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1. 发明申请

US20100279348A1 YEAST STRAINS FOR PROTEIN PRODUCTION 有权
标题翻译：用于蛋白质生产的YEAST菌株
公开(公告)号：US20100279348A1
公开(公告)日：2010-11-04
申请号：US12744959
申请日：2008-12-15
申请人： Juergen Nett
发明人： Juergen Nett
IPC分类号： C12P21/00 , C12N1/19 , C12N1/15 , C07H21/04 , C12N15/79
CPC分类号： C12N15/815 , C12N9/88 , C12N2800/102 , C12Y401/01021
摘要： Method and system for expression systems, based on ade1 and ade2 auxotrophic strains of yeast and fungi, including P. pastoris are disclosed. The expression systems are useful for increased cellular productivity of transformed cell lines and for production of recombinant glycoproteins at industrial scale.
摘要翻译：公开了基于ade1和ade2营养缺陷菌株的酵母和真菌，包括巴斯德毕赤酵母的表达系统的方法和系统。表达系统对于提高转化细胞系的细胞生产力和用于在工业规模生产重组糖蛋白是有用的。

2. 发明申请

US20070037248A1 Production of modified glycoproteins having multiple antennary structures 失效
标题翻译：具有多个触角结构的修饰的糖蛋白的生产
公开(公告)号：US20070037248A1
公开(公告)日：2007-02-15
申请号：US10546101
申请日：2004-02-20
申请人： Piotr Bobrowicz , Stephen Hamilton , Tillman Gerngross , Stefan Wildt , Byung-Kwon Choi , Juergen Nett , Robert Davidson
发明人： Piotr Bobrowicz , Stephen Hamilton , Tillman Gerngross , Stefan Wildt , Byung-Kwon Choi , Juergen Nett , Robert Davidson
IPC分类号： C07K14/47 , C07H21/04 , C12P21/06 , C12N1/18 , C12N15/74
CPC分类号： C12P21/005 , C12N9/1051
摘要： The present invention relates to eukaryotic host cells, especially lower eukaryotic host cells, having modified oligosaccharides which may be modified further by heterologous expression of a set of glycosyltransferases, sugar and sugar nucleotide transporters to become host-strains for the production of mammalian, e.g., human therapeutic glycoproteins. The process provides an engineered host cell which can be used to express and target any desirable gene(s) involved in glycosylation. Host cells with modified lipid-linked oligosaccharides are created or selected. N-glycans made in the engineered host cells exhibit GnTIII, GnTIV, GnTV, GnT VI or GnTIX activity, which produce bisected and/or multiantennary N-glycan structures and may be modified further by heterologous expression of one or more enzymes, e.g., glycosyltransferases, sugar, sugar nucleotide transporters, to yield human-like glycoproteins. For the production of therapeutic proteins, this method may be adapted to engineer cell lines in which any desired glycosylation structure may be obtained.
摘要翻译：本发明涉及具有修饰的寡糖的真核宿主细胞，特别是较低的真核宿主细胞，其可以通过异源表达一组糖基转移酶，糖和糖核苷酸转运蛋白进一步修饰，以成为用于产生哺乳动物的宿主菌株，人类治疗糖蛋白。该方法提供了可用于表达和靶向参与糖基化的任何所需基因的工程化宿主细胞。制备或选择具有修饰的脂质连接寡糖的宿主细胞。在工程化宿主细胞中制备的N-聚糖表现出GnTIII，GnTIV，GnTV，GnT VI或GnTIX活性，其产生二等分和/或多元N-聚糖结构，并且可以通过异源表达一种或多种酶，例如糖基转移酶，糖，糖核苷酸转运蛋白，以产生人样糖蛋白。为了生产治疗性蛋白质，该方法可适用于工程化可能获得任何所需糖基化结构的细胞系。

3. 发明申请

US20130295608A1 YEAST STRAIN FOR THE PRODUCTION OF PROTEINS WITH MODIFIED O-GLYCOSYLATION 有权
标题翻译： YEAST菌株生产具有改性O-糖蛋白的蛋白质
公开(公告)号：US20130295608A1
公开(公告)日：2013-11-07
申请号：US13978714
申请日：2012-02-20
申请人： Piotr Bobrowicz , William J. Cook , Stephen Hamilton , Juergen Nett , Terrance A. Stadheim , Stefan Wildt
发明人： Piotr Bobrowicz , William J. Cook , Stephen Hamilton , Juergen Nett , Terrance A. Stadheim , Stefan Wildt
IPC分类号： C07K14/39
CPC分类号： C07K14/39 , C12N9/90 , C12P21/005
摘要： Lower eukaryotic host cells have been recombinantly engineered to produce glycoprotein having human-like O-glycosylation. The glycoproteins are useful for the production of glycoprotein compositions with advantages for the production of human therapeutics.
摘要翻译：已经重组设计了较低真核宿主细胞以产生具有人类O-糖基化的糖蛋白。糖蛋白可用于生产具有用于生产人类治疗剂的优点的糖蛋白组合物。

4. 发明申请

US20120100622A1 PICHIA PASTORIS LOCI ENCODING ENZYMES IN THE URACIL BIOSYNTHETIC PATHWAY 审中-公开
标题翻译： PICHIA PASTORIS LOCI ENCODING ENZYMES IN URACIL BIOSYNEE PATHWAY
公开(公告)号：US20120100622A1
公开(公告)日：2012-04-26
申请号：US13272661
申请日：2011-10-13
申请人： Juergen Nett
发明人： Juergen Nett
IPC分类号： C12N15/81 , C12N15/53 , C12N1/19
CPC分类号： C12N15/52 , C12N15/815 , C12P17/12
摘要： Disclosed are the URA1, URA2, URA4, and URA6 genes encoding various enzymes in the uracil biosynthesis pathway of Pichia pastoris. The loci in the Pichia pastoris genome encoding these enzymes are useful sites for stable integration of heterologous nucleic acid molecules into the Pichia pastoris genome. The genes or gene fragments encoding the particular enzymes may be used as selection markers for constructing recombinant Pichia pastoris.
摘要翻译：公开了编码巴斯德毕赤酵母尿嘧啶生物合成途径中各种酶的URA1，URA2，URA4和URA6基因。编码这些酶的巴斯德毕赤酵母基因组中的基因座是将异源核酸分子稳定整合到巴斯德毕赤酵母基因组中的有用位点。可以将编码特定酶的基因或基因片段用作构建重组巴斯德毕赤酵母的选择标记。

5. 发明授权

US07479389B2 ARG1, ARG2, ARG3, HIS1, HIS2, HIS5, HIS6 genes and methods for stable genetic integration 失效
标题翻译： ARG1，ARG2，ARG3，HIS1，HIS2，HIS5，HIS6基因和稳定遗传整合的方法
公开(公告)号：US07479389B2
公开(公告)日：2009-01-20
申请号：US11071690
申请日：2005-03-02
申请人： Juergen Nett , Tillman Gerngross
发明人： Juergen Nett , Tillman Gerngross
IPC分类号： C12N15/74 , C12N15/00 , C12P21/00 , C12N1/19 , C07K14/00 , C07H21/00
CPC分类号： C12N15/52 , C12N15/81
摘要： Novel genes encoding P. pastoris ARG1, ARG2, ARG3, HIS1, HIS2, HIS5 and HIS6 are disclosed. A method for inactivating alternately at least two biosynthetic pathways in a methylotrophic yeast is provided. A method for producing and selecting yeast strains characterized as being capable of genetic integration of heterologous sequences into the host genome using the genes involved in the biosynthetic pathways is also disclosed.
摘要翻译：公开了编码巴斯德毕赤酵母ARG1，ARG2，ARG3，HIS1，HIS2，HIS5和HIS6的新型基因。提供了在甲基营养酵母中交替灭活至少两种生物合成途径的方法。还公开了用于生产和选择酵母菌株的方法，其特征在于能够使用参与生物合成途径的基因将异源序列遗传整合到宿主基因组中。

