PT2877467T - 2-(azaindol-2-il)benzimidazóis como inibidores de pad4 - Google Patents
2-(azaindol-2-il)benzimidazóis como inibidores de pad4Info
- Publication number
- PT2877467T PT2877467T PT127405819T PT12740581T PT2877467T PT 2877467 T PT2877467 T PT 2877467T PT 127405819 T PT127405819 T PT 127405819T PT 12740581 T PT12740581 T PT 12740581T PT 2877467 T PT2877467 T PT 2877467T
- Authority
- PT
- Portugal
- Prior art keywords
- azaindol
- benzimidazoles
- pad4 inhibitors
- pad4
- inhibitors
- Prior art date
Links
- VEZJRJGLFIXQHG-UHFFFAOYSA-N 2-(1h-benzimidazol-2-yl)-1h-benzimidazole Chemical class C1=CC=C2NC(C=3NC4=CC=CC=C4N=3)=NC2=C1 VEZJRJGLFIXQHG-UHFFFAOYSA-N 0.000 title 1
- 239000003112 inhibitor Substances 0.000 title 1
Classifications
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12740581.9A EP2877467B1 (en) | 2012-07-26 | 2012-07-26 | 2-(azaindol-2-yl)benzimidazoles as pad4 inhibitors |
| PCT/EP2012/064649 WO2014015905A1 (en) | 2012-07-26 | 2012-07-26 | 2 - (azaindol- 2 -yl) benz imidazoles as pad4 inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PT2877467T true PT2877467T (pt) | 2017-01-02 |
Family
ID=49996626
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT127405819T PT2877467T (pt) | 2012-07-26 | 2012-07-26 | 2-(azaindol-2-il)benzimidazóis como inibidores de pad4 |
Country Status (22)
| Country | Link |
|---|---|
| US (4) | US9127003B2 (enExample) |
| EP (1) | EP2877467B1 (enExample) |
| JP (1) | JP6063567B2 (enExample) |
| KR (1) | KR101916443B1 (enExample) |
| CN (1) | CN104470919B (enExample) |
| AU (1) | AU2012386257B2 (enExample) |
| BR (1) | BR112015001545B1 (enExample) |
| CA (1) | CA2879341C (enExample) |
| CY (1) | CY1118524T1 (enExample) |
| DK (1) | DK2877467T3 (enExample) |
| ES (1) | ES2609126T3 (enExample) |
| HR (1) | HRP20161530T1 (enExample) |
| HU (1) | HUE033294T2 (enExample) |
| IN (1) | IN2014KN02935A (enExample) |
| LT (1) | LT2877467T (enExample) |
| PL (1) | PL2877467T3 (enExample) |
| PT (1) | PT2877467T (enExample) |
| RS (1) | RS55684B1 (enExample) |
| RU (1) | RU2611010C2 (enExample) |
| SI (1) | SI2877467T1 (enExample) |
| SM (2) | SMT201700052T1 (enExample) |
| WO (1) | WO2014015905A1 (enExample) |
Families Citing this family (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2986199C (en) * | 2015-05-21 | 2023-07-18 | Glaxosmithkline Intellectual Property Development Limited | Benzoimidazole derivatives as pad4 inhibitors |
| AR107030A1 (es) * | 2015-12-09 | 2018-03-14 | Padlock Therapeutics Inc | Inhibidores aza-bencimidazol de pad4 |
| AR107032A1 (es) * | 2015-12-09 | 2018-03-14 | Padlock Therapeutics Inc | Inhibidores bicíclicos de pad4 |
| AR107694A1 (es) | 2016-02-23 | 2018-05-23 | Padlock Therapeutics Inc | Heteroarilos inhibidores de pad4 |
| CN107188867A (zh) * | 2016-03-14 | 2017-09-22 | 中国科学院天津工业生物技术研究所 | 精氨酸脱亚氨酶4的抑制剂 |
| WO2018022897A1 (en) * | 2016-07-27 | 2018-02-01 | Padlock Therapeutics, Inc. | Covalent inhibitors of pad4 |
| CN110248934B (zh) * | 2016-09-12 | 2022-05-24 | 帕德罗科治疗公司 | 杂芳基pad4抑制剂 |
| WO2018102262A1 (en) * | 2016-12-02 | 2018-06-07 | University Of Massachusetts | Inhibitors of protein arginine deiminases (pads) and methods of preparation and use thereof |
| CN108689946B (zh) * | 2017-04-12 | 2022-10-18 | 中国科学院上海药物研究所 | 2-取代硫基乙酰胺类化合物及其制备方法和应用 |
| SG11202002032SA (en) * | 2017-09-22 | 2020-04-29 | Jubilant Epipad LLC | Heterocyclic compounds as pad inhibitors |
| CA3076476A1 (en) * | 2017-10-18 | 2019-04-25 | Jubilant Epipad LLC | Imidazo-pyridine compounds as pad inhibitors |
| BR112020008851A2 (pt) | 2017-11-06 | 2020-10-20 | Jubilant Prodel LLC | composto da fórmula i, processo de preparação de compostos da fórmula i, composição farmacêutica, método para o tratamento e/ou prevenção de várias doenças, uso, método para o tratamento de câncer, método de tratamento de câncer e método para o tratamento e/ou prevenção de câncer e doenças infecciosas |
| PL3704120T3 (pl) | 2017-11-24 | 2024-09-16 | Jubilant Episcribe Llc | Związki heterocykliczne jako inhibitory prmt5 |
| WO2019161803A1 (zh) | 2018-02-26 | 2019-08-29 | 南京药捷安康生物科技有限公司 | 肽酰精氨酸脱亚胺酶抑制剂及其用途 |
| SG11202008950PA (en) | 2018-03-13 | 2020-10-29 | Jubilant Prodel LLC | Bicyclic compounds as inhibitors of pd1/pd-l1 interaction/activation |
| US12448374B2 (en) | 2018-06-07 | 2025-10-21 | Disarm Therapeutics, Inc. | Inhibitors of SARM1 |
| JP7447080B2 (ja) | 2018-08-08 | 2024-03-11 | ブリストル－マイヤーズ スクイブ カンパニー | Ｐａｄ４阻害剤としての置換チエノピロール |
| US20220402950A1 (en) * | 2018-08-08 | 2022-12-22 | Bristol-Myers Squibb Company | Substituted benzimidazoles as pad4 inhibitors |
| EP3833439B1 (en) * | 2018-08-08 | 2023-07-12 | Bristol-Myers Squibb Company | Benzimidazole inhibitors of pad enzymes |
| AU2019319835A1 (en) * | 2018-08-08 | 2021-03-25 | Bristol-Myers Squibb Company | Indole and azaindole inhibitors of PAD enzymes |
| CN109369513B (zh) * | 2018-11-20 | 2020-08-25 | 都创(上海)医药科技有限公司 | 一种fbdd常用分子片段的制备方法 |
| CN113164508B (zh) | 2018-12-19 | 2025-07-08 | 达萨玛治疗公司 | 与神经保护剂组合的sarm1抑制剂 |
| EP3994128A4 (en) * | 2019-07-03 | 2022-12-07 | University of Massachusetts | INHIBITORS OF PROTEIN ARGININE DEIMINASE 1, AND PROCESSES FOR THEIR PREPARATION AND USE |
| WO2021057910A1 (zh) * | 2019-09-27 | 2021-04-01 | 南京药捷安康生物科技有限公司 | 肽酰精氨酸脱亚胺酶抑制剂及其用途 |
| KR20220137694A (ko) | 2020-02-06 | 2022-10-12 | 브리스톨-마이어스 스큅 컴퍼니 | 면역억제제로서 유용한 마크로시클릭 pad4 억제제 |
| TW202140477A (zh) * | 2020-02-12 | 2021-11-01 | 美商必治妥美雅史谷比公司 | 雜環ｐａｄ４抑制劑 |
| CN111265526B (zh) * | 2020-04-09 | 2021-03-19 | 黑龙江中医药大学 | 一种治疗胃癌的药物及其制备方法 |
| CN115551862B (zh) | 2020-04-30 | 2024-04-12 | 吉利德科学公司 | 肽基精氨酸脱亚胺酶的大环抑制剂 |
| CA3192236A1 (en) | 2020-09-10 | 2022-03-17 | Tony Lahoutte | Antibody fragment against fap |
| US20230365589A1 (en) | 2020-09-18 | 2023-11-16 | Sumitomo Pharma Co., Ltd. | Novel amine derivatives |
| EP4267562A1 (en) | 2020-12-22 | 2023-11-01 | Gilead Sciences, Inc. | Inhibitors of peptidylarginine deiminases |
| EP4267587A2 (en) | 2020-12-22 | 2023-11-01 | Gilead Sciences, Inc. | Inhibitors of peptidylarginine deiminases |
| WO2023083365A1 (en) | 2021-11-15 | 2023-05-19 | Qilu Regor Therapeutics Inc. | Pad4 inhibitors and use thereof |
| WO2023203135A1 (en) | 2022-04-22 | 2023-10-26 | Precirix N.V. | Improved radiolabelled antibody |
| AU2023264245A1 (en) | 2022-05-02 | 2024-12-19 | Precirix N.V. | Pre-targeting |
| KR20250027599A (ko) * | 2022-05-26 | 2025-02-26 | 셀진 코포레이션 | 헤테로시클릭 pad4 억제제 |
| JP2025537627A (ja) * | 2022-11-24 | 2025-11-19 | ヘリオス ファミン バイオファーマ カンパニー リミテッド | セレン含有複素環式化合物およびその使用 |
| KR20260041867A (ko) | 2023-07-21 | 2026-03-27 | 브리스톨-마이어스 스큅 컴퍼니 | Pad4 조정제의 시트룰린화 및 활성을 평가하는 방법 |
| WO2026020127A2 (en) | 2024-07-19 | 2026-01-22 | Bristol-Myers Squibb Company | Methods of assessing citrullination and activity of pad2 modulators |
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| AU570439B2 (en) | 1983-03-28 | 1988-03-17 | Compression Labs, Inc. | A combined intraframe and interframe transform coding system |
| SI0820279T1 (en) | 1995-04-14 | 2002-12-31 | Smithkline Beecham Corporation | Metered dose inhaler for albuterol |
| TW533865U (en) | 1997-06-10 | 2003-05-21 | Glaxo Group Ltd | Dispenser for dispensing medicament and actuation indicating device |
| HK1039325B (en) * | 1998-09-18 | 2006-02-24 | Abbott Gmbh & Co. Kg | 4-aminopyrrolopyrimidines as kinase inhibitors |
| US6315112B1 (en) | 1998-12-18 | 2001-11-13 | Smithkline Beecham Corporation | Method and package for storing a pressurized container containing a drug |
| US6390291B1 (en) | 1998-12-18 | 2002-05-21 | Smithkline Beecham Corporation | Method and package for storing a pressurized container containing a drug |
| US6119853A (en) | 1998-12-18 | 2000-09-19 | Glaxo Wellcome Inc. | Method and package for storing a pressurized container containing a drug |
| US6352152B1 (en) | 1998-12-18 | 2002-03-05 | Smithkline Beecham Corporation | Method and package for storing a pressurized container containing a drug |
| JP2003512353A (ja) * | 1999-10-19 | 2003-04-02 | メルク エンド カムパニー インコーポレーテッド | チロシンキナーゼ阻害剤 |
| EP1990343B1 (en) | 1999-12-24 | 2012-04-04 | Aventis Pharma Limited | Azaindoles |
| GB0115393D0 (en) | 2001-06-23 | 2001-08-15 | Aventis Pharma Ltd | Chemical compounds |
| WO2003000690A1 (en) | 2001-06-25 | 2003-01-03 | Aventis Pharmaceuticals Inc. | Synthesis of heterocyclic compounds employing microwave technology |
| CN1901958B (zh) | 2003-11-03 | 2011-03-09 | 葛兰素集团有限公司 | 流体分配装置 |
| JP2007511596A (ja) | 2003-11-17 | 2007-05-10 | ファイザー・プロダクツ・インク | 癌の治療において有用なピロロピリミジン化合物 |
