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1. 发明申请

US20060204496A1 Agonist antibody against heteroreceptor 审中-公开
标题翻译：抗异种受体的激动剂抗体
公开(公告)号：US20060204496A1
公开(公告)日：2006-09-14
申请号：US10540643
申请日：2003-11-28
申请人： Tetsuo Kojima , Chiaki Senoo , Osamu Natori , Keiko Kasutani , Shiny Ishi
发明人： Tetsuo Kojima , Chiaki Senoo , Osamu Natori , Keiko Kasutani , Shiny Ishi
IPC分类号： A61K39/395 , C07K16/28
CPC分类号： C07K16/2866 , C07K2317/31 , C07K2317/622
摘要： Animals were immunized with either the A or B chain of a receptor, and then mRNA was extracted from the spleen cells of the animals, and the variable regions of the L and H chains were isolated by RT-PCR using primers for variable regions comprising CDRs. Single-chain Fv was synthesized by assembly PCR to construct a phage library. Clones for antigen-bound antibodies were concentrated and cloned by panning. An expression vector for scFv-CH1-Fc was prepared by inserting a single-chain variable region between CH1-hinge-CH2-CH3 and the signal sequence for animal cells. Various combinations of such expression vectors were introduced into cells to express antibodies, and antibody clones exhibiting ligand-like activity were selected.
摘要翻译：用受体的A或B链免疫动物，然后从动物的脾细胞中提取mRNA，并且通过RT-PCR分离L和H链的可变区，使用包含CDR的可变区的引物。通过装配PCR合成单链Fv构建噬菌体文库。通过淘选浓缩抗原结合抗体的克隆并克隆。通过在CH1铰链-CH2-CH3和动物细胞的信号序列之间插入单链可变区来制备scFv-CH1-Fc的表达载体。将这些表达载体的各种组合引入细胞中以表达抗体，并选择显示配体样活性的抗体克隆。

2. 发明申请

US20080075712A1 Double Specific Antibodies Substituting For Functional Proteins 审中-公开
标题翻译：双功能抗体替代功能蛋白
公开(公告)号：US20080075712A1
公开(公告)日：2008-03-27
申请号：US10575905
申请日：2003-10-14
申请人： Kunihiro Hattori , Tetsuo Kojima , Taro Miyazaki , Tetsuhiro Soeda , Chiaki Senoo , Osamu Natori , Keiko Kasutani , Shinya Ishii
发明人： Kunihiro Hattori , Tetsuo Kojima , Taro Miyazaki , Tetsuhiro Soeda , Chiaki Senoo , Osamu Natori , Keiko Kasutani , Shinya Ishii
IPC分类号： A61K39/395 , A61P31/12 , A61P35/00 , A61P37/00 , A61P7/00 , C07K16/00 , C07K16/36
CPC分类号： C07K16/36 , C07K16/2866 , C07K2317/31 , C07K2317/622
摘要： The present inventors succeeded in separating bispecific antibodies that functionally substitute for ligands of type I interferon receptors comprising two types of molecules: AR1 chain and AR2 chain. Furthermore, the present inventors succeeded in producing bispecific antibodies that substitute for the enzyme reaction-accelerating function of blood coagulation factor VIII/activated blood coagulation factor VIII, which bind to both blood coagulation factor IX/activated blood coagulation factor IX and blood coagulation factor X.
摘要翻译：本发明人成功地分离了功能上代替包含两种类型的分子：AR1链和AR2链的I型干扰素受体的配体的双特异性抗体。此外，本发明人成功地制备了代替凝血因子VIII /活化凝血因子VIII的酶反应促进功能的双特异性抗体，其结合凝血因子IX /活化凝血因子IX和凝血因子X 。

3. 发明申请

US20050164307A1 Methods of screening agonistic antibody 有权
标题翻译：筛选激素抗体的方法
公开(公告)号：US20050164307A1
公开(公告)日：2005-07-28
申请号：US10511993
申请日：2003-04-25
申请人： Tetsuo Kojima , Chiaki Senoo
发明人： Tetsuo Kojima , Chiaki Senoo
IPC分类号： A61P25/00 , A61P37/00 , C12P21/08 , C40B30/04 , G01N33/50 , G01N33/68 , G01N33/53 , G01N33/567
CPC分类号： C40B30/04 , G01N33/5008
摘要： Cell strains with ligand-dependent (factor-dependent) proliferation are super-infected with antibody libraries against each of the various receptor chains. Antibody genes are recovered from strains that autonomously grow by the autocrine stimulation by agonistic antibodies formed by appropriate combinations, enabling effective screening of agonistic antibodies. In this method, effective screening can be carried out using antibodies as libraries. Furthermore, the manipulations are simple, and there is no need for complicated operations.
摘要翻译：具有配体依赖性（因子依赖性）增殖的细胞株通过针对各种受体链的抗体文库进行超感染。从通过自分泌刺激通过适当组合形成的激动性抗体自主生长的菌株回收抗体基因，能够有效筛选激动性抗体。在该方法中，可以使用抗体作为文库进行有效的筛选。此外，操作简单，不需要复杂的操作。

