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1. 发明申请

WO2010075414A3 METHOD FOR DETECTION OF XMRV 审中-公开
标题翻译：检测XMRV的方法
公开(公告)号：WO2010075414A3
公开(公告)日：2010-10-07
申请号：PCT/US2009069244
申请日：2009-12-22
申请人： CLEVELAND CLINIC FOUNDATION , SILVERMAN ROBERT H , KLEIN ERIC A , WEIGHT CHRISTOPHER J , NGUYEN CARVELL T , GUPTA JAYDIP DAS
发明人： SILVERMAN ROBERT H , KLEIN ERIC A , WEIGHT CHRISTOPHER J , NGUYEN CARVELL T , GUPTA JAYDIP DAS
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q1/702 , C12Q2600/16
摘要： The present invention relates to the identification of Xenotropic murine leukemia virus (XMRV) nucleic acid by polymerase chain reaction (PCR) analysis (e.g., real time PCR (RT/PCR); nested RT/PCR using Tth DNA polymerase and Hot start polymerase) and the uses thereof. In particular, the invention provides methods for the detection, and in particular early detection, of XMRV in RNA isolated from samples (e.g., urine samples; expressed prostate secretion (EPS)) of prostate cancer patients and normal individuals.
摘要翻译：本发明涉及通过聚合酶链式反应（PCR）分析（例如实时PCR（RT / PCR）;使用Tth DNA聚合酶和热启动聚合酶的巢式RT / PCR）鉴定异嗜性鼠白血病病毒（XMRV）及其用途。具体而言，本发明提供了用于检测并且特别是早期检测前列腺癌患者和正常个体的样品（例如，尿液样品;表达的前列腺分泌物（EPS））中分离的RNA中的XMRV的方法。

2. 发明申请

WO2009124184A3 AZABENZANTHRONES FOR THE TREATMENT OF VIRAL INFECTIONS, CANCER OR RESTENOSIS 审中-公开
标题翻译：用于治疗病毒感染或癌症的AZABENZANTHRONES
公开(公告)号：WO2009124184A3
公开(公告)日：2010-01-21
申请号：PCT/US2009039294
申请日：2009-04-02
申请人： CLEVELAND CLINIC FOUNDATION , SILVERMAN ROBERT H , JHA BABAL KHANT
发明人： SILVERMAN ROBERT H , JHA BABAL KHANT
IPC分类号： A61K31/473 , A61P9/00 , A61P9/10 , A61P31/12 , A61P35/00
CPC分类号： A61K31/473
摘要： A method of activating RNase L in a subject in need thereof comprises administering to the subject an effective amount of a compound represented in Structural Formula (I) or a pharmaceutically acceptable salt thereof. The activation of RNase L treats a viral infection, cancer or restenosis.
摘要翻译：在有需要的受试者中激活核糖核酸酶L的方法包括向受试者施用有效量的结构式（I）表示的化合物或其药学上可接受的盐。 RNA酶L的激活治疗病毒感染，癌症或再狭窄。

3. 发明申请

WO0183691A2 SYSTEM FOR IDENTIFYING AND ANALYZING EXPRESSION OF ARE-CONTAINING GENES 审中-公开
标题翻译：用于识别和分析含有基因的表达的系统
公开(公告)号：WO0183691A2
公开(公告)日：2001-11-08
申请号：PCT/US0111993
申请日：2001-04-12
申请人： CLEVELAND CLINIC FOUNDATION , KING FAISAL SPECIALIST HOSPITA , ABU KHABAR KHALID S , WILLIAMS BRYAN R G , FREVEL MATHIAS , SILVERMAN ROBERT H
发明人： ABU-KHABAR KHALID S , WILLIAMS BRYAN R G , FREVEL MATHIAS , SILVERMAN ROBERT H
IPC分类号： C12N15/09 , C12M1/00 , C12M1/34 , C12N20060101 , C12Q1/68 , G01N33/483 , G06F19/20 , G06F19/22 , G06F19/28 , C12N
CPC分类号： G06F19/28 , C12Q1/6897 , G06F19/20 , G06F19/22
摘要： Adenylate-uridylate-rich (ARE) elements present in the 3' untranslated region (UTR) of gene and mRNA sequences are disclosed. THE ARE motif comprises a sequence encompassed by: SEQ ID NO: 1 or 2, with further limitations. Computational methods of identifying genes or coding sequences in a database which comprise ARE elements are disclosed. The computational methods can be used for gene discovery, and sequence analysis. Methods of identifying, isolating and amplyfying ARE-element-associated polynucleotides using PCR, RT-PCR, hybridization, etc. are disclosed. PCR primers, oligonucleotide arrays, polynucleotide libraries, computer programs, and computer systems relating to ARE elements are disclosed.
摘要翻译：公开了存在于基因和mRNA序列的3'非翻译区（UTR）中的腺苷酸 - 富含尿苷酸（ARE）的元件。 ARE基序包含由SEQ ID NO：1或2包含的序列，其进一步的限制。公开了在包含ARE元素的数据库中识别基因或编码序列的计算方法。计算方法可用于基因发现和序列分析。公开了使用PCR，RT-PCR，杂交等鉴定，分离和纯化ARE-元件相关多核苷酸的方法。公开了与ARE元件相关的PCR引物，寡核苷酸阵列，多核苷酸文库，计算机程序和计算机系统。

4. 发明申请

WO0122970A9 THERAPY WITH 2-5A AND INTERFERON 审中-公开
标题翻译：用2-5A和INTERFERON治疗
公开(公告)号：WO0122970A9
公开(公告)日：2002-08-01
申请号：PCT/US0041038
申请日：2000-09-29
申请人： CLEVELAND CLINIC FOUNDATION , SILVERMAN ROBERT H , RUSCH LORRAINE
发明人： SILVERMAN ROBERT H , RUSCH LORRAINE
IPC分类号： C07H21/02 , A61K9/127 , A61K31/7125 , A61K38/21 , A61K45/06 , A61P35/00 , A61K31/70
CPC分类号： A61K31/7048 , A61K31/7125 , A61K38/21 , A61K45/06 , A61K47/543 , A61K31/70 , A61K2300/00
摘要： New methods of treating malignancies in a subject are provided. Such methods comprise administering 2', 5' oligoadenylate (2-5A) or a biostable analog of 2-5A to the subject. In some embodiments, IFN is also administered to the subject. Examples of cancers which may be treated according to the present method include, but are not limited to, hairy cell leukemia, Kaposi's sarcoma, CML, B-cell and T-cell lymphomas, melanomas, myelomas, renal cell carcinoma, ovarian, breast, bronchogenic, bladder, and gastrointestinal carcinomas and acute leukemias, malignant glioma and fibrosarcoma. Methods of treating viral diseases in a subject are also provided. Such methods comprise administering interferon and 2', 5' oligoadenylate (2-5A) or a biostable analog of to a subject. Examples of viral diseases which may be treated according to this method include, but are not limited to, hepatitis C, hepatitis B, and viral infections caused by human papilloma virus or a picornavirus. A method of selectively inducing programmed cell death (apoptosis) in cancer cells either in vitro or in vivo is also provided. The method comprises administering 2-5A or a biostable analog thereof to the cancer cells.
摘要翻译：提供了治疗受试者的恶性肿瘤的新方法。这样的方法包括向受试者施用2'，5'寡聚腺苷酸（2-5A）或2-5A的生物稳定类似物。在一些实施方案中，也向受试者施用IFN。可以根据本发明方法治疗的癌症的实例包括但不限于毛细胞白血病，卡波西肉瘤，CML，B细胞和T细胞淋巴瘤，黑素瘤，骨髓瘤，肾细胞癌，卵巢癌，乳腺癌，支气管，膀胱和胃肠癌和急性白血病，恶性胶质瘤和纤维肉瘤。还提供了治疗受试者中病毒性疾病的方法。这样的方法包括给予受试者的干扰素和2'，5'寡聚腺苷酸（2-5A）或生物稳定的类似物。可以根据该方法治疗的病毒性疾病的实例包括但不限于丙型肝炎，乙型肝炎和由人乳头瘤病毒或小核糖核酸病毒引起的病毒感染。还提供了在体外或体内选择性诱导癌细胞中程序性细胞死亡（细胞凋亡）的方法。该方法包括向癌细胞施用2-5A或其生物稳定的类似物。

5. 发明申请

WO0174295A3 PHOSPHOLIPID SCRAMBLASES AND METHODS OF USE THEREOF 审中-公开
标题翻译：磷光体萤光体及其使用方法
公开(公告)号：WO0174295A3
公开(公告)日：2002-02-21
申请号：PCT/US0110388
申请日：2001-03-30
申请人： SCRIPPS RESEARCH INST , CLEVELAND CLINIC FOUNDATION , SIMS PETER J , SILVERMAN ROBERT H , WIEDMER THERESE
发明人： SIMS PETER J , SILVERMAN ROBERT H , WIEDMER THERESE
IPC分类号： A61P31/12 , A61P43/00 , C07K14/47 , C12N9/00 , A61K38/00 , C07H21/04 , C12N1/20 , C12N15/00
CPC分类号： C07K14/47 , A01K2217/05
摘要： The present invention is based on a family of membrane proteins, Phospholipid Scramblases (PLSCR), that mediate accelerated trans-bilayer movement of plasma membrane phospholipids in response to elevated cytoplasmic calcium. At least one Phospholipid Scramblase gene is highly inducible by interferon. Interferon-induced expression of Phospholipid Scramblase 1 (and/or related genes) alters the physical and functional properties of the cell surface so as to (1) inhibit tumor cell proliferation and survival; (2) inhibit maturation and release of membrane-enveloped viruses; and/or (3) promote clearance of virus-infected cells and cancer cells through the reticuloendothelial system. The present invention provides Phospholipid Scramblase polypeptides, polynucleotide sequences that encode Phospholipid Scramblase polypeptides, and antibodies that are immunoreactive with the polypeptides. The finding that human Phospholipid Scramblase 1 polypeptides are induced by interferons, indicates a role for the Scramblase polypeptides in treating and preventing cancer and viral infection.
摘要翻译：本发明基于膜蛋白家族磷脂抗体（PLSCR），其介导响应于升高的细胞质钙的质膜磷脂的加速反式双层运动。至少一种磷脂类Scramblase基因可被干扰素高度诱导。干扰素诱导的磷脂抗体表达Scramblase 1（和/或相关基因）改变细胞表面的物理和功能特性，从而（1）抑制肿瘤细胞增殖和存活; （2）抑制膜包膜病毒的成熟和释放; 和/或（3）通过网状内皮系统促进病毒感染的细胞和癌细胞的清除。本发明提供了磷脂类Scramblase多肽，编码磷脂类Scramblase多肽的多核苷酸序列，以及与多肽免疫反应的抗体。人类磷脂类Scramblase 1多肽由干扰素诱导的发现表明，Scramblase多肽在治疗和预防癌症和病毒感染中起作用。

6. 发明专利

AU1494801A Therapy with 2-5a and interferon 未知
公开(公告)号：AU1494801A
公开(公告)日：2001-04-30
申请号：AU1494801
申请日：2000-09-29
申请人： CLEVELAND CLINIC FOUNDATION
发明人： SILVERMAN ROBERT H , RUSCH LORRAINE
IPC分类号： C07H21/02 , A61K9/127 , A61K31/7125 , A61K38/21 , A61K45/06 , A61P35/00 , A61K31/70

