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1. 发明申请

US20070224212A1 Stable Peptide Mimetic of Hiv Gp41 Fusion Intermediate 有权
标题翻译：稳定肽模拟的HIF Gp41融合中间体
公开(公告)号：US20070224212A1
公开(公告)日：2007-09-27
申请号：US11628483
申请日：2005-05-27
申请人： Elisabetta Bianchi , Antonello Pessi , Romas Geleziunas , David Bramhill
发明人： Elisabetta Bianchi , Antonello Pessi , Romas Geleziunas , David Bramhill
IPC分类号： C12Q1/70
CPC分类号： C07K14/005 , A61K38/00 , A61K39/00 , A61K39/12 , C12N2740/15022 , C12N2740/16122 , C12N2740/16134 , G01N2333/16 , G01N2500/02
摘要： Methods of covalently-stabilizing alpha-helical, chimeric peptides constrained within a homotrimeric or heterotrimeric coiled-coil structure are disclosed. The coiled-coil structures made by the methods disclosed within this specification mimic all or a portion of the internal, trimeric coiled-coil motif contained within the fusogenic conformation of an enveloped virus membrane-fusion protein, particularly the internal coiled-coil domain of the HIV gp41 ectodomain. The HIV-derived, chimeric peptides disclosed comprise a non-HIV, soluble, trimeric form of a coiled-coil fused in helical phase to all or a portion of the N-helix of HIV gp41 and are covalently-stabilized in a homotrimeric or heterotrimeric coiled-coil structure through the formation of disulfide or chemoselective bonds between said peptides. The covalently-stabilized, HIV-derived, homotrimeric or heterotrimeric coiled-coil structures made by the methods disclosed herein represent a close mimetic of a HIV gp41 fusion intermediate and are potent inhibitors of HIV infectivity. These HIV-derived chimeric peptides may provide for therapeutic treatment against HIV infection by inhibiting the virus-host cell membrane fusion process.
摘要翻译：公开了限制在同三聚体或异三聚体卷曲螺旋结构内的共价稳定的α-螺旋嵌合肽的方法。通过本说明书中公开的方法制备的盘绕线圈结构模拟包含在包膜病毒膜 - 融合蛋白的融合构象内的内部三聚体卷曲螺旋基序的全部或一部分，特别是内部卷曲螺旋结构域 HIV gp41胞外域。所公开的HIV衍生的嵌合肽包含螺旋状螺旋状的非HIV，可溶性三聚体形式，其与HIV gp41的全部或部分N-螺旋融合，并且以同三聚或异三聚体共价稳定通过在所述肽之间形成二硫键或化学选择性键来进行卷曲螺旋结构。由本文公开的方法制备的共价稳定的HIV衍生的同源三聚体或异三聚体卷曲螺旋结构代表HIV gp41融合中间体的密切模拟物，并且是HIV感染性的有效抑制剂。这些HIV衍生的嵌合肽可以通过抑制病毒宿主细胞膜融合过程来提供针对HIV感染的治疗性治疗。

