Patents Assigned to Tokyo Metropolitan Institute of Medical Science
  • Patent number: 11051496
    Abstract: The present invention provides a mouse with liver damage, having a high degree of damage against the mouse's original hepatocytes while having a uPA gene in a heterozygous form, and a method for efficiently preparing the mouse. Specifically, the method for preparing a mouse with liver damage having the uPA gene in a heterozygous form comprises the following steps of: (i) transforming mouse ES cells with a DNA fragment containing a liver-specific promoter/enhancer and cDNA that encodes a urokinase-type plasminogen activator operably linked under the control thereof; (ii) injecting the transformed mouse ES cells obtained in step (i) into a host embryo; (iii) transplanting the host embryo obtained in step (ii) via the injection of the ES cells into the uterus of a surrogate mother mouse, so as to obtain a chimeric mouse; and (iv) crossing the chimeric mice obtained in step (iii), so as to obtain a transgenic mouse in which the DNA fragment is introduced in a heterozygous form.
    Type: Grant
    Filed: March 23, 2018
    Date of Patent: July 6, 2021
    Assignees: TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE, CHUGAI SEIYAKU KABUSHIKI KAISHA, PHOENIXBIO CO., LTD.
    Inventors: Michinori Kohara, Koichi Jishage, Yosuke Kawase, Chise Mukaidani, Hiroki Oshita, Satoko Hamamura
  • Publication number: 20200360363
    Abstract: A novel therapeutic agent effective for the treatment of intellectual disability or autism is disclosed. The therapeutic agent for intellectual disability or autism contains, as an active component(s), at least one selected from the group consisting of tipifarnib and lonafarnib. Examples of the intellectual disability include memory impairment. Examples of the memory impairment include memory impairment caused by abnormality of the Tsc1 gene and/or Tsc2 gene, and epilepsy-induced memory impairment. Also provided is a method of treating intellectual disability or autism, comprising administering an effective amount of at least one selected from the group consisting of tipifarnib and lonafarnib to a patient with intellectual disability or autism.
    Type: Application
    Filed: November 7, 2018
    Publication date: November 19, 2020
    Applicant: TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE
    Inventors: Kanato YAMAGATA, Tadayuki SHIMADA, Hiroko SUGIURA, Shin YASUDA
  • Patent number: 10634684
    Abstract: An object of the present invention is to provide a method for efficiently identifying a polyubiquitinated substrate which is generally not easily identified. The method for identifying a polyubiquitinated substrate includes (1) a step of expressing a trypsin-resistant polyubiquitin chain-binding protein and a ubiquitin ligase in a cell, (2) a step of isolating a complex that contains the trypsin-resistant polyubiquitin chain-binding protein from the cell having undergone the step (1), (3) a step of subjecting the complex isolated by the step (2) to trypsin digestion, and (4) a step of identifying a peptide that has a ubiquitination site from a digested material obtained by the step (3).
    Type: Grant
    Filed: November 13, 2014
    Date of Patent: April 28, 2020
    Assignee: TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE
    Inventors: Yukiko Yoshida, Yasushi Saeki, Hikaru Tsuchiya, Arisa Murakami, Keiji Tanaka
  • Patent number: 10632187
    Abstract: Disclosed is a hemagglutinin-binding peptide producing an anti-influenza virus effect higher than that of existing peptides. Also disclosed are hemagglutinin-binding peptides comprising a polypeptide having any of the following amino acid sequences (i) to (iv): (i) Thr-MeGly-Asp-MePhe-MePhe-Ser-MeSer-His-Tyr-Thr-Val-Pro-Arg (SEQ ID NO: 1); (ii) Arg-Val-Ser-MePhe-Thr-Tyr-MePhe-MeSer-Tyr-Thr-Pro-Ser (SEQ ID NO: 2); (iii) an amino acid sequence with deletions, additions, or substitutions of one or several amino acids in SEQ ID NO: 1 or 2; and (iv) an amino acid sequence having 90% or more sequence identity to that of SEQ ID NO: 1 or 2.
