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1. 发明授权

EP1747280B1 METHODS FOR REDUCING OR ELIMINATING ALPHA-MANNOSIDASE RESISTANT GLYCANS IN THE PRODUCTION OF GLYCOPROTEINS 有权
标题翻译：在糖蛋白生产中减少或消除α-甘露糖苷酶抗性甘油的方法
公开(公告)号：EP1747280B1
公开(公告)日：2018-01-17
申请号：EP05731774.5
申请日：2005-04-29
申请人： GlycoFi, Inc.
发明人： BOBROWICZ, Piotr
IPC分类号： C12P21/00 , C12N15/80 , C12N9/10 , C07K14/39
CPC分类号： C07K14/39 , C12N9/1051 , C12N15/80 , C12P21/005
摘要： The present invention provides methods to reduce or eliminate alpha-mannosidase resistant glycans on glycoproteins in yeast. The reduction or elimination of alpha-mannosidase resistant glycans on glycoproteins results from the disruption of the newly isolated P. pastoris AMR2 gene encoding beta1,2-mannosyltransferase. The present invention also discloses novel genes, polypeptides, antibodies, vectors and host cells relating to alpha-mannosidase resistance on glycans.

2. 发明授权

EP2285404B1 YEAST STRAIN FOR THE PRODUCTION OF PROTEINS WITH TERMINAL ALPHA-1,3-LINKED GALACTOSE 有权
标题翻译：酵母菌株用于生产具有末端α-1,3-连接的半乳糖蛋白
公开(公告)号：EP2285404B1
公开(公告)日：2016-12-21
申请号：EP09755723.5
申请日：2009-05-28
申请人： GlycoFi, Inc.
发明人： SETHURAMAN, Natarajan , DAVIDSON, Robert, C. , STADHEIM, Terrance, A. , WILDT, Stefan
IPC分类号： A61K39/00 , A61K39/395 , C07K16/22 , C07K16/24 , C07K16/28 , C12N15/09 , C12N15/10 , C12P21/00
CPC分类号： C07K14/435 , C12N15/80 , C12P21/005
摘要： Lower eukaryotic host cells have been engineered to produce glycoprotein having at least one terminal α-galactosyl epitope. The glycoproteins are useful for the production of highly antigenic glycoprotein compositions with advantages for the production of vaccines.

3. 发明授权

EP2333096B1 Expression of class 2 mannosidase and class III mannosidase in lower eukaryotic cells 失效
公开(公告)号：EP2333096B1
公开(公告)日：2013-10-16
申请号：EP10012603.6
申请日：2004-02-20
申请人： GlycoFi, Inc.
发明人： Hamilton, Stephen R.
IPC分类号： C12P21/00 , C12N9/10 , C12N9/24 , C12N1/14 , C12N5/10 , C12R1/645
CPC分类号： C12P21/005 , A01K2217/075 , C12N9/1051 , C12N9/2488 , C12N15/79 , C12Y302/01024 , C12Y302/01114

4. 发明公开

EP1737969A4 PRODUCTION OF GALACTOSYLATED GLYCOPROTEINS IN LOWER EUKARYOTES 有权
标题翻译：生产GALAKTOSYLIERTER糖蛋白低等真核生物
公开(公告)号：EP1737969A4
公开(公告)日：2011-09-28
申请号：EP05732293
申请日：2005-04-15
申请人： GLYCOFI INC
发明人： DAVIDSON ROBERT , GERNGROSS TILLMAN , WILDT STEFAN , CHOI BYUNG-KWON , NETT JUERGEN , BOBROWICZ PIOTR , HAMILTON STEPHEN
IPC分类号： C12N1/19 , C07K16/00 , C12N1/18 , C12N9/10 , C12N9/90 , C12P21/00 , C12P21/06
CPC分类号： C12N9/1051 , C12N9/90 , C12P21/005
摘要： The present invention provides a novel lower eukaryotic host cell producing human-like glycoproteins characterized as having a terminal beta-galactose residue and essentially lacking fucose and sialic acid residues. The present invention also provides a method for catalyzing the transfer of a galactose residue from UDP-galactose onto an acceptor substrate in a recombinant lower eukaryotic host cell, which can be used as a therapeutic glycoprotein.

5. 发明公开

EP2341128A1 Methods for eliminating mannosylphosphorylation of glycans in the production of glycoproteins 审中-公开
标题翻译： Verfahren zur Elimination der Mannosylphosphorylierung von Glykanen bei der Herstellung von Glykoproteinen
公开(公告)号：EP2341128A1
公开(公告)日：2011-07-06
申请号：EP10180809.5
申请日：2004-12-22
申请人： GlycoFi, Inc.
发明人： Bobrowicz, Piotr , Stadheim, Terrance , Wildt, Stefan
IPC分类号： C12N1/15 , C12N1/19
CPC分类号： C12N9/1051 , C07K14/39 , C12P21/005
摘要： The present invention relates to the elimination of mannosylphosphorylation on the glycans of glycoproteins in the yeast genus Pichia. The elimination of mannosylphosphorylated glycoproteins results from the disruption of the PNO1 gene and the newly isolated P. pastoris MNN4B gene. The present invention further relates to methods for producing modified glycan structures in host cells that are free of glycan mannosylphosphorylation.
摘要翻译：本发明涉及消除毕赤酵母中糖蛋白聚糖上的甘露糖基磷酸化。消除甘露糖基磷酸化糖蛋白是由PNO1基因和新分离的巴斯德毕赤酵母MNN4B基因的破坏引起的。本发明还涉及在不含聚糖甘露糖基磷酸化的宿主细胞中产生修饰聚糖结构的方法。

6. 发明公开

EP2339013A1 Methods for producing modified glycoproteins 有权
标题翻译：生产修饰糖蛋白的方法
公开(公告)号：EP2339013A1
公开(公告)日：2011-06-29
申请号：EP10012383.5
申请日：2001-06-27
申请人： GlycoFi, Inc.
发明人： Gerngross, Tilman U.
IPC分类号： C12P21/00 , C12N9/10 , C12N9/24 , C12N1/14 , C12N5/10 , C12R1/645
CPC分类号： C12P21/005 , C07K2319/04 , C07K2319/05 , C12N1/14 , C12N9/1048 , C12N9/2488 , C12N15/79 , C12N15/80 , C12N15/81 , C12Y302/01 , C12Y302/01113
摘要： Cell lines having genetically modified glycosylation pathways that allow them to carry out a sequence of enzymatic reactions, which mimic the processing of glycoproteins in humans, have been developed. Recombinant proteins expressed in these engineered hosts yield glycoproteins more similar, if not substantially identical to their human counterparts. The lower eukaryotes, which ordinarily produce high-mannose containing N-glycans, including unicellular and multicellular fungi are modified to produce N-glycans such as Man 5 GlcNAc 2 or other structures along human glycosylation pathways. This is achieved using a combination of engineering and/or selection of strains which: do not express certain enzymes which create the undesirable complex structures characteristic of the fungal glycoproteins, which express exogenous enzymes selected either to have optimal activity under the conditions present in the fungi where activity is desired, or which are targeted to an organelle where optimal activity is achieved, and combinations thereof wherein the genetically engineered eukaryote expresses multiple exogenous enzymes required to produce "human-like" glycoproteins.
摘要翻译：已经开发了具有遗传修饰的糖基化途径的细胞系，其使得它们能够进行模拟糖蛋白在人类中的加工的一系列酶促反应。在这些工程宿主中表达的重组蛋白质产生的糖蛋白与它们的人类对应物如果不是基本相同，则它们更相似。通常产生含高甘露糖的N-聚糖（包括单细胞和多细胞真菌）的低等真核生物被修饰以产生N-聚糖，例如Man5GlcNAc2或沿着人糖基化途径的其他结构。这是通过工程和/或选择菌株来实现的：不表达某些产生真菌糖蛋白特征的不希望的复合结构的酶，所述真菌糖蛋白表达选择在真菌存在条件下具有最佳活性的外源酶其中需要活性或靶向实现最佳活性的细胞器及其组合，其中所述基因工程真核生物表达产生“人样”糖蛋白所需的多种外源酶。

7. 发明公开

EP2324121A1 IMPROVED VECTORS AND YEAST STRAINS FOR PROTEIN PRODUCTION: CA2+ ATPASE OVEREXPRESSION 有权
标题翻译：改进的载体和蛋白生产酵母菌株：钙+ -ATP酶过度表达
公开(公告)号：EP2324121A1
公开(公告)日：2011-05-25
申请号：EP09791322.2
申请日：2009-08-10
申请人： GlycoFi, Inc.
发明人： CHOI, Byung-Kwon
IPC分类号： C12P21/00 , C12N5/10 , C12N15/81
CPC分类号： C07K16/00 , C12N15/815 , C12P21/005
摘要： Lower eukaryote host cells in which an endogenous or heterologous Ca
2+ ATPase is overexpressed are described. Also described are lower eukaryote host cells in which a calreticulin and/or ERp57 protein are overexpressed. These host cells are useful for producing recombinant glycoproteins that have reduced
O -glycosylation.

8. 发明公开

EP2316963A1 Combinatorial DNA library for producing modified N-glycans in lower eukaryotes 有权
标题翻译：制造的组合DNA文库修饰的N-葡聚糖在低等真核生物
公开(公告)号：EP2316963A1
公开(公告)日：2011-05-04
申请号：EP10013052.5
申请日：2004-02-20
申请人： GlycoFi, Inc.
发明人： Gerngross, Tillman U. , Wildt, Stefan , Choi, Byung-Kwon , Nett, Juergen Hermann , Bobrowicz, Piotr , Hamilton, Stephen R. , Davidson, Robert C.
IPC分类号： C12P21/00 , C12N9/10 , C12N9/24 , C12N1/14 , C12N5/10 , C12R1/645
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.

9. 发明公开

EP2235198A4 YEAST STRAINS FOR PROTEIN PRODUCTION 有权
标题翻译： Hefestämmefürdie Proteinproduktion
公开(公告)号：EP2235198A4
公开(公告)日：2011-01-05
申请号：EP08867314
申请日：2008-12-15
申请人： GLYCOFI INC
发明人： NETT JUERGEN
IPC分类号： C12P21/06 , C12N15/81 , C12N15/90
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：公开了基于酵母和真菌的ade1和ade2营养缺陷型菌株的表达系统的方法和系统，包括巴斯德毕赤酵母。表达系统可用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。

10. 发明公开

EP1954815A4 PRODUCTION OF GLYCOPROTEINS WITH REDUCED O-GLYCOSYLATION 有权
标题翻译：具有减少的O-糖基化糖蛋白MANUFACTURING
公开(公告)号：EP1954815A4
公开(公告)日：2010-07-07
申请号：EP06837184
申请日：2006-11-10
申请人： GLYCOFI INC
发明人： BOBROWICZ PIOTR , COOK JAMES W , KETT WARREN
IPC分类号： C12N1/15 , A61K38/00 , C12N1/16 , C12N1/19
CPC分类号： C07K16/32 , C07K2317/41 , C12P21/005

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