20090298085A1 Detection of Extracellular Tumor-Associated Nucleic Acid in Blood Plasma or Serum Using Nucleic Acid Amplification Assays 有权
标题翻译：使用核酸扩增测定检测血浆或血清中细胞外肿瘤相关核酸
公开(公告)号：US20090298085A1
公开(公告)日：2009-12-03
申请号：US12534578
申请日：2009-08-03
申请人： Christopher D. Gocke , Michael S. Kopreski , Floyd A. Benko
发明人： Christopher D. Gocke , Michael S. Kopreski , Floyd A. Benko
IPC分类号： C12Q1/68
CPC分类号： C07K14/82 , C07K14/47 , C07K14/4746 , C07K2319/00 , C12Q1/683 , C12Q1/686 , C12Q1/6865 , C12Q1/6886 , C12Q1/708 , C12Q2600/112 , C12Q2600/154 , C12Q2600/156 , C12Q2600/16 , C12Q2535/125
摘要： This invention relates to detection of specific extracellular nucleic acid in plasma or serum fractions of human or animal blood associated with neoplastic or proliferative disease. Specifically, the invention relates to detection of nucleic acid derived from mutant oncogenes or other tumor-associated DNA, and to those methods of detecting and monitoring extracellular mutant oncogenes or tumor-associated DNA found in the plasma or serum fraction of blood by using rapid DNA extraction followed by nucleic acid amplification with or without enrichment for mutant DNA. In particular, the invention relates to the detection, identification, or monitoring of the existence, progression or clinical status of benign, premalignant, or malignant neoplasms in humans or other animals that contain a mutation that is associated with the neoplasm through detection of the mutated nucleic acid of the neoplasm in plasma or serum fractions. The invention permits the detection of extracellular, tumor-associated nucleic acid in the serum or plasma of humans or other animals recognized as having a neoplastic or proliferative disease or in individuals without any prior history or diagnosis of neoplastic or proliferative disease. The invention provides the ability to detect extracellular nucleic acid derived from genetic sequences known to be associated with neoplasia, such as oncogenes, as well as genetic sequences previously unrecognized as being associated with neoplastic or proliferative disease. The invention thereby provides methods for early identification of colorectal, pancreatic, lung, breast, bladder, ovarian, lymphoma and all other malignancies carrying tumor-related mutations of DNA and methods for monitoring cancer and other neoplastic disorders in humans and other animals.
摘要翻译：本发明涉及在与肿瘤或增生性疾病相关的人或动物血液的血浆或血清部分中检测特异性细胞外核酸。具体地，本发明涉及来自突变致癌基因或其他肿瘤相关DNA的核酸的检测，以及通过使用快速DNA检测和监测在血浆或血清部分中发现的细胞外突变致癌基因或肿瘤相关DNA的方法提取后进行核酸扩增，扩增或不扩增突变DNA。特别地，本发明涉及通过检测突变体的检测，鉴定或监测包含与赘生物相关的突变的人或其他动物中的良性，恶化前或恶性肿瘤的存在，进展或临床状态血浆或血清级分中的肿瘤核酸。本发明允许检测被认为具有肿瘤或增殖性疾病的人或其他动物的血清或血浆中的细胞外，肿瘤相关核酸，或者在没有任何先前的肿瘤或增殖性疾病的历史或诊断的个体中。本发明提供了检测源自已知与肿瘤形成相关的遗传序列的细胞外核酸的能力，例如癌基因，以及先前未被认识为与肿瘤或增殖性疾病相关的遗传序列。因此，本发明提供了用于早期鉴定结直肠，胰腺，肺，乳腺，膀胱，卵巢，淋巴瘤和携带DNA的肿瘤相关突变的所有其他恶性肿瘤的方法以及用于监测人和其他动物中的癌症和其他肿瘤性疾病的方法。

6. 发明申请

US20090233276A1 Method Enabling the Use of Extracellular Ribonucleic Acid (RNA) Extracted from Plasma or Serum to Detect, Monitor or Evaluate Cancer or Premalignant Conditions 审中-公开
标题翻译：使用从血浆或血清提取的细胞外核糖核酸（RNA）检测，监测或评估癌症或恶病前病症的方法
公开(公告)号：US20090233276A1
公开(公告)日：2009-09-17
申请号：US11739522
申请日：2007-04-24
申请人： Michael S. Kopreski
发明人： Michael S. Kopreski
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6806 , C12Q2600/156 , C12Q2600/158 , C12Q2521/119
摘要： This invention relates to the use of tumor-derived or associated extracellular ribonucleic acid (RNA) found circulating in the plasma or serum fraction of blood for the detection, monitoring, or evaluation of cancer or premalignant conditions. Extracellular RNA may circulate as non-bound RNA, protein-bound RNA, lipid-RNA complexes, lipoprotein (proteolipid)-RNA complexes, protein-RNA complexes including within or in association with ribonucleoprotein complexes, nucleosomes, or within apoptotic bodies. Any intracellular RNA found in plasma or serum can additionally be detected by this invention. Specifically, this invention enables the extraction of circulating RNA from plasma or serum and utilizes nucleic acid amplification assays for the identification, detection, inference, monitoring, or evaluation of any neoplasm, benign, premalignant, or malignant, in humans or other animals, which might be associated with that RNA. Further, this invention allows the qualitative or quantitative detection of tumor-derived or associated extracellular RNA circulating in the plasma or serum of humans or animals with or without any prior knowledge of the presence of cancer or premalignant tissue.
摘要翻译：本发明涉及在血浆或血清血清部分循环发现的肿瘤衍生或相关细胞外核糖核酸（RNA）用于癌症或癌前病症的检测，监测或评估。细胞外RNA可以作为非结合RNA，蛋白质结合的RNA，脂质RNA复合物，脂蛋白（蛋白脂质）-RNA复合物，蛋白质-RNA复合物，包括核糖核蛋白复合物，核小体或凋亡小体内或之内的蛋白质 - RNA复合物循环。在血浆或血清中发现的任何细胞内RNA可另外通过本发明检测。具体地，本发明能够从血浆或血清中提取循环RNA，并利用核酸扩增测定法来鉴定，检测，推断，监测或评估人类或其他动物中的任何肿瘤，良性，恶化前或恶性，其中可能与该RNA相关。此外，本发明允许定性或定量检测在具有或没有任何先前知道癌或癌前组织存在的情况下在人或动物的血浆或血清中循环的肿瘤衍生或相关的细胞外RNA。

7. 发明授权

US06939675B2 Detection of extracellular tumor-associated nucleic acid in blood plasma or serum using nucleic acid amplification assays 失效
标题翻译：使用核酸扩增测定法检测血浆或血清中的细胞外肿瘤相关核酸
公开(公告)号：US06939675B2
公开(公告)日：2005-09-06
申请号：US10298816
申请日：2002-11-18
申请人： Christopher D. Gocke , Michael S. Kopreski , Floyd A. Benko
发明人： Christopher D. Gocke , Michael S. Kopreski , Floyd A. Benko
IPC分类号： C07K14/47 , C07K14/82 , C12Q1/68 , C12Q1/70 , C12P19/34
CPC分类号： C07K14/82 , C07K14/47 , C07K14/4746 , C07K2319/00 , C12Q1/683 , C12Q1/686 , C12Q1/6865 , C12Q1/6886 , C12Q1/708 , C12Q2600/112 , C12Q2600/154 , C12Q2600/156 , C12Q2600/16 , C12Q2535/125
摘要： This invention relates to detection of specific extracellular nucleic acid in plasma or serum fractions of human or animal blood associated with neoplastic or proliferative disease. Specifically, the invention relates to detection of nucleic acid derived from mutant oncogenes or other tumor-associated DNA, and to those methods of detecting and monitoring extracellular mutant oncogenes or tumor-associated DNA found in the plasma or serum fraction of blood by using rapid DNA extraction followed by nucleic acid amplification with or without enrichment for mutant DNA. In particular, the invention relates to the detection, identification, or monitoring of the existence, progression or clinical status of benign, premalignant, or malignant neoplasms in humans or other animals that contain a mutation that is associated with the neoplasm through detection of the mutated nucleic acid of the neoplasm in plasma or serum fractions. The invention permits the detection of extracellular, tumor-associated nucleic acid in the serum or plasma of humans or other animals recognized as having a neoplastic or proliferative disease or in individuals without any prior history or diagnosis of neoplastic or proliferative disease. The invention provides the ability to detect extracellular nucleic acid derived from genetic sequences known to be associated with neoplasia, such as oncogenes, as well as genetic sequences previously unrecognized as being associated with neoplastic or proliferative disease. The invention thereby provides methods for early identification of colorectal, pancreatic, lung, breast, bladder, ovarian, lymphoma and all other malignancies carrying tumor-related mutations of DNA and methods for monitoring cancer and other neoplastic disorders in humans and other animals.
摘要翻译：本发明涉及在与肿瘤或增生性疾病相关的人或动物血液的血浆或血清部分中检测特异性细胞外核酸。具体地，本发明涉及来自突变致癌基因或其他肿瘤相关DNA的核酸的检测，以及通过使用快速DNA检测和监测在血浆或血清部分中发现的细胞外突变致癌基因或肿瘤相关DNA的方法提取后进行核酸扩增，扩增或不扩增突变DNA。特别地，本发明涉及通过检测突变体的检测，鉴定或监测包含与赘生物相关的突变的人或其他动物中的良性，恶化前或恶性肿瘤的存在，进展或临床状态血浆或血清级分中的肿瘤核酸。本发明允许检测被认为具有肿瘤或增殖性疾病的人或其他动物的血清或血浆中的细胞外，肿瘤相关核酸，或者在没有任何先前的肿瘤或增殖性疾病的历史或诊断的个体中。本发明提供了检测源自已知与肿瘤形成相关的遗传序列的细胞外核酸的能力，例如癌基因，以及先前未被认识为与肿瘤或增殖性疾病相关的遗传序列。因此，本发明提供了用于早期鉴定结直肠，胰腺，肺，乳腺，膀胱，卵巢，淋巴瘤和携带DNA的肿瘤相关突变的所有其他恶性肿瘤的方法以及用于监测人和其他动物中的癌症和其他肿瘤性疾病的方法。

