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    RECOMBINANT BACTERIA ENGINEERED TO TREAT DISEASES AND DISORDERS ASSOCIATED WITH AMINO ACID METABOLISM AND METHODS OF USE THEREOF
    1.
    发明申请
    RECOMBINANT BACTERIA ENGINEERED TO TREAT DISEASES AND DISORDERS ASSOCIATED WITH AMINO ACID METABOLISM AND METHODS OF USE THEREOF 审中-公开
    用于治疗与氨基酸代谢有关的疾病和病症的重组细菌及其使用方法

    公开(公告)号：WO2017123676A1

    公开(公告)日：2017-07-20

    申请号：PCT/US2017/013074

    申请日：2017-01-11

    申请人： SYNLOGIC, INC.

    发明人： FALB, Dean ,  KOTULA, Jonathan, W. ,  ISABELLA, Vincent, M. ,  MILLER, Paul, F. ,  TUCKER, Alex ,  MILLET, Yves ,  FISHER, Adam B.

    IPC分类号： C12N9/78 ,  A61K35/74 ,  A61K35/741 ,  C07K14/195 ,  C12N1/00 ,  C12N15/52 ,  C12N15/74

    CPC分类号： C12N9/78 ,  A61K35/74 ,  A61K35/741 ,  C07K14/195 ,  C12N1/20 ,  C12N15/52 ,  C12N15/70 ,  C12N15/74

    摘要： The present disclosure provides recombinant bacterial cells that have been engineered with genetic circuitry which allow the recombinant bacterial cells to sense a patient's internal environment and respond by turning an engineered metabolic pathway on or off. When turned on, the recombinant bacterial cells complete all of the steps in a metabolic pathway to achieve a therapeutic effect in a host subject. These recombinant bacterial cells are designed to drive therapeutic effects throughout the body of a host from a point of origin of the microbiome. Specifically, the present disclosure provides recombinant bacterial cells that comprise an amino acid catabolism enzyme for the treatment of diseases and disorders associated with amino acid metabolism, including cancer, in a subject. The disclosure further provides pharmaceutical compositions and methods of treating disorders associated with amino acid metabolism, such as cancer.

    摘要翻译： 本公开内容提供了已经用遗传电路工程化的重组细菌细胞，所述遗传电路允许重组细菌细胞感测患者的内部环境并通过打开或关闭工程化的代谢途径来响应。 打开时，重组细菌细胞完成代谢途径中的所有步骤以在宿主受试者中实现治疗效果。 这些重组细菌细胞被设计为从微生物组的起源点驱动整个宿主体内的治疗效果。 具体而言，本公开提供了包含氨基酸分解代谢酶的重组细菌细胞，其用于治疗受试者中与氨基酸代谢相关的疾病和病症，包括癌症。 本公开进一步提供了治疗与氨基酸代谢有关的疾病例如癌症的药物组合物和方法。

    BACTERIA ENGINEERED TO TREAT NONALCOHOLIC STEATOHEPATITIS (NASH)
    2.
    发明申请
    BACTERIA ENGINEERED TO TREAT NONALCOHOLIC STEATOHEPATITIS (NASH) 审中-公开
    细菌工程治疗非酒精性磷酸血症（NASH）

    公开(公告)号：WO2017139708A1

    公开(公告)日：2017-08-17

    申请号：PCT/US2017/017563

    申请日：2017-02-10

    申请人： SYNLOGIC, INC.

    发明人： MILLER, Paul, F. ,  ISABELLA, Vincent, M. ,  FALB, Dean ,  KOTULA, Jonathan, W. ,  MACHINANI, Suman ,  MILLET, Yves ,  FISHER, Adam, B. ,  LI, Ning ,  TUCKER, Alex

    IPC分类号： C12N1/00 ,  A61K35/741

    CPC分类号： A61K35/741 ,  C07K14/195 ,  C07K14/605 ,  C07K2319/01 ,  C12N15/52 ,  C12P7/52

    摘要： The present disclosure provides engineered bacterial cells comprising a heterologous gene encoding a propionate biosynthesis gene cassette; a butyrate biosynthesis gene cassette; GLP-1; a propionate biosynthesis gene cassette and a butyrate biosynthesis gene cassette; a propionate biosynthesis gene cassette and GLP-1; a butyrate biosynthesis gene cassette and GLP-1; or a propionate biosynthesis gene cassette, a butyrate biosynthesis gene cassette, and GLP- 1. In another aspect, the engineered bacterial cells further comprise a bacterial kill switch. The disclosure further provides pharmaceutical compositions comprising the engineered bacteria, and methods for treating liver disease, such as nonalcoholic steatohepatitis (NASH), using the pharmaceutical compositions of the disclosure.

