Patents by Inventor Kiyoshi Nokihara
Kiyoshi Nokihara has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Publication number: 20220041656Abstract: Disclosed are a novel compound having a higher angiogenic effect than that of a known peptide-based angiogenic agent, and an angiogenic agent including the novel compound. The compound is represented by the following formula [1]: Cyclic(Cys-O2Oc-SVV(F/Y)GLRG-Cys)-NH2 (wherein the number of oxyethylene units, represented by O2Oc, is within the range of 2 to 6), the following formula [II]: Cyclic(O2Oc-SVV(F/Y)GLRQ)-NH2 [II] (wherein the number of oxyethylene units, represented by O2Oc, is within the range of 2 to 6), or the following formula [III]: O2Oc-SVV(F/Y)GLR-NH2 [III] (wherein the number of oxyethylene units, represented by O2Oc, is within the range of 2 to 6).Type: ApplicationFiled: October 31, 2019Publication date: February 10, 2022Applicant: HiPep LaboratoriesInventors: Kiyoshi NOKIHARA, Yuki TOMINAGA, Atsushi KITAGAWA, Shun NOKIHARA
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Patent number: 9857369Abstract: A substrate for biochips which has a high probe loading amounts and a uniform immobilization density, and which further has a high detection sensitivity and a high reproducibility by preventing a non-specific adsorption of proteins, when used as a substrate for biochips for immobilizing probes composed of biologically relevant substances such as proteins and nucleic acids, is disclosed. Amino groups can be bound to the surface of the substrate uniformly, at a high density and stably by covalently immobilizing an amino group-containing polymer on the surface of the substrate. The probe immobilization rate is high and immobilizing density was uniform by immobilizing a probe composed of a biologically relevant substance such as a protein or nucleic acid by utilizing the amino groups. Further, detection sensitivity and reproducibility are high by inhibiting non-specific adsorption of proteins.Type: GrantFiled: July 22, 2014Date of Patent: January 2, 2018Assignees: HIPEP LABORATORIES, NIPPON LIGHT METAL COMPANY, LTD.Inventors: Kiyoshi Nokihara, Akiyoshi Hirata, Yasuo Oka, Yasushi Takebayashi
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Patent number: 9778256Abstract: A biochip substrate which is free from cross-contamination due to spot spreading or contact with spots adjacent to each other, and a biochip using the same. A biochip substrate on which multiple valleys for immobilizing biological substances are formed so as to prevent cross-contamination due to spot spreading or contact with spots adjacent to each other, and a biochip using the same are provided. Moreover, it is found out that a desired binding in a target molecule contained in a test sample occurs at a detectable level in a solution system even in the case where a valley have such a small capacity as 1 nL to 10 nL.Type: GrantFiled: June 16, 2006Date of Patent: October 3, 2017Assignees: HIPEP LABORATORIES, NIPPON LIGHT METAL COMPANY, LTD.Inventors: Kiyoshi Nokihara, Yasuo Oka
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Publication number: 20140336081Abstract: A substrate for biochips which has a high probe loading amounts and a uniform immobilization density, and which further has a high detection sensitivity and a high reproducibility by preventing a non-specific adsorption of proteins, when used as a substrate for biochips for immobilizing probes composed of biologically relevant substances such as proteins and nucleic acids, is disclosed. Amino groups can be bound to the surface of the substrate uniformly, at a high density and stably by covalently immobilizing an amino group-containing polymer on the surface of the substrate. The probe immobilization rate is high and immobilizing density was uniform by immobilizing a probe composed of a biologically relevant substance such as a protein or nucleic acid by utilizing the amino groups. Further, detection sensitivity and reproducibility are high by inhibiting non-specific adsorption of proteins.Type: ApplicationFiled: July 22, 2014Publication date: November 13, 2014Applicants: NIPPON LIGHT METAL COMPANY, LTD., HIPEP LABORATORIESInventors: Kiyoshi NOKIHARA, Akiyoshi HIRATA, Yasuo OKA, Yasushi TAKEBAYASHI
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Patent number: 8822607Abstract: A substrate for biochips which has a high probe loading amounts and a uniform immobilization density, and which further has a high detection sensitivity and a high reproducibility by preventing a non-specific adsorption of proteins, when used as a substrate for biochips for immobilizing probes composed of biologically relevant substances such as proteins and nucleic acids, is disclosed. Amino groups can be bound to the surface of the substrate uniformly, at a high density and stably by covalently immobilizing an amino group-containing polymer on the surface of the substrate. The probe immobilization rate is high and immobilizing density was uniform by immobilizing a probe composed of a biologically relevant substance such as a protein or nucleic acid by utilizing the amino groups. Further, detection sensitivity and reproducibility are high by inhibiting non-specific adsorption of proteins.Type: GrantFiled: June 30, 2009Date of Patent: September 2, 2014Assignees: Hipep Laboratories, Nippon Light Metal Company, Ltd.Inventors: Kiyoshi Nokihara, Akiyoshi Hirata, Yasuo Oka, Yasushi Takebayashi
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Patent number: 8455400Abstract: A substrate for biochips with which immobilization is easy, which does not exhibit self-fluorescence, which is easy to manufacture, and which is excellent in flatness and surface precision, is disclosed. A substrate having a substrate body of the biochip, which is made of a metal, and a carbon layer having functional groups formed on the metal substrate body is used as a substrate for biochips. Since the substrate body of the substrate for biochips is made of a metal, the substrate is not only easy to manufacture, but also free from cracking and chipping, so that it allows easy handling, and high flatness and surface precision can be attained. Therefore, the problem that the optical system is hard to focus when detecting fluorescence does not occur. Moreover, since the substrate body is made of a metal, it does not emit fluorescence by itself. In addition, since the carbon layer has functional groups such as amino groups, biologically relevant substances can be easily immobilized.Type: GrantFiled: May 24, 2006Date of Patent: June 4, 2013Assignees: Hipep Laboratories, Nippon Light Metal Company, Ltd.Inventors: Kiyoshi Nokihara, Yasuo Oka
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Patent number: 8148141Abstract: Disclosed is a peptide-immobilized substrate for measuring a target protein, with which the peptide can have a structure required for being recognized by the target protein, with which the accurate loading amount of the peptide can be attained, and by which a trace amount of the target protein may be measured accurately and simply. The peptide-immobilized substrate for measuring a target protein according to the present invention comprises a chemically synthesized peptide having an expected spatial structure or having a binding ability with the target protein, which peptide can bind with the target protein and is immobilized on the substrate.Type: GrantFiled: May 7, 2002Date of Patent: April 3, 2012Assignee: HiPep LaboratoriesInventors: Kiyoshi Nokihara, Hisakazu Mihara
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Publication number: 20110319347Abstract: Disclosed is an antioxidant which can exhibit a higher antioxidant ability than known antioxidative peptides. The antioxidant according to the present invention comprises mimosine and/or a mimosine-containing peptide(s). The mimosine-containing peptide is a peptide which comprises at least one mimosine residue in its amino acid sequence. Mimosine has stronger antioxidant potency than known antioxidative tripeptides even when used as it is alone, and therefore is useful as an antioxidant. In addition, the antioxidant action of a peptide can be increased by introducing mimosine thereinto, thereby obtaining a peptide with higher antioxidant potency than the original one.Type: ApplicationFiled: March 11, 2010Publication date: December 29, 2011Inventors: Kiyoshi Nokihara, Naeko Miyazato
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Patent number: 8057743Abstract: Means for overcoming the problems which the conventional glass microchannel chips have are disclosed. That is, a microchannel chip in which microchannels can be formed at a low cost, and which has a high chemical resistance is disclosed. The microchannel chip is constituted by a substrate made of carbon, which has a channel in its surface; and a cover composed of a glass plate bonded to the substrate. The cover is bonded to the substrate by heating at least a part of the contact surface at which the substrate is in contact with the cover.Type: GrantFiled: June 13, 2008Date of Patent: November 15, 2011Assignees: Hipep Laboratories, Nippon Light Metal Company, Ltd.Inventors: Kiyoshi Nokihara, Yasuo Oka
