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1. 发明授权

US09273300B2 Methods and compositions for modulating sialic acid production and treating hereditary inclusion body myopathy 有权
标题翻译：调节唾液酸生产和治疗遗传性包涵体肌病的方法和组合物
公开(公告)号：US09273300B2
公开(公告)日：2016-03-01
申请号：US12526239
申请日：2008-02-07
申请人： Phillip Maples , Chris Jay , John J. Nemunaitis
发明人： Phillip Maples , Chris Jay , John J. Nemunaitis
IPC分类号： A61K48/00 , A61K9/16 , A61K9/50 , C12N9/90 , C12N15/85
CPC分类号： A61K48/005 , C12N9/90 , C12N15/85 , C12Y501/03014
摘要： According to certain embodiments of the present invention, methods for modulating the production of sialic acid in a system are provided, which comprise providing the system with a wild-type GNE-encoding nucleic acid sequence. According to such embodiments, the system may comprise a cell, muscular tissue, or other desirable targets. Similarly, the present invention encompasses methods for producing wild-type GNE in a system that comprises a mutated endogenous GNE-encoding sequence. In other words, the present invention includes providing, for example, a cell or muscular tissue that harbors a mutated (defective) GNE-encoding sequence with a functional wild-type GNE encoding sequence.
摘要翻译：根据本发明的某些实施方案，提供了调节系统中唾液酸生产的方法，其包括向系统提供编码野生型GNE的核酸序列。根据这样的实施例，该系统可以包括细胞，肌肉组织或其它期望的靶。类似地，本发明包括在包含突变的内源GNE编码序列的系统中产生野生型GNE的方法。换句话说，本发明包括例如提供具有功能性野生型GNE编码序列的突变（缺陷）GNE编码序列的细胞或肌肉组织。

2. 发明申请

US20160175461A1 METHODS AND COMPOSITIONS FOR MODULATING SIALIC ACID PRODUCTION AND TREATING HEREDITARY INCLUSION BODY MYOPATHY 审中-公开
标题翻译：调节酸乳酸生产和治疗包括身体肌肉酸痛的方法和组合物
公开(公告)号：US20160175461A1
公开(公告)日：2016-06-23
申请号：US15056929
申请日：2016-02-29
申请人： STRIKE BIO, INC.
发明人： Phillip B. Maples , Chris M. Jay , John J. Nemunaitis
IPC分类号： A61K48/00 , C12N9/90 , C12N15/85
CPC分类号： A61K48/005 , C12N9/90 , C12N15/85 , C12Y501/03014
摘要： According to certain embodiments of the present invention, methods for modulating the production of sialic acid in a system are provided, which comprise providing the system with a wild-type GNE-encoding nucleic acid sequence. According to such embodiments, the system may comprise a cell, muscular tissue, or other desirable targets. Similarly, the present invention encompasses methods for producing wild-type GNE in a system that comprises a mutated endogenous GNE-encoding sequence. In other words, the present invention includes providing, for example, a cell or muscular tissue that harbors a mutated (defective) GNE-encoding sequence with a functional wild-type GNE encoding sequence.
摘要翻译：根据本发明的某些实施方案，提供了调节系统中唾液酸生产的方法，其包括向系统提供编码野生型GNE的核酸序列。根据这样的实施例，该系统可以包括细胞，肌肉组织或其它期望的靶。类似地，本发明包括在包含突变的内源GNE编码序列的系统中产生野生型GNE的方法。换句话说，本发明包括例如提供具有功能性野生型GNE编码序列的突变（缺陷）GNE编码序列的细胞或肌肉组织。

3. 发明申请

US20080085540A1 Method of engineering a cytidine monophosphate-sialic acid synthetic pathway in fungi and yeast 审中-公开
标题翻译：在真菌和酵母中制备胞苷一磷酸唾液酸合成途径的方法
公开(公告)号：US20080085540A1
公开(公告)日：2008-04-10
申请号：US11977978
申请日：2007-10-26
申请人： Stephen Hamilton
发明人： Stephen Hamilton
IPC分类号： C12P21/04
CPC分类号： C12P19/26 , C12N9/1205 , C12N9/1241 , C12N9/16 , C12N9/88 , C12N9/90 , C12N15/52 , C12N15/815 , C12P21/005 , C12Y207/07043 , C12Y501/03014
摘要： The present invention provides methods for generating CMP-sialic acid in a non-human host which lacks endogenous CMP-Sialic by providing the host with enzymes involved in CMP-sialic acid synthesis from a bacterial, mammalian or hybrid CMP-sialic acid biosynthetic pathway. Novel fungal hosts expressing a CMP-sialic acid biosynthetic pathway for the production of sialylated glycoproteins are also provided.
摘要翻译：本发明提供了通过向宿主提供参与来自细菌，哺乳动物或混合CMP-唾液酸生物合成途径的CMP-唾液酸合成的酶，在缺乏内源性CMP-唾液酸的非人宿主中产生CMP-唾液酸的方法。还提供了表达用于产生唾液酸化糖蛋白的CMP-唾液酸生物合成途径的新型真菌宿主。