2. 发明授权

US07811577B2 Covalently stabilized chimeric coiled-coil HIV gp41 N-peptides with improved antiviral activity 有权
标题翻译：具有改善的抗病毒活性的共价稳定的嵌合卷曲螺旋HIV gp41 N-肽
公开(公告)号：US07811577B2
公开(公告)日：2010-10-12
申请号：US11628483
申请日：2005-05-27
申请人： Elisabetta Bianchi , Antonello Pessi , Romas Geleziunas , David Bramhill
发明人： Elisabetta Bianchi , Antonello Pessi , Romas Geleziunas , David Bramhill
IPC分类号： A61K39/00 , A61K39/21
CPC分类号： C07K14/005 , A61K38/00 , A61K39/00 , A61K39/12 , C12N2740/15022 , C12N2740/16122 , C12N2740/16134 , G01N2333/16 , G01N2500/02
摘要： Methods of covalently-stabilizing alpha-helical, chimeric peptides constrained within a homotrimeric or heterotrimeric coiled-coil structure are disclosed. The coiled-coil structures made by the methods disclosed within this specification mimic all or a portion of the internal, trimeric coiled-coil motif contained within the fusogenic conformation of an enveloped virus membrane-fusion protein, particularly the internal coiled-coil domain of the HIV gp41 ectodomain. The HIV-derived, chimeric peptides disclosed comprise a non-HIV, soluble, trimeric form of a coiled-coil fused in helical phase to all or a portion of the N-helix of HIV gp41 and are covalently-stabilized in a homotrimeric or heterotrimeric coiled-coil structure through the formation of disulfide or chemoselective bonds between said peptides. The covalently-stabilized, HIV-derived, homotrimeric or heterotrimeric coiled-coil structures made by the methods disclosed herein represent a close mimetic of a HIV gp41 fusion intermediate and are potent inhibitors of HIV infectivity. These HIV-derived chimeric peptides may provide for therapeutic treatment against HIV infection by inhibiting the virus-host cell membrane fusion process.
摘要翻译：公开了限制在同三聚体或异三聚体卷曲螺旋结构内的共价稳定的α-螺旋嵌合肽的方法。通过本说明书中公开的方法制备的盘绕线圈结构模拟包含在包膜病毒膜 - 融合蛋白的融合构象内的内部三聚体卷曲螺旋基序的全部或一部分，特别是内部卷曲螺旋结构域 HIV gp41胞外域。所公开的HIV衍生的嵌合肽包含螺旋状螺旋状的非HIV，可溶性三聚体形式，其与HIV gp41的全部或部分N-螺旋融合，并以共三聚体或异三聚体共价稳定通过在所述肽之间形成二硫键或化学选择性键来进行卷曲螺旋结构。由本文公开的方法制备的共价稳定的HIV衍生的同源三聚体或异三聚体卷曲螺旋结构代表HIV gp41融合中间体的密切模拟物，并且是HIV感染性的有效抑制剂。这些HIV衍生的嵌合肽可以通过抑制病毒宿主细胞膜融合过程来提供针对HIV感染的治疗性治疗。

3. 发明申请

US20110224097A1 VIABLE GRAM NEGATIVE BACTERIA LACKING OUTER MEMBRANE AGONISTS OF TLR4/MD-2 有权
标题翻译： TLR4 / MD-2的可视化GRAM负面细菌缺失外膜激素
公开(公告)号：US20110224097A1
公开(公告)日：2011-09-15
申请号：US13046562
申请日：2011-03-11
申请人： David Bramhill , Uwe Mamat
发明人： David Bramhill , Uwe Mamat
IPC分类号： C40B40/02 , C12N1/20 , C12N1/21 , C12N1/00 , C12N15/63 , C12N15/70 , C12P19/34 , C12P21/00
CPC分类号： C12N15/70 , C12N15/1037 , C12N15/78 , C12P19/34 , C12P21/02 , C40B40/02
摘要： Viable Gram-negative bacteria or components thereof comprising outer membranes that substantially lack a ligand, such as Lipid A or 6-acyl lipidpolysaccharide, that acts as an agonist of TLR4/MD2. The bacteria may comprise reduced activity of arabinose-5-phosphate isomerases and one or more suppressor mutations, for example in a transporter thereby increasing the transporters capacity to transport Lipid IVA or in membrane protein YhjD. One or more genes (e.g., IpxL, IpxM, pagP, IpxP, and/or eptA) may be substantially deleted and/or one or more enzymes (e.g., LpxL, LpxM, PagP, LpxP, and/or EptA) may be substantially inactive. The bacteria may be competent to take up extracellular DNA, may be donor bacteria, or may be members of a library. The present invention also features methods of creating and utilizing such bacteria.
摘要翻译：可行的革兰氏阴性细菌或其组分包含充当TLR4 / MD2的激动剂的基本上不含配体例如脂质A或6-酰基脂多聚糖的外膜。细菌可以包含降低的阿拉伯糖-5-磷酸异构酶的活性和一种或多种抑制突变，例如在转运蛋白中，由此增加运输脂质IVA或膜蛋白YhjD的转运蛋白能力。基本上可以删除一个或多个基因（例如，IpxL，IpxM，pagP，IpxP和/或eptA）和/或一个或多个酶（例如，LpxL，LpxM，PagP，LpxP和/或EptA）不活跃细菌可能有能力摄取细胞外DNA，可能是供体细菌，也可能是文库的成员。本发明还涉及产生和利用这种细菌的方法。