6. 发明授权

US08936918B2 Yeast strain for the production of proteins with modified O-glycosylation 有权
标题翻译：用于生产具有修饰的O-糖基化的蛋白质的酵母菌株
公开(公告)号：US08936918B2
公开(公告)日：2015-01-20
申请号：US13978714
申请日：2012-02-20
申请人： Piotr Bobrowicz , William J. Cook , Stephen Hamilton , Juergen Nett , Terrance A. Stadheim , Stefan Wildt
发明人： Piotr Bobrowicz , William J. Cook , Stephen Hamilton , Juergen Nett , Terrance A. Stadheim , Stefan Wildt
IPC分类号： C12P21/06 , C07K14/39 , C12P21/00 , C12N9/90
CPC分类号： C07K14/39 , C12N9/90 , C12P21/005
摘要： Lower eukaryotic host cells have been recombinantly engineered to produce glycoprotein having human-like O-glycosylation. The glycoproteins are useful for the production of glycoprotein compositions with advantages for the production of human therapeutics.
摘要翻译：已经重组设计了较低真核宿主细胞以产生具有人类O-糖基化的糖蛋白。糖蛋白可用于生产具有用于生产人类治疗剂的优点的糖蛋白组合物。

7. 发明授权

US08883483B2 Combinatorial DNA library for producing modified N-glycans in lower eukaryotes 有权
标题翻译：用于在低等真核生物中生产修饰的N-聚糖的组合DNA文库
公开(公告)号：US08883483B2
公开(公告)日：2014-11-11
申请号：US13156804
申请日：2011-06-09
申请人： Tillman U. Gerngross , Stefan Wildt , Byung-kwon Choi , Juergen Nett , Piotr Bobrowicz , Stephen Hamilton , Robert Davidson
发明人： Tillman U. Gerngross , Stefan Wildt , Byung-kwon Choi , Juergen Nett , Piotr Bobrowicz , Stephen Hamilton , Robert Davidson
IPC分类号： C12N15/04 , C12N1/16 , C07K14/47 , C12N9/10 , C12N15/10 , C12N15/79
CPC分类号： C12P21/005 , C07K14/47 , C12N9/1051 , C12N15/1082 , C12N15/79
摘要： The present invention relates to eukaryotic host cells having modified oligosaccharides which may be modified further by heterologous expression of a set of glycosyltransferases, sugar transporters and mannosidases to become host-strains for the production of mammalian, e.g., human therapeutic glycoproteins. The invention provides nucleic acid molecules and combinatorial libraries which can be used to successfully target and express mammalian enzymatic activities such as those involved in glycosylation to intracellular compartments in a eukaryotic host cell. The process provides an engineered host cell which can be used to express and target any desirable gene(s) involved in glycosylation. Host cells with modified oligosaccharides are created or selected. N-glycans made in the engineered host cells have a Man5GlcNAc2 core structure which may then be modified further by heterologous expression of one or more enzymes, e.g., glycosyltransferases, sugar transporters and mannosidases, to yield human-like glycoproteins. For the production of therapeutic proteins, this method may be adapted to engineer cell lines in which any desired glycosylation structure may be obtained.
摘要翻译：本发明涉及具有修饰的寡糖的真核宿主细胞，其可以通过异源表达一组糖基转移酶，糖转运体和甘露糖苷酶进一步修饰，以成为用于产生哺乳动物例如人治疗性糖蛋白的宿主菌株。本发明提供核酸分子和组合文库，其可用于成功靶向和表达哺乳动物酶活性，例如参与糖基化的真核宿主细胞中的细胞内区室的那些。该方法提供了可用于表达和靶向参与糖基化的任何所需基因的工程化宿主细胞。建立或选择具有修饰寡糖的宿主细胞。在工程化宿主细胞中制备的N-聚糖具有Man5GlcNAc2核心结构，然后可以通过异源表达一种或多种酶，例如糖基转移酶，糖转运蛋白和甘露糖苷酶来进一步修饰，以产生人样糖蛋白。为了生产治疗性蛋白质，该方法可适用于工程化可能获得任何所需糖基化结构的细胞系。

8. 发明申请

US20090124000A1 Recombinant Vectors 有权
标题翻译：重组载体
公开(公告)号：US20090124000A1
公开(公告)日：2009-05-14
申请号：US12227203
申请日：2007-05-18
申请人： Juergen Nett , Robert Davidson
发明人： Juergen Nett , Robert Davidson
IPC分类号： C12N15/81
CPC分类号： C12N15/815 , C12N15/905
摘要： Methods and materials are provided for integrating heterologous nucleic acids into the genome of a cell or virus without disrupting expression of genes adjacent to the insertion site.
摘要翻译：提供的方法和材料用于将异源核酸整合到细胞或病毒的基因组中，而不会破坏与插入位点相邻的基因的表达。

9. 发明申请

US20080139470A1 Erythropoietin compositions 有权
标题翻译：红细胞生成素组成
公开(公告)号：US20080139470A1
公开(公告)日：2008-06-12
申请号：US11804510
申请日：2007-05-18
申请人： Natarajan Sethuraman , Juergen Nett , Robert Davidson
发明人： Natarajan Sethuraman , Juergen Nett , Robert Davidson
IPC分类号： A61K38/00 , C07K14/505 , C12P21/04 , A61P7/00
CPC分类号： C07K14/505 , C12P21/005
摘要： Methods and materials are provided for the production of compositions of erythropoietin protein, wherein said compositions comprise a pre-selected N-linked glycosylation pattern as the predominant N-glycoform.
摘要翻译：提供了用于生产促红细胞生成素蛋白质组合物的方法和材料，其中所述组合物包含预先选择的N-连接的糖基化模式作为主要的N-糖基型。

10. 发明申请

US20050208617A1 N-acetylglucosamintransferase III expression in lower eukaryotes 失效
标题翻译： N-乙酰葡萄糖转移酶III在低等真核生物中的表达
公开(公告)号：US20050208617A1
公开(公告)日：2005-09-22
申请号：US10680963
申请日：2003-10-07
申请人： Piotr Bobrowicz , Stephen Hamilton , Tilman Gerngross , Stefan Wildt , Byung-Kwon Choi , Juergen Nett , Robert Davidson
发明人： Piotr Bobrowicz , Stephen Hamilton , Tilman Gerngross , Stefan Wildt , Byung-Kwon Choi , Juergen Nett , Robert Davidson
IPC分类号： A61K38/00 , C07K14/39 , C07K14/47 , C12N1/18 , C12N9/10 , C12N15/12 , C12N15/74 , C12P21/00 , C12P21/06
CPC分类号： C07K14/39 , A61K38/00 , C07K2319/05 , C12N9/1051 , C12P21/005 , Y02A50/396
摘要： The present invention relates to eukaryotic host cells having modified oligosaccharides which may be modified further by heterologous expression of a set of glycosyltransferases, sugar transporters and mannosidases to become host-strains for the production of mammalian, e.g., human therapeutic glycoproteins. The process provides an engineered host cell which can be used to express and target any desirable gene(s) involved in glycosylation. Host cells with modified lipid-linked oligosaccharides are created or selected. N-glycans made in the engineered host cells exhibit GnTIII activity, which produce bisected N-glycan structures and may be modified further by heterologous expression of one or more enzymes, e.g., glycosyltransferases, sugar transporters and mannosidases, to yield human-like glycoproteins. For the production of therapeutic proteins, this method may be adapted to engineer cell lines in which any desired glycosylation structure may be obtained.
摘要翻译：本发明涉及具有修饰的寡糖的真核宿主细胞，其可以通过异源表达一组糖基转移酶，糖转运体和甘露糖苷酶进一步修饰，以成为用于产生哺乳动物例如人治疗性糖蛋白的宿主菌株。该方法提供了可用于表达和靶向参与糖基化的任何所需基因的工程化宿主细胞。制备或选择具有修饰的脂质连接寡糖的宿主细胞。在工程化的宿主细胞中制备的N-聚糖表现出GnTIII活性，其产生二等分的N-聚糖结构，并且可以通过异源表达一种或多种酶（例如糖基转移酶，糖转运蛋白和甘露糖苷酶）进一步修饰，以产生人样糖蛋白。为了生产治疗性蛋白质，该方法可适用于工程化可能获得任何所需糖基化结构的细胞系。

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