8. 发明授权

US06759217B2 Method enabling use of extracellular RNA extracted from plasma or serum to detect, monitor or evaluate cancer 失效
标题翻译：能够使用从血浆或血清提取的细胞外RNA检测，监测或评估癌症的方法
公开(公告)号：US06759217B2
公开(公告)日：2004-07-06
申请号：US09966515
申请日：2001-09-28
申请人： Michael S. Kopreski
发明人： Michael S. Kopreski
IPC分类号： C12P1934
CPC分类号： C12Q1/6806 , C12Q1/6886 , C12Q2600/158 , Y10T436/143333
摘要： The methods of the invention detect epidermal growth factor RNA, epidermal growth factor receptor RNA, her-2/neu RNA, c-myc RNA, heterogeneous nuclear ribonucleoprotein A2/B1 RNA or any combination thereof in blood plasma, serum, and other bodily fluids. The inventive methods are useful for detection, diagnosis, monitoring, treatment, or evaluation of neoplastic disease.
摘要翻译：本发明的方法在血浆，血清和其他体液中检测表皮生长因子RNA，表皮生长因子受体RNA，her-2 / neu RNA，c-myc RNA，异源核核糖核蛋白A2 / B1 RNA或其任何组合。本发明的方法可用于肿瘤疾病的检测，诊断，监测，治疗或评估。

