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1. 发明授权

US08093036B2 Methods for producing hyaluronan in a recombinant host cell 有权
公开(公告)号：US08093036B2
公开(公告)日：2012-01-10
申请号：US12891548
申请日：2010-09-27
申请人： Alan Sloma , Leslie Naggiar, legal representative , Regine Behr , William Widner , Maria Tang , David Sternberg , Linda Sternberg, legal representative , Stephen Brown
发明人： Alan Sloma , Regine Behr , William Widner , Maria Tang , David Sternberg , Stephen Brown
IPC分类号： C12N1/20 , C12N15/74 , C12N15/00 , C12P21/06 , C12P19/04 , C12P19/36 , C12P1/00 , C12N9/00 , C12N9/24 , C12N9/88 , C07H21/04
CPC分类号： C12P19/26 , C12N9/1051 , C12N15/52
摘要： The present invention relates to methods for producing a hyaluronic acid, comprising: (a) cultivating a Bacillus host cell under conditions suitable for production of the hyaluronic acid, wherein the Bacillus host cell comprises a nucleic acid construct comprising a hyaluronan synthase encoding sequence operably linked to a promoter sequence foreign to the hyaluronan synthase encoding sequence; and (b) recovering the hyaluronic acid from the cultivation medium. The present invention also relates to an isolated nucleic acid sequence encoding a hyaluronan synthase operon comprising a hyaluronan synthase gene and a UDP-glucose 6-dehydrogenase gene, and optionally one or more genes selected from the group consisting of a UDP-glucose pyrophosphorylase gene, UDP-N-acetylglucosamine pyrophosphorylase gene, and glucose-6-phosphate isomerase gene. The present invention also relates to isolated nucleic acid sequences encoding a UDP-glucose 6-dehydrogenase, UDP-glucose pyrophosphorylase, and UDP-N-acetylglucosamine pyrophosphorylase.

2. 发明授权

US08137951B2 Methods for producing hyaluronan in a recombinant host cell 有权
标题翻译：在重组宿主细胞中产生透明质酸的方法
公开(公告)号：US08137951B2
公开(公告)日：2012-03-20
申请号：US13084230
申请日：2011-04-11
申请人： Alan Sloma , Leslie Naggiar, legal representative , Regine Behr , William Widner , Maria Tang , David Sternberg , Linda Sternberg, legal representative , Stephen Brown
发明人： Alan Sloma , Regine Behr , William Widner , Maria Tang , David Sternberg , Stephen Brown
IPC分类号： C12N1/20 , C12N15/74 , C12N15/00 , C12P21/00 , C12P9/26 , C12P1/00 , C12N9/00 , C12N9/24 , C12N9/88 , C07H21/04
CPC分类号： C12P19/26 , C12N9/1051 , C12N15/52
摘要： The present invention relates to methods for producing a hyaluronic acid, comprising: (a) cultivating a Bacillus host cell under conditions suitable for production of the hyaluronic acid, wherein the Bacillus host cell comprises a nucleic acid construct comprising a hyaluronan synthase encoding sequence operably linked to a promoter sequence foreign to the hyaluronan synthase encoding sequence; and (b) recovering the hyaluronic acid from the cultivation medium. The present invention also relates to an isolated nucleic acid sequence encoding a hyaluronan synthase operon comprising a hyaluronan synthase gene and a UDP-glucose 6-dehydrogenase gene, and optionally one or more genes selected from the group consisting of a UDP-glucose pyrophosphorylase gene, UDP-N-acetylglucosamine pyrophosphorylase gene, and glucose-6-phosphate isomerase gene. The present invention also relates to isolated nucleic acid sequences encoding a UDP-glucose 6-dehydrogenase, UDP-glucose pyrophosphorylase, and UDP-N-acetylglucosamine pyrophosphorylase.
摘要翻译：本发明涉及透明质酸的制备方法，其包括：（a）在适于产生透明质酸的条件下培养芽孢杆菌属宿主细胞，其中所述芽孢杆菌宿主细胞包含可操作地连接的透明质酸合酶编码序列的核酸构建体涉及透明质酸合酶编码序列外源的启动子序列; 和（b）从培养基中回收透明质酸。本发明还涉及编码包含透明质酸合酶基因和UDP-葡萄糖-6-脱氢酶基因的透明质酸合酶操纵子的分离的核酸序列，以及任选地一种或多种选自UDP-葡萄糖焦磷酸化酶基因， UDP-N-乙酰葡糖胺焦磷酸化酶基因和葡萄糖-6-磷酸异构酶基因。本发明还涉及编码UDP-葡萄糖-6-脱氢酶，UDP-葡萄糖焦磷酸化酶和UDP-N-乙酰葡糖胺焦磷酸化酶的分离的核酸序列。

