PE20141067A1 - Compuestos para el tratamiento de la adiccion - Google Patents
Compuestos para el tratamiento de la adiccionInfo
- Publication number
- PE20141067A1 PE20141067A1 PE2013002811A PE2013002811A PE20141067A1 PE 20141067 A1 PE20141067 A1 PE 20141067A1 PE 2013002811 A PE2013002811 A PE 2013002811A PE 2013002811 A PE2013002811 A PE 2013002811A PE 20141067 A1 PE20141067 A1 PE 20141067A1
- Authority
- PE
- Peru
- Prior art keywords
- optionally substituted
- compounds
- alkyl
- treatment
- benzamide
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title abstract 4
- 206010012335 Dependence Diseases 0.000 title abstract 2
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical class [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 abstract 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 abstract 2
- 102000005369 Aldehyde Dehydrogenase Human genes 0.000 abstract 1
- 108020002663 Aldehyde Dehydrogenase Proteins 0.000 abstract 1
- 241000124008 Mammalia Species 0.000 abstract 1
- 102000009645 Mitochondrial Aldehyde Dehydrogenase Human genes 0.000 abstract 1
- 108010009513 Mitochondrial Aldehyde Dehydrogenase Proteins 0.000 abstract 1
- 206010013663 drug dependence Diseases 0.000 abstract 1
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical class [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 abstract 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 abstract 1
- 239000003112 inhibitor Substances 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 208000011117 substance-related disease Diseases 0.000 abstract 1
Classifications
-
- 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
- A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/58—Pyridine rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Addiction (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Psychiatry (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
SE REFIERE A COMPUESTOS DE FORMULA (I) DONDE R1 ES H, ALQUILO C1-6 OPCIONALMENTE SUSTITUIDO, CH2OH, ENTRE OTROS; R2 ES H, ALQUILO C1-6 OPCIONALMENTE SUSTITUIDO, CICLOALQUILO O HALO; R3, R4, R5, R6, R9, R10, R11, R12, R13 SON INDEPENDIENTEMENTE H, HIDROXILO, ALQUILO OPCIONALMENTE SUSTITUIDO, ALQUILENO OPCIONALMENTE SUSTITUIDO, HETEROARILO OPCIONALMENTE SUSTITUIDO, ACILO, AMINOCARBONILO, ENTRE OTROS; R7 ES H O ALQUILO C1-6 OPCIONALMENETE SUSTITUIDO. SON COMPUESTOS PREFERIDOS: 2,6-DICLORO-4-(2-METOXIETOXI)-N-(4-(2-OXO-1,2-DIHIDROPIRIDIN-4-IL)BENCIL)BENZAMIDA; 2,6-DICLORO-N-[4-(2-OXO-1,2-DIHIDRO-PIRIDIN-4-IL)BENCIL]-BENZAMIDA; ENTRE OTROS. REFERIDO ADEMAS A UNA COMPOSICION FARMACEUTICA. DICHOS COMPUESTOS SON INHIBIDORES DE LA ALDEHIDO DESHIDROGENASA (ALDH-2) MITOCONDRIAL HUMANA, SIENDO UTILES PARA EL TRATAMIENTO DE LA DEPENDENCIA A DROGAS DE ADICCION EN MAMIFEROS
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201161503923P | 2011-07-01 | 2011-07-01 |
Publications (1)
Publication Number | Publication Date |
---|---|
PE20141067A1 true PE20141067A1 (es) | 2014-09-05 |
Family
ID=46513858
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PE2013002811A PE20141067A1 (es) | 2011-07-01 | 2012-06-29 | Compuestos para el tratamiento de la adiccion |
