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1. 发明申请

WO1993022331A1 HUMAN CRABP-I AND CRABP-II 审中-公开
标题翻译：人CRABP-I和CRABP-II
公开(公告)号：WO1993022331A1
公开(公告)日：1993-11-11
申请号：PCT/US1993003936
申请日：1993-04-27
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , ASTROM, Anders , VOORHEES, John, J. , PETTERSON, Ulrika , TAVAKKOL, Amir
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
IPC分类号： C07H21/04
CPC分类号： C12Q1/6897 , C07K14/70567 , G01N2333/70567 , G01N2500/00
摘要： The sequences encoding two isoforms of human cellular retinoic acid binding proteins, CRABP-I and CRABP-II, have been cloned and sequenced and are set forth with their corresponding amino acid sequences in SEQ ID NOS. 1-4. The indentification of human CRABP nucleic and amino acid sequences provides the basis for the construction of recombinant human CRABP vectors and expression constructs. Human CRABP can also be synthesized or produced ex vivo, e.g. in bacterial or other production systems. Ligand binding assays, including recombinant and chimeric receptor reporter assays, and direct and competition hybridization assays employing the human CRABP sequences herein described can be used to test drugs for retinoic induction and tissue specificity for pathologies in which retinoids are implicated. Immunoassays utilizing antibodies or binding fragments produced to human CRABP can also be used to test patient tissues for the presence and levels of CRABP for diagnosis and to monitor treatment. The indentification of the nucleic and amino acids sequences for human CRABP-I and CRABP-II also contributes to the elucidation of the function and interaction of the retinoid-binding proteins. The CRABP-II gene, isolated from a human placenta genomic library, spans 6 kilobases and includes 4 exons. One major transcription initiation site was mapped to an A residue 137 nucleotides upstream of the ATG initiation codon. CRABP-II mRNA was rapidly induced within 2-6 hours in culture by retinoic acid, primarily due to an increased rate of transcription which required on-going synthesis. The human CRABP-II gene is thus apparently transcriptionally regulated by a newly synthesized regulator protein. Once the CRABP-II is produced, message stabilization may provide means by which elevated CRABP-II in mRNA is maintained.
摘要翻译：编码人类细胞视黄酸结合蛋白（CRABP-1和CRABP-II）的两种同工型的序列已被克隆并测序，并以SEQ ID NOS中相应的氨基酸序列进行阐述。 1-4。人类CRABP核酸和氨基酸序列的鉴定提供了构建重组人类CRABP载体和表达构建体的基础。人类CRABP也可以离体合成或产生，例如，在细菌或其他生产系统中。配体结合测定法，包括重组和嵌合受体报告基因测定，以及使用本文所述的人类CRABP序列的直接和竞争杂交测定法，可用于检测视黄酸诱导药物和组胺特异性，其中涉及类维生素A。利用针对人类CRABP产生的抗体或结合片段的免疫测定法也可用于测试患者组织中CRABP的存在和水平以进行诊断和监测治疗。人CRABP-1和CRABP-II的核酸和氨基酸序列的鉴定也有助于阐明类视黄醇结合蛋白的功能和相互作用。从人胎盘基因组文库分离的CRABP-II基因跨越6千碱基并且包括4个外显子。一个主要的转录起始位点被映射到ATG起始密码子上游137个核苷酸的A残基。 CRABP-II mRNA在视黄酸培养2-6小时内迅速诱导，主要是由于需要持续合成的转录速率增加。因此，人类CRABP-II基因显然被新合成的调节蛋白转录调节。一旦CRABP-II产生，信号稳定可以提供维持mRNA中升高的CRABP-II的方式。

