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1. 发明申请

WO1996041640A1 BRADYKININ ANALOGS AS SELECTIVE THROMBIN INHIBITORS 审中-公开
标题翻译：作为选择性硫蛋白抑制剂的BRADYKININ ANALOGS
公开(公告)号：WO1996041640A1
公开(公告)日：1996-12-27
申请号：PCT/US1996009940
申请日：1996-06-07
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , SCHMAIER, Alvin, H. , HASAN, Ahmed, A., K.
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
IPC分类号： A61K38/02
CPC分类号： A61K38/57 , A61K38/08 , A61K38/10 , C07K5/1019 , C07K7/02 , C07K7/18 , C07K14/001
摘要： Thrombin-induced and ADP-induced platelet and other cell activation is inhibited without affecting thrombin's other proteolytic activity by administration of a bradykinin sequence related analogous peptide. Bradykinin analogs are peptides to which substitutions, additions or deletions have been made to the first four amino acids of the amino acid sequence of native bradykinin. The bradykinin analogs described inhibit alpha -thrombin-induced and ADP-induced platelet activation and secretion, inhibit alpha -thrombin-induced calcium mobilization, and prevent alpha -thrombin from cleaving its platelet receptor. The bradykinin analogs may comprise single- or multiple-chain peptides.
摘要翻译：通过施用缓激肽序列相关的类似肽，凝血酶诱导和ADP诱导的血小板和其他细胞活化被抑制而不影响凝血酶的其它蛋白水解活性。缓激肽类似物是对天然缓激肽的氨基酸序列的前四个氨基酸进行取代，添加或缺失的肽。所描述的缓激肽类似物抑制α-凝血酶诱导和ADP诱导的血小板活化和分泌，抑制α-凝血酶诱导的钙动员，并防止α-凝血酶裂解其血小板受体。缓激肽类似物可以包含单链或多链肽。

2. 发明申请

WO1997040145A1 INACTIVATION RESISTANT FACTOR VIII 审中-公开
标题翻译：灭绝因子VIII
公开(公告)号：WO1997040145A1
公开(公告)日：1997-10-30
申请号：PCT/US1997006563
申请日：1997-04-24
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , KAUFMAN, Randal, J. , PIPE, Steven, W. , AMANO, Kagehiro
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
IPC分类号： C12N09/48
CPC分类号： C07K14/755 , A61K38/00
摘要： The present invention provides novel purified and isolated nucleic acid sequences encoding procoagulant-active FVIII proteins. The nucleic acid sequences of the present invention encode amino acid sequences corresponding to known human FVIII sequences, wherein residue Phe309 is mutated. The nucleic acid sequences of the present invention also encode amino acid sequences corresponding to known human FVIII sequences, wherein the APC cleavage sites, Arg336 and Ile562, are mutated. The nucleic acid sequences of the prsent invention further encode amino acid sequences corresponding to known human FVIII sequences, wherein the B-domain is deleted, the von Willebrand factor binding site is deleted, a thrombin cleavage site is mutated and an amino acid sequence spacer is inserted between the A2- and A3-domains. Methods of producing the FVIII proteins of the invention, nucleotide sequences encoding such proteins, pharmaceutical compositions containing the nucleotide sequences or proteins, as well as methods of treating patients suffering from hemophilia, are also provided.
摘要翻译：本发明提供了编码促凝血活性FVIII蛋白的新型纯化和分离的核酸序列。本发明的核酸序列编码对应于已知人FVIII序列的氨基酸序列，其中残基Phe309被突变。本发明的核酸序列还编码对应于已知人FVIII序列的氨基酸序列，其中APC切割位点Arg336和Ile562突变。本发明的核酸序列进一步编码对应于已知人FVIII序列的氨基酸序列，其中缺失B结构域，缺失血管性血友病因子结合位点，突变凝血酶切割位点，氨基酸序列间隔物为插入在A2-和A3-域之间。还提供了产生本发明的FVIII蛋白的方法，编码这种蛋白质的核苷酸序列，含有核苷酸序列或蛋白质的药物组合物，以及治疗患有血友病的患者的方法。