Country Status (32)
Country | Link |
---|---|
US (6) | US8558001B2 (es) |
EP (2) | EP2993170B1 (es) |
JP (1) | JP5943998B2 (es) |
KR (2) | KR101664915B1 (es) |
CN (1) | CN103635460B (es) |
AP (1) | AP3544A (es) |
AR (1) | AR086792A1 (es) |
AU (1) | AU2012279332B2 (es) |
BR (1) | BR112014000033A2 (es) |
CA (1) | CA2840763C (es) |
CL (1) | CL2013003597A1 (es) |
CO (1) | CO6821964A2 (es) |
CR (1) | CR20130659A (es) |
DK (1) | DK2993170T3 (es) |
EA (1) | EA025573B1 (es) |
EC (1) | ECSP13013087A (es) |
ES (2) | ES2656716T3 (es) |
HK (2) | HK1197236A1 (es) |
IL (1) | IL230657B (es) |
MA (1) | MA35404B1 (es) |
MD (1) | MD4436B1 (es) |
MX (1) | MX337611B (es) |
PE (1) | PE20141067A1 (es) |
PL (1) | PL2726460T3 (es) |
PT (1) | PT2726460E (es) |
SG (1) | SG10201605355RA (es) |
SI (1) | SI2726460T1 (es) |
TW (1) | TWI567061B (es) |
UA (1) | UA109199C2 (es) |
UY (1) | UY34165A (es) |
WO (1) | WO2013006400A1 (es) |
ZA (1) | ZA201308977B (es) |
Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012149106A1 (en) | 2011-04-29 | 2012-11-01 | The Board Of Trustees Of The Leland Stanford Junior University | Compositions and methods for increasing proliferation of adult salivary stem cells |
US9115096B2 (en) | 2011-05-10 | 2015-08-25 | Gilead Sciences, Inc. | Fused heterocyclic compounds as ion channel modulators |
TWI567061B (zh) | 2011-07-01 | 2017-01-21 | 吉李德科學股份有限公司 | 用於治療成癮之化合物 |
NO3175985T3 (es) | 2011-07-01 | 2018-04-28 | ||
TWI622583B (zh) | 2011-07-01 | 2018-05-01 | 基利科學股份有限公司 | 作為離子通道調節劑之稠合雜環化合物 |
CN105358531B (zh) * | 2013-03-14 | 2017-11-14 | 利兰-斯坦福大学初级学院的董事会 | 线粒体醛脱氢酶‑2调节剂和其使用方法 |
TWI651329B (zh) * | 2013-12-13 | 2019-02-21 | 美商維泰克斯製藥公司 | 作為鈉通道調節劑之吡啶酮醯胺之前藥 |
US10077669B2 (en) | 2014-11-26 | 2018-09-18 | United Technologies Corporation | Non-metallic engine case inlet compression seal for a gas turbine engine |
US10289971B2 (en) | 2015-02-13 | 2019-05-14 | Atlassian Pty Ltd | Issue and trigger rebalancing in a ranked issue management system |
RS63872B1 (sr) * | 2016-08-19 | 2023-02-28 | Univ Bristol | Derivati citizina za lečenje zavisnosti |
JOP20180040A1 (ar) | 2017-04-20 | 2019-01-30 | Gilead Sciences Inc | مثبطات pd-1/pd-l1 |
JP2020536970A (ja) * | 2017-10-16 | 2020-12-17 | アミグダラ ニューロサイエンシス インコーポレイテッド | 嗜癖を予防するための組み合わせ療法 |
IL300572A (en) | 2018-02-13 | 2023-04-01 | Gilead Sciences Inc | PD–1/PD–L1 inhibitors |
CA3093130C (en) | 2018-04-19 | 2023-10-17 | Gilead Sciences, Inc. | Pd-1/pd-l1 inhibitors |
PE20210004A1 (es) | 2018-05-14 | 2021-01-05 | Gilead Sciences Inc | Inhibidores de mcl-1 |
TWI809427B (zh) | 2018-07-13 | 2023-07-21 | 美商基利科學股份有限公司 | Pd‐1/pd‐l1抑制劑 |
WO2020023792A1 (en) * | 2018-07-27 | 2020-01-30 | Amygdala Neurosciences, Inc. | Combination therapy for nicotine addiction |
EP3863424A4 (en) * | 2018-10-12 | 2022-08-03 | Amygdala Neurosciences, Inc. | ADDICTION TREATMENT OF AN ALCOHOLIC PATIENT POPULATION |
KR102635333B1 (ko) | 2018-10-24 | 2024-02-15 | 길리애드 사이언시즈, 인코포레이티드 | Pd-1/pd-l1 억제제 |
WO2023244574A1 (en) | 2022-06-14 | 2023-12-21 | Amygdala Neurosciences, Inc. | Aldh-2 inhibitor compounds and methods of use |
WO2023244563A1 (en) | 2022-06-14 | 2023-12-21 | Amygdala Neurosciences, Inc. | Aldh-2 inhibitor compounds and methods of use |
Family Cites Families (22)
Publication number | Priority date | Publication date | Assignee | Title |
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US3845770A (en) | 1972-06-05 | 1974-11-05 | Alza Corp | Osmatic dispensing device for releasing beneficial agent |
US4326525A (en) | 1980-10-14 | 1982-04-27 | Alza Corporation | Osmotic device that improves delivery properties of agent in situ |
US5364620A (en) | 1983-12-22 | 1994-11-15 | Elan Corporation, Plc | Controlled absorption diltiazem formulation for once daily administration |
US5023252A (en) | 1985-12-04 | 1991-06-11 | Conrex Pharmaceutical Corporation | Transdermal and trans-membrane delivery of drugs |
US4992445A (en) | 1987-06-12 | 1991-02-12 | American Cyanamid Co. | Transdermal delivery of pharmaceuticals |
US5001139A (en) | 1987-06-12 | 1991-03-19 | American Cyanamid Company | Enchancers for the transdermal flux of nivadipine |
US4902514A (en) | 1988-07-21 | 1990-02-20 | Alza Corporation | Dosage form for administering nilvadipine for treating cardiovascular symptoms |
US5204369A (en) | 1991-07-01 | 1993-04-20 | The Endowment For Research In Human Biology | Method for the inhibition of aldh-i useful in the treatment of alcohol dependence or alcohol abuse |
WO1999058124A1 (en) | 1998-05-12 | 1999-11-18 | The Endowment For Research In Human Biology, Inc. | Methods and assays useful in the treatment of alcohol dependence or alcohol abuse |
EP1542675A4 (en) | 2002-06-27 | 2008-11-19 | Endowment For Res In Human Bio | COMPOUNDS USEFUL IN THE INHIBITION OF ALDH |
JP2004182657A (ja) * | 2002-12-04 | 2004-07-02 | Eisai Co Ltd | Hdlレベル上昇促進剤 |
US20080004260A1 (en) | 2006-06-29 | 2008-01-03 | Transcept Pharmaceuticals, Inc. | Compositions of 5-HT3 antagonists and dopamine D2 antagonists for treatment of dopamine-associated chronic conditions |
US8158810B2 (en) | 2006-07-27 | 2012-04-17 | Gilead Sciences, Inc. | ALDH-2 inhibitors in the treatment of addiction |
US20080207610A1 (en) | 2006-07-27 | 2008-08-28 | Jeff Zablocki | Aldh-2 inhibitors in the treatment of addiction |
KR20090033417A (ko) | 2006-07-27 | 2009-04-03 | 씨브이 쎄러퓨틱스, 인코포레이티드 | 중독의 치료에서의 aldh-2 저해제 |
WO2008112164A2 (en) | 2007-03-08 | 2008-09-18 | The Board Of Trustees Of The Leland Stanford Junior University | Mitochondrial aldehyde dehydrogenase-2 modulators and methods of use thereof |
MX2010008111A (es) | 2008-01-24 | 2010-11-30 | Endowment For Res In Human Biology Inc | Inhibidores de aldh-2 en el tratamiento de adicciones. |
AU2009241727B2 (en) | 2008-05-01 | 2013-05-02 | Vitae Pharmaceuticals, Inc | Cyclic inhibitors of 11beta-hydroxysteroid dehydrogenase 1 |
EP2337563B1 (en) | 2008-09-08 | 2014-04-09 | The Board of Trustees of The Leland Stanford Junior University | Modulators of aldehyde dehydrogenase activity and methods of use thereof |
JP2012506856A (ja) * | 2008-10-28 | 2012-03-22 | ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティ | アルデヒドデヒドロゲナーゼのモジュレーターおよびその使用方法 |