    摘要翻译： 本公开提供了包含编码丙酸生物合成基因盒的异源基因的工程细菌细胞; 丁酸生物合成基因盒; GLP-1; 丙酸生物合成基因盒和丁酸生物合成基因盒; 丙酸生物合成基因盒和GLP-1; 丁酸生物合成基因盒和GLP-1; 或丙酸生物合成基因盒，丁酸生物合成基因盒和GLP-1。另一方面，工程化细菌细胞还包含细菌杀伤开关。 本公开进一步提供了包含工程化细菌的药物组合物，以及使用本公开的药物组合物治疗肝病如非酒精性脂肪性肝炎（NASH）的方法。

    BACTERIA ENGINEERED TO TREAT NONALCOHOLIC STEATOHEPATITIS (NASH)
    4.
    发明申请
    BACTERIA ENGINEERED TO TREAT NONALCOHOLIC STEATOHEPATITIS (NASH) 审中-公开
    细菌工程治疗非酒精性磷酸血症（NASH）

    公开(公告)号：WO2017139708A8

    公开(公告)日：2017-08-17

    申请号：PCT/US2017/017563

    申请日：2017-02-10

    申请人： SYNLOGIC, INC.

    发明人： MILLER, Paul, F. ,  ISABELLA, Vincent, M. ,  FALB, Dean ,  KOTULA, Jonathan, W. ,  MACHINANI, Suman ,  MILLET, Yves ,  FISHER, Adam, B. ,  LI, Ning ,  TUCKER, Alex

    IPC分类号： C12N1/00 ,  A61K35/741

    摘要： The present disclosure provides engineered bacterial cells comprising a heterologous gene encoding a propionate biosynthesis gene cassette; a butyrate biosynthesis gene cassette; GLP-1; a propionate biosynthesis gene cassette and a butyrate biosynthesis gene cassette; a propionate biosynthesis gene cassette and GLP-1; a butyrate biosynthesis gene cassette and GLP-1; or a propionate biosynthesis gene cassette, a butyrate biosynthesis gene cassette, and GLP-1. In another aspect, the engineered bacterial cells further comprise a bacterial kill switch. The disclosure further provides pharmaceutical compositions comprising the engineered bacteria, and methods for treating liver disease, such as nonalcoholic steatohepatitis (NASH), using the pharmaceutical compositions of the disclosure.

    摘要翻译： 本公开提供了包含编码丙酸生物合成基因盒的异源基因的工程细菌细胞; 丁酸生物合成基因盒; GLP-1; 丙酸生物合成基因盒和丁酸生物合成基因盒; 丙酸生物合成基因盒和GLP-1; 丁酸生物合成基因盒和GLP-1; 或丙酸生物合成基因盒，丁酸生物合成基因盒和GLP-1。 另一方面，工程菌细胞还包含细菌杀伤开关。 本公开进一步提供了包含工程化细菌的药物组合物，以及使用本公开的药物组合物治疗肝病如非酒精性脂肪性肝炎（NASH）的方法。

    BACTERIA ENGINEERED TO TREAT DISORDERS ASSOCIATED WITH BILE SALTS
    7.
    发明申请
    BACTERIA ENGINEERED TO TREAT DISORDERS ASSOCIATED WITH BILE SALTS 审中-公开

    公开(公告)号：WO2017123592A8

    公开(公告)日：2017-07-20

    申请号：PCT/US2017/012946

    申请日：2017-01-11

    申请人： SYNLOGIC, INC.

    发明人： FALB, Dean ,  KOTULA, Jonathan, W. ,  ISABELLA, Vincent, M. ,  MILLER, Paul, F. ,  TUCKER, Alex

    IPC分类号： C12N1/21 ,  A61K35/741 ,  C12N9/80

    摘要： The present disclosure provides recombinant bacterial cells comprising a heterologous gene encoding a bile salt hydrolase enzyme and/or a 7α-dehydroxylating enzyme. In another aspect, the recombinant bacterial cells further comprise a bacterial kill switch. The disclosure further provides pharmaceutical compositions comprising the recombinant bacteria, and methods for treating disorders associated with bile salts, such as cardiovascular disease, metabolic disease, liver disease (such as cirrhosis or nonalcoholic steatohepatitis (NASH), C. difficile infection, and cancer, using the pharmaceutical compositions of the disclosure.

    BACTERIA ENGINEERED TO TREAT DISORDERS INVOLVING PROPIONATE CATABOLISM
    8.
    发明申请
    BACTERIA ENGINEERED TO TREAT DISORDERS INVOLVING PROPIONATE CATABOLISM 审中-公开
    BACTERIA工程师处理涉及推测的病例的疾病

    公开(公告)号：WO2017023818A1

    公开(公告)日：2017-02-09

    申请号：PCT/US2016/044922

    申请日：2016-07-29

    申请人： SYNLOGIC, INC.

