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81. 发明申请

US20180016564A1 ALPHA-GALACTOSIDASE A FROM MATERIAL CONTAINING CONTAMINANT HOST CELL PROTEINS 审中-公开
公开(公告)号：US20180016564A1
公开(公告)日：2018-01-18
申请号：US15545194
申请日：2016-01-21
申请人： JCR Pharmaceuticals Co., Ltd.
发明人： Tsuyoshi FUKUI , Atsuko KAWASAKI , Yukichi HATANO , Yae ITO , Kazutoshi MIHARA , Atsushi SUGIMURA
IPC分类号： C12N9/40 , A61K38/00
CPC分类号： C12N9/2465 , A61K38/00 , C12Y302/01022
摘要： Disclosed is a method for production of recombinant human alpha-galactosidase A (rh alpha-Gal A) in a large scale, with a high purity. The method comprises the steps of (a) culturing rh alpha-Gal A-producing mammalian cells in a serum-free medium, (b) collecting culture supernatant, (c) subjecting the culture supernatant to anion-exchange column chromatography, (d) to hydrophobic column chromatography, (e) to a column chromatography employing as solid phase a material having affinity for phosphate group, (f) to cation-exchange column chromatography, (g) to dye-affinity column chromatography, and (h) to gel filtration column chromatography, in the order.

82. 发明申请

US20170360900A1 HUMAN ALPHA-GALACTOSIDASE VARIANTS 审中-公开
公开(公告)号：US20170360900A1
公开(公告)日：2017-12-21
申请号：US15529383
申请日：2015-12-02
申请人： Codexis, Inc.
发明人： Nicholas J. Agard , Mathew G. Miller , Xiyun Zhang , Gjalt W. Huisman
IPC分类号： A61K38/47 , C12N9/40 , A61K9/00
CPC分类号： A61K38/47 , A61K9/0019 , C12N9/2465 , C12Y302/01022
摘要： The present invention provides engineered human alpha-galactosidase polypeptides and compositions thereof. The engineered human alpha-galactosidase polypeptides have been optimized to provide improved stability under both acidic (pH 7) conditions. The invention also relates to the use of the compositions comprising the engineered human alpha-galactosidase polypeptides for therapeutic purposes.

83. 发明授权

US09220737B2 Plant cell culture expressing human lysosomal proteins and uses thereof 有权
标题翻译：表达人溶酶体蛋白质的植物细胞培养物及其用途
公开(公告)号：US09220737B2
公开(公告)日：2015-12-29
申请号：US14292966
申请日：2014-06-02
申请人： Protalix Ltd.
发明人： Yoseph Shaaltiel , Gideon Baum , Daniel Bartfeld , Sharon Hashmueli , Ayala Lewkowicz
IPC分类号： A61K36/23 , C12N9/24 , C12N9/42 , C12N9/40 , C12N15/82 , C12P21/00
CPC分类号： A61K38/47 , A61K9/0053 , A61K36/23 , C07K2319/04 , C12N9/2405 , C12N9/2434 , C12N9/2465 , C12N15/8257 , C12P21/005 , C12Y302/01022 , C12Y302/01045
摘要： A device, system and method for producing glycosylated proteins in plant culture, particularly proteins having a high mannose glycosylation, while targeting such proteins with an ER signal and/or by-passing the Golgi. The invention further relates to vectors and methods for expression and production of enzymatically active high mannose lysosomal enzymes using transgenic plant root, particularly carrot cells. More particularly, the invention relates to host cells, particularly transgenic suspended carrot cells, vectors and methods for high yield expression and production of biologically active high mannose Glucocerebrosidase (GCD). The invention further provides for compositions and methods for the treatment of lysosomal storage diseases.
摘要翻译：用于在植物培养物中生产糖基化蛋白质的装置，系统和方法，特别是具有高甘露糖糖基化的蛋白质，同时用ER信号靶向这种蛋白质和/或旁路高尔基体。本发明进一步涉及使用转基因植物根特别是胡萝卜细胞表达和产生酶活性高甘露糖溶酶体酶的载体和方法。更具体地，本发明涉及宿主细胞，特别是转基因悬浮的胡萝卜细胞，用于高产量表达和生产生物活性高甘露糖葡糖脑苷脂酶（GCD）的载体和方法。本发明还提供了用于治疗溶酶体贮积病的组合物和方法。