4. 发明公开

US20240309416A1 A GENETICALLY ENGINEERED BACTERIUM AND ITS APPLICATION IN THE PREPARATION OF SIALYLLACTOSE 审中-公开
公开(公告)号：US20240309416A1
公开(公告)日：2024-09-19
申请号：US18576640
申请日：2022-10-12
申请人： SYNAURA BIOTECHNOLOGY (SHANGHAI) CO., LTD.
发明人： Yan WU , Jing TANG , Shu WANG , Zhenhua TIAN , Fei YAO , Miao LI , Hong XU , Chenxi HUANG , Yurou LIU
IPC分类号： C12P19/26 , C12N1/20 , C12N9/10 , C12N9/12 , C12N9/16 , C12N9/90 , C12N15/70 , C12P19/18 , C12R1/19
CPC分类号： C12P19/26 , C12N1/205 , C12N9/1029 , C12N9/1081 , C12N9/1085 , C12N9/1096 , C12N9/1241 , C12N9/1294 , C12N9/16 , C12N9/90 , C12N15/70 , C12P19/18 , C12R2001/19 , C12Y203/01004 , C12Y204/99001 , C12Y204/99004 , C12Y205/01056 , C12Y206/01016 , C12Y207/07043 , C12Y207/09002 , C12Y301/03 , C12Y501/03014
摘要： The invention discloses a genetically engineered bacterium and its application in the preparation of sialyllactose. The genetically engineered bacterium has an N-acetylneuraminic acid biosynthesis pathway, includes multiple copies of a gene neuB for encoding sialic acid synthase, and the gene neuB is initiated for expression by a strong promoter. Using the genetically engineered bacteria of the invention to produce sialyllactose has the advantages of high yield and low overall cost.

5. 发明申请

US20150167038A1 METHOD AND AGENTS FOR PRODUCING N-ACETYLNEURAMINIC ACID (NEUNAC) 审中-公开
标题翻译：生产N-乙酰氨基酸（NEUNAC）的方法和试剂
公开(公告)号：US20150167038A1
公开(公告)日：2015-06-18
申请号：US14515120
申请日：2014-10-15
申请人： Technische Universitat Wien
发明人： Astrid MACH-AIGNER , Robert Mach , Matthias G. Steiger
IPC分类号： C12P19/26 , C12N9/12 , C12N9/90
CPC分类号： C12P19/26 , C12N9/1085 , C12N9/1241 , C12N9/90 , C12N15/80 , C12Y205/01056 , C12Y207/07043 , C12Y501/03008 , C12Y501/03014
摘要： The invention relates to an isolated nucleic acid molecule comprising at least one promoter that is active in fungal cells of the trichoderma species, wherein a nucleic acid sequence encoding an N-acetylglucosamine-2-epimerase and/or an N-acetylneuraminic acid synthase is operatively bound to each promoter. The at least one promoter that is active in fungal cells is a constitutive promoter.
摘要翻译：本发明涉及分离的核酸分子，其包含至少一种在木霉种的真菌细胞中具有活性的启动子，其中编码N-乙酰葡糖胺-2-差向异构酶和/或N-乙酰神经氨酸合酶的核酸序列是有效的与每个启动子结合。在真菌细胞中活性的至少一种启动子是组成型启动子。

6. 发明申请

US20110027373A1 METHODS AND COMPOSITIONS FOR MODULATING SIALIC ACID PRODUCTION AND TREATING HEREDITARY INCLUSION BODY MYOPATHY 有权
标题翻译：调节酸乳酸生产和治疗包括身体肌肉酸痛的方法和组合物
公开(公告)号：US20110027373A1
公开(公告)日：2011-02-03
申请号：US12526239
申请日：2008-02-07
申请人： Phillip Maples , Chris Jay , John J. Nemunaitis
发明人： Phillip Maples , Chris Jay , John J. Nemunaitis
IPC分类号： A61K9/00 , A61K31/711 , A61P21/00
CPC分类号： A61K48/005 , C12N9/90 , C12N15/85 , C12Y501/03014
摘要： According to certain embodiments of the present invention, methods for modulating the production of sialic acid in a system are provided, which comprise providing the system with a wild-type GNE-encoding nucleic acid sequence. According to such embodiments, the system may comprise a cell, muscular tissue, or other desirable targets. Similarly, the present invention encompasses methods for producing wild-type GNE in a system that comprises a mutated endogenous GNE-encoding sequence. In other words, the present invention includes providing, for example, a cell or muscular tissue that harbors a mutated (defective) GNE-encoding sequence with a functional wild-type GNE encoding sequence.
摘要翻译：根据本发明的某些实施方案，提供了调节系统中唾液酸生产的方法，其包括向系统提供编码野生型GNE的核酸序列。根据这样的实施例，该系统可以包括细胞，肌肉组织或其它期望的靶。类似地，本发明包括在包含突变的内源GNE编码序列的系统中产生野生型GNE的方法。换句话说，本发明包括例如提供具有功能性野生型GNE编码序列的突变（缺陷）GNE编码序列的细胞或肌肉组织。

7. 发明申请

US20050260729A1 Method of engineering a cytidine monophosphate-sialic acid synthetic pathway in fungi and yeast 审中-公开
标题翻译：在真菌和酵母中制备胞苷一磷酸唾液酸合成途径的方法
公开(公告)号：US20050260729A1
公开(公告)日：2005-11-24
申请号：US11084624
申请日：2005-03-17
申请人： Stephen Hamilton
发明人： Stephen Hamilton
IPC分类号： C12N1/14 , C12N1/18 , C12N9/10 , C12N9/12 , C12N9/16 , C12N9/88 , C12N9/90 , C12N15/52 , C12N15/81 , C12P19/26 , C12P21/00
CPC分类号： C12P19/26 , C12N9/1205 , C12N9/1241 , C12N9/16 , C12N9/88 , C12N9/90 , C12N15/52 , C12N15/815 , C12P21/005 , C12Y207/07043 , C12Y501/03014
摘要： The present invention provides methods for generating CMP-sialic acid in a non-human host which lacks endogenous CMP-Sialic by providing the host with enzymes involved in CMP-sialic acid synthesis from a bacterial, mammalian or hybrid CMP-sialic acid biosynthetic pathway. Novel fungal hosts expressing a CMP-sialic acid biosynthetic pathway for the production of sialylated glycoproteins are also provided.
摘要翻译：本发明提供了通过向宿主提供参与来自细菌，哺乳动物或混合CMP-唾液酸生物合成途径的CMP-唾液酸合成的酶，在缺乏内源性CMP-唾液酸的非人宿主中产生CMP-唾液酸的方法。还提供了表达用于产生唾液酸化糖蛋白的CMP-唾液酸生物合成途径的新型真菌宿主。

8. 发明授权

US08940876B2 Method for preparing recombinant glycoproteins with high sialic acid content 有权
标题翻译：制备高唾液酸含量的重组糖蛋白的方法
公开(公告)号：US08940876B2
公开(公告)日：2015-01-27
申请号：US13390671
申请日：2011-02-01
申请人： Jung Hoe Kim , Young Dok Son , Jin Young Hwang , Yeon Tae Jeong
发明人： Jung Hoe Kim , Young Dok Son , Jin Young Hwang , Yeon Tae Jeong
IPC分类号： C07K14/505 , C07K14/705 , C07K14/52 , C12P21/00 , C12N9/90 , C12N9/12 , C12N9/10
CPC分类号： C07K14/505 , C07K14/524 , C07K14/705 , C12N9/1081 , C12N9/1205 , C12N9/90 , C12P21/005 , C12Y501/03014
摘要： The present disclosure relates to a method for preparing recombinant glycoproteins with high sialic acid content. More specifically, for UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE/MNK) enzyme where point mutation was induced by substituting arginine at position 263 by leucine only or by further substituting arginine at position 266 by glutamine, epimerase activity is constantly maintained, and overexpressed cells thereof experience an increase in intracellular cytidine monophosphate (CMP)-sialic acid content, irrespective of CMP-sialic acid concentration. Particularly, since in an glycoprotein (such as, erythropoietin and thrombopoietin)-producing host cell where point mutationinduced GNE/MNK, human alpha-2,3-sialyltransferase and a CMP-sialic acid transporter gene are simultaneously overexpressed, intracellular content of CMP-sialic acid and sialic acid in glycoprotein increases in cells, overexpression in a host cell producing a sialylated recombinant glycoprotein the three genes above may be useful for preparing glycoprotein with increased sialic acid content.
摘要翻译：本公开涉及一种制备高唾液酸含量的重组糖蛋白的方法。更具体地，对于通过仅通过亮氨酸取代位置263处的精氨酸或通过用谷氨酰胺进一步取代位置266处的精氨酸而诱发点突变的UDP-GlcNAc 2-差向异构酶/ ManNAc激酶（GNE / MNK）酶，不断维持差向异构酶活性，并且其过表达的细胞经历细胞内胞苷酸单磷酸（CMP） - 唾液酸含量的增加，而不考虑CMP-唾液酸浓度。特别是，由于在产生点突变诱导的GNE / MNK的糖蛋白（例如促红细胞生成素和血小板生成素）中，人α-2,3-唾液酸转移酶和CMP-唾液酸转运蛋白基因同时过表达，因此CMP- 糖蛋白中的唾液酸和唾液酸在细胞中增加，在产生唾液酸化重组糖蛋白的宿主细胞中过表达，上述三种基因可能用于制备具有增加的唾液酸含量的糖蛋白。

