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1. 发明授权

US07358347B1 MEN1, the gene associated with multiple endocrine neoplasia type 1, menin polypeptides and uses thereof 失效
标题翻译： MEN1，与多发性内分泌肿瘤1型有关的基因，menin多肽及其用途
公开(公告)号：US07358347B1
公开(公告)日：2008-04-15
申请号：US09380337
申请日：1998-03-04
申请人： Settara Chandrasekharappa , Siradanahalli Guru , Pachiappan Manickam , Francis S. Collins , Michael R. Emmert-Buck , Larisa V. Debelenko , Irina A. Lubensky , Lance A. Liotta , Sunita K. Agarwal , Allen M. Spiegel , A. Lee Burns , Stephen J. Marx , Zhengping Zhuang
发明人： Settara Chandrasekharappa , Siradanahalli Guru , Pachiappan Manickam , Francis S. Collins , Michael R. Emmert-Buck , Larisa V. Debelenko , Irina A. Lubensky , Lance A. Liotta , Sunita K. Agarwal , Allen M. Spiegel , A. Lee Burns , Stephen J. Marx , Zhengping Zhuang
IPC分类号： C07H21/00 , C07H21/02 , C07H21/04 , C12Q1/68 , C12P19/26 , C12P19/34
CPC分类号： C12Q1/6886 , C12Q2600/156
摘要： The invention relates to the discovery of a novel tumor suppressor gene which is associated with multiple endocrine neoplasia type 1. The gene has been designated MEN1 and the gene product is menin. The absence of this protein and associated mutations in the corresponding gene have been identified in individuals suffering from multiple endocrine neoplasia type 1. The identification of this marker for multiple endocrine neoplasia type 1 has diagnostic uses as well as for gene therapy.
摘要翻译：本发明涉及一种与多发性内分泌肿瘤1型相关的新型肿瘤抑制基因的发现。该基因被命名为MEN1，该基因产物是menin。在具有1型多发性内分泌肿瘤1型的个体中已经鉴定了相应基因中不存在该蛋白质和相关突变。鉴定该多重内分泌肿瘤1型的该标志物具有诊断用途以及基因治疗。

2. 发明授权

US5843644A Isolation of cellular material under microscopic visualization using an adhesive/extraction reagent tipped probe 失效
标题翻译：使用粘合剂/提取试剂尖端探针在微观可视化下分离细胞材料
公开(公告)号：US5843644A
公开(公告)日：1998-12-01
申请号：US203780
申请日：1994-03-01
申请人： Lance A. Liotta , Zhengping Zhuang , Michael R. Buck , William G. Stetler-Stevenson , Irina A. Lubensky , Mark J. Roth
发明人： Lance A. Liotta , Zhengping Zhuang , Michael R. Buck , William G. Stetler-Stevenson , Irina A. Lubensky , Mark J. Roth
IPC分类号： G01N33/48 , C12M1/26 , C12M1/34 , G01N1/02 , G01N1/04 , G01N1/08 , G01N1/28 , G01N1/31 , G01N15/14 , G01N33/483 , G01N33/50 , G01N35/00 , G02B21/32 , C12Q1/68
CPC分类号： G02B21/32 , G01N1/2813 , G01N1/286 , G01N33/50 , G01N1/04 , G01N1/08 , G01N1/2806 , G01N1/31 , G01N2001/028 , G01N2001/2833 , G01N2001/284 , G01N2035/00237 , Y10S435/808 , Y10S436/805
摘要： A method of direct extraction of cellular material from a tissue sample which involves: forming an image field of cells of the tissue sample utilizing a microscope, identifying at least one zone of cells of interest from the image field of cells which at least one zone of cells of interest includes different types of cells than adjacent zones of cells, and extracting the at least one zone of cells of interest from the tissue sample. The extracted zone(s) of cells is subjected to analysis. The overall process of identifying, extracting, transporting, and analyzing the extracted zones(s) of cells can be fully automated.
摘要翻译：一种从组织样品直接提取细胞材料的方法，该方法包括：使用显微镜形成组织样品的细胞的图像场，从细胞的图像区域识别感兴趣的细胞的至少一个区域，至少一个区域感兴趣的细胞包括与细胞的相邻区域不同的细胞类型，以及从组织样品提取感兴趣的细胞的至少一个区域。对提取的细胞区进行分析。识别，提取，运送和分析提取的细胞区域的整个过程可以完全自动化。

3. 发明授权

US07226731B1 PB 39, a gene dysregulated in prostate cancer, and uses thereof 失效
标题翻译： PB39，前列腺癌失调的基因及其用途
公开(公告)号：US07226731B1
公开(公告)日：2007-06-05
申请号：US09743825
申请日：1999-07-23
申请人： Rodrigo F. Chuaqui , Kristina A. Cole , Lance A. Liotta , Michael R. Emmert-Buck
发明人： Rodrigo F. Chuaqui , Kristina A. Cole , Lance A. Liotta , Michael R. Emmert-Buck
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q2600/158
摘要： A novel gene, PB39, that is up-regulated, or over-expressed, in prostate cancer has been identified. The gene has been identified by means of its cDNA obtained by reverse transcription of the corresponding mRNA. Microdissection of prostate glands that had been surgically removed from prostate cancer patients revealed a novel up-regulated transcript in an aggressive prostate carcinoma. Differential analysis for the presence of this gene was carried out from the same glands by comparing transcription in microdissected normal prostatic epithelium versus that in microdissected invasive tumor. The transcript was over-expressed in 5 of 10 prostate carcinomas examined. A variant transcript was over-expressed in 4 of 4 prostate carcinomas, and was found in 1 of 4 normal samples. The invention provides a purified and isolated nucleic acid that includes the sequence of PB39 or its complement, the sequence of a variant of PB39 or its complement, and a primer or probe, that includes a sequence that is a fragment of these sequences. Additionally, the polypeptide encoded by these genes, an antibody to the polypeptide, and methods of detection of PB39 or its gene product are provided.
摘要翻译：已经鉴定出在前列腺癌中上调或过度表达的新基因PB39。该基因已通过其相应mRNA的逆转录获得的cDNA鉴定。从前列腺癌患者手术切除的前列腺的显微解剖显示在侵袭性前列腺癌中有一种新的上调的转录物。通过比较显微解剖正常前列腺上皮中的转录与微切割侵袭性肿瘤中的转录，从相同腺体进行差异分析。在检查的10个前列腺癌中的5个中，转录物过表达。在4个前列腺癌中的4个中，变体转录物过表达，并且在4个正常样品中的1个中发现。本发明提供了纯化和分离的核酸，其包括PB39或其互补序列，PB39或其互补序列变体的序列，以及引物或探针，其包括作为这些序列的片段的序列。另外，提供了由这些基因编码的多肽，多肽的抗体，以及检测PB39或其基因产物的方法。

4. 发明授权

US06204030B1 Isolation of cellular material under microscopic visualization 失效
标题翻译：在微观可视化下分离细胞材料
公开(公告)号：US06204030B1
公开(公告)日：2001-03-20
申请号：US09388805
申请日：1999-09-02
申请人： Lance A. Liotta , Michael E. Buck , Rhonda Ann Weiss , Zhengping Zhuang , Robert F. Bonner
发明人： Lance A. Liotta , Michael E. Buck , Rhonda Ann Weiss , Zhengping Zhuang , Robert F. Bonner
IPC分类号： C12P1912
CPC分类号： G02B21/32 , C12M33/02 , G01N1/04 , G01N1/08 , G01N1/2806 , G01N1/2813 , G01N1/286 , G01N1/31 , G01N15/1468 , G01N33/50 , G01N2001/028 , G01N2001/2833 , G01N2001/284 , G01N2035/00237 , Y10T436/25 , Y10T436/25125 , Y10T436/25375
摘要： A method of microdissection which involves: forming an image field of cells of the tissue sample utilizing a microscope, identifying at least one zone of cells of interest from the image field of cells which at least one zone of cells of interest includes different types of cells than adjacent zones of cells, and extracting the at least one zone of cells of interest from the tissue sample. The extraction is achieved by contacting the tissue sample with a transfer surface that can be selectively activated so that regions thereof adhere to the zone of cells of interest to be extracted. The transfer surface includes an activatable adhesive layer which provides chemical or electrostatic adherence to the selected regions of the tissue sample. After the transfer surface is activated the transfer surface and tissue sample are separated. During separation the zone of cells of interest remains adhered to the transfer surface and is thus separated from the tissue sample.
摘要翻译：一种显微切割的方法，其包括：使用显微镜形成组织样品的细胞的图像场，从细胞的图像区域鉴定感兴趣的细胞的至少一个区域，所述细胞的至少一个区域包括不同类型的细胞而不是相邻的细胞区域，并且从组织样品中提取感兴趣的细胞的至少一个区域。通过使组织样品与可以选择性活化的转移表面接触使得其区域粘附到待提取的感兴趣的细胞区域来实现提取。转移表面包括可激发的粘合剂层，其向组织样品的选定区域提供化学或静电粘附。转移表面被激活后，分离转移表面和组织样品。在分离期间，感兴趣的细胞区域保持粘附到转移表面，并因此与组织样品分离。

5. 发明授权

US6010888A Isolation of cellular material under microscopic visualization 失效
公开(公告)号：US6010888A
公开(公告)日：2000-01-04
申请号：US925894
申请日：1997-09-08
申请人： Lance A. Liotta , Michael E. Buck , Rhonda Ann Weiss , Zhengping Zhuang , Robert F. Bonner
发明人： Lance A. Liotta , Michael E. Buck , Rhonda Ann Weiss , Zhengping Zhuang , Robert F. Bonner
IPC分类号： G01N33/48 , C12M1/26 , C12M1/34 , G01N1/02 , G01N1/04 , G01N1/08 , G01N1/28 , G01N1/31 , G01N15/14 , G01N33/483 , G01N33/50 , G01N35/00 , G02B21/32 , C12P19/12
CPC分类号： G02B21/32 , C12M33/02 , G01N1/2813 , G01N1/286 , G01N33/50 , G01N1/04 , G01N1/08 , G01N1/2806 , G01N1/31 , G01N15/1468 , G01N2001/028 , G01N2001/2833 , G01N2001/284 , G01N2035/00237 , Y10T436/25 , Y10T436/25125 , Y10T436/25375
摘要： A method of microdissection which involves: forming an image field of cells of the tissue sample utilizing a microscope, identifying at least one zone of cells of interest from the image field of cells which at least one zone of cells of interest includes different types of cells than adjacent zones of cells, and extracting the at least one zone of cells of interest from the tissue sample. The extraction is achieved by contacting the tissue sample with a transfer surface that can be selectively activated so that regions thereof adhere to the zone of cells of interest to be extracted. The transfer surface includes an activatable adhesive layer which provides chemical or electrostatic adherence to the selected regions of the tissue sample. After the transfer surface is activated the transfer surface and tissue sample are separated. During separation the zone of cells of interest remains adhered to the transfer surface and is thus separated from the tissue sample.

6. 发明授权

US06569639B2 Isolation of cellular material under microscopic visualization 失效
标题翻译：在微观可视化下分离细胞材料
公开(公告)号：US06569639B2
公开(公告)日：2003-05-27
申请号：US09765937
申请日：2001-01-18
申请人： Lance A. Liotta , Michael E. Buck , Rhonda Ann Weiss , Zhengping Zhuang , Robert F. Bonner
发明人： Lance A. Liotta , Michael E. Buck , Rhonda Ann Weiss , Zhengping Zhuang , Robert F. Bonner
IPC分类号： G01N130
CPC分类号： G02B21/32 , C12M33/02 , G01N1/04 , G01N1/08 , G01N1/2806 , G01N1/2813 , G01N1/286 , G01N1/31 , G01N15/1468 , G01N33/50 , G01N2001/028 , G01N2001/2833 , G01N2001/284 , G01N2035/00237 , Y10T436/25 , Y10T436/25125 , Y10T436/25375
摘要： A method of microdissection which involves: forming an image field of cells of the tissue sample utilizing a microscope, identifying at least one zone of cells of interest from the image field of cells which at least one zone of cells of interest includes different types of cells than adjacent zones of cells, and extracting the at least one zone of cells of interest from the tissue sample. The extraction is achieved by contacting the tissue sample with a transfer surface that can be selectively activated so that regions thereof adhere to the zone of cells of interest to be extracted. The transfer surface includes an activatable adhesive layer which provides chemical or electrostatic adherence to the selected regions of the tissue sample. After the transfer surface is activated the transfer surface and tissue sample are separated. During separation the zone of cells of interest remains adhered to the transfer surface and is thus separated from the tissue sample.
摘要翻译：一种显微切割的方法，其包括：使用显微镜形成组织样品的细胞的图像场，从细胞的图像区域鉴定感兴趣的细胞的至少一个区域，所述细胞的至少一个区域包括不同类型的细胞而不是相邻的细胞区域，并且从组织样品中提取感兴趣的细胞的至少一个区域。通过使组织样品与可以选择性活化的转移表面接触使得其区域粘附到待提取的感兴趣的细胞区域来实现提取。转移表面包括可激发的粘合剂层，其向组织样品的选定区域提供化学或静电粘附。转移表面被激活后，分离转移表面和组织样品。在分离期间，感兴趣的细胞区域保持粘附到转移表面，并因此与组织样品分离。

7. 发明授权

US09086414B2 Phosphorylated C-ErbB2 as a superior predictive theranostic marker for the diagnosis and treatment of cancer 有权
标题翻译：磷酸化的C-ErbB2作为癌症诊断和治疗的优越预测因素
公开(公告)号：US09086414B2
公开(公告)日：2015-07-21
申请号：US13003206
申请日：2009-07-08
申请人： Emanuel F. Petricoin, III , Lance A. Liotta , Virginia Espina , Julia D. Wulfkuhle
发明人： Emanuel F. Petricoin, III , Lance A. Liotta , Virginia Espina , Julia D. Wulfkuhle
IPC分类号： A61K39/395 , A01N43/48 , G01N33/53 , G01N33/543 , G01N33/574 , C12Q1/68 , A61K31/517 , G01N1/30 , A61K39/00
CPC分类号： G01N33/57492 , A61K31/517 , A61K39/39558 , A61K2039/505 , C12Q1/6841 , C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , G01N1/30 , G01N33/54366 , G01N33/574 , G01N33/57415 , G01N2033/57403 , G01N2333/71 , G01N2800/52
摘要： The present invention provides reliable methods to identify subsets of subjects with a cancer of epithelial origin characterized by a high level of phosphorylated c-erbB2 which does not correlate with the over-expression of total c-erbB2 as measured by IHC or FISH, for selection and inclusion for c-erbB2-direct treatment and therapy. Furthermore, the present invention provides a reliable method to determine whether a subject with a cancer of epithelial origin who has been determined to be c-erbB2 positive by IHC and by FISH should be excluded from c-erbB2-direct treatment because of a non-significant level of phosphorylated c-erbB2 in epithelial tumor tissue.
摘要翻译：本发明提供了可靠的方法来鉴定具有上皮起源癌症的受试者的亚群，其特征在于高水平的磷酸化c-erbB2，其与通过IHC或FISH测量的总c-erbB2的过表达不相关，用于选择并包括c-erbB2直接治疗和治疗。此外，本发明提供了一种可靠的方法，用于确定由IHC和FISH确定为c-erbB2阳性的具有上皮起源癌症的受试者是否应从c-erbB2直接治疗中排除，磷酸化c-erbB2在上皮肿瘤组织中的显着水平。

8. 发明授权

US09012240B2 Hydrogel nanoparticle based immunoassay 有权
标题翻译：基于水凝胶纳米颗粒的免疫测定
公开(公告)号：US09012240B2
公开(公告)日：2015-04-21
申请号：US13061507
申请日：2009-08-26
申请人： Lance A. Liotta , Alessandra Luchini , Emanuel F. Petricoin , Virginia Espina
发明人： Lance A. Liotta , Alessandra Luchini , Emanuel F. Petricoin , Virginia Espina
IPC分类号： G01N33/549 , G01N33/53 , G01N33/544 , G01N33/558 , G01N33/52 , G01N33/543
CPC分类号： G01N33/521 , G01N33/54333 , G01N33/54346
摘要： An immunoassay device incorporating porous polymeric capture nanoparticles within either the sample collection vessel or pre-impregnated into a porous substratum within fluid flow path of the analytical device is presented. This incorporation of capture particles within the immunoassay device improves sensitivity while removing the requirement for pre-processing of samples prior to loading the immunoassay device. A preferred embodiment is coreshell bait containing capture nanoparticles which perform three functions in one step, in solution: a) molecular size sieving, b) target analyte sequestration and concentration, and c) protection from degradation. The polymeric matrix of the capture particles may be made of co-polymeric materials having a structural monomer and an affinity monomer, the affinity monomer having properties that attract the analyte to the capture particle. This device is useful for point of care diagnostic assays for biomedical applications and as field deployable assays for environmental, pathogen and chemical or biological threat identification.
摘要翻译：提供了在分析装置的流体流动路径内将多孔聚合物捕获纳米颗粒结合到样品采集容器中或预浸渍到多孔基质内的免疫测定装置。这种在免疫测定装置内的捕获颗粒的并入提高了灵敏度，同时在加载免疫测定装置之前消除了样品预处理的要求。优选的实施方案是含有捕获纳米颗粒的芯壳诱饵，其在一个步骤中在溶液中进行三个功能：a）分子筛分，b）目标分析物螯合和浓缩，以及c）防止降解。捕获颗粒的聚合物基质可以由具有结构单体和亲和单体的共聚物制成，亲和单体具有将分析物吸引到捕获颗粒的性质。该设备可用于生物医学应用的护理点诊断分析以及环境，病原体和化学或生物威胁鉴定的现场部署测定。

9. 发明授权

US08460859B2 Tissue preservation and fixation method 有权
标题翻译：组织保存和固定方法
公开(公告)号：US08460859B2
公开(公告)日：2013-06-11
申请号：US12447773
申请日：2007-10-26
申请人： Virginia A. Espina , Lance A. Liotta , David Geho
发明人： Virginia A. Espina , Lance A. Liotta , David Geho
IPC分类号： A01N1/00
CPC分类号： G01N1/30 , A01N1/00
摘要： This invention relates, e.g., to a composition that, at room temperature, when contacted with a sample comprising phosphoproteins, can fix and stabilize cellular phosphoproteins, preserve cellular morphology, and allow the sample to be frozen to generate a cryostat frozen section suitable for molecular analysis. The composition comprises (1) a fixative that is effective to fix the phosphoproteins, and that has a sufficient water content to be soluble for a stabilizer and/or a permeability enhancing agent); (2) a stabilizer, comprising (a) a kinase inhibitor and (b) a phosphatase inhibitor and, optionally, (c) a protease (e.g., proteinase) inhibitor; and (3) a permeability enhancing agent (e.g. PEG). Methods are described for preserving phosphoproteins, using such a composition. Also described are endogenous surrogate markers for monitoring protein degradation, including the loss of posttranslational modifications (such as phosphorylation), e.g. the following removal of a cell or tissue from a subject; and exogenous molecular sentinels (e.g. phosphoproteins attached to magnetic nanoparticles) that allow one to evaluate the processing history of a cellular or tissue population sample.
摘要翻译：本发明涉及例如在室温下与包含磷蛋白的样品接触时可以固定和稳定细胞磷酸蛋白的组合物，保留细胞形态，并允许样品冷冻以产生适于分子的低温恒温器冷冻切片分析。组合物包含（1）固定磷酸蛋白有效的固定剂，并且其具有足够的水含量可溶于稳定剂和/或渗透性增强剂）; （2）稳定剂，其包含（a）激酶抑制剂和（b）磷酸酶抑制剂和任选的（c）蛋白酶（例如蛋白酶）抑制剂; 和（3）渗透性增强剂（例如PEG）。描述了使用这种组合物来保存磷蛋白的方法。还描述了用于监测蛋白质降解的内源替代标记，包括翻译后修饰（例如磷酸化）的丧失，例如，以下从受试者中除去细胞或组织; 和外源性分子前哨蛋白（例如连接到磁性纳米颗粒的磷酸蛋白），其允许评价细胞或组织群体样品的加工历史。

10. 发明申请

US20110207627A1 EX VIVO THERAPEUTICS SCREENING OF LIVING BONE MARROW CELLS FOR MULTIPLE MYELOMA 审中-公开
标题翻译：用于多发性骨髓瘤的生物骨髓细胞的筛查治疗
公开(公告)号：US20110207627A1
公开(公告)日：2011-08-25
申请号：US13057978
申请日：2009-08-12
申请人： Lance A. Liotta , Emanuel F. Petricoin, III , Virginia Espina
发明人： Lance A. Liotta , Emanuel F. Petricoin, III , Virginia Espina
IPC分类号： C12Q1/02 , G01N33/566 , C40B30/04 , C12Q1/37 , C12Q1/48 , H01J49/26
CPC分类号： G01N33/56972 , G01N33/5011 , G01N2333/70596 , G01N2510/00 , G01N2800/52
摘要： Methods of selecting a treatment for a patient with multiple myeloma are provided. Prior to commencing a treatment regime, bone marrow aspirates are isolated from a patient and incubated with one or more candidate therapeutics. The methods identify the therapy or combination of therapies most likely to yield the best results for a particular individual. In addition to improving clinical outcome, such theranostic evaluations dramatically reduce health care costs, by avoiding ineffective therapies. Screening assays for identifying treatments for multiple myeloma also are provided.
摘要翻译：提供了选择多发性骨髓瘤患者的治疗方法。在开始治疗方案之前，从患者中分离骨髓抽吸物并与一种或多种候选治疗剂一起温育。该方法确定最有可能为特定个体产生最佳结果的治疗或疗法组合。除了改善临床结果之外，这种诊断性评估通过避免无效疗法，大大降低了医疗保健成本。还提供了用于鉴定多发性骨髓瘤治疗的筛选试验。

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