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    Non-natural MIC proteins
    1.
    发明授权
    Non-natural MIC proteins 有权
    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

    Applicant: David W. Martin, Jr. ,  Steven R. Williams

    Inventor： David W. Martin, Jr. ,  Steven R. Williams

    IPC: A61K38/16 ,  C07K14/00 ,  C07K16/00 ,  A01N63/00

    CPC classification number: C07K14/70539 ,  A61K38/1774 ,  C07K2319/33 ,  Y02A50/389 ,  Y02A50/393

    Abstract: 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.

    Abstract translation: 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 。

    Method and composition for identifying substances which activate transcription of the LDL receptor gene
    4.
    发明授权
    Method and composition for identifying substances which activate transcription of the LDL receptor gene 失效
    识别激活LDL受体基因转录的物质的方法和组合物

    公开(公告)号：US5378603A

    公开(公告)日：1995-01-03

    申请号：US33081

    申请日：1987-03-30

    Applicant: Michael S. Brown ,  Joseph L. Goldstein ,  David W. Russell ,  Thomas C. Sudhof ,  David W. Martin, Jr.

    Inventor： Michael S. Brown ,  Joseph L. Goldstein ,  David W. Russell ,  Thomas C. Sudhof ,  David W. Martin, Jr.

    IPC: C07K14/525 ,  C07K14/61 ,  C12N9/72 ,  C12N15/85 ,  C12Q1/68 ,  C12N15/09

    CPC classification number: C12N9/6459 ,  C07K14/525 ,  C07K14/61 ,  C12N15/85 ,  C12Q1/6897 ,  C12Y304/21069 ,  Y10S436/817

    Abstract: Disclosed are discreet functionally translocatable DNA segments, termed Sterol Regulatory Elements (SRE's) , which are fused to heterologous structural genes to provide sterol regulatory capability to the thus formed hybrid gene. The hybrid genes respond to sterols by decreasing the production of messenger RNA. The SRE segments contain as their primary functional nucleotide sequence, a 16 bp sequence referred to as direct repeats 2, isolated from the 5' regions of the human LDL receptor gene. DNA segments which include this 16 nucleotide long sequence similarly confer sterol regulatory capability to previously known promoters such as the HSV TK promoter. Also disclosed are discreet sequences which confer positive transcription promotion to heterologous structural genes and promoters without conferring sterol responsivity. Methods are disclosed for employing these genetic control elements in a myriad of embodiments which provide for a fine-tune control of heterologous genes. Methods are also disclosed for employing the SRE in a screening assay for drugs capable of stimulating the cell to synthesize LDL receptors.

    Abstract translation: 公开了细小的功能可转位DNA片段，称为Sterol调节元件（SRE's），其与异源结构基因融合以向由此形成的杂合基因提供固醇调节能力。 杂交基因通过降低信使RNA的产生来响应甾醇。 SRE片段含有作为其主要功能核苷酸序列，从人类LDL受体基因的5'区域分离的称为直接重复序列2的16bp序列。 包括该16个核苷酸长序列的DNA片段类似地赋予先前已知的启动子如HSV TK启动子的甾醇调节能力。 还公开了对异源结构基因和启动子赋予阳性转录促进剂而不赋予固醇反应性的谨慎的序列。 公开了在无数个实施例中使用这些遗传控制元件的方法，其提供异源基因的微调控制。 还公开了在能够刺激细胞合成LDL受体的药物的筛选测定中使用SRE的方法。

    Modified bacteriocins and methods for their use
    6.
    发明授权
    Modified bacteriocins and methods for their use 有权
    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

    Applicant: David W. Martin, Jr. ,  Andrew C. Jamieson ,  Dean M. Scholl ,  Steven R. Williams

    Inventor： David W. Martin, Jr. ,  Andrew C. Jamieson ,  Dean M. Scholl ,  Steven R. Williams

    IPC: C07H21/04 ,  C12P21/04

    CPC classification number: C07K14/21 ,  C07K2319/35 ,  C07K2319/74

    Abstract: 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.

    Abstract translation: 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。

    Diffocin and methods of use thereof
    10.
    发明授权
    Diffocin and methods of use thereof 有权
    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

    Applicant: Dean M. Scholl ,  Dana M. Gebhart ,  Steven R. Williams ,  Gregory R. Govoni ,  David W. Martin, Jr.

    Inventor： Dean M. Scholl ,  Dana M. Gebhart ,  Steven R. Williams ,  Gregory R. Govoni ,  David W. Martin, Jr.

    IPC: C12N1/20 ,  C12N7/00 ,  C07H21/00 ,  C07K14/00

    CPC classification number: C07K14/33

    Abstract: 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.

    Abstract translation: 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。

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