JP6410400B2 - 細胞ベース治療または遺伝子治療用の癌特異的自殺遺伝子 - Google Patents
細胞ベース治療または遺伝子治療用の癌特異的自殺遺伝子 Download PDFInfo
- Publication number
- JP6410400B2 JP6410400B2 JP2014552351A JP2014552351A JP6410400B2 JP 6410400 B2 JP6410400 B2 JP 6410400B2 JP 2014552351 A JP2014552351 A JP 2014552351A JP 2014552351 A JP2014552351 A JP 2014552351A JP 6410400 B2 JP6410400 B2 JP 6410400B2
- Authority
- JP
- Japan
- Prior art keywords
- cells
- cell
- myc
- mip
- omomyc
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4702—Regulators; Modulating activity
- C07K14/4703—Inhibitors; Suppressors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/48—Reproductive organs
- A61K35/54—Ovaries; Ova; Ovules; Embryos; Foetal cells; Germ cells
- A61K35/545—Embryonic stem cells; Pluripotent stem cells; Induced pluripotent stem cells; Uncharacterised stem cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/82—Translation products from oncogenes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0696—Artificially induced pluripotent stem cells, e.g. iPS
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/40—Regulators of development
- C12N2501/48—Regulators of apoptosis
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2510/00—Genetically modified cells
Description
本発明は、米国国立癌研究所により認可された認可番号第CA142798号に基づく米国政府の支援を受けてなされたものである。米国政府は、本発明に一定の権利を有する。
本発明は、誘導されたときに、幹細胞または前駆細胞由来の健常組織または他の(非癌性)細胞に対して大きな影響を及ぼすことなく、幹細胞または前駆細胞由来の癌性細胞を選択的に殺滅する誘導可能な癌特異的自殺遺伝子構築体を含むように改変された、胚性幹細胞、誘導多能性幹細胞、成体幹細胞、または他の前駆細胞を含む、多能性または多分化能幹細胞を提供する。前記自殺遺伝子構築体は、健常細胞及び組織に対して大きな悪影響を及ぼすことなく癌細胞内で腫瘍抑制因子として働く優性阻害型MYC干渉タンパク質(D−MIP)を発現する。前記自殺遺伝子構築体はまた、遺伝子治療ベクターの存在に関連して癌が発生する遺伝子治療に用いることもできる。さらに、前記自殺遺伝子構築体は、癌性細胞と、遺伝子治療ベクターにより改変された非癌性細胞とを識別して、癌性細胞だけを殺滅することができる。
p53+/+及びp53−/−iPS細胞の生成及び特性評価
p53+/+iPS細胞及びp53−/−iPS細胞へのOmomycの形質導入
p53+/+iPS細胞及びp53−/−iPS細胞からのインビボ腫瘍形成
Omomyc誘導は腫瘍退縮を引き起こす
健常なiPS由来組織におけるOmomyc発現の効果
OmomycERによる白血病の治療
iPS由来の神経腫瘍の生成及び治療
Chambers, S.M., et al. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat. Biotechnol 27, 275-280 (2009).
Davis, A. C., Wims, M., Spotts, G. D., Hann, S. R. & Bradley, A. A null c-myc mutation causes lethality before 10.5 days of gestation in homozygotes and reduced fertility in heterozygous female mice. Genes Dev 7, 671-682, (1993).
Felsher, D. W. & Bishop, J. M. Reversible tumorigenesis by MYC in hematopoietic lineages. Mol. Cell 4, 199-207, (1999).
Fukazawa et al. Inhibition of MYC Effectively Targets KRAS Mutation-positive Lung Cancer Expressing High Levels of MYC. Anticancer Res. 30:4193-4200 (2010).
Hanna, J. H., Saha, K. & Jaenisch, R. Pluripotency and Cellular Reprogramming: Facts, Hypotheses, Unresolved Issues. Cell 143, 508-525, (2010).
Hong, H. Suppression of induced pluripotent stem cell generation by the p53-p21 pathway. Nature 460, 1132-1135, (2009).
Jain, M. et al. Sustained Loss of a Neoplastic Phenotype by Brief Inactivation of MYC. Science 297, 102-104, (2002).
Kawamura, T. Linking the p53 tumour suppressor pathway to somatic cell reprogramming. Nature 460, 1140-1144, (2009).
