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1. 发明申请

US20120039879A1 STREPTAVIDIN HAVING LOW IMMUNOGENICITY AND USE THEREOF 有权
标题翻译：具有低免疫原性的STREPTAVIDIN及其使用
公开(公告)号：US20120039879A1
公开(公告)日：2012-02-16
申请号：US13202102
申请日：2010-02-19
申请人： Tatsuhiko Kodama , Takao Hamakubo , Hirofumi Doi , Akira Sugiyama , Kouhei Tsumoto
发明人： Tatsuhiko Kodama , Takao Hamakubo , Hirofumi Doi , Akira Sugiyama , Kouhei Tsumoto
IPC分类号： A61K39/395 , G01N33/82 , C07K19/00 , C07K14/36 , C12N15/31
CPC分类号： B82Y5/00 , A61K47/6898 , C07K14/36 , C07K16/14 , C07K2317/56 , C07K2317/622 , C07K2317/92
摘要： It is an object of the present invention to provide a mutant streptavidin wherein the immunogenicity (antigenicity) in mammals of a streptavidin is reduced. The present invention provides a mutant streptavidin, which comprises an amino acid sequence in which (a) the arginine residue at position 72 is substituted with another amino acid residue, and (b) any one or more of the tyrosine residue at position 10, the tyrosine residue at position 71, the glutamic acid residue at position 89, the arginine residue at position 91, and the glutamic acid residue at position 104 are substituted with other amino acid residues, with respect to the amino acid sequence of a core streptavidin as shown in SEQ ID NO: 2, and which has decreased immunogenicity as compared with that of a wild-type streptavidin.
摘要翻译：本发明的目的是提供一种突变型链霉抗生物素蛋白，其中链霉亲和素的哺乳动物中的免疫原性（抗原性）降低。本发明提供一种突变链霉抗生物素蛋白，其包含其中（a）第72位的精氨酸残基被另一个氨基酸残基取代的氨基酸序列，和（b）第10位的任何一个或多个酪氨酸残基，相对于核心链霉亲和素的氨基酸序列，如图所示，位置71的酪氨酸残基，89位的谷氨酸残基，91位的精氨酸残基和104位的谷氨酸残基被其它氨基酸残基取代与野生型链霉抗生物素蛋白相比具有降低的免疫原性。

2. 发明授权

US08089185B2 Actuator having a rotation prevention link plate 失效
标题翻译：具有旋转防止链板的致动器
公开(公告)号：US08089185B2
公开(公告)日：2012-01-03
申请号：US12305872
申请日：2007-04-19
申请人： Kenta Hatano , Hirofumi Doi , Toshihiko Miyake
发明人： Kenta Hatano , Hirofumi Doi , Toshihiko Miyake
IPC分类号： H02K7/06
CPC分类号： H02K7/06
摘要： An actuator having an output axis which is moved linearly by a rotatory force, and a boss for holding the above-mentioned output axis in such a way that the output axis can move linearly includes a connecting member for propagating the linear motion of the above-mentioned output axis to an external device. The above-mentioned connecting member is comprised of a joint connected to the above-mentioned output axis, and a link plate having an end rotatably connected to the above-mentioned joint, and another end rotatably connected to the external device. A mechanism for preventing rotation of the above-mentioned output axis is constructed of only a connecting portion for connecting the above-mentioned joint, the above-mentioned link plate, and the above-mentioned external device to one another.
摘要翻译：具有通过旋转力线性移动的输出轴的致动器和用于保持上述输出轴线的凸起，使得输出轴线性线性地移动，具有用于传播上述输出轴的直线运动的连接部件，提到的输出轴到外部设备。上述连接构件包括连接到上述输出轴线的接头和具有可旋转地连接到上述接头的端部的连接板，以及可旋转地连接到外部设备的另一端。用于防止上述输出轴的旋转的机构仅由用于将上述接头，上述连接板和上述外部装置彼此连接的连接部分构成。

3. 发明申请

US20080262201A1 Method and a system for predicting protein functional site, a method for improving protein function, and a function-modified protein 有权
标题翻译：用于预测蛋白质功能位点的方法和系统，改善蛋白质功能的方法和功能修饰的蛋白质
公开(公告)号：US20080262201A1
公开(公告)日：2008-10-23
申请号：US11806448
申请日：2007-05-31
申请人： Hirofumi Doi , Hideaki Hiraki , Akio Kanai
发明人： Hirofumi Doi , Hideaki Hiraki , Akio Kanai
IPC分类号： C07K1/00 , G01N33/50
CPC分类号： C12N15/10 , C12N9/1252 , C12N15/102 , Y02A90/22
摘要： The present application provides a method for predicting the functional site of a protein using data of the entire proteins of an organism of which genome data or cDNA data is known. More specifically, the present application provides a method for predicting a protein functional site, comprising the steps of calculating the frequency of occurrence of an oligopeptide in the entire proteins, calculating the value of each amino-acid residue contributing to the frequency of occurrence as the representative value of the function, and predicting the protein functional site by using the representative value of function as an indicator. The present also provides a system for predicting a functional site for automatically performing said methods. Additionally, the present application provides a method for preparing a function-modified protein comprising subjecting the amino-acid residues composing the functional site identified by the method described above to artificial mutation, and a novel thermophilic DNA polymerase prepared by the method.
摘要翻译：本申请提供了使用其基因组数据或cDNA数据已知的生物体的全部蛋白质的数据来预测蛋白质的功能位点的方法。更具体地，本申请提供了一种用于预测蛋白质功能位点的方法，包括以下步骤：计算整个蛋白质中寡肽的发生频率，计算作为发生频率的每个氨基酸残基的值作为发生频率功能的代表性值，并通过使用功能的代表值作为指标预测蛋白质功能位点。本发明还提供一种用于预测用于自动执行所述方法的功能部位的系统。此外，本申请提供了制备功能修饰蛋白质的方法，包括将构成通过上述方法鉴定的功能位点的氨基酸残基进行人工突变，以及通过该方法制备的新型嗜热DNA聚合酶。

4. 发明申请

US20070148150A1 MKK7 activation inhibitor 审中-公开
公开(公告)号：US20070148150A1
公开(公告)日：2007-06-28
申请号：US11705900
申请日：2007-02-14
申请人： Hirofumi Doi , Shinya Hosogi , Naoya Wada
发明人： Hirofumi Doi , Shinya Hosogi , Naoya Wada
IPC分类号： A61K38/54 , C12N9/99
CPC分类号： C07K14/47 , A61K38/1709 , G01N2500/00 , A61K2300/00
摘要： PAK4 and JIK, both of which bind to MKK7 and directly phosphorylate MKK7, were found in the present invention. The present invention provides an inhibitor of c-Jun phosphorylation caused by JNK3 and a method for inhibiting the same, and an agent for preventing and/or treating a disorder attributable to c-Jun phosphorylation caused by JNK3 and a method for preventing and/or treating the same, all of which comprise inhibiting one member selected from the following: the binding of PAK4 to MKK7, the phosphorylation of MKK7 by PAK4, the binding of JIK to MKK7, and the phosphorylation of MKK7 by JIK. Further, the present invention provides a method for identifying a compound that inhibits the binding of PAK4 to MKK7, the phosphorylation of MKK7 caused by PAK4, the binding of JIK to MKK7, or the phosphorylation of MKK7 caused by JIK, as well as the compound obtained thereby. Furthermore, the present invention provides a pharmaceutical composition containing an effective amount of at least one member selected from the group consisting of the aforementioned compound and the aforementioned inhibitor.

5. 发明申请

US20060264363A1 Inhibition of nerve cell death by inhibiting degradation of shc3, atf6 or crebl1 by htra2 and method of ameliorating neurodegenerative diseases 审中-公开
标题翻译：通过抑制htra2抑制shc3，atf6或crebl1的降解和改善神经变性疾病的方法抑制神经细胞死亡
公开(公告)号：US20060264363A1
公开(公告)日：2006-11-23
申请号：US10562942
申请日：2004-09-30
申请人： Hirofumi Doi , Ken Saito
发明人： Hirofumi Doi , Ken Saito
IPC分类号： A61K48/00 , A61K38/54
CPC分类号： G01N33/6896 , A61K45/00 , G01N2500/02 , G01N2510/00
摘要： A novel protein involved in cell-death and a gene encoding the protein, the use thereof to screen for an anti-cell-death factor for use in the treatment of a disorder caused by excessive cell-death or to screen for a remedy for a disorder caused by aberrant suppression of cell-death, and the screening method are provided. Human HtrA2 and human HtrA2-expressing cells and animals to screen for an anti-cell-death factor for use in the treatment of a disorder caused by excessive cell-death, a method for screening for an anti-cell-death factor for use in the treatment of disorder caused by excessive cell-death, and a method for screening for a remedy for a disorder caused by aberrant suppression of cell-death.
摘要翻译：涉及细胞死亡的新蛋白质和编码蛋白质的基因，其用于筛选用于治疗由过度细胞死亡引起的病症的抗细胞死亡因子或筛选用于提供由细胞死亡的异常抑制引起的疾病和筛选方法。人HtrA2和人HtrA2表达细胞和动物筛选用于治疗由过度细胞死亡引起的病症的抗细胞死亡因子，筛选抗细胞死亡因子的方法用于治疗由过度细胞死亡引起的疾病，以及筛选由细胞死亡异常抑制引起的疾病的治疗方法。

6. 发明申请

US20060172360A1 Mkk7 activation inhibitor 失效
标题翻译： Mkk7激活抑制剂
公开(公告)号：US20060172360A1
公开(公告)日：2006-08-03
申请号：US10519465
申请日：2003-06-27
申请人： Hirofumi Doi , Shinya Hosogi , Naoya Wada
发明人： Hirofumi Doi , Shinya Hosogi , Naoya Wada
IPC分类号： A61K38/54 , C12Q1/48
CPC分类号： C07K14/47 , A61K38/1709 , G01N2500/00 , A61K2300/00
摘要： PAK4 and JIK, both of which bind to MKK7 and directly phosphorylate MKK7, were found in the present invention. The present invention provides an inhibitor of c-Jun phosphorylation caused by JNK3 and a method for inhibiting the same, and an agent for preventing and/or treating a disorder attributable to c-Jun phosphorylation caused by JNK3 and a method for preventing and/or treating the same, all of which comprise inhibiting one member selected from the following: the binding of PAK4 to MKK7, the phosphorylation of MKK7 by PAK4, the binding of JIK to MKK7, and the phosphorylation of MKK7 by JIK. Further, the present invention provides a method for identifying a compound that inhibits the binding of PAK4 to MKK7, the phosphorylation of MKK7 caused by PAK4, the binding of JIK to MKK7, or the phosphorylation of MKK7 caused by JIK, as well as the compound obtained thereby. Furthermore, the present invention provides a pharmaceutical composition containing an effective amount of at least one member selected from the group consisting of the aforementioned compound and the aforementioned inhibitor.
摘要翻译：在本发明中发现PAK4和JIK两者都结合MKK7并直接磷酸化MKK7。本发明提供了由JNK3引起的c-Jun磷酸化抑制剂及其抑制方法，以及用于预防和/或治疗由JNK3引起的由c-Jun磷酸化引起的病症的药剂，以及用于预防和/或所有这些都包括抑制选自以下的一种：PAK4与MKK7的结合，PAK4的MKK7的磷酸化，JIK与MKK7的结合以及通过JIK的MKK7的磷酸化。此外，本发明提供了鉴定抑制PAK4与MKK7结合的化合物，由PAK4引起的MKK7的磷酸化，JIK与MKK7的结合或由JIK引起的MKK7的磷酸化的化合物的方法，以及化合物由此获得。此外，本发明提供含有有效量的选自上述化合物和上述抑制剂中的至少一种的药物组合物。

7. 发明申请

US20050164198A1 Mutant sequence analyzer 审中-公开
标题翻译：突变序列分析仪
公开(公告)号：US20050164198A1
公开(公告)日：2005-07-28
申请号：US10513928
申请日：2003-05-12
申请人： Kensaku Imai , Hisayuki Horai , Hirofumi Doi
发明人： Kensaku Imai , Hisayuki Horai , Hirofumi Doi
IPC分类号： C12M1/00 , C12Q1/68 , G06F17/30 , G06F19/22 , H04R23/00 , G06F19/00 , G01N33/48 , G01N33/50
CPC分类号： H04R23/008 , G16B30/00
摘要： All DNA's of a mutant of a sequencing target organic species (e.g., a resistant bacterium, a tumor cell, or a virus) are extracted, and shotgun libraries are generated for the DNA's. DNA fragments are sequentially fetched from these libraries, and each fragment is subjected to sequencing using an automated DNA sequencer. Fragment sequence information such as base sequences of the respective DNA fragments of the mutant output from the sequencer is stored in a fragment sequence database.
摘要翻译：提取测序目标有机物种（例如抗性细菌，肿瘤细胞或病毒）的突变体的所有DNA，并为DNA产生猎枪文库。从这些文库顺序取出DNA片段，并使用自动化DNA测序仪对每个片段进行测序。片段序列信息，例如从定序器输出的突变体的各个DNA片段的碱基序列存储在片段序列数据库中。

8. 发明申请

US20050037449A1 Agent for controlling circadian rhythm disorder 审中-公开
标题翻译：用于控制昼夜节律紊乱的药剂
公开(公告)号：US20050037449A1
公开(公告)日：2005-02-17
申请号：US10901923
申请日：2004-07-29
申请人： Hirofumi Doi , Naoya Wada
发明人： Hirofumi Doi , Naoya Wada
IPC分类号： A61K38/00 , A61K39/00 , A61K45/00 , A61P25/00 , C12Q1/48 , G01N33/68 , C12Q1/68 , A61K31/66
CPC分类号： G01N33/6893 , C12Q1/485 , G01N2500/02
摘要： A method for controlling circadian rhythm disorders is described, characterized by inhibiting the phosphorylation of BMAL1 by c-Jun N-terminal kinase 3 (JNK3) due to the interaction between JNK3 and BMAL1; a method for preventing and/or treating diseases caused by circadian rhythm disorders; and a method for identifying a compound that inhibit phosphorylation of BMAL1 by JNK3. Also provided are: an agent for controlling circadian rhythm disorders, having the above characteristics; an agent for treating and/or preventing diseases caused by circadian rhythm disorders; a compound obtained by the identification method described above; an agent for inhibiting the phosphorylation of BMAL1 by JNK3, containing the compound; an agent for recovering the suppressed transcriptional activity of the complexes containing BMAL1 and CLOCK and for inhibiting the phosphorylation the same, containing an agent for inhibiting the expression and/or function of JNK3; and a pharmaceutical composition containing one of these.
摘要翻译：描述了一种控制昼夜节律紊乱的方法，其特征在于由于JNK3与BMAL1之间的相互作用，通过c-Jun N-末端激酶3（JNK3）抑制BMAL1的磷酸化; 用于预防和/或治疗由昼夜节律紊乱引起的疾病的方法; 以及通过JNK3鉴定抑制BMAL1磷酸化的化合物的方法。还提供：具有上述特征的用于控制昼夜节律紊乱的药剂; 用于治疗和/或预防由昼夜节律紊乱引起的疾病的药剂; 通过上述鉴定方法获得的化合物; 用于抑制含有该化合物的JNK3的BMAL1磷酸化的试剂; 用于回收含有BMAL1和CLOCK的复合物的抑制转录活性并抑制其磷酸化的试剂，其含有抑制JNK3的表达和/或功能的试剂; 和含有这些之一的药物组合物。

9. 发明授权

US06744156B2 Stepping motor having a predetermined number of teeth corresponding to magnetically stable points per rotor rotation 失效
标题翻译：步进电机具有对应于每个转子旋转的磁稳定点的预定齿数
公开(公告)号：US06744156B2
公开(公告)日：2004-06-01
申请号：US09963418
申请日：2001-09-27
申请人： Hirofumi Doi
发明人： Hirofumi Doi
IPC分类号： H02K3700
CPC分类号： H02K37/14 , H02K5/225 , H02K7/116 , H02K16/04
摘要： There is disclosed a stepping motor capable of increasing assembling work efficiency when the tooth of the gear to be driven provided to a driven member is connected to the tooth of the output shaft gear of the rotor of the stepping motor. The number of teeth for an output shaft gear is set to a predetermined ratio with respect to the number of magnetically stable points per rotation of the rotor, such that the gear to be driven can be held by a reference position stopper when a coil is electrified by a regulated electrification pattern. Thus, while the coil is electrified by the regulated electrification pattern, and the gear to be driven is held by the reference position stopper, the tooth respectively of the gear to be driven, and the output shaft gear are connected to each other. Therefore, these teeth are engaged with each other in a normal position with respect to a reference position.
摘要翻译：公开了一种步进电动机，其能够提高组装工作效率，同时将被驱动齿轮的齿设置在从动部件上，与步进电动机的转子的输出轴齿轮的齿连接。输出轴齿轮的齿数相对于转子每旋转的磁稳定点的数量设定为规定比例，使得当线圈通电时被驱动的齿轮可被基准位置止动器保持通过规范的电气化模式。因此，当线圈由调节的带电模式带电时，被驱动的齿轮被基准位置止动器保持，被驱动齿轮和输出轴齿轮彼此连接。因此，这些齿相对于基准位置在正常位置彼此接合。

10. 发明授权

US5928866A Method for preparing mutant genes 失效
标题翻译：突变基因的制备方法
公开(公告)号：US5928866A
公开(公告)日：1999-07-27
申请号：US573419
申请日：1995-12-15
申请人： Fumio Imamoto , Yoshizumi Ishino , Mitsuru Furusawa , Hirofumi Doi
发明人： Fumio Imamoto , Yoshizumi Ishino , Mitsuru Furusawa , Hirofumi Doi
IPC分类号： C12N15/10 , C12Q1/68
CPC分类号： C12N15/102
摘要： This invention provides A method for preparing mutant genes, which comprises the steps of constructing a recombinant plasmid DNA by inserting a gene fragment into a plasmid DNA having a unidirectional origin, introducing the recombinant plasmid DNA into host cell lacking DNA error-correcting function to transform the host cell, and culturing the transformant cell in a condition that any mutations of the inserted gene is detectable. According to the present invention, diverse mutant genes can be prepared in a short period of time.
摘要翻译：本发明提供了一种制备突变基因的方法，包括以下步骤：通过将基因片段插入到具有单向来源的质粒DNA中构建重组质粒DNA，将重组质粒DNA引入缺少DNA错误校正功能的宿主细胞中以转化宿主细胞，并且在插入的基因的任何突变是可检测的条件下培养转化体细胞。根据本发明，可以在短时间内制备各种突变基因。

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