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1. 发明授权

US07563441B2 Anti-P-selectin antibodies 有权
标题翻译：抗P-选择素抗体
公开(公告)号：US07563441B2
公开(公告)日：2009-07-21
申请号：US11102403
申请日：2005-04-08
申请人： Yvo Graus , Jacques Himber , Miranda Jansen-Molenaar , Dorothee Kling , Erhard Kopetzki , Paul Parren , Frank Rebers , Beat Steiner , Anne Stern , Pamela Strein , Kay-Gunnar Stubenrauch , Jan van de Winkel , Martine van Vugt
发明人： Yvo Graus , Jacques Himber , Miranda Jansen-Molenaar , Dorothee Kling , Erhard Kopetzki , Paul Parren , Frank Rebers , Beat Steiner , Anne Stern , Pamela Strein , Kay-Gunnar Stubenrauch , Jan van de Winkel , Martine van Vugt
IPC分类号： A61K39/395 , C07K16/28
CPC分类号： C07K16/2854 , C07K2317/21 , C07K2317/52 , C07K2317/56 , C07K2317/565 , C07K2317/76 , C07K2317/92 , Y10S435/81
摘要： This invention relates to anti-P-selectin antibodies and, in particular, to anti-P-selectin antibodies and variants thereof that contain an Fc part derived from human origin and do not bind complement factor C1q. These antibodies have new and inventive properties causing a benefit for a patient suffering from critical limb ischemia or peripheral arterial occlusive disease (CLI/PAOD).
摘要翻译：本发明涉及抗P-选择素抗体，特别涉及含有源自人源的Fc部分并且不结合补体因子C1q的抗P-选择素抗体及其变体。这些抗体具有新的和本发明的性质，为患有严重肢体缺血或外周动脉闭塞性疾病（CLI / PAOD）的患者带来益处。

2. 发明授权

US07824684B2 Methods of inhibiting the binding of P-selectin to PSGL-1 with anti-P-selectin antibodies 有权
标题翻译：用抗P-选择蛋白抗体抑制P-选择素与PSGL-1结合的方法
公开(公告)号：US07824684B2
公开(公告)日：2010-11-02
申请号：US12768150
申请日：2010-04-27
申请人： Yvo Graus , Jacques Himber , Miranda Jansen-Molenaar , Dorothee Kling , Erhard Kopetzki , Paul Parren , Frank Rebers , Beat Steiner , Anne Stern , Pamela Strein , Kay-Gunnar Stubenrauch , Jan van de Winkel , Martine van Vugt
发明人： Yvo Graus , Jacques Himber , Miranda Jansen-Molenaar , Dorothee Kling , Erhard Kopetzki , Paul Parren , Frank Rebers , Beat Steiner , Anne Stern , Pamela Strein , Kay-Gunnar Stubenrauch , Jan van de Winkel , Martine van Vugt
IPC分类号： A61K39/395 , C07K16/28
CPC分类号： C07K16/2854 , C07K2317/21 , C07K2317/52 , C07K2317/56 , C07K2317/565 , C07K2317/76 , C07K2317/92 , Y10S435/81
摘要： This invention relates to anti-P-selectin antibodies and, in particular, to anti-P-selectin antibodies and variants thereof that contain an Fc part derived from human origin and do not bind complement factor C1q. These antibodies have new and inventive properties causing a benefit for a patient suffering from critical limb ischemia or peripheral arterial occlusive disease (CLI/PAOD).
摘要翻译：本发明涉及抗P-选择素抗体，特别涉及含有源自人源的Fc部分并且不结合补体因子C1q的抗P-选择素抗体及其变体。这些抗体具有新的和本发明的性质，为患有严重肢体缺血或外周动脉闭塞性疾病（CLI / PAOD）的患者带来益处。

