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1. 发明申请

WO2008036341A2 COMPOSITIONS AND METHODS RELATING TO GLUCAGON RECEPTOR ANTIBODIES 审中-公开
标题翻译：与GLUCAGON受体抗体相关的组合物和方法
公开(公告)号：WO2008036341A2
公开(公告)日：2008-03-27
申请号：PCT/US2007020349
申请日：2007-09-19
申请人： AMGEN INC , YAN HAI , HU SHAW-FEN SYLVIA , BOONE THOMAS C , LINDBERG RICHARD A
发明人： YAN HAI , HU SHAW-FEN SYLVIA , BOONE THOMAS C , LINDBERG RICHARD A
CPC分类号： C07K16/2869 , A61K2039/505 , C07K14/723 , C07K2317/21 , C07K2317/34 , C07K2317/56 , C07K2317/565 , C07K2317/76 , C07K2317/92
摘要： The present disclosure provides compositions and methods relating to antigen binding proteins, in particular, antibodies which specifically bind to the human glucagon receptor. The disclosure provides nucleic acids encoding such antigen binding proteins and antibodies and methods of making and using such antibodies including methods of treating and preventing type 2 diabetes and related disorders by administering such antibodies to a subject in need of such treatment.
摘要翻译：本公开提供了与抗原结合蛋白特别是特异性结合人胰高血糖素受体的抗体相关的组合物和方法。本公开提供了编码这种抗原结合蛋白的核酸和抗体，以及制备和使用这些抗体的方法，包括通过向需要这种治疗的受试者施用此类抗体来治疗和预防2型糖尿病和相关疾病的方法。

2. 发明申请

WO2013012927A3 OLIGODENDROGLIOMA DRIVER GENES 审中-公开
公开(公告)号：WO2013012927A3
公开(公告)日：2013-03-21
申请号：PCT/US2012047211
申请日：2012-07-18
申请人： UNIV JOHNS HOPKINS , UNIV DUKE , VOGELSTEIN BERT , KINZLER KENNETH W , BETTEGOWDA CHETAN , AGRAWAL NISHANT , PAPADOPOULOS NICKOLAS , BIGNER DARELL , YAN HAI , MCLENDON ROGER
发明人： VOGELSTEIN BERT , KINZLER KENNETH W , BETTEGOWDA CHETAN , AGRAWAL NISHANT , PAPADOPOULOS NICKOLAS , BIGNER DARELL , YAN HAI , MCLENDON ROGER
IPC分类号： C12Q1/68 , C12N15/11
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , C12Q2600/118 , C12Q2600/156 , C12Q2600/158
摘要： Oligodendrogliomas are the second most common malignant brain tumor in adults. These tumors often contain a chromosomal abnormality involving a pericentromeric fusion of chromosomes 1 and 19, resulting in losses of the entire short arm of the former and the long arm of the latter. To identify the molecular genetic basis for this alteration, we performed exomic sequencing of seven anaplastic oligodendrogliomas with chromosome 1p and 19q losses. Among other changes, we found that that CIC (homolog of the Drosophila gene capicua) on chromosome 19q was somatically mutated in six of the seven cases and that FUBP1 (far upstream element (FUSE) binding protein) on chromosome 1p was somatically mutated in two of the seven cases. Examination of 27 additional oligodendrogliomas revealed 12 and 3 more tumors with mutations of CIC and FUBP1, respectively, 58% of which were predicted to result in truncations of the encoded proteins. These results suggest a critical role for these genes in the biology and pathology of oligodendrocytes.
摘要翻译：少突神经胶质瘤是成人中第二常见的恶性脑肿瘤。这些肿瘤通常含有涉及染色体1和19的pericentromer融合的染色体异常，导致前者的整个短臂和后者的长臂损失。为了确定这种改变的分子遗传基础，我们对染色体1p和19q丢失的7个间变性少突神经胶质瘤进行了外显子测序。在其他变化中，我们发现染色体19q上的CIC（果蝇基因capicua的同源物）在七个病例中的六个中发生体细胞突变，并且染色体1p上的FUBP1（远端上游元件（FUSE）结合蛋白）在两个体细胞突变在七宗个案中。 27例额外少突胶质瘤的检查发现12例和3例多发CIC和FUBP1突变的肿瘤，其中58％预计会导致编码蛋白截短。这些结果表明这些基因在少突胶质细胞的生物学和病理学中起关键作用。

