KR20150093819A - 약제 조성물 - Google Patents
약제 조성물 Download PDFInfo
- Publication number
- KR20150093819A KR20150093819A KR1020157018488A KR20157018488A KR20150093819A KR 20150093819 A KR20150093819 A KR 20150093819A KR 1020157018488 A KR1020157018488 A KR 1020157018488A KR 20157018488 A KR20157018488 A KR 20157018488A KR 20150093819 A KR20150093819 A KR 20150093819A
- Authority
- KR
- South Korea
- Prior art keywords
- compound
- pentamethyl
- dimethyl
- oxo
- cyclopenta
- 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.)
- Withdrawn
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- DSNLMYRCHYFVDO-UHFFFAOYSA-N [5a,5b,8,8,11a-pentamethyl-9-(oxan-2-yloxy)-1-prop-1-en-2-yl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysen-3a-yl]methyl 4-methylbenzenesulfonate Chemical compound C1CC(C2(CCC3C(C)(C)C(OC4OCCCC4)CCC3(C)C2CC2)C)(C)C2C2C(C(=C)C)CCC21COS(=O)(=O)C1=CC=C(C)C=C1 DSNLMYRCHYFVDO-UHFFFAOYSA-N 0.000 claims abstract description 14
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- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 2
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- CZFFBEXEKNGXKS-UHFFFAOYSA-N raltegravir Chemical compound O1C(C)=NN=C1C(=O)NC(C)(C)C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N1C CZFFBEXEKNGXKS-UHFFFAOYSA-N 0.000 description 1
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- 230000002829 reductive effect Effects 0.000 description 1
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- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
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- 150000003892 tartrate salts Chemical class 0.000 description 1
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Images
Classifications
-
- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
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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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
-
- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
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- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/74—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J19/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 by a lactone ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
- C07J63/008—Expansion of ring D by one atom, e.g. D homo steroids
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
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- Organic Chemistry (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Bioinformatics & Cheminformatics (AREA)
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- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- AIDS & HIV (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Plant Substances (AREA)
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| US61/737,177 | 2012-12-14 | ||
| PCT/US2013/075196 WO2014093941A1 (en) | 2012-12-14 | 2013-12-14 | Pharmaceutical compositions |
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| KR20150093819A true KR20150093819A (ko) | 2015-08-18 |
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| KR1020157018488A Withdrawn KR20150093819A (ko) | 2012-12-14 | 2013-12-14 | 약제 조성물 |
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| CA (1) | CA2893959A1 (enExample) |
| CL (1) | CL2015001660A1 (enExample) |
| CR (1) | CR20150313A (enExample) |
| EA (1) | EA201590862A1 (enExample) |
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| IL (1) | IL238807A0 (enExample) |
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| SG (2) | SG11201503807TA (enExample) |
| WO (1) | WO2014093941A1 (enExample) |
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| JO3387B1 (ar) | 2011-12-16 | 2019-03-13 | Glaxosmithkline Llc | مشتقات بيتولين |
| SG11201503807TA (en) * | 2012-12-14 | 2015-06-29 | Glaxosmithkline Llc | Pharmaceutical compositions |
| SI2822954T1 (sl) | 2012-12-21 | 2016-07-29 | Gilead Sciences, Inc. | Policiklične karbamoilpiridonske spojine in njihova farmacevtska uporaba |
| WO2014105926A1 (en) | 2012-12-31 | 2014-07-03 | Hetero Research Foundation | Novel betulinic acid proline derivatives as hiv inhibitors |
| PT3019503T (pt) | 2013-07-12 | 2017-11-27 | Gilead Sciences Inc | Compostos carbamoílpiridona- policíclicos e seu uso para o tratamento de infecções por hiv |
| NO2865735T3 (enExample) | 2013-07-12 | 2018-07-21 | ||
| TW201613936A (en) | 2014-06-20 | 2016-04-16 | Gilead Sciences Inc | Crystalline forms of(2R,5S,13aR)-8-hydroxy-7,9-dioxo-n-(2,4,6-trifluorobenzyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazepine-10-carboxamide |
| NO2717902T3 (enExample) | 2014-06-20 | 2018-06-23 | ||
| TWI744723B (zh) | 2014-06-20 | 2021-11-01 | 美商基利科學股份有限公司 | 多環型胺甲醯基吡啶酮化合物之合成 |
| US20170129916A1 (en) | 2014-06-26 | 2017-05-11 | Hetero Research Foundation | Novel betulinic proline imidazole derivatives as hiv inhibitors |
| KR20170056702A (ko) * | 2014-09-26 | 2017-05-23 | 글락소스미스클라인 인털렉츄얼 프로퍼티 (넘버 2) 리미티드 | 지효성 약제학적 조성물 |
| TWI695003B (zh) | 2014-12-23 | 2020-06-01 | 美商基利科學股份有限公司 | 多環胺甲醯基吡啶酮化合物及其醫藥用途 |
| MA40886B1 (fr) | 2015-02-09 | 2020-03-31 | Hetero Research Foundation | Nouveau triterpénone en c-3 avec des dérivés d'amide inverse en c-28 en tant qu'inhibiteurs du vih |
| US10370405B2 (en) | 2015-03-16 | 2019-08-06 | Hetero Labs Limited | C-3 novel triterpenone with C-28 amide derivatives as HIV inhibitors |
| WO2016161382A1 (en) | 2015-04-02 | 2016-10-06 | Gilead Sciences, Inc. | Polycyclic-carbamoylpyridone compounds and their pharmaceutical use |
| WO2018042331A1 (en) * | 2016-08-31 | 2018-03-08 | Glaxosmithkline Intellectual Property (No.2) Limited | Combinations and uses and treatments thereof |
| WO2018042332A1 (en) * | 2016-08-31 | 2018-03-08 | Glaxosmithkline Intellectual Property (No.2) Limited | Combinations and uses and treatments thereof |
| KR20260015342A (ko) | 2017-07-21 | 2026-02-02 | 비이브 헬쓰케어 컴퍼니 | Hib 감염 및 aids를 치료하기 위한 요법 |
Family Cites Families (35)
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| GB8815265D0 (en) | 1988-06-27 | 1988-08-03 | Wellcome Found | Therapeutic nucleosides |
| US5358721A (en) * | 1992-12-04 | 1994-10-25 | Alza Corporation | Antiviral therapy |
| EP1292562A1 (en) | 2000-05-23 | 2003-03-19 | Univerzita palackeho V Olomouci | Triterpenoid derivatives |
| US7163700B2 (en) * | 2001-07-31 | 2007-01-16 | Capricorn Pharma, Inc. | Amorphous drug beads |
| US20080206161A1 (en) * | 2002-10-25 | 2008-08-28 | Dov Tamarkin | Quiescent foamable compositions, steroids, kits and uses thereof |
| US20050142205A1 (en) * | 2003-07-18 | 2005-06-30 | Julia Rashba-Step | Methods for encapsulating small spherical particles prepared by controlled phase separation |
| US20060019934A1 (en) * | 2004-05-20 | 2006-01-26 | Saxena Brij B | Anti-HIV-1 activity of betulinol derivatives |
| TW200628161A (en) | 2004-11-12 | 2006-08-16 | Panacos Pharmaceuticals Inc | Novel betulin derivatives, preparation thereof and use thereof |
| CN1682740A (zh) * | 2005-03-11 | 2005-10-19 | 中国药科大学 | 五环三萜类化合物在制备糖原磷酸化酶抑制剂中的应用 |
| EP1869063A2 (en) | 2005-03-29 | 2007-12-26 | Regents Of The University Of Minnesota | Methods of manufacturing bioactive 3-esters of betulinic aldehyde and betulinic acid |
| TWI457136B (zh) | 2005-04-04 | 2014-10-21 | Tibotec Pharm Ltd | Ｈｉｖ-感染之預防 |
| WO2006117666A2 (en) * | 2005-04-29 | 2006-11-09 | Pfizer Inc. | Dosage forms, pharmaceutical compositions and methods for sub-tenon delivery |
| EP1986654A2 (en) | 2006-02-21 | 2008-11-05 | Achillion Pharmaceuticals, Inc. | Substituted taraxastanes useful for treating viral infections |
| FI121468B (fi) | 2006-06-07 | 2010-11-30 | Valtion Teknillinen | Betuliiniperäiset yhdisteet antimikrobisina aineina |
| UA97641C2 (xx) | 2006-06-23 | 2012-03-12 | Тиботек Фармасьютикелз Лтд. | Водна суспензія 4-$$4-$$4-(2-ціаноетеніл)-2,6-диметилфеніл]аміно]-2-піримідиніл]аміно]бензонітрилу (tmc278)$водная суспензия 4-$$4-$$4-(2-цианоэтенил)-2,6-диметилфенил]амино]-2-пиримидинил]амино]бензонитрила (тмс278) |
| WO2008127364A2 (en) | 2006-10-13 | 2008-10-23 | Myriad Genetics, Inc. | Antiviral compounds and use thereof |
| AR063546A1 (es) * | 2006-11-03 | 2009-01-28 | Panacos Pharmaceuticals Inc | DERIVADOS DE TRITERPENO, METODOS PARA SU PREPARACION, COMPOSICIONES FARMACEUTICAS QUE LOS COMPRENDEN Y SU USO EN LA FABRICACION DE MEDICAMENTOS PARA EL TRATAMIENTO DE INFECCIoN POR EL VIRUS VIH. |
| CA2693044C (en) * | 2007-07-12 | 2017-03-14 | Tibotec Pharmaceuticals | Crystalline form of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2 pyrimidinyl]amino]benzonitrile |
| EP2250185A4 (en) | 2008-01-03 | 2011-11-16 | Virochem Pharma Inc | NEW LUPANDERIVATE |
| JP2011508747A (ja) * | 2008-01-03 | 2011-03-17 | バイロケム ファーマ インコーポレイテッド | 新規のｃ−２１ケトルパン誘導体、それらの調製および使用 |
| DE102008037025C5 (de) * | 2008-08-08 | 2016-07-07 | Jesalis Pharma Gmbh | Verfahren zur Herstellung kristalliner Wirkstoff-Mikropartikel bzw. einer Wirkstoffpartikel-Festkörperform |
| US8778990B2 (en) | 2008-11-04 | 2014-07-15 | Trustees Of Dartmouth College | Betulinic acid derivatives and methods of use thereof |
| CZ2008723A3 (cs) | 2008-11-13 | 2010-01-13 | Univerzita Palackého v Olomouci | 2-Deoxyglykosidy triterpenoidu, zpusob jejich prípravy a jejich použití jako lécivo |
| MX351942B (es) * | 2008-12-11 | 2017-11-03 | Shionogi & Co | Sintesis de inhibidores de integrasa de vih de carbamoil-piridona e intermediarios. |
| US8802727B2 (en) | 2009-07-14 | 2014-08-12 | Hetero Research Foundation, Hetero Drugs Limited | Pharmaceutically acceptable salts of betulinic acid derivatives |
| US9067966B2 (en) | 2009-07-14 | 2015-06-30 | Hetero Research Foundation, Hetero Drugs Ltd. | Lupeol-type triterpene derivatives as antivirals |
| US20120302534A1 (en) * | 2010-02-11 | 2012-11-29 | Daxin Gao | Derivatives of betulin |
| TWI577377B (zh) * | 2010-09-16 | 2017-04-11 | Ｖｉｉｖ醫療保健公司 | 醫藥組合物 |
| WO2013020246A1 (en) | 2011-08-08 | 2013-02-14 | Glaxosmithkline Llc | Methylene derivatives of betulin |
| WO2013020245A1 (en) | 2011-08-08 | 2013-02-14 | Glaxosmithkline Llc | Carbonyl derivatives of betulin |
| AU2012352129B2 (en) | 2011-12-14 | 2016-02-04 | Glaxosmithkline Llc | Propenoate derivatives of betulin |
| JO3387B1 (ar) | 2011-12-16 | 2019-03-13 | Glaxosmithkline Llc | مشتقات بيتولين |
| US20150209273A1 (en) | 2012-08-28 | 2015-07-30 | Glaxosmithkline Llc | Pharmaceutical Compositions |
| SG11201503807TA (en) * | 2012-12-14 | 2015-06-29 | Glaxosmithkline Llc | Pharmaceutical compositions |
| KR20170056702A (ko) | 2014-09-26 | 2017-05-23 | 글락소스미스클라인 인털렉츄얼 프로퍼티 (넘버 2) 리미티드 | 지효성 약제학적 조성물 |
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- 2013-12-14 KR KR1020157018488A patent/KR20150093819A/ko not_active Withdrawn
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- 2013-12-14 MA MA38182A patent/MA38182A1/fr unknown
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- 2013-12-14 HK HK15110448.0A patent/HK1209638A1/xx unknown
- 2013-12-14 US US14/651,673 patent/US9795619B2/en not_active Expired - Fee Related
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- 2013-12-14 SG SG10201704467SA patent/SG10201704467SA/en unknown
- 2013-12-14 MX MX2015007563A patent/MX2015007563A/es unknown
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2015
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- 2015-05-25 PH PH12015501156A patent/PH12015501156A1/en unknown
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2017
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Also Published As
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| CL2015001660A1 (es) | 2015-10-02 |
| US9795619B2 (en) | 2017-10-24 |
| HK1209638A1 (en) | 2016-04-08 |
| EP2931285A1 (en) | 2015-10-21 |
| ZA201503594B (en) | 2018-11-28 |
| EP2931285A4 (en) | 2016-06-01 |
| MX2015007563A (es) | 2015-10-14 |
| WO2014093941A1 (en) | 2014-06-19 |
| IL238807A0 (en) | 2015-06-30 |
| SG11201503807TA (en) | 2015-06-29 |
| US20180042944A1 (en) | 2018-02-15 |
| CR20150313A (es) | 2015-10-19 |
| CN104902905A (zh) | 2015-09-09 |
| MA38182A1 (fr) | 2018-04-30 |
| PE20151326A1 (es) | 2015-10-12 |
| PH12015501156A1 (en) | 2015-08-10 |
| AU2013358897B2 (en) | 2017-01-05 |
| CA2893959A1 (en) | 2014-06-19 |
| AU2013358897A1 (en) | 2015-07-02 |
| JP2016503030A (ja) | 2016-02-01 |
| US20150313917A1 (en) | 2015-11-05 |
| BR112015013695A2 (pt) | 2017-07-11 |
| SG10201704467SA (en) | 2017-06-29 |
| EA201590862A1 (ru) | 2016-05-31 |
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| PA0105 | International application |
Patent event date: 20150709 Patent event code: PA01051R01D Comment text: International Patent Application |
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| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |