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    Multiple Gene Expression Including sORF Constructs and Methods with Polyproteins, Pro-Proteins and Proteolysis
    2.
    发明申请
    Multiple Gene Expression Including sORF Constructs and Methods with Polyproteins, Pro-Proteins and Proteolysis 审中-公开
    包括多聚蛋白，前蛋白和蛋白水解的sORF构建体和方法的多基因表达

    公开(公告)号：US20110034368A1

    公开(公告)日：2011-02-10

    申请号：US12822598

    申请日：2010-06-24

    申请人： Gerald R. CARSON ,  Jochen G. SALFELD ,  Dean A. REGIER ,  Jijie GU ,  Wendy GION ,  Yune Z. KUNES

    发明人： Gerald R. CARSON ,  Jochen G. SALFELD ,  Dean A. REGIER ,  Jijie GU ,  Wendy GION ,  Yune Z. KUNES

    IPC分类号： A61K38/16 ,  C12P21/06 ,  C12P21/02 ,  C12N5/10 ,  C12N1/21 ,  C12N1/15 ,  C12N1/19 ,  C12N15/63 ,  C07K14/00 ,  C07K16/00 ,  C07K16/28 ,  C07K16/24

    CPC分类号： C12N15/67 ,  C07K16/00 ,  C07K2319/50 ,  C07K2319/92 ,  C12N15/1055 ,  C12P21/02 ,  C12P21/06

    摘要： Disclosed are useful constructs and methods for the expression of proteins using primary translation products that are processed within a recombinant host cell. Constructs comprising a single open reading frame (sORF) are described for protein expression including expression of multiple polypeptides. A primary translation product (a pro-protein or a polyprotein) contains polypeptides such as inteins or hedgehog family auto-processing domains, or variants thereof, inserted in frame between multiple protein subunits of interest. The primary product can also contain cleavage sequences such as other proteolytic cleavage or protease recognition sites, or signal peptides which contain recognition sequences for signal peptidases, separating at least two of the multiple protein subunits. The sequences of the inserted auto-processing polypeptides or cleavage sites can be manipulated to enhance the efficiency of expression of the separate multiple protein subunits. Also disclosed are independent aspects of conducting efficient expression, secretion, and/or multimeric assembly of proteins such as immunoglobulins. Where the polyprotein contains immunoglobulin heavy and light chain segments or fragments capable of antigen recognition, in an embodiment a selectable stoichiometric ratio is at least two copies of a light chain segment per heavy chain segment, with the result that the production of properly folded and assembled functional antibody is made. Modified signal peptides, including such from immunoglobulin light chains, are described.

    摘要翻译： 公开了使用在重组宿主细胞内处理的主要翻译产物来表达蛋白质的有用构建体和方法。 描述了包含单个开放阅读框（sORF）的构建体用于蛋白质表达，包括多个多肽的表达。 初级翻译产物（前蛋白质或多蛋白质）含有多肽，例如内含肽或刺猬蛋白家族自身处理结构域或其变体，其插入到感兴趣的多个蛋白质亚基之间。 初级产物还可以含有切割序列，如其他蛋白水解切割或蛋白酶识别位点，或含有信号肽酶识别序列的信号肽，分离多个蛋白质亚基中的至少两个。 可以操纵插入的自动处理多肽或切割位点的序列，以提高分离的多个蛋白质亚基的表达效率。 还公开了进行蛋白质例如免疫球蛋白的有效表达，分泌和/或多聚体装配的独立方面。 当多蛋白含有免疫球蛋白重链和轻链片段或能够进行抗原识别的片段时，在一个实施方案中，可选择的化学计量比为每个重链段的轻链片段的至少两个拷贝，结果是正确折叠和组装 制备功能性抗体。 描述了包含免疫球蛋白轻链的修饰的信号肽。

    Multiple Gene Expression Including sORF Constructs and Methods with Polyproteins, Pro-Proteins and Proteolysis
    5.
    发明申请
    Multiple Gene Expression Including sORF Constructs and Methods with Polyproteins, Pro-Proteins and Proteolysis 审中-公开
    包括多聚蛋白，前蛋白和蛋白水解的sORF构建体和方法的多基因表达

    公开(公告)号：US20130243789A1

    公开(公告)日：2013-09-19

    申请号：US13739304

    申请日：2013-01-11

    申请人： Gerald R. Carson ,  Jochen G. Salfeld ,  Dean A. Regier ,  Jijie Gu ,  Wendy Gion ,  Yune Z. Kunes

    发明人： Gerald R. Carson ,  Jochen G. Salfeld ,  Dean A. Regier ,  Jijie Gu ,  Wendy Gion ,  Yune Z. Kunes

    IPC分类号： C12N15/67

    CPC分类号： C12N15/67 ,  C07K16/00 ,  C07K2319/50 ,  C07K2319/92 ,  C12N15/1055 ,  C12P21/02 ,  C12P21/06

    摘要： Disclosed are useful constructs and methods for the expression of proteins using primary translation products that are processed within a recombinant host cell. Constructs comprising a single open reading frame (sORF) are described for protein expression including expression of multiple polypeptides. A primary translation product (a pro-protein or a polyprotein) contains polypeptides such as inteins or hedgehog family auto-processing domains, or variants thereof, inserted in frame between multiple protein subunits of interest. Also disclosed are independent aspects of conducting efficient expression, secretion, and/or multimeric assembly of proteins such as immunoglobulins.

    摘要翻译： 公开了使用在重组宿主细胞内处理的主要翻译产物来表达蛋白质的有用构建体和方法。 描述了包含单个开放阅读框（sORF）的构建体用于蛋白质表达，包括多个多肽的表达。 初级翻译产物（前蛋白质或多蛋白质）含有多肽，例如内含肽或刺猬蛋白家族自身处理结构域或其变体，其插入到感兴趣的多个蛋白质亚基之间。 还公开了进行蛋白质例如免疫球蛋白的有效表达，分泌和/或多聚体装配的独立方面。

    SORF CONSTRUCTS AND MULTIPLE GENE EXPRESSION
    6.
    发明申请
    SORF CONSTRUCTS AND MULTIPLE GENE EXPRESSION 审中-公开
    SORF构造和多基因表达

    公开(公告)号：US20110150861A1

    公开(公告)日：2011-06-23

    申请号：US12914556

    申请日：2010-10-28

    申请人： Gerald R. Carson ,  Wendy R. Gion ,  Yune Z. Kunes ,  Walter F. Leise, III ,  Rachel A. Davis-Taber ,  Emma Fung

    发明人： Gerald R. Carson ,  Wendy R. Gion ,  Yune Z. Kunes ,  Walter F. Leise, III ,  Rachel A. Davis-Taber ,  Emma Fung

    IPC分类号： A61K39/395 ,  C12N15/63 ,  C12N1/00 ,  C12N1/21 ,  C12N1/11 ,  C12N5/10 ,  C12N1/19 ,  C12N1/15 ,  C12P21/00 ,  C07K16/00 ,  C07K16/24 ,  A61K38/00 ,  A61P43/00

    CPC分类号： C07K16/00 ,  C07K16/241 ,  C07K16/244 ,  C07K2317/14 ,  C07K2317/21 ,  C07K2317/76 ,  C07K2319/50 ,  C07K2319/92

    摘要： Embodiments of the invention relate to vector constructs and methods for expression of polypeptides including multimeric products such as therapeutic antibodies. Particular constructs allow for the generation of expression products from a single open reading frame (sORF). An embodiment provides an isolated or purified expression vector for generating one or more recombinant protein products comprising a single open reading frame insert; said insert comprising a signal peptide nucleic acid sequence encoding a signal peptide; a first nucleic acid sequence encoding a first polypeptide; a first intervening nucleic acid sequence encoding a first protein cleavage site, wherein said first protein cleavage site is provided by an intein segment of a Ion protease gene of Pyrococcus or a klbA gene of Pyrococcus or Methanococcus, or a modified intein segment derived therefrom; and a second nucleic acid sequence encoding a second polypeptide. Certain embodiments of constructs and methods employ an intein segment of a Ion protease gene of Pyrococcus abyssi, Pyrococcus furiosus, or Pyrococcus horikoshii OT3; or an intein segment of a klbA gene of Pyrococcus abyssi, Pyrococcus furiosus, or Methanococcus jannaschii; or other intein segment.