UY33469A (es) * | 2010-06-29 | 2012-01-31 | Irm Llc Y Novartis Ag | Composiciones y metodos para modular la via de señalizacion de wnt |
TWI567061B (zh) * | 2011-07-01 | 2017-01-21 | 吉李德科學股份有限公司 | 用於治療成癮之化合物 |
-
2012
- 2012-06-26 TW TW101122794A patent/TWI567061B/zh active
- 2012-06-27 UY UY0001034165A patent/UY34165A/es not_active Application Discontinuation
- 2012-06-28 AR ARP120102331A patent/AR086792A1/es not_active Application Discontinuation
- 2012-06-29 MX MX2013014938A patent/MX337611B/es active IP Right Grant
- 2012-06-29 US US13/537,536 patent/US8558001B2/en active Active
- 2012-06-29 WO PCT/US2012/044809 patent/WO2013006400A1/en active Application Filing
- 2012-06-29 AP AP2013007282A patent/AP3544A/xx active
- 2012-06-29 PE PE2013002811A patent/PE20141067A1/es not_active Application Discontinuation
- 2012-06-29 PL PL12735394T patent/PL2726460T3/pl unknown
- 2012-06-29 MD MDA20140009A patent/MD4436B1/ro not_active IP Right Cessation
- 2012-06-29 SG SG10201605355RA patent/SG10201605355RA/en unknown
- 2012-06-29 KR KR1020147002302A patent/KR101664915B1/ko active IP Right Grant
- 2012-06-29 DK DK15184883.5T patent/DK2993170T3/da active
- 2012-06-29 BR BR112014000033A patent/BR112014000033A2/pt active Search and Examination
- 2012-06-29 UA UAA201314148A patent/UA109199C2/ru unknown
- 2012-06-29 PT PT127353944T patent/PT2726460E/pt unknown
- 2012-06-29 KR KR1020167023967A patent/KR20160106207A/ko not_active Application Discontinuation
- 2012-06-29 AU AU2012279332A patent/AU2012279332B2/en not_active Ceased
- 2012-06-29 EP EP15184883.5A patent/EP2993170B1/en active Active
- 2012-06-29 ES ES15184883.5T patent/ES2656716T3/es active Active
- 2012-06-29 EA EA201391635A patent/EA025573B1/ru not_active IP Right Cessation
- 2012-06-29 CA CA2840763A patent/CA2840763C/en active Active
- 2012-06-29 JP JP2014519122A patent/JP5943998B2/ja active Active
- 2012-06-29 CN CN201280032944.6A patent/CN103635460B/zh not_active Expired - Fee Related
- 2012-06-29 EP EP12735394.4A patent/EP2726460B1/en active Active
- 2012-06-29 ES ES12735394.4T patent/ES2553829T3/es active Active
- 2012-06-29 SI SI201230340T patent/SI2726460T1/sl unknown
-
2013
- 2013-03-08 US US13/791,422 patent/US8575353B2/en active Active
- 2013-08-13 US US13/966,029 patent/US9000015B2/en active Active
- 2013-11-28 ZA ZA2013/08977A patent/ZA201308977B/en unknown
- 2013-12-13 CR CR20130659A patent/CR20130659A/es unknown
- 2013-12-16 CL CL2013003597A patent/CL2013003597A1/es unknown
- 2013-12-18 CO CO13295408A patent/CO6821964A2/es active IP Right Grant
- 2013-12-18 EC ECSP13013087 patent/ECSP13013087A/es unknown
- 2013-12-30 MA MA36629A patent/MA35404B1/fr unknown
-
2014
- 2014-01-26 IL IL230657A patent/IL230657B/en active IP Right Grant
- 2014-10-27 HK HK14110733A patent/HK1197236A1/xx not_active IP Right Cessation
-
2015
- 2015-03-16 US US14/659,042 patent/US9610299B2/en active Active
-
2016
- 2016-05-12 HK HK16105461.1A patent/HK1217487A1/zh not_active IP Right Cessation
-
2017
- 2017-03-31 US US15/476,569 patent/US9987295B2/en active Active
-
2018
- 2018-05-08 US US15/974,171 patent/US10507215B2/en not_active Expired - Fee Related
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