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1. 发明申请

US20130261052A1 INHIBITION OF MEMAPSIN 1 CLEAVAGE IN THE TREATMENT OF DIABETES 有权
标题翻译：在治疗糖尿病中抑制MEMAPSIN 1 CLEAVAGE
公开(公告)号：US20130261052A1
公开(公告)日：2013-10-03
申请号：US13794031
申请日：2013-03-11
申请人： Jordan Tang , Xiangping Huang , Deborah Downs
发明人： Jordan Tang , Xiangping Huang , Deborah Downs
IPC分类号： C07D239/84 , C07D417/12 , C07C311/08 , C07D513/04 , C07D241/04 , C07K5/02 , C07D403/12 , C07D413/12
CPC分类号： C07D239/84 , A61K31/166 , A61K31/18 , A61K31/495 , A61K38/05 , C07C311/08 , C07D241/04 , C07D403/12 , C07D413/12 , C07D417/12 , C07D513/04 , C07K5/0207
摘要： Proteases such as memapsin-1 are import enzymes, playing roles in a variety of diseases including diabetes. The inventors have developed inhibitors of memapsin 1 and methods of use therefore in the treatment of disease.
摘要翻译：蛋白酶如memapsin-1是进口酶，在各种疾病，包括糖尿病中发挥作用。本发明人已经开发了复合蛋白1的抑制剂和因此用于治疗疾病的方法。

2. 发明申请

US20100015154A1 IMMUNOGENIC MEMAPSIN 2 B-SECRETASE PEPTIDES AND METHODS OF USE 有权
标题翻译：免疫球蛋白2 B分泌肽及其使用方法
公开(公告)号：US20100015154A1
公开(公告)日：2010-01-21
申请号：US12489314
申请日：2009-06-22
申请人： Wan-Pin Chang , Jordan Tang
发明人： Wan-Pin Chang , Jordan Tang
IPC分类号： A61K39/395 , C07K16/00 , C12N5/06 , C07K14/435 , C07K7/08 , A61K39/00
CPC分类号： C07K16/28 , A61K39/00 , A61K39/0007 , A61K2039/505 , A61K2039/55566 , A61K2039/6081 , C07K16/40 , C07K2317/34 , C07K2317/76
摘要： This application pertains to antibodies which specifically bind to immunogenic memapsin 2β-secretase peptides for use in the treatment of Alzheimer's disease and memapsin 2β-secretase disorders. The application also pertains to immunogenic compositions comprising memapsin 2β-secretase peptides and uses thereof.
摘要翻译：本申请涉及特异性结合用于治疗阿尔茨海默氏病和复发蛋白2beta分泌酶障碍的免疫原性膜蛋白2β-分泌酶肽的抗体。本申请还涉及包含memapsin 2beta分泌酶肽及其用途的免疫原性组合物。

3. 发明申请

US20070117793A1 Compounds Which Inhibit Beta-Secretase Activity and Methods of Use 有权
标题翻译：抑制β-分泌酶活性的化合物和使用方法
公开(公告)号：US20070117793A1
公开(公告)日：2007-05-24
申请号：US11463558
申请日：2006-08-09
申请人： Arun Ghosh , Nagaswamy Kumaragurubaran , Chunfeng Liu , Thippeswamy Devasamudram , Hui Lei , Lisa Swanson , Sudha Ankala , Jordan Tang , Geoffrey Bilcer
发明人： Arun Ghosh , Nagaswamy Kumaragurubaran , Chunfeng Liu , Thippeswamy Devasamudram , Hui Lei , Lisa Swanson , Sudha Ankala , Jordan Tang , Geoffrey Bilcer
IPC分类号： A61K31/551 , A61K31/497 , A61K31/501 , A61K31/506 , A61K31/473 , A61K31/4709 , A61K31/427 , A61K31/422 , A61K31/4178 , A61K31/4184
CPC分类号： C07D213/74 , C07C233/78 , C07C311/08 , C07C311/29 , C07C2601/14 , C07D207/09 , C07D209/14 , C07D211/26 , C07D213/36 , C07D213/40 , C07D213/61 , C07D213/65 , C07D215/12 , C07D233/64 , C07D235/14 , C07D241/12 , C07D261/08 , C07D263/32 , C07D277/28 , C07D295/108 , C07D295/13 , C07D295/205 , C07D295/32 , C07D307/52 , C07D307/62 , C07D309/04 , C07D317/58 , C07D417/12 , C07D493/04
摘要： The present invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating Alzheimer's disease.
摘要翻译：本发明提供新颖的β-分泌酶抑制剂及其使用方法，包括治疗阿尔茨海默氏病的方法。

4. 发明授权

US07989597B2 Immunogenic memapsin 2 β-secretase peptides and methods of use 有权
标题翻译：免疫原性突变蛋白2和分泌蛋白酶肽及其使用方法
公开(公告)号：US07989597B2
公开(公告)日：2011-08-02
申请号：US12489314
申请日：2009-06-22
申请人： Wan-Pin Chang , Jordan Tang
发明人： Wan-Pin Chang , Jordan Tang
IPC分类号： C07K16/00 , C12P21/08 , A61K39/395
CPC分类号： C07K16/28 , A61K39/00 , A61K39/0007 , A61K2039/505 , A61K2039/55566 , A61K2039/6081 , C07K16/40 , C07K2317/34 , C07K2317/76
摘要： This application pertains to antibodies which specifically bind to immunogenic memapsin 2β-secretase peptides for use in the treatment of Alzheimer's disease and memapsin 2β-secretase disorders. The application also pertains to immunogenic compositions comprising memapsin 2β-secretase peptides and uses thereof.
摘要翻译：本申请涉及特异性结合用于治疗阿尔茨海默氏病和复发蛋白2和分泌系统疾病的免疫原性蛋白2和分泌酶肽的抗体。本申请还涉及含有胶原蛋白2和分泌分泌肽及其用途的免疫原性组合物。

5. 发明申请

US20080176939A1 COMPOUNDS WHICH INHIBIT BETA-SECRETASE ACTIVITY AND METHODS OF USE THEREOF 审中-公开
标题翻译：抑制β-分泌酶活性的化合物及其使用方法
公开(公告)号：US20080176939A1
公开(公告)日：2008-07-24
申请号：US11832540
申请日：2007-08-01
申请人： Arun K. Ghosh , Nagaswamy Kumaragurubaran , Chunfeng Liu , Thippeswamy Devasamudram , Hui Lei , Lisa Swanson , Sudha Ankala , Jordan Tang , Geoffrey Bilcer
发明人： Arun K. Ghosh , Nagaswamy Kumaragurubaran , Chunfeng Liu , Thippeswamy Devasamudram , Hui Lei , Lisa Swanson , Sudha Ankala , Jordan Tang , Geoffrey Bilcer
IPC分类号： A61K31/18 , C07C271/06 , A61K31/27 , A61P25/28 , C07C311/00
CPC分类号： C07D213/74 , C07C233/78 , C07C311/08 , C07C311/29 , C07C2601/14 , C07D207/09 , C07D209/14 , C07D211/26 , C07D213/36 , C07D213/40 , C07D213/61 , C07D213/65 , C07D215/12 , C07D233/64 , C07D235/14 , C07D241/12 , C07D261/08 , C07D263/32 , C07D277/28 , C07D295/108 , C07D295/13 , C07D295/205 , C07D295/32 , C07D307/52 , C07D307/62 , C07D309/04 , C07D317/58 , C07D417/12 , C07D493/04
摘要： The present invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating Alzheimer's disease.
摘要翻译：本发明提供新颖的β-分泌酶抑制剂及其使用方法，包括治疗阿尔茨海默氏病的方法。

6. 发明申请

US20080021196A1 INHIBITORS OF MEMAPSIN 2 AND USE THEREOF 失效
标题翻译： MEMAPSIN 2的抑制剂及其用途
公开(公告)号：US20080021196A1
公开(公告)日：2008-01-24
申请号：US11763342
申请日：2007-06-14
申请人： Jordan TANG , Arun Ghosh
发明人： Jordan TANG , Arun Ghosh
IPC分类号： C07C7/06 , C07C229/24
CPC分类号： C07K5/1021 , A61K38/00 , A61K39/00 , C07K1/1136 , C07K5/06026 , C07K5/06043 , C07K5/0806 , C07K2299/00 , C12N9/6421 , C12N9/6478 , Y02A90/26 , Y10S514/879
摘要： Methods for the production of purified, catalytically active, recombinant memapsin 2 have been developed. The substrate and subsite specificity of the catalytically active enzyme have been determined. The substrate and subsite specificity information was used to design substrate analogs of the natural memapsin 2 substrate that can inhibit the function of memapsin 2. The substrate analogs are based on peptide sequences, shown to be related to the natural peptide substrates for memapsin 2. The substrate analogs contain at least one analog of an amide bond which is not capable of being cleaved by memapsin 2. Processes for the synthesis of two substrate analogues including isosteres at the sites of the critical amino acid residues were developed and the substrate analogues, OMR99-1 and OM99-2, were synthesized. OM99-2 is based on an octapeptide Glu-Val-Asn-Leu-Ala-Ala-Glu-Phe (SEQ ID NO:28) with the Leu-Ala peptide bond substituted by a transition-state isostere hydroxyethylene group (FIG. 1). The inhibition constant of OM99-2 is 1.6×10−9 M against recombinant pro-memapsin 2. Crystallography of memapsin 2 bound to this inhibitor was used to determine the three dimensional structure of the protein, as well as the importance of the various residues in binding. This information can be used by those skilled in the art to design new inhibitors, using commercially available software programs and techniques familiar to those in organic chemistry and enzymology, to design new inhibitors to memapsin 2, useful in diagnostics and for the treatment and/or prevention of Alzheimer's disease.
摘要翻译：已经开发了用于生产纯化的，催化活性的重组突变蛋白2的方法。已经确定了催化活性酶的底物和亚位点特异性。底物和亚位点特异性信息用于设计可以抑制膜蛋白2功能的天然memapsin 2底物的底物类似物。底物类似物基于肽序列，显示与memapsin 2的天然肽底物相关。底物类似物含有至少一个酰胺键的类似物，该类似物不能被膜蛋白2切割。开发了两个底物类似物合成的关键氨基酸残基位点处的等位基因，底物类似物OMR99- 1和OM99-2。 OM99-2基于由过渡态等电位羟基亚乙基取代的Leu-Ala肽键的八肽Glu-Val-Asn-Leu-Ala-Ala-Glu-Phe（SEQ ID NO：28）（图1 ）。 OM99-2的抑制常数相对于重组pro-memapsin为1.6×10 -9 M。使用与该抑制剂结合的胶原蛋白2的结晶学来确定蛋白质的三维结构，以及各种残留物在结合中的重要性。本领域技术人员可以使用本信息来设计新的抑制剂，使用商业上可获得的有机化学和酶学方面熟悉的软件程序和技术来设计新的抑制剂2，可用于诊断和治疗和/或预防阿尔茨海默病。

7. 发明申请

US20070092517A1 TRUNCATED MEMAPSIN 2 COMPOSITIONS AND TREATMENTS 审中-公开
标题翻译：截短的MEMAPSIN 2组合物和治疗
公开(公告)号：US20070092517A1
公开(公告)日：2007-04-26
申请号：US11463501
申请日：2006-08-09
申请人： Wan Chang , Deborah Downs , Jordan Tang
发明人： Wan Chang , Deborah Downs , Jordan Tang
IPC分类号： A61K39/395 , C07K14/47 , C07K16/18
CPC分类号： A61K38/488 , A61K2039/505 , C07K16/40 , C12N9/6421
摘要： The present invention provides novel methods of reducing memapsin 2 β-secretase activity in a subject, decreasing levels of β-amyloid peptide in the brain of a subject, treating Alzheimer's disease and/or reducing the size and/or number of β-amyloid plaques in the brain of a subject. The methods may include the step of administering an effective amount of truncated memapsin 2 protein, anti-truncated memapsin 2 antibody, and/or nucleic acid encoding a truncated memapsin 2 protein or anti-truncated memapsin 2 antibody. The present invention also provides related pharmaceutical compositions and uses thereof.
摘要翻译：本发明提供了减少受试者中复制蛋白2β-分泌酶活性的新方法，降低受试者脑中β-淀粉样蛋白肽的水平，治疗阿尔茨海默氏病和/或减少β-淀粉样斑块的大小和/或数量在一个主题的大脑中。所述方法可以包括施用有效量的截短的复合蛋白2蛋白，抗截短的胶原蛋白2抗体和/或编码截短的胶原蛋白2的蛋白质或抗截短的胶原蛋白2抗体的核酸的步骤。本发明还提供了相关的药物组合物及其用途。

8. 发明授权

US06225103B1 Cloning and characterization of napsin 失效
标题翻译： napsin的克隆和表征
公开(公告)号：US06225103B1
公开(公告)日：2001-05-01
申请号：US08974691
申请日：1997-11-20
申请人： Gerald Keolsch , Xinli Lin , Jordan Tang
发明人： Gerald Keolsch , Xinli Lin , Jordan Tang
IPC分类号： A61K3857
CPC分类号： C12N9/6478
摘要： A previously unknown aspartic protease capable of cleavage of proteins by hydrolysis, referred to herein as “napsin”, has been cloned from a human liver library. Two cDNA clones have been cloned, sequenced and expressed. These encode isozymes of the protease, referred to as “napsin A” and “napsin B”. The gene has also be obtained and partially sequenced. A process for rapid purification of the enzyme using immobilized petpstatin has also been developed, and enzyme isolated from human kidney tissue. Polyclonal antibodies to the enzymes have been made which are also useful for isolation and detection of the enzyme. Similarities to other aspartic proteases, especially cathepsin D, establish the usefulness of the enzyme in diagnostic assays as well as as a protease. Either or both the amount or type of napsin expressed in a particular tissue can be determined using labelled antibodies or nucleotide probes to the napsin.
摘要翻译：已经从人肝脏文库克隆了能够通过水解裂解蛋白质的以前未知的天冬氨酸蛋白酶，这里称为“重叠蛋白酶”（Napsin））。已经克隆，测序和表达了两个cDNA克隆。这些编码蛋白酶的同功酶，称为“napsin A”和“napsin B”。该基因也可获得并部分测序。还开发了使用固定的petpstatin快速纯化酶的方法，并从人肾组织中分离酶。已经制备了对酶的多克隆抗体，其也可用于分离和检测酶。与其他天冬氨酸蛋白酶，特别是组织蛋白酶D的相似性确定了酶在诊断测定中的用途以及作为蛋白酶。在特定组织中表达的napsin的量或类型中的任一个或两者可以使用标记的抗体或对napsin的核苷酸探针来确定。

9. 发明申请

US20050239684A1 Compounds which inhibit beta-secretase activity and methods of use thereof 失效
标题翻译：抑制β-分泌酶活性的化合物及其使用方法
公开(公告)号：US20050239684A1
公开(公告)日：2005-10-27
申请号：US10944117
申请日：2004-09-17
申请人： Arun Ghosh , Jordan Tang , Hui Lei , Thippeswamy Devasamudram , Chunfeng Liu , Geoffrey Bilcer
发明人： Arun Ghosh , Jordan Tang , Hui Lei , Thippeswamy Devasamudram , Chunfeng Liu , Geoffrey Bilcer
IPC分类号： A61K38/00 , A61P25/28 , C07D207/16 , C07D213/30 , C07D213/40 , C07D215/14 , C07D215/36 , C07D215/54 , C07D307/14 , C07D307/16 , C07D307/20 , C07D307/93 , C07D493/04 , C07D521/00 , C07K5/03 , C07K7/02 , C07K14/00 , C07K14/47 , A61K38/17
CPC分类号： C07D307/93 , C07D207/16 , C07D213/30 , C07D213/40 , C07D215/14 , C07D215/36 , C07D215/54 , C07D231/12 , C07D233/56 , C07D249/08 , C07D307/14 , C07D307/16 , C07D307/20 , C07D493/04
摘要： The present invention provides novel beta-secretase inhibitors and methods for their use, including methods of treating of Alzheimer's disease.
摘要翻译：本发明提供新颖的β-分泌酶抑制剂及其使用方法，包括治疗阿尔茨海默氏病的方法。

10. 发明授权

US09096541B2 Inhibition of memapsin 1 cleavage in the treatment of diabetes 有权
标题翻译：抑制糖皮质激素1切割治疗糖尿病
公开(公告)号：US09096541B2
公开(公告)日：2015-08-04
申请号：US13794031
申请日：2013-03-11
申请人： Jordan Tang , Xiangping Huang , Deborah Downs , Arun K. Ghosh
发明人： Jordan Tang , Xiangping Huang , Deborah Downs , Arun K. Ghosh
IPC分类号： A61K31/166 , A61K31/4965 , A61K38/05 , C07D239/84 , C07D403/12 , C07D417/12 , C07D413/12 , C07D513/04 , C07D241/04 , C07K5/02 , C07C311/08 , A61K31/495 , A61K31/18
CPC分类号： C07D239/84 , A61K31/166 , A61K31/18 , A61K31/495 , A61K38/05 , C07C311/08 , C07D241/04 , C07D403/12 , C07D413/12 , C07D417/12 , C07D513/04 , C07K5/0207
摘要： Proteases such as memapsin-1 are import enzymes, playing roles in a variety of diseases including diabetes. The inventors have developed inhibitors of memapsin 1 and methods of use therefore in the treatment of disease.
摘要翻译：蛋白酶如memapsin-1是进口酶，在各种疾病，包括糖尿病中发挥作用。本发明人已经开发了复合蛋白1的抑制剂和因此用于治疗疾病的方法。

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