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1. 发明申请

WO2005115354A2 COMPOSITIONS AND METHODS FOR BONE FORMATION AND REMODELING 审中-公开
标题翻译：用于骨形成和重建的组合物和方法
公开(公告)号：WO2005115354A2
公开(公告)日：2005-12-08
申请号：PCT/US2005/017199
申请日：2005-05-18
申请人： ENZO THERAPEUTICS, INC. , ZHANG, Yazhou , LIU, Peng , LI, Xiaofeng , ZHANG, Jie , SHAN, Jufang , ENGELHARDT, Dean , WU, Dianqing
发明人： ZHANG, Yazhou , LIU, Peng , LI, Xiaofeng , ZHANG, Jie , SHAN, Jufang , ENGELHARDT, Dean , WU, Dianqing
IPC分类号： A61K9/68
CPC分类号： G01N33/6893 , A61K38/00 , G01N33/6887 , G01N2500/00 , G01N2800/10 , G01N2800/108
摘要： The mechanism by which the high bone mass (HBM) mutation (G171V) of the Wnt coreceptor LRP5 regulates the canonical Wnt signaling was investigated. The mutation was previously shown to reduce Dkk protein-1-mediated antagonism, suggesting that the first YWTD repeat domain where G171 is located may be responsible for Dkk protein-mediated antagonism. However, we found that the third YWTD repeat, but not the first repeat domain, is required for DKK1-mediated antagonism. Instead, we found that the G171V mutation disrupted the interaction of LRP5 with Mesd, a chaperon protein for LRP5/6 molecules on the cell surface. Although the reduction in the level of cell surface LRP5 molecules led to a reduction in Wnt signaling in a paracrine paradigm, the mutation did not appear to affect the activity of coexpressed Wnt in an autocrine paradigm. Together with the observation that osteoblast cells produce autocrine canonical Wnt, Wnt7b, and that osteocytes produce paracrine Dkk1, we believe that the G171V mutation may cause an increase in Wnt activity in osteoblastls by reducing the numnber of targets for paracrine Dkk1 to antagonize without affecting the activity of autocrine Wnt.
摘要翻译：研究了Wnt共同受体LRP5的高骨量（HBM）突变（G171V）调节规范Wnt信号传导的机制。以前显示突变可以降低Dkk蛋白-1介导的拮抗作用，这表明G171位于第一个YWTD重复结构域可能是Dkk蛋白介导的拮抗作用的原因。然而，我们发现第三个YWTD重复，但不是第一个重复结构域，是DKK1介导的拮抗作用所必需的。相反，我们发现G171V突变破坏了LRP5与Mesd的相互作用，Mesd是细胞表面上LRP5 / 6分子的伴侣蛋白。尽管细胞表面LRP5分子水平的降低导致旁分泌范例中Wnt信号传导的降低，但突变似乎不影响共表达Wnt在自分泌范式中的活性。连同观察到，成骨细胞产生自分泌标准Wnt，Wnt7b，并且该骨细胞产生旁分泌Dkk1，我们认为G171V突变可能通过减少旁分泌Dkk1的靶标的数目来拮抗而引起成骨细胞中Wnt活性的增加而不影响成骨细胞自分泌Wnt的活性。

2. 发明申请

WO2005112981A3 COMPOSITIONS AND METHODS FOR THE STIMULATION OR ENHANCEMENT OF BONE FORMATION AND THE SELF-RENEWAL OF CELLS 审中-公开
公开(公告)号：WO2005112981A3
公开(公告)日：2005-12-01
申请号：PCT/US2005/017420
申请日：2005-05-18
申请人： ENZO THERAPEUTICS, INC. , LI, Xiaofeng , LIU, Peng , LIU, Wenzhong , ENGELHARDT, Dean
发明人： LI, Xiaofeng , LIU, Peng , LIU, Wenzhong , ENGELHARDT, Dean , WU, Dianqing
IPC分类号： A61K38/00 , A61P19/00 , A61P19/08 , A61P19/10
摘要： Compositions and methods for the treatment of bon diseases, bone fractures, bone injuries and other bone abnormalities involving the use of Dkk protein, a Wnt antagonist, a Wnt inhibitor, or any other related protein for the stimulation or enhancement of mineralization and for stimulating the renewal of cells. One Dkk protein, Dickkopf-2 (Dkk-2) acts to stimulate bone formation independently of Wnt proteins which may be inhibited and/or antagonized by Dkk-2. Dkk-2 displayed enhanced specific targeting ability and enhanced biological activity in stimulating or enhancing mineralization. Dkk-2 also played a role in the differentiation and self-renewal of hematopoietic stem cells and mesenchymal stem cells, particularly in osteoblastogenesis and osteoclastogenesis.

3. 发明申请

WO2006102070A2 SCLEROSTIN AND THE INHIBITION OF WNT SIGNALING AND BONE FORMATION 审中-公开
标题翻译： SCLEROSTIN和WNT信号和骨形成的抑制
公开(公告)号：WO2006102070A2
公开(公告)日：2006-09-28
申请号：PCT/US2006/009697
申请日：2006-03-17
申请人： ENZO BIOCHEM, INC. , WU, Dianqing, Dan , LI, Xiaofeng
发明人： WU, Dianqing, Dan , LI, Xiaofeng
IPC分类号： A61K38/17
CPC分类号： G01N33/6893 , G01N33/6887 , G01N2500/00 , G06F19/12
摘要： The loss of the SOST gene product sclerosti? leads to sclerosteosis characterized byihigh bone mass (HBM). In this report, we found that sclerostin could antagonize canonical, Wnt signaling in human embryonic kidney A293 cells and mouse osteoblastic MC3T3 cells. This sclerostin-mediated antagonism could be reversed by over-expression of Wnt coreceptor LRP5. In addition, we found that sclerostin bound to LRP5 as well as LRP6 and identified the first two YWTD-EGF repeat domains of LRP5 as being responsible for the binding. Although these two repeat domains are required for transducing canonical Wnt signals, canonical Wnt did not appear to compete with sclerostin for binding to LRP5. Examination of the expression of sclerostin and Wnt7b, an autocrine canonical Wnt, during primary calvarial osteoblast differentiation revealed that sclerostin is expressed at the late stages of osteoblast differentiation coinciding with the expression of osteogenic marker osteocalcin and trailing after the expression of Wnt7b. Given the plethora of evidence indicating that canonical Wnt signaling stimulates osteogenesis, we believe that the HBM phenotype associated with the loss of sclerostin may at least in part be attributed to an increase in canonical Wnt signaling resulting from the reduction in sclerostin-mediated Wnt antagonism.
摘要翻译： SOST基因产物硬化的损失？导致以高骨质量（HBM）为特征的硬皮病。在本报告中，我们发现硬皮蛋白可以拮抗人类胚胎肾A293细胞和小鼠成骨细胞MC3T3细胞中的典型Wnt信号传导。这种硬脂蛋白介导的拮抗作用可以通过Wnt共同受体LRP5的过度表达来逆转。此外，我们发现硬骨素与LRP5以及LRP6结合，并鉴定出LRP5的前两个YWTD-EGF重复结构域负责结合。虽然这两个重复结构域是转导规范Wnt信号所必需的，但是典型的Wnt似乎没有与硬皮蛋白竞争结合LRP5。在原发性颅骨成骨细胞分化过程中，考察了sclerostin和Wnt7b（一种自分泌标准Wnt）的表达，表明硬骨素在成骨细胞分化后期表达，与成骨标志物骨钙素表达相符，Wnt7b表达后表达。鉴于许多证据表明典型的Wnt信号传导刺激成骨，我们认为与硬化蛋白的丧失有关的HBM表型可能至少部分归因于由于硬骨素介导的Wnt拮抗作用降低导致的典型Wnt信号传导的增加。

4. 发明申请

WO2010017472A1 COMPOSITIONS AND METHODS AFFECTING THE SIGNALING PATHWAYS OF LRP RECEPTORS 审中-公开
标题翻译：影响LRP受体信号通路的组成和方法
公开(公告)号：WO2010017472A1
公开(公告)日：2010-02-11
申请号：PCT/US2009/053146
申请日：2009-08-07
申请人： ENZO BIOCHEM, INC. , RABBANI, Elazar , LI, Xiaofeng , LIU, Dakai , ZHANG, Yazhou , JIN, Richard , BHATTACHARYYA, Riddhi , CHENG, Wei , ZHANG, Guangrong , LIANG, Yuanxing , ENEA, Vincenzo , DONEGAN, James, J.
发明人： RABBANI, Elazar , LI, Xiaofeng , LIU, Dakai , ZHANG, Yazhou , JIN, Richard , BHATTACHARYYA, Riddhi , CHENG, Wei , ZHANG, Guangrong , LIANG, Yuanxing , ENEA, Vincenzo , DONEGAN, James, J.
IPC分类号： G01N33/53
CPC分类号： A61K31/538 , A61K31/015 , A61K31/185 , A61K31/192 , A61K31/235 , A61K31/395 , A61K31/535 , A61K38/00 , G01N33/5011 , G01N33/5041 , G01N33/564 , G01N33/92 , G01N2333/705 , G01N2800/24
摘要： The present invention relates to the field of therapeutic methods, compositions and uses thereof, that affect, directly or indirectly, the behavior of LRP receptors. These compositions and methods result in the treatment of inflammatory, immunological and metabolic conditions. More particularly, the methods and compositions of the invention are directed to the identification of small molecules, drugs and/or pharmacological agents that affect the Wnt pathway by affecting normal complex formation among various signaling receptors, the LRP5 and LRP6 receptor, and related ligands.
摘要翻译：本发明涉及直接或间接影响LRP受体的行为的治疗方法，组合物和用途领域。这些组合物和方法导致治疗炎症，免疫和代谢疾病。更具体地，本发明的方法和组合物涉及通过影响各种信号传导受体（LRP5和LRP6受体）和相关配体之间的正常复合物形成来鉴定影响Wnt途径的小分子，药物和/或药理学试剂。

5. 发明申请

WO2010019878A1 METHODS FOR IDENTIFYING COMPOUNDS WHICH INHIBIT BINDING OF ANTHRAX PROTEIN TO LRP5/6 RECEPTORS. 审中-公开
标题翻译：用于鉴定化合物的方法，其抑制ANRRAX蛋白与LRP5 / 6受体的结合。
公开(公告)号：WO2010019878A1
公开(公告)日：2010-02-18
申请号：PCT/US2009/053882
申请日：2009-08-14
申请人： ENZO BIOCHEM, INC. , LIU, Dakai , JIN, Richard , LI, Xiaofeng , ZHANG, Yazhou , CHENG, Wei , BHATTACHARYYA, Riddhi
发明人： LIU, Dakai , JIN, Richard , LI, Xiaofeng , ZHANG, Yazhou , CHENG, Wei , BHATTACHARYYA, Riddhi
IPC分类号： G01N33/53 , G01N33/68
CPC分类号： A61K31/538 , G01N33/5041 , G01N33/6803 , G01N2333/51
摘要： The present invention identifies compounds that disrupt the interaction between anthrax proteins and LRP5/6 receptors, resulting in a reduction in anthrax toxicity. The compounds act to disrupt the intracellular transport of toxin complexes into a target cell. The present invention also provides methods for testing the effect of compounds on Wnt activity, through the use of in vitro experiments involving cells that have in at least one gene mutation involved in the Wnt pathway.
摘要翻译：本发明鉴定了破坏炭疽蛋白与LRP5 / 6受体之间相互作用的化合物，导致炭疽毒性降低。这些化合物起着破坏细胞内毒素复合物进入靶细胞的作用。本发明还提供了通过使用涉及在Wnt途径中涉及至少一个基因突变的细胞的体外实验来测试化合物对Wnt活性的影响的方法。

6. 发明申请

WO2013003178A1 SULFATION OF WNT PATHWAY PROTEINS 审中-公开
标题翻译： WNT途径蛋白的硫化
公开(公告)号：WO2013003178A1
公开(公告)日：2013-01-03
申请号：PCT/US2012/043451
申请日：2012-06-21
申请人： ENZO BIOCHEM, INC. , RABBANI, Joshua , DONEGAN, James J. , LI, Xiaofeng
发明人： RABBANI, Joshua , DONEGAN, James J. , LI, Xiaofeng
IPC分类号： C07K14/51 , C07K7/04
CPC分类号： A61K38/1709 , A61K38/08 , A61K38/10 , C07K14/47 , C07K14/51 , C07K14/705 , C07K14/71
摘要： Provided is a composition comprising a peptide comprising amino acids and/or amino acid analogs comprising a continuous sequence of a sclerostin fragment comprising Tyr43 or Tyr213. Also provided is a composition comprising a peptide comprising less than about 75 amino acids and/or amino acid analogs including an amino acid or amino acid analog capable of being sulfated, where the composition is capable of inhibiting sclerostin binding to an LRP. Further provided is a composition comprising a peptide comprising less than about 75 amino acids and/or amino acid analogs including an amino acid or amino acid analog capable of being post-translationally sulfated, where the composition is capable of inhibiting binding of a protein ligand comprising a sulfation site to its binding partner. Additionally provided is a method of enhancing a Wnt signaling pathway comprising contacting an LRP5/6 receptor in the Wnt signaling pathway with either of the above-described compositions that comprise a sequence of a sclerostin fragment or is capable of inhibiting sclerostin binding to an LRP, where the tyrosine or tyrosine analog is not sulfated, in a manner sufficient to enhance the Wnt signaling pathway. Further provided is a method of treating a subject having a disease exacerbated by inhibition of a Wnt signaling pathway comprising administering either of the above-described compositions that comprise a sequence of a sclerostin fragment or is capable of inhibiting sclerostin binding to an LRP, where the tyrosine or tyrosine analog is not sulfated, to the subject in a manner sufficient to reduce the inhibition of the Wnt signaling pathway. Also, a method of inhibiting binding of a protein ligand comprising a sulfation site to its binding partner is provided. The method comprises adding the above-described composition that is capable of inhibiting binding of a protein ligand to its binding partner to the protein ligand and its binding partner in a manner sufficient to inhibit binding of the protein ligand to its binding partner.
摘要翻译：提供了包含包含氨基酸和/或氨基酸类似物的肽的组合物，其包含包含Tyr43或Tyr213的硬化蛋白片段的连续序列。还提供了包含包含少于约75个氨基酸和/或氨基酸类似物的肽的组合物，其包含能够被硫酸化的氨基酸或氨基酸类似物，其中该组合物能够抑制与LRP结合的硬皮蛋白。还提供了一种组合物，其包含包含小于约75个氨基酸和/或氨基酸类似物的肽，其包含能够翻译后硫酸化的氨基酸或氨基酸类似物，其中组合物能够抑制蛋白质配体的结合，所述蛋白质配体包含硫酸化位点到其结合配偶体。另外提供了增强Wnt信号传导途径的方法，包括使Wnt信号传导途径中的LRP5 / 6受体与包含硬化蛋白片段序列的任一上述组合物接触或能够抑制硬化蛋白酶与LRP结合，其中酪氨酸或酪氨酸类似物不被硫酸化，以足以增强Wnt信号通路的方式。还提供了一种治疗具有通过抑制Wnt信号传导途径加重疾病的受试者的方法，包括施用包含硬化蛋白酶片段序列的上述组合物或能够抑制硬化蛋白与LRP的结合，其中酪氨酸或酪氨酸类似物不以足以降低Wnt信号传导途径抑制的方式硫酸化。此外，提供了抑制包含硫酸化位点的蛋白质配体与其结合配偶体的结合的方法。该方法包括加入能够以足以抑制蛋白质配体与其结合配偶体的结合的方式将蛋白质配体与其结合配偶体结合至蛋白质配体及其结合配偶体的上述组合物。

7. 发明申请

WO2007030485A2 NONLINEAR PULSE OSCILLATOR METHODS AND APPARATUS 审中-公开
标题翻译：非线性脉冲振荡器方法和装置
公开(公告)号：WO2007030485A2
公开(公告)日：2007-03-15
申请号：PCT/US2006/034634
申请日：2006-09-06
申请人： PRESIDENT AND FELLOWS OF HARVARD COLLEGE , RICKETTS, David , HAM, Donhee , LI, Xiaofeng
发明人： RICKETTS, David , HAM, Donhee , LI, Xiaofeng
IPC分类号： H03B5/18
CPC分类号： H03L7/099 , H03B5/1221 , H03B5/1234 , H03B5/1243 , H03K5/12
摘要： Methods and apparatus for implementing stable self-starting and self-sustaining high-speed electrical nonlinear pulse (e.g., soliton, cnoidal wave, or quasi-soliton) oscillators. Chip- scale nonlinear pulse oscillator devices may be fabricated using III- V semiconductor materials (e.g., GaAs) to attain soliton pulse widths on the order of a few picoseconds or less (e.g., 1 to 2 picoseconds, corresponding to frequencies of approximately 300 GHz or greater). In one example, a nonlinear pulse oscillator is implemented as a closed loop structure that comprises a nonlinear transmission line and a distributed nonlinear amplifier arrangement configured to provide a self-adjusting gain as a function of an average voltage of the oscillator signal. In another example, a nonlinear oscillator employing a lumped nonlinear amplifier and a nonlinear transmission line in a closed loop arrangement may be used in combination with a two-port nonlinear transmission line that provides additional pulse compression for pulses circulating in the oscillator.
摘要翻译：用于实现稳定的自启动和自持的高速电非线性脉冲（例如，孤子，cnoidal波或准孤子）振荡器的方法和装置。可以使用III-V半导体材料（例如，GaAs）来制造芯片级非线性脉冲振荡器器件，以获得几皮秒或更少数量级的孤子脉冲宽度（例如，1到2皮秒，对应于大约300GHz的频率或更大）。在一个示例中，非线性脉冲振荡器被实现为闭环结构，其包括非线性传输线和配置为提供作为振荡器信号的平均电压的函数的自调节增益的分布式非线性放大器布置。在另一示例中，采用集总非线性放大器和闭环布置中的非线性传输线的非线性振荡器可以与为在振荡器中循环的脉冲提供额外的脉冲压缩的双端口非线性传输线路组合使用。

8. 发明申请

WO2014139483A1 ELECTRONIC FLAMELESS CANDLE 审中-公开
标题翻译：电子无焰蜡烛
公开(公告)号：WO2014139483A1
公开(公告)日：2014-09-18
申请号：PCT/CN2014/073557
申请日：2014-03-17
申请人： LI, Xiaofeng
发明人： LI, Xiaofeng
IPC分类号： F21S13/00 , F21V35/00 , H05B37/00 , F21Y101/02
CPC分类号： F21S10/04 , A61L9/03 , A61L2209/111 , A61L2209/12 , A61L2209/133 , F21S6/001 , F21S9/02 , F21S10/043 , F21V23/04 , F21V23/0471 , F21V33/0088 , F21V33/0092 , F21W2121/00 , F21Y2101/00 , F21Y2113/13 , F21Y2115/10
摘要： An electronic flameless candle(10) including a body (20) having a top surface(22), a bottom surface(24), a sidewall(26) between the top surface(22) and the bottom surface(24), and a cavity(48) defined by the top surface(22), the bottom surf ace(24) and the sidewall(26), the body(20) configured in shape and size to simulate a true flame candle. The candle (10) may also include a light source(56) operably connected to the body(20), the light source(56) electrically operated to illuminate in a way that simulates a natural flicker of a real candle flame. The candle (10) may also include a scent component(40), operably connected to the body(20), the scent component(40) configured to emit a scent when heated and/or a sensor component(70), operably connected to the body(20), the sensor component(70) configured to sense an environmental condition and affect a mode of the light source(56) upon the sensing of the environmental condition.
摘要翻译：一种包括具有顶表面（22），底表面（24），在顶表面（22）和底表面（24）之间的侧壁（26））的主体（20）的电子无焰蜡烛（10）由顶表面（22），底部冲浪（24）和侧壁（26）限定的空腔（48），主体（20）被配置成模拟真实火焰蜡烛的形状和尺寸。蜡烛（10）还可以包括可操作地连接到主体（20）的光源（56），光源（56）电动操作以照亮模拟自然闪烁的真实蜡烛火焰的方式。蜡烛（10）还可以包括可操作地连接到主体（20）的香味组分（40），被配置为在加热时发出气味的气味组分（40）和/或传感器组件（70），可操作地连接到所述主体（20），所述传感器部件（70）被配置为感测环境状况并且在感测到所述环境条件时影响所述光源（56）的模式。

9. 发明申请

WO2009067578A2 NEW VITAMIN D RECEPTOR ACTIVATORS AND METHODS OF MAKING 审中-公开
标题翻译：新维生素D受体激活剂及其制备方法
公开(公告)号：WO2009067578A2
公开(公告)日：2009-05-28
申请号：PCT/US2008/084142
申请日：2008-11-20
申请人： ABBOTT LABORATORIES , VON GELDERN, Thomas W. , BURKALOW, Jufang H. , BARNES, David M. , HAIGHT, Anghony R. , HENGEVELD, John E. , LI, Xiaofeng , MCLAUGHLIN, Maureen A. , NOONAN, William T. , PEI, Zhonghua , WU-WONG, Jinshyun Ruth
发明人： VON GELDERN, Thomas W. , BURKALOW, Jufang H. , BARNES, David M. , HAIGHT, Anghony R. , HENGEVELD, John E. , LI, Xiaofeng , MCLAUGHLIN, Maureen A. , NOONAN, William T. , PEI, Zhonghua , WU-WONG, Jinshyun Ruth
IPC分类号： C07C401/00
CPC分类号： C07C401/00 , C07C2601/14 , C07C2602/24
摘要： The invention relates to compounds that are vitamin D receptor activators, compositions comprising such compounds, methods of using such compounds and compositions, processes for preparing such compounds, and intermediates obtained during such processes.
摘要翻译：本发明涉及作为维生素D受体激活剂的化合物，包含这些化合物的组合物，使用这些化合物和组合物的方法，制备此类化合物的方法以及在此过程中获得的中间体。

10. 发明申请

WO2021126775A1 SCENTED ELECTRONIC CANDLE 审中-公开
公开(公告)号：WO2021126775A1
公开(公告)日：2021-06-24
申请号：PCT/US2020/064878
申请日：2020-12-14
申请人： L&L CANDLE COMPANY, LLC , LI, Xiaofeng
发明人： LI, Xiaofeng
IPC分类号： F21S10/04 , F21V33/00 , F21V23/04 , F21V21/002 , F21V15/01 , F21V1/16 , F21W121/00 , A61L2209/12 , A61L2209/133 , A61L2209/15 , A61L9/037 , F21S10/046 , F21Y2115/10
摘要： Methods, systems and devices associated with a scented electronic candle are described. In one example, an electronic candle includes an outer shell with one or more openings configured to allow a fragrance to exit to an ambient environment of the electronic candle. The outer shell comprises a central opening such that a flame element protrudes at least partially through the central opening. The device includes a light emitting component to emit a light onto the movable flame, and a mounting base positioned below the movable flame element. The device also includes a scent storage component removably coupled to the mounting base. The scent storage component includes a container to store a fragrance and an absorption member configured to draw the fragrance to the ambient environment of the electronic candle through the one or more small openings of the outer shell.

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