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1.发明授权公开(公告)号：US07858745B2
公开(公告)日：2010-12-28
申请号：US11760399
申请日：2007-06-08
Applicant: Arnon Lavie , Manfred Konrad , Farhad Ravandi
Inventor： Arnon Lavie , Manfred Konrad , Farhad Ravandi
CPC classification number: B82Y5/00 , A61K47/6815 , A61K47/6899 , C07K16/2803 , C07K2319/30 , C12N9/1205
Abstract: The invention provides methods for enhancing efficiency of prodrugs by specifically engineered enzymes with enhanced activity towards nucleoside analogs used in cancer chemotherapy, and delivering the enzymes to specific target cells in a patient. The invention also provides modified deoxycytidine kinase (dCK) mutants with such enhanced activity. Furthermore, the invention provides antibody-conjugated enzymes that can be specifically delivered to leukemic blast cells in vivo or ex vivo.
Abstract translation: 本发明提供了通过特异性工程化的酶提高前药的效率的方法，所述酶具有增强的对癌症化疗中使用的核苷类似物的活性，并将酶递送到患者中的特定靶细胞。 本发明还提供具有这种增强活性的修饰的脱氧胞苷激酶（dCK）突变体。 此外，本发明提供可以在体内或体外特异性递送至白血病胚胎细胞的抗体缀合的酶。
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2.发明申请公开(公告)号：US20070258968A1
公开(公告)日：2007-11-08
申请号：US11760399
申请日：2007-06-08
Applicant: Arnon Lavie , Manfred Konrad , Farhad Ravandi
Inventor： Arnon Lavie , Manfred Konrad , Farhad Ravandi
CPC classification number: B82Y5/00 , A61K47/6815 , A61K47/6899 , C07K16/2803 , C07K2319/30 , C12N9/1205
Abstract: The invention provides methods for enhancing efficiency of prodrugs by specifically engineered enzymes with enhanced activity towards nucleoside analogs used in cancer chemotherapy, and delivering the enzymes to specific target cells in a patient. The invention also provides modified deoxycytidine kinase (dCK) mutants with such enhanced activity. Furthermore, the invention provides antibody-conjugated enzymes that can be specifically delivered to leukemic blast cells in vivo or ex vivo.
Abstract translation: 本发明提供了通过特异性工程化的酶提高前药的效率的方法，所述酶具有增强的对癌症化疗中使用的核苷类似物的活性，并将酶递送到患者中的特定靶细胞。 本发明还提供具有这种增强活性的修饰的脱氧胞苷激酶（dCK）突变体。 此外，本发明提供可以在体内或体外特异性递送至白血病胚胎细胞的抗体缀合的酶。
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3.发明授权公开(公告)号：US07419811B2
公开(公告)日：2008-09-02
申请号：US10791155
申请日：2004-03-01
Applicant: Arnon Lavie , Manfred Konrad , Farhad Ravandi
Inventor： Arnon Lavie , Manfred Konrad , Farhad Ravandi
CPC classification number: B82Y5/00 , A61K47/6815 , A61K47/6899 , C07K16/2803 , C07K2319/30 , C12N9/1205
Abstract: The invention provides methods for enhancing efficiency of prodrugs by specifically engineered enzymes with enhanced activity towards nucleoside analogs used in cancer chemotherapy, and delivering the enzymes to specific target cells in a patient. The invention also provides modified deoxycytidine kinase (dCK) mutants with such enhanced activity. Furthermore, the invention provides antibody-conjugated enzymes that can be specifically delivered to leukemic blast cells in vivo or ex vivo.
Abstract translation: 本发明提供了通过特异性工程化的酶提高前药的效率的方法，所述酶具有增强的对癌症化疗中使用的核苷类似物的活性，并将酶递送到患者中的特定靶细胞。 本发明还提供具有这种增强活性的修饰的脱氧胞苷激酶（dCK）突变体。 此外，本发明提供可以在体内或体外特异性递送至白血病胚胎细胞的抗体缀合的酶。
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4.发明申请公开(公告)号：US20050008648A1
公开(公告)日：2005-01-13
申请号：US10791155
申请日：2004-03-01
Applicant: Arnon Lavie , Manfred Konrad , Farhad Ravandi
Inventor： Arnon Lavie , Manfred Konrad , Farhad Ravandi
IPC: A61K39/395 , A61K47/48 , C07K16/28 , C12N9/00 , C12N9/12
CPC classification number: B82Y5/00 , A61K47/6815 , A61K47/6899 , C07K16/2803 , C07K2319/30 , C12N9/1205
Abstract: The invention provides methods for enhancing efficiency of prodrugs by specifically engineered enzymes with enhanced activity towards nucleoside analogs used in cancer chemotherapy, and delivering the enzymes to specific target cells in a patient. The invention also provides modified deoxycytidine kinase (dCK) mutants with such enhanced activity. Furthermore, the invention provides antibody-conjugated enzymes that can be specifically delivered to leukemic blast cells in vivo or ex vivo.
Abstract translation: 本发明提供了通过特异性工程化的酶提高前药的效率的方法，所述酶具有增强的对癌症化疗中使用的核苷类似物的活性，并将酶递送到患者中的特定靶细胞。 本发明还提供具有这种增强活性的修饰的脱氧胞苷激酶（dCK）突变体。 此外，本发明提供可以在体内或体外特异性递送至白血病胚胎细胞的抗体缀合的酶。
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5.发明申请公开(公告)号：US20110129470A1
公开(公告)日：2011-06-02
申请号：US12993660
申请日：2009-05-18
Applicant: Arnon Lavie , Manfred Konrad
Inventor： Arnon Lavie , Manfred Konrad
CPC classification number: C12N9/1205 , A61K38/00
Abstract: The invention provides methods for enhancing efficiency of prodrugs by specifically engineered enzymes with altered or enhanced activity and broader substrate specificity towards nucleoside analogs used in cancer chemotherapy, and delivering the enzymes to specific target cells in a patient. The invention also provides modified deoxycytidine kinase (dCK) mutants with such enhanced activities. Furthermore, the invention provides antibody-conjugated enzymes, pharmaceutical composition and kit containing the same, that can be specifically delivered to tumor cells.
Abstract translation: 本发明提供了通过特异性工程化的酶提高前药的效力的方法，其具有改变的或增强的活性，并且对癌症化学疗法中使用的核苷类似物具有更广泛的底物特异性，并将酶递送到患者中的特定靶细胞。 本发明还提供具有这种增强活性的修饰的脱氧胞苷激酶（dCK）突变体。 此外，本发明提供抗体缀合的酶，药物组合物和含有该酶的试剂盒，其可以特异性递送至肿瘤细胞。
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Patent Agency Ranking
6.发明授权公开(公告)号：US08349318B2
公开(公告)日：2013-01-08
申请号：US12993660
申请日：2009-05-18
Applicant: Arnon Lavie , Manfred Konrad
Inventor： Arnon Lavie , Manfred Konrad
CPC classification number: C12N9/1205 , A61K38/00
Abstract: The invention provides methods for enhancing efficiency of prodrugs by specifically engineered enzymes with altered or enhanced activity and broader substrate specificity towards nucleoside analogs used in cancer chemotherapy, and delivering the enzymes to specific target cells in a patient. The invention also provides modified deoxycytidine kinase (dCK) mutants with such enhanced activities. Furthermore, the invention provides antibody-conjugated enzymes, pharmaceutical composition and kit containing the same, that can be specifically delivered to tumor cells.
Abstract translation: 本发明提供了通过特异性工程化的酶提高前药的效力的方法，其具有改变的或增强的活性，并且对癌症化学疗法中使用的核苷类似物具有更广泛的底物特异性，并将酶递送到患者中的特定靶细胞。 本发明还提供具有这种增强活性的修饰的脱氧胞苷激酶（dCK）突变体。 此外，本发明提供抗体缀合的酶，药物组合物和含有该酶的试剂盒，其可以特异性递送至肿瘤细胞。
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公开(公告)号：US20140248212A1
公开(公告)日：2014-09-04
申请号：US14354770
申请日：2012-08-06
Applicant: Caius G. Radu , Johannes Czernin , Dean O. Campbell , Shahriar S. Yaghoubi , Nagichettiar Satyamurthy , Arnon Lavie
Inventor： Caius G. Radu , Johannes Czernin , Dean O. Campbell , Shahriar S. Yaghoubi , Nagichettiar Satyamurthy , Arnon Lavie
CPC classification number: A61K51/0491 , C12N9/1211 , C12Q1/485 , C12Y207/01021
Abstract: Embodiments of the invention include a PET/SPECT reporter gene system that uses enhanced non-immunogenic versions of a human mitochondrial thymidine kinase 2 expressed in cytoplasm to preferentially trap novel PET/SPECT radiolabeled L and D-enantiomer analogs of the natural substrate thymidine. Such highly sensitive, non-immunogenic reporter genes function in combination with a set of novel, radiolabeled probes in whole body molecular imaging applications using positron emission tomography (PET) or single photon emission computed tomography (SPECT).
Abstract translation: 本发明的实施方案包括使用在细胞质中表达的人线粒体胸苷激酶2的增强的非免疫原性型优先捕获天然底物胸苷的新型PET / SPECT放射性标记的L和D-对映异构体类似物的PET / SPECT报告基因系统。 这种高度敏感的，非免疫的报告基因与使用正电子发射断层扫描（PET）或单光子发射计算机断层摄影（SPECT）的全身分子成像应用中的一组新型放射性标记的探针结合起作用。
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公开(公告)号：US20090068158A1
公开(公告)日：2009-03-12
申请号：US12052565
申请日：2008-03-20
Applicant: Jeffrey A. Medin , Arnon Lavie , Daniel H. Fowler , Boro Dropulic
Inventor： Jeffrey A. Medin , Arnon Lavie , Daniel H. Fowler , Boro Dropulic
IPC: A61K35/12 , A61K31/7088 , C12N15/87 , C12N5/10 , C12N15/63
CPC classification number: A61K48/005 , A61K38/00 , C12N9/1229 , C12N15/86 , C12N2740/16043 , C12Y207/04009 , Y02A50/473
Abstract: The invention relates to a composition comprising: a stably integrating delivery vector; a modified mammalian thymidylate kinase (tmpk) wherein the modified mammalian tmpk increases phosphorylation of a prodrug relative to phosphorylation of the prodrug by wild-type human tmpk. The invention also relates to use of these compositions in methods of treatment of diseaseuuius such as graft versus host disease and cancer.
Abstract translation: 本发明涉及一种组合物，其包含：稳定整合递送载体; 修饰的哺乳动物胸苷酸激酶（tmpk），其中修饰的哺乳动物tmpk增加了前体药物相对于通过野生型人类tmpk磷酸化前药的磷酸化。 本发明还涉及这些组合物在治疗疾病如移植物抗宿主病和癌症的方法中的用途。
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公开(公告)号：US20110014165A1
公开(公告)日：2011-01-20
申请号：US12843238
申请日：2010-07-26
Applicant: Jeffrey A. Medin , Arnon Lavie , Daniel H. Fowler
Inventor： Jeffrey A. Medin , Arnon Lavie , Daniel H. Fowler
CPC classification number: A61K38/45 , A01K2267/0331 , C12N9/1229 , C12N2799/027 , C12N2840/203 , C12Y207/04009 , Y02A50/473
Abstract: The invention relates to a composition comprising a stably integrating delivery vector; and a modified mammalian thymidylate kinase (tmpk) wherein the modified mammalian tmpk increases phosphorylation of a prodrug relative to phosphorylation of the prodrug by wild-type human tmpk. The invention also relates to use of these compositions in methods of treatment of diseases such as graft versus host disease and cancer.
Abstract translation: 本发明涉及包含稳定整合递送载体的组合物; 和修饰的哺乳动物胸苷酸激酶（tmpk），其中修饰的哺乳动物tmpk增加了前体药物相对于通过野生型人类tmpk磷酸化前药的磷酸化。 本发明还涉及这些组合物在治疗疾病如移植物抗宿主病和癌症的方法中的用途。
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公开(公告)号：US20090074733A1
公开(公告)日：2009-03-19
申请号：US11559757
申请日：2006-11-14
Applicant: Jeffrey A. Medin , Arnon Lavie , Daniel H. Fowler
Inventor： Jeffrey A. Medin , Arnon Lavie , Daniel H. Fowler
CPC classification number: A61K38/45 , A01K2267/0331 , C12N9/1229 , C12N2799/027 , C12N2840/203 , C12Y207/04009 , Y02A50/473
Abstract: The invention relates to a composition comprising: a stably integrating delivery vector; a modified mammalian thymidylate kinase (tmpk) wherein the modified mammalian tmpk increases phosphorylation of a prodrug relative to phosophorylation of the prodrug by wild-type human tmpk. The invention also relates to use of these compositions in methods of treatment of diseases such as graft versus host disease and cancer.
Abstract translation: 本发明涉及一种组合物，其包含：稳定整合递送载体; 修饰的哺乳动物胸苷酸激酶（tmpk），其中修饰的哺乳动物tmpk增加了前体药物相对于野生型人类tmpk前药的磷酸化的磷酸化。 本发明还涉及这些组合物在治疗疾病如移植物抗宿主病和癌症的方法中的用途。
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