3. 发明申请

WO2005010145A3 METHOD AND COMPOSITIONS FOR DETECTION AND ENUMERATION OF GENETIC VARIATIONS 审中-公开
标题翻译：用于检测和遗传变异计算的方法和组合物
公开(公告)号：WO2005010145A3
公开(公告)日：2005-08-11
申请号：PCT/US2004015587
申请日：2004-06-09
申请人： UNIV JOHNS HOPKINS , DRESSMAN DEVIN , YAN HAI , KINZLER KENNETH W , VOGELSTEIN BERT
发明人： DRESSMAN DEVIN , YAN HAI , KINZLER KENNETH W , VOGELSTEIN BERT
IPC分类号： C07H21/04 , C12N20060101 , C12N15/10 , C12Q1/68
CPC分类号： C12Q1/6858 , C07H21/04 , C12N15/1075 , C12Q1/686 , C12Q2565/537 , C12Q2563/149 , C12Q2563/143
摘要： Many areas of biomedical research depend on the analysis of uncommon variations in individual genes or transcripts. Here we describe a method that can quantify such variation at a scale and ease heretofore unattainable. Each DNA molecule in a collection of such molecules is converted into a single particle to which thousands of copies of DNA identical in sequence to the original are bound. This population of beads then corresponds to a one-to-one representation of the starting DNA molecules. Variation within the original population of DNA molecules can then be simply assessed by counting fluorescently-labeled particles via flow cytometry. Millions of individual DNA molecules can be assessed in this fashion with standard laboratory equipment. Moreover, specific variants can be isolated by flow sorting and employed for further experimentation. This approach can be used for the identification and quantification of rare mutations as well as to study variations in gene sequences or transcripts in specific populations or tissues.
摘要翻译：生物医学研究的许多领域取决于对个别基因或转录本中罕见变异的分析。在这里我们描述一种方法，可以量化这种变化的规模和缓解迄今为止无法实现。这些分子集合中的每个DNA分子都被转化为一个单一的颗粒，数千个拷贝的DNA序列与原始序列相同。然后这个珠子群对应于起始DNA分子的一对一表示。然后可以通过流式细胞术计数荧光标记的颗粒来简单评估原始DNA分子群体内的变化。数百万个体DNA分子可以用这种方式用标准的实验室设备进行评估。此外，可以通过流分选分离特定的变体并用于进一步的实验。这种方法可用于鉴定和量化罕见突变，以及研究特定人群或组织中基因序列或转录本的变异。

4. 发明申请

WO2012054915A3 HOMOZYGOUS AND HETEROZYGOUS IDH1 GENE-DEFECTIVE HUMAN ASTROCYTOMA CELL LINES 审中-公开
标题翻译：异基因和异源IDH1基因缺陷人类ASTROCYTOMA细胞系
公开(公告)号：WO2012054915A3
公开(公告)日：2012-07-19
申请号：PCT/US2011057466
申请日：2011-10-24
申请人： UNIV DUKE , YAN HAI , BIGNER DARELL , GENGLIN JIN
发明人： YAN HAI , BIGNER DARELL , GENGLIN JIN
IPC分类号： C12N5/071 , C12N5/10 , C12Q1/02
CPC分类号： C12N5/0693
摘要： We provide IDH1 gene-defective cell lines (e.g., IDH1R132H heterozygous and IDH1R132H homozygous) derived from dissociated human astrocytoma samples. The cells can be used alone or in combination with each other or other cell types as a tool for determining the impact of IDH1R132H on cellular biology, tumorigenesis, and metabolic profiles. The cell lines may be used to test and identify therapeutic targets and to screen for molecular therapeutic agents.
摘要翻译：我们提供衍生自解离的人类星形细胞瘤样品的IDH1基因缺陷型细胞系（例如，IDH1R132H杂合型和IDH1R132H纯合子）。细胞可以单独使用，也可以彼此组合使用，也可以作为确定IDH1R132H对细胞生物学，肿瘤发生和代谢特征影响的工具。细胞系可用于测试和鉴定治疗靶标并筛选分子治疗剂。