| FR2862971B1 (fr) * | 2003-11-28 | 2006-03-24 | Sod Conseils Rech Applic | Nouveaux derives de benzimidazole et d'imidazo-pyridine et leur utilisation en tant que medicament |
| US7429611B2 (en) | 2004-09-23 | 2008-09-30 | Bristol-Myers Squibb Company | Indole inhibitors of 15-lipoxygenase |
| US20100197657A1 (en) | 2007-09-25 | 2010-08-05 | Chang Ronald K | 2-aryl or heteroaryl indole derivatives |
| WO2009155042A1 (en) | 2008-05-28 | 2009-12-23 | Wyeth | 3-substituted-1h-indole compounds, their use as mtor kinase and pi3 kinase inhibitors, and their syntheses |
| RU2011106786A (ru) * | 2008-07-23 | 2012-08-27 | Вертекс Фармасьютикалз Инкорпорейтед (Us) | Ингибиторы пиразолопиридинкиназы |
| SG174125A1 (en) * | 2009-04-02 | 2011-10-28 | Merck Serono Sa | Dihydroorotate dehydrogenase inhibitors |
| US20100305093A1 (en) | 2009-04-09 | 2010-12-02 | Exelixis, Inc. | Inhibitors of mTOR and Methods of Making and Using |
-
2012
- 2012-07-26 DK DK12740581.9T patent/DK2877467T3/en active
- 2012-07-26 SM SM20170052T patent/SMT201700052T1/it unknown
- 2012-07-26 PL PL12740581T patent/PL2877467T3/pl unknown
- 2012-07-26 CN CN201280074868.5A patent/CN104470919B/zh active Active
- 2012-07-26 ES ES12740581.9T patent/ES2609126T3/es active Active
- 2012-07-26 HR HRP20161530TT patent/HRP20161530T1/hr unknown
- 2012-07-26 WO PCT/EP2012/064649 patent/WO2014015905A1/en not_active Ceased
- 2012-07-26 RU RU2014152456A patent/RU2611010C2/ru active
- 2012-07-26 HU HUE12740581A patent/HUE033294T2/en unknown
- 2012-07-26 KR KR1020157005099A patent/KR101916443B1/ko active Active
- 2012-07-26 CA CA2879341A patent/CA2879341C/en active Active
- 2012-07-26 AU AU2012386257A patent/AU2012386257B2/en active Active
- 2012-07-26 BR BR112015001545-0A patent/BR112015001545B1/pt active IP Right Grant
- 2012-07-26 LT LTEP12740581.9T patent/LT2877467T/lt unknown
- 2012-07-26 US US14/416,937 patent/US9127003B2/en active Active
- 2012-07-26 RS RS20170121A patent/RS55684B1/sr unknown
- 2012-07-26 JP JP2015523426A patent/JP6063567B2/ja active Active
- 2012-07-26 SI SI201230769A patent/SI2877467T1/sl unknown
- 2012-07-26 IN IN2935KON2014 patent/IN2014KN02935A/en unknown
- 2012-07-26 PT PT127405819T patent/PT2877467T/pt unknown
- 2012-07-26 EP EP12740581.9A patent/EP2877467B1/en active Active
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2015
- 2015-08-03 US US14/816,246 patent/US9518054B2/en active Active
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2016
- 2016-11-15 US US15/352,340 patent/US9833449B2/en active Active
-
2017
- 2017-01-24 SM SM201700052T patent/SMT201700052B/it unknown
- 2017-01-27 CY CY20171100128T patent/CY1118524T1/el unknown
- 2017-11-20 US US15/817,562 patent/US10039755B2/en active Active
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