7. 发明专利

BR9404382A 未知
公开(公告)号：BR9404382A
公开(公告)日：1999-06-15
申请号：BR9404382
申请日：1994-03-03
申请人： CLEVELAND CLINIC FOUNDATION
发明人： SILVERMAN ROBERT H , HASSEL BRET A , ZHOU AIMIN
IPC分类号： C12N9/22 , C12N15/55 , C12N1/21 , C12N5/10
摘要： Isolated 2-5A-dependent RNases, an interferon-induced enzyme which is activated by 5'-phosphorylated, 2',5'-linked oligoadenylates (2-5A) and implicated in both the molecular mechanisms of interferon action and in the fundamental control of RNA stability in mammalian cells, and encoding sequences therefor are disclosed. The expression cloning and analysis of murine and human 2-5A-dependent RNases is also disclosed. Recombinant human 2-5A-dependent RNase produced in vitro bound an activating affinity matrix, 2-5A-cellulose, resulting in ribonuclease activity. The 2-5A binding properties of the recombinant and naturally occurring forms of 2-5A-dependent RNase are basically identical. Interferon induction of 2-5A-dependent RNase expression is demonstrated by measuring the mRNA levels in cells treated with interferon and cycloheximide. Analysis of aligned murine and human 2-5A-dependent RNase sequences revealed several features, including similarity to RNase E which is implicated in the control of mRNA stability in E. coli. A duplicated phosphate-binding loop motif is determined by deletion analysis and site-directed mutagenesis to function in the binding of 2-5A.

8. 发明专利

AU4746997A Mammals and cells with a homozygous disruption in the rnase gene and methods therefor 未知
公开(公告)号：AU4746997A
公开(公告)日：1998-04-24
申请号：AU4746997
申请日：1997-10-03
申请人： CLEVELAND CLINIC FOUNDATION THE
发明人： SILVERMAN ROBERT H , ZHOU AIMIN
IPC分类号： C12N9/22 , C12N15/85 , A61K48/00 , C12N15/00 , C12N15/79
摘要： The present invention provides a mutant, non-human mammal, particularly a mutant mouse, having a homozygous disruption in the RNase L gene thereof. Since the homozygous disruption in the RNase L gene leads to minimal if any production of RNase L in the mutant mammals, such mutant mammals are useful for assessing the effect of antiviral drugs on the induction, synthesis, or activation of RNase L. The present invention also relates to mutant, non-human, embryonic stem cell lines having a heterozygous disruption of the RNase L gene thereof, to isolated mammalian cells having a homozygous disruption in the RNase L gene thereof, and to a DNA construct comprising a DNA sequence of a disrupted coding exon of a RNase L gene.

9. 发明专利

AU6382796A Transgenic plants co-expressing a functional human 2-5a syst em 未知
公开(公告)号：AU6382796A
公开(公告)日：1996-12-30
申请号：AU6382796
申请日：1996-06-07
申请人： CLEVELAND CLINIC FOUNDATION THE
发明人： SILVERMAN ROBERT H , MITRA AMITAVA
IPC分类号： A01H5/00 , A01H1/00 , C12N9/12 , C12N9/22 , C12N15/09 , C12N15/82
摘要： Novel transgenic plants having the ability to express a functional 2-5A system, i.e., a 2-5A synthetase which produces 5'-phosphorylated, 2',5'-linked oligoadenylates (2-5A) in response to double stranded RNA (dsRNA), and a 2-5A-dependent (RNase L), are disclosed. The novel transgenic plants expressing the functional 2-5A system, such as novel transgenic tobacco plants, are immune to and resistant against viral infection. When the novel transgenic tobacco plants are exposed to three different types of plant viruses, i.e., TMV, TEV and AIMV, such viral exposure leads to necrotic local lesions in such transgenic tobacco plants instead of typical systemic infections.

10. 发明专利

CA2603863A1 GAMMARETROVIRUS ASSOCIATED WITH CANCER 未知
公开(公告)号：CA2603863A1
公开(公告)日：2006-10-19
申请号：CA2603863
申请日：2006-04-07
申请人： CLEVELAND CLINIC FOUNDATION , UNIV CALIFORNIA
发明人： SILVERMAN ROBERT H , DERISI JOSEPH , KLEIN ERIC A , GANEM DON , CASEY GRAHAM
IPC分类号： C12N7/00 , A61K39/21 , C07K14/15 , C12N5/10 , C12N7/02 , C12N15/11 , C12N15/63 , C12Q1/68 , G01N33/50 , G01N33/569

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