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1. 发明申请

US20060252096A1 Single chain antibody with cleavable linker 审中-公开
标题翻译：具有可切割连接子的单链抗体
公开(公告)号：US20060252096A1
公开(公告)日：2006-11-09
申请号：US11411436
申请日：2006-04-25
申请人： Dongxing Zha , Byung-Kwon Choi , Tillman Gerngross
发明人： Dongxing Zha , Byung-Kwon Choi , Tillman Gerngross
IPC分类号： G01N33/53 , C07H21/04 , C12P21/06 , C12N1/18 , C07K16/44 , C12N15/74
CPC分类号： G01N33/531 , C07K16/00 , C07K2317/41 , C07K2317/50 , C07K2317/52 , C07K2317/56 , C07K2317/622 , C07K2319/00 , C07K2319/02 , C07K2319/50
摘要： Disclosed are antibodies and methods for making antibodies with desired glycosylation and efficient production. Host cells transformed with a nucleic acid encoding a fusion protein comprising a signal sequence, light and heavy immunoglobulin chains, each comprising a variable region and a constant region and separated by a spacer peptide comprising at least one proteolytic cleavage site are cultured to express the nucleic acids and are cleaved by appropriate proteases to produce antibodies.
摘要翻译：公开了用于制备具有所需糖基化和有效生产的抗体的抗体和方法。培养用编码融合蛋白的核酸转化的宿主细胞，其包含信号序列轻链和重免疫球蛋白链，每个包含可变区和恒定区，并由包含至少一个蛋白水解切割位点的间隔肽分离，以表达核酸酸，并被适当的蛋白酶切割以产生抗体。

2. 发明申请

US20060040353A1 Production of galactosylated glycoproteins in lower eukaryotes 有权
标题翻译：低等真核生物中半乳糖基化糖蛋白的产生
公开(公告)号：US20060040353A1
公开(公告)日：2006-02-23
申请号：US11108088
申请日：2005-04-15
申请人： Robert Davidson , Tillman Gerngross , Stefan Wildt , Byung-Kwon Choi , Juergen Nett , Piotr Bobrowicz , Stephen Hamilton
发明人： Robert Davidson , Tillman Gerngross , Stefan Wildt , Byung-Kwon Choi , Juergen Nett , Piotr Bobrowicz , Stephen Hamilton
IPC分类号： C07H21/04 , C12P21/06 , C12P19/28 , C12N9/10 , C12N1/18 , C12N15/74
CPC分类号： C12P21/005 , C12N9/1051 , C12N15/1082 , C12N15/79 , Y10S435/911
摘要： The present invention provides a novel lower eukaryotic host cell producing human-like glycoproteins characterized as having a terminal β-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.
摘要翻译：本发明提供了一种产生人样糖蛋白的新型低级真核宿主细胞，其特征在于具有末端β-半乳糖残基并且基本上缺乏岩藻糖和唾液酸残基。本发明还提供了一种催化将半乳糖残基从UDP-半乳糖转移到可用作治疗性糖蛋白的重组低等真核宿主细胞中的受体底物上的方法。

3. 发明授权

US08815544B2 Production of galactosylated glycoproteins in lower eukaryotes 有权
标题翻译：低等真核生物中半乳糖基化糖蛋白的产生
公开(公告)号：US08815544B2
公开(公告)日：2014-08-26
申请号：US12840529
申请日：2010-07-21
申请人： Robert Davidson , Tillman Gerngross , Stefan Wildt , Byung-Kwon Choi , Juergen Hermann Nett , Piotr Bobrowicz , Stephen Robin Hamilton
发明人： Robert Davidson , Tillman Gerngross , Stefan Wildt , Byung-Kwon Choi , Juergen Hermann Nett , Piotr Bobrowicz , Stephen Robin Hamilton
IPC分类号： C12P21/02 , C12P19/04 , A61K38/00
CPC分类号： C12P21/005 , C12N9/1051 , C12N15/1082 , C12N15/79 , Y10S435/911
摘要： The present invention provides a novel lower eukaryotic host cell producing human-like glycoproteins characterized as having a terminal β-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.
摘要翻译：本发明提供了一种产生人类糖蛋白的新型低级真核宿主细胞，其特征在于具有末端半乳糖残基并且基本上缺乏岩藻糖和唾液酸残基。本发明还提供了一种催化将半乳糖残基从UDP-半乳糖转移到可用作治疗性糖蛋白的重组低等真核宿主细胞中的受体底物上的方法。

4. 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。

5. 发明申请

US20050265988A1 Glycosylated glucocerebrosidase expression in fungal hosts 审中-公开
标题翻译：真菌宿主中糖基化葡糖脑苷脂酶的表达
公开(公告)号：US20050265988A1
公开(公告)日：2005-12-01
申请号：US11083446
申请日：2005-03-18
申请人： Byung-Kwon Choi , Sandra Rios , Stefan Wildt , Tillman Gerngross
发明人： Byung-Kwon Choi , Sandra Rios , Stefan Wildt , Tillman Gerngross
IPC分类号： A61K38/47 , C07H21/04 , C12N1/18 , C12N9/24 , C12N15/74 , C12P21/06
CPC分类号： A61K38/47 , C12N9/2402 , C12Y302/01045
摘要： A recombinant fungal host cell producing recombinant glucocerebrosidase is provided. A functional recombinant glucocerebrosidase produced in recombinant fungal host cells is also provided. Methods for producing and isolating functional recombinant glucocerebrosidase from fungal hosts are also provided.
摘要翻译：提供了重组真菌宿主细胞产生重组葡糖脑苷脂酶。还提供了在重组真菌宿主细胞中产生的功能性重组葡糖脑苷脂酶。还提供了从真菌宿主生产和分离功能性重组葡糖脑苷脂酶的方法。

6. 发明授权

US08445227B2 N-acetylglucosaminyltransferase III expression in lower eukaryotes 有权
公开(公告)号：US08445227B2
公开(公告)日：2013-05-21
申请号：US12540849
申请日：2009-08-13
申请人： Piotr Bobrowicz , Stephen R. Hamilton , Tillman U. Gerngross , Stefan Wildt , Byung-Kwon Choi , Juergen Hermann Nett , Robert C. Davidson
发明人： Piotr Bobrowicz , Stephen R. Hamilton , Tillman U. Gerngross , Stefan Wildt , Byung-Kwon Choi , Juergen Hermann Nett , Robert C. Davidson
IPC分类号： C12N15/00
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.

7. 发明授权

US07795002B2 Production of galactosylated glycoproteins in lower eukaryotes 有权
标题翻译：低等真核生物中半乳糖基化糖蛋白的产生
公开(公告)号：US07795002B2
公开(公告)日：2010-09-14
申请号：US11108088
申请日：2005-04-15
申请人： Robert Davidson , Tillman Ulf Gerngross , Stefan Wildt , Byung-Kwon Choi , Juergen Hermann Nett , Piotr Bobrowicz , Stephen Robin Hamilton
发明人： Robert Davidson , Tillman Ulf Gerngross , Stefan Wildt , Byung-Kwon Choi , Juergen Hermann Nett , Piotr Bobrowicz , Stephen Robin Hamilton
IPC分类号： C12N15/04 , A61K38/00
CPC分类号： C12P21/005 , C12N9/1051 , C12N15/1082 , C12N15/79 , Y10S435/911
摘要： The present invention provides a novel lower eukaryotic host cell producing human-like glycoproteins characterized as having a terminal β-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.
摘要翻译：本发明提供了一种产生人类糖蛋白的新型低级真核宿主细胞，其特征在于具有末端半乳糖残基并且基本上缺乏岩藻糖和唾液酸残基。本发明还提供了一种催化将半乳糖残基从UDP-半乳糖转移到可用作治疗性糖蛋白的重组低等真核宿主细胞中的受体底物上的方法。

8. 发明申请

US20100016561A1 N-Acetylglucosaminyltransferase III Expression in Lower Eukaryotes 有权
公开(公告)号：US20100016561A1
公开(公告)日：2010-01-21
申请号：US12540849
申请日：2009-08-13
申请人： Piotr Bobrowicz , Stephen R. Hamilton , Tillman U. Gerngross , Stefan Wildt , Byung-Kwon Choi , Juergen Hermann Nett , Robert C. Davidson
发明人： Piotr Bobrowicz , Stephen R. Hamilton , Tillman U. Gerngross , Stefan Wildt , Byung-Kwon Choi , Juergen Hermann Nett , Robert C. Davidson
IPC分类号： C07K14/00 , 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.

9. 发明申请

US20090155847A1 Combinatorial DNA library for producing modified N-glycans in lower eukaryotes 有权
公开(公告)号：US20090155847A1
公开(公告)日：2009-06-18
申请号：US12291373
申请日：2008-11-07
申请人： Tillman U. Gerngross , Stefan Wildt , Byung-Kwon Choi , Juergen Hermann Nett , Piotr Bobrowicz , Stephen R. Hamilton , Robert C. Davidson
发明人： Tillman U. Gerngross , Stefan Wildt , Byung-Kwon Choi , Juergen Hermann Nett , Piotr Bobrowicz , Stephen R. Hamilton , Robert C. Davidson
IPC分类号： C12P21/00
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.

10. 发明授权

US07449308B2 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：US07449308B2
公开(公告)日：2008-11-11
申请号：US10371877
申请日：2003-02-20
申请人： Tillman U. Gerngross , Stefan Wildt , Byung-Kwon Choi , Juergen Hermann Nett , Piotr Bobrowicz , Stephen R. Hamilton , Robert C. Davidson
发明人： Tillman U. Gerngross , Stefan Wildt , Byung-Kwon Choi , Juergen Hermann Nett , Piotr Bobrowicz , Stephen R. Hamilton , Robert C. Davidson
IPC分类号： C12N15/00
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。在工程化的宿主细胞中制备的N-聚糖具有可以通过异源表达一种或多种酶（例如糖基转移酶）而进一步修饰的Man III / 糖转运蛋白和甘露糖苷酶，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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