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31. 发明授权

US09069700B2 Structural model of G protein-coupled receptor and method for designing ligand capable of binding to G protein-coupled receptor using the structural model 有权
标题翻译： G蛋白偶联受体的结构模型和使用结构模型设计能够结合G蛋白偶联受体的配体的方法
公开(公告)号：US09069700B2
公开(公告)日：2015-06-30
申请号：US13692859
申请日：2012-12-03
申请人： Suntory Holdings Limited
发明人： Masaji Ishiguro
IPC分类号： G06F19/12 , G01N33/566 , G06F19/16 , C07K14/72 , G01N33/68
CPC分类号： G06F19/12 , C07K14/723 , C07K2299/00 , G01N33/566 , G01N33/6803 , G06F19/16
摘要： The present invention provides a method for constructing a three-dimensional structural model of an activated intermediate of a G protein-coupled protein receptor (GPCR) or a complex between a GPCR and a ligand. The three-dimensional structural model may be used to identify, screen, search, evaluate, or design GPCR agonists or antagonists. In a representative embodiment, a three-dimensional structural model of a photoactivated intermediate of rhodopsin is constructed using molecule modeling software and structural coordinates of the crystal structure of rhodopsin. The three-dimensional structural model of rhodopsin is subsequently used to construct structural models of activated intermediates of other GPCRs.
摘要翻译：本发明提供了构建G蛋白偶联蛋白受体（GPCR）或GPCR与配体之间复合物的活化中间体的三维结构模型的方法。三维结构模型可用于识别，筛选，搜索，评估或设计GPCR激动剂或拮抗剂。在代表性的实施方案中，使用分子建模软件和视紫红质的晶体结构的结构坐标构建视紫红质的光活化中间体的三维结构模型。视紫红质的三维结构模型随后用于构建其他GPCR活化中间体的结构模型。

32. 发明授权

US09067981B1 Hybrid amyloid-beta antibodies 有权
标题翻译：杂交淀粉样β抗体
公开(公告)号：US09067981B1
公开(公告)日：2015-06-30
申请号：US12608869
申请日：2009-10-29
申请人： Guriqbal Basi , Dale B. Schenk , Hadar Hana Feinberg , William I. Weis
发明人： Guriqbal Basi , Dale B. Schenk , Hadar Hana Feinberg , William I. Weis
IPC分类号： C07K16/18 , A61K39/395
CPC分类号： C07K16/18 , A61K39/3955 , C07K2299/00 , C07K2317/24 , C07K2317/34 , C07K2317/55 , C07K2317/565 , C07K2317/60
摘要： The present invention provides crystals including amino acids 1-7 of SEQ ID NO:1 and a Fab fragment of 12A11, 12B4, 10D5 or 3D6, as well as of amino acids 1-40 of SEQ ID NO:1 and a Fab fragment of 12A11 or 3D6, as well as methods for preparing the crystals. The present invention also provides a computer implemented method for analyzing binding of a candidate antibody fragment to a peptide including an epitope of amino acids 1-7 of SEQ ID NO:1, a method for identifying an antibody fragment that can mimic the Fab fragment of 12A11, a method for identifying an antibody fragment that can mimic the Fab fragment of 3D6, a method for identifying a candidate antibody fragment that binds to a peptide including an epitope of amino acids 1-7 of SEQ ID NO:1, and a method for designing a humanized antibody that binds to a peptide comprising an epitope of amino acids 1-7 of SEQ ID NO:1.
摘要翻译：本发明提供了包含SEQ ID NO：1的氨基酸1-7和12A11,12B4,10D5或3D6的Fab片段以及SEQ ID NO：1的氨基酸1-40的晶体和包含SEQ ID NO： 12A11或3D6，以及制备晶体的方法。本发明还提供了一种用于分析候选抗体片段与包含SEQ ID NO：1的氨基酸1-7的表位的肽的结合的计算机实施方法，用于鉴定可以模拟SEQ ID NO：1的Fab片段的抗体片段的方法 12A11，鉴定可以模拟3D6的Fab片段的抗体片段的方法，鉴定与包含SEQ ID NO：1的氨基酸1-7的表位的肽结合的候选抗体片段的方法，以及方法用于设计与包含SEQ ID NO：1的氨基酸1-7的表位的肽结合的人源化抗体。

33. 发明申请

US20150175692A1 ANTI-IL-17A ANTIBODIES AND THEIR USE IN TREATING AUTOIMMUNE AND INFLAMMATORY DISORDERS 有权
标题翻译：抗IL-17A抗体及其在治疗自身免疫和炎症疾病中的应用
公开(公告)号：US20150175692A1
公开(公告)日：2015-06-25
申请号：US14174942
申请日：2014-02-07
申请人： Franco E. DI PADOVA , Thomas HUBER , Jean-Michel Rene RONDEAU
发明人： Franco E. DI PADOVA , Thomas HUBER , Jean-Michel Rene RONDEAU
IPC分类号： C07K16/24
CPC分类号： C07K16/244 , A61K39/3955 , A61K2039/505 , C07K2299/00 , C07K2317/14 , C07K2317/21 , C07K2317/24 , C07K2317/33 , C07K2317/34 , C07K2317/54 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/76 , C07K2317/92
摘要： The present disclosure relates to antibodies and proteins comprising an antigen-binding portion thereof that specifically bind to the pro-inflammatory cytokine IL-17A. The disclosure more specifically relates to specific antibodies and proteins that are IL-17A antagonists (inhibit the activities of IL-17A and IL-17AF) and are capable of inhibiting IL-17A induced cytokine production in in vitro assays, and having an inhibitory effect in an antigen-induced arthritis model in vivo. The disclosure further relates to compositions and methods of use for said antibodies and proteins to treat pathological disorders that can be treated by inhibiting IL-17A or IL17AF mediated activity, such as rheumatoid arthritis, psoriasis, systemic lupus erythematosus (SLE), lupus nephritis, chronic obstructive pulmonary disease, asthma or cystic fibrosis or other autoimmune and inflammatory disorders.
摘要翻译：本公开涉及包含特异性结合促炎细胞因子IL-17A的抗原结合部分的抗体和蛋白质。本公开更具体地涉及作为IL-17A拮抗剂的特异性抗体和蛋白质（抑制IL-17A和IL-17AF的活性），并且能够在体外测定中抑制IL-17A诱导的细胞因子产生，并具有抑制作用在抗原诱导的关节炎模型体内。本公开还涉及用于所述抗体和蛋白质以治疗可通过抑制IL-17A或IL17AF介导的活性例如类风湿性关节炎，牛皮癣，系统性红斑狼疮（SLE），狼疮肾炎等治疗的病理学疾病的组合物和方法，慢性阻塞性肺疾病，哮喘或囊性纤维化或其他自身免疫性和炎症性疾病。

34. 发明申请

US20150166648A1 Compositions and Methods for Crystallizing Antibodies 审中-公开
标题翻译：抗体结晶的组成和方法
公开(公告)号：US20150166648A1
公开(公告)日：2015-06-18
申请号：US14297325
申请日：2014-06-05
申请人： AbbVie Inc.
发明人： Wolfgang Fraunhofer , David W. Borhani , Gerhard Winter , Stefan Gottschalk
IPC分类号： C07K16/24 , C30B29/58 , C07K1/30
CPC分类号： C07K16/241 , A61K2039/505 , C07K1/306 , C07K2299/00 , C07K2317/14 , C07K2317/54 , C07K2317/76 , C30B29/58 , Y02A50/388
摘要： The present invention relates to a batch crystallization method for crystallizing anti-human TNFalpha (hTNFalpha) antibody and antibody fragments which allows the production of said antibody on an industrial scale; a method of controlling the size of antibody crystals, for example, crystals of anti-hTNFalpha antibody fragments, compositions containing said crystals as well as methods of use of said crystals and compositions.
摘要翻译：本发明涉及用于结晶抗人TNFα（hTNFα）抗体的分批结晶方法和允许以工业规模生产所述抗体的抗体片段; 控制抗体晶体大小的方法，例如抗hTNFα抗体片段的晶体，含有所述晶体的组合物以及所述晶体和组合物的使用方法。

35. 发明授权

US09056915B2 Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9) 有权
公开(公告)号：US09056915B2
公开(公告)日：2015-06-16
申请号：US14459768
申请日：2014-08-14
申请人： Amgen Inc.
发明人： Simon Mark Jackson , Nigel Pelham Clinton Walker , Derek Evan Piper , Bei Shan , Wenyan Shen , Chadwick Terence King , Randal Robert Ketchem , Christopher Mehlin , Teresa Arazas Carabeo
IPC分类号： C07K16/40 , A61K39/00 , A61K31/22 , A61K31/366 , A61K31/40 , A61K31/405 , A61K31/44 , A61K31/47 , A61K31/505 , A61K31/66 , A61K39/395 , A61K45/06 , C12N15/113
CPC分类号： C07K16/40 , A61K31/22 , A61K31/366 , A61K31/40 , A61K31/405 , A61K31/44 , A61K31/47 , A61K31/505 , A61K31/66 , A61K39/395 , A61K39/3955 , A61K45/06 , A61K2039/505 , C07K2299/00 , C07K2317/14 , C07K2317/34 , C07K2317/76 , C07K2317/92 , C12N15/1137 , A61K2300/00
摘要： Antigen binding proteins that interact with Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) are described. Methods of treating hypercholesterolemia and other disorders by administering a pharmaceutically effective amount of an antigen binding protein to PCSK9 are described. Methods of detecting the amount of PCSK9 in a sample using an antigen binding protein to PCSK9 are described.

36. 发明申请

US20150150860A1 Small Molecules Modulator of Epigenetic Regulation and Their Therapeutic Applications 有权
标题翻译：小分子调控器的表观遗传调控及其治疗应用
公开(公告)号：US20150150860A1
公开(公告)日：2015-06-04
申请号：US14465644
申请日：2014-08-21
申请人： UNIVERSITY OF SOUTHERN CALIFORNIA
发明人： Lin CHEN , Nimanthi JAYATHILAKA , Aidong HAN , Nicos PETASIS
IPC分类号： A61K31/444 , C07D213/40 , A61K31/167 , C07C233/43
CPC分类号： A61K31/444 , A61K31/00 , A61K31/167 , C07C233/43 , C07D213/40 , C07K2299/00 , G01N33/6875 , G01N2500/00
摘要： Disclosed are methods and compositions for modulating the function of transcription factors, especially transcription factors that recruit epigenetic regulators (histone modifying enzymes) to specific DNA promoters. The targeted transcription factors include but are not limited to the myocyte enhancing factor (MEF2), the forkhead/winged helix transcription factor FOXP3 and the transcription factor GATA3. Also disclosed are small molecule modulators of MEF2 and its associated factors that include but not limited to histone deacetylases (HDACs), p300/CBP and Cabin1 and the therapeutic applications thereof
摘要翻译：公开了用于调节转录因子的功能的方法和组合物，特别是将表观遗传调节因子（组蛋白修饰酶）募集到特异性DNA启动子的转录因子。目标转录因子包括但不限于肌细胞增强因子（MEF2），叉头/翼状螺旋转录因子FOXP3和转录因子GATA3。还公开了MEF2的小分子调节剂及其相关因子，包括但不限于组蛋白脱乙酰酶（HDAC），p300 / CBP和Cabin1及其治疗应用

37. 发明授权

US09040049B2 ADAM-15 antibodies and immunogenic peptides 有权
标题翻译： ADAM-15抗体和免疫原性肽
公开(公告)号：US09040049B2
公开(公告)日：2015-05-26
申请号：US12934541
申请日：2009-03-24
申请人： Salman Rahman , Yatin Patel , Holger Gerhardt , Andrea Emma Lundkvist
发明人： Salman Rahman , Yatin Patel , Holger Gerhardt , Andrea Emma Lundkvist
IPC分类号： A61K39/00 , A61K39/395 , A61K39/40 , A61K49/00 , C07K16/40 , C12N15/113
CPC分类号： C07K16/40 , A61K2039/505 , C07K2299/00 , C07K2317/14 , C07K2317/33 , C07K2317/34 , C07K2317/73 , C07K2317/75 , C07K2317/76 , C12N15/1137 , C12N2310/14 , C12N2310/141
摘要： The present invention relates to antibodies and antigen-binding fragments thereof, immunogenic peptide(s), and siRNA molecules which are capable of inhibiting neovascularization and/or angiogenesis and endothelial cell proliferation. The invention relates to antibodies and antigen-binding fragments thereof with specificity towards the metalloprotease domain of ADAM 15 and to immunogenic peptide(s) that elicits such antibodies. The invention also relates to compositions and kits comprising the antibodies and immunogenic peptide(s) of the invention, as well as methods and uses of the antibodies and antigen-binding fragments thereof and immunogenic peptide(s), as well as siRNA molecules.
摘要翻译：本发明涉及能够抑制新生血管形成和/或血管生成和内皮细胞增殖的抗体及其抗原结合片段，免疫原性肽和siRNA分子。本发明涉及对ADAM15的金属蛋白酶结构域具有特异性的抗体及其抗原结合片段以及引发此类抗体的免疫原性肽。本发明还涉及包含本发明的抗体和免疫原性肽的组合物和试剂盒，以及抗体及其抗原结合片段和免疫原性肽以及siRNA分子的方法和用途。

38. 发明申请

US20150142326A1 SYSTEMS AND METHODS FOR IDENTIFYING THERMODYNAMICALLY RELEVANT POLYMER CONFORMATIONS 审中-公开
标题翻译：识别热力学相关聚合物结构的系统和方法
公开(公告)号：US20150142326A1
公开(公告)日：2015-05-21
申请号：US14409419
申请日：2013-06-21
申请人： ZYMEWORKS INC.
发明人： Gregory Lakatos , Siddharth Srinivasan , Surjit Bhimarao Dixit
IPC分类号： G06F19/16
CPC分类号： G16B15/00 , C07K1/00 , C07K2299/00 , G01N33/68 , G16C20/30 , G16C20/70
摘要： Systems, methods and non-transitory computer readable media identify favored polymer conformations. One or more residues are identified and may be replaced in the polymer, or the original primary sequence of the polymer may be retained. The conformations of residues in a subset of residues in a region of the identified one or more residues are altered. This conformational adjustment is repeated for other subsets of residues in the region of the identified one or more residues, and for other conformations, thereby deriving a plurality of polymer structures. A set of clusters is generated for each residue of the polymer using the conformationally adjusted structures, thereby creating sets of clusters. Structures in the plurality of structures are grouped into subgroups when the structures fall into the same clusters across a threshold number of the sets of clusters. One or more physical properties are determined for structures in subgroups, thereby identifying one or more thermodynamically relevant polymer conformations for the polymer.
摘要翻译：系统，方法和非暂时计算机可读介质标识有利的聚合物构象。鉴定出一个或多个残基并且可以在聚合物中被替换，或者可以保留聚合物的原始一级序列。所鉴定的一个或多个残基区域中的残基子集中的残基的构象被改变。在所鉴定的一个或多个残基的区域中的其它子集的残基重复该构象调整，并对其它构型重复，从而导出多个聚合物结构。使用构象调整的结构为聚合物的每个残基生成一组簇，由此产生簇集。当结构通过阈值数量的集群集合落入相同的集群时，多个结构中的结构被分组成子组。确定亚组中的结构的一种或多种物理性质，从而鉴定聚合物的一个或多个热力学相关的聚合物构象。

39. 发明申请

US20150110786A1 COMPOSITIONS FOR INHIBITION OF QUIESCIN SULFHYDRYL OXIDASE (QSOX1) AND USES OF SAME 有权
标题翻译：喹喔啉硫氧化酶（QSOX1）的抑制组合物及其用途
公开(公告)号：US20150110786A1
公开(公告)日：2015-04-23
申请号：US14383571
申请日：2013-03-07
申请人： Yeda Research and Development Co. Ltd.
发明人： Deborah Fass , Iris Grossman , Tal Ilani , Assaf Alon
IPC分类号： C07K16/40
CPC分类号： C07K16/40 , A61K2039/505 , C07K2299/00 , C07K2317/33 , C07K2317/55 , C07K2317/565 , C07K2317/622 , C07K2317/76 , C07K2317/92 , C12Y108/03002
摘要： A method of inhibiting or preventing laminin assembly in a basement membrane is disclosed. The method comprising contacting a tissue with an agent which inhibits QSOX1 activity or expression, thereby inhibiting or preventing laminin assembly in the basement membrane.
摘要翻译：公开了抑制或预防基底膜中层粘连蛋白组合的方法。该方法包括使组织与抑制QSOX1活性或表达的试剂接触，由此抑制或预防基底膜中的层粘连蛋白的组装。

40. 发明申请

US20150105315A1 Polypeptide Fragments Comprising Endonuclease Activity and Their Use 有权
标题翻译：包含核酸内切酶活性的多肽片段及其用途
公开(公告)号：US20150105315A1
公开(公告)日：2015-04-16
申请号：US14519525
申请日：2014-10-21
申请人： Denis Bouvier , Thibaut Crepin , Rob Ruigrok , Alexander Dias , Stephen Cusack
发明人： Denis Bouvier , Thibaut Crepin , Rob Ruigrok , Alexander Dias , Stephen Cusack
IPC分类号： C12N9/22 , G06F19/12 , C12N9/12 , C12Q1/44 , G06F19/16 , A61K31/192
CPC分类号： C12N9/22 , A61K31/192 , C07K2299/00 , C12N9/127 , C12Q1/44 , G01N2333/922 , G01N2500/02 , G06F19/12 , G06F19/16
摘要： The present invention relates to polypeptide fragments comprising an amino-terminal fragment of the PA subunit of a viral RNA-dependent RNA polymerase or variants thereof possessing endonuclease activity, wherein said PA subunit is from a virus belonging to the Orthomyxoviridae family. This invention also relates to (i) crystals of the polypeptide fragments which are suitable for structure determination of said polypeptide fragments using X-ray crystallography and (ii) computational methods using the structural coordinates of said polypeptide to screen for and design compounds that modulate, preferably inhibit the endonucleolytically active site within the polypeptide fragment. In addition, this invention relates to methods identifying compounds that bind to the PA polypeptide fragments possessing endonuclease activity and preferably inhibit said endonucleolytic activity, preferably in a high throughput setting. This invention also relates to compounds and pharmaceutical compositions comprising the identified compounds for the treatment of disease conditions due to viral infections caused by viruses of the Orthomyxoviridae family.
摘要翻译：本发明涉及包含病毒RNA依赖性RNA聚合酶的PA亚基的氨基末端片段或其具有核酸内切酶活性的变体的多肽片段，其中所述PA亚单位来自属于正粘病毒科的病毒。本发明还涉及（i）适合于使用X射线晶体学结构测定所述多肽片段的多肽片段的晶体，以及（ii）使用所述多肽的结构坐标筛选和设计调节化合物的计算方法，优选抑制多肽片段内的核内解离活性位点。此外，本发明涉及鉴定结合具有核酸内切酶活性的PA多肽片段的化合物的方法，优选抑制所述内切核酸酶活性，优选以高通量设置。本发明还涉及包含鉴定的化合物的化合物和药物组合物，用于治疗由正粘病毒科家族病毒引起的病毒感染导致的疾病状况。

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