    发明人： FALB, Dean ,  MILLER, Paul ,  TUCKER, Alex ,  KOTULA, Jonathan ,  ISABELLA, Vincent ,  MILLET, Yves

    IPC分类号： C12N1/00 ,  A61K35/74

    CPC分类号： A61K35/74 ,  Y02A50/473

    摘要： The present disclosure provides engineered bacterial cells comprising a heterologous gene encoding a propionate catabolism enzyme. In another aspect, the engineered bacterial cells further comprise at least one heterologous gene encoding a transporter of propionate or a kill switch. The disclosure further provides pharmaceutical compositions comprising the engineered bacteria, and methods for treating disorders involving the catabolism of propionate, such as Propionic Acidemia and Methylmalonic Acidemia, using the pharmaceutical compositions.

    摘要翻译： 本公开提供了包含编码丙酸分解代谢酶的异源基因的工程化细菌细胞。 在另一方面，工程细菌细胞还包含至少一种编码丙酸转运蛋白或杀死转基因的异源基因。 本公开进一步提供了包含工程细菌的药物组合物，以及使用药物组合物治疗涉及丙酸酯分解代谢的疾病如丙酸血症和甲基丙二酸血症的方法。

    BACTERIA ENGINEERED TO TREAT DISORDERS ASSOCIATED WITH BILE SALTS
    9.
    发明申请
    BACTERIA ENGINEERED TO TREAT DISORDERS ASSOCIATED WITH BILE SALTS 审中-公开
    细菌工程处理与胆汁酸相关的疾病

    公开(公告)号：WO2017123592A1

    公开(公告)日：2017-07-20

    申请号：PCT/US2017/012946

    申请日：2017-01-11

    申请人： SYNLOGIC, INC.

    发明人： FALB, Dean ,  KOTULA, Jonathan, W. ,  ISABELLA, Vincent, M. ,  MILLER, Paul, F. ,  TUCKER, Alex

    IPC分类号： C12N1/21 ,  A61K35/741 ,  C12N9/80

    CPC分类号： A61K35/741 ,  C12N9/80 ,  C12N15/70 ,  C12Y305/01024

    摘要： The present disclosure provides recombinant bacterial cells comprising a heterologous gene encoding a bile salt hydrolase enzyme and/or a 7α-dehydroxylating enzyme. In another aspect, the recombinant bacterial cells further comprise a bacterial kill switch. The disclosure further provides pharmaceutical compositions comprising the recombinant bacteria, and methods for treating disorders associated with bile salts, such as cardiovascular disease, metabolic disease, liver disease (such as cirrhosis or nonalcoholic steatohepatitis (NASH), C. difficile infection, and cancer, using the pharmaceutical compositions of the disclosure.

    摘要翻译： 本发明提供了包含编码胆汁盐水解酶和/或7α-脱羟基化酶的异源基因的重组细菌细胞。 另一方面，重组细菌细胞还包含细菌杀伤开关。 本公开内容进一步提供了包含重组细菌的药物组合物，以及用于治疗与胆汁盐有关的病症如心血管疾病，代谢疾病，肝病（如肝硬化或非酒精性脂肪性肝炎（NASH），艰难梭菌感染和癌症）的方法， 使用本公开的药物组合物。

    RECOMBINANT BACTERIA ENGINEERED FOR BIOSAFETY, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE THEREOF
    10.
    发明申请
    RECOMBINANT BACTERIA ENGINEERED FOR BIOSAFETY, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE THEREOF 审中-公开
    生物安全工程重组细菌，药物组合物及其使用方法

    公开(公告)号：WO2016210373A2

    公开(公告)日：2016-12-29

    申请号：PCT/US2016/039427

    申请日：2016-06-24

    申请人： SYNLOGIC, INC.

    发明人： KOTULA, Jonathan ,  FALB, Dean ,  MILLER, Paul ,  ISABELLA, Vincent ,  TUCKER, Alex

    IPC分类号： C12R1/19 ,  A61K35/741 ,  A61K35/744 ,  C12N1/20 ,  A23L33/135

    CPC分类号： A23L33/135 ,  A61K35/741 ,  A61K38/00 ,  C07K14/195 ,  C07K14/245 ,  C07K2319/55 ,  C12N15/70 ,  C12N15/746

    摘要： The present disclosure provides methods for treating a disease or disorder by administering a programmed recombinant bacterial cell to a subject, wherein the programmed recombinant bacterial cell expresses a heterologous gene in response to an exogenous environmental condition in the subject, and wherein the programmed recombinant bacterial cell is no longer viable after either sensing the presence or absence of the same or a different exogenous environmental signal, which ultimately leads to the expression of a toxin which kills the recombinant bacterial cell. The disclosure further comprises the programmed recombinant bacterial cells, and pharmaceutical compositions comprising the programmed recombinant bacterial cells.

    摘要翻译： 本公开提供了通过向受试者施用编程的重组细菌细胞来治疗疾病或病症的方法，其中所述编程的重组细菌细胞响应于所述受试者中的外源性环境条件表达异源基因，并且其中所述编程的重组细菌细胞 在感测到存在或不存在相同或不同的外源环境信号之后不再可行，其最终导致杀死重组细菌细胞的毒素的表达。 本公开还包括编程的重组细菌细胞和包含编程的重组细菌细胞的药物组合物。