Patents Assigned to BONAC CORPORATION
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Publication number: 20230357767Abstract: The present invention aims to provide a new nucleic acid molecule for suppressing expression of the target gene, which (1) has a gene expression suppressing activity equivalent to or higher than that of siRNA, (2) shows no off-target effect of the sense strand, and (3) makes it possible to design a wider range of antisense strand sequences (extends the range of targetable sequences). Since the nucleic acid molecule of the following formula: wherein each symbol is as defined in the DESCRIPTION, has the superior properties of the above-mentioned (1) to (3), it is extremely useful as a novel gene expression inhibitor that replaces conventional siRNA.Type: ApplicationFiled: August 25, 2021Publication date: November 9, 2023Applicant: BONAC CORPORATIONInventors: Atsushi SHIBATA, Tadaaki OHGI, Tomoaki ABE, Chisato EMURA, Eriko AOKI, Hisao SHIROHZU, Yusuke IWAKAMI, Melisa ACOSTA RAMIREZ, Kota NAITO
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Publication number: 20230183283Abstract: The present invention aims to provide a method of producing, more efficiently at a high purity, a phosphoramidite preferable for the production (synthesis) of a nucleic acid. Using a coupling reaction of an ether represented by the following chemical formula (105), an enantiomer, tautomer or stereoisomer thereof, or a salt thereof, and a glycoside compound, phosphoramidite that enables efficient synthesis of nucleic acid can be obtained: wherein n is a positive integer, and R and R? are the same or different and each is a hydrogen atom or a hydroxyl-protecting group.Type: ApplicationFiled: October 13, 2017Publication date: June 15, 2023Applicant: BONAC CORPORATIONInventors: Tadaaki OHGI, Eriko AOKI, Takashi KINOSHITA, Akihiro ITOH, Chisato EMURA
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Patent number: 11518994Abstract: The invention provides an artificial sgRNA and a CRISPR/Cas9 system by combining the artificial sgRNA and Cas9. Activity of the sgRNA can be retained even when a nucleotide linker region for forming a single strand by linking the 3?-terminal of crRNA and the 5?-terminal of tracrRNA in sgRNA is substituted with an amino acid derivative linker, when the linker region existing between stem-loop 1 and stem-loop 2 of tracrRNA and/or the loop portion of stem-loop 2 are/is substituted with an amino acid derivative linker, or when an amino acid derivative linker is added/inserted into the vicinity of the 5?-terminal and/or the 3?-terminal of sgRNA. Stability in vivo can be improved by introducing one or more amino acid derivative linkers into the sgRNA.Type: GrantFiled: January 30, 2017Date of Patent: December 6, 2022Assignee: BONAC CORPORATIONInventors: Eriko Aoki, Tadaaki Ohgi, Takashi Kinoshita
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Patent number: 11142769Abstract: The present invention provides a single-stranded nucleic acid molecule having a delivery function and capable of inhibiting expression of a target gene. The single-stranded nucleic acid molecule of the present invention is a single-stranded nucleic acid molecule composed of a region (Xc), a linker region (Lx) and a region (X), wherein said region (Xc) is complementary to said region (X), at least one of said region (X) and said region (Xc) contains an expression inhibitory sequence that inhibits expression of the target gene, and a bio-related substance having a delivery function is bonded to at least one selected from the group consisting of the 5?-terminus, the 3?-terminus, and said linker region (Lx).Type: GrantFiled: March 26, 2016Date of Patent: October 12, 2021Assignee: BONAC CORPORATIONInventors: Eriko Aoki, Shiori Kato, Tadaaki Ohgi
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Publication number: 20210188895Abstract: The invention provides a single-stranded nucleic acid molecule and a production method thereof. The single-stranded nucleic acid molecule is represented by formula (I): wherein each symbol is as described in the description.Type: ApplicationFiled: October 12, 2018Publication date: June 24, 2021Applicant: BONAC CORPORATIONInventors: Tadaaki OHGI, Chisato EMURA, Takashi KINOSHITA
