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1. 发明申请

US20110281301A1 THE SECRETORY CAPACITY IN HOST CELLS 审中-公开
标题翻译：宿主细胞中的秘密能力
公开(公告)号：US20110281301A1
公开(公告)日：2011-11-17
申请号：US12742299
申请日：2008-10-06
申请人： Hitto Kaufmann , Eric Becker , Lore Florin , Barbara Enenkel , Kerstin Sautter , Rebecca Bischoff
发明人： Hitto Kaufmann , Eric Becker , Lore Florin , Barbara Enenkel , Kerstin Sautter , Rebecca Bischoff
IPC分类号： C12P21/00 , C12N5/10 , C12N15/85
CPC分类号： C12N5/0018 , C07K16/00 , C12N2501/48 , C12N2501/60 , C12N2510/02
摘要： The invention concerns the field of protein production and cell culture technology. It describes a method of producing a heterologous protein of interest in a cell comprising a. Increasing the expression or activity of a secretion enhancing gene, and b. Increasing the expression or activity of an anti-apoptotic gene, and c. Effecting the expression of said protein of interest, whereby the secretion enhancing gene is a gene encoding a protein whose expression or activity is induced during one of the following cellular processes: plasma-cell differentiation, unfolded protein response (UPR), endoplasmic reticulum overload response (EOR).
摘要翻译：本发明涉及蛋白质生产和细胞培养技术领域。它描述了在包含a的细胞中产生感兴趣的异源蛋白质的方法。增加分泌增强基因的表达或活性，b。增加抗凋亡基因的表达或活性，c。影响所述目的蛋白质的表达，由此分泌增强基因是编码在以下细胞过程之一期间诱导其表达或活性的蛋白质的基因：血浆细胞分化，展开的蛋白质应答（UPR），内质网过载反应（EOR）。

2. 发明申请

US20080300207A1 PROTEIN PRODUCTION 有权
标题翻译：蛋白质生产
公开(公告)号：US20080300207A1
公开(公告)日：2008-12-04
申请号：US12040198
申请日：2008-02-29
申请人： Hitto Kaufmann , Lore Florin , Eric Becker , Monilola Olayioye , Angelika Hausser , Tim Fugmann
发明人： Hitto Kaufmann , Lore Florin , Eric Becker , Monilola Olayioye , Angelika Hausser , Tim Fugmann
IPC分类号： A61K31/70 , C12P21/04 , C12N5/06 , C12N15/00 , C12N1/19 , A61P31/00 , C12Q1/02 , C12N5/04 , C07K7/00 , C07K16/18
CPC分类号： C12N15/63 , C07K14/435 , C07K14/47 , C07K14/4702 , C07K16/00 , C07K2319/036 , C12N15/67 , C12N15/85 , C12P21/00 , C12Q1/68 , G01N33/68
摘要： The invention concerns the field of protein production and cell culture technology. CERT is identified as a novel in vivo PKD substrate. Phosphorylation on serine 132 by PKD decreases the affinity of CERT towards its lipid target phosphatidylinositol 4-phosphate at Golgi membranes and reduces ceramide transfer activity, identifying PKD as a regulator of lipid homeostasis. The present invention shows that CERT in turn is critical for PKD activation and PKD dependent protein cargo transport to the plasma membrane. The interdependence of PKD and CERT is thus a key to the maintenance of Golgi membrane integrity and secretory transport.
摘要翻译：本发明涉及蛋白质生产和细胞培养技术领域。 CERT被确定为体内PKD底物的新颖。通过PKD在丝氨酸132上的磷酸化降低了CERT对高尔基体膜上的脂质靶磷脂酰肌醇4-磷酸的亲和力，降低了神经酰胺转移活性，鉴定了PKD作为脂质体内平衡的调节剂。本发明显示CERT又对于PKD激活和PKD依赖蛋白质运送到质膜的关键。因此，PKD和CERT的相互依存关系是维持高尔基体膜完整性和分泌转运的关键。

3. 发明授权

US08962312B2 Production host cell lines 有权
标题翻译：生产宿主细胞系
公开(公告)号：US08962312B2
公开(公告)日：2015-02-24
申请号：US12507252
申请日：2009-07-22
申请人： Hitto Kaufmann , Lore Florin , Eric Becker , Joey M. Studts
发明人： Hitto Kaufmann , Lore Florin , Eric Becker , Joey M. Studts
IPC分类号： C12N15/85 , C12P21/02 , C07K16/00 , C12N9/06 , C12N15/63
CPC分类号： C12P21/02 , C07K16/00 , C12N9/003
摘要： The invention concerns the field of cell culture technology. The invention describes production host cell lines comprising vector constructs comprising a DHFR expression cassette. Those cell lines have improved growth characteristics in comparison to DHFR-deficient or DHFR-reduced cell lines such as CHO DG44 and CHO DUKX-B11. The invention especially concerns two cell lines, a representative of each cell line is deposited with the DSMZ under the number DSM ACC2909 (CHOpper® Discovery) and DSM ACC2910 (CHOpper® Standard). The invention further concerns a method of producing proteins using the cells generated by the described method.
摘要翻译：本发明涉及细胞培养技术领域。本发明描述了包含载体构建体的生产宿主细胞系，其包含DHFR表达盒。与DHFR缺陷型或DHFR降低的细胞系如CHO DG44和CHO DUKX-B11相比，这些细胞系具有改善的生长特性。本发明特别涉及两种细胞系，每种细胞系的代表以DSM ACC2909（发现）和DSM ACC2910（标准品）的形式存放于DSMZ。本发明还涉及使用由所述方法产生的细胞产生蛋白质的方法。

4. 发明授权

US08535940B2 Cell growth 有权
标题翻译：细胞生长
公开(公告)号：US08535940B2
公开(公告)日：2013-09-17
申请号：US12524219
申请日：2008-01-22
申请人： Hitto Kaufmann , Lore Florin , Eric Becker
发明人： Hitto Kaufmann , Lore Florin , Eric Becker
IPC分类号： A61K39/395 , C12N5/10 , A61P35/00 , C12P21/00
CPC分类号： C12N5/0602 , C12N9/003 , C12N2501/70 , C12N2501/998 , C12N2510/02
摘要： The invention concerns the field of cell culture technology. It concerns a method of improving cell growth, especially the growth of biopharmaceutical producer host cells. The invention further concerns a method of producing proteins using the cells generated by the described method.
摘要翻译：本发明涉及细胞培养技术领域。它涉及改善细胞生长的方法，特别是生物制药生产者宿主细胞的生长。本发明还涉及使用由所述方法产生的细胞产生蛋白质的方法。

5. 发明申请

US20130177919A1 PROTEIN PRODUCTION 审中-公开
公开(公告)号：US20130177919A1
公开(公告)日：2013-07-11
申请号：US12528828
申请日：2008-02-29
申请人： Hitto Kaufmann , Lore Florin , Eric Becker , Monilola Olayioye , Angelika Hausser , Tim Fugmann
发明人： Hitto Kaufmann , Lore Florin , Eric Becker , Monilola Olayioye , Angelika Hausser , Tim Fugmann
IPC分类号： C12N15/85 , G01N33/68 , C12Q1/68 , C07K14/47 , C12P21/00
CPC分类号： C12N15/63 , C07K14/435 , C07K14/47 , C07K14/4702 , C07K16/00 , C07K2319/036 , C12N15/67 , C12N15/85 , C12P21/00 , C12Q1/68 , G01N33/68
摘要： The invention concerns the field of protein production and cell culture technology. CERT is identified as a novel in vivo PKD substrate. Phosphorylation on serine 132 by PKD decreases the affinity of CERT towards its lipid target phosphatidylinositol 4-phosphate at Golgi membranes and reduces ceramide transfer activity, identifying PKD as a regulator of lipid homeostasis. The present invention shows that CERT in turn is critical for PKD activation and PKD dependent protein cargo transport to the plasma membrane. The interdependence of PKD and CERT is thus a key to the maintenance of Golgi membrane integrity and secretory transport.

6. 发明申请

US20120100553A1 CHO/CERT CELL LINES 有权
标题翻译： CHO / CERT细胞系
公开(公告)号：US20120100553A1
公开(公告)日：2012-04-26
申请号：US13318509
申请日：2010-05-04
申请人： Lore Florin , Eric Becker , Hitto Kaufmann
发明人： Lore Florin , Eric Becker , Hitto Kaufmann
IPC分类号： C12N5/10 , C12P21/00 , C12Q1/68
CPC分类号： C07K14/47
摘要： The invention concerns the field of cell culture technology. The invention describes production host cell lines comprising vector constructs comprising a CERT S132 A expression cassette. Those cell lines have improved growth characteristics and high CERT S132A expression levels. The invention especially concerns two cell lines deposited with the DSMZ under the number DSM ACC2989 (CHO/CERT 2.20) and DSM AC-C2990 (CHO/CERT 2.41). The invention further concerns a method of generating such preferred production host cells and a method of producing proteins using the two cell lines deposited with the DSMZ under the number DSM ACC2989 (CHO/CERT 2.20) and DSM ACC2990 (CHO/CERT 2.41).
摘要翻译：本发明涉及细胞培养技术领域。本发明描述了包含载体构建体的生产宿主细胞系，其包含CERT S132A表达盒。这些细胞系具有改善的生长特性和较高的CERT S132A表达水平。本发明特别涉及以DSM ACC2989（CHO / CERT 2.20）和DSM AC-C2990（CHO / CERT 2.41）存放于DSMZ的两种细胞系。本发明还涉及产生这种优选的生产宿主细胞的方法，以及使用保藏在帝斯曼数据DSM ACC2989（CHO / CERT 2.20）和DSM ACC2990（CHO / CERT 2.41）上的DSMZ的两种细胞系产生蛋白质的方法。

7. 发明授权

US09340592B2 CHO/CERT cell lines 有权
标题翻译： CHO / CERT细胞系
公开(公告)号：US09340592B2
公开(公告)日：2016-05-17
申请号：US13318509
申请日：2010-05-04
申请人： Lore Florin , Eric Becker , Hitto Kaufmann
发明人： Lore Florin , Eric Becker , Hitto Kaufmann
IPC分类号： C12N15/85 , C12N15/63 , A61K31/711 , C12P21/08 , C07K14/47
CPC分类号： C07K14/47
摘要： The invention concerns the field of cell culture technology. The invention describes production host cell lines comprising vector constructs comprising a CERT S132 A expression cassette. Those cell lines have improved growth characteristics and high CERT S132A expression levels. The invention especially concerns two cell lines deposited with the DSMZ under the number DSM ACC2989 (CHO/CERT 2.20) and DSM AC-C2990 (CHO/CERT 2.41). The invention further concerns a method of generating such preferred production host cells and a method of producing proteins using the two cell lines deposited with the DSMZ under the number DSM ACC2989 (CHO/CERT 2.20) and DSM ACC2990 (CHO/CERT 2.41).
摘要翻译：本发明涉及细胞培养技术领域。本发明描述了包含载体构建体的生产宿主细胞系，其包含CERT S132A表达盒。这些细胞系具有改善的生长特性和较高的CERT S132A表达水平。本发明特别涉及以DSM ACC2989（CHO / CERT 2.20）和DSM AC-C2990（CHO / CERT 2.41）存放于DSMZ的两种细胞系。本发明还涉及产生这种优选的生产宿主细胞的方法，以及使用保藏在帝斯曼数据DSM ACC2989（CHO / CERT 2.20）和DSM ACC2990（CHO / CERT 2.41）上的DSMZ的两种细胞系产生蛋白质的方法。

8. 发明申请

US20100086967A1 CELL GROWTH 有权
标题翻译：细胞生长
公开(公告)号：US20100086967A1
公开(公告)日：2010-04-08
申请号：US12524219
申请日：2008-01-22
申请人： Hitto Kaufmann , Lore Florin , Eric Becker
发明人： Hitto Kaufmann , Lore Florin , Eric Becker
IPC分类号： C12P21/00 , C12N5/00 , C12N15/00 , C12N5/07
CPC分类号： C12N5/0602 , C12N9/003 , C12N2501/70 , C12N2501/998 , C12N2510/02
摘要： The invention concerns the field of cell culture technology. It concerns a method of improving cell growth, especially the growth of biopharmaceutical producer host cells. The invention further concerns a method of producing proteins using the cells generated by the described method.
摘要翻译：本发明涉及细胞培养技术领域。它涉及改善细胞生长的方法，特别是生物制药生产者宿主细胞的生长。本发明还涉及使用由所述方法产生的细胞产生蛋白质的方法。

9. 发明授权

US08221999B2 Protein production 有权
标题翻译：蛋白质生产
公开(公告)号：US08221999B2
公开(公告)日：2012-07-17
申请号：US12040198
申请日：2008-02-29
申请人： Hitto Kaufmann , Lore Florin , Eric Becker , Monilola Olayioye , Angelika Hausser , Tim Fugmann
发明人： Hitto Kaufmann , Lore Florin , Eric Becker , Monilola Olayioye , Angelika Hausser , Tim Fugmann
IPC分类号： C12P21/06
CPC分类号： C12N15/63 , C07K14/435 , C07K14/47 , C07K14/4702 , C07K16/00 , C07K2319/036 , C12N15/67 , C12N15/85 , C12P21/00 , C12Q1/68 , G01N33/68
摘要： The invention concerns the field of protein production and cell culture technology. CERT is identified as a novel in vivo PKD substrate. Phosphorylation on serine 132 by PKD decreases the affinity of CERT towards its lipid target phosphatidylinositol 4-phosphate at Golgi membranes and reduces ceramide transfer activity, identifying PKD as a regulator of lipid homeostasis. The present invention shows that CERT in turn is critical for PKD activation and PKD dependent protein cargo transport to the plasma membrane. The interdependence of PKD and CERT is thus a key to the maintenance of Golgi membrane integrity and secretory transport.
摘要翻译：本发明涉及蛋白质生产和细胞培养技术领域。 CERT被确定为体内PKD底物的新颖。通过PKD在丝氨酸132上的磷酸化降低了CERT对高尔基体膜上的脂质靶磷脂酰肌醇4-磷酸的亲和力，降低了神经酰胺转移活性，鉴定了PKD作为脂质体内平衡的调节剂。本发明显示CERT又对于PKD激活和PKD依赖蛋白质运送到质膜的关键。因此，PKD和CERT的相互依存关系是维持高尔基体膜完整性和分泌转运的关键。

10. 发明申请

US20090018099A1 PROTEIN PRODUCTION 审中-公开
标题翻译：蛋白质生产
公开(公告)号：US20090018099A1
公开(公告)日：2009-01-15
申请号：US12184626
申请日：2008-08-01
申请人： Hitto Kaufmann , Lore Florin , Eric Becker , Monilola Olayioye , Angelika Hausser , Tim Fugmann
发明人： Hitto Kaufmann , Lore Florin , Eric Becker , Monilola Olayioye , Angelika Hausser , Tim Fugmann
IPC分类号： A61K31/7105 , C12Q1/68 , C12N5/00 , A61P35/00
CPC分类号： C07K14/4702 , C07K16/00 , C07K2319/036 , C12N15/67 , C12N15/85
摘要： The invention concerns the field of protein production and cell culture technology. CERT is identified as a novel in vivo PKD substrate. Phosphorylation on serine 132 by PKD decreases the affinity of CERT towards its lipid target phosphatidylinositol 4-phosphate at Golgi membranes and reduces ceramide transfer activity, identifying PKD as a regulator of lipid homeostasis. The present invention shows that CERT in turn is critical for PKD activation and PKD dependent protein cargo transport to the plasma membrane. The interdependence of PKD and CERT is thus a key to the maintenance of Golgi membrane integrity and secretory transport.
摘要翻译：本发明涉及蛋白质生产和细胞培养技术领域。 CERT被确定为体内PKD底物的新颖。通过PKD在丝氨酸132上的磷酸化降低了CERT对高尔基体膜上的脂质靶磷脂酰肌醇4-磷酸的亲和力，降低了神经酰胺转移活性，鉴定了PKD作为脂质体内平衡的调节剂。本发明显示CERT又对于PKD激活和PKD依赖蛋白质运送到质膜的关键。因此，PKD和CERT的相互依存关系是维持高尔基体膜完整性和分泌转运的关键。

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