CN104497084B - 用于治疗用途的7-脱氮嘌呤核苷 - Google Patents
用于治疗用途的7-脱氮嘌呤核苷 Download PDFInfo
- Publication number
- CN104497084B CN104497084B CN201410643709.3A CN201410643709A CN104497084B CN 104497084 B CN104497084 B CN 104497084B CN 201410643709 A CN201410643709 A CN 201410643709A CN 104497084 B CN104497084 B CN 104497084B
- Authority
- CN
- China
- Prior art keywords
- compound
- ddd
- nmr
- compounds
- carboxyl
- 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
- 0 *c1c(c(-c2c[s]cc2)c[n]2[C@@](C3O)OC(CO)=C3O)c2ncn1 Chemical compound *c1c(c(-c2c[s]cc2)c[n]2[C@@](C3O)OC(CO)=C3O)c2ncn1 0.000 description 9
- HWTAXOKFGJAVJF-QQNFCMCUSA-N Nc1ncnc2c1c(-c1c[nH]nn1)c[n]2[C@@H](C1O)O[C@H](CO)C1O Chemical compound Nc1ncnc2c1c(-c1c[nH]nn1)c[n]2[C@@H](C1O)O[C@H](CO)C1O HWTAXOKFGJAVJF-QQNFCMCUSA-N 0.000 description 2
- DNOOKHXUFNXPQV-PMDJAVJWSA-N C/C=C(/c1c[n]([C@@H](C(C23)O)O[C@@]2(CO)C3O)c(N)c1/C(/N)=N\C=C)\OC Chemical compound C/C=C(/c1c[n]([C@@H](C(C23)O)O[C@@]2(CO)C3O)c(N)c1/C(/N)=N\C=C)\OC DNOOKHXUFNXPQV-PMDJAVJWSA-N 0.000 description 1
- ZSRQLPAMXXBDGY-XXSAVOACSA-N C/C=C\C(\c1c[n]([C@@H](C2O)O[C@H](CO)C2O)c2c1C(N)=NCN2)=N/N Chemical compound C/C=C\C(\c1c[n]([C@@H](C2O)O[C@H](CO)C2O)c2c1C(N)=NCN2)=N/N ZSRQLPAMXXBDGY-XXSAVOACSA-N 0.000 description 1
- CFYMGDGAYLUOFX-NWQNDRTJSA-N CC1[C@H]([n]2c3ncnc(N)c3c(C#C)c2)O[C@H](CO)C1O Chemical compound CC1[C@H]([n]2c3ncnc(N)c3c(C#C)c2)O[C@H](CO)C1O CFYMGDGAYLUOFX-NWQNDRTJSA-N 0.000 description 1
- HIQQKOHTONSNRP-BAQGIRSFSA-N CN/C=C(/c1c[n](C(C2O)OC(CO)=C2O)c2c1C(N)NC=N2)\NC Chemical compound CN/C=C(/c1c[n](C(C2O)OC(CO)=C2O)c2c1C(N)NC=N2)\NC HIQQKOHTONSNRP-BAQGIRSFSA-N 0.000 description 1
- AAYFBWZEIFWMPD-QBQQJPCDSA-N C[C@](CO[C@@H]1CO)(C1O)O Chemical compound C[C@](CO[C@@H]1CO)(C1O)O AAYFBWZEIFWMPD-QBQQJPCDSA-N 0.000 description 1
- BILAWYACANCGMX-WPZCJLIBSA-N Nc1c(c(-c2c[o]cc2)c[n]2[C@@H](C3O)OC(CO)=C3O)c2ncn1 Chemical compound Nc1c(c(-c2c[o]cc2)c[n]2[C@@H](C3O)OC(CO)=C3O)c2ncn1 BILAWYACANCGMX-WPZCJLIBSA-N 0.000 description 1
- GKVXOMXWUVTROI-UHFFFAOYSA-N Nc1c(c(-c2ccc(C=O)cc2)c[nH]2)c2ncn1 Chemical compound Nc1c(c(-c2ccc(C=O)cc2)c[nH]2)c2ncn1 GKVXOMXWUVTROI-UHFFFAOYSA-N 0.000 description 1
- ZPWSANPBBJYNKX-WWZQUFADSA-N Nc1c(c(C2C=CC=C3C=CC=CC23)c[n]2[C@@H](C3O)O[C@H](CO)C3O)c2ncn1 Chemical compound Nc1c(c(C2C=CC=C3C=CC=CC23)c[n]2[C@@H](C3O)O[C@H](CO)C3O)c2ncn1 ZPWSANPBBJYNKX-WWZQUFADSA-N 0.000 description 1
- WHSIXKUPQCKWBY-VTFQDDHLSA-N Nc1c(c(I)c[n]2[C@@H](C3O)O[C@H](CO)C3O)c2ncn1 Chemical compound Nc1c(c(I)c[n]2[C@@H](C3O)O[C@H](CO)C3O)c2ncn1 WHSIXKUPQCKWBY-VTFQDDHLSA-N 0.000 description 1
- PPLPKPZUSDAREU-VLCAEQNZSA-N OC[C@H](C(C1O)O)O[C@H]1N(C1N=CN=CC11)C=C1c1ccc[nH]1 Chemical compound OC[C@H](C(C1O)O)O[C@H]1N(C1N=CN=CC11)C=C1c1ccc[nH]1 PPLPKPZUSDAREU-VLCAEQNZSA-N 0.000 description 1
- DJUFPPKYABJIKC-UHFFFAOYSA-O [NH3+]c1c(c(-c2ncc[s]2)c[n]2C(C3O)OC(CO)C3O)c2ncn1 Chemical compound [NH3+]c1c(c(-c2ncc[s]2)c[n]2C(C3O)OC(CO)C3O)c2ncn1 DJUFPPKYABJIKC-UHFFFAOYSA-O 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/14—Pyrrolo-pyrimidine radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17165609P | 2009-04-22 | 2009-04-22 | |
| US61/171,656 | 2009-04-22 | ||
| CN201080027802.1A CN102459300B (zh) | 2009-04-22 | 2010-04-19 | 用于治疗用途的新的7-脱氮嘌呤核苷 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201080027802.1A Division CN102459300B (zh) | 2009-04-22 | 2010-04-19 | 用于治疗用途的新的7-脱氮嘌呤核苷 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104497084A CN104497084A (zh) | 2015-04-08 |
| CN104497084B true CN104497084B (zh) | 2018-06-05 |
Family
ID=42768153
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410643709.3A Active CN104497084B (zh) | 2009-04-22 | 2010-04-19 | 用于治疗用途的7-脱氮嘌呤核苷 |
| CN201080027802.1A Active CN102459300B (zh) | 2009-04-22 | 2010-04-19 | 用于治疗用途的新的7-脱氮嘌呤核苷 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201080027802.1A Active CN102459300B (zh) | 2009-04-22 | 2010-04-19 | 用于治疗用途的新的7-脱氮嘌呤核苷 |
Country Status (15)
| Country | Link |
|---|---|
| US (3) | US9321800B2 (https=) |
| EP (1) | EP2421879B1 (https=) |
| JP (2) | JP5721275B2 (https=) |
| CN (2) | CN104497084B (https=) |
| AU (3) | AU2010238985B2 (https=) |
| CA (2) | CA2759131C (https=) |
| DK (1) | DK2421879T3 (https=) |
| ES (1) | ES2437917T3 (https=) |
| HR (1) | HRP20131021T1 (https=) |
| MX (1) | MX2011011160A (https=) |
| NZ (2) | NZ700583A (https=) |
| PL (1) | PL2421879T3 (https=) |
| PT (1) | PT2421879E (https=) |
| SI (1) | SI2421879T1 (https=) |
| WO (1) | WO2010121576A2 (https=) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT2421879E (pt) * | 2009-04-22 | 2013-12-09 | Acad Of Science Czech Republic | Novos 7-deazapurina nucleósidos para utilizações terapêuticas |
| KR20120113228A (ko) * | 2009-12-18 | 2012-10-12 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 베타 세포 복제 촉진 화합물 및 그 사용 방법 |
| CN102319254B (zh) * | 2011-07-20 | 2013-06-19 | 上海交通大学 | 5-碘代杀菌核素在制备抗肿瘤药物中的应用 |
| CZ305466B6 (cs) * | 2013-11-04 | 2015-10-14 | Ústav organické chemie a biochemie Akademie věd České republiky, v. v. i. | Substituované 7-deazapurinové ribonukleosidy pro terapeutické použití |
| KR102562866B1 (ko) | 2014-11-14 | 2023-08-04 | 네르비아노 메디칼 사이언시스 에스.알.엘. | 단백질 키나아제 억제제로서의 6-아미노-7-바이사이클로-7-데아자-퓨린 유도체 |
| EP3454856B1 (en) | 2016-05-10 | 2024-09-11 | C4 Therapeutics, Inc. | Heterocyclic degronimers for target protein degradation |
| CN109790143A (zh) | 2016-05-10 | 2019-05-21 | C4医药公司 | 用于靶蛋白降解的胺连接的c3-戊二酰亚胺降解决定子体 |
| ES2990061T3 (es) | 2016-05-10 | 2024-11-28 | C4 Therapeutics Inc | Degronímeros espirocíclicos para la degradación de proteínas diana |
| CN109641874A (zh) | 2016-05-10 | 2019-04-16 | C4医药公司 | 用于靶蛋白降解的c3-碳连接的戊二酰亚胺降解决定子体 |
| CA3029170C (en) | 2016-06-29 | 2021-02-16 | Ustav Organicke Chemie A Biochemie Av Cr, V.V.I. | Substituted thienopyrrolopyrimidine ribonucleosides for therapeutic use |
| CZ307334B6 (cs) | 2016-08-02 | 2018-06-13 | Ăšstav organickĂ© chemie a biochemie AV ÄŚR, v.v.i. | Substituované heteropentadieno-pyrrolopyrimidinové ribonukleosidy pro terapeutické použití |
| WO2018136661A1 (en) | 2017-01-18 | 2018-07-26 | Andrews Steven W | SUBSTITUTED PYRAZOLO[1,5-a]PYRAZINE COMPOUNDS AS RET KINASE INHIBITORS |
| CN110769822A (zh) | 2017-06-20 | 2020-02-07 | C4医药公司 | 用于蛋白降解的n/o-连接的降解决定子和降解决定子体 |
| EP3697800A1 (en) | 2017-10-19 | 2020-08-26 | Universiteit Gent | Nucleoside analogues for the treatment of parasitic infections |
| EP3740490A1 (en) | 2018-01-18 | 2020-11-25 | Array Biopharma, Inc. | Substituted pyrazolo[3,4-d]pyrimidine compounds as ret kinase inhibitors |
| JP7060694B2 (ja) * | 2018-01-18 | 2022-04-26 | アレイ バイオファーマ インコーポレイテッド | Ｒｅｔキナーゼ阻害剤としての置換ピロロ［２，３－ｄ］ピリミジン化合物 |
| US11472802B2 (en) | 2018-01-18 | 2022-10-18 | Array Biopharma Inc. | Substituted pyrazolyl[4,3-c]pyridine compounds as RET kinase inhibitors |
| CZ308104B6 (cs) | 2018-03-12 | 2020-01-08 | Ăšstav organickĂ© chemie a biochemie AV ÄŚR, v. v. i. | Pyridinopyrrolopyrimidinové ribonukleosidy pro terapeutické použití |
| US12173026B2 (en) | 2018-08-07 | 2024-12-24 | Merck Sharp & Dohme Llc | PRMT5 inhibitors |
| CN112996794A (zh) | 2018-09-10 | 2021-06-18 | 阿雷生物药品公司 | 作为ret激酶抑制剂的稠合杂环化合物 |
| CN114008064A (zh) * | 2019-06-18 | 2022-02-01 | 大鹏药品工业株式会社 | 具有吡咯并嘧啶骨架的新型的磷酸酯化合物或其药学上可接受的盐 |
| CN115515593A (zh) * | 2020-02-17 | 2022-12-23 | 勒芬天主教大学 | 作为药物的新的6-取代的7-脱氮嘌呤和相应的核苷 |
| KR102639275B1 (ko) * | 2021-06-08 | 2024-02-21 | 퓨쳐메디신 주식회사 | 다중 표적 인산화효소 저해 활성을 갖는 뉴클레오사이드 유도체 및 이를 포함하는 암의 예방 및 치료용 약학적 조성물 |
| CN118355022A (zh) | 2021-09-28 | 2024-07-16 | 安特卫普大学 | 用于治疗寄生虫感染的核苷类似物 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005044835A1 (en) * | 2003-10-27 | 2005-05-19 | Genelabs Technologies, Inc. | METHODS FOR PREPARING 7-(2'-SUBSTITUTED-ß-D-RIBOFURANOSYL)-4-(NR2R3)-5-(SUBSTITUTED ETHYN-1-YL)-PYRROLO[2,3-D]PYRIMIDINE DERIVATIVES |