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Patent number: 11027023Abstract: The present invention provides a natural type miRNA, which is a single-stranded nucleic acid containing X region and Y region, wherein the 3?-terminus of said X region and the 5?-terminus of said Y region are linked via a linker region of a non-nucleotide structure, the X region contains (a) a guide strand sequence or (b) a passenger strand sequence of a mature miRNA, when the X region contains (a), the Y region contains a passenger strand sequence of the mature miRNA, when the X region contains (b), the Y region contains a guide strand sequence of the mature miRNA, and the guide strand sequence and the passenger strand sequence form a double-stranded structure.Type: GrantFiled: December 25, 2015Date of Patent: June 8, 2021Assignee: BONAC CORPORATIONInventors: Eriko Aoki, Yasuhiko Yoshida, Shiori Kato, Tadaaki Ohgi
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Patent number: 10934542Abstract: The invention provides an artificial match-type miRNA utilizing miRNA. In particular, the invention provides a single strand nucleic acid containing an X region and a Y region, wherein the 3?-terminal of the X region and the 5?-terminal of the Y region are linked via a linker region of a non-nucleotide structure, the X region contains a guide strand sequence of a mature miRNA, and the Y region contains a sequence completely complementary to the X region is an artificial match-type miRNA. The artificial match-type miRNA can suppress expression of the target gene.Type: GrantFiled: December 27, 2014Date of Patent: March 2, 2021Assignees: BONAC CORPORATION, TOKYO MEDICAL UNIVERSITYInventors: Masahiko Kuroda, Shinichiro Ohno, Eriko Aoki, Yasuhiko Yoshida, Shiori Kato, Tadaaki Ohgi
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Patent number: 10751426Abstract: The present invention provides a composition containing a single-stranded nucleic acid molecule consisting of a nucleotide sequence shown by 5?-AGCAGAGUACACACAGCAUAUACC-P-GGUAUAUGCUGUGUGUACUCUGCUUC-P-G-3? (SEQ ID NO: 1) (in the sequence, P is a proline derivative linker represented by (I) in the DESCRIPTION) and a buffer, and having the following features: (a) being in the form of a solution at ambient temperature; and (b) a content of the nucleic acid molecule after storage at 25° C., relative humidity 60% for 4 weeks, of not less than 80% relative to the content at the time of start of the storage.Type: GrantFiled: October 28, 2016Date of Patent: August 25, 2020Assignees: BONAC CORPORATIONInventors: Taimu Yamada, Hidekazu Toyofuku, Kohei Tahara, Risako Onodera, Hirofumi Takeuchi
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Publication number: 20200038427Abstract: The present invention aims to provide a nucleic acid molecule having improved stability in serum and capable of exhibiting a gene expression regulation function after transfer into the cell. A cyclic nucleic acid molecule represented by the following formula (A): wherein each symbol is as described in the DESCRIPTION can be synthesized easily at a low cost, and can inhibit the translation of a protein encoded by the gene. Since the cyclic nucleic acid molecule of the present invention can inhibit the expression of a target gene as described above, for example, it is useful as a pharmaceutical product, a diagnostic agent, an agricultural chemical, and a tool for conducting research on agriculture, medical science, life science, and the like.Type: ApplicationFiled: March 30, 2018Publication date: February 6, 2020Applicant: BONAC CORPORATIONInventors: Tadaaki OHGI, Chisato EMURA, Junichi YASUOKA, Yutaka EGUCHI
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Publication number: 20190382758Abstract: The invention provides an artificial sgRNA and a CRISPR/Cas9 system by combining the artificial sgRNA and Cas9. Activity of the sgRNA can be retained even when a nucleotide linker region for forming a single strand by linking the 3?-terminal of crRNA and the 5?-terminal of tracrRNA in sgRNA is substituted with an amino acid derivative linker, when the linker region existing between stem-loop 1 and stem-loop 2 of tracrRNA and/or the loop portion of stem-loop 2 are/is substituted with an amino acid derivative linker, or when an amino acid derivative linker is added/inserted into the vicinity of the 5?-terminal and/or the 3?-terminal of sgRNA. Stability in vivo can be improved by introducing one or more amino acid derivative linkers into the sgRNA.Type: ApplicationFiled: January 30, 2017Publication date: December 19, 2019Applicant: BONAC CORPORATIONInventors: Eriko AOKI, Tadaaki OHGI, Takashi KINOSHITA
