CY1120821T1 - Παραγωγα ταμοξιφαινης για θεραπεια νεοπλασματικων ασθενειων, ειδικα με υψηλο επιπεδο πρωτεϊνης her2 - Google Patents
Παραγωγα ταμοξιφαινης για θεραπεια νεοπλασματικων ασθενειων, ειδικα με υψηλο επιπεδο πρωτεϊνης her2Info
- Publication number
- CY1120821T1 CY1120821T1 CY181101155T CY181101155T CY1120821T1 CY 1120821 T1 CY1120821 T1 CY 1120821T1 CY 181101155 T CY181101155 T CY 181101155T CY 181101155 T CY181101155 T CY 181101155T CY 1120821 T1 CY1120821 T1 CY 1120821T1
- Authority
- CY
- Cyprus
- Prior art keywords
- treatment
- general formula
- her2 protein
- aliphatic
- tamoxifaine
- Prior art date
Links
- 201000010099 disease Diseases 0.000 title abstract 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract 3
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 title abstract 2
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 title abstract 2
- -1 aliphatic triphenylphosphonate derivatives Chemical class 0.000 abstract 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 abstract 3
- 150000003839 salts Chemical class 0.000 abstract 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 abstract 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 abstract 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 abstract 2
- 229910019142 PO4 Inorganic materials 0.000 abstract 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 abstract 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Natural products C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 abstract 2
- 150000004820 halides Chemical class 0.000 abstract 2
- 230000001613 neoplastic effect Effects 0.000 abstract 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 abstract 2
- 239000010452 phosphate Substances 0.000 abstract 2
- 229960001603 tamoxifen Drugs 0.000 abstract 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 abstract 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 abstract 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 abstract 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 abstract 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 abstract 1
- 125000001931 aliphatic group Chemical group 0.000 abstract 1
- 125000003342 alkenyl group Chemical group 0.000 abstract 1
- 125000000217 alkyl group Chemical group 0.000 abstract 1
- 229940072107 ascorbate Drugs 0.000 abstract 1
- 235000010323 ascorbic acid Nutrition 0.000 abstract 1
- 239000011668 ascorbic acid Substances 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 230000002438 mitochondrial effect Effects 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 230000008685 targeting Effects 0.000 abstract 1
- 229940095064 tartrate Drugs 0.000 abstract 1
Classifications
-
- 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
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/54—Quaternary phosphonium compounds
- C07F9/5456—Arylalkanephosphonium compounds
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
- 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
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/54—Quaternary phosphonium compounds
- C07F9/5442—Aromatic phosphonium compounds (P-C aromatic linkage)
-
- 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
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/54—Quaternary phosphonium compounds
- C07F9/5449—Polyphosphonium compounds
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B23/00—Methine or polymethine dyes, e.g. cyanine dyes
- C09B23/0008—Methine or polymethine dyes, e.g. cyanine dyes substituted on the polymethine chain
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B23/00—Methine or polymethine dyes, e.g. cyanine dyes
- C09B23/0008—Methine or polymethine dyes, e.g. cyanine dyes substituted on the polymethine chain
- C09B23/0025—Methine or polymethine dyes, e.g. cyanine dyes substituted on the polymethine chain the substituent being bound through an oxygen atom
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B23/00—Methine or polymethine dyes, e.g. cyanine dyes
- C09B23/14—Styryl dyes
- C09B23/141—Bis styryl dyes containing two radicals C6H5-CH=CH-
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B69/00—Dyes not provided for by a single group of this subclass
- C09B69/001—Dyes containing an onium group attached to the dye skeleton via a bridge
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
- C09B69/00—Dyes not provided for by a single group of this subclass
- C09B69/008—Dyes containing a substituent, which contains a silicium atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Epidemiology (AREA)
Abstract
Το αντικείμενο της εφεύρεσης είναι νέα μιτοχονδριακά στοχευόμενα Ε/Ζ ισομερή των αλειφατικών τριφαινυλοφωσφόνιων παραγώγων της ταμοξιφαίνης, όπου η αλειφατική αλυσίδα είναι αλκύλιο ή αλκενύλιο και τα αντίστοιχα άλατα της τριτοταγούς αμίνης που επιλέγονται από οργανικά άλατα όπως κιτρικό, γαλακτικό, τρυγικό, οξαλικό, ασκορβικό, μεσυλικό, τοσυλικό ή ανόργανα άλατα όπως π.χ. θειικό, αλογονίδιο ή φωσφορικό ή/και το μείγμα τους (Mito TAX) που έχουν το γενικό τύπο I, όπου το n = 8 έως 12 και το Ζ επιλέγεται από οργανικά άλατα όπως κιτρικό, οξικό, γαλακτικό, τρυγικό, οξαλικό, ασκορβικό, μεσυλικό, τοσυλικό ή ανόργανα άλατα όπως θειικό, αλογονίδιο, φωσφορικό και έχουν γενικό τύπο ΙΑ, όπου n = 6 έως 10 και το Ζ έχει την προαναφερθείσα σημασία. Μπορούν να χρησιμοