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1. 发明授权

US07585957B2 Site specific system for generating diversity protein sequences 有权
标题翻译：用于产生多样性蛋白序列的位点特异性系统
公开(公告)号：US07585957B2
公开(公告)日：2009-09-08
申请号：US11197219
申请日：2005-08-03
申请人： Jeffery F. Miller , Sergei Doulatov , Asher Hodes , Min Xu , Mari Gingery , David W. Martin, Jr.
发明人： Jeffery F. Miller , Sergei Doulatov , Asher Hodes , Min Xu , Mari Gingery , David W. Martin, Jr.
IPC分类号： C07H21/02 , C12N5/00 , C12N1/00 , C12N15/00 , C40B40/06
CPC分类号： C12N15/1024 , C12N15/102 , C12N15/1034 , C12N15/1058
摘要： This invention relates to the diversification of nucleic acid sequences by use of a nucleic acid molecule containing a region of sequence that acts as a template for diversification. The invention thus provides nucleic acid molecules to be diversified, as well as those which act as the template region (TR) and in concert with the TR for directional, site-specific diversification. Further provided are methods of preparing and using these nucleic acid sequences.
摘要翻译：本发明涉及通过使用含有充当用于多样化的模板的序列区域的核酸分子来实现核酸序列的多样化。因此，本发明提供要多样化的核酸分子，以及用作模板区域（TR）并与TR一起用于定向，位点特异性多样化的核酸分子。还提供了制备和使用这些核酸序列的方法。

2. 发明授权

US5264357A Nucleic acids vectors and cells for the synthesis of membrane anchor fusion polypeptides 失效
标题翻译：用于合成膜锚固融合多肽的核酸载体和细胞
公开(公告)号：US5264357A
公开(公告)日：1993-11-23
申请号：US811048
申请日：1991-12-19
申请人： Ingrid W. Caras , Michael A. Davitz , Victor Nussenzweig , David W. Martin, Jr.
发明人： Ingrid W. Caras , Michael A. Davitz , Victor Nussenzweig , David W. Martin, Jr.
IPC分类号： A61K38/00 , C07K14/035 , C07K14/705 , C07K16/26 , C07K16/28 , C12N15/12 , C12N15/62 , G01N33/68 , C12N5/10
CPC分类号： G01N33/6842 , B82Y5/00 , C07K14/005 , C07K14/70596 , C07K16/26 , C07K16/2896 , C12N15/62 , C12N15/625 , G01N33/68 , A61K38/00 , C07K2319/00 , C07K2319/02 , C07K2319/035 , C07K2319/32 , C07K2319/40 , C07K2319/75 , C07K2319/912 , C12N2710/16622 , G01N2333/705
摘要： Novel fusions of a phospholipid anchor domain and a polypeptide heterologous to the anchor domain donor polypeptide are provided for industrial use. Therapeutic administration of the fusions enables the targeting of biological activity to cell membrane surfaces.
摘要翻译：提供磷脂锚定结构域和与锚定域供体多肽异源的多肽的新融合用于工业用途。融合物的治疗施用使得能够将生物活性靶向细胞膜表面。

3. 发明授权

US08673291B2 Diffocin and methods of use thereof 有权
标题翻译： Diffocin及其使用方法
公开(公告)号：US08673291B2
公开(公告)日：2014-03-18
申请号：US13117467
申请日：2011-05-27
申请人： Dean M. Scholl , Dana M. Gebhart , Steven R. Williams , Gregory R. Govoni , David W. Martin, Jr.
发明人： Dean M. Scholl , Dana M. Gebhart , Steven R. Williams , Gregory R. Govoni , David W. Martin, Jr.
IPC分类号： C12N1/20 , C12N7/00 , C07H21/00 , C07K14/00
CPC分类号： C07K14/33
摘要： This disclosure relates to the discovery and isolation of the entire cluster of genes encoding R-type high molecular weight bacteriocins that specifically kill Clostridium difficile bacteria, dangerous human pathogens. Also disclosed are methods of producing the R-type bacteriocins in innocuous producer cells that, unlike C. difficile, do not die in the presence of oxygen. Disclosed also is the specific gene of the isolated gene cluster that determines the killing spectrum of the R-type bacteriocin and the demonstration that the killing spectra of diffocins can be altered by engineering orf1374 of the diffocin genetic locus. This invention offers a potent bactericidal agent and a means to make it in order to kill selectively C. difficile bacteria in the environment of the gastrointestinal tract where they can cause great harm and even death of the infected patient or farm animal.
摘要翻译：本公开涉及发现和分离编码特异性杀伤艰难梭菌（Clostridium difficile bacteria），危险人类病原体的R型高分子量细菌素的整个基因簇。还公开了在无害生物细胞中生产R型细菌素的方法，其与艰难梭菌不同，不在氧的存在下死亡。还公开了分离的基因簇的特异性基因，其确定了R型细菌素的杀伤谱，并且证明了可以通过工程化的diffocin遗传基因座的orf1374改变diffocins的杀伤谱。本发明提供了一种有效的杀菌剂和一种使其成为在肠胃环境中选择性杀死艰难梭菌的细菌的手段，在这些细菌中它们可能会对受感染的病人或农场动物造成极大的伤害甚至死亡。