5. 发明申请

WO2012064721A2 MEDULLOBLASTOMA GENES AS TARGETS FOR DIAGNOSIS AND THERAPEUTICS 审中-公开
标题翻译：作为诊断和治疗目标的MEDLOBLASTOMA基因
公开(公告)号：WO2012064721A2
公开(公告)日：2012-05-18
申请号：PCT/US2011059751
申请日：2011-11-08
申请人： UNIV JOHNS HOPKINS , UNIV DUKE , VOGELSTEIN BERT , KINZLER KENNETH W , PAPADOPOULOS NICKOLAS , PARSONS DONALD WILLIAMS , LEARY REBECCA J , LI MENG , ZHANG XIAOSONG , JONES SIAN , RIGGINS GREGORY J , VELCULESCU VICTOR , BIGNER DARELL , YAN HAI
发明人： VOGELSTEIN BERT , KINZLER KENNETH W , PAPADOPOULOS NICKOLAS , PARSONS DONALD WILLIAMS , LEARY REBECCA J , LI MENG , ZHANG XIAOSONG , JONES SIAN , RIGGINS GREGORY J , VELCULESCU VICTOR , BIGNER DARELL , YAN HAI
IPC分类号： G01N33/574 , C12Q1/68 , G01N33/50
CPC分类号： C12Q1/6886 , C12Q2600/112 , C12Q2600/156 , G01N33/57407
摘要： Medulloblastoma (MB) is the most common malignant brain tumor of children. To identify the genetic alterations in this tumor type, we searched for copy number alterations using high density microarrays and sequenced all known protein-coding genes and miRNA genes using Sanger sequencing. We found that, on average, each tumor had 11 gene alterations, markedly fewer than in common adult cancers. In addition to alterations in the Hedgehog and Wnt pathways, our analysis led to the discovery of genes not previously known to be altered in MBs. Most notably, inactivating mutations of the histone H3K4 trimethylase genes MLL2 or MLL3 were identified in 16% of MB patients. These results demonstrate key differences between the genetic landscapes of adult and childhood cancers, highlight dysregulation of developmental pathways as an important mechanism underlying MBs, and identify a role for a specific type of histone methylation in human tumorigenesis.
摘要翻译：髓母细胞瘤（MB）是儿童最常见的恶性脑肿瘤。为了鉴定这种肿瘤类型的遗传改变，我们使用高密度微阵列搜索拷贝数改变，并使用Sanger测序对所有已知的蛋白质编码基因和miRNA基因进行测序。我们发现平均而言，每个肿瘤有11个基因改变，明显少于常见的成人癌症。除了Hedgehog和Wnt途径的改变之外，我们的分析还导致发现以前不知道在MB中改变的基因。最值得注意的是，在16％的MB患者中鉴定出组蛋白H3K4三甲基化酶基因MLL2或MLL3的失活突变。这些结果表明成人和儿童癌症的遗传景观之间的主要区别，突出发展途径的失调作为潜在的MB的重要机制，并确定在人类肿瘤特定类型的组蛋白甲基化的作用。

6. 发明申请

WO2012061105A3 HOMOZYGOUS AND HETEROZYGOUS IDH1 GENE-DEFECTIVE CELL LINES DERIVED FROM HUMAN COLORECTAL CELLS 审中-公开
公开(公告)号：WO2012061105A3
公开(公告)日：2012-06-28
申请号：PCT/US2011057615
申请日：2011-10-25
申请人： UNIV DUKE , YAN HAI , BIGNER DARELL , DUNCAN CHRISTOPHER GENTRY
发明人： YAN HAI , BIGNER DARELL , DUNCAN CHRISTOPHER GENTRY
IPC分类号： C12N5/10 , A01K67/027 , C12N5/09 , C12N15/85
CPC分类号： C12N15/85 , C12N5/0693 , C12N15/902 , C12N2510/00 , C12N2799/025 , C12N2800/30
摘要： IDH1 gene-defective cell lines (e.g., IDH1R132H heterozygous) have been made from a robust cell line, HCT116. The IDH1 gene-defective cell lines can be used to determine the effect of IDH1R132H on cell biology, tumorigenesis, and cellular metabolic profiles. These cell lines can be used to test potential therapeutic targets and to screen potential therapeutic agents. Kits and xenografts are also contemplated.