3. 发明申请

WO1997031011A1 MICROSATELLITE MARKERS FOR IDENTIFYING CANINE GENETIC DISEASES OR TRAITS 审中-公开
标题翻译：用于鉴定犬类遗传病或斑马鱼的微生物标记
公开(公告)号：WO1997031011A1
公开(公告)日：1997-08-28
申请号：PCT/US1997002396
申请日：1997-02-18
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , BOARD OF TRUSTEES OPERATING MICHIGAN STATE UNIVERSITY , BREWER, George, J. , VENTA, Patrick, J. , YUZBASIYAN-GURKAN, Vilma
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , BOARD OF TRUSTEES OPERATING MICHIGAN STATE UNIVERSITY
IPC分类号： C07H21/04
CPC分类号： C12Q1/6883 , C12Q2600/156 , C12Q2600/172
摘要： Microsatellite markers are provided which are useful in identifying linked markers for canine genetic diseases and traits. The microsatellite markers are derived from regions of genomic DNA which contain a repeat motif, flanked by unique sequences. The number of units contained within the repeat motif is variable, such that various different alleles are present in any given population. The microsatellite markers and their progeny are especially useful in detecting genetic diseases not phenotypically visible and identifying carriers of recessive diseases, as illustrated in the figure. In a preferred embodiment, microsatellite markers are provided which may be used to detect the canine copper toxicosis gene.
摘要翻译：提供了微卫星标记，可用于鉴定犬遗传疾病和性状的连锁标记。微卫星标记源自含有重复基序的基因组DNA区域，其侧翼为独特序列。包含在重复序列中的单元数目是可变的，使得在任何给定群体中存在各种不同的等位基因。微卫星标记及其后代特别适用于检测不表型可见的遗传疾病，并鉴定隐性疾病的携带者，如图所示。在优选的实施方案中，提供可用于检测犬铜毒性基因的微卫星标记。

4. 发明申请

WO1997025755A1 SLOT SPIRAL ANTENNA WITH INTEGRATED BALUN AND FEED 审中-公开
标题翻译： SLOT螺旋天线与集成的巴伦和饲料
公开(公告)号：WO1997025755A1
公开(公告)日：1997-07-17
申请号：PCT/US1996020500
申请日：1996-12-23
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , NURNBERGER, Michael, W. , VOLAKIS, John, L.
IPC分类号： H01Q13/16
CPC分类号： H01Q9/27 , H01Q13/16 , H01Q13/18
摘要： A slot spiral (18) antenna with a planar integrated balun and feed. The slot spiral is produced using standard printed circuit techniques and comprises a dielectric substrate having a conductive layer which is etched to form the radiating slot spiral. An integrated microstrip feed (16) is included to provide a balanced feed to the slot spiral. Impedance matching is preformed between the microstrip feed and the slotline of the slot spiral to maximize energy transfer. A shallow reflecting cavity is included to limit the spiral radiation to one direction. The described antenna apparatus provides a simple, broadband spiral antenna suitable for incorporating into the skin of a moving vehicle. A covering layer may act as a dielecric lens. Outer parts of the slot spiral may be covered with a lossy absorber for termination. The feed point may be off-center with respect to the spiral.
摘要翻译：具有平面集成平衡 - 不平衡转换器和进给的槽螺旋（18）天线。槽螺旋使用标准印刷电路技术制造，并且包括具有被蚀刻以形成辐射槽螺旋的导电层的电介质基板。包括集成的微带馈送（16）以向槽螺旋提供平衡的馈送。阻抗匹配在微带馈线和槽螺旋槽槽之间进行，以最大限度地提高能量传递。包括浅反射腔以将螺旋辐射限制在一个方向。所描述的天线装置提供一种适合于并入移动车辆的皮肤的简单的宽带螺旋天线。覆盖层可以用作薄膜晶体。狭槽螺旋的外部部分可以用有损耗的吸收器覆盖以终止。馈电点可能相对于螺旋偏心。

5. 发明申请

WO1997010817A1 AMINO CERAMIDE-LIKE COMPOUNDS AND THERAPEUTIC METHODS OF USE 审中-公开
标题翻译：氨基酸类化合物和治疗方法的使用
公开(公告)号：WO1997010817A1
公开(公告)日：1997-03-27
申请号：PCT/US1996014219
申请日：1996-09-05
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , SHAYMAN, James, A. , RADIN, Norman, S.
IPC分类号： A61K31/16
CPC分类号： A61K31/5375 , A61K31/164 , A61K31/165 , A61K31/40 , A61K31/445 , A61K31/495
摘要： Novel amino ceramide-like compounds are provided which inhibit glucosyl ceramide (GlcCer) formation by inhibiting the enzyme GlcCer synthase, thereby lowering the level of glycosphingolipids. The compounds of the present invention have improved GlcCer synthase inhibition activity and are therefore highly useful in therapeutic methods for treating various conditions and diseases associated with altered glycosphingolipid levels.
摘要翻译：提供了通过抑制酶GlcCer合酶抑制葡糖基神经酰胺（GlcCer）形成的新型氨基神经酰胺样化合物，从而降低了鞘糖脂的水平。本发明的化合物具有改善的GlcCer合成酶抑制活性，因此在用于治疗与改变的鞘糖脂水平相关的各种病症和疾病的治疗方法中是非常有用的。

6. 发明申请

WO1997003087A1 NOVEL REGULATORY GENES 审中-公开
标题翻译：新法规基因
公开(公告)号：WO1997003087A1
公开(公告)日：1997-01-30
申请号：PCT/US1996011702
申请日：1996-07-12
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , KURNIT, David, M. , CHIANG, Pei-Wan , SONG, Woo-Joo
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
IPC分类号： C07H21/04
CPC分类号： G01N33/5091 , A61K38/00 , A61K48/00 , C07K14/4702 , G01N2333/47 , G01N2333/4703
摘要： This invention provides polynucleotides coding for mammalian polypeptides that are multiple function regulatory proteins (MFRP) and fragments of the polynucleotides. These polynucleotides are isolated from the native environment or they are recombinantly produced. Also provided by this invention are purified, naturally occurring MFRP and recombinantly produced MFRP and polypeptide fragments of these proteins. Antibodies, both polyclonal and monoclonal, are further provided herein as well as the hybridoma cell lines which produce the monoclonal antibodies. These antibodies are characterized by specifically binding the proteins and polypeptide fragments of this invention. Compositions containing an excipient and any of the polynucleotides, proteins, polypeptides and antibodies of this invention are further provided herein. Finally, diagnostic and therapeutic uses of these compositions also are provided by this invention.
摘要翻译：本发明提供编码作为多功能调节蛋白（MFRP）和多核苷酸片段的哺乳动物多肽的多核苷酸。这些多核苷酸是从天然环境中分离出来的，或者是重组产生的。本发明还提供纯化的天然存在的MFRP并重组产生这些蛋白质的MFRP和多肽片段。本文还提供了多克隆和单克隆抗体以及产生单克隆抗体的杂交瘤细胞系。这些抗体的特征在于特异性地结合本发明的蛋白质和多肽片段。包含本发明的赋形剂和任何多核苷酸，蛋白质，多肽和抗体的组合物在本文中进一步提供。最后，这些组合物的诊断和治疗用途也由本发明提供。

7. 发明申请

WO1996024180A1 APPARATUS FOR PROVIDING A PHASE SHIFT IN A PULSE AND METHOD OF USE THEREOF 审中-公开
标题翻译：用于在脉冲中提供相位移位的装置及其使用方法
公开(公告)号：WO1996024180A1
公开(公告)日：1996-08-08
申请号：PCT/US1996001018
申请日：1996-01-23
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , SQUIER, Jeffrey, A. , KANE, Steven, J.
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
IPC分类号： H01S03/00
CPC分类号： H01S3/0057 , H01S3/0812 , H01S3/1106
摘要： The invention provides a method an apparatus for imparting phase shift in one or more pulses. The apparatus comprises at least one optical diffraction grating element; where each one of the grating elements comprises a grating having a constant line spacing (d) and a dielectric body in light coupling arrangement with the grating. The dielectric body has a side through which the pulse traverses. The side is at an angle alpha (alpha) with respect to the grating. Alpha alpha defines a path of the pulse in the dielectric body corresponding to an incident angle THETA i (theta incident) between the path and a plane normal to the grating. The incident angle theta i and grating line spacing (d) cooperate to provide negative second-order dispersion (SOD) and negative third-order dispersion (TOD) so as to compensate for any positive SOD and any positive TOD initially present in the pulse.
摘要翻译：本发明提供一种用于在一个或多个脉冲中施加相移的装置的方法。该装置包括至少一个光学衍射光栅元件; 其中每个光栅元件包括具有恒定线间距（d）的光栅和与光栅的光耦合布置的电介质体。介电体具有脉冲穿过的一侧。侧面相对于光栅为α（α）角。 Alpha alpha定义介质体中的脉冲的路径，其对应于路径和垂直于光栅的平面之间的入射角度THETA i（θ入射）。入射角θi和光栅线间距（d）协同提供负二阶色散（SOD）和负三阶色散（TOD），以补偿脉冲中最初存在的任何正SOD和任何正TOD。

8. 发明申请

WO1996019244A1 DNA ENCODING A 20 Kd CDK6 INHIBITING PROTEIN 审中-公开
标题翻译： DNA编码20 Kd CDK6抑制蛋白
公开(公告)号：WO1996019244A1
公开(公告)日：1996-06-27
申请号：PCT/US1995016553
申请日：1995-12-19
申请人： THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL , THE REGENTS OF THE UNIVERSITY OF MICHIGAN , XIONG, Yue , GUAN, Kun-Liang
发明人： THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL , THE REGENTS OF THE UNIVERSITY OF MICHIGAN
IPC分类号： A61K48/00
CPC分类号： C12N9/12 , A61K38/00 , C07K14/4703 , C07K16/18
摘要： A nucleic acid encoding a CDK inhibiting protein, particularly a CDK6 inhibiting protein, is selected from the group consisting of: (a) DNA having the nucleotide sequence given herein as SEQ ID NO:1 (which encodes the protein having the amino acid sequence given herein as SEQ ID NO:2), and which are referred to as p20; b) nucleic acids which hybridize to DNA of (a) above and which encode a CDK inhibiting protein; and (c) nucleic acids which differ from the nucleic acids of (a) or (b) above due to the degeneracy of the genetic code, and which encode a CDK inhibiting protein encoded by a nucleic acid of (a) or (b) above. Constructs containing such nucleic acids, cells containing such constructs, proteins encoded by such nucleic acids, antibodies which bind thereto, antisense oligonuclotides corresponding to such nucleic acids, and methods of using the same are also disclosed.
摘要翻译：编码CDK抑制蛋白质，特别是CDK6抑制蛋白质的核酸选自：（a）具有本文给出的核苷酸序列的SEQ ID NO：1的DNA（其编码具有给定氨基酸序列的蛋白质）本文作为SEQ ID NO：2），其被称为p20; b）与上述（a）的DNA杂交并编码CDK抑制蛋白质的核酸; 和（c）由于遗传密码的简并性而编码由（a）或（b）的核酸编码的CDK抑制蛋白的上述（a）或（b）的核酸不同的核酸，以上。还公开了含有这种核酸的构建体，含有这种构建体的细胞，由这些核酸编码的蛋白质，与其结合的抗体，对应于该核酸的反义寡核苷酸，及其使用方法。