4. 发明授权

US5763224A Decay accelerating factor (DAF) and nucleic acids encoding it 失效
标题翻译：衰变加速因子（DAF）和编码它的核酸
公开(公告)号：US5763224A
公开(公告)日：1998-06-09
申请号：US358283
申请日：1994-12-19
申请人： Ingrid W. Caras , Michael A. Davitz , Victor Nussenzweig , David W. Martin, Jr.
发明人： Ingrid W. Caras , Michael A. Davitz , Victor Nussenzweig , David W. Martin, Jr.
IPC分类号： A61K9/127 , A61K38/00 , C07K14/035 , C07K14/575 , C07K14/705 , C07K16/26 , C07K16/28 , C12N15/12 , C12N15/62 , G01N33/68
CPC分类号： G01N33/68 , A61K9/1271 , B82Y5/00 , C07K14/005 , C07K14/575 , C07K14/705 , C07K14/70596 , C07K16/26 , C07K16/2896 , C12N15/62 , C12N15/625 , A61K38/00 , C07K2319/00 , C07K2319/02 , C07K2319/035 , C07K2319/32 , C07K2319/40 , C07K2319/75 , C07K2319/912 , C12N2710/16622 , G01N2333/705 , Y10S436/829 , Y10S530/829
摘要： This application relates to nucleic acids encoding decay accelerating factor (hereinafter abbreviated as DAF), as well as vectors and cells which comprise such nucleic acids. Additionally, nucleic acids which encode variants of DAF, such as insertion, deletion or substitution variants, are described. This application also relates to the preparation of DAF in recombinant cell culture. In particular, it is concerned with the large scale manufacture of DAF suitable for pharmaceutical or diagnostic use.
摘要翻译：本申请涉及编码衰变加速因子（以下简写为DAF）的核酸以及包含这种核酸的载体和细胞。另外，描述了编码DAF变体的核酸，例如插入，缺失或取代变体。本申请还涉及重组细胞培养中DAF的制备。特别是涉及适合于制药或诊断用途的DAF的大规模生产。

5. 发明授权

US08796420B2 Non-natural MIC proteins 有权
标题翻译：非天然MIC蛋白
公开(公告)号：US08796420B2
公开(公告)日：2014-08-05
申请号：US13176601
申请日：2011-07-05
申请人： David W. Martin, Jr. , Steven R. Williams
发明人： David W. Martin, Jr. , Steven R. Williams
IPC分类号： A61K38/16 , C07K16/00 , A01N63/00 , C07K19/00 , C12N5/0783
CPC分类号： C07K14/473 , A61K38/00 , C07K14/70539 , C07K2318/00 , C07K2319/33 , Y02A50/389 , Y02A50/393
摘要： This invention describes soluble, monovalent, non-natural protein molecules that can activate NK cells and certain T-cells to attack specific cellular target cells by attaching the NKG2D-binding portions of monovalent MICA or MICB protein, i.e. their α1-α2 platform domain, to the intended target cell specifically. The α1-α2 domain is contiguous with a heterologous α3 domain that has been genetically modified to bind directly or indirectly to the extracellular aspect of the target cell, thereby serving as the targeting domain. The genetic modification to create a non-natural and non-terminal targeting motif within the α3 domain can include a portion of an antibody, another protein molecule or portion thereof, a peptide, or a non-natural, modified α3 domain of a MIC protein.
摘要翻译：本发明描述了通过连接单价MICA或MICB蛋白（即它们的α1-α2平台结构域）的NKG2D结合部分可以激活NK细胞和某些T细胞以攻击特异性细胞靶细胞的可溶性，一价，非天然蛋白质分子，具体到目的细胞。 α1-α2结构域与已经被遗传修饰的异源α3结构域连续，直接或间接地结合到靶细胞的细胞外方面，从而作为靶向结构域。在α3结构域内产生非天然和非末端靶向基序的遗传修饰可以包括MIC蛋白质的一部分抗体，另一蛋白质分子或其部分，肽或非天然修饰的α3结构域。

