Patents by Inventor Hideyoshi Harashima
Hideyoshi Harashima 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: 20260048021Abstract: The present invention provides: a neutral lipid capable of suppressing the phase transition of endosomal membranes caused by phosphatidylcholine from being inhibited; and a lipid nanoparticle containing the neutral lipid. The present invention pertains to an ionic neutral lipid comprising a compound represented by general formula (I). [In formula (I), R1 is a C1-22 hydrocarbon group; three R1 groups in one molecule may be the same as or different from each other; a1 and a2 are each independently an integer of 0 to 4; b1 and b2 are 0 or 1, satisfying b1+b2=1; R2 and R3 are each independently a hydrogen atom or a C1-3 alkyl group; and R4 is an anionic group.Type: ApplicationFiled: May 31, 2023Publication date: February 19, 2026Applicant: National University Corporation Hokkaido UniversityInventors: Yusuke SATO, Hideyoshi HARASHIMA, Yuichi SUZUKI
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Publication number: 20260021046Abstract: The present invention relates to lipid nanoparticles capable of delivering a target substance to hepatic stellate cells. The lipid nanoparticles are for delivering a target substance to hepatic stellate cells and comprise a pH-sensitive cationic lipid including a hydrophilic portion and two hydrophobic portions, wherein an acid dissociation constant pKa of a lipid membrane constituting the lipid nanoparticles is greater than or equal to 6.7 and less than 8.2.Type: ApplicationFiled: March 9, 2023Publication date: January 22, 2026Inventors: Hideyoshi HARASHIMA, Abubakr Ahmed Younis MAHMOUD, Yusuke SATO
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Publication number: 20250346554Abstract: A method for purifying a composition, the method including a step of dissolving a composition including a compound represented by Formula (1) [in Formula (1), R1 represents —N(R2)—R2 (R2 represents a C1 to C4 alkyl group), each R3 and R4 represents a C3 to C8 alkanediyl group, R5 represents a hydroxyl group, R6 represents —R7—OH (R7 represents a C4 to C12 alkanediyl group) or a hydrogen atom, and n represents an integer of 0 or 1] in an aqueous layer to perform liquid-liquid extraction, in which an oil layer used for the liquid-liquid extraction includes one or more kinds of liquids selected from the group consisting of a ketone-based liquid, an ester-based liquid, and an ether-based liquid, all of which have a solubility parameter (SP value) of 14.8 to 20.5 (MPa1/2).Type: ApplicationFiled: December 14, 2022Publication date: November 13, 2025Applicants: JSR CORPORATION, NATIONAL UNIVERSITY CORPORATION HOKKAIDO UNIVERSITYInventors: Yuta MIYAZAKI, Takayuki ARAI, Masayoshi ITO, Hashiru NEGISHI, Hideyoshi HARASHIMA, Yusuke SATO
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Patent number: 12458605Abstract: The present invention addresses the problem of providing lipid nanoparticles which function as gene transfer carriers capable of selective transfer to the liver or spleen. Lipid nanoparticles which contain a pH-sensitive cationic lipid represented by formula (I) [a represents an integer of 3-5; b represents 0 or 1; R1 and R2 each independently represent a group represented by general formula (A) (R11 and R12 each independently represent a linear or branched C2-15 alkyl group; c represents 0 or 1; v represents an integer of 4-12); and X represents a group represented by general formula (B)(d represents an integer of 0-3; and R3 and R4 each independently represent a C1-4 alkyl group or C2-4 alkenyl group, while R3 and R4 may form a 5- to 7-membered non-aromatic heterocycle) or represents a 5- to 7-membered non-aromatic heterocyclic group]. (I) (R1)(R2)C(OH)—(CH2)a-(O—CO)b-X. (A): (R11)(R12)—CH—(CO—O)c-(CH2)v-. (B):—(CH2)d-N(R3)(R4).Type: GrantFiled: October 1, 2021Date of Patent: November 4, 2025Assignees: National University Corporation Hokkaido University, Nitto Denko CorporationInventors: Yusuke Sato, Hideyoshi Harashima, Kazuki Hashiba, Masamitsu Taguchi, Sachiko Sakamoto, Takuya Shishido, Ayaka Otsu, Yoshiki Maeda
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Patent number: 12365921Abstract: The present invention addresses the problem of providing a lipid nanoparticle in which a nucleic acid, etc., required in genome editing is encapsulated and which can be produced by an alcohol dilution method using flow channels and contributes to high genome editing efficiency. The present invention pertains to a lipid nanoparticle which comprises a lipid component, a DNA nuclease, a guide RNA and a single-stranded oligonucleotide, wherein: the lipid component comprises a pH-sensitive cationic lipid, a neutral phospholipid and a polyalkylene glycol-modified lipid; the ratio of the pH-sensitive cationic lipid relative to the total lipids constituting the lipid nanoparticle is 30-50 mol %; the ratio of the neutral phospholipid relative to the total lipids constituting the lipid nanoparticle is 20-50 mol %; and the ratio of the polyalkylene glycol-modified lipid relative to the total lipids constituting the lipid nanoparticle is 1-4 mol %.Type: GrantFiled: May 27, 2020Date of Patent: July 22, 2025Assignee: National University Corporation Hokkaido UniversityInventors: Yusuke Sato, Hideyoshi Harashima, Manabu Tokeshi, Masatoshi Maeki