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Publication number: 20110152409Abstract: A substrate for biochips which has a high probe loading amounts and a uniform immobilization density, and which further has a high detection sensitivity and a high reproducibility by preventing a non-specific adsorption of proteins, when used as a substrate for biochips for immobilizing probes composed of biologically relevant substances such as proteins and nucleic acids, is disclosed. Amino groups can be bound to the surface of the substrate uniformly, at a high density and stably by covalently immobilizing an amino group-containing polymer on the surface of the substrate. The probe immobilization rate is high and immobilizing density was uniform by immobilizing a probe composed of a biologically relevant substance such as a protein or nucleic acid by utilizing the amino groups. Further, detection sensitivity and reproducibility are high by inhibiting non-specific adsorption of proteins.Type: ApplicationFiled: June 30, 2009Publication date: June 23, 2011Inventors: Kiyoshi Nokihara, Akiyoshi Hirata, Yasuo Oka, Yasushi Takebayashi
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Publication number: 20100184622Abstract: A substrate for biochips with which immobilization is easy, which does not exhibit self-fluorescence, which is easy to manufacture, and which is excellent in flatness and surface precision, is disclosed. A substrate having a substrate body of the biochip, which is made of a metal, and a carbon layer having functional groups formed on the metal substrate body is used as a substrate for biochips. Since the substrate body of the substrate for biochips is made of a metal, the substrate is not only easy to manufacture, but also free from cracking and chipping, so that it allows easy handling, and high flatness and surface precision can be attained. Therefore, the problem that the optical system is hard to focus when detecting fluorescence does not occur. Moreover, since the substrate body is made of a metal, it does not emit fluorescence by itself. In addition, since the carbon layer has functional groups such as amino groups, biologically relevant substances can be easily immobilized.Type: ApplicationFiled: May 24, 2005Publication date: July 22, 2010Inventors: Kiyoshi Nokihara, Yasuo Oka
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Publication number: 20100178222Abstract: Means for overcoming the problems which the conventional glass microchannel chips have are disclosed. That is, a microchannel chip in which microchannels can be formed at a low cost, and which has a high chemical resistance is disclosed. The microchannel chip is constituted by a substrate made of carbon, which has a channel in its surface; and a cover composed of a glass plate bonded to the substrate. The cover is bonded to the substrate by heating at least a part of the contact surface at which the substrate is in contact with the cover.Type: ApplicationFiled: June 13, 2008Publication date: July 15, 2010Inventors: Kiyoshi Nokihara, Yasuo Oka
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Publication number: 20100130380Abstract: A biochip substrate which is free from cross-contamination due to spot spreading or contact with spots adjacent to each other, and a biochip using the same. A biochip substrate on which multiple valleys for immobilizing biological substances are formed so as to prevent cross-contamination due to spot spreading or contact with spots adjacent to each other, and a biochip using the same are provided. Moreover, it is found out that a desired binding in a target molecule contained in a test sample occurs at a detectable level in a solution system even in the case where a valley have such a small capacity as 1 nL to 10 nL.Type: ApplicationFiled: June 16, 2006Publication date: May 27, 2010Inventors: Kiyoshi Nokihara, Yasuo Oka
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Patent number: 7091175Abstract: A novel angiogenesis drug which can be clinically used for therapies of human or the like is disclosed. The angiogenesis drug according to the present invention comprises a peptide as an effective component, which has a prescribed amino acid sequence and has an angiogenesis action.Type: GrantFiled: October 2, 2002Date of Patent: August 15, 2006Inventors: Kiyoshi Nokihara, Yoshinosuke Hamada, Nariaki Matsuura, Junzo Takahashi
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Publication number: 20050084902Abstract: Disclosed is a peptide-immobilized substrate for measuring a target protein, with which the peptide can have a structure required for being recognized by the target protein, with which the accurate loading amount of the peptide can be attained, and by which a trace amount of the target protein may be measured accurately and simply. The peptide-immobilized substrate for measuring a target protein according to the present invention comprises a chemically synthesized peptide having an. expected spatial structure or having a binding ability with the target protein, which peptide can bind with the target protein and is immobilized on the substrate.Type: ApplicationFiled: May 7, 2002Publication date: April 21, 2005Inventors: Kiyoshi Nokihara, Hisakazu Mihara