4. 发明授权

US07732149B2 Methods of screening agonistic antibodies 有权
标题翻译：筛选激动性抗体的方法
公开(公告)号：US07732149B2
公开(公告)日：2010-06-08
申请号：US10511993
申请日：2003-04-25
申请人： Tetsuo Kojima , Chiaki Senoo
发明人： Tetsuo Kojima , Chiaki Senoo
IPC分类号： G01N33/53
CPC分类号： C40B30/04 , G01N33/5008
摘要： Cell strains with ligand-dependent (factor-dependent) proliferation are super-infected with antibody libraries against each of the various receptor chains. Antibody genes are recovered from strains that autonomously grow by the autocrine stimulation by agonistic antibodies formed by appropriate combinations, enabling effective screening of agonistic antibodies. In this method, effective screening can be carried out using antibodies as libraries. Furthermore, the manipulations are simple, and there is no need for complicated operations.
摘要翻译：具有配体依赖性（因子依赖性）增殖的细胞株通过针对各种受体链的抗体文库进行超感染。从通过自分泌刺激通过适当组合形成的激动性抗体自主生长的菌株回收抗体基因，能够有效筛选激动性抗体。在该方法中，可以使用抗体作为文库进行有效的筛选。此外，操作简单，不需要复杂的操作。

5. 发明授权

US08787042B2 DC power supply including arrangement to reduce switching loss and a snubber circuit to suppress surge voltages 有权
标题翻译：直流电源包括用于减少开关损耗的装置和缓冲电路以抑制浪涌电压
公开(公告)号：US08787042B2
公开(公告)日：2014-07-22
申请号：US13367653
申请日：2012-02-07
申请人： Yuichiro Nozaki , Tetsuo Kojima , Masafumi Makino
发明人： Yuichiro Nozaki , Tetsuo Kojima , Masafumi Makino
IPC分类号： H02M3/335 , H02M1/34
CPC分类号： H02M3/3378 , Y02B70/1433
摘要： In a DC power supply in which a DC power source and a transformer are connected via a power conversion circuit and a secondary winding of the transformer is connected to a load via a rectifier diode bridge and a filter circuit to supply power to the load, a resonance reactor is provided on an output side of the transformer, a resonant switch circuit including a parallel circuit of a diode and a semiconductor switch and a resonant capacitor is connected in parallel to the rectifier diode bridge and a snubber circuit including a snubber capacitor, a snubber diode and a diode for discharge is connected to a serial resonant circuit including the resonance reactor and the resonant capacitor in the resonant switch circuit to absorb a surge voltage.
摘要翻译：在其中直流电源和变压器通过功率转换电路连接的直流电源和变压器的次级绕组经由整流二极管桥和滤波电路连接到负载以向负载供电，谐振电抗器设置在变压器的输出侧，包括二极管和半导体开关的并联电路和谐振电容器的谐振开关电路并联连接到整流二极管桥和包括缓冲电容器的缓冲电路，缓冲二极管和用于放电的二极管连接到包括谐振电抗器和谐振开关电路中的谐振电容器的串联谐振电路以吸收浪涌电压。

6. 发明申请

US20130330345A1 MULTI-SPECIFIC ANTIGEN-BINDING MOLECULE HAVING ALTERNATIVE FUNCTION TO FUNCTION OF BLOOD COAGULATION FACTOR VIII 有权
标题翻译：具有替代功能的多特异性抗原结合分子对血液凝血因子VIII的功能
公开(公告)号：US20130330345A1
公开(公告)日：2013-12-12
申请号：US13885421
申请日：2011-11-17
申请人： Tomoyuki Igawa , Zenjiro Sampei , Tetsuo Kojima , Tetsuhiro Soeda , Atsushi Muto , Takehisa Kitazawa , Yukiko Nishida , Chifumi Imai , Tsukasa Suzuki , Kazutaka Yoshihashi
发明人： Tomoyuki Igawa , Zenjiro Sampei , Tetsuo Kojima , Tetsuhiro Soeda , Atsushi Muto , Takehisa Kitazawa , Yukiko Nishida , Chifumi Imai , Tsukasa Suzuki , Kazutaka Yoshihashi
IPC分类号： C07K16/40
CPC分类号： C07K16/40 , C07K16/36 , C07K2317/31 , C07K2317/51 , C07K2317/56 , C07K2317/565 , C07K2317/75 , C07K2317/76 , C07K2317/94
摘要： Various bispecific antibodies that specifically bind to both blood coagulation factor IX/activated blood coagulation factor IX and blood coagulation factor X and functionally substitute for the cofactor function of blood coagulation factor VIII, that is, the function to promote activation of blood coagulation factor X by activated blood coagulation factor IX, were produced. From these antibodies, multispecific antigen-binding molecules having a high activity of functionally substituting for blood coagulation factor VIII were successfully discovered.
摘要翻译：各种双特异性抗体特异性结合血液凝固因子IX /活化血液凝固因子IX和血液凝固因子X，并功能取代血液凝固因子VIII的辅因子功能，即促进凝血因子X活化的功能活化血液凝固因子IX。从这些抗体中，成功发现了具有高功能取代凝血因子VIII活性的多特异性抗原结合分子。

7. 发明授权

US08597911B2 Process for producing antibodies 失效
标题翻译：生产抗体的方法
公开(公告)号：US08597911B2
公开(公告)日：2013-12-03
申请号：US10560098
申请日：2004-06-11
申请人： Taro Miyazaki , Tetsuo Kojima
发明人： Taro Miyazaki , Tetsuo Kojima
IPC分类号： C12N15/13
CPC分类号： C07K16/468 , C07K16/00 , C07K16/2866 , C07K2317/626 , C12N2510/02
摘要： Focusing on the fact that antibody molecules with one H chain are not secreted when using the “knobs-into-holes” method, the present inventors revealed that desired bispecific antibodies can be preferentially formed by first expressing the H and L chains of one arm, and then suppressing their expression, followed by expressing the H and L chains of the other arm so that first desired HL molecules (HaLa and HbLb) are constructed, and then the H chains are paired with each other (H2L2). The present invention was thus completed.
摘要翻译：关注当使用“旋钮孔”方法时，不分泌具有一个H链的抗体分子的事实，本发明人揭示了可以通过首先表达一个臂的H和L链来优先形成所需的双特异性抗体，然后抑制其表达，然后表达另一臂的H链和L链，使得构建第一所需的HL分子（HaLa和HbLb），然后H链彼此配对（H2L2）。从而完成了本发明。

8. 发明申请

US20120224396A1 DC POWER SUPPLY 有权
标题翻译：直流电源
公开(公告)号：US20120224396A1
公开(公告)日：2012-09-06
申请号：US13367653
申请日：2012-02-07
申请人： Yuichiro NOZAKI , Tetsuo Kojima , Masafumi Makino
发明人： Yuichiro NOZAKI , Tetsuo Kojima , Masafumi Makino
IPC分类号： H02M3/335
CPC分类号： H02M3/3378 , Y02B70/1433
摘要： In a DC power supply in which a DC power source and a transformer are connected via a power conversion circuit and a secondary winding of the transformer is connected to a load via a rectifier diode bridge and a filter circuit to supply power to the load, a resonance reactor is provided on an output side of the transformer, a resonant switch circuit including a parallel circuit of a diode and a semiconductor switch and a resonant capacitor is connected in parallel to the rectifier diode bridge and a snubber circuit including a snubber capacitor, a snubber diode and a diode for discharge is connected to a serial resonant circuit including the resonance reactor and the resonant capacitor in the resonant switch circuit to absorb a surge voltage.
摘要翻译：在其中直流电源和变压器通过功率转换电路连接的直流电源和变压器的次级绕组经由整流二极管桥和滤波电路连接到负载以向负载供电，谐振电抗器设置在变压器的输出侧，包括二极管和半导体开关的并联电路和谐振电容器的谐振开关电路并联连接到整流二极管桥和包括缓冲电容器的缓冲电路，缓冲二极管和用于放电的二极管连接到包括谐振电抗器和谐振开关电路中的谐振电容器的串联谐振电路以吸收浪涌电压。

9. 发明申请

US20100003254A1 Antibody Substituting for Function of Blood Coagulation Factor VIII 审中-公开
标题翻译：抗体代替血液凝固因子VIII的功能
公开(公告)号：US20100003254A1
公开(公告)日：2010-01-07
申请号：US11910836
申请日：2006-03-31
申请人： Kunihiro Hattori , Tetsuo Kojima , Hiroyuki Saito , Taro Miyazaki , Tetsuhiro Soeda
发明人： Kunihiro Hattori , Tetsuo Kojima , Hiroyuki Saito , Taro Miyazaki , Tetsuhiro Soeda
IPC分类号： A61K39/395 , C07K16/00 , A61P7/00
CPC分类号： C07K16/36 , C07K16/40 , C07K16/468 , C07K2317/24 , C07K2317/31 , C07K2317/56 , C07K2317/622 , C07K2317/75
摘要： The present inventors produced a variety of bispecific antibodies that specifically bind to both F. IX/F. IXa and F. X, and functionally substitute for F. VIIIa, i.e., have a cofactor function to promote F. X activation via F. IXa. Among these antibodies, the antibody A44/B26 reduced coagulation time by 50 seconds or more as compared to that observed when the antibody was not added. The present inventors produced a commonly shared L chain antibody from this antibody using L chains of A44, and showed that A44L can be used as commonly shared L chains, although the activity of the resulting antibody is reduced compared to the original antibody (A44HL-B26HL). Further, with appropriate CDR shuffling, the present inventors successfully produced highly active multispecific antibodies that functionally substitute for coagulation factor VIII.
摘要翻译：本发明人生产了特异性结合F.IX / F两种的各种双特异性抗体。 IXa和F.X，并且功能上替代F.CⅧa，即具有辅因子功能以通过F.Ixa促进F.X活化。在这些抗体中，与未添加抗体时相比，抗体A44 / B26的凝固时间缩短了50秒以上。本发明人使用A44的L链从该抗体生产共同的L链抗体，并且表明尽管与原始抗体（A44HL-B26HL）相比，所得抗体的活性降低，但A44L可以用作共同的L链）。此外，通过适当的CDR改组，本发明人成功地制备了功能性替代凝血因子VIII的高活性多特异性抗体。

10. 发明申请

US20050232328A1 Solid-state laser system 失效
标题翻译：固态激光系统
公开(公告)号：US20050232328A1
公开(公告)日：2005-10-20
申请号：US11090174
申请日：2005-03-28
申请人： Junichi Nishimae , Tetsuo Kojima
发明人： Junichi Nishimae , Tetsuo Kojima
IPC分类号： H01S3/08 , G02B27/09 , H01S3/00 , H01S3/06 , H01S3/07 , H01S3/081 , H01S3/091 , H01S3/10 , H01S3/16 , H01S3/23
CPC分类号： H01S3/0602 , H01S3/005 , H01S3/07 , H01S3/08 , H01S3/08072 , H01S3/0815 , H01S3/091 , H01S3/2316
摘要： A simple and high-reliability constitution provides a solid-state laser system that allows a high-output, long-pulse-width laser beam to be obtained. A solid-state laser system that includes a solid-state laser medium 1, a light source 2 for pumping the solid-state laser medium 1, two reflecting mirrors 3 and 4 for flanking the solid-state laser medium 1, thereby constituting a laser resonator, is constituted in such a manner that a virtual-mirror plane 5 is defined in the space between the solid-state laser medium 1 and the reflecting mirror 4; a lens 6 is provided between the virtual-mirror plane 5 and the reflecting mirror 4; and, by means of the forward and backward paths along the route from the virtual-mirror plane to the reflecting mirror by way of the lens, the virtual-mirror plane in the forward path and the virtual-mirror plane in the backward path are made in an optically conjugated relationship with each other.
摘要翻译：简单且高可靠性的结构提供了一种能够获得高输出，长脉冲宽度的激光束的固态激光系统。一种固态激光系统，包括固体激光介质1，用于泵浦固态激光介质1的光源2，用于固定固体激光介质1侧面的两个反射镜3和4，从而构成激光谐振器构成为在固体激光介质1和反射镜4之间的空间中限定虚拟镜面5; 在虚拟镜面5和反射镜4之间设置透镜6; 借助于通过镜头从虚拟镜面到反射镜的路径的前进和后退路径，使前向路径中的虚拟镜面和后向路径中的虚拟镜面成为彼此具有光学共轭关系。

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