3. 发明申请

US20110014662A1 Methods for producing hyaluronan in a recombinant host cell 有权
标题翻译：在重组宿主细胞中产生透明质酸的方法
公开(公告)号：US20110014662A1
公开(公告)日：2011-01-20
申请号：US12891548
申请日：2010-09-27
申请人： Alan Sloma , Leslie Naggiar , Regine Behr , William Widner , Maria Tang , David Sternberg , Linda Sternberg , Stephen Brown
发明人： Alan Sloma , Leslie Naggiar , Regine Behr , William Widner , Maria Tang , David Sternberg , Linda Sternberg , Stephen Brown
IPC分类号： C12P19/04
CPC分类号： C12P19/26 , C12N9/1051 , C12N15/52
摘要： The present invention relates to methods for producing a hyaluronic acid, comprising: (a) cultivating a Bacillus host cell under conditions suitable for production of the hyaluronic acid, wherein the Bacillus host cell comprises a nucleic acid construct comprising a hyaluronan synthase encoding sequence operably linked to a promoter sequence foreign to the hyaluronan synthase encoding sequence; and (b) recovering the hyaluronic acid from the cultivation medium. The present invention also relates to an isolated nucleic acid sequence encoding a hyaluronan synthase operon comprising a hyaluronan synthase gene and a UDP-glucose 6-dehydrogenase gene, and optionally one or more genes selected from the group consisting of a UDP-glucose pyrophosphorylase gene, UDP-N-acetylglucosamine pyrophosphorylase gene, and glucose-6-phosphate isomerase gene. The present invention also relates to isolated nucleic acid sequences encoding a UDP-glucose 6-dehydrogenase, UDP-glucose pyrophosphorylase, and UDP-N-acetylglucosamine pyrophosphorylase
摘要翻译：本发明涉及透明质酸的制备方法，其包括：（a）在适于产生透明质酸的条件下培养芽孢杆菌属宿主细胞，其中所述芽孢杆菌宿主细胞包含可操作地连接的透明质酸合酶编码序列的核酸构建体涉及透明质酸合酶编码序列外源的启动子序列; 和（b）从培养基中回收透明质酸。本发明还涉及编码包含透明质酸合酶基因和UDP-葡萄糖-6-脱氢酶基因的透明质酸合酶操纵子的分离的核酸序列，以及任选的一种或多种选自UDP-葡萄糖焦磷酸化酶基因， UDP-N-乙酰葡糖胺焦磷酸化酶基因和葡萄糖-6-磷酸异构酶基因。本发明还涉及编码UDP-葡萄糖-6-脱氢酶，UDP-葡萄糖焦磷酸化酶和UDP-N-乙酰葡糖胺焦磷酸化酶的分离的核酸序列

