MX2017001493A - Eleccion de micro acidos ribonucleicos (arn) como diana para trastornos metabolicos. - Google Patents
Eleccion de micro acidos ribonucleicos (arn) como diana para trastornos metabolicos.Info
- Publication number
- MX2017001493A MX2017001493A MX2017001493A MX2017001493A MX2017001493A MX 2017001493 A MX2017001493 A MX 2017001493A MX 2017001493 A MX2017001493 A MX 2017001493A MX 2017001493 A MX2017001493 A MX 2017001493A MX 2017001493 A MX2017001493 A MX 2017001493A
- Authority
- MX
- Mexico
- Prior art keywords
- metabolic disorders
- targeting micrornas
- micrornas
- targeting
- mir
- Prior art date
Links
- 208000030159 metabolic disease Diseases 0.000 title 1
- 108091070501 miRNA Proteins 0.000 title 1
- 230000008685 targeting Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract 2
- 108091007774 MIR107 Proteins 0.000 abstract 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Chemical class Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 abstract 1
- 230000000295 complement effect Effects 0.000 abstract 1
- 208000037765 diseases and disorders Diseases 0.000 abstract 1
- 108091037473 miR-103 stem-loop Proteins 0.000 abstract 1
Classifications
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- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
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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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
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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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
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- 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
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
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- 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
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- 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
- A61P3/06—Antihyperlipidemics
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- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
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- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/11—Antisense
- C12N2310/113—Antisense targeting other non-coding nucleic acids, e.g. antagomirs
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
- C12N2310/141—MicroRNAs, miRNAs
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/315—Phosphorothioates
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/321—2'-O-R Modification
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/323—Chemical structure of the sugar modified ring structure
- C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
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- C12N2310/00—Structure or type of the nucleic acid
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- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/345—Spatial arrangement of the modifications having at least two different backbone modifications
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
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- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/50—Physical structure
- C12N2310/51—Physical structure in polymeric form, e.g. multimers, concatemers
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- C12N2320/00—Applications; Uses
- C12N2320/30—Special therapeutic applications
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Diabetes (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Child & Adolescent Psychology (AREA)
- Cardiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462034739P | 2014-08-07 | 2014-08-07 | |
| US201462062749P | 2014-10-10 | 2014-10-10 | |
| US201562143434P | 2015-04-06 | 2015-04-06 | |
| PCT/US2015/043926 WO2016022753A1 (en) | 2014-08-07 | 2015-08-06 | Targeting micrornas for metabolic disorders |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2017001493A true MX2017001493A (es) | 2017-05-09 |
Family
ID=53836884
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2017001493A MX2017001493A (es) | 2014-08-07 | 2015-08-06 | Eleccion de micro acidos ribonucleicos (arn) como diana para trastornos metabolicos. |
Country Status (17)
| Country | Link |
|---|---|
| US (4) | US9487783B2 (enExample) |
| EP (1) | EP3177721A1 (enExample) |
| JP (1) | JP2017523790A (enExample) |
| KR (1) | KR20170033439A (enExample) |
| CN (1) | CN106559995A (enExample) |
| AU (1) | AU2015301057A1 (enExample) |
| BR (1) | BR112017001931A2 (enExample) |
| CA (1) | CA2953883A1 (enExample) |
| CL (1) | CL2017000312A1 (enExample) |
| CO (1) | CO2017000950A2 (enExample) |
| IL (1) | IL249819A0 (enExample) |
| MA (1) | MA40463A (enExample) |
| MX (1) | MX2017001493A (enExample) |
| RU (1) | RU2017105342A (enExample) |
| SG (1) | SG11201610877PA (enExample) |
| TW (1) | TW201613949A (enExample) |