Kriks, S, Shim, J.W., Piao J., Ganat, Y.M., Wakeman, D.R., Xie, Z., Carrillo-Reid, L., Auyeung, G., Antonacci, C., Buch, A., Yang, L., Beal, M.F., Surmeier, D.J., Kordower, J.H., Tabar, V. & Studer, L. Dopamine Neurons Derived from Human ES Cells Efficiently Engraft in Animal Models of Parkinson's Disease. Nature 480, 547-51 (2011).
Knoepfler, P. S. Deconstructing Stem Cell Tumorigenicity: A Roadmap to Safe Regenerative Medicine. Stem Cells 27, 1050-1056, (2009).
Lin, C.H., Jackson, A.L., Guo, J., Linsley, P.S. & Eisenman, R.N. Myc-regulated microRNAs attenuate embryonic stem cell differentiation. Embo J. 28, 3157-3170 (2009).
Littlewood, T.D., Hancock, D.C., Danielian, P.S., Parker, M. G., & Evan, G.I. A Modified Oestrogen Receptor Ligand-binding Domain as an Improved Switch for the Regulation of Hereologous Proteins. Nucleic Acids Res. 23, 1686-1690 (1995).
Marion, R. M. et al. A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity. Nature 460, 1149-1153, (2009).
Meyer, N. & Penn, L.Z. Reflecing on 25 years with MYC. Nature Rev. Cancer 8, 976-990 (2008).
Nakagawa, M., Takizawa, N., Narita, M., Ichisaka, T. & Yamanaka, S. Promotion of direct reprogramming by transformation-deficient MYC. Proc Natl Acad Sci U S A 107, 14152-14157, (2010).
Okita, K., Ichisaka, T. & Yamanaka, S. Generation of germline-competent induced pluripotent stem cells. Nature 448, 313-317, (2007).
Papapetrou, E. P. et al. Stoichiometric and temporal requirements of Oct4, Sox2, Klf4, and c-MYC expression for efficient human iPSC induction and differentiation. Proc Natl Acad Sci U S A 106, 12759-12764, (2009).
Papapetrou, E. P. et al. Genomic safe harbors permit high beta-globin transgene expression in thalassemia induced pluripotent stem cells. Nat Biotechnol 29, 73-78, (2011a).
Papapetrou, E.P. & Sadelain, M. Generation of transgene-free human induced pluripotent stem cells with an excisable single polycistronic vector. Nat Protoc 6, 1251-1273 (2011b).
Savino et al. the Action Mechanism of the MYC Inhibitor Termed Omomyc May Give Clues on How to Target MYC for Cancer Therapy. PLoS One 6, e22284 (Epub 2011).
Schuldiner, M., Itskovitz-Eldor, J. & Benvenisty, N. Selective ablation of human embryonic stem cells expressing a "suicide" gene. Stem cells 21, 257-265, (2003).
Shachaf, C. M. et al. MYC inactivation uncovers pluripotent differentiation and tumour dormancy in hepatocellular cancer. Nature 431, 1112-1117, (2004).
Shih, C. C., Forman, S. J., Chu, P. & Slovak, M. Human embryonic stem cells are prone to generate primitive, undifferentiated tumors in engrafted human fetal tissues in severe combined immunodeficient mice. Stem Cells Dev 16, 893-902, (2007).
Smith, K.N., Singh, A.M. & Dalton, S. Myc Represses Primitive Endoderm Differentiation in Pluripotent Stem Cells. Cell Stem Cell 7, 343-354 (2010).
Sodir N. et al. Endogenous MYC Maintains the Tumor Microenvironment. Genes Dev. 25:907-916 (2011).
Soucek, L. Design and properties of a MYC derivative that efficiently homodimerizes. Oncogene 17, 2463-2472, (1998).
Soucek, L. et al. Modelling MYC inhibition as a cancer therapy. Nature 455, 679-683, (2008).
Soucek, L. Omomyc, a potential MYC dominant negative, enhances MYC-induced apoptosis. Cancer Res. 62, 3507-3510, (2002).
Soucek, L., Nasi, S. & Evan, G. I. Omomyc expression in skin prevents MYC-induced papillomatosis. Cell Death Differ. 11, 1038-1045, (2004).
Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663-676, (2006).
Van Eyss, B. & Eilers, M. Addicted to MYC--But Why? Genes Dev. 25895-897 (2011).
Wernig, M. et al. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature 448, 318-324, (2007).
Wernig, M., Meissner, A., Cassady, J. P. & Jaenisch, R. c-MYC is dispensable for direct reprogramming of mouse fibroblasts. Cell Stem Cell 2, 10-12, (2008).
Claims (10)
- 遺伝子治療のための薬剤を製造する方法であって、
前記薬剤は、対象の遺伝子治療の過程で生じるMYC依存性癌の腫瘍形成または腫瘍成長を抑制することが可能となるように構成され、
前記方法は、
単離された多能性幹細胞、多分化能幹細胞、または前駆細胞のいずれかの細胞に、誘導因子によって誘導可能な優性阻害型MYC干渉タンパク質(D−MIP)構築体をエクスビボで形質導入するステップと、
前記細胞に、前記遺伝子治療での使用のために治療遺伝子をエクスビボで形質導入するステップとを含み、
前記薬剤は前記D−MIP構築体及び治療遺伝子が形質導入された前記細胞を含み、
前記薬剤は、前記薬剤が前記対象に投与された後に前記対象に癌が検出された場合に、前記誘導因子によって前記対象内で前記D−MIP構築体を活性化させ、それにより前記MYC依存性癌の前記腫瘍形成または腫瘍成長を抑制することが可能となるように構成されていることを特徴とする方法。 - 請求項1に記載の方法であって、
前記幹細胞が、哺乳類の誘導多能性幹細胞(iPS細胞)、または胚性幹細胞(ES細胞)であることを特徴とする方法。 - 請求項2に記載の方法であって、
前記哺乳類が、ヒト、霊長類、ウシ、またはマウスであることを特徴とする方法。 - 請求項1に記載の方法であって、
前記幹細胞が、成体幹細胞、組織特異的幹細胞、胚性幹細胞、または臍帯血幹細胞であることを特徴とする方法。 - 請求項1に記載の方法であって、
前記前駆細胞が、造血前駆細胞、皮膚前駆細胞、骨前駆細胞、または神経前駆細胞であることを特徴とする方法。 - 請求項1に記載の方法であって、
前記D−MIP構築体が、OmomycまたはOmomycERであることを特徴とする方法。 - 請求項1〜6のいずれか一項に記載の方法であって、
前記細胞は、遺伝子治療ベクターで形質導入され、
前記遺伝子治療ベクターは、
第1の制御要素に作用可能に連結される治療遺伝子と、
誘導可能な第2の制御要素に作用可能に連結されるD−MIP構築体とを含むことを特徴とする方法。 - 請求項7に記載の方法であって、
前記遺伝子治療ベクターが、レンチウイルスベクター、アデノウイルスベクター、またはアデノ随伴ウイルスベクターであることを特徴とする方法。 - 請求項7または8に記載の方法であって、
前記D−MIPが、Omomycであるか、または
前記D−MIP及び前記第2の制御要素によりOmomycERを形成することを特徴とする方法。 - 請求項1に記載の方法であって、
前記細胞が、前記対象の自己細胞であることを特徴とする方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261586366P | 2012-01-13 | 2012-01-13 | |
US61/586,366 | 2012-01-13 | ||
PCT/US2013/021316 WO2013106774A1 (en) | 2012-01-13 | 2013-01-11 | Cancer-specific suicide gene for cell-based and gene therapy |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2015504678A JP2015504678A (ja) | 2015-02-16 |
JP6410400B2 true JP6410400B2 (ja) | 2018-10-24 |
Family
ID=48781966
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014552351A Active JP6410400B2 (ja) | 2012-01-13 | 2013-01-11 | 細胞ベース治療または遺伝子治療用の癌特異的自殺遺伝子 |
Country Status (6)
Country | Link |
---|---|
US (2) | US20150299278A1 (ja) |
EP (1) | EP2802648B1 (ja) |
JP (1) | JP6410400B2 (ja) |
AU (1) | AU2013207785B2 (ja) |
CA (1) | CA2863327A1 (ja) |
WO (1) | WO2013106774A1 (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11542524B2 (en) | 2017-11-29 | 2023-01-03 | Research Development Foundation | Elimination of proliferating cells from stem cell-derived grafts |
US20220307013A1 (en) * | 2019-08-30 | 2022-09-29 | The Regents Of The University Of California | Gene fragment overexpression screening methodologies, and uses thereof |
CN113564203B (zh) * | 2021-07-02 | 2023-01-10 | 中国科学院动物研究所 | HSV1-tk/GCV诱导型血液系统缺陷小鼠模型的制备方法及应用 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20100303775A1 (en) * | 2009-05-27 | 2010-12-02 | The Salk Institute For Biological Studies | Generation of Genetically Corrected Disease-free Induced Pluripotent Stem Cells |
-
2013
- 2013-01-11 CA CA2863327A patent/CA2863327A1/en not_active Abandoned
- 2013-01-11 AU AU2013207785A patent/AU2013207785B2/en active Active
- 2013-01-11 WO PCT/US2013/021316 patent/WO2013106774A1/en active Application Filing
- 2013-01-11 EP EP13736077.2A patent/EP2802648B1/en active Active
- 2013-01-11 JP JP2014552351A patent/JP6410400B2/ja active Active
- 2013-01-11 US US14/372,198 patent/US20150299278A1/en not_active Abandoned
-
2018
- 2018-01-02 US US15/860,172 patent/US20180305426A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
EP2802648B1 (en) | 2019-08-28 |
AU2013207785B2 (en) | 2018-08-30 |
US20180305426A1 (en) | 2018-10-25 |
US20150299278A1 (en) | 2015-10-22 |
EP2802648A1 (en) | 2014-11-19 |
WO2013106774A1 (en) | 2013-07-18 |
JP2015504678A (ja) | 2015-02-16 |