4. 发明授权

US07811806B2 Methods for producing hyaluronan in a recombinant host cell 有权
标题翻译：在重组宿主细胞中产生透明质酸的方法
公开(公告)号：US07811806B2
公开(公告)日：2010-10-12
申请号：US10326185
申请日：2002-12-20
申请人： Alan Sloma , Regine Behr , William Widner , Maria Tang , David Sternberg , Stephen Brown
发明人： Alan Sloma , Regine Behr , William Widner , Maria Tang , David Sternberg , Stephen Brown
IPC分类号： C12N1/20 , C12N15/74 , C12N15/00 , C12P21/06 , C12P19/04 , C12P19/26
CPC分类号： C12P19/26 , C12N9/1051 , C12N15/52
摘要： The present invention relates to methods for producing a hyaluronic acid, comprising: (a) cultivating a Bacillus host cell under conditions suitable for production of the hyaluronic acid, wherein the Bacillus host cell comprises a nucleic acid construct comprising a hyaluronan synthase encoding sequence operably linked to a promoter sequence foreign to the hyaluronan synthase encoding sequence; and (b) recovering the hyaluronic acid from the cultivation medium. The present invention also relates to an isolated nucleic acid sequence encoding a hyaluronan synthase operon comprising a hyaluronan synthase gene and a UDP-glucose 6-dehydrogenase gene, and optionally one or more genes selected from the group consisting of a UDP-glucose pyrophosphorylase gene, UDP-N-acetylglucosamine pyrophosphorylase gene, and glucose-6-phosphate isomerase gene. The present invention also relates to isolated nucleic acid sequences encoding a UDP-glucose 6-dehydrogenase, UDP-glucose pyrophosphorylase, and UDP-N-acetylglucosamine pyrophosphorylase.
摘要翻译：本发明涉及透明质酸的制备方法，其包括：（a）在适于产生透明质酸的条件下培养芽孢杆菌属宿主细胞，其中所述芽孢杆菌宿主细胞包含可操作地连接的透明质酸合酶编码序列的核酸构建体涉及透明质酸合酶编码序列外源的启动子序列; 和（b）从培养基中回收透明质酸。本发明还涉及编码包含透明质酸合酶基因和UDP-葡萄糖-6-脱氢酶基因的透明质酸合酶操纵子的分离的核酸序列，以及任选地一种或多种选自UDP-葡萄糖焦磷酸化酶基因， UDP-N-乙酰葡糖胺焦磷酸化酶基因和葡萄糖-6-磷酸异构酶基因。本发明还涉及编码UDP-葡萄糖-6-脱氢酶，UDP-葡萄糖焦磷酸化酶和UDP-N-乙酰葡糖胺焦磷酸化酶的分离的核酸序列。

5. 发明申请

US20110189737A1 Methods for producing hyaluronan in a recombinant host cell 有权
公开(公告)号：US20110189737A1
公开(公告)日：2011-08-04
申请号：US13084230
申请日：2011-04-11
申请人： Alan Sloma , Regine Behr , William Widner , Maria Tang , David Sternberg , Stephen Brown , Leslie Naggiar , Linda Sternberg
发明人： Alan Sloma , Regine Behr , William Widner , Maria Tang , David Sternberg , Stephen Brown , Leslie Naggiar , Linda Sternberg
IPC分类号： C12P19/04
CPC分类号： C12P19/26 , C12N9/1051 , C12N15/52
摘要： The present invention relates to methods for producing a hyaluronic acid, comprising: (a) cultivating a Bacillus host cell under conditions suitable for production of the hyaluronic acid, wherein the Bacillus host cell comprises a nucleic acid construct comprising a hyaluronan synthase encoding sequence operably linked to a promoter sequence foreign to the hyaluronan synthase encoding sequence; and (b) recovering the hyaluronic acid from the cultivation medium. The present invention also relates to an isolated nucleic acid sequence encoding a hyaluronan synthase operon comprising a hyaluronan synthase gene and a UDP-glucose 6-dehydrogenase gene, and optionally one or more genes selected from the group consisting of a UDP-glucose pyrophosphorylase gene, UDP-N-acetylglucosamine pyrophosphorylase gene, and glucose-6-phosphate isomerase gene. The present invention also relates to isolated nucleic acid sequences encoding a UDP-glucose 6-dehydrogenase, UDP-glucose pyrophosphorylase, and UDP-N-acetylglucosamine pyrophosphorylase