    Type: Grant
    Filed: May 3, 2019
    Date of Patent: April 28, 2020
    Assignees: PeptiDream Inc., Tokyo Metropolitan Institute of Medical Science
    Inventors: Kiichi Kubota, Patrick Reid, Michinori Kohara, Keiichi Masuya, Masaki Ohuchi
  • Publication number: 20190335724
    Abstract: The present invention provides a mouse with liver damage, having a high degree of damage against the mouse's original hepatocytes while having a uPA gene in a heterozygous form, and a method for efficiently preparing the mouse. Specifically, the method for preparing a mouse with liver damage having the uPA gene in a heterozygous form comprises the following steps of: (i) transforming mouse ES cells with a DNA fragment containing a liver-specific promoter/enhancer and cDNA that encodes a urokinase-type plasminogen activator operably linked under the control thereof; (ii) injecting the transformed mouse ES cells obtained in step (i) into a host embryo; (iii) transplanting the host embryo obtained in step (ii) via the injection of the ES cells into the uterus of a surrogate mother mouse, so as to obtain a chimeric mouse; and (iv) crossing the chimeric mice obtained in step (iii), so as to obtain a transgenic mouse in which the DNA fragment is introduced in a heterozygous form.
    Type: Application
    Filed: March 23, 2018
    Publication date: November 7, 2019
    Applicants: TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE, CHUGAI SEIYAKU KABUSHIKI KAISHA, PHOENIXBIO CO., LTD.
    Inventors: Michinori KOHARA, Koichi JISHAGE, Yosuke KAWASE, Chise MUKAIDANI, Hiroki OSHITA, Satoko HAMAMURA
  • Patent number: 10328143
    Abstract: Object of the present invention is to provide a hemagglutinin-binding peptide producing an anti-influenza virus effect higher than that of existing peptides. The present invention provides, for example, a hemagglutinin-binding peptide comprising a polypeptide having any of the following amino acid sequences (i) to (iv): (i) Thr-MeGly-Asp-MePhe-MePhe-Ser-MeSer-His-Tyr-Thr-Val-Pro-Arg (SEQ ID NO: 1); (ii) Arg-Val-Ser-MePhe-Thr-Tyr-MePhe-MeSer-Tyr-Thr-Pro-Ser (SEQ ID NO: 2); (iii) an amino acid sequence with deletions, additions, or substitutions of one or several amino acids in SEQ ID NO: 1 or 2; and (iv) an amino acid sequence having 90% or more sequence identity to that of SEQ ID NO: 1 or 2.
    Type: Grant
    Filed: October 23, 2015
    Date of Patent: June 25, 2019
    Assignees: PeptiDream Inc., Tokyo Metropolitan Institute of Medical Science
    Inventors: Kiichi Kubota, Patrick Reid, Michinori Kohara, Keiichi Masuya, Masaki Ohuchi
  • Patent number: 10327675
    Abstract: The present invention has an objective of evaluating a motor function of a subject with a neurodegenerative disease with high accuracy using a motor function analysis system that utilizes a wrist joint movement of the subject. The motor function analysis system includes: a display unit for displaying image information including a moving target image and a cursor image for tracking the target image; a moving unit used by the subject to move the cursor image; and an analyzer for detecting the tracking status of the target image tracked by the cursor image and analyzing the frequency of the movement components contained in the tracking status.
    Type: Grant
    Filed: April 30, 2014
    Date of Patent: June 25, 2019
    Assignee: TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE
    Inventors: Shinji Kakei, Jongho Lee, Satoshi Orimo, Akira Inaba, Yasuhiro Okada
  • Patent number: 10160979
    Abstract: The present invention can induce stronger cellular immunity to hepatitis C and provide a treatment means and a prevention means that are effective in completely eliminating the hepatitis C virus (HCV). Provided is a pharmaceutical composition for the treatment and/or prevention of hepatitis C, said composition comprising a recombinant vaccinia virus (a) and a recombinant vector (b) and characterized in that after one of the recombinant vaccinia virus (a) and the recombinant vector (b) is administered for initial immunity, the other is administered for additional immunity. The recombinant vaccinia virus (a) contains an expression promoter and all or a portion of the cDNA of the HCV genome. The recombinant vector (b) contains an expression promoter and all or a portion of the cDNA of the HCV (where the cDNA contained in the recombinant vector (b) has a different base sequence than that included in the recombinant vaccinia virus (a)).
    Type: Grant
    Filed: November 11, 2015
    Date of Patent: December 25, 2018
    Assignees: Tokyo Metropolitan Institute of Medical Science, National Institutes of Biomedical Innovation, Health and Nutrition, KM Biologics Co., Ltd.
    Inventors: Michinori Kohara, Yasuhiro Yasutomi, Yumiko Shiogama
  • Publication number: 20180255753
    Abstract: A non-human mammal and an offspring thereof, obtainable by a somatic cell nuclear transfer method using a nucleus of a CD4-positive T cell as a nuclear donor. The non-human mammal of the present invention surely and efficiently shows allergic reactions specific to various antigens that are shown to have associations with an immune allergic disease, such as mites and cedar pollens, so that the non-human mammal can be suitably used as the developmental models of allergic diseases for studies of various diseases by studying or pursuing possibilities of applications to the diseases.
    Type: Application
    Filed: December 2, 2015
    Publication date: September 13, 2018
    Applicant: TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE
    Inventors: Osamu KAMINUMA, Kimiko INOUE, Kazufumi KATAYAMA, Atsuo OGURA
  • Patent number: 9955675
    Abstract: The present invention provides a mouse with liver damage, having a high degree of damage against the mouse's original hepatocytes while having a uPA gene in a heterozygous form, and a method for efficiently preparing the mouse. Specifically, the method for preparing a mouse with liver damage having the uPA gene in a heterozygous form comprises the following steps of: (i) transforming mouse ES cells with a DNA fragment containing a liver-specific promoter/enhancer and cDNA that encodes a urokinase-type plasminogen activator operably linked under the control thereof; (ii) injecting the transformed mouse ES cells obtained in step (i) into a host embryo; (iii) transplanting the host embryo obtained in step (ii) via the injection of the ES cells into the uterus of a surrogate mother mouse, so as to obtain a chimeric mouse; and (iv) crossing the chimeric mice obtained in step (iii), so as to obtain a transgenic mouse in which the DNA fragment is introduced in a heterozygous form.
    Type: Grant
    Filed: April 25, 2013
    Date of Patent: May 1, 2018
    Assignees: TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE, CHUGAI SEIYAKU KABUSHIKI KAISHA, PHOENIXBIO CO., LTD.
    Inventors: Michinori Kohara, Koichi Jishage, Yosuke Kawase, Chise Mukaidani, Hiroki Oshita, Satoko Hamamura
  • Patent number: 9891229
    Abstract: Protein ubiquitylation, an essential post-translational modification, regulates almost every cellular process including protein degradation, protein trafficking, signal transduction, and DNA damage response in eukaryotic cells. The diverse functions of ubiquitylation are thought to be mediated by distinct chain topologies resulting from eight different ubiquitin linkages, chain lengths, and complexities. Currently, ubiquitin linkages are generally thought to be a critical determinant of ubiquitin signaling. However, ubiquitin chain lengths, another key element of ubiquitin signaling, have not been well documented especially in vivo situation during past three decades from the discovery of ubiquitin. The reason of this was simply because no method has been available for determination of ubiquitin chain length in endogenous ubiquitylated substrates. In the present invention, a practical technique for determining the actual length of substrate-attached polyubiquitin chains from biological samples is established.
    Type: Grant
    Filed: September 21, 2017
    Date of Patent: February 13, 2018
    Assignee: Tokyo Metropolitan Institute of Medical Science
    Inventors: Yasushi Saeki, Hikaru Tsuchiya, Ai Kaiho, Keiji Tanaka
  • Patent number: 9891228
    Abstract: Protein ubiquitylation, an essential post-translational modification, regulates almost every cellular process including protein degradation, protein trafficking, signal transduction, and DNA damage response in eukaryotic cells. The diverse functions of ubiquitylation are thought to be mediated by distinct chain topologies resulting from eight different ubiquitin linkages, chain lengths, and complexities. Currently, ubiquitin linkages are generally thought to be a critical determinant of ubiquitin signaling. However, ubiquitin chain lengths, another key element of ubiquitin signaling, have not been well documented especially in vivo situation during past three decades from the discovery of ubiquitin. The reason of this was simply because no method has been available for determination of ubiquitin chain length in endogenous ubiquitylated substrates. In the present invention, a practical technique for determining the actual length of substrate-attached polyubiquitin chains from biological samples is established.
    Type: Grant
    Filed: November 5, 2014
    Date of Patent: February 13, 2018
    Assignee: Tokyo Metropolitan Institute of Medical Science
    Inventors: Yasushi Saeki, Hikaru Tsuchiya, Ai Kaiho, Keiji Tanaka
  • Publication number: 20170357750
    Abstract: The present invention provides a method for evaluating (predicting, etc.) an individual difference (the tendency of every individual) in terms of drug sensitivity and disease vulnerability, comprising using a gene polymorphism of a cyclic AMP responsive element binding protein gene or the like. The method for evaluating drug sensitivity and the method for evaluating disease vulnerability according to the present invention comprise associating a gene polymorphism of a cyclic AMP responsive element binding protein gene or a haplotype constituted by the gene polymorphism with the drug sensitivity and disease vulnerability of an individual.
    Type: Application
    Filed: July 10, 2017
    Publication date: December 14, 2017
    Applicant: TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE
    Inventors: Kazutaka IKEDA, Daisuke NISHIZAWA, Kenichi FUKUDA
  • Patent number: 9804174
    Abstract: A antibody has as a target molecule a ubiquitin protein comprising a phosphorylated serine residue at position 65. In addition, a method is provided for specifically detecting Parkinson's disease at an early stage, in which a target molecule is a ubiquitin protein comprising a phosphorylated serine residue at position 65, a pharmaceutical composition for definitively treating or preventing Parkinson's disease, and a method for screening for the pharmaceutical composition.
    Type: Grant
    Filed: February 13, 2015
    Date of Patent: October 31, 2017
    Assignee: Tokyo Metropolitan Institute of Medical Science
    Inventors: Noriyuki Matsuda, Fumika Koyano, Kei Okatsu, Etsu Go, Mayumi Kimura, Yasushi Saeki
  • Patent number: 9802992
    Abstract: The present invention has the object of providing a cell into which a protein, which can serve as a polymerization nucleus of a protein polymer, or polymer thereof is introduced, and a method for producing the cell. The invention relates to a cell into which a protein, which can serve as a polymerization nucleus of a protein polymer, or a polymer thereof is introduced, a method for producing the cell, and a method of screening for a compound inhibiting an intracellular accumulation of a protein containing fibril structures, wherein the method comprises bringing a candidate substance into contact with the cell.
    Type: Grant
    Filed: December 6, 2006
    Date of Patent: October 31, 2017
    Assignee: TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE
    Inventors: Takashi Nonaka, Sayuri Watanabe, Masami Masuda, Masato Hasegawa
  • Patent number: 9632092
    Abstract: The present invention provides antibodies useful for diagnosing and treating tumors as well as methods of screening for antitumor agents. More specifically, tumors can be diagnosed and treated using an anti-phosphorylated p62 antibody that recognizes phosphorylation of serine at position 351 of an amino acid sequence of SEQ ID No. 1 or at a position corresponding thereto. An antitumor agent can be obtained by screening for a substance that inhibits the phosphorylation or that dephosphorylates the phosphorylated serine.
    Type: Grant
    Filed: July 9, 2015
    Date of Patent: April 25, 2017
    Assignee: Tokyo Metropolitan Institute of Medical Science
    Inventors: Masaaki Komatsu, Yoshinobu Ichimura
  • Patent number: 9624279
    Abstract: The purpose of the present invention is to develop a method for amplifying in vitro to a large amount of a homogenous insoluble aggregate that is equivalent to an insoluble aggregate formed in the brain of a patient. A method of producing an insoluble aggregate including TDP-43 protein and fragments thereof according to the present invention includes the steps of: (1) introducing an insoluble fraction originated from the brain of a neurodegenerative disease patient into a cell culture in which the intact TDP-43 protein can be expressed in a constitutive manner; (2) culturing the cultured cell into which the insoluble fraction has been introduced; and (3) separating an insoluble fraction from the cultured cell. Optionally, the method may additionally include a step of amplifying the insoluble aggregate of the neurodegenerative-disease-related protein in the cultured cell.
    Type: Grant
    Filed: May 18, 2012
    Date of Patent: April 18, 2017
    Assignee: TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE
    Inventors: Takashi Nonaka, Masami Masuda, Makiko Yamashita, Haruhiko Akiyama, Masato Hasegawa
  • Patent number: 9315790
    Abstract: The present invention provides a pharmaceutical composition comprising a protein having ?-galactosidase activity for treating Fabry disease, which causes no allergic side effect, which is highly stable in blood (plasma) and which can readily be taken up by a cell of an affected organ. The pharmaceutical composition for treating Fabry disease of the invention comprises, for example, a protein which acquires an ?-galactosidase activity through alteration of the structure of the active site of wild-type human ?-N-acetylgalactosaminidase.
    Type: Grant
    Filed: September 13, 2013
    Date of Patent: April 19, 2016
    Assignees: TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE, ALTIF LABORATORIES INC.
    Inventors: Hitoshi Sakuraba, Youichi Tajima, Ikuo Kawashima, Seiichi Aikawa, Fumiko Aikawa
  • Patent number: 9193964
    Abstract: The present invention provides, as an enzyme which can be used for enzyme replacement therapy for Fabry disease, a protein having ?-galactosidase activity, which shows no allergic adverse side effect, shows a high stability in blood, and can be easily incorporated into a cell of an affected organ. The protein of the present invention is a protein which has acquired ?-galactosidase activity by changing the structure of the active site of wild-type human ?-N-acetylgalactosaminidase.
    Type: Grant
    Filed: January 23, 2014
    Date of Patent: November 24, 2015
    Assignees: TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE, ALTIF LABORATORIES
    Inventors: Hitoshi Sakuraba, Youichi Tajima, Mai Ito, Seiichi Aikawa, Fumiko Aikawa
  • Patent number: 9175269
    Abstract: The present invention provides modified hepatitis C virus genomic RNA, comprising nucleotide sequences of genomic RNA portions of two or more types of hepatitis C viruses, which comprises a 5? untranslated region, a core protein coding sequence, an E1 protein coding sequence, a p7 protein coding sequence, an E2 protein coding sequence, an NS2 protein coding sequence, an NS3 protein coding sequence, an NS4A protein coding sequence, an NS4B protein coding sequence, an NS5A protein coding sequence, an NS5B protein coding sequence, and a 3? untranslated region, and which can be autonomously replicated. In particular, the present invention relates to modified hepatitis C virus genomic RNA, which can be autonomously replicated by substitution of the RNA sequence portion encoding NS3, NS4, NS5A, and NS5B proteins of hepatitis C virus genomic RNA with a partial RNA sequence encoding NS3, NS4, NS5A, and NS5B proteins of a JFH1 strain shown in SEQ ID NO: 1.
    Type: Grant
    Filed: January 4, 2013
    Date of Patent: November 3, 2015
    Assignees: TORAY INDUSTRIES, INC., TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE
    Inventors: Takaji Wakita, Takanobu Kato, Tomoko Date, Michiko Miyamoto, Ralf Bartenschlager, Jun-ichi Tanabe, Saburo Sone