9. 发明申请

US20110275073A1 Method for detecting tumor-associated DNA in blood or blood fractions 有权
$Method for detecting tumor-associated DNA in blood or blood fractions$
标题翻译：用于检测血液或血液部分中肿瘤相关DNA的方法
公开(公告)号：US20110275073A1
公开(公告)日：2011-11-10
申请号：US13100253
申请日：2011-05-03
申请人： Christopher D. Gocke , Michael S. Kopreski
发明人： Christopher D. Gocke , Michael S. Kopreski
IPC分类号： C12Q1/68
CPC分类号： C07K14/82 , C07K14/47 , C07K14/4746 , C07K2319/00 , C12Q1/683 , C12Q1/686 , C12Q1/6865 , C12Q1/6886 , C12Q1/708 , C12Q2600/112 , C12Q2600/154 , C12Q2600/156 , C12Q2600/16 , C12Q2535/125
摘要： This invention relates to detection of specific extracellular nucleic acid in plasma or serum fractions of human or animal blood associated with neoplastic or proliferative disease. Specifically, the invention relates to detection of nucleic acid derived from mutant oncogenes or other tumor-associated DNA, and to those methods of detecting and monitoring extracellular mutant oncogenes or tumor-associated DNA found in the plasma or serum fraction of blood by using rapid DNA extraction followed by nucleic acid amplification with or without enrichment for mutant DNA. In particular, the invention relates to the detection, identification, or monitoring of the existence, progression or clinical status of benign, premalignant, or malignant neoplasms in humans or other animals that contain a mutation that is associated with the neoplasm through detection of the mutated nucleic acid of the neoplasm in plasma or serum fractions. The invention permits the detection of extracellular, tumor-associated nucleic acid in the serum or plasma of humans or other animals recognized as having a neoplastic or proliferative disease or in individuals without any prior history or diagnosis of neoplastic or proliferative disease. The invention provides the ability to detect extracellular nucleic acid derived from genetic sequences known to be associated with neoplasia, such as oncogenes, as well as genetic sequences previously unrecognized as being associated with neoplastic or proliferative disease. The invention thereby provides methods for early identification of colorectal, pancreatic, lung, breast, bladder, ovarian, lymphoma and all other malignancies carrying tumor-related mutations of DNA and methods for monitoring cancer and other neoplastic disorders in humans and other animals.
摘要翻译：本发明涉及在与肿瘤或增生性疾病相关的人或动物血液的血浆或血清部分中检测特异性细胞外核酸。具体地，本发明涉及来自突变致癌基因或其他肿瘤相关DNA的核酸的检测，以及通过使用快速DNA检测和监测在血浆或血清部分中发现的细胞外突变致癌基因或肿瘤相关DNA的方法提取后进行核酸扩增，扩增或不扩增突变DNA。特别地，本发明涉及通过检测突变体的检测，鉴定或监测包含与赘生物相关的突变的人或其他动物中的良性，恶化前或恶性肿瘤的存在，进展或临床状态血浆或血清级分中的肿瘤核酸。本发明允许检测被认为具有肿瘤或增殖性疾病的人或其他动物的血清或血浆中的细胞外，肿瘤相关核酸，或者在没有任何先前的肿瘤或增殖性疾病的历史或诊断的个体中。本发明提供了检测源自已知与肿瘤形成相关的遗传序列的细胞外核酸的能力，例如癌基因，以及先前未被认识为与肿瘤或增殖性疾病相关的遗传序列。因此，本发明提供了用于早期鉴定结直肠，胰腺，肺，乳腺，膀胱，卵巢，淋巴瘤和携带DNA的肿瘤相关突变的所有其他恶性肿瘤的方法以及用于监测人和其他动物中的癌症和其他肿瘤性疾病的方法。

10. 发明授权

US08048629B2 Detection of extracellular tumor-associated nucleic acid in blood plasma or serum 有权
标题翻译：检测血浆或血清中细胞外肿瘤相关核酸
公开(公告)号：US08048629B2
公开(公告)日：2011-11-01
申请号：US11835398
申请日：2007-08-07
申请人： Christopher D. Gocke , Michael S. Kopreski
发明人： Christopher D. Gocke , Michael S. Kopreski
IPC分类号： C12Q1/68 , C12P19/34 , A61K48/00
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/154
摘要： This invention relates to detection of specific extracellular DNA in plasma or serum fractions of human or animal blood associated with neoplastic, pre-malignant or proliferative disease. Specifically, the invention relates to detection tumor-associated DNA, and to those methods of detecting and monitoring tumor-associated DNA found in the plasma or serum fraction of blood by using DNA extraction and amplification with or without enrichment for DNA. The invention allows the selection and monitoring of patients for various cancer therapies including receptor tyrosine kinase inhibitor therapies.
摘要翻译：本发明涉及检测与肿瘤，恶变前或增殖性疾病相关的人或动物血液的血浆或血清部分中的特异性细胞外DNA。具体地，本发明涉及检测肿瘤相关DNA，以及通过使用具有或不具有DNA富集的DNA提取和扩增来检测和监测在血浆或血液血清部分中发现的肿瘤相关DNA的那些方法。本发明允许患者选择和监测各种癌症治疗，包括受体酪氨酸激酶抑制剂治疗。

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