3. 发明申请

US20050226876A1 Anti-P-selectin antibodies 有权
标题翻译：抗P-选择素抗体
公开(公告)号：US20050226876A1
公开(公告)日：2005-10-13
申请号：US11102403
申请日：2005-04-08
申请人： Yvo Graus , Jacques Himber , Miranda Jansen-Molenaar , Dorothee Kling , Erhard Kopetzki , Paul Parren , Frank Rebers , Beat Steiner , Anne Stern , Pamela Strein , Kay-Gunnar Stubenrauch , Jan van de Winkel , Martine van Vugt
发明人： Yvo Graus , Jacques Himber , Miranda Jansen-Molenaar , Dorothee Kling , Erhard Kopetzki , Paul Parren , Frank Rebers , Beat Steiner , Anne Stern , Pamela Strein , Kay-Gunnar Stubenrauch , Jan van de Winkel , Martine van Vugt
IPC分类号： A61K39/395 , C07K16/28 , C07K16/46 , C07H21/04 , C12N5/06 , C12N15/09
CPC分类号： C07K16/2854 , C07K2317/21 , C07K2317/52 , C07K2317/56 , C07K2317/565 , C07K2317/76 , C07K2317/92 , Y10S435/81
摘要： This invention relates to anti-P-selectin antibodies and, in particular, to anti-P-selectin antibodies and variants thereof that contain an Fc part derived from human origin and do not bind complement factor C1q. These antibodies have new and inventive properties causing a benefit for a patient suffering from critical limb ischemia or peripheral arterial occlusive disease (CLI/PAOD).
摘要翻译：本发明涉及抗P-选择素抗体，特别涉及含有源自人源的Fc部分并且不结合补体因子C1q的抗P-选择素抗体及其变体。这些抗体具有新的和本发明的性质，为患有严重肢体缺血或外周动脉闭塞性疾病（CLI / PAOD）的患者带来益处。

4. 再颁专利

USRE43568E1 Anti-P-selectin antibodies 有权
标题翻译：抗P-选择素抗体
公开(公告)号：USRE43568E1
公开(公告)日：2012-08-07
申请号：US13187586
申请日：2011-07-21
申请人： Yvo Graus , Jacques Himber , Miranda Jansen-Molenaar , Dorothee Kling , Erhard Kopetzki , Paul Parren , Frank Rebers , Beat Steiner , Anne Stern , Pamela Strein , Kay-Gunnar Stubenrauch , Jan Van de Winkel , Martine Van Vugt
发明人： Yvo Graus , Jacques Himber , Miranda Jansen-Molenaar , Dorothee Kling , Erhard Kopetzki , Paul Parren , Frank Rebers , Beat Steiner , Anne Stern , Pamela Strein , Kay-Gunnar Stubenrauch , Jan Van de Winkel , Martine Van Vugt
IPC分类号： A61K39/395 , C07K16/28
CPC分类号： C07K16/2854 , C07K2317/21 , C07K2317/52 , C07K2317/56 , C07K2317/565 , C07K2317/76 , C07K2317/92 , Y10S435/81
摘要： This invention relates to anti-P-selectin antibodies and, in particular, to anti-P-selectin antibodies and variants thereof that contain an Fc part derived from human origin and do not bind complement factor C1q. These antibodies have new and inventive properties causing a benefit for a patient suffering from critical limb ischemia or peripheral arterial occlusive disease (CLI/PAOD).
摘要翻译：本发明涉及抗P-选择素抗体，特别涉及含有源自人源的Fc部分并且不结合补体因子C1q的抗P-选择素抗体及其变体。这些抗体具有新的和本发明的性质，为患有严重肢体缺血或外周动脉闭塞性疾病（CLI / PAOD）的患者带来益处。

5. 发明授权

US07754867B2 Nucleic acid molecules encoding anti-P-selectin antibodies 有权
标题翻译：编码抗P-选择蛋白抗体的核酸分子
公开(公告)号：US07754867B2
公开(公告)日：2010-07-13
申请号：US12481623
申请日：2009-06-10
申请人： Yvo Graus , Jacques Himber , Miranda Jansen-Molenaar , Dorothee Kling , Erhard Kopetzki , Paul Parren , Frank Rebers , Beat Steiner , Anne Stern , Pamela Strein , Kay-Gunnar Stubenrauch , Jan van de Winkel , Martine van Vugt
发明人： Yvo Graus , Jacques Himber , Miranda Jansen-Molenaar , Dorothee Kling , Erhard Kopetzki , Paul Parren , Frank Rebers , Beat Steiner , Anne Stern , Pamela Strein , Kay-Gunnar Stubenrauch , Jan van de Winkel , Martine van Vugt
IPC分类号： C12N15/13 , C12N15/12 , C12N15/63 , C12N5/10
CPC分类号： C07K16/2854 , C07K2317/21 , C07K2317/52 , C07K2317/56 , C07K2317/565 , C07K2317/76 , C07K2317/92 , Y10S435/81
摘要： This invention relates to anti-P-selectin antibodies and, in particular, to anti-P-selectin antibodies and variants thereof that contain an Fc part derived from human origin and do not bind complement factor C1q. These antibodies have new and inventive properties causing a benefit for a patient suffering from critical limb ischemia or peripheral arterial occlusive disease (CLI/PAOD).
摘要翻译：本发明涉及抗P-选择素抗体，特别涉及含有源自人源的Fc部分并且不结合补体因子C1q的抗P-选择素抗体及其变体。这些抗体具有新的和本发明的性质，为患有严重肢体缺血或外周动脉闭塞性疾病（CLI / PAOD）的患者带来益处。

6. 发明申请

US20090311779A1 ANTI-P-SELECTIN ANTIBODIES 有权
标题翻译：抗P-选择素抗体
公开(公告)号：US20090311779A1
公开(公告)日：2009-12-17
申请号：US12481623
申请日：2009-06-10
申请人： Yvo Graus , Jacques Himber , Miranda Jansen-Molenaar , Dorothee Kling , Erhard Kopetzki , Paul Parren , Frank Rebers , Beat Steiner , Anne Stern , Pamela Strein , Kay-Gunnar Stubenrauch , Jan van de Winkel , Martine van Vugt
发明人： Yvo Graus , Jacques Himber , Miranda Jansen-Molenaar , Dorothee Kling , Erhard Kopetzki , Paul Parren , Frank Rebers , Beat Steiner , Anne Stern , Pamela Strein , Kay-Gunnar Stubenrauch , Jan van de Winkel , Martine van Vugt
IPC分类号： C12N5/10 , C07H21/04 , C12N15/63
CPC分类号： C07K16/2854 , C07K2317/21 , C07K2317/52 , C07K2317/56 , C07K2317/565 , C07K2317/76 , C07K2317/92 , Y10S435/81
摘要： This invention relates to anti-P-selectin antibodies and, in particular, to anti-P-selectin antibodies and variants thereof that contain an Fc part derived from human origin and do not bind complement factor C1q. These antibodies have new and inventive properties causing a benefit for a patient suffering from critical limb ischemia or peripheral arterial occlusive disease (CLI/PAOD).
摘要翻译：本发明涉及抗P-选择素抗体，特别涉及含有源自人源的Fc部分并且不结合补体因子C1q的抗P-选择素抗体及其变体。这些抗体具有新的和本发明的性质，为患有严重肢体缺血或外周动脉闭塞性疾病（CLI / PAOD）的患者带来益处。

7. 再颁专利

USRE44359E1 Nucleic acid molecules encoding anti-P-selectin antibodies 有权
标题翻译：编码抗P-选择蛋白抗体的核酸分子
公开(公告)号：USRE44359E1
公开(公告)日：2013-07-09
申请号：US13471899
申请日：2012-05-15
申请人： Yvo Graus , Jacques Himber , Miranda Jansen-Molenaar , Dorothee Kling , Erhard Kopetzki , Paul Parren , Frank Rebers , Beat Steiner , Anne Stern , Pamela Braemer , Kay-Gunnar Stubenrauch , Jan van de Winkel , Martine van Vugt
发明人： Yvo Graus , Jacques Himber , Miranda Jansen-Molenaar , Dorothee Kling , Erhard Kopetzki , Paul Parren , Frank Rebers , Beat Steiner , Anne Stern , Pamela Braemer , Kay-Gunnar Stubenrauch , Jan van de Winkel , Martine van Vugt
IPC分类号： C12N15/13 , C12N15/12 , C12N15/63 , C12N5/10
CPC分类号： C07K16/2854 , C07K2317/21 , C07K2317/52 , C07K2317/56 , C07K2317/565 , C07K2317/76 , C07K2317/92 , Y10S435/81
摘要： This invention relates to anti-P-selectin antibodies and, in particular, to anti-P-selectin antibodies and variants thereof that contain an Fc part derived from human origin and do not bind complement factor C1q. These antibodies have new and inventive properties causing a benefit for a patient suffering from critical limb ischemia or peripheral arterial occlusive disease (CLI/PAOD).
摘要翻译：本发明涉及抗P-选凝素抗体，特别涉及含有源自人源的Fc部分并且不结合补体因子C1q的抗P-选择蛋白抗体及其变体。这些抗体具有新的和本发明的性质，为患有严重肢体缺血或外周动脉闭塞性疾病（CLI / PAOD）的患者带来益处。

8. 发明申请

US20100249379A1 PROTEIN EXPRESSION FROM MULTIPLE NUCLEIC ACIDS 有权
标题翻译：来自多种核酸的蛋白质表达
公开(公告)号：US20100249379A1
公开(公告)日：2010-09-30
申请号：US12681781
申请日：2008-10-09
申请人： Ulrich Goepfert , Hendrik Knoetgen , Erhard Kopetzki , Anne Stern
发明人： Ulrich Goepfert , Hendrik Knoetgen , Erhard Kopetzki , Anne Stern
IPC分类号： C07K16/28 , C12P21/08
CPC分类号： C12N15/85 , C07K16/18 , C07K16/28 , C07K16/2812 , C07K16/2854 , C07K16/2866 , C07K16/2896 , C07K2317/14 , C07K2317/21 , C07K2317/51 , C07K2317/515 , C12P21/00
摘要： The current invention reports a method for the recombinant production of a secreted heterologous immunoglobulin in a CHO cell comprising the following steps: i) providing a CHO cell, which is adapted to growth in suspension culture, adapted to growth in serum-free medium, mycoplasma free, and virus free, ii) providing a vector comprising a prokaryotic origin of replication, a first nucleic acid conferring resistance to a prokaryotic selection agent, a second nucleic acid encoding the heavy chain of said heterologous immunoglobulin, a third nucleic acid encoding the light chain of said heterologous immunoglobulin, a fourth nucleic acid conferring resistance to a eukaryotic selection agent, iii) transfecting said CHO cell, wherein said transfecting comprises a) transfecting said CHO cell with said vector comprising a fourth nucleic acid conferring resistance to a first eukaryotic selection agent, b) selecting a CHO cell by growth in cultivation medium containing said first eukaryotic selection agent, c) transfecting said selected CHO cell with said vector comprising a fourth nucleic acid conferring resistance to a second eukaryotic selection agent different to said first eukaryotic selection agent, d) selecting a CHO cell by selected growth in cultivation medium containing said first and said second eukaryotic selection agent, iv) cultivating said transfected CHO cell in a medium in the presence of said first and second eukaryotic selection agent, under conditions suitable for the expression of said second, and third nucleic acid, and v) recovering said secreted heterologous immunoglobulin from the cultivation medium.
摘要翻译：本发明报告了在CHO细胞中重组产生分泌的异源免疫球蛋白的方法，其包括以下步骤：i）提供适于在悬浮培养物中生长的CHO细胞，适于在无血清培养基中生长，支原体免费和无病毒，ii）提供包含原核复制起点的载体，赋予原核选择剂抗性的第一核酸，编码所述异源免疫球蛋白的重链的第二核酸，编码光的第三核酸所述异源免疫球蛋白链，赋予对真核选择剂的抗性的第四核酸，iii）转染所述CHO细胞，其中所述转染包括a）用包含第四核酸的所述载体转染所述CHO细胞，所述第四核酸赋予对第一真核选择性的抗性试剂，b）通过在含有所述第一种真核生物的培养基中生长来选择CHO细胞 c）用所述载体转染所述选择的CHO细胞，所述载体包含赋予与所述第一真核选择试剂不同的第二真核选择剂的抗性的第四核酸，d）通过在含有所述第一和第二真核选择试剂的培养基中选择生长来选择CHO细胞，所述第二真核选择剂，iv）在所述第一和第二真核选择剂的存在下，在适于表达所述第二和第三核酸的条件下，在培养基中培养所述转染的CHO细胞，和v）回收所述分泌的异源免疫球蛋白。

9. 发明授权

US08771988B2 Protein expression from multiple nucleic acids 有权
标题翻译：来自多个核酸的蛋白质表达
公开(公告)号：US08771988B2
公开(公告)日：2014-07-08
申请号：US12681781
申请日：2008-10-09
申请人： Ulrich Goepfert , Hendrik Knoetgen , Erhard Kopetzki , Anne Stern
发明人： Ulrich Goepfert , Hendrik Knoetgen , Erhard Kopetzki , Anne Stern
IPC分类号： C12P21/08
CPC分类号： C12N15/85 , C07K16/18 , C07K16/28 , C07K16/2812 , C07K16/2854 , C07K16/2866 , C07K16/2896 , C07K2317/14 , C07K2317/21 , C07K2317/51 , C07K2317/515 , C12P21/00
摘要： The current invention reports a method for the recombinant production of a secreted heterologous immunoglobulin in a CHO cell comprising the following steps: i) providing a CHO cell, which is adapted to growth in suspension culture, adapted to growth in serum-free medium, mycoplasma free, and virus free, ii) providing a vector comprising a prokaryotic origin of replication, a first nucleic acid conferring resistance to a prokaryotic selection agent, a second nucleic acid encoding the heavy chain of said heterologous immunoglobulin, a third nucleic acid encoding the light chain of said heterologous immunoglobulin, a fourth nucleic acid conferring resistance to a eukaryotic selection agent, iii) transfecting said CHO cell, wherein said transfecting comprises a) transfecting said CHO cell with said vector comprising a fourth nucleic acid conferring resistance to a first eukaryotic selection agent, b) selecting a CHO cell by growth in cultivation medium containing said first eukaryotic selection agent, c) transfecting said selected CHO cell with said vector comprising a fourth nucleic acid conferring resistance to a second eukaryotic selection agent different to said first eukaryotic selection agent, d) selecting a CHO cell by selected growth in cultivation medium containing said first and said second eukaryotic selection agent, iv) cultivating said transfected CHO cell in a medium in the presence of said first and second eukaryotic selection agent, under conditions suitable for the expression of said second, and third nucleic acid, and v) recovering said secreted heterologous immunoglobulin from the cultivation medium.
摘要翻译：本发明报告了在CHO细胞中重组产生分泌的异源免疫球蛋白的方法，其包括以下步骤：i）提供适于在悬浮培养物中生长的CHO细胞，适于在无血清培养基中生长，支原体免费和无病毒，ii）提供包含原核复制起点的载体，赋予原核选择剂抗性的第一核酸，编码所述异源免疫球蛋白的重链的第二核酸，编码光的第三核酸所述异源免疫球蛋白链，赋予对真核选择剂的抗性的第四核酸，iii）转染所述CHO细胞，其中所述转染包括a）用包含第四核酸的所述载体转染所述CHO细胞，所述第四核酸赋予对第一真核选择性的抗性试剂，b）通过在含有所述第一种真核生物的培养基中生长来选择CHO细胞 c）用所述载体转染所述选择的CHO细胞，所述载体包含赋予与所述第一真核选择剂不同的第二真核选择剂的抗性的第四核酸，d）通过在含有所述第一和第二真核选择剂的培养基中选择生长来选择CHO细胞，所述第二真核选择剂，iv）在所述第一和第二真核选择剂的存在下，在适于表达所述第二和第三核酸的条件下，在培养基中培养所述转染的CHO细胞，和v）回收所述分泌的异源免疫球蛋白。

10. 发明授权

US07008764B1 Optimization of cells for endogenous gene activation 有权
标题翻译：内源基因激活的细胞优化
公开(公告)号：US07008764B1
公开(公告)日：2006-03-07
申请号：US09203500
申请日：1998-12-01
申请人： Konrad Honold , Thomas Holtschke , Anne Stern
发明人： Konrad Honold , Thomas Holtschke , Anne Stern
IPC分类号： C12Q1/68
CPC分类号： C07K14/505 , C12N15/63 , C12N15/65 , C12N15/85 , C12N15/90 , C12N15/907 , C12N2800/30 , C12N2830/002 , C12Q1/6897
摘要： The invention concerns a process for optimizing the gene expression in cells. A first aspect concerns a process for changing the expression of a nucleic acid sequence which is present endogenously in a eukaryotic cell by introduction of a heterologous expression control sequence into the genome of the cell by means of homologous recombination as well as site-specific recombinase-mediated excision of inserted foreign DNA and its replacement by further heterologous expression control sequences or/and amplification genes. In addition the invention concerns the introduction of one or several nucleic acid sequences to which an activator protein or an activator protein complex binds e.g. a hypoxia-inducible factor (HIF), into the genome of a eukaryotic cell by homologous recombination in order to change the expression of a target gene. Furthermore the invention concerns a process for testing the influence of 5′ or 3′ non-coding nucleic acid fragments on the expression of a target gene by determining the expression of a reporter gene. In addition the invention concerns a process for providing a DHFR-negative eukaryotic cell containing a recombinase target sequence as well as the expression of a nucleic acid sequence inserted into the recombinase target sequence.
摘要翻译：本发明涉及优化细胞中基因表达的方法。第一方面涉及一种通过将异源表达控制序列通过同源重组以及位点特异性重组酶导入到细胞基因组中而在真核细胞中内源性存在的核酸序列的表达的方法。介导的插入的外源DNA的切除及其通过进一步的异源表达控制序列或/和扩增基因的替代。此外，本发明涉及一种或几种核酸序列的引入，活化蛋白或活化蛋白复合物例如与其结合。缺氧诱导因子（HIF），通过同源重组进入真核细胞的基因组，以改变靶基因的表达。此外，本发明涉及通过测定报告基因的表达来测试5'或3'非编码核酸片段对靶基因表达的影响的方法。此外，本发明涉及提供含有重组酶靶序列的DHFR阴性真核细胞以及插入重组酶靶序列中的核酸序列的表达的方法。

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