4. 发明申请

US20130189247A1 Multimeric Proteins Comprising Immunoglobulin Constant Domains 审中-公开
标题翻译：包含免疫球蛋白常数域的多聚体蛋白质
公开(公告)号：US20130189247A1
公开(公告)日：2013-07-25
申请号：US13578538
申请日：2011-02-11
申请人： David Bramhill , Kurt R. Gehlsen , Dimiter S. Dimitrov , Rui Gong
发明人： David Bramhill , Kurt R. Gehlsen , Dimiter S. Dimitrov , Rui Gong
IPC分类号： C07K16/00
CPC分类号： C07K16/00 , A61K2039/505 , C07K16/1063 , C07K16/28 , C07K16/2812 , C07K16/468 , C07K2317/21 , C07K2317/32 , C07K2317/524 , C07K2317/569 , C07K2317/60 , C07K2317/64 , C07K2317/66 , C07K2317/76 , C07K2317/94 , C07K2318/10 , Y02A50/386 , Y02A50/388 , Y02A50/466
摘要： The present invention relate to small binding proteins comprising two or more protein domains derived from a CH2 domain or CH2-like domain of an immunoglobulin in which the CH2 domains have been altered to recognize one or more target proteins and, in some embodiments, retain, or have modified, certain secondary effector functions.
摘要翻译：本发明涉及包含两个或多个衍生自免疫球蛋白的CH2结构域或CH2样结构域的蛋白质结构域的小结合蛋白，其中CH2结构域已被改变以识别一种或多种靶蛋白，并且在一些实施方案中保留，或具有修改的某些二级效应器功能。

5. 发明申请

US20120230981A1 CH2 Domain Template Molecules Derived From Rational Grafting Of Donor Loops Onto CH2 Scaffolds 有权
标题翻译： CH2结构域模板分子衍生自供体循环的合理移植到CH2支架
公开(公告)号：US20120230981A1
公开(公告)日：2012-09-13
申请号：US13370831
申请日：2012-02-10
申请人： David Bramhill , Gopalan Raghunathan
发明人： David Bramhill , Gopalan Raghunathan
IPC分类号： C07K16/00 , A61K39/395 , C40B30/04 , C07K17/00
CPC分类号： C07K16/461 , C07K16/005 , C07K16/42 , C07K2317/524 , C07K2317/92 , C07K2317/94 , C40B30/04 , G01N33/6854
摘要： Novel CH2 domain template molecules wherein donor loops from a database of domains are transferred to a CH2 domain scaffold. At least one or up to three loops from a donor are transferred to the CH2 domain. The donor loops may be chosen based on length, e.g., the donor loop may have a length that is similar to that of a structural loop in the CH2 domain scaffold.
摘要翻译：其中将来自结构域数据库的供体环转移到CH2结构域支架的新型CH2结构域模板分子。来自供体的至少一个或多达三个环被转移到CH2结构域。可以基于长度来选择供体环，例如，供体环可以具有与CH2结构域支架中的结构环的长度相似的长度。

