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1. 发明授权

US08562991B2 Antibody molecules that bind to IL-6 receptor 有权
标题翻译：结合IL-6受体的抗体分子
公开(公告)号：US08562991B2
公开(公告)日：2013-10-22
申请号：US12680087
申请日：2009-09-25
申请人： Tomoyuki Igawa , Shinya Ishii , Atsuhiko Maeda , Mika Sakurai , Tetsuo Kojima , Tatsuhiko Tachibana , Hirotake Shiraiwa , Hiroyuki Tsunoda , Yoshinobu Higuchi
发明人： Tomoyuki Igawa , Shinya Ishii , Atsuhiko Maeda , Mika Sakurai , Tetsuo Kojima , Tatsuhiko Tachibana , Hirotake Shiraiwa , Hiroyuki Tsunoda , Yoshinobu Higuchi
IPC分类号： A61K39/395
CPC分类号： C07K16/2866 , A61K39/00 , A61K2039/505 , C07K16/461 , C07K2317/24 , C07K2317/41 , C07K2317/76 , C07K2317/92
摘要： The present invention provides pharmaceutical compositions comprising second-generation molecules that are superior than TOCILIZUMAB, by altering the amino acid sequences of the variable and constant regions of TOCILIZUMAB, which is a humanized anti-IL-6 receptor IgG1 antibody, to enhance the antigen-neutralizing ability and increase the pharmacokinetics, so that the therapeutic effect is exerted with a less frequency of administration, and the immunogenicity, safety and physicochemical properties (stability and homogeneity) are improved. The present invention also provides methods for producing these pharmaceutical compositions. The present inventors have successfully generated second-generation molecules that are superior to TOCILIZUMAB by appropriately combining amino acid sequence alterations in the CDR domains, variable regions, and constant regions.
摘要翻译：本发明通过改变作为人源化抗IL-6受体IgG1抗体的TOCILIZUMAB的可变区和恒定区的氨基酸序列来提供优于TOCILIZUMAB的第二代分子的药物组合物，以增强抗原 - 中和能力增强，药代动力学改善，治疗效果较差，免疫原性，安全性和物理化学性质（稳定性和均一性）均有改善。本发明还提供了制备这些药物组合物的方法。通过适当地组合CDR结构域，可变区和恒定区中的氨基酸序列改变，本发明人成功地生产出优于TOCILIZUMAB的第二代分子。

2. 发明申请

US20110098450A1 Antibody Molecules 有权
标题翻译：抗体分子
公开(公告)号：US20110098450A1
公开(公告)日：2011-04-28
申请号：US12680087
申请日：2009-09-25
申请人： Tomoyuki Igawa , Shinya Ishii , Atsuhiko Maeda , Mika Sakurai , Tetsuo Kojima , Tatsuhiko Tachibana , Hirotake Shiraiwa , Hiroyuki Tsunoda , Yoshinobu Higuchi
发明人： Tomoyuki Igawa , Shinya Ishii , Atsuhiko Maeda , Mika Sakurai , Tetsuo Kojima , Tatsuhiko Tachibana , Hirotake Shiraiwa , Hiroyuki Tsunoda , Yoshinobu Higuchi
IPC分类号： C07K16/28 , C07H21/00 , C12N15/63 , C12P21/02 , C12N5/10
CPC分类号： C07K16/2866 , A61K39/00 , A61K2039/505 , C07K16/461 , C07K2317/24 , C07K2317/41 , C07K2317/76 , C07K2317/92
摘要： The present invention provides pharmaceutical compositions comprising second-generation molecules that are superior than TOCILIZUMAB, by altering the amino acid sequences of the variable and constant regions of TOCILIZUMAB, which is a humanized anti-IL-6 receptor IgG1 antibody, to enhance the antigen-neutralizing ability and increase the pharmacokinetics, so that the therapeutic effect is exerted with a less frequency of administration, and the immunogenicity, safety and physicochemical properties (stability and homogeneity) are improved. The present invention also provides methods for producing these pharmaceutical compositions. The present inventors have successfully generated second-generation molecules that are superior to TOCILIZUMAB by appropriately combining amino acid sequence alterations in the CDR domains, variable regions, and constant regions.
摘要翻译：本发明通过改变作为人源化抗IL-6受体IgG1抗体的TOCILIZUMAB的可变区和恒定区的氨基酸序列来提供优于TOCILIZUMAB的第二代分子的药物组合物，以增强抗原 - 中和能力增强，药代动力学改善，治疗效果较差，免疫原性，安全性和物理化学性质（稳定性和均一性）均有改善。本发明还提供了制备这些药物组合物的方法。通过适当地组合CDR结构域，可变区和恒定区中的氨基酸序列改变，本发明人成功地生产出优于TOCILIZUMAB的第二代分子。

3. 发明申请

US20120253016A1 ANTIBODY MOLECULES THAT BIND TO IL-6 RECEPTOR 审中-公开
标题翻译：与IL-6受体结合的抗体分子
公开(公告)号：US20120253016A1
公开(公告)日：2012-10-04
申请号：US13524528
申请日：2012-06-15
申请人： Tomoyuki Igawa , Shinya Ishii , Atsuhiko Maeda , Mika Sakurai , Tetsuo Kojima , Tatsuhiko Tachibana , Hirotake Shiraiwa , Hiroyuki Tsunoda , Yoshinobu Higuchi
发明人： Tomoyuki Igawa , Shinya Ishii , Atsuhiko Maeda , Mika Sakurai , Tetsuo Kojima , Tatsuhiko Tachibana , Hirotake Shiraiwa , Hiroyuki Tsunoda , Yoshinobu Higuchi
IPC分类号： C07K16/00 , C12N15/63 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/13 , C12P21/02
CPC分类号： C07K16/2866 , A61K39/00 , A61K2039/505 , C07K16/461 , C07K2317/24 , C07K2317/41 , C07K2317/76 , C07K2317/92
摘要： The present invention provides pharmaceutical compositions comprising second-generation molecules that are superior than TOCILIZUMAB, by altering the amino acid sequences of the variable and constant regions of TOCILIZUMAB, which is a humanized anti-IL-6 receptor IgG1 antibody, to enhance the antigen-neutralizing ability and increase the pharmacokinetics, so that the therapeutic effect is exerted with a less frequency of administration, and the immunogenicity, safety and physicochemical properties (stability and homogeneity) are improved. The present invention also provides methods for producing these pharmaceutical compositions. The present inventors have successfully generated second-generation molecules that are superior to TOCILIZUMAB by appropriately combining amino acid sequence alterations in the CDR domains, variable regions, and constant regions.
摘要翻译：本发明通过改变作为人源化抗IL-6受体IgG1抗体的TOCILIZUMAB的可变区和恒定区的氨基酸序列来提供优于TOCILIZUMAB的第二代分子的药物组合物，以增强抗原 - 中和能力增强，药代动力学改善，治疗效果较差，免疫原性，安全性和物理化学性质（稳定性和均一性）均有改善。本发明还提供了制备这些药物组合物的方法。通过适当地组合CDR结构域，可变区和恒定区中的氨基酸序列改变，本发明人成功地生产出优于TOCILIZUMAB的第二代分子。

4. 发明申请

US20110111406A1 ANTIGEN-BINDING MOLECULE CAPABLE OF BINDING TO TWO OR MORE ANTIGEN MOLECULES REPEATEDLY 审中-公开
标题翻译：抗原结合分子能够绑定到两个或更多的抗原分子重复
公开(公告)号：US20110111406A1
公开(公告)日：2011-05-12
申请号：US12936587
申请日：2009-04-10
申请人： Tomoyuki Igawa , Shinya Ishii , Atsuhiko Maeda , Takashi Nakai
发明人： Tomoyuki Igawa , Shinya Ishii , Atsuhiko Maeda , Takashi Nakai
IPC分类号： C12Q1/68 , C07K16/00 , C07K16/44 , C12N5/071 , G01N33/53 , C12P21/02
CPC分类号： C12N15/1037 , A61K39/12 , A61K39/145 , A61K2039/505 , A61K2039/544 , A61K2039/545 , A61K2039/552 , C07K16/244 , C07K16/248 , C07K16/2866 , C07K2317/24 , C07K2317/56 , C07K2317/565 , C07K2317/622 , C07K2317/76 , C07K2317/77 , C07K2317/92 , C12N2760/16111 , C12N2760/16134 , C12N2770/20071 , G01N33/6854 , G01N2500/00
摘要： The present inventors discovered that antibodies having weaker antigen-binding activity at the early endosomal pH in comparison with that at the pH of plasma are capable of binding to multiple antigen molecules with a single antibody molecule, have long half-lives in plasma, and have improved durations of time in which they can bind to antigen.
摘要翻译：本发明人发现，与血浆pH值相比，在早期内体体内具有较弱抗原结合活性的抗体能够用单一抗体分子与多个抗原分子结合，血浆半衰期长改善其与抗原结合的时间持续时间。