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Patent number: 10377788Abstract: The invention provides a production method of a glycoside compound or a salt thereof, which includes subjecting a thioether compound and an alcohol compound to a coupling reaction in the presence of a halogenating agent, a desiccant and a Lewis acid, and then distillation in the presence of at least one kind of additive selected from a sulfur-containing antioxidant and a maleimide group-containing compound to give a thioether compound and a step of subjecting a glycoside compound and a thioether compound to a coupling reaction in the presence of a halogenating agent, a desiccant and a Lewis acid to give a glycoside compound. By this method, a phosphoramidite preferable for the production (synthesis) of a nucleic acid can be produced more efficiently at a high purity.Type: GrantFiled: April 1, 2016Date of Patent: August 13, 2019Assignee: BONAC CORPORATIONInventors: Eriko Aoki, Takashi Kinoshita, Akihiro Itoh, Tadaaki Ohgi
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Patent number: 10337009Abstract: The invention provides a single-stranded nucleic acid molecule of (A) or (B) containing a TGF-?1 gene expression inhibitory sequence. The single-stranded nucleic acid molecule (A) consists of region (Xc), linker region (Lx) and region (X) from the 5?-side to the 3?-side, wherein linker region (Lx) has a non-nucleotide structure containing at least one of a pyrrolidine skeleton and a piperidine skeleton, and at least one of region (X) and region (Xc) contains the expression inhibitory sequence.Type: GrantFiled: December 15, 2015Date of Patent: July 2, 2019Assignee: BONAC CORPORATIONInventors: Takahiro Matsumoto, Hidekazu Toyofuku
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Patent number: 10238752Abstract: The invention provides a single-stranded nucleic acid capable of inhibiting expression of a target gene having a delivery function. The nucleic acid contains, from the 5?-side to the 3?-side, a 5?-side region (Xc), a linker region (Lx), an inner region (Z), a linker region (Ly) and a 3?-side region (Yc) in this order, wherein the inner region (Z) is constituted by linkage of the inner 5?-side region (X) and the inner 3?-side region (Y), the 5?-side region (Xc) is complementary to the inner 5?-side region (X), the 3?-side region (Yc) is complementary to the inner 3?-side region (Y), at least one of the inner region (Z), the 5?-side region (Xc) and the 3?-side region (Yc) comprises an expression inhibitory sequence that inhibits expression of a target gene, and at least one of the 5?-terminus, the 3?-terminus, the linker region (Lx) and the linker region (Ly) is bound to a bio-related substance.Type: GrantFiled: April 25, 2017Date of Patent: March 26, 2019Assignee: Bonac CorporationInventors: Tadaaki Ohgi, Eriko Aoki, Chisato Emura, Tomohiro Hamasaki
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Patent number: 10233446Abstract: The invention provides a microRNA inhibitor that has two or more sequences complementary to the sequence of microRNA to be the target of inhibition, which two or more complementary sequences are linked via one or more linker residues.Type: GrantFiled: June 30, 2016Date of Patent: March 19, 2019Assignee: Bonac CorporationInventors: Tadaaki Ohgi, Hisao Shirohzu, Hiroshi Suzuki, Tomohiro Hamasaki, Takayuki Mizutani
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Publication number: 20190010503Abstract: The present invention provides a single-stranded nucleic acid molecule inhibiting expression of a prorenin gene or a prorenin receptor gene, comprising only region (X), linker region (Lx) and region (Xc), wherein the aforementioned linker region (Lx) has a non-nucleotide structure comprising at least one of a pyrrolidine skeleton and a piperidine skeleton, and at least one of the aforementioned region (X) and the aforementioned region (Xc) comprises an expression inhibitory sequence comprising a nucleotide sequence consisting of at least 18 continuous nucleotides in any of an expression inhibitory sequence of a prorenin gene shown in SEQ ID NO: 1 to 5 and an expression inhibitory sequence of prorenin receptor gene shown in SEQ ID NO: 6 to 11.Type: ApplicationFiled: December 29, 2016Publication date: January 10, 2019Applicants: NATIONAL UNIVERSITY CORPORATION HOKKAIDO UNIVERSITY, TOKYO MEDICAL UNIVERSITY, BONAC CORPORATIONInventors: Susumu ISHIDA, Atsuhiro KANDA, Masahiko KURODA, Hidekazu TOYOFUKU
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Publication number: 20180339064Abstract: The present invention provides a composition containing a single-stranded nucleic acid molecule consisting of a nucleotide sequence shown by 5?-AGCAGAGUACACACAGCAUAUACC-P-GGUAUAUGCUGUGUGUACUCUGCUUC-P-G-3? (SEQ ID NO: 1) (in the sequence, P is a proline derivative linker represented by (I) in the DESCRIPTION) and a buffer, and having the following features: (a) being in the form of a solution at ambient temperature; and (b) a content of the nucleic acid molecule after storage at 25° C., relative humidity 60% for 4 weeks, of not less than 80% relative to the content at the time of start of the storage.Type: ApplicationFiled: October 28, 2016Publication date: November 29, 2018Applicants: BONAC CORPORATIONInventors: Taimu YAMADA, Hidekazu TOYOFUKU, Kohei TAHARA, Risako ONODERA, Hirofumi TAKEUCHI
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Publication number: 20180326091Abstract: The present invention provides a natural type miRNA, which is a single-stranded nucleic acid containing X region and Y region, wherein the 3?-terminus of said X region and the 5?-terminus of said Y region are linked via a linker region of a non-nucleotide structure, the X region contains (a) a guide strand sequence or (b) a passenger strand sequence of a mature miRNA, when the X region contains (a), the Y region contains a passenger strand sequence of the mature miRNA, when the X region contains (b), the Y region contains a guide strand sequence of the mature miRNA, and the guide strand sequence and the passenger strand sequence form a double-stranded structure.Type: ApplicationFiled: December 25, 2015Publication date: November 15, 2018Applicant: BONAC CORPORATIONInventors: Eriko AOKI, Yasuhiko YOSHIDA, Shiori KATO, Tadaaki OHGI
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Patent number: 9988415Abstract: The invention provides a glucoside compound, which is capable of providing a phosphoramidite, which can be produced at low cost and can produce a nucleic acid in high yield and with high purity. The glycoside compound has the formula wherein B, R1, R2, and R3 are as described herein.Type: GrantFiled: March 3, 2016Date of Patent: June 5, 2018Assignee: BONAC CORPORATIONInventors: Eriko Aoki, Hiroshi Suzuki, Akihiro Itoh
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Publication number: 20180119151Abstract: The present invention provides a single-stranded nucleic acid molecule having a delivery function and capable of inhibiting expression of a target gene. The single-stranded nucleic acid molecule of the present invention is a single-stranded nucleic acid molecule composed of a region (Xc), a linker region (Lx) and a region (X), wherein said region (Xc) is complementary to said region (X), at least one of said region (X) and said region (Xc) contains an expression inhibitory sequence that inhibits expression of the target gene, and a bio-related substance having a delivery function is bonded to at least one selected from the group consisting of the 5?-terminus, the 3?-terminus, and said linker region (Lx).Type: ApplicationFiled: March 26, 2016Publication date: May 3, 2018Applicant: BONAC CORPORATIONInventors: Eriko AOKI, Shiori KATO, Tadaaki OHGI
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Publication number: 20180099004Abstract: The present invention provides a single stranded nucleic acid molecule represented by the following formula (I): (I) (SEQ?ID?NO:?1) 5?-uagcaccauuugaaaucaguguucc-P- ggaacacugauuucaaauggugcuauu-3? wherein —P— shows a proline derivative linker represented by the following formula (Ia): an agent for treating corneal diseases such as ocular surface disorders and the like, comprising the single stranded nucleic acid molecule as an active ingredient.Type: ApplicationFiled: April 15, 2016Publication date: April 12, 2018Applicants: THE UNIVERSITY OF TOKYO, TOKYO MEDICAL UNIVERSITY, BONAC CORPORATIONInventors: Hirofumi TAKEUCHI, Tomohiko USUI, Masahiko KURODA, Masakatsu TAKANASHI, Shinichiro OHNO, Hidekazu TOYOFUKU, Kohei TAHARA, Risako ONODERA