2. 发明申请

WO1993019743A1 METHOD OF TREATMENT OF HYPERPIGMENTATION IN BLACK SKIN WITH RETINOIC ACID AND METHOD OF LIGHTENING BLACK SKIN WITH RETINOIC ACID 审中-公开
标题翻译：治疗黑皮肤高脂肪酸的方法及其制备方法
公开(公告)号：WO1993019743A1
公开(公告)日：1993-10-14
申请号：PCT/US1993002711
申请日：1993-03-31
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , VOORHEES, John, J. , ELLIS, Charles, N. , GRIFFITHS, Christopher, E., M.
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
IPC分类号： A61K31/07
CPC分类号： A61Q19/02 , A61K8/49 , A61K8/494 , A61K8/671 , A61K31/07 , A61K31/20 , A61K31/203 , A61K31/41 , A61K31/415 , A61K31/495 , A61K2800/782 , A61K2300/00
摘要： Hyperpigmentation of black skin may be treated by topical application of retinoic acid to the skin. Topical application of retinoic acid is also effective for lightening normal black skin.
摘要翻译：黑皮肤色素沉着过度可能会通过局部应用视黄酸来治疗皮肤。视黄酸的局部应用对于减轻正常的黑色皮肤也是有效的。

3. 发明申请

WO1993019729A1 RETINOIC ACID AS A SKIN TANNING AGENT IN PERSONS OF LIGHT SKIN COLOR 审中-公开
标题翻译：作为轻皮肤颜色的皮肤TANNING代理的反义酸
公开(公告)号：WO1993019729A1
公开(公告)日：1993-10-14
申请号：PCT/US1993002712
申请日：1993-03-31
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , VOORHEES, John, J. , GRIFFITHS, Christopher, E., M. , ELLIS, Charles, N.
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN
IPC分类号： A61K07/42
CPC分类号： A61Q19/04 , A61K8/671 , A61K31/07 , A61K31/20 , Y10S514/844 , Y10S514/847 , Y10S514/944
摘要： Topical application of retinoic acid is effective for increasing the tyrosinase activity in the skin of people having light skin. Thus, topical application of retinoic acid may be used to effect a suntan in people having light skin and as a consequence protect against photodamage.

4. 发明公开

EP1142110A1 DEVICE INCLUDING A MICROMECHANICAL RESONATOR HAVING AN OPERATING FREQUENCY AND METHOD OF EXTENDING SAME 审中-公开
标题翻译：微机械谐振器含器件与扩大SAME工作频率和方法的
公开(公告)号：EP1142110A1
公开(公告)日：2001-10-10
申请号：EP00902413.4
申请日：2000-01-14
申请人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , Nguyen, Clark T.C. , McCorquodale, Michael , Wang, Kun
发明人： THE REGENTS OF THE UNIVERSITY OF MICHIGAN , Nguyen, Clark T.C. , McCorquodale, Michael , Wang, Kun
IPC分类号： H03H9/24
CPC分类号： H03H9/24 , H01H59/0009 , H01H2059/0072 , H03H3/0078 , H03H9/2452 , H03H9/462 , H03H9/465
摘要： A flexural-mode, micromechanical resonator utilizing a non-intrusive support structure to achieve measured Q's as high as 8,400 at VHF frequencies from 30-90 MHz is manufactured using polysilicon surface micromachining technology. Also, a method for extending the operating frequency of the resonator as well as other types of micromechanical resonators is disclosed. One embodiment of the method is called a differential-signaling technique. The other embodiment of the method is called a dimple-down technique. The support structure includes one or more torsional-mode support springs (16) in the form of beams that effectively isolate a resonator beam from its anchors (18) via quarter-wavelength impedance transformations, minimizing anchor dissipation and allowing the resonator to achieve high Q with high stiffness in the VHF frequency range. The resonator also includes one or more spacers (26) in the form of dimples formed on the flexural resonator beam (12) or the substrate. In operation, the dimples (26) determine a capacitive-transducer gap of the resonator. When a large DC-bias voltage is applied between a drive electrode (20) and the resonator beam (12), the dimples (26) provide a predetermined minimum distance between the flexural resonator beam (12) and the drive electrode (20).

5. 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。

6. 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。

7. 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。

8. 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。

9. 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。

10. 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。

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