    摘要翻译： 本发明的实施方案涉及用于表达多肽的载体构建体和方法，包括多聚体产物，例如治疗性抗体。 特定结构允许从单个开放阅读框（sORF）生成表达产物。 一个实施方案提供了用于产生一种或多种包含单个开放阅读框插入物的重组蛋白产物的分离或纯化的表达载体; 所述插入片段包含编码信号肽的信号肽核酸序列; 编码第一多肽的第一核酸序列; 编码第一蛋白切割位点的第一插入核酸序列，其中所述第一蛋白切割位点由Pyrococcus的离子蛋白酶基因的内含肽片段或Pyrococcus或Methanococcus的klbA基因或由其衍生的修饰的内含肽片段提供; 和编码第二多肽的第二核酸序列。 构建体和方法的某些实施方案采用激烈球菌（Pyrococcus abyssi），激烈火球菌（Pyrococcus furiosus）或火球菌（Pyrococcus horikoshii）OT3的离子蛋白酶基因的内含肽片段; 或激烈球菌（Crrococcus abyssi），激烈火球菌（Pyrococcus furiosus）或季戊糖（Methanococcus jannaschii）的klbA基因的内含肽片段; 或其他内含肽片段。

    Human C3b/C4b receptor (CR1)
    7.
    发明授权
    Human C3b/C4b receptor (CR1) 失效
    人C3b / C4b受体（CR1）

    公开(公告)号：US5981481A

    公开(公告)日：1999-11-09

    申请号：US470652

    申请日：1995-06-06

    申请人： Douglas T. Fearon ,  Lloyd B. Klickstein ,  Winnie W. Wong ,  Gerald R. Carson ,  Michael F. Concino ,  Stephen H. Ip ,  Savvas C. Makrides ,  Henry C. Marsh, Jr.

    发明人： Douglas T. Fearon ,  Lloyd B. Klickstein ,  Winnie W. Wong ,  Gerald R. Carson ,  Michael F. Concino ,  Stephen H. Ip ,  Savvas C. Makrides ,  Henry C. Marsh, Jr.

    IPC分类号： A61K38/00 ,  C07K14/705 ,  A61K38/18 ,  C07K14/46 ,  C12P21/00

    CPC分类号： C07K14/70596 ,  A61K38/00

    摘要： The present invention relates to the C3b/C4b receptor (CR1) gene and its encoded protein. The invention further provides for the expression of the CR1 protein and fragments thereof. The genes and proteins of the invention have uses in diagnosis and therapy of disorders involving complement activity, and various immune system or inflammatory disorders. In specific embodiments of the present invention detailed in the examples sections infra, the cloning, nucleotide sequence, and deduced amino acid sequence of a full-length CR1 cDNA and fragments thereof are described. The expression of the CR1 protein and fragments thereof is also described. Also described is the expression of a secreted CR1 molecule lacking a transmembrane region. The secreted CR1 molecule is shown to be useful in reducing damage caused by inflammation and in reducing myocardial infarct size and preventing reperfusion injury.

    摘要翻译： 本发明涉及C3b / C4b受体（CR1）基因及其编码蛋白。 本发明进一步提供CR1蛋白及其片段的表达。 本发明的基因和蛋白质在诊断和治疗涉及补体活性的疾病以及各种免疫系统或炎性疾病中具有应用。 在下文实施例部分详述的本发明的具体实施方案中，描述了全长CR1 cDNA及其片段的克隆，核苷酸序列和推导的氨基酸序列。 还描述了CR1蛋白及其片段的表达。 还描述了缺乏跨膜区的分泌型CR1分子的表达。 分泌的CR1分子显示可用于减少由炎症引起的损伤和降低心肌梗死面积并防止再灌注损伤。