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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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Patent Agency Ranking
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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6.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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公开(公告)号：US06489443B2
公开(公告)日：2002-12-03
申请号：US09350120
申请日：1999-07-09
Applicant: Jürgen Römisch , Jörg Weisse , Jean Luc Veron , Juliana Djordjevich , Wilfried Freudenberg , Michel Grandgeorge , Barbara Kalina , Peter Kappus , Manfred Konrad , Gregory S. Rood , Werner Thill
Inventor： Jürgen Römisch , Jörg Weisse , Jean Luc Veron , Juliana Djordjevich , Wilfried Freudenberg , Michel Grandgeorge , Barbara Kalina , Peter Kappus , Manfred Konrad , Gregory S. Rood , Werner Thill
IPC: C07K100
CPC classification number: C07K14/745 , C07K1/34 , C07K14/765 , C07K16/065
Abstract: A process for the preparation of a protein solution is described which is not prone to flock or particle formation even on heat treatment, the heat treatment being carried out in a glass vessel which has been rinsed out beforehand with a detergent solution and then with distilled water or another detergent-free solvent.
Abstract translation: 描述了用于制备蛋白质溶液的方法，即使在热处理时也不容易发生绒毛或颗粒形成，热处理在预先用洗涤剂溶液冲洗的玻璃容器中进行，然后用蒸馏水 或另一种不含洗涤剂的溶剂。
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8.发明授权Method and circuit for exciting an ultrasonic generator and the use thereof for atomizing a liquid 失效用于激发超声波发生器的方法和电路及其用于雾化液体的用途
公开(公告)号：US4868521A
公开(公告)日：1989-09-19
申请号：US232731
申请日：1988-08-16
Applicant: Manfred Konrad
Inventor： Manfred Konrad
CPC classification number: B05B17/0669 , B05B17/0607 , B06B1/0253 , B06B2201/77
Abstract: A method and a circuit for exciting an ultrasonic generator comprises a control loop which includes the ultrasonic generator itself and a voltage-controlled oscillator. The control loop keeps the active power consumption to a desired value, which is compared in a comparator with the instantaneous active power consumption. One output of a further rectangular oscillator is connected to the control input of the voltage-controlled oscillator. The rectangular oscillator is put into operation if in the control loop there are no control oscillations or only those which are smaller than a predetermined threshold. The output of the rectangular oscillator is connected across one diode to the control input of the voltage-controlled oscillator and across another diode to the controlled input of comparator. The additional signal is applied to the voltage-controlled oscillator, apart from the control signal of the control loop. The cycle of the additional signal is longer than the change time constant at the control input of the voltage-controlled oscillator and the additional signal swing is selected in such a way that the frequency of oscillator passes through a predetermined frequency range.
Abstract translation: 用于激发超声波发生器的方法和电路包括包括超声波发生器本身和压控振荡器的控制回路。 控制回路将有功功率保持在期望值，在比较器中与瞬时有功功率消耗进行比较。 另一个矩形振荡器的一个输出端连接到压控振荡器的控制输入端。 如果在控制环路中没有控制振荡或只有小于预定阈值的振荡器，则矩形振荡器投入运行。 矩形振荡器的输出通过一个二极管连接到压控振荡器的控制输入端，另一个二极管连接到比较器的受控输入端。 除了控制回路的控制信号之外，附加信号被施加到压控振荡器。 附加信号的周期比压控振荡器的控制输入处的变化时间常数长，并且以使得振荡器的频率经过预定频率范围的方式选择附加信号摆幅。
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