6. 发明申请

US20120149067A1 Methods for producing hyaluronan in a recombinant host cell 有权
标题翻译：在重组宿主细胞中产生透明质酸的方法
公开(公告)号：US20120149067A1
公开(公告)日：2012-06-14
申请号：US13401663
申请日：2012-02-21
申请人： Alan Sloma , Leslie Naggiar , Regine Behr , William Widner , Maria Tang , David Sternberg , Linda Sternberg , Stephen Brown
发明人： Alan Sloma , Leslie Naggiar , Regine Behr , William Widner , Maria Tang , David Sternberg , Linda Sternberg , Stephen Brown
IPC分类号： C12P19/28
CPC分类号： C12P19/26 , C12N9/1051 , C12N15/52
摘要： The present invention relates to methods for producing a hyaluronic acid, comprising: (a) cultivating a Bacillus host cell under conditions suitable for production of the hyaluronic acid, wherein the Bacillus host cell comprises a nucleic acid construct comprising a hyaluronan synthase encoding sequence operably linked to a promoter sequence foreign to the hyaluronan synthase encoding sequence; and (b) recovering the hyaluronic acid from the cultivation medium. The present invention also relates to an isolated nucleic acid sequence encoding a hyaluronan synthase operon comprising a hyaluronan synthase gene and a UDP-glucose 6-dehydrogenase gene, and optionally one or more genes selected from the group consisting of a UDP-glucose pyrophosphorylase gene, UDP-N-acetylglucosamine pyrophosphorylase gene, and glucose-6-phosphate isomerase gene. The present invention also relates to isolated nucleic acid sequences encoding a UDP-glucose 6-dehydrogenase, UDP-glucose pyrophosphorylase, and UDP-N-acetylglucosamine pyrophosphorylase
摘要翻译：本发明涉及透明质酸的制备方法，其包括：（a）在适于产生透明质酸的条件下培养芽孢杆菌属宿主细胞，其中所述芽孢杆菌宿主细胞包含可操作地连接的透明质酸合酶编码序列的核酸构建体涉及透明质酸合酶编码序列外源的启动子序列; 和（b）从培养基中回收透明质酸。本发明还涉及编码包含透明质酸合酶基因和UDP-葡萄糖-6-脱氢酶基因的透明质酸合酶操纵子的分离的核酸序列，以及任选地一种或多种选自UDP-葡萄糖焦磷酸化酶基因， UDP-N-乙酰葡糖胺焦磷酸化酶基因和葡萄糖-6-磷酸异构酶基因。本发明还涉及编码UDP-葡萄糖-6-脱氢酶，UDP-葡萄糖焦磷酸化酶和UDP-N-乙酰葡糖胺焦磷酸化酶的分离的核酸序列

7. 发明授权

US08574886B2 Methods for producing hyaluronan in a recombinant host cell 有权
标题翻译：在重组宿主细胞中产生透明质酸的方法
公开(公告)号：US08574886B2
公开(公告)日：2013-11-05
申请号：US13401663
申请日：2012-02-21
申请人： Regine Behr , William Widner , Maria Tang , Stephen Brown , Leslie Naggiar , Linda Sternberg
发明人： Alan Sloma , Regine Behr , William Widner , Maria Tang , David Sternberg , Stephen Brown
IPC分类号： C12N1/20 , C12N15/74 , C12N15/00 , C12P19/04 , C12P19/26 , C12P19/28 , C12P1/00 , C12P21/06 , C07H21/04
CPC分类号： C12P19/26 , C12N9/1051 , C12N15/52
摘要： The present invention relates to methods for producing a hyaluronic acid, comprising: (a) cultivating a Bacillus host cell under conditions suitable for production of the hyaluronic acid, wherein the Bacillus host cell comprises a nucleic acid construct comprising a hyaluronan synthase encoding sequence operably linked to a promoter sequence foreign to the hyaluronan synthase encoding sequence; and (b) recovering the hyaluronic acid from the cultivation medium. The present invention also relates to an isolated nucleic acid sequence encoding a hyaluronan synthase operon comprising a hyaluronan synthase gene and a UDP-glucose 6-dehydrogenase gene, and optionally one or more genes selected from the group consisting of a UDP-glucose pyrophosphorylase gene, UDP-N-acetylglucosamine pyrophosphorylase gene, and glucose-6-phosphate isomerase gene. The present invention also relates to isolated nucleic acid sequences encoding a UDP-glucose 6-dehydrogenase, UDP-glucose pyrophosphorylase, and UDP-N-acetylglucosamine pyrophosphorylase.
摘要翻译：本发明涉及透明质酸的制备方法，其包括：（a）在适于产生透明质酸的条件下培养芽孢杆菌属宿主细胞，其中所述芽孢杆菌宿主细胞包含可操作地连接的透明质酸合酶编码序列的核酸构建体涉及透明质酸合酶编码序列外源的启动子序列; 和（b）从培养基中回收透明质酸。本发明还涉及编码包含透明质酸合酶基因和UDP-葡萄糖-6-脱氢酶基因的透明质酸合酶操纵子的分离的核酸序列，以及任选地一种或多种选自UDP-葡萄糖焦磷酸化酶基因， UDP-N-乙酰葡糖胺焦磷酸化酶基因和葡萄糖-6-磷酸异构酶基因。本发明还涉及编码UDP-葡萄糖-6-脱氢酶，UDP-葡萄糖焦磷酸化酶和UDP-N-乙酰葡糖胺焦磷酸化酶的分离的核酸序列。