9. 发明申请

WO1995012171A2 METHOD AND APPARATUS FOR ADAPTIVE CONTROL OF HUMAN-MACHINE SYSTEMS EMPLOYING DISTURBANCE RESPONSE 审中-公开
标题翻译：人机系统自适应控制的方法与装置应对干扰响应
公开(公告)号：WO1995012171A2
公开(公告)日：1995-05-04
申请号：PCT/US1994012179
申请日：1994-10-24
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , BELL, David, A. , BELL, Lon, E. , LEVINE, Simon , KOREN, Yoram
IPC分类号： G06F17/00
CPC分类号： B60W40/08 , A61G5/04 , A61G2203/14 , B60W2300/38 , Y10S180/907 , Y10S297/04 , Y10S706/905
摘要： Adaptive control of a system with a human in the loop is accomplished by sensing human operator reactions to a disturbance in the system and characterizing the operator response to the disturbance. The operator response is characterized in one of several forms by predicting a response based on a model quantifying a response based on statistics or merely measuring a response for accumulation of data to be employed by an artificial intelligent system. The disturbance which provides the human operator reaction, is applied or occurs naturally based on other stimulus and is measured by the system. Quantifying the results of the disturbance and the operator response comparison allows selection of a control mode by identifying one or more categories of reactions response or a graduated modification of the control law employed in the system. Various modes or categories for control of the system incorporate different sensitivities on a macro scale or an entirely different control algorithm. Graduated adaptation alters sensitivity or other perimeters in the system at a micro level incrementally throughout given ranges of control.
摘要翻译：通过感测人类操作员对系统中的干扰的反应并表征操作者对干扰的响应来实现对环路中的人的系统的自适应控制。操作员响应以几种形式之一表征，通过基于基于统计量量化响应的模型来预测响应，或者仅测量人造智能系统将要使用的数据的累积响应。提供人员操作反应的干扰，以其他刺激为基础自然发生，并由系统测量。量化干扰的结果和操作者响应比较允许通过识别系统中使用的控制规则的一个或多个类别的反应响应或分级修改来选择控制模式。用于系统控制的各种模式或类别在宏观尺度或完全不同的控制算法上包含不同的灵敏度。渐变自适应在给定的控制范围内以微观级别改变系统中的灵敏度或其他周长。

10. 发明申请

WO1994029436A1 METHODS FOR SELECTIVELY STIMULATING PROLIFERATION OF T CELLS 审中-公开
标题翻译：选择性刺激T细胞增殖的方法
公开(公告)号：WO1994029436A1
公开(公告)日：1994-12-22
申请号：PCT/US1994006255
申请日：1994-06-03
申请人： THE UNITED STATES OF AMERICA represented by THE SECRETARY OF THE NAVY , THE REGENTS OF THE UNIVERSITY OF MICHIGAN , REPLIGEN CORPORATION
发明人： THE UNITED STATES OF AMERICA represented by THE SECRETARY OF THE NAVY , THE REGENTS OF THE UNIVERSITY OF MICHIGAN , REPLIGEN CORPORATION , JUNE, Carl, H. , THOMPSON, Craig, B. , NABEL, Gary, J. , GRAY, Gary, S. , RENNERT, Paul, D.
IPC分类号： C12N05/08
CPC分类号： C12N5/0636 , A61K35/17 , A61K38/00 , A61K48/00 , C07K14/70532 , C07K16/2809 , C07K16/2818 , C07K16/2896 , C07K2317/34 , C07K2317/74 , C12N2501/51 , C12N2501/515 , C12N2501/599
摘要： Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR)/CD3 complex or the CD2 surface protein. To induce proliferation of an activated population T cells, an accessory molecule on the surface of the T cells, such as CD28, is stimulated with a ligand which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.
摘要翻译：描述了通过激活T细胞群并用结合附属分子的配体刺激T细胞表面上的辅助分子来诱导T细胞群体增殖的方法。 T细胞增殖发生在没有外源生长因子或附属细胞的情况下。通过刺激T细胞受体（TCR）/ CD3复合物或CD2表面蛋白来完成T细胞活化。为了诱导活化的群体T细胞的增殖，T细胞表面上的辅助分子如CD28被与配合分子结合的配体刺激。通过本发明方法扩增的T细胞群体可以被遗传转导并用于免疫治疗，或可用于诊断方法。

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