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Publication number: 20040266696Abstract: A novel angiogenesis drug which can be clinically used for therapies of human or the like is disclosed. The angiogenesis drug according to the present invention comprises a peptide as an effective component, which has a prescribed amino acid sequence and has an angiogenesis action.Type: ApplicationFiled: June 1, 2004Publication date: December 30, 2004Inventors: Kiyoshi Nokihara, Yoshinosuke Hamada, Nariaki Matsuura, Junzo Takahashi
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Patent number: 5670647Abstract: A method for recovering an optically pure amino acid derivative from a waste liquor collected after a coupling reaction in peptide synthesis, comprising the steps of (a) adding into the waste liquor, in which an uncoupled amino acid derivative or an uncoupled small peptide fragment is contained, a compound selected from the group consisting of 1-hydroxybenzotriazole (HOBt), 1-hydroxy-7-azabenzotriazole (HOAt), 3-hydroxy-4-oxo-3,4-dihydro-1,2,3-benzotriazine (HOObt) and N-hydroxy-5-norbornen-2,3-dicarboxylic acid imide(HONB); (b) concentrating the waste liquor obtained in step (a); (c) treating a residue obtained in step (b) with an acidic buffer solution containing a tertiary amine; and (d) extracting and purifying the uncoupled amino acid derivative or the uncoupled small peptide fragment under acidic conditions.Type: GrantFiled: March 1, 1996Date of Patent: September 23, 1997Assignee: Shimadzu CorporationInventors: Kiyoshi Nokihara, Michael Kiffe
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Patent number: 5470703Abstract: The present invention relates to a method for peptide C-terminal fragment sequence analysis, in which the fragment collection is carried out on an allylamine group-derivatized polymer membrane or on allylamine group-derivatized glass fiber filter paper; the collected C-terminal fragment is immobilized thereon using a water-soluble carbodiimide etc.; and the obtained immobilized product is subjected directly to amino acid sequence analysis. The present invention also relates to an apparatus for collecting a peptide fragment. According to the method of the present invention, peptides which are rich in hydrophobic groups in their C-terminus and are therefore difficult to trap with polyvalent ion carriers, currently used in the gas-phase sequencer, can be completely analyzed up to their C-terminus. Also, amino acid sequence analysis can be made even when the amount of C-terminal fragments is very small.Type: GrantFiled: October 15, 1993Date of Patent: November 28, 1995Assignee: Shimadzu CorporationInventors: Kiyoshi Nokihara, Rintaro Yamamoto
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Patent number: 5460786Abstract: A cleavage apparatus for obtaining a free peptide after assembly of a peptide on a solid support by solid-phase peptide synthesis equipped with a cleavage cocktail transport line installed between the column for cleavage containing a peptidyl resin and a cleavage cocktail supply bottle, through which a cleavage cocktail is supplied from the bottle to the column and recovered into the cleavage cocktail supply bottle from the column. This apparatus can provide easy, safe, rapid and reliable cleavage in a large scale peptide synthesis.Type: GrantFiled: February 7, 1994Date of Patent: October 24, 1995Assignee: Shimadzu CorporationInventor: Kiyoshi Nokihara
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Patent number: 5442122Abstract: The present invention is directed to a compound represented by the following formula (I), ##STR1## and a linker for peptide synthesis using the above compound. When the linker of the present invention is used for the solid-phase peptide synthesis, it is possible to synthesize those peptides which are sensitive to acid and difficult to synthesize by conventional methods. Also, side reactions can be prevented, and the desired product is produced at a high purity because cleavage can be achieved under milder conditions or in shorter times. In other words, efficient peptide synthesis is possible.Type: GrantFiled: November 3, 1993Date of Patent: August 15, 1995Assignee: Shimadzu CorporationInventors: Masaki Noda, Kiyoshi Nokihara