| WO (1) | WO2016022753A1 (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2015301057A1 (en) | 2014-08-07 | 2017-01-19 | Regulus Therapeutics Inc. | Targeting micrornas for metabolic disorders |
| IL262728B2 (en) * | 2016-05-06 | 2023-10-01 | Astrazeneca Ab | Oligonucleotides conjugated to the GLP-1 receptor ligand complex and their uses |
| CA3043768A1 (en) | 2016-11-29 | 2018-06-07 | PureTech Health LLC | Exosomes for delivery of therapeutic agents |
| KR101869308B1 (ko) * | 2017-02-28 | 2018-06-20 | 대구가톨릭대학교산학협력단 | Srebp-1 디코이 올리고디옥시뉴클레오티드 및 이를 유효성분으로 함유하는 지방간 질환의 예방 또는 치료용 약학 조성물 |
| JP7486423B2 (ja) * | 2018-01-17 | 2024-05-17 | ユニバーシティ オブ コネチカット | 糖尿病、肝炎、および／または炎症性肝疾患を治療するための方法 |
| JP2021531252A (ja) * | 2018-07-02 | 2021-11-18 | アプタミアール セラピューティクス インコーポレイテッド | ヒト脂肪細胞への治療薬の標的化送達 |
| JP2021531278A (ja) * | 2018-07-20 | 2021-11-18 | レグルス セラピューティクス インコーポレイテッド | オリゴヌクレオチドの経口送達のための方法 |
| US10844383B1 (en) | 2019-09-18 | 2020-11-24 | Dasman Diabetes Institute | Microrna dyslipidemia inhibitor |
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| US7683036B2 (en) | 2003-07-31 | 2010-03-23 | Regulus Therapeutics Inc. | Oligomeric compounds and compositions for use in modulation of small non-coding RNAs |
| DK1661905T3 (da) | 2003-08-28 | 2012-07-23 | Takeshi Imanishi | Hidtil ukendte syntetiske nukleinsyrer af N-O-krydsbindingstype |
| WO2006078278A2 (en) | 2004-04-27 | 2006-07-27 | Alnylam Pharmaceuticals, Inc. | Single-stranded and double-stranded oligonucleotides comprising a 2-arylpropyl moiety |
| EP2290067B1 (en) | 2004-05-28 | 2014-12-10 | Asuragen, Inc. | Methods and compositions involving microRNA |
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| AU2005333165B2 (en) | 2004-11-12 | 2012-07-19 | Asuragen, Inc. | Methods and compositions involving miRNA and miRNA inhibitor molecules |
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| EP1919512B1 (en) | 2005-08-10 | 2014-11-12 | Alnylam Pharmaceuticals Inc. | Chemically modified oligonucleotides for use in modulating micro rna and uses thereof |
| DK1931780T3 (en) | 2005-08-29 | 2016-01-25 | Regulus Therapeutics Inc | Antisense-forbindelser med forøget anti-microrna-aktivitet |
| EP2388328A1 (en) | 2006-01-27 | 2011-11-23 | Isis Pharmaceuticals, Inc. | Oligomeric compounds and compositions for the use in modulation of micrornas |
| PL2314594T3 (pl) | 2006-01-27 | 2014-12-31 | Isis Pharmaceuticals Inc | Zmodyfikowane w pozycji 6 analogi bicykliczne kwasów nukleinowych |
| CA2649045C (en) | 2006-04-03 | 2019-06-11 | Santaris Pharma A/S | Pharmaceutical composition comprising anti-mirna antisense oligonucleotides |
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-
2015
- 2015-08-06 AU AU2015301057A patent/AU2015301057A1/en not_active Abandoned
- 2015-08-06 MA MA040463A patent/MA40463A/fr unknown
- 2015-08-06 KR KR1020177005873A patent/KR20170033439A/ko not_active Withdrawn
- 2015-08-06 EP EP15750573.6A patent/EP3177721A1/en not_active Withdrawn
- 2015-08-06 CN CN201580039229.9A patent/CN106559995A/zh active Pending
- 2015-08-06 JP JP2017506667A patent/JP2017523790A/ja not_active Ceased
- 2015-08-06 US US14/819,648 patent/US9487783B2/en not_active Expired - Fee Related
- 2015-08-06 MX MX2017001493A patent/MX2017001493A/es unknown
- 2015-08-06 BR BR112017001931A patent/BR112017001931A2/pt not_active Application Discontinuation
- 2015-08-06 WO PCT/US2015/043926 patent/WO2016022753A1/en not_active Ceased
- 2015-08-06 CA CA2953883A patent/CA2953883A1/en not_active Abandoned
- 2015-08-06 TW TW104125684A patent/TW201613949A/zh unknown
- 2015-08-06 RU RU2017105342A patent/RU2017105342A/ru not_active Application Discontinuation
- 2015-08-06 SG SG11201610877PA patent/SG11201610877PA/en unknown
-
2016
- 2016-09-22 US US15/272,619 patent/US9862950B2/en not_active Expired - Fee Related
- 2016-12-28 IL IL249819A patent/IL249819A0/en unknown
-
2017
- 2017-02-01 CO CONC2017/0000950A patent/CO2017000950A2/es unknown
- 2017-02-07 CL CL2017000312A patent/CL2017000312A1/es unknown
- 2017-10-05 US US15/725,843 patent/US10138484B2/en not_active Expired - Fee Related
-
2018
- 2018-09-25 US US16/140,881 patent/US20190153444A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| BR112017001931A2 (pt) | 2017-11-28 |
| SG11201610877PA (en) | 2017-02-27 |
| AU2015301057A1 (en) | 2017-01-19 |
| KR20170033439A (ko) | 2017-03-24 |
| IL249819A0 (en) | 2017-03-30 |
| CL2017000312A1 (es) | 2017-10-06 |
| WO2016022753A1 (en) | 2016-02-11 |
| RU2017105342A (ru) | 2018-09-13 |
| CN106559995A (zh) | 2017-04-05 |
| MA40463A (fr) | 2017-06-14 |
| US10138484B2 (en) | 2018-11-27 |
| US20170067051A1 (en) | 2017-03-09 |
| RU2017105342A3 (enExample) | 2019-03-05 |
| US20190153444A1 (en) | 2019-05-23 |
| US9487783B2 (en) | 2016-11-08 |
| JP2017523790A (ja) | 2017-08-24 |
| US20160046940A1 (en) | 2016-02-18 |
| US20180171334A1 (en) | 2018-06-21 |
| TW201613949A (en) | 2016-04-16 |
| US9862950B2 (en) | 2018-01-09 |
| CA2953883A1 (en) | 2016-02-11 |
| EP3177721A1 (en) | 2017-06-14 |
| CO2017000950A2 (es) | 2017-06-30 |
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