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Publication number: 20250205362Abstract: The present invention provides lipid nanoparticles each containing a pH-sensitive cationic lipid represented by formula (I) [wherein a represents an integer of 3 to 5; b represents 0 or 1; R1 and R2 each independently represent a group represented by general formula (A) (wherein R11 and R12 each independently represent a linear or branched C1-15 alkyl group; c represents an integer of 1 to 7; and e represents an integer of 4 to 12); and X represents a group represented by general formula (B) (wherein d represents an integer of 0 to 3; and R3 and R4 each independently represent a C1-4 alkyl group or a C2-4 alkenyl group, in which R3 and R4 may be bonded to each other to form a 5- to 7-membered nonaromatic hetero ring) or a 5- to 7-membered nonaromatic hetero ring group]. (R1)(R2)C(OH)—(CH2)a-(O—CO)b-X (I) (R11)(R12)HC—(CH2)c-(CO—O)—(CH2)e-(A) —(CH2)d-N(R3)(R4) (B) [Chem.Type: ApplicationFiled: February 6, 2023Publication date: June 26, 2025Applicant: NATIONAL UNIVERSITY CORPORATION HOKKAIDO UNIVERSITYInventors: Yusuke Sato, Hideyoshi Harashima, Haruno Onuma
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Publication number: 20250195571Abstract: Provided herein are a method for isolation and transplantation of intact mitochondria to a lymphoid organ (a primary lymphoid tissue or a secondary lymphoid tissue), a composition of cells prepared by using a method described herein, and a method for manufacturing cells described herein. In particular, provided herein are methods of isolating intact mitochondria from a donor cell. Also provided herein are methods of transplanting mitochondria into a recipient cell. In some aspects, the methods can be performed in vivo. Further provided are a composition of cells that include the cells prepared using the methods of the present invention.Type: ApplicationFiled: March 5, 2025Publication date: June 19, 2025Applicant: LUCA Science Inc.Inventors: Masashi SUGANUMA, Hideyoshi HARASHIMA, Yuma YAMADA, Daisuke SASAKI, Takafumi YOKOTA
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Patent number: 12268714Abstract: Provided herein are a method for isolation and transplantation of intact mitochondria to a lymphoid organ (a primary lymphoid tissue or a secondary lymphoid tissue), a composition of cells prepared by using a method described herein, and a method for manufacturing cells described herein. In particular, provided herein are methods of isolating intact mitochondria from a donor cell. Also provided herein are methods of transplanting mitochondria into a recipient cell. In some aspects, the methods can be performed in vivo. Further provided are a composition of cells that include the cells prepared using the methods of the present invention.Type: GrantFiled: September 13, 2019Date of Patent: April 8, 2025Assignee: LUCA Science Inc.Inventors: Masashi Suganuma, Hideyoshi Harashima, Yuma Yamada, Daisuke Sasaki, Takafumi Yokota
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Patent number: 12269001Abstract: Provided are: a flow channel structure with which lipid particles or micelles, which are useful as nano-sized carriers, for example, in drug delivery systems, are produced with good control of particle size; and a method for forming lipid particles or micelles using the same. Said flow channel structure has a two-dimensional structure such as one in which multiple structural elements (baffles) of a specified width are alternately disposed from the two side faces in a micro-sized flow channel through which feedstock solutions are flowed.Type: GrantFiled: April 13, 2018Date of Patent: April 8, 2025Assignee: National University Corporation Hokkaido UniversityInventors: Manabu Tokeshi, Masatoshi Maeki, Yusuke Sato, Hideyoshi Harashima
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Publication number: 20240238202Abstract: The present invention provides lipid nanoparticles that contain a pH-sensitive cationic lipid and a polyalkylene glycol-modified lipid. The pH-sensitive cationic lipid fraction of the total lipids that constitute the lipid nanoparticles is 10-25 mol %, the polyalkylene glycol-modified lipid fraction of the total lipids that constitute the lipid nanoparticles is 0.5-1.75 mol %, and the number average particle size of the lipid nanoparticles is at least 150 nm.Type: ApplicationFiled: May 19, 2022Publication date: July 18, 2024Applicant: NATIONAL UNIVERSITY CORPORATION HOKKAIDO UNIVERSITYInventors: Yusuke Sato, Kosuke Sasaki, Hideyoshi Harashima
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Publication number: 20240050477Abstract: The present invention provides a lipid nanoparticle and the like containing a pH-sensitive cationic lipid represented by formula (1) (in formula (1), R1 and R2 are each independently a straight-chain C10-14 alkyl group, a straight-chain C10-20 alkenyl group having one or two unsaturated bonds, or —CH(R5)(R6)(where R5 and R6 are each independently a straight-chain C5-10 alkyl group); p represents an integer of 3-8; and R3 and R4 are each independently a methyl group or an ethyl group].Type: ApplicationFiled: February 17, 2022Publication date: February 15, 2024Applicant: NATIONAL UNIVERSITY CORPORATION HOKKAIDO UNIVERSITYInventors: Takashi Nakamura, Hideyoshi Harashima, Yusuke Sato, Koharu Yamada, Taisei Nakade
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Publication number: 20240024252Abstract: The present invention addresses the problem of providing lipid nanoparticles which function as gene transfer carriers capable of selective transfer to the liver or spleen. Lipid nanoparticles which contain a pH-sensitive cationic lipid represented by formula (I) [a represents an integer of 3-5; b represents 0 or 1; R1 and R2 each independently represent a group represented by general formula (A) (R11 and R12 each independently represent a linear or branched C2-15 alkyl group; c represents 0 or 1; v represents an integer of 4-12); and X represents a group represented by general formula (B)(d represents an integer of 0-3; and R3 and R4 each independently represent a C1-4 alkyl group or C2-4 alkenyl group, while R3 and R4 may form a 5- to 7-membered non-aromatic heterocycle) or represents a 5- to 7-membered non-aromatic heterocyclic group]. (I) (R1)(R2)C(OH)—(CH2)a—(O—CO)b—X. (A): (R11)(R12)—CH—(CO—O)c—(CH2)v-. (B):—(CH2)d-N(R3)(R4).Type: ApplicationFiled: October 1, 2021Publication date: January 25, 2024Inventors: Yusuke SATO, Hideyoshi HARASHIMA, Kazuki HASHIBA, Masamitsu TAGUCHI, Sachiko SAKAMOTO, Takuya SHISHIDO, Ayaka OTSU, Yoshiki MAEDA
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Patent number: 11814640Abstract: The problem to be solved is to provide a novel expression vector capable of effectively expressing a target protein in mitochondria and suppressing undesirable expression of the target protein in cell organelles other than mitochondria. The present invention provides a recombinant expression vector for expressing a target protein in mitochondria of animal cells, and a lipid membrane structure having the vector encapsulated therein, wherein the recombinant expression vector has a promoter sequence exhibiting a transcription activity in the nuclei of animal cells, and has, under the control of the promoter sequence, a coding region which codes a target protein and includes one or more TGAs as codons corresponding to tryptophan. The recombinant expression vector according to the present invention can more efficiently and selectively express a target protein in mitochondria, and can be used as a more safe and effective drug for treating mitochondrial diseases.Type: GrantFiled: November 28, 2016Date of Patent: November 14, 2023Assignee: LUCA Science Inc.Inventors: Hideyoshi Harashima, Yuma Yamada, Takuya Ishikawa, Hidetaka Akita
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Publication number: 20230132645Abstract: A lipid membrane structure includes, as lipid components, a lipid compound represented by Formula (I): [in the formula, a represents an integer of 3 to 5; b represents an integer of 0 or 1; R1 and R2 each independently represents a linear hydrocarbon group that may have —CO—O—; and X represents a 5- to 7-membered non-aromatic heterocyclic group or a group represented by Formula (B) (in the formula, d represents an integer of 0 to 3, and R3 and R4 each independently represents a C1-4 alkyl group or a C2-4 alkenyl group, where, R3 and R4 may be bonded to each other to form a 5- to 7-membered non-aromatic heterocycle (where, one or two C1-4 alkyl groups or C2-4 alkenyl groups may be substituted on the ring)].Type: ApplicationFiled: November 17, 2022Publication date: May 4, 2023Applicant: NATIONAL UNIVERSITY CORPORATION HOKKAIDO UNIVERSITYInventors: Hideyoshi Harashima, Yusuke Sato
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Publication number: 20230106719Abstract: The present invention addresses the problem of providing a dissolving agent which improves the solubility of a compound such as curcumin that contains an aromatic ring without changing the structure of this compound. The present invention is a compound which is represented by general formula (1). (In the formula, R1 is an alkyl group having 7 to 24 carbon atoms or an alkenyl group; A1 represents an optionally substituted aryl group; Z1 represents a single bond, an alkylene group having from 1 to 6 carbon atoms, or an alkenylene group having from 2 to 5 carbon atoms; and Z2 represents a divalent linking group.Type: ApplicationFiled: February 12, 2021Publication date: April 6, 2023Inventors: Hideyoshi Harashima, Yusuke Sato, Saed Amjad Yousef Abbasi, Shinji Yamashita, Haruki Higashino
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Publication number: 20230043700Abstract: According to the present invention, there is provided a composition comprising a population of mitochondria with a smaller size and a population of lipid membrane-based vesicles encapsulating mitochondria in a closed space and a method for producing the composition.Type: ApplicationFiled: December 25, 2020Publication date: February 9, 2023Inventors: Masashi SUGANUMA, Yuma YAMADA, Hideyoshi HARASHIMA, Daisuke SASAKI, Mitsue HIBINO, Yoshihiro OHTA
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Patent number: 11517528Abstract: A lipid membrane structure includes, as lipid components, a lipid compound represented by Formula (I): (R1)(R2)C(OH)—(CH3)a—(O—CO)b—X??(I) [in the formula, a represents an integer of 3 to 5; b represents an integer of 0 or 1; R1 and R2 each independently represents a linear hydrocarbon group that may have —CO—O—; and X represents a 5- to 7-membered non-aromatic heterocyclic group or a group represented by Formula (B) (in the formula, d represents an integer of 0 to 3, and R3 and R4 each independently represents a C1-4 alkyl group or a C2-4 alkenyl group, where, R3 and R4 may be bonded to each other to form a 5- to 7-membered non-aromatic heterocycle (where, one or two C1-4 alkyl groups or C2-4 alkenyl groups may be substituted on the ring)].Type: GrantFiled: June 15, 2018Date of Patent: December 6, 2022Assignee: NATIONAL UNIVERSITY CORPORATION HOKKAIDO UNIVERSITYInventors: Hideyoshi Harashima, Yusuke Sato
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Publication number: 20220370351Abstract: The present invention pertains to a flow path structure body for forming self-assembling molecular particles. The flow path structure body has a base body and a flow path structure provided to the interior thereof, the flow path structure having a first introduction channel 10 and a second introduction channel 20 that are independent of one another on the upstream side of the flow path structure, and the introduction channels merging at a merging site. The flow path structure has a dilution flow path 40 that is bent three-dimensionally toward the downstream side of the merging site. The dilution flow path 40 has two or more Y structural elements 50 that protrude out in the Y direction and one or more Z structural elements 60 that protrude out in the Z direction within the dilution flow path, and at least two adjacent Y structural elements protrude out alternately in the Y direction.Type: ApplicationFiled: October 4, 2019Publication date: November 24, 2022Inventors: Masatoshi Maeki, Manabu Tokeshi, Hideyoshi Harashima, Yusuke Sato, Niko Kimura
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Patent number: 11395798Abstract: The present invention provides an O/W type emulsion having a volume median diameter of not more than 100 nm and containing a compound represented by the formula (1) wherein Xa and Xb are each independently X1, X2 or a 1,4-piperazinediyl group; s is 1 or 2, R4 is an alkyl group having 1-6 carbon atoms, na and nb are each independently 0 or 1, R1a, R1b, R2a and R2b are each independently an alkylene group having 1-6 carbon atoms, Ya and Yb are each independently an ester bond, or the like, and R3a and R3b are each independently a liposoluble vitamin residue or the like.Type: GrantFiled: June 29, 2016Date of Patent: July 26, 2022Assignees: NOF CORPORATION, NATIONAL UNIVERSITY CORPORATION HOKKAIDO UNIVERSITYInventors: Kota Tange, Yuta Nakai, Hidetaka Akita, Hiroki Tanaka, Ayaka Watanabe, Naoya Miura, Hideyoshi Harashima
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Publication number: 20220213509Abstract: The present invention addresses the problem of providing a lipid nanoparticle in which a nucleic acid, etc., required in genome editing is encapsulated and which can be produced by an alcohol dilution method using flow channels and contributes to high genome editing efficiency. The present invention pertains to a lipid nanoparticle which comprises a lipid component, a DNA nuclease, a guide RNA and a single-stranded oligonucleotide, wherein: the lipid component comprises a pH-sensitive cationic lipid, a neutral phospholipid and a polyalkylene glycol-modified lipid; the ratio of the pH-sensitive cationic lipid relative to the total lipids constituting the lipid nanoparticle is 30-50 mol %; the ratio of the neutral phospholipid relative to the total lipids constituting the lipid nanoparticle is 20-50 mol %; and the ratio of the polyalkylene glycol-modified lipid relative to the total lipids constituting the lipid nanoparticle is 1-4 mol %.Type: ApplicationFiled: May 27, 2020Publication date: July 7, 2022Inventors: Yusuke SATO, Hideyoshi HARASHIMA, Manabu TOKESHI, Masatoshi MAEKI