84. 发明授权

US09034626B2 Methods of preparing tissues for xenotransplantation using alpha-galactosidases 有权
标题翻译：使用α-半乳糖苷酶制备异种移植组织的方法
公开(公告)号：US09034626B2
公开(公告)日：2015-05-19
申请号：US14507010
申请日：2014-10-06
申请人： Velico Medical, Inc.
发明人： Qiyong Peter Liu , Henrik Clausen
IPC分类号： C12Q1/34 , C12N9/40 , A61K35/32 , C12N5/077
CPC分类号： C12N5/0654 , A61K35/32 , A61K35/35 , A61L27/3687 , A61L27/3695 , C12N5/0652 , C12N9/2465 , C12N2501/73 , C12N2506/09 , C12N2506/13 , C12N2506/1315 , C12N2506/14 , C12N2506/25 , C12Y302/01022
摘要： This invention relates to novel α-galactosidases for the enzymatic removal of the immunodominant monosaccharides on blood products and tissues. Specifically this invention provides a novel family of α3 glycosidases, used for the enzymatic removal of type B antigens from blood group B and AB reactive blood products, and the Galili antigen from non-human animal tissues, thereby converting these to non-immunogenic cells and tissues suitable for transplantation.
摘要翻译：本发明涉及用于在血液制品和组织上酶促去除免疫优势单糖的新型α-半乳糖苷酶。具体地说，本发明提供了一种新型的α3糖苷酶家族，用于从血型B和AB反应性血液制品中酶切除B型抗原，从非人动物组织中提取Galectin抗原，从而将其转化为非免疫原性细胞，适合移植的组织。

85. 发明申请

US20150079066A1 MEANS AND METHODS FOR GENERATING IMPROVED PROTEINS 有权
标题翻译：产生改良蛋白质的方法和方法
公开(公告)号：US20150079066A1
公开(公告)日：2015-03-19
申请号：US14395049
申请日：2013-04-18
申请人： VIB VZW , KATHOLIEKE UNIVERSITEIT LEUVEN, K.U.LEUVEN R&D
发明人： Frederic Rousseau , Joost Schymkowitz , Ashok Ganesan , Aleksandra Siekierska , Frederik De Smet , Joost Van Durme
IPC分类号： C12N9/40 , C40B30/02 , C07K14/32 , G06F19/16 , C07K14/435
CPC分类号： C12N9/2465 , C07K14/32 , C07K14/43595 , C40B30/02 , G06F19/16
摘要： The disclosure provides a general method for the production of protein variants with a reduced aggregation propensity without affecting the thermodynamic stability of the variant with respect to the wild-type protein.
摘要翻译：本公开提供了生产具有降低的聚集倾向的蛋白质变体的一般方法，而不影响变体相对于野生型蛋白质的热力学稳定性。

86. 发明申请

US20140220553A1 Enzymatic Conversion of Blood Group A, B, and AB Red Blood Cells Using alpha-N-Acetylgalactosaminidases and alpha-Galactosidases with Unique Substrate Specificities and Kinetic Properties 审中-公开
标题翻译：使用具有独特底物特异性和动力学性质的α-N-乙酰半乳糖胺酶和α-半乳糖苷酶对A组，B组和AB组血液细胞进行酶转化
公开(公告)号：US20140220553A1
公开(公告)日：2014-08-07
申请号：US14201407
申请日：2014-03-07
申请人： Velico Medical, Inc.
发明人： Henrik Clausen , Humberto de la Vega , Cheryl Hill , Qiyong Peter Liu
IPC分类号： C12N5/078 , C12N9/40 , C12Q1/34
CPC分类号： C12N5/0641 , C12N9/2402 , C12N9/2465 , C12Q1/34 , C12R1/465 , C12Y302/01022 , C12Y302/01049
摘要： This invention relates to enzymatic removal of type A and B antigens from blood group A, B, and AB reactive cells in blood products, and thereby converting these to non-A and non-B reactive cells. The invention further relates to using unique α-N-acetylgalactosaminidases and α-galactosidases with superior kinetic properties for removing the immunodominant monosaccharides of the blood group A and B antigens and improved performance in enzymatic conversion of red blood cells. The preferred unique α-N-acetylgalactosaminidases and α-galactosidases exhibit the following characteristics: (i) exclusive, preferred or no less than 10% substrate specificity for the type A and B branched polysaccharide structures relative to measurable activity with simple mono- and disaccharide structures and aglycon derivatives hereof: (ii) optimal performance at neutral pH with blood group oligosaccharides and in enzymatic conversion of cells: and (iii) a favorable kinetic constant Km with mono- and oligosaccharide substrates. The conversion methods of the invention use significantly lower amounts of recombinant glycosidase enzymes than previous and result in complete sera-conversion of all blood group A and B red cells.
摘要翻译：本发明涉及从血型A，B，AB型反应性细胞中分离A型和B型抗原，从而将其转化为非A型和非B型细胞。本发明还涉及使用独特的α-N-乙酰半乳糖胺酶和具有优异动力学性质的α-半乳糖苷酶，用于去除血型A和B抗原的免疫优势单糖，并提高了红细胞酶促转化的表现。优选的独特的α-N-乙酰半乳糖胺酶和α-半乳糖苷酶具有以下特征：（i）相对于简单的单糖和二糖的可测量的活性，对于A型和B型支链多糖结构，独特的，优选的或不低于10％的底物特异性结构和糖苷配基衍生物：（ii）在中性pH下用血液寡糖和细胞的酶转化中的最佳性能：和（iii）具有单糖和寡糖底物的有利的动力学常数Km。本发明的转化方法比以前使用显着更低量的重组糖苷酶，并导致所有血型A和B红细胞的完全血清转化。

87. 发明申请

US20140171493A1 HIGHLY FUNCTIONAL ENZYME HAVING ALPHA-GALACTOSIDASE ACTIVITY 有权
标题翻译：具有ALPHA-GALACTOSIDASE活性的高功能酶
公开(公告)号：US20140171493A1
公开(公告)日：2014-06-19
申请号：US14162135
申请日：2014-01-23
申请人： ALTIF LABORATORIES , Tokyo Metropolitan Institute of Medical Science
发明人： Hitoshi Sakuraba , Youichi Tajima , Mai Ito , Seiichi Aikawa , Fumiko Aikawa
IPC分类号： C12N9/40
CPC分类号： C12N9/2465 , A61K38/00 , C12N9/2402 , C12Y302/01022 , C12Y302/01049
摘要： The present invention provides, as an enzyme which can be used for enzyme replacement therapy for Fabry disease, a protein having α-galactosidase activity, which shows no allergic adverse side effect, shows a high stability in blood, and can be easily incorporated into a cell of an affected organ. The protein of the present invention is a protein which has acquired α-galactosidase activity by changing the structure of the active site of wild-type human α-N-acetylgalactosaminidase.
摘要翻译：本发明提供作为法布里病的酶替代疗法的酶，不具有过敏性副作用的具有α-半乳糖苷酶活性的蛋白质在血液中显示高稳定性，并且可以容易地加入到受影响器官的细胞。本发明的蛋白质是通过改变野生型人α-N-乙酰半乳糖胺酶活性位点的结构而获得α-半乳糖苷酶活性的蛋白质。

88. 发明授权

US08124073B2 Targeting of glycoprotein therapeutics 有权
标题翻译：靶向糖蛋白治疗
公开(公告)号：US08124073B2
公开(公告)日：2012-02-28
申请号：US11970907
申请日：2008-01-08
申请人： James Stefano
发明人： James Stefano
IPC分类号： A61K38/54 , A61K38/43 , A61K31/00 , A61K38/47 , A61K38/00 , A61K38/14 , C12N9/40 , C12N9/96
CPC分类号： A61K38/47 , A61K47/60 , A61K47/61 , A61K47/64 , C12N9/2465 , C12N9/96 , C12Y302/01022
摘要： Methods of making ligand-decorated polymer conjugates of therapeutic glycoproteins are described. Improved targeting of glycoproteins to specific tissues is achieved by masking the natural carbohydrate and other surface determinants with high molecular weight polymers, such as, e.g., PEG, polysialic acid, etc., which in turn are decorated with target-specific ligands. In some embodiments, acid-labile linkages in such conjugates or rapidly degradable masking groups allow for the intracellular release of the polymer from the glycoprotein, for example, under conditions found in lysosomes.
摘要翻译：描述了制备治疗性糖蛋白的配体缀合的聚合物缀合物的方法。通过用高分子量聚合物（例如PEG，聚唾液酸等）掩蔽天然碳水化合物和其它表面决定簇来实现糖蛋白靶向特定组织的改进，其又用靶特异性配体装饰。在一些实施方案中，这种缀合物或快速可降解的掩蔽基团中的酸不稳定键可以允许聚合物从糖蛋白的细胞内释放，例如在溶酶体中发现的条件下。

89. 发明申请

US20120003715A1 Process for Producing Recombinant Lyosomal Using Insect Larvae 审中-公开
标题翻译：使用昆虫幼虫生产重组染色体的方法
公开(公告)号：US20120003715A1
公开(公告)日：2012-01-05
申请号：US13255863
申请日：2009-03-13
申请人： Victor Infante Viñolo , Rosa Maria Osuna Aguilar , Juan Jose Infante Viñolo
发明人： Victor Infante Viñolo , Rosa Maria Osuna Aguilar , Juan Jose Infante Viñolo
IPC分类号： C12N9/12 , C12N9/38 , C12N9/16 , C12N9/78 , C12N9/40 , C12N9/26 , C12N9/44 , C12N9/00 , C12N9/24 , C12N9/20
CPC分类号： C12Y302/01023 , A01K67/0337 , A01K2227/706 , A01K2267/01 , A61K38/47 , C12N9/2471 , C12N2799/026
摘要： A method for expressing and industrial scale production of recombinant lysosomal enzymes utilizing insect larva including the steps of infecting an insect larva population of the species Spodoptera littoralis via a recombinant baculovirus liquid suspension which permits the expression of at least one gene coding for a protein of interest, at least one of these genes coding for a lysosomal enzyme expressed in the insect larva, collecting of the previously infected insect larva expressing in a sufficient significant quantity the protein of interest and recovering the protein of interest from the collected insect larva.
摘要翻译：一种使用昆虫幼虫表达和工业规模生产重组溶酶体酶的方法，包括通过重组杆状病毒液体悬浮液感染种类斜纹夜蛾属的昆虫幼体群体的步骤，其允许表达至少一种编码感兴趣的蛋白质的基因，编码在昆虫幼虫中表达的溶酶体酶的这些基因中的至少一个，收集先前感染的昆虫幼虫，其以足够的显着量表达感兴趣的蛋白质，并从收集的昆虫幼虫中回收感兴趣的蛋白质。

90. 发明授权

US07622485B2 Method of enhancing lysosomal α-galactosidase A 有权
公开(公告)号：US07622485B2
公开(公告)日：2009-11-24
申请号：US10868133
申请日：2004-06-14
申请人： Jian-Qiang Fan , Satoshi Ishii
发明人： Jian-Qiang Fan , Satoshi Ishii
IPC分类号： A61K31/445 , A61K31/435 , C07D211/40 , C12N9/40
CPC分类号： A61K31/445 , A61K31/70 , A61K31/7008 , C07D451/06 , C12N9/2465
摘要： A method of enhancing the activity of lysosomal α-Galactosidase A (α-Gal A) in mammalian cells and for treatment of Fabry disease by administration of 1-deoxy-galactonojirimycin and related compounds.

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