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1. 发明授权

US07253150B1 Gene delivery vehicle expressing the aptosis-inducing proteins VP2 and/or apoptin 失效
标题翻译：表达引发诱导蛋白VP2和/或凋亡蛋白的基因递送载体
公开(公告)号：US07253150B1
公开(公告)日：2007-08-07
申请号：US09403213
申请日：1998-04-15
申请人： Matheus Hubertus Maria Noteborn , Alexandra Maria Pietersen
发明人： Matheus Hubertus Maria Noteborn , Alexandra Maria Pietersen
IPC分类号： A01N43/04 , A61K31/70
CPC分类号： C07K14/005 , A61K38/00 , A61K48/00 , C07K2319/00 , C12N15/86 , C12N2710/10343 , C12N2740/13043 , C12N2750/10022
摘要： The invention relates to gene delivery vehicles which comprise nucleic acid molecules encoding apoptosis-inducing proteins VP2 and/or apoptin (VP3) like activity. VP2 and VP3 are viral proteins of the Chicken Anaemia Virus. Also, the invention relates to anti-tumor therapies. Infection of various human tumor cells with the gene delivery vehicles of the invention will result in the induction of apoptosis in tumor cells and much reduced apoptosis, if at all, in normal diploid, non-transformed/non-malignant cells. Also the invention relates to the diagnosis of cancer, and related forms of hyperplasia, metaplasia and dysplasia.
摘要翻译：本发明涉及包含编码凋亡诱导蛋白VP2和/或凋亡素（VP3）活性的核酸分子的基因递送载体。 VP2和VP3是鸡贫血病毒的病毒蛋白。此外，本发明涉及抗肿瘤治疗。使用本发明的基因递送载体对各种人肿瘤细胞的感染将导致在肿瘤细胞中诱导细胞凋亡，并且如果在正常的二倍体，非转化/非恶性细胞中完全减少凋亡。本发明还涉及癌症的诊断以及相关形式的增生，化生和发育不良。

2. 发明授权

US6162461A Chicken anemia virus mutants and vaccines and uses based on the viral proteins VP1, VP2 and VP3 or sequences of that virus coding therefor 失效
标题翻译：基于病毒蛋白VP1，VP2和VP3或其编码的病毒序列的鸡贫血病毒突变体和疫苗和用途
公开(公告)号：US6162461A
公开(公告)日：2000-12-19
申请号：US482161
申请日：1995-06-07
申请人： Matheus Hubertus Maria Noteborn , Guus Koch
发明人： Matheus Hubertus Maria Noteborn , Guus Koch
IPC分类号： A61K38/00 , A61K39/00 , A61K39/12 , A61P31/20 , C07H21/04 , C07K14/005 , C07K14/01 , C12N5/06 , C12N7/01 , C12N15/33 , C12N15/86 , C12Q1/70 , G01N33/569 , A61K38/16 , A61K9/127 , C12N15/87
CPC分类号： C07K14/005 , A61K38/00 , A61K39/00 , C12N15/86 , C12N2750/10022 , C12N2750/14143 , C12N2830/00 , C12N2830/60 , G01N33/56983
摘要： The coding information for three putative chicken anemia virus proteins (VP1, VP2, VP3) was inserted into a baculovirus vector and expressed in insect cells. The immunogenic properties of the chicken anemia virus (CAV) proteins produced separately or together in insect-cell cultures were analyzed by inoculating them into chickens. Only lysates of insect cells which have synthesized equivalent amounts of all three recombinant CAV proteins or cells which synthesized mainly VP1 plus VP2 induced neutralizing antibodies directed against CAV in inoculated chickens. Progeny of those chickens were protected against clinical disease after CAV challenge. Inoculation of a mixture of lysates of cells that were separately infected with VP1-, VP2- and VP3-recombinant baculovirus did not induce significant levels of neutralizing antibody directed against CAV and their progeny were not protected against CAV challenge. Our results indicate that expression in the same cell of at least two CAV proteins, VP1 plus VP2, is required to obtain sufficient protection in chickens. Therefore, recombinant CAV proteins produced by baculovirus vectors can be used as a sub-unit vaccine against CAV infections.
摘要翻译：将三种推定的鸡贫血病毒蛋白（VP1，VP2，VP3）的编码信息插入杆状病毒载体中，并在昆虫细胞中表达。通过将它们接种到鸡中来分析在昆虫细胞培养物中单独或一起产生的鸡贫血病毒（CAV）蛋白的免疫原性。只有合成了相当量的所有三种重组CAV蛋白或主要合成VP1加VP2的细胞的昆虫细胞裂解液才能诱导接种鸡中抗CAV的中和抗体。在CAV攻击后，这些鸡的后代受到临床疾病的保护。分别感染VP1，VP2和VP3-重组杆状病毒的细胞裂解液的混合物接种不诱导针对CAV的显着水平的中和抗体，并且其后代不受CAV攻击的保护。我们的研究结果表明，需要在至少两种CAV蛋白VP1加VP2的相同细胞中表达以获得足够的鸡保护。因此，由杆状病毒载体产生的重组CAV蛋白可用作针对CAV感染的亚单位疫苗。

3. 发明授权

US07741440B2 Apoptin-associating protein 失效
标题翻译：凋亡蛋白相关蛋白
公开(公告)号：US07741440B2
公开(公告)日：2010-06-22
申请号：US11879370
申请日：2007-07-16
申请人： Mathieu Hubertus M. Noteborn , Astrid Adriana A. M. Danen-van Oorschot , Jennifer Leigh Rohn , Bertram Weiss , Luisella Toschi
发明人： Mathieu Hubertus M. Noteborn , Astrid Adriana A. M. Danen-van Oorschot , Jennifer Leigh Rohn , Bertram Weiss , Luisella Toschi
IPC分类号： C07K14/00 , C07H21/04
CPC分类号： A61K38/162 , A01K2217/05 , A61K38/1709 , A61K48/005 , C07K14/4747 , C07K16/40 , C12N2501/48 , C12N2510/00 , C12N2750/10011 , G01N33/68 , G01N2510/00
摘要： The invention relates to the field of apoptosis. The invention provides novel therapies, for example, novel combinatorial therapies or novel therapeutic compounds that can work alone, sequentially to, or jointly with Apoptin, especially in those cases wherein p53 is completely or partially non-functional.
摘要翻译：本发明涉及细胞凋亡领域。本发明提供了新的治疗方法，例如新的组合疗法或可以单独，顺序地或与Apoptin共同工作的新型治疗化合物，特别是在p53完全或部分不起作用的情况下。

4. 发明申请

US20080176231A1 Apoptin-associating proteiins 失效
标题翻译：凋亡蛋白相关蛋白
公开(公告)号：US20080176231A1
公开(公告)日：2008-07-24
申请号：US11818169
申请日：2007-06-12
申请人： Mathieu Hubertus Maria Noterorn , Astrid Adriana Anna Maria Danen-Van Oorschot
发明人： Mathieu Hubertus Maria Noterorn , Astrid Adriana Anna Maria Danen-Van Oorschot
IPC分类号： G01N33/574 , C12Q1/68 , C07K14/00 , C07K2/00 , C12P21/02 , C07K16/00
CPC分类号： C07K16/18 , A61K38/00 , A61K48/00 , C07K14/4747
摘要： The invention relates to the field of apoptosis. The invention provides novel therapeutic possibilities, for example novel combinatorial therapies or novel therapeutic compounds that can work alone, sequentially to, or jointly with apoptin, especially in those cases wherein p53 is (partly) non-functional.
摘要翻译：本发明涉及细胞凋亡领域。本发明提供新颖的治疗可能性，例如可以独立地，顺序地或与凋亡素联合工作的新型组合疗法或新型治疗化合物，特别是在p53（部分）非功能性的情况下。

5. 发明授权

US07319034B2 Modifications of apoptin 失效
标题翻译：凋亡素的修饰
公开(公告)号：US07319034B2
公开(公告)日：2008-01-15
申请号：US10083849
申请日：2001-10-19
申请人： Mathieu Hubertus Maria Noteborn , Jennifer Leigh Rohn , Dominik Mumberg , Peter Donner
发明人： Mathieu Hubertus Maria Noteborn , Jennifer Leigh Rohn , Dominik Mumberg , Peter Donner
IPC分类号： C12N15/85
CPC分类号： C07K14/005 , A61K38/00 , A61K38/162 , A61K48/00 , C07K14/4747 , C07K16/18 , C07K2319/00 , C12N2750/10022 , C12N2750/10043
摘要： Phosphorylated Apoptin is described. Apoptin is tumor-specifically phosphorylated and part of the Apoptin apoptotic pathway in tumor cells is elucidated. New therapeutic possibilities, for example, novel therapeutic compounds that can work alone or, sequentially to, or jointly with other known compounds. Also, the use of tumor-specifically phosphorylation of Apoptin for diagnostic purposes is described. Such a diagnostic purpose can, for example, be a method for detecting the presence of cancer cells or cells that are cancer prone or a method to identify a putative cancer inducing agent or a method for the in vitro treatment effect of Apoptin on tumor cells by testing the phosphorylation state of Apoptin. Even more, the invention provides possibilities to further elucidate the apoptotic pathway and to identify for example crucial mediators of phosphorylation in human tumor cells. Interfering with such a mediator could provide new anti-cancer therapies.
摘要翻译：描述了磷酸化的Apoptin。凋亡素是肿瘤特异性磷酸化的，并且阐明肿瘤细胞中部分凋亡途径的凋亡途径。新的治疗可能性，例如，可以单独或连续地或与其它已知化合物一起工作的新型治疗化合物。此外，描述了用于诊断目的的使用肿瘤特异性磷酸化的Apoptin。这样的诊断目的可以是例如用于检测癌细胞或癌症倾向的细胞的存在的方法或者鉴定推定的癌症诱导剂的方法或者通过以下方法检测凋亡素对肿瘤细胞的体外治疗效果的方法测试Apoptin的磷酸化状态。更进一步地，本发明提供进一步阐明凋亡途径并鉴定例如人肿瘤细胞中磷酸化的关键介质的可能性。干扰这种介质可以提供新的抗癌疗法。

6. 发明申请

US20050271624A1 Use of apoptosis inducing agents in the treatment of (auto) immune diseases 审中-公开
标题翻译：使用细胞凋亡诱导剂治疗（自身）免疫疾病
公开(公告)号：US20050271624A1
公开(公告)日：2005-12-08
申请号：US11067001
申请日：2005-02-25
申请人： Mathieu Hubertus Noteborn , Alexandra Pietersen
发明人： Mathieu Hubertus Noteborn , Alexandra Pietersen
IPC分类号： C12N15/09 , A61K35/76 , A61K38/00 , A61K38/16 , A61K45/00 , A61K48/00 , A61P29/00 , A61P37/00 , A61P37/02 , A61P37/06 , A61P43/00 , C12Q1/02 , G01N33/50 , C12N15/861
CPC分类号： A61K38/162
摘要： The invention relates to therapies for (auto) immune diseases. Synthesis or presence of apoptotic activity in cells causing or related to (auto) immune diseases, such as synoviocytes in rheumatoid arthritis, will result in the induction of apoptosis. The invention also relates to gene-delivery vehicles, which comprise nucleic acid molecules encoding apoptosis-inducing proteins with apopti-like activity.
摘要翻译：本发明涉及（自身）免疫疾病的疗法。导致或与自身免疫疾病相关的细胞（如类风湿性关节炎中的滑膜细胞）的凋亡活性的合成或存在将导致细胞凋亡的诱导。本发明还涉及基因递送载体，其包含编码具有凋亡样活性的凋亡诱导蛋白的核酸分子。

7. 发明授权

US07427658B2 Chicken anemia virus mutants and vaccines and uses based on the viral proteins VP1, VP2 and VP3 or sequences of that virus coding therefor 失效
标题翻译：基于病毒蛋白VP1，VP2和VP3或其编码的病毒序列的鸡贫血病毒突变体和疫苗和用途
公开(公告)号：US07427658B2
公开(公告)日：2008-09-23
申请号：US09740676
申请日：2000-12-18
申请人： Mathieu Hubertus Maria Noteborn , Guus Koch
发明人： Mathieu Hubertus Maria Noteborn , Guus Koch
IPC分类号： C07K7/08 , C07K14/01 , C07K16/46 , C07K19/00 , C12N15/62 , C12N1/21 , C12N5/10 , C12N15/34 , A61K39/12 , A61K39/395
CPC分类号： C07K14/005 , A61K38/00 , A61K39/00 , C12N15/86 , C12N2750/10022 , C12N2750/14143 , C12N2830/00 , C12N2830/60 , G01N33/56983
摘要： The coding information for three putative chicken anemia virus proteins (VP1, VP2, VP3) was inserted into a baculovirus vector and expressed in insect cells. Only lysates of insect cells which have synthesized equivalent amounts of all three recombinant CAV proteins or cells which synthesized mainly VP1 plus VP2 induced neutralizing antibodies directed against CAV in inoculated chickens. Progeny of those chickens were protected against clinical disease after CAV challenge. Inoculation of a mixture of lysates of cells that were separately infected with VP1-, VP2- and VP3-recombinant baculovirus did not induce significant levels of neutralizing antibody directed against CAV and their progeny were not protected against CAV challenge. Expression in the same cell of at least VP1 plus VP2 is required to obtain sufficient protection in chickens. Therefore, recombinant CAV proteins produced by baculovirus vectors can be used as a sub-unit vaccine against CAV infections.
摘要翻译：将三种推定的鸡贫血病毒蛋白（VP1，VP2，VP3）的编码信息插入杆状病毒载体中，并在昆虫细胞中表达。只有合成了相当量的所有三种重组CAV蛋白或主要合成VP1加VP2的细胞的昆虫细胞裂解液才能诱导接种鸡中抗CAV的中和抗体。在CAV攻击后，这些鸡的后代受到临床疾病的保护。分别感染VP1，VP2和VP3-重组杆状病毒的细胞裂解液的混合物接种不诱导针对CAV的显着水平的中和抗体，并且其后代不受CAV攻击的保护。在至少VP1加VP2的相同细胞中的表达需要在鸡中获得足够的保护。因此，由杆状病毒载体产生的重组CAV蛋白可用作针对CAV感染的亚单位疫苗。

8. 发明申请

US20080058267A1 Apoptin-associating protein 失效
标题翻译：凋亡蛋白相关蛋白
公开(公告)号：US20080058267A1
公开(公告)日：2008-03-06
申请号：US11879370
申请日：2007-07-16
申请人： Mathieu Hubertus Noteborn , Astrid Adriana Danen-van Oorschot , Jennifer Rohn , Bertram Weiss , Luisella Toschi
发明人： Mathieu Hubertus Noteborn , Astrid Adriana Danen-van Oorschot , Jennifer Rohn , Bertram Weiss , Luisella Toschi
IPC分类号： A61K38/16 , A61K31/70 , A61P35/00 , A61P37/00 , C07H21/04 , C07K14/00 , C07K16/00 , C12N15/00 , G01N33/53
CPC分类号： A61K38/162 , A01K2217/05 , A61K38/1709 , A61K48/005 , C07K14/4747 , C07K16/40 , C12N2501/48 , C12N2510/00 , C12N2750/10011 , G01N33/68 , G01N2510/00
摘要： The invention relates to the field of apoptosis. The invention provides novel therapies, for example, novel combinatorial therapies or novel therapeutic compounds that can work alone, sequentially to, or jointly with Apoptin, especially in those cases wherein p53 is completely or partially non-functional.
摘要翻译：本发明涉及细胞凋亡领域。本发明提供了新的治疗方法，例如可以独立地，顺序地或与Apoptin共同工作的新型组合疗法或新的治疗化合物，特别是在p53完全或部分不功能的情况下。

9. 发明授权

US07256274B2 Apoptin-associating protein 失效
标题翻译：凋亡蛋白相关蛋白
公开(公告)号：US07256274B2
公开(公告)日：2007-08-14
申请号：US09733416
申请日：2000-12-08
申请人： Mathieu Hubertus M. Noteborn , Astrid Adriana A. M. Danen-van Oorschot , Jennifer Leigh Rohn , Bertram Weiss , Luisella Toschi
发明人： Mathieu Hubertus M. Noteborn , Astrid Adriana A. M. Danen-van Oorschot , Jennifer Leigh Rohn , Bertram Weiss , Luisella Toschi
IPC分类号： C07H21/04
CPC分类号： A61K38/162 , A01K2217/05 , A61K38/1709 , A61K48/005 , C07K14/4747 , C07K16/40 , C12N2501/48 , C12N2510/00 , C12N2750/10011 , G01N33/68 , G01N2510/00
摘要： The invention relates to the field of apoptosis. The invention provides novel therapeutic possibilities, for example novel combinatorial therapies or novel therapeutic compounds that can work alone, sequentially to, or jointly with Apoptin, especially in those cases wherein p53 is (partly) nonfunctional.
摘要翻译：本发明涉及细胞凋亡领域。本发明提供新颖的治疗可能性，例如可以独立地，顺序地或与Apoptin共同工作的新型组合疗法或新型治疗化合物，特别是在p53是（部分）非功能性的情况下。

10. 发明申请

US20100279947A1 Modifications of apoptin 审中-公开
标题翻译：凋亡素的修饰
公开(公告)号：US20100279947A1
公开(公告)日：2010-11-04
申请号：US11998194
申请日：2007-11-28
申请人： Mathieu Hubertus Maria Noteborn , Jennifer Leigh Rohn , Dominik Mumberg , Peter Donner
发明人： Mathieu Hubertus Maria Noteborn , Jennifer Leigh Rohn , Dominik Mumberg , Peter Donner
IPC分类号： A61K38/16 , C07K14/005 , C12N15/63 , C12N5/10 , C07K16/08 , C07H21/04 , G01N33/53 , A61P35/00
CPC分类号： C07K14/005 , A61K38/00 , A61K38/162 , A61K48/00 , C07K14/4747 , C07K16/18 , C07K2319/00 , C12N2750/10022 , C12N2750/10043
摘要： Phosphorylated Apoptin is described. Apoptin is tumor-specifically phosphorylated and part of the Apoptin apoptotic pathway in tumor cells is elucidated. New therapeutic possibilities, for example, novel therapeutic compounds that can work alone or, sequentially to, or jointly with other known compounds. Also, the use of tumor-specifically phosphorylation of Apoptin for diagnostic purposes is described. Such a diagnostic purpose can, for example, be a method for detecting the presence of cancer cells or cells that are cancer prone or a method to identify a putative cancer inducing agent or a method for the in vitro treatment effect of Apoptin on tumor cells by testing the phosphorylation state of Apoptin. Even more, the invention provides possibilities to further elucidate the apoptotic pathway and to identify for example crucial mediators of phosphorylation in human tumor cells. Interfering with such a mediator could provide new anti-cancer therapies.
摘要翻译：描述了磷酸化的Apoptin。凋亡素是肿瘤特异性磷酸化的，并且阐明肿瘤细胞中部分凋亡途径的凋亡途径。新的治疗可能性，例如，可以单独或连续地或与其它已知化合物一起工作的新型治疗化合物。此外，描述了用于诊断目的的使用肿瘤特异性磷酸化的Apoptin。这样的诊断目的可以是例如用于检测癌细胞或癌症倾向的细胞的存在的方法或者鉴定推定的癌症诱导剂的方法或者通过以下方法检测凋亡素对肿瘤细胞的体外治疗效果的方法测试Apoptin的磷酸化状态。更进一步地，本发明提供进一步阐明凋亡途径并鉴定例如人肿瘤细胞中磷酸化的关键介质的可能性。干扰这种介质可以提供新的抗癌疗法。

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