| CN1653077A (zh) * | 2002-05-06 | 2005-08-10 | 健亚生物科技公司 | 治疗c型肝炎病毒感染的核苷衍生物 |
| US20060079468A1 (en) * | 2003-10-27 | 2006-04-13 | Genelabs Technologies, Inc. | Nucleoside compounds for treating viral infections |
| WO2010026153A1 (en) * | 2008-09-03 | 2010-03-11 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | Nucleoside derivatives as inhibitors of viral polymerases |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL108523A0 (en) * | 1993-02-03 | 1994-05-30 | Gensia Inc | Pharmaceutical compositions containing adenosine kinase inhibitors for preventing or treating conditions involving inflammatory responses and pain |
| SK286630B6 (sk) * | 2001-01-22 | 2009-02-05 | Merck & Co., Inc. | Nukleozidové deriváty, farmaceutický prostriedok s ich obsahom a ich použitie |
| WO2003051899A1 (en) * | 2001-12-17 | 2003-06-26 | Ribapharm Inc. | Deazapurine nucleoside libraries and compounds |
| US20040157892A1 (en) | 2003-02-12 | 2004-08-12 | Crompton Co./Cie | Pesticidal fluoroethyl pyrazoles |
| CA2542776A1 (en) * | 2003-10-27 | 2005-05-12 | Genelabs Technologies, Inc. | Nucleoside compounds for treating viral infections |
| WO2006033709A2 (en) * | 2004-07-29 | 2006-03-30 | Metabasis Therapeutics, Inc. | Novel nucleoside derivatives |
| PT2231689T (pt) * | 2008-01-18 | 2016-10-07 | Inst Of Organic Chemistry And Biochemistry Of The Acad Of Sciences Of The Czech Republic | Novos nucleósidos 7-deazapurina citostáticos |
| MX2010014501A (es) * | 2008-06-23 | 2011-02-25 | Janssen Pharmaceutica Nv | Antagonistas de piperidil acrilamida de receptor 2 de citocina quimioatrayente. |
| PT2421879E (pt) * | 2009-04-22 | 2013-12-09 | Acad Of Science Czech Republic | Novos 7-deazapurina nucleósidos para utilizações terapêuticas |
-
2010
- 2010-04-19 PT PT107344335T patent/PT2421879E/pt unknown
- 2010-04-19 EP EP10734433.5A patent/EP2421879B1/en active Active
- 2010-04-19 JP JP2012506333A patent/JP5721275B2/ja active Active
- 2010-04-19 SI SI201030450T patent/SI2421879T1/sl unknown
- 2010-04-19 ES ES10734433.5T patent/ES2437917T3/es active Active
- 2010-04-19 CN CN201410643709.3A patent/CN104497084B/zh active Active
- 2010-04-19 WO PCT/CZ2010/000050 patent/WO2010121576A2/en not_active Ceased
- 2010-04-19 DK DK10734433.5T patent/DK2421879T3/da active
- 2010-04-19 CA CA2759131A patent/CA2759131C/en active Active
- 2010-04-19 CN CN201080027802.1A patent/CN102459300B/zh active Active
- 2010-04-19 NZ NZ700583A patent/NZ700583A/en active IP Right Revival
- 2010-04-19 NZ NZ596301A patent/NZ596301A/en unknown
- 2010-04-19 HR HRP20131021AT patent/HRP20131021T1/hr unknown
- 2010-04-19 CA CA2966647A patent/CA2966647A1/en not_active Abandoned
- 2010-04-19 AU AU2010238985A patent/AU2010238985B2/en active Active
- 2010-04-19 MX MX2011011160A patent/MX2011011160A/es active IP Right Grant
- 2010-04-19 PL PL10734433T patent/PL2421879T3/pl unknown
- 2010-04-19 US US14/394,262 patent/US9321800B2/en active Active
-
2014
- 2014-10-20 JP JP2014213410A patent/JP6087889B2/ja active Active
-
2015
- 2015-07-22 AU AU2015205885A patent/AU2015205885B2/en active Active
-
2016
- 2016-03-17 US US15/073,502 patent/US9624257B2/en active Active
-
2017
- 2017-03-08 US US15/453,702 patent/US10294262B2/en active Active
- 2017-06-19 AU AU2017204148A patent/AU2017204148B2/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1653077A (zh) * | 2002-05-06 | 2005-08-10 | 健亚生物科技公司 | 治疗c型肝炎病毒感染的核苷衍生物 |
| WO2005044835A1 (en) * | 2003-10-27 | 2005-05-19 | Genelabs Technologies, Inc. | METHODS FOR PREPARING 7-(2'-SUBSTITUTED-ß-D-RIBOFURANOSYL)-4-(NR2R3)-5-(SUBSTITUTED ETHYN-1-YL)-PYRROLO[2,3-D]PYRIMIDINE DERIVATIVES |
| US20060079468A1 (en) * | 2003-10-27 | 2006-04-13 | Genelabs Technologies, Inc. | Nucleoside compounds for treating viral infections |
| WO2010026153A1 (en) * | 2008-09-03 | 2010-03-11 | Istituto Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. | Nucleoside derivatives as inhibitors of viral polymerases |
Non-Patent Citations (4)
| Title |
|---|
| 7-Functionalized 7-deazapurine β-D and β-L-ribonucleosides related to tubercidin and 7-deazainosine: glycosylation of pyrrolo[2,3-d]pyrimidines with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D or β-L-ribofuranose;Frank Seela，等;《Tetrahedron》;20070924;第63卷(第39期);第9850–9861页 * |
| 7-去氮腺苷衍生物的合成及生物活性研究;张亮仁，等;《中国药物化学杂志》;20030430;第13卷(第2期);第63-66页 * |
| Pyrrolopyrimidine Nucleosides VIII. Synthesis of sangivamycin derivatives possessing exocyclic heterocycles at C5;Karl H. Schram，等;《J. Carbohydrates Nucleosides Nucleotides》;19741231;第1卷(第1期);第39-54页 * |
| Study on the Synthesis and PKA-I Binding Activities of 5-Alkynyl Tubercidin Analogues;Liangren Zhang，等;《Bioorganic & Medicinal Chemistry》;20020430;第10卷(第4期);第907–912页 * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104497084B (zh) | 用于治疗用途的7-脱氮嘌呤核苷 | |
| CN101977923B (zh) | 抑制细胞生长的7-脱氮嘌呤核苷 | |
| CN103497192B (zh) | Toll样受体调节剂 | |
| HK1209129B (zh) | 用於治疗用途的7-脱氮嘌呤核苷 | |
| HK1166325B (en) | Novel 7-deazapurine nucleosides for therapeutic uses | |
| HK1234411A1 (en) | Novel cytostatic 7-deazapurine nucleosides |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1209129 Country of ref document: HK |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant |