公开(公告)号：US07096406B2

公开(公告)日：2006-08-22

申请号：US10097499

申请日：2002-03-15

申请人： Keisuke Kanazawa ,  Hiroaki Watanabe ,  Yoshinobu Higuchi ,  Hideki Arakawa ,  Yoshiki Okumura ,  Yutaka Sekino

发明人： Keisuke Kanazawa ,  Hiroaki Watanabe ,  Yoshinobu Higuchi ,  Hideki Arakawa ,  Yoshiki Okumura ,  Yutaka Sekino

IPC分类号： G11C29/00 ,  H03M13/00

CPC分类号： G06F11/1072 ,  G11C11/5621

摘要： A N-level cell memory controlled by the memory controller of the invention have an internal configuration in which the plurality of data input/output terminals connected to the second data bus are separated into first through Mth data input/output terminal groups, such that there is no redundancy in the n bits of data associated with one N-level cell. Together with this, the memory controller separates the plurality of data bits on the first data bus into first through Mth data groups, the ECC circuits generate error-correction codes for each of these data groups, and the first through Mth data groups and first through Mth error correction codes are input to the first through Mth data input/output terminals of the N-level cell memory, via the second data bus.

公开(公告)号：US07266664B2

公开(公告)日：2007-09-04

申请号：US10077778

申请日：2002-02-20

申请人： Yoshinobu Higuchi ,  Shinji Mizutani ,  Keisuke Kanazawa

发明人： Yoshinobu Higuchi ,  Shinji Mizutani ,  Keisuke Kanazawa

IPC分类号： G06F12/00

CPC分类号： G11C11/005 ,  G06F13/1673 ,  G06F13/1684

摘要： A memory device includes a nonvolatile memory capable of storing data, a volatile memory capable of being random-accessed, and a controller for transferring data between the nonvolatile memory and the volatile memory and enabling a pseudo access as if the volatile memory were externally directly accessed in accordance with an instruction through an external bus when the data transfer is not performed.

摘要翻译： 存储器装置包括能够存储数据的非易失性存储器，能够被随机存取的易失性存储器，以及用于在非易失性存储器和易失性存储器之间传送数据的控制器，并且能够进行伪访问，就好像外部直接访问易失性存储器一样 当不执行数据传输时，根据通过外部总线的指令。

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。

公开(公告)号：US08431127B2

公开(公告)日：2013-04-30

申请号：US12746229

申请日：2008-12-05

申请人： Yoshinobu Higuchi ,  Keiko Kasutani ,  Hidetomo Kitamura ,  Masakazu Hasegawa

发明人： Yoshinobu Higuchi ,  Keiko Kasutani ,  Hidetomo Kitamura ,  Masakazu Hasegawa

IPC分类号： A61K39/395 ,  C07K16/28

CPC分类号： C07K16/2869 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/76

摘要： The present inventors isolated clone BM095 from a human antibody phage library, which had a strong growth inhibitory activity in the IL-31-dependent Ba/F3 cell growth assay system. When administered to pruritus model mice, the anti-mouse NR10 neutralizing antibody exhibited a marked symptom-suppressing effect. Thus, it was revealed that anti-NR10 neutralizing antibodies are useful as therapeutic agents for pruritus.

摘要翻译： 本发明人从人抗体噬菌体文库中分离克隆BM095，其在IL-31依赖性Ba / F3细胞生长测定系统中具有强的生长抑制活性。 当施用于瘙痒模型小鼠时，抗小鼠NR10中和抗体表现出明显的症状抑制作用。 因此，显示抗NR10中和抗体可用作瘙痒的治疗剂。

公开(公告)号：USD585448S1

公开(公告)日：2009-01-27

申请号：US29300057

申请日：2008-02-15

申请人： Tomonori Kawaguchi ,  Masahiro Takase ,  Minako Eguchi ,  Jun Ebisawa ,  Chikako Hasegawa ,  Yoshinobu Higuchi

设计人： Tomonori Kawaguchi ,  Masahiro Takase ,  Minako Eguchi ,  Jun Ebisawa ,  Chikako Hasegawa ,  Yoshinobu Higuchi

公开(公告)号：US06294354B1

公开(公告)日：2001-09-25

申请号：US08878177

申请日：1997-06-18

申请人： Masahiro Iwamoto ,  Yoshinobu Higuchi ,  Maurizio Pacifici ,  Joel Rosenbloom

发明人： Masahiro Iwamoto ,  Yoshinobu Higuchi ,  Maurizio Pacifici ,  Joel Rosenbloom

IPC分类号： C12P2186

CPC分类号： C07K14/465

摘要： This invention provides cell-calcification inhibitory proteins as well as genes encoding the proteins. Based on the discovery of a novel isoform gene of the c-erg gene (herein referred to as “C-11 gene”) which is an erg gene derived from chickens, the nucleotide sequence of the gene has been determined, and then the expression of a protein encoded by such gene (herein referred to as “C-11 protein”) has been confirmed. Further, it has been discovered that when the c-erg or C-11 gene is introduced into osteoblasts, the calcification of the cells is inhibited.

摘要翻译： 本发明提供了细胞钙化抑制蛋白以及编码蛋白质的基因。 基于发现一种来自鸡的erg基因的c-gerg基因（本文中称为“C-11基因”）的新型同种型基因，已经确定了该基因的核苷酸序列， 的这种基因编码的蛋白质（本文中称为“C-11蛋白质”）已被证实。 此外，已经发现，当将c-g或C-11基因导入成骨细胞时，细胞的钙化被抑制。

公开(公告)号：US20090275030A1

公开(公告)日：2009-11-05

申请号：US12353382

申请日：2009-01-14

申请人： Masahiro IWAMOTO ,  Yoshinobu Higuchi ,  Maurizio Pacifici ,  Joel Rosenbloom

发明人： Masahiro IWAMOTO ,  Yoshinobu Higuchi ,  Maurizio Pacifici ,  Joel Rosenbloom

IPC分类号： C12Q1/68 ,  C07K14/00 ,  C07H21/04 ,  C07K16/00

CPC分类号： C07K14/465

摘要： This invention provides cell-calcification inhibitory proteins as well as genes encoding the proteins. Based on the discovery of a novel isoform gene of the c-erg gene (herein referred to as “C-11 gene”) which is an erg gene derived from chickens, the nucleotide sequence of the gene has been determined, and then the expression of a protein encoded by such gene (herein referred to as “C-11 protein”) has been confirmed. Further, it has been discovered that when the c-erg or C-11 gene is introduced into osteoblasts, the calcification of the cells is inhibited.

摘要翻译： 本发明提供了细胞钙化抑制蛋白以及编码蛋白质的基因。 基于发现一种来自鸡的erg基因的c-gerg基因（本文中称为“C-11基因”）的新型同种型基因，已经确定了该基因的核苷酸序列， 的这种基因编码的蛋白质（本文中称为“C-11蛋白质”）已被证实。 此外，已经发现，当将c-g或C-11基因导入成骨细胞时，细胞的钙化被抑制。

公开(公告)号：US07494970B2

公开(公告)日：2009-02-24

申请号：US10851328

申请日：2004-05-24

申请人： Masahiro Iwamoto ,  Yoshinobu Higuchi ,  Maurizio Pacifici ,  Joel Rosenbloom

发明人： Masahiro Iwamoto ,  Yoshinobu Higuchi ,  Maurizio Pacifici ,  Joel Rosenbloom

IPC分类号： C07K14/00

CPC分类号： C07K14/465

摘要： This invention provides cell-calcification inhibitory proteins as well as genes encoding the proteins. Based on the discovery of a novel isoform gene of the c-erg gene (herein referred to as “C-11 gene”) which is an erg gene derived from chickens, the nucleotide sequence of the gene has been determined, and then the expression of a protein encoded by such gene (herein referred to as “C-11 protein”) has been confirmed. Further, it has been discovered that when the c-erg or C-11 gene is introduced into osteoblasts, the calcification of the cells is inhibited.

摘要翻译： 本发明提供了细胞钙化抑制蛋白以及编码蛋白质的基因。 基于发现一种来自鸡的erg基因的c-gerg基因（本文中称为“C-11基因”）的新型同种型基因，已经确定了该基因的核苷酸序列， 的这种基因编码的蛋白质（本文中称为“C-11蛋白质”）已被证实。 此外，已经发现，当将c-g或C-11基因导入成骨细胞时，细胞的钙化被抑制。

公开(公告)号：US06549459B2

公开(公告)日：2003-04-15

申请号：US09978014

申请日：2001-10-17

申请人： Yoshinobu Higuchi

发明人： Yoshinobu Higuchi

IPC分类号： G11C1606

CPC分类号： G11C29/82 ,  G06F11/1024

摘要： In a flash memory, error management units which store information on a physical occurrence position of an error which occurred during data reading are prepared by as much as the number of bits which can be corrected by an error correction code, in a redundant portion of a physical page. If the number of positions on which the error have occurred in a same physical page exceeds the number of the prepared error management units, then it is judged that the defect is uncorrectable.

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。