6. 发明授权

US09458454B2 Viable gram negative bacteria with reduced proteolytic activity lacking outer membrane agonists of TLR4/MD-2 有权
标题翻译：具有降低的蛋白水解活性的活的革兰氏阴性细菌缺乏TLR4 / MD-2的外膜激动剂
公开(公告)号：US09458454B2
公开(公告)日：2016-10-04
申请号：US14343974
申请日：2012-09-07
申请人： David Bramhill , Uwe Mamat
发明人： David Bramhill , Uwe Mamat
IPC分类号： C12N1/00 , C12N15/10 , C12N9/52 , C12N15/70 , C12N15/78 , C12P19/34 , C12P21/00
CPC分类号： C12N15/1037 , C12N9/52 , C12N15/70 , C12N15/78 , C12P19/34 , C12P21/00
摘要： Viable Gram-negative bacteria or components thereof comprising outer membranes that substantially lack a ligand, such as Lipid A or 6-acyl lipidpolysaccharide, that acts as an agonist of TLR4/MD-2. The bacteria may comprise reduced activity of arabinose-5-phosphate isomerases and one or more suppressor mutations, for example in a transporter thereby increasing the transporter's capacity to transport lipid IVA or in membrane protein YhjD. One or more genes (e.g., lpxL, lpxM, pagP, lpxP, and/or eptA) may be substantially deleted and/or one or more enzymes (e.g., LpxL, LpxM, PagP, LpxP, and/or EptA) may be substantially inactive. The bacteria may be competent to take up extracellular DNA, may be donor bacteria, or may be members of a library. The present invention also features methods of creating and utilizing such bacteria.
摘要翻译：可行的革兰氏阴性细菌或其组分包含充当TLR4 / MD-2的激动剂的基本上不含配体例如脂质A或6-酰基脂多聚糖的外膜。细菌可以包含降低的阿拉伯糖-5-磷酸异构酶的活性和一种或多种抑制突变，例如在转运蛋白中，从而增加转运蛋白转运脂质IVA或膜蛋白YhjD的能力。基本上可以删除一个或多个基因（例如，lpxL，lpxM，pagP，lpxP和/或eptA），和/或一个或多个酶（例如LpxL，LpxM，PagP，LpxP和/或EptA）不活跃细菌可能有能力摄取细胞外DNA，可能是供体细菌，也可能是文库的成员。本发明还涉及产生和利用这种细菌的方法。

7. 发明申请

US20140221251A1 VIABLE GRAM NEGATIVE BACTERIA WITH REDUCED PROTEOLYTIC ACTIVITY LACKING OUTER MEMBRANE AGONISTS OF TLR4/MD-2 有权
标题翻译：具有减少的抗肿瘤活性的可视化GRAM阴性细菌缺少TLR4 / MD-2的外膜激动剂
公开(公告)号：US20140221251A1
公开(公告)日：2014-08-07
申请号：US14343974
申请日：2012-09-07
申请人： David Bramhill , Uwe Mamat
发明人： David Bramhill , Uwe Mamat
IPC分类号： C12N15/70 , C12N15/10 , C12P21/00 , C12N15/78 , C12P19/34
CPC分类号： C12N15/1037 , C12N9/52 , C12N15/70 , C12N15/78 , C12P19/34 , C12P21/00
摘要： Viable Gram-negative bacteria or components thereof comprising outer membranes that substantially lack a ligand, such as Lipid A or 6-acyl lipidpolysaccharide, that acts as an agonist of TLR4/MD-2. The bacteria may comprise reduced activity of arabinose-5-phosphate isomerases and one or more suppressor mutations, for example in a transporter thereby increasing the transporter's capacity to transport lipid IVA or in membrane protein YhjD. One or more genes (e.g., lpxL, lpxM, pagP, lpxP, and/or eptA) may be substantially deleted and/or one or more enzymes (e.g., LpxL, LpxM, PagP, LpxP, and/or EptA) may be substantially inactive. The bacteria may be competent to take up extracellular DNA, may be donor bacteria, or may be members of a library. The present invention also features methods of creating and utilizing such bacteria.
摘要翻译：可行的革兰氏阴性细菌或其组分包含充当TLR4 / MD-2的激动剂的基本上不含配体例如脂质A或6-酰基脂多糖的外膜。细菌可以包含降低的阿拉伯糖-5-磷酸异构酶的活性和一种或多种抑制突变，例如在转运蛋白中，从而增加转运蛋白转运脂质IVA或膜蛋白YhjD的能力。基本上可以删除一个或多个基因（例如，lpxL，lpxM，pagP，lpxP和/或eptA），和/或一个或多个酶（例如LpxL，LpxM，PagP，LpxP和/或EptA）不活跃细菌可能有能力摄取细胞外DNA，可能是供体细菌，也可能是文库的成员。本发明还涉及产生和利用这种细菌的方法。