7. 发明申请

WO2004081495A3 MICROMACHINED VIBRATORY GYROSCOPE WITH ELECTROSTATIC COUPLING 审中-公开
标题翻译：具有静电耦合的微型振动陀螺仪
公开(公告)号：WO2004081495A3
公开(公告)日：2005-04-21
申请号：PCT/US2004006453
申请日：2004-03-03
申请人： BEI TECHNOLOGIES INC , CONTI TEMIC MICROELECTRONIC , CONTINENTAL TEVES AG & CO OHG , YAN HAI , BURGHARDT ROLAND , HARTMANN BERNHARD , KAPSER KONRAD , ROSE MATTHIAS
发明人： YAN HAI , BURGHARDT ROLAND , HARTMANN BERNHARD , KAPSER KONRAD , ROSE MATTHIAS
IPC分类号： G01C19/5712 , G01C19/56
CPC分类号： G01C19/5719 , Y10T74/1275
摘要： Micromachined vibratory gyroscope having two or more coplanar movable masses suspended over a planar substrate. Two perpendicular axes (x and y) are defined within the substrate plane, while a third, the z-axis or input axis, is defined to be perpendicular to the substrate plane. The movements of the two masses along the x-axis are coupled through an electrostatic coupling means so that the natural resonant frequency of the in-phase mode and that of the anti-phase mode are separated from each other for the resonances along the x-axis. When the two masses are driven to vibrate along the x-axis in the anti-phase mode and the device experiences rotation about the z-axis, Coriolis forces act differentially on the masses in the Ydirection, causing the two masses to dither in an anti-phase motion along the y-axis. The anti-phase dithering along the y-axis can be sensed directly by a rate sensor to measure the rate of rotation about the z-axis. Alternatively, the anti-phase dithering of the first and second bodies along the y-axis can be transferred to other movable bodies (i.e., rate-sensing masses) whose movement is then sensed to measure the rate of rotation about the z-axis. The sensing bodies are preferably suspended in such manner that, in the absence of Coriolis forces, the x-axis motion of the vibrating masses does not affect the sensing bodies. That inhibits motion of the sensing bodies in response to linear acceleration within the plane of the substrate, but permits those bodies to respond readily to the Corollas-induced motion about an axis perpendicular to the substrate plane.
摘要翻译：微机械振动陀螺仪具有悬挂在平面基板上的两个或更多个共面可移动质量块。两个垂直轴（x和y）被限定在衬底平面内，而第三个z轴或输入轴被定义为垂直于衬底平面。沿着x轴的两个质量块的移动通过静电耦合装置耦合，使得同相模式和反相模式的固有谐振频率彼此分离，用于沿x轴的谐振，轴。当两个质量被驱动以反相模式沿着x轴振动并且该装置经历围绕z轴的旋转时，科里奥利力在Y方向上的质量作用差异地导致两个质量在反向沿y轴的相位运动。可以通过速率传感器直接感测沿y轴的反相抖动，以测量围绕z轴的旋转速率。或者，沿着y轴的第一和第二主体的相位抖动可以传递到其它可移动体（即，速率感测质量），其移动然后被感测以测量围绕z轴的旋转速率。感测体优选地以这样的方式悬挂，即在没有科里奥利力的情况下，振动块的x轴运动不影响感测体。这可以抑制感测体响应于衬底平面内的线性加速度的运动，但是允许这些物体容易地响应于围绕垂直于衬底平面的轴的花冠诱发的运动。

8. 发明申请

WO02066684A3 GENOME-BASED PERSONALIZED MEDICINE 审中-公开
标题翻译：基于基因的个人化医学
公开(公告)号：WO02066684A3
公开(公告)日：2003-10-16
申请号：PCT/US0204686
申请日：2002-02-19
申请人： UNIV JOHNS HOPKINS , VOGELSTEIN BERT , KINZLER KENNETH W , YAN HAI , PAPADOPOULOS NICKOLAS
发明人： VOGELSTEIN BERT , KINZLER KENNETH W , YAN HAI , PAPADOPOULOS NICKOLAS
IPC分类号： C12Q1/68 , C12N5/12
CPC分类号： C12Q1/6876 , C12N2503/00 , C12Q2600/106 , C12Q2600/156
摘要： Individual alleles can be isolated from every chromosome within somatic cell hybrids generated from a single fusion event. Nucleic acids or proteins from the hybrids can be analyzed for polymorphisms to provide unambiguous determinations. Information thus obtained can be used to develop and implment personalized medical interventions for individuals having particular polymorphic markers.
摘要翻译：可以从单个融合事件产生的体细胞杂交体内的每个染色体分离个体等位基因。可以分析来自杂交体的核酸或蛋白质的多态性以提供明确的测定。由此获得的信息可用于为具有特定多态性标记的个体开发和隐含个性化医疗干预。

9. 发明申请

WO2013003583A3 SOMATIC MUTATIONS IN ATRX IN BRAIN CANCER 审中-公开
标题翻译： ATRX在脑癌中的体细胞突变
公开(公告)号：WO2013003583A3
公开(公告)日：2013-04-04
申请号：PCT/US2012044631
申请日：2012-06-28
申请人： UNIV DUKE , UNIV JOHNS HOPKINS , YAN HAI , BIGNER DARELL , VOGELSTEIN BERT , KINZLER KENNETH W , MEEKER ALAN , HRUBAN RALPH , PAPADAPOULOS NICKOLAS , DIAZ LUIS , JIAO YUCHEN
发明人： YAN HAI , BIGNER DARELL , VOGELSTEIN BERT , KINZLER KENNETH W , MEEKER ALAN , HRUBAN RALPH , PAPADAPOULOS NICKOLAS , DIAZ LUIS , JIAO YUCHEN
IPC分类号： G01N33/53 , A61K31/7105 , A61K39/00 , C12Q1/68
CPC分类号： C12Q1/6886 , C07K16/40 , C12N15/1137 , C12Q2600/118 , C12Q2600/156 , G01N33/57407
摘要： We determined the sequence of ATRX and DAXX in 447 cancers from various sites. We found mutations most commonly in pediatric glioblastoma multiformae (GBM) (11.1%), adult GBM (6.5%), oligodendrogliomas (7.7%) and medulloblastomas (1.5%); and showed that Alternative Lengthening of Telomeres (ALT), a telomerase-independent telomere maintenance mechanism found in cancers that have not activated telomerase, perfectly correlated with somatic mutations of either gene. In contrast, neuroblastomas, and adenocarcinomas of the ovary, breast, and pancreas were negative for mutations in ATRX and DAXX. Alterations in ATRX or DAXX define a specific molecular pathway that is closely associated with an alternative telomere maintenance function in human cancers.
摘要翻译：我们在来自不同地点的447种癌症中确定了ATRX和DAXX的序列。我们发现小儿胶质母细胞瘤多形性（GBM）（11.1％），成人GBM（6.5％），少突胶质细胞瘤（7.7％）和成神经管细胞瘤（1.5％）中最常见突变; 并表明端粒替代延长（ALT）是一种端粒酶非依赖性端粒维持机制，在未激活端粒酶的癌症中发现，与任一基因的体细胞突变完全相关。相反，神经母细胞瘤和卵巢癌，乳腺癌和胰腺腺癌的ATRX和DAXX突变均为阴性。 ATRX或DAXX的改变定义了与人类癌症中替代的端粒维持功能密切相关的特定分子途径。

10. 发明申请

WO2012061105A2 HOMOZYGOUS AND HETEROZYGOUS IDH1 GENE-DEFECTIVE CELL LINES DERIVED FROM HUMAN COLORECTAL CELLS 审中-公开
标题翻译：人类和异源性IDH1从人类细胞细胞衍生的基因缺陷细胞系
公开(公告)号：WO2012061105A2
公开(公告)日：2012-05-10
申请号：PCT/US2011057615
申请日：2011-10-25
申请人： UNIV DUKE , YAN HAI , BIGNER DARRELL , DUNCAN CHRIS
发明人： YAN HAI , BIGNER DARRELL , DUNCAN CHRIS
IPC分类号： C12N5/10 , A01K67/027 , C12N5/09 , C12N15/85
CPC分类号： C12N15/85 , C12N5/0693 , C12N15/902 , C12N2510/00 , C12N2799/025 , C12N2800/30
摘要： IDH1 gene-defective cell lines (e.g., IDH1R132H heterozygous) have been made from a robust cell line, HCT116. The IDH1 gene-defective cell lines can be used to determine the effect of IDH1R132H on cell biology, tumorigenesis, and cellular metabolic profiles. These cell lines can be used to test potential therapeutic targets and to screen potential therapeutic agents. Kits and xenografts are also contemplated.
摘要翻译： IDH1基因缺陷型细胞系（例如，IDH1R132H杂合子）已经从稳健的细胞系HCT116制备出来。 IDH1基因缺陷细胞系可用于确定IDH1R132H对细胞生物学，肿瘤发生和细胞代谢特征的影响。这些细胞系可用于测试潜在的治疗靶标并筛选潜在的治疗剂。也可以考虑试剂盒和异种移植物。

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