9. 发明申请

US20130266987A1 METHOD AND AGENTS FOR PRODUCING N-ACETYLNEURAMINIC ACID (NEUNAC) 审中-公开
公开(公告)号：US20130266987A1
公开(公告)日：2013-10-10
申请号：US13993979
申请日：2011-12-22
申请人： Astrid Mach-Aigner , Robert Mach , Matthias G. Steiger
发明人： Astrid Mach-Aigner , Robert Mach , Matthias G. Steiger
IPC分类号： C12N15/80 , C12P19/26
CPC分类号： C12P19/26 , C12N9/1085 , C12N9/1241 , C12N9/90 , C12N15/80 , C12Y205/01056 , C12Y207/07043 , C12Y501/03008 , C12Y501/03014
摘要： The invention relates to an isolated nucleic acid molecule comprising at least one promoter that is active in fungal cells of the trichoderma species, wherein a nucleic acid sequence encoding an N-acetylglucosamine-2-epimerase and/or an N-acetylneuraminic acid synthase is operatively bound to each promoter. The at least one promoter that is active in fungal cells is a constitutive promoter.

10. 发明申请

US20120149874A1 METHOD FOR PREPARING RECOMBINANT GLYCOPROTEINS WITH HIGH SIALIC ACID CONTENT 有权
标题翻译：用高碱性内容物制备重组蛋白糖的方法
公开(公告)号：US20120149874A1
公开(公告)日：2012-06-14
申请号：US13390671
申请日：2011-02-01
申请人： Jung Hoe Kim , Young Dok Son , Jin Young Hwang , Yeon Tae Jeong
发明人： Jung Hoe Kim , Young Dok Son , Jin Young Hwang , Yeon Tae Jeong
IPC分类号： C07K14/435 , C12N9/18 , C12N9/10 , C07K14/575 , C12N15/81 , C07K14/745 , C12N15/85 , C12N1/19 , C12N5/10 , C12P21/00 , C07K14/755
CPC分类号： C07K14/505 , C07K14/524 , C07K14/705 , C12N9/1081 , C12N9/1205 , C12N9/90 , C12P21/005 , C12Y501/03014
摘要： The present disclosure relates to a method for preparing recombinant glycoproteins with high sialic acid content. More specifically, for UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE/MNK) enzyme where point mutation was induced by substituting arginine at position 263 by leucine only or by further substituting arginine at position 266 by glutamine, epimerase activity is constantly maintained, and overexpressed cells thereof experience an increase in intracellular cytidine monophosphate (CMP)-sialic acid content, irrespective of CMP-sialic acid concentration. Particularly, since in an glycoprotein(such as, erythropoietin and thrombopoietin)-producing host cell where point mutationinduced GNE/MNK, human alpha-2,3-sialyltransferase and a CMP-sialic acid transporter gene are simultaneously overexpressed, intracellular content of CMP-sialic acid and sialic acid in glycoprotein increases in cells, overexpression in a host cell producing a sialylated recombinant glycoprotein the three genes above may be useful for preparing glycoprotein with increased sialic acid content.
摘要翻译：本公开涉及一种制备高唾液酸含量的重组糖蛋白的方法。更具体地，对于通过仅通过亮氨酸取代位置263处的精氨酸或通过用谷氨酰胺进一步取代位置266处的精氨酸而诱发点突变的UDP-GlcNAc 2-差向异构酶/ ManNAc激酶（GNE / MNK）酶，不断维持差向异构酶活性，并且其过表达的细胞经历细胞内胞苷酸单磷酸（CMP） - 唾液酸含量的增加，而不考虑CMP-唾液酸浓度。特别是，由于在产生点突变诱导的GNE / MNK的糖蛋白（例如促红细胞生成素和血小板生成素）中，人α-2,3-唾液酸转移酶和CMP-唾液酸转运蛋白基因同时过表达，因此CMP- 糖蛋白中的唾液酸和唾液酸在细胞中增加，在产生唾液酸化重组糖蛋白的宿主细胞中过表达，上述三种基因可能用于制备具有增加的唾液酸含量的糖蛋白。

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