8. 发明授权

US09156917B2 CH2 domain template molecules derived from rational grafting of donor loops onto CH2 scaffolds 有权
标题翻译：衍生自将供体环合成接枝到CH2支架上的CH2结构域模板分子
公开(公告)号：US09156917B2
公开(公告)日：2015-10-13
申请号：US13370831
申请日：2012-02-10
申请人： David Bramhill , Gopalan Raghunathan
发明人： David Bramhill , Gopalan Raghunathan
IPC分类号： C07K16/46 , C07K16/00 , C07K16/42 , C40B30/04 , G01N33/68
CPC分类号： C07K16/461 , C07K16/005 , C07K16/42 , C07K2317/524 , C07K2317/92 , C07K2317/94 , C40B30/04 , G01N33/6854
摘要： Novel CH2 domain template molecules wherein donor loops from a database of domains are transferred to a CH2 domain scaffold. At least one or up to three loops from a donor are transferred to the CH2 domain. The donor loops may be chosen based on length, e.g., the donor loop may have a length that is similar to that of a structural loop in the CH2 domain scaffold.
摘要翻译：其中将来自结构域数据库的供体环转移到CH2结构域支架的新型CH2结构域模板分子。来自供体的至少一个或多达三个环被转移到CH2结构域。可以基于长度来选择供体环，例如，供体环可以具有与CH2结构域支架中的结构环的长度相似的长度。

9. 发明授权

US09068186B2 Viable gram negative bacteria lacking outer membrane agonists of TLR4/MD-2 有权
标题翻译：缺乏TLR4 / MD-2外膜激动剂的革兰氏阴性细菌
公开(公告)号：US09068186B2
公开(公告)日：2015-06-30
申请号：US13046562
申请日：2011-03-11
申请人： David Bramhill , Uwe Mamat
发明人： David Bramhill , Uwe Mamat
IPC分类号： C12N1/20 , C12N15/70 , C12N15/10 , C12N15/78 , C12P19/34 , C12P21/02 , C40B40/02
CPC分类号： C12N15/70 , C12N15/1037 , C12N15/78 , C12P19/34 , C12P21/02 , C40B40/02
摘要： Viable Gram-negative bacteria or components thereof comprising outer membranes that substantially lack a ligand, such as Lipid A or 6-acyl lipidpolysaccharide, that acts as an agonist of TLR4/MD2. The bacteria may comprise reduced activity of arabinose-5-phosphate isomerases and one or more suppressor mutations, for example in a transporter thereby increasing the transporters capacity to transport Lipid IVA or in membrane protein YhjD. One or more genes (e.g., IpxL, IpxM, pagP, IpxP, and/or eptA) may be substantially deleted and/or one or more enzymes (e.g., LpxL, LpxM, PagP, LpxP, and/or EptA) may be substantially inactive. The bacteria may be competent to take up extracellular DNA, may be donor bacteria, or may be members of a library. The present invention also features methods of creating and utilizing such bacteria.
摘要翻译：可行的革兰氏阴性细菌或其组分包含充当TLR4 / MD2的激动剂的基本上不含配体例如脂质A或6-酰基脂多聚糖的外膜。细菌可以包含降低的阿拉伯糖-5-磷酸异构酶的活性和一种或多种抑制突变，例如在转运蛋白中，由此增加运输脂质IVA或膜蛋白YhjD的转运蛋白能力。基本上可以删除一个或多个基因（例如，IpxL，IpxM，pagP，IpxP和/或eptA）和/或一个或多个酶（例如，LpxL，LpxM，PagP，LpxP和/或EptA）不活跃细菌可能有能力摄取细胞外DNA，可能是供体细菌，也可能是文库的成员。本发明还涉及产生和利用这种细菌的方法。

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