CA2863327A1 (en) | 2013-07-18 |
EP2802648A4 (en) | 2015-07-29 |
AU2013207785A1 (en) | 2014-07-31 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Cheng et al. | Protecting against wayward human induced pluripotent stem cells with a suicide gene | |
Sánchez-Danés et al. | Efficient generation of A9 midbrain dopaminergic neurons by lentiviral delivery of LMX1A in human embryonic stem cells and induced pluripotent stem cells | |
KR101731068B1 (ko) | 체세포로부터 희소돌기아교 전구세포로의 직접교차분화 유도용 조성물 및 이의 이용 | |
Wu et al. | Development of an inducible caspase-9 safety switch for pluripotent stem cell–based therapies | |
Liu et al. | Mouse-induced pluripotent stem cells generated under hypoxic conditions in the absence of viral infection and oncogenic factors and used for ischemic stroke therapy | |
US20180305426A1 (en) | Cancer-specific suicide gene for cell-based and gene therapy | |
US20200190535A1 (en) | Adult stem cell line introduced with hepatocyte growth factor gene and neurogenic transcription factor gene with basic helix-loop-helix motif and uses thereof | |
JP2005523012A (ja) | 癌モデル | |
Neyrinck et al. | The human somatostatin receptor type 2 as an imaging and suicide reporter gene for pluripotent stem cell-derived therapy of myocardial infarction | |
US20070274971A1 (en) | Method of Proliferating Precursor Cells | |
US20200385685A1 (en) | Robust differentiation of human pluripotent stem cells into endothelial cells using transcription factor etv2 | |
Lunn et al. | Intraspinal transplantation of neurogenin-expressing stem cells generates spinal cord neural progenitors | |
KR101993045B1 (ko) | 체세포에서 유도담관줄기세포로의 교차분화방법 | |
KR20220024104A (ko) | 파킨슨병을 위한 자가 세포 대체 요법 | |
EP4074329A1 (en) | Induction of proliferous pancreatic islet precursor cell-like cells by transient expression of mycl and induction of differentiation into insulin-positive cells | |
TWI769410B (zh) | 新穎誘導性多能幹細胞(ipscs)及其應用 | |
Liu et al. | Induced pluripotent stem cells-podocytes promote repair in acute kidney injury is dependent on Mafb/CCR5/Nampt axis-mediated M2 macrophage polarization | |
Huang et al. | Induced pluripotent stem cell technologies for tissue engineering | |
Simmons et al. | Human striatal progenitor cells that contain inducible safeguards and overexpress BDNF rescue Huntington's disease phenotypes in R6/2 mice | |
WO2019093047A1 (ja) | インビトロでの機能的な外分泌腺の製造方法、および、当該方法によって製造される外分泌腺 | |
Thiruvalluvan | Induced pluripotent stem cells: cell therapy and disease modeling | |
JP2024519218A (ja) | 成熟角膜内皮細胞を作製する方法 | |
CN117716020A (zh) | 产生成熟肝细胞的方法 | |
WO2012020843A1 (ja) | 形質転換動物及び形質転換幹細胞、並びにそれらの利用 | |
王立宾 et al. | Immunogenicity and Functional Evaluation of iPSC-Derived Organs for Transplantation |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20160107 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20170124 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20170421 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20170623 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20170721 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20171205 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180302 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20180828 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20180924 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6410400 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |