公开(公告)号：US10174319B2

公开(公告)日：2019-01-08

申请号：US15309588

申请日：2015-05-13

Applicant: KNC LABORATORIES CO., LTD. ,  KOBE GAKUIN EDUCATIONAL FOUNDATION

Inventor： Masafumi Matsuo ,  Seiji Matsuda

IPC: A61K48/00 ,  C07H21/02 ,  C07H21/04 ,  C12N15/113 ,  A61K31/7088 ,  A61K31/7115 ,  A61K31/712

Abstract: Insertion of variant exons of CD44 gene of cancer stem cells into its mRNA is inhibited whereupon the cancer stem cells lose their properties so that they are rendered sensitive to anticancer agents and radiation, possibly leading to cancer treatment.A drug for cancer treatment, comprising an antisense oligonucleotide capable of inducing skipping of variant exon(s) of CD44 gene to thereby increase expression of normal CD44 mRNA, a pharmaceutically acceptable salt thereof, a solvate thereof or a prodrug thereof. An oligonucleotide of 20-23 bp having the entirety or a part of any one of the nucleotide sequences as shown in SEQ ID NOS: 1 to 19, a pharmaceutically acceptable salt thereof, a solvate thereof or a prodrug thereof. A drug for inducing skipping of at least one variant exon selected from the group consisting of variant exons 8, 9 and 10 of CD44 gene, comprising the above-described oligonucleotide, a pharmaceutically acceptable salt thereof, a solvate thereof or a prodrug thereof.

公开(公告)号：US09771316B2

公开(公告)日：2017-09-26

申请号：US14761897

申请日：2014-01-21

Applicant: OSAKA UNIVERSITY ,  KNC LABORATORIES CO., LTD.

Inventor： Yoshikatsu Kanai ,  Shushi Nagamori ,  Yoshihiko Kitaura ,  Masahiro Neya ,  Naohiro Matsushita

IPC: C07C217/48 ,  C07D215/233 ,  C07D215/26 ,  C07D409/06 ,  C07D405/06 ,  C07D417/06 ,  C07D413/06 ,  C07D403/12 ,  C07C255/54 ,  C07C271/16 ,  C07C271/20 ,  C07D215/22 ,  C07D333/20 ,  C07C211/09 ,  C07D401/12 ,  C07D405/04 ,  C07C317/22 ,  C07C317/28 ,  C07D409/04 ,  C07C217/04 ,  C07C217/72 ,  C07D413/04 ,  C07C323/20 ,  C07C323/25 ,  C07D417/04 ,  C07D263/32 ,  C07D277/28 ,  C07D209/48 ,  C07C255/37 ,  C07D295/08 ,  C07D213/68 ,  C07D307/52

CPC classification number: C07C217/48 ,  C07C211/09 ,  C07C217/04 ,  C07C217/72 ,  C07C255/37 ,  C07C255/54 ,  C07C271/16 ,  C07C271/20 ,  C07C317/22 ,  C07C317/28 ,  C07C323/20 ,  C07C323/25 ,  C07D209/48 ,  C07D213/68 ,  C07D215/22 ,  C07D215/233 ,  C07D215/26 ,  C07D263/32 ,  C07D277/28 ,  C07D295/08 ,  C07D307/52 ,  C07D333/20 ,  C07D401/12 ,  C07D403/12 ,  C07D405/04 ,  C07D405/06 ,  C07D409/04 ,  C07D409/06 ,  C07D413/04 ,  C07D413/06 ,  C07D417/04 ,  C07D417/06

Abstract: The invention provides a compound having a selective inhibitory activity against highly-expressed LAT-1 in tumor cell. The compound is represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof, and a LAT-1 inhibitor comprising the same.

公开(公告)号：US20240132893A1

公开(公告)日：2024-04-25

申请号：US18278498

申请日：2022-02-21

Applicant: KNC LABORATORIES CO., LTD.

Inventor： Masafumi MATSUO ,  Kazuhiro MAETA

IPC: C12N15/113 ,  A23K20/153 ,  A23L33/13 ,  A61P21/00

CPC classification number: C12N15/1136 ,  A23K20/153 ,  A23L33/13 ,  A61P21/00 ,  C12N2310/11 ,  C12N2310/321

Abstract: A method of inhibiting the function of myostatin is provided.
An antisense oligonucleotide of 15-30 bases or a salt or a solvate thereof, wherein the antisense oligonucleotide has a nucleotide sequence complementary to a target sequence in exon 3 of the myostatin gene and is capable of allowing the expression of a splicing variant of myostatin. A pharmaceutical drug, a food, a feed, an agent for promoting myocyte proliferation and/or hypertrophy, an agent for increasing muscle mass and/or suppressing muscle weakness, an agent for switching the splicing of the myostatin gene from production of myostatin to production of a splicing variant thereof, an agent for decreasing myostatin signaling, and an anticancer agent, each of which comprises the above antisense oligonucleotide or a salt or a solvate thereof.