8. 发明授权

US5958728A Methods for producing polypeptides in mutants of bacillus cells 失效
标题翻译：在芽孢杆菌细胞突变体中产生多肽的方法
公开(公告)号：US5958728A
公开(公告)日：1999-09-28
申请号：US972661
申请日：1997-11-18
申请人： Alan Sloma , David Sternberg , Lee F. Adams , Stephen Brown
发明人： Alan Sloma , David Sternberg , Lee F. Adams , Stephen Brown
IPC分类号： C12N1/21 , C12N15/75 , C12P21/00
CPC分类号： C12N15/75
摘要： The present invention relates to methods of producing a polypeptide, comprising: (a) cultivating a mutant of a Bacillus cell, wherein the mutant (i) comprises a first nucleic acid sequence encoding the polypeptide and a second nucleic acid sequence comprising a modification of at least one of the genes responsible for the biosynthesis or secretion of a surfactin or isoform thereof under conditions conducive for the production of the polypeptide and (ii) the mutant produces less of the surfactin or isoform thereof than the Bacillus cell when cultured under the same conditions; and (b) isolating the polypeptide from the cultivation medium. The present invention also relates to mutants of Bacillus cells and methods for producing the mutants.
摘要翻译：本发明涉及产生多肽的方法，包括：（a）培养芽孢杆菌细胞的突变体，其中所述突变体（i）包含编码所述多肽的第一核酸序列和第二核酸序列，所述第二核酸序列包含在有利于产生多肽的条件下，负责生物合成或分泌表面活化素或其同种型的基因中的至少一个和（ii）当在相同条件下培养时，突变体产生比芽孢杆菌细胞更少的表面活性素或同种型 ; 和（b）从培养基中分离多肽。本发明还涉及芽孢杆菌细胞的突变体和产生突变体的方法。

9. 发明授权

US08870883B2 Method for less invasive knee resection 有权
标题翻译：低侵入性膝关节切除术的方法
公开(公告)号：US08870883B2
公开(公告)日：2014-10-28
申请号：US13016774
申请日：2011-01-28
申请人： Robert Metzger , Stephen Brown , Garrett A. Sheffer
发明人： Robert Metzger , Stephen Brown , Garrett A. Sheffer
IPC分类号： A61B17/56 , A61B17/15 , A61B17/14 , A61B17/02
CPC分类号： A61B17/155 , A61B17/02 , A61B17/14 , A61B17/142 , A61B17/157
摘要： Various method and apparatuses may be used to perform a procedure, such as a resection of a portion of the anatomy for preparation of the implants of a prosthetic. Various resecting member, including saw blades having selected geometries and shapes, can be used to assist in the resection of an anatomy to provide for implantation of a prosthetic. In addition, a cutting block assembly may be used to guide the resecting member. The cutting block assembly may be moveably mounted relative to the portion to be resected.
摘要翻译：可以使用各种方法和装置来执行手术，例如切除解剖结构的一部分以准备假体的植入物。可以使用包括具有选定几何形状和形状的锯片的各种切除构件来辅助切除解剖结构以提供假体植入。此外，可以使用切割块组件来引导切除部件。切割块组件可相对于要切除的部分可移动地安装。

10. 发明授权

US08663956B2 Recombinant microorganisms for production C4-dicarboxylic acids 失效
标题翻译：用于生产C4-二羧酸的重组微生物
公开(公告)号：US08663956B2
公开(公告)日：2014-03-04
申请号：US13588322
申请日：2012-08-17
申请人： Sarah McFarland , Stephen Brown , Sheryl Luttringer
发明人： Sarah McFarland , Stephen Brown , Sheryl Luttringer
IPC分类号： C12N1/15
CPC分类号： C12N15/8243 , C12N9/88
摘要： Provided herein are host cells comprising carbonic anhydrase activity, wherein the cells are capable of producing C4-dicarboxylic acid. Also provided are methods of producing C4-dicarboxylic acid comprising (a) cultivating the host cells having carbonic anhydrase activity in a medium under suitable conditions to produce C4-dicarboxylic acid; and (b) recovering the C4-dicarboxylic acid.
摘要翻译：本文提供了包含碳酸酐酶活性的宿主细胞，其中细胞能够产生C4-二羧酸。还提供了生产C4-二羧酸的方法，其包括（a）在合适条件下培养在培养基中具有碳酸酐酶活性的宿主细胞以产生C4-二羧酸; 和（b）回收C4-二羧酸。

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