5. 发明申请

US20140234340A1 ANTIGEN-BINDING MOLECULE CAPABLE OF BINDING TO PLURALITY OF ANTIGEN MOLECULES REPEATEDLY 审中-公开
标题翻译：抗原分子分子与抗原分子重复结合的抗原结合分子
公开(公告)号：US20140234340A1
公开(公告)日：2014-08-21
申请号：US13990158
申请日：2011-11-30
申请人： Tomoyuki Igawa , Shinya Ishii , Miho Funaki , Naoka Hironiwa , Atsuhiko Maeda , Junichi Nezu , Yoshinao Ruike , Takeshi Baba , Shun Shimizu
发明人： Tomoyuki Igawa , Shinya Ishii , Miho Funaki , Naoka Hironiwa , Atsuhiko Maeda , Junichi Nezu , Yoshinao Ruike , Takeshi Baba , Shun Shimizu
IPC分类号： C07K16/18
摘要： An objective of the present invention is to provide methods for promoting antigen uptake into cells by antigen-binding molecules, methods for increasing the number of times of antigen binding by one antigen-binding molecule, methods for promoting reduction of the antigen concentration in plasma by administering antigen-binding molecules, and methods for improving the plasma retention of an antigen-binding molecule, as well as antigen-binding molecules that allow enhanced antigen uptake into cells, antigen-binding molecules having an increased number of times of antigen binding, antigen-binding molecules that can promote reduction of the antigen concentration in plasma when administered, antigen-binding molecules with improved plasma retention, pharmaceutical compositions comprising the above antigen-binding molecules, and methods for producing them. The present inventors revealed that the above objective can be achieved by using antigen-binding molecules that show calcium-dependent antigen-antibody reaction.
摘要翻译：本发明的目的是提供通过抗原结合分子促进抗原摄入细胞的方法，增加一个抗原结合分子的抗原结合次数的方法，用于促进血浆中抗原浓度降低的方法施用抗原结合分子，以及用于改善抗原结合分子的血浆保留的方法以及允许增强抗原摄入细胞的抗原结合分子，具有增加的抗原结合次数的抗原结合分子，抗原当施用时可促进血浆中抗原浓度的降低的结合分子，具有改善的血浆滞留的抗原结合分子，包含上述抗原结合分子的药物组合物及其制备方法。本发明人发现，通过使用显示钙依赖性抗原 - 抗体反应的抗原结合分子，可以实现上述目的。

6. 发明申请

US20130011866A1 ANTIGEN-BINDING MOLECULE CAPABLE OF BINDING TO TWO OR MORE ANTIGEN MOLECULES REPEATEDLY 审中-公开
公开(公告)号：US20130011866A1
公开(公告)日：2013-01-10
申请号：US13595139
申请日：2012-08-27
申请人： Tomoyuki Igawa , Shinya Ishii , Atsuhiko Maeda , Takashi Nakai
发明人： Tomoyuki Igawa , Shinya Ishii , Atsuhiko Maeda , Takashi Nakai
IPC分类号： G01N33/53
CPC分类号： C12N15/1037 , A61K39/12 , A61K39/145 , A61K2039/505 , A61K2039/544 , A61K2039/545 , A61K2039/552 , C07K16/244 , C07K16/248 , C07K16/2866 , C07K2317/24 , C07K2317/56 , C07K2317/565 , C07K2317/622 , C07K2317/76 , C07K2317/77 , C07K2317/92 , C12N2760/16111 , C12N2760/16134 , C12N2770/20071 , G01N33/6854 , G01N2500/00
摘要： The present inventors discovered that antibodies having weaker antigen-binding activity at the early endosomal pH in comparison with that at the pH of plasma are capable of binding to multiple antigen molecules with a single antibody molecule, have long half-lives in plasma, and have improved durations of time in which they can bind to antigen.

7. 发明申请

US20130131319A1 ANTIBODIES WITH MODIFIED AFFINITY TO FCRN THAT PROMOTE ANTIGEN CLEARANCE 审中-公开
标题翻译：具有改良亲和力的抗体促进抗原清除
公开(公告)号：US20130131319A1
公开(公告)日：2013-05-23
申请号：US13637415
申请日：2011-03-30
申请人： Tomoyuki Igawa , Shinya Ishii , Atsuhiko Maeda , Takashi Nakai
发明人： Tomoyuki Igawa , Shinya Ishii , Atsuhiko Maeda , Takashi Nakai
IPC分类号： C07K16/42
CPC分类号： C07K16/283 , A61K2039/505 , A61K2039/545 , C07K14/70535 , C07K16/18 , C07K16/248 , C07K16/28 , C07K16/2866 , C07K16/4241 , C07K2317/24 , C07K2317/31 , C07K2317/51 , C07K2317/52 , C07K2317/71 , C07K2317/72 , C07K2317/76 , C07K2317/77 , C07K2317/92 , C07K2317/94 , C07K2319/30
摘要： An objective of the present invention is to provide methods for facilitating antigen-binding molecule-mediated antigen uptake into cells, methods for facilitating the reduction of antigen concentration in plasma, methods for increasing the number of antigens to which a single antigen-binding molecule can bind, methods for improving pharmacokinetics of antigen-binding molecules, antigen-binding molecules improved for facilitated antigen uptake into cells, antigen-binding molecules capable of facilitating the reduction of antigen concentration in plasma, antigen-binding molecules capable of repeatedly binding to antigens, antigen-binding molecules with improved pharmacokinetics, pharmaceutical compositions comprising such an antigen-binding molecule, and methods for producing those described above. The present inventors discovered that antigen uptake into cells is facilitated by an antibody having human FcRn-binding activity at the plasma pH and a lower antigen-binding activity at the early endosomal pH than at the plasma pH; such antibodies can increase the number of antigens to which a single antibody molecule can bind; the reduction of antigen in plasma can be facilitated by administering such an antibody; and antibody pharmacokinetics can be improved by using such antibodies.
摘要翻译：本发明的目的是提供促进抗原结合分子介导的抗原向细胞摄取的方法，促进血浆中抗原浓度降低的方法，增加单一抗原结合分子所能抗原数目的方法结合，用于改善抗原结合分子的药代动力学的方法，改进用于促进抗原摄入细胞的抗原结合分子，能够促进血浆中抗原浓度降低的抗原结合分子，能够重复结合抗原的抗原结合分子，具有改善的药代动力学的抗原结合分子，包含这种抗原结合分子的药物组合物，以及用于制备上述那些的方法。本发明人发现，通过在血浆pH下具有人FcRn结合活性的抗体和在早期内体体内的pH低于等离子体pH下抗原结合活性较低的抗体促进了对细胞的吸收; 这样的抗体可以增加单个抗体分子可以结合的抗原的数量; 可以通过施用这样的抗体来促进血浆中抗原的降低; 可以通过使用这样的抗体来改善抗体药代动力学。

8. 发明授权

US08623360B2 Antigen-binding molecule capable of binding to two or more antigen molecules repeatedly 有权
公开(公告)号：US08623360B2
公开(公告)日：2014-01-07
申请号：US13595139
申请日：2012-08-27
申请人： Tomoyuki Igawa , Shinya Ishii , Atsuhiko Maeda , Takashi Nakai
发明人： Tomoyuki Igawa , Shinya Ishii , Atsuhiko Maeda , Takashi Nakai
IPC分类号： A61K39/00 , A61K39/395 , C07K16/00
摘要： The present inventors discovered that antibodies having weaker antigen-binding activity at the early endosomal pH in comparison with that at the pH of plasma are capable of binding to multiple antigen molecules with a single antibody molecule, have long half-lives in plasma, and have improved durations of time in which they can bind to antigen.

9. 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 。

10. 发明授权

US06753932B2 Method and apparatus for controlling convergence of color signals 失效
标题翻译：用于控制彩色信号收敛的方法和装置
公开(公告)号：US06753932B2
公开(公告)日：2004-06-22
申请号：US09859275
申请日：2001-05-17
申请人： Shinya Ishii , Nobuo Yamazaki
发明人： Shinya Ishii , Nobuo Yamazaki
IPC分类号： H04N322
CPC分类号： H04N9/28 , H04N3/2335 , H04N17/045
摘要： An image processing apparatus is disclosed by which correction of convergence and correction of distortion of an image can be performed with a high degree of accuracy. Correction data to be used for correction of position errors of the three colors of red, green and blue obtained by an adjustment apparatus in advance are stored in a storage section. The stored correction data are outputted to a correction waveform outputting section through a control circuit when necessary. The correction waveform outputting section produces correction waveforms based on the correction data inputted thereto and outputs the correction waveforms to a clock signal generation circuit. The clock signal generation circuit generates clocks, and the video data of red, green and blue stored in the memory are read out in response to the clock signals.
摘要翻译：公开了一种图像处理装置，通过该图像处理装置可以高精度地执行图像的收敛和失真校正。用于校正由调节装置预先获得的红色，绿色和蓝色三种颜色的位置误差的校正数据被存储在存储部分中。存储的校正数据在必要时通过控制电路输出到校正波形输出部。校正波形输出部根据输入的校正数据生成校正波形，并将校正波形输出到时钟信号生成电路。时钟信号产生电路产生时钟，并且响应于时钟信号读出存储在存储器中的红色，绿色和蓝色的视频数据。

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