公开(公告)号：US20230272403A1

公开(公告)日：2023-08-31

申请号：US18016041

申请日：2021-07-19

Applicant: KNC LABORATORIES CO., LTD. ,  KOBE GAKUIN EDUCATIONAL FOUNDATION

Inventor： Masafumi MATSUO ,  Kazuhiro MAETA ,  Tsuyoshi FUJIHARA ,  Itaru OKAMOTO ,  Masahiro NEYA

IPC: C12N15/113 ,  A61P31/12

CPC classification number: C12N15/1137 ,  C12Y304/17023 ,  A61P31/12 ,  C12N2310/11 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2320/33

Abstract: An antisense oligonucleotide is provided which induces exon skipping in ACE2 gene. An antisense oligonucleotide of 15-30 bases or a salt or a solvate thereof, wherein the antisense oligonucleotide has a nucleotide sequence complementary to a target site in exon 18 of angiotensin-converting enzyme 2 gene and is capable of inducing exon skipping in angiotensin-converting enzyme 2 gene. A pharmaceutical drug comprising the antisense oligonucleotide or a salt or a solvate thereof; and an agent for inhibiting the expression of angiotensin-converting enzyme 2 protein and/or for enhancing the expression of soluble angiotensin-converting enzyme 2.

公开(公告)号：US20210230598A1

公开(公告)日：2021-07-29

申请号：US17257412

申请日：2019-07-03

Applicant: NATIONAL UNIVERSITY CORPORATION TOKAI NATIONAL HIGHER EDUCATION AND RESEARCH SYSTEM ,  KNC LABORATORIES CO., LTD.

Inventor： Gen SOBUE ,  Kentaro SAHASHI ,  Shinsuke ISHIGAKI ,  Kuniyuki ENDO ,  Tsuyoshi FUJIHARA ,  Masahiro NEYA ,  Seiji MATSUDA

IPC: C12N15/113 ,  A61P25/28

Abstract: The present invention provides a tau exon 10 skipping-promoting antisense oligonucleotide containing at least one 2′-O, 4′-C-ethylene-bridged nucleic acid, and a nucleotide sequence complementary to a sequence consisting of at least 10 continuous nucleotides in a region consisting of the nucleotide sequence shown in SEQ ID NO: 44 in exon 10 of a tau mRNA precursor. In addition, the present invention provides a tau exon 10 skipping-suppressing antisense oligonucleotide containing at least one 2′-O, 4′-C-ethylene-bridged nucleic acid, and a nucleotide sequence complementary to a sequence consisting of at least 10 continuous nucleotides in a region consisting of the nucleotide sequence shown in SEQ ID NO: 45 in intron 10 of a tau mRNA precursor.

公开(公告)号：US11028390B2

公开(公告)日：2021-06-08

申请号：US16630141

申请日：2018-07-06

Applicant: OSAKA UNIVERSITY ,  KNC LABORATORIES CO., LTD. ,  Aichi Medical University

Inventor： Yoshitaka Nagai ,  Kazuhiro Maeta ,  Toshihide Takeuchi ,  Masahiro Neya ,  Tsuyoshi Fujihara ,  Seiji Matsuda ,  Gen Sobue ,  Shinsuke Ishigaki ,  Kentaro Sahashi

IPC: A61K48/00 ,  C12N15/11 ,  C07H21/02 ,  C07H21/04 ,  C12N15/113 ,  A61P25/28 ,  A61K31/712

Abstract: The present invention provides a suppression type antisense oligonucleotide targeting TDP-43 mRNA, containing a nucleotide sequence complementary to a sequence consisting of at least 10 continuous nucleotides in a nucleotide sequence shown in any of SEQ ID NOs: 2-4, and a promotion type antisense oligonucleotide targeting TDP-43 mRNA, containing a nucleotide sequence complementary to a sequence consisting of at least 10 continuous nucleotides in a nucleotide sequence shown in SEQ ID NO: 5.

公开(公告)号：US20210087220A1

公开(公告)日：2021-03-25

申请号：US16958100

申请日：2018-12-26

Applicant: KNC LABORATORIES CO., LTD.

Inventor： Tsuyoshi FUJIHARA ,  Kenichi NAKAMURA ,  Toru KUROME ,  Daisuke SASAHARA ,  Akiko SHIMAHARA ,  Masahiro NEYA

IPC: C07H21/04

Abstract: The purpose of the present invention is to provide a method for purifying and preparing a highly liposoluble phosphoramidite, as well as a capping reaction using the highly liposoluble phosphoramidite compound, and as well as a method for preparing oligonucleotide by a liquid phase process using a pseudo solid phase protecting group said method comprising the capping reaction step. The present invention also provides a method for preparing a compound represented by formula (I) [wherein, R1, R2 and R3 are defined as described in the Detailed Description], which comprises the following steps: (1) reacting an aliphatic alcohol and a trivalent phosphorus compound in organic solvent in the presence of an activator or an organic base; (2) washing the resulting reaction mixture with water in a reparatory funnel; (3) recovering the organic layer after the step (2) and concentrating it (with the proviso that the organic solvent used in the step (1) is a nitrile solvent, the steps (2) to (3) may be omitted); (4) solubilizing the resulting residue obtained in the step (3) in an aliphatic hydrocarbon solvent (with the proviso that the organic solvent used in the step (1) is an aliphatic hydrocarbon solvent, the steps (2) to (3) may be omitted); (5) washing the aliphatic hydrocarbon solution prepared in the step (4) with a nitrile solvent in a separatory funnel; (6) recovering the aliphatic hydrocarbon solution after the step (5) to obtain a solution of a phosphoramidite compound. Also the present invention provides also a solution containing highly liposoluble phosphoramidite compound obtained by the preparation method, a capping reagent comprising the same solution and optionally an additive, a capping reaction using the same capping reagent, as well as a method for preparing (oligo)nucleotide by using the pseudo solid phase protecting group, said method comprising the capping reaction step.

公开(公告)号：US20200165610A1

公开(公告)日：2020-05-28

申请号：US16630141

申请日：2018-07-06

Applicant: OSAKA UNIVERSITY ,  KNC LABORATORIES CO., LTD. ,  NATIONAL UNIVERSITY CORPORATION NAGOYA UNIVERSITY

Inventor： Yoshitaka NAGAI ,  Kazuhiro MAETA ,  Toshihide TAKEUCHI ,  Masahiro NEYA ,  Tsuyoshi FUJIHARA ,  Seiji MATSUDA ,  Gen SOBUE ,  Shinsuke ISHIGAKI ,  Kentaro SAHASHI

IPC: C12N15/113 ,  A61K31/712 ,  A61P25/28

Abstract: The present invention provides a suppression type antisense oligonucleotide targeting TDP-43 mRNA, containing a nucleotide sequence complementary to a sequence consisting of at least 10 continuous nucleotides in a nucleotide sequence shown in any of SEQ ID NOs: 2-4, and a promotion type antisense oligonucleotide targeting TDP-43 mRNA, containing a nucleotide sequence complementary to a sequence consisting of at least 10 continuous nucleotides in a nucleotide sequence shown in SEQ ID NO: 5.

公开(公告)号：US20170137810A1

公开(公告)日：2017-05-18

申请号：US15309588

申请日：2015-05-13

Applicant: KNC LABORATORIES CO., LTD. ,  KOBE GAKUIN EDUCATIONAL FOUNDATION

Inventor： Masafumi MATSUO ,  Seiji MATSUDA

IPC: C12N15/113

CPC classification number: C12N15/113 ,  A61K31/7088 ,  A61K31/7115 ,  A61K31/712 ,  A61K48/00 ,  C12N2310/111 ,  C12N2310/314 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2320/33

Abstract: Insertion of variant exons of CD44 gene of cancer stem cells into its mRNA is inhibited whereupon the cancer stem cells lose their properties so that they are rendered sensitive to anticancer agents and radiation, possibly leading to cancer treatment.A drug for cancer treatment, comprising an antisense oligonucleotide capable of inducing skipping of variant exon(s) of CD44 gene to thereby increase expression of normal CD44 mRNA, a pharmaceutically acceptable salt thereof, a solvate thereof or a prodrug thereof. An oligonucleotide of 20-23 bp having the entirety or a part of any one of the nucleotide sequences as shown in SEQ ID NOS: 1 to 19, a pharmaceutically acceptable salt thereof, a solvate thereof or a prodrug thereof. A drug for inducing skipping of at least one variant exon selected from the group consisting of variant exons 8, 9 and 10 of CD44 gene, comprising the above-described oligonucleotide, a pharmaceutically acceptable salt thereof, a solvate thereof or a prodrug thereof.