6. 发明授权

US07732586B2 Modified bacteriocins and methods for their use 有权
标题翻译：改良的细菌素及其使用方法
公开(公告)号：US07732586B2
公开(公告)日：2010-06-08
申请号：US11748432
申请日：2007-05-14
申请人： David W. Martin, Jr. , Andrew C. Jamieson , Dean M. Scholl , Steven R. Williams
发明人： David W. Martin, Jr. , Andrew C. Jamieson , Dean M. Scholl , Steven R. Williams
IPC分类号： C07H21/04 , C12P21/04
CPC分类号： C07K14/21 , C07K2319/35 , C07K2319/74
摘要： Modified forms of naturally occurring bacteriocins, such as the R-type pyocins of Pseudomonas aeruginosa, are disclosed. The bacteriocins are modified at the ends of their tail fibers in a region responsible for binding specificity and affinity to their cognate binding partners, or receptors, such as those on the surface of bacteria. Methods for the use of the modified bacteriocins, such as to bind receptors, including virulence or fitness factors, on the surfaces of bacteria, are also described.
摘要翻译：公开了天然存在的细菌素的修饰形式，例如铜绿假单胞菌的R型py虫。细菌素在其尾纤维的末端被修饰，负责对其同源结合配偶体或受体（例如细菌表面上的那些）的结合特异性和亲和力。还描述了在细菌表面上使用修饰的细菌素，例如结合受体（包括毒力或适应因子）的方法。

7. 发明授权

US06632634B1 Decay accelerating factor (DAF) and nucleic acid encoding it 失效
标题翻译：衰变加速因子（DAF）和核酸编码
公开(公告)号：US06632634B1
公开(公告)日：2003-10-14
申请号：US09014240
申请日：1998-01-27
申请人： Ingrid W. Caras , Michael A. Davitz , Victor Nussenzweig , David W. Martin, Jr.
发明人： Ingrid W. Caras , Michael A. Davitz , Victor Nussenzweig , David W. Martin, Jr.
IPC分类号： C07H2104
CPC分类号： G01N33/68 , A61K9/1271 , A61K38/00 , B82Y5/00 , C07K14/005 , C07K14/575 , C07K14/705 , C07K14/70596 , C07K16/26 , C07K16/2896 , C07K2319/00 , C07K2319/02 , C07K2319/035 , C07K2319/32 , C07K2319/40 , C07K2319/75 , C07K2319/912 , C12N15/62 , C12N15/625 , C12N2710/16622 , G01N2333/705 , Y10S436/829 , Y10S530/829
摘要： Novel fusions of a GPI signal domain and a polypeptide heterologous to the GPI signal domain donor polypeptide are provided for industrial use. Therapeutic administration of the GPI-linked product of the fusions enables the targeting of biological activity to cell membrane surfaces.
摘要翻译：提供GPI信号结构域和与GPI信号域供体多肽异源的多肽的新型融合用于工业用途。 GPI连接的融合产物的治疗性给药可以将生物活性靶向细胞膜表面。

8. 发明授权

US5639440A Method for evaluating immunogenicity 失效
标题翻译：免疫原性评估方法
公开(公告)号：US5639440A
公开(公告)日：1997-06-17
申请号：US428932
申请日：1995-04-25
申请人： David W. Martin, Jr.
发明人： David W. Martin, Jr.
IPC分类号： A61K39/00 , C07K14/61 , C07K14/755 , C12N9/72 , C12N15/85 , G01N33/50 , A61K49/00 , C12N15/00
CPC分类号： A01K67/0278 , C07K14/61 , C07K14/755 , C12N15/8509 , C12N9/6459 , C12Y304/21069 , G01N33/5088 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2227/105 , A01K2267/03 , A01K2267/0337 , A61K39/00
摘要： Biological effects of agents for diagnostic or therapeutic use are evaluated by administration of the agents to transgenic animals which are transformed with heterologous DNA and which are immune tolerant to the expression product of the heterologous DNA. In a further embodiment, preparations that are immunogenic in the transgenic animal model are purified by reverse immunoaffinity chromatography on antibody obtained from responding transgenic animals.
摘要翻译：用于诊断或治疗用途的药剂的生物学效应通过将所述药剂施用于用异源DNA转化且对异源DNA的表达产物具有免疫耐受性的转基因动物来评估。在进一步的实施方案中，在转基因动物模型中具有免疫原性的制剂通过从响应的转基因动物获得的抗体上的反向免疫亲和层析纯化。

9. 发明授权

US5109113A Membrane anchor fusion polypeptides 失效
标题翻译：膜锚融合多肽
公开(公告)号：US5109113A
公开(公告)日：1992-04-28
申请号：US83757
申请日：1987-08-06
申请人： Ingrid W. Caras , Michael A. Davitz , Victor Nussenzweig , David W. Martin, Jr.
发明人： Ingrid W. Caras , Michael A. Davitz , Victor Nussenzweig , David W. Martin, Jr.
IPC分类号： C12N9/00 , A61K38/00 , A61K38/22 , A61K38/43 , A61K38/46 , A61K39/395 , A61P7/02 , A61P29/00 , A61P37/00 , C07K1/20 , C07K1/22 , C07K14/00 , C07K14/035 , C07K14/08 , C07K14/47 , C07K14/575 , C07K14/705 , C07K16/00 , C07K16/26 , C07K19/00 , C12N1/21 , C12N15/09 , C12N15/62 , C12P21/00 , C12P21/02 , C12R1/19 , G01N33/68
CPC分类号： G01N33/6842 , B82Y5/00 , C07K14/005 , C07K14/575 , C07K14/70596 , C07K16/26 , C12N15/62 , C12N15/625 , G01N33/68 , A61K38/00 , C07K2319/00 , C07K2319/02 , C07K2319/035 , C07K2319/32 , C07K2319/40 , C07K2319/75 , C07K2319/912 , C12N2710/16622 , G01N2333/705 , Y10S530/806 , Y10S530/807 , Y10S530/808
摘要： Novel fusions of a phospholipid anchor domain and a polypeptide heterologous to the anchor domain donor polypeptide are provided for industrial use. Therapeutic administration of the fusions enables the targeting of biological activity to cell membrane surfaces.
摘要翻译：提供磷脂锚定结构域和与锚定域供体多肽异源的多肽的新融合用于工业用途。融合物的治疗施用使得能够将生物活性靶向细胞膜表面。

10. 发明授权

US08658765B2 Non-natural MIC proteins 有权
标题翻译：非天然MIC蛋白
公开(公告)号：US08658765B2
公开(公告)日：2014-02-25
申请号：US12982827
申请日：2010-12-30
申请人： David W. Martin, Jr. , Steven R. Williams
发明人： David W. Martin, Jr. , Steven R. Williams
IPC分类号： A61K38/16 , C07K14/00 , C07K16/00 , A01N63/00
CPC分类号： C07K14/70539 , A61K38/1774 , C07K2319/33 , Y02A50/389 , Y02A50/393
摘要： This invention describes soluble, monovalent, non-natural protein molecules that can activate NK cells and certain T-cells to attack specific cellular target cells by attaching the NKG2D-binding portions of monovalent MICA or MICB protein, i.e. their α1-α2 platform domain, to the intended target cell specifically. The α1-α2 domain is contiguous with a heterologous α3 domain that has been genetically modified to bind directly or indirectly to the extracellular aspect of the target cell, thereby serving as the targeting domain. The genetic modification to create a non-natural and non-terminal targeting motif within the α3 domain can include a portion of an antibody, another protein molecule or portion thereof, a peptide, or a non-natural, modified α3 domain of a MIC protein.
摘要翻译：本发明描述了通过连接单价MICA或MICB蛋白（即它们的α1-α2平台结构域）的NKG2D结合部分可以激活NK细胞和某些T细胞以攻击特定细胞靶细胞的可溶性，一价，非天然蛋白质分子，具体到目的细胞。 α1-α2结构域与经过遗传修饰的异源α3结构域连续，直接或间接地结合靶细胞的细胞外区域，从而作为靶向结构域。在α3结构域内产生非天然和非末端靶向基序的遗传修饰可包括MIC蛋白的一部分抗体，另一蛋白质分子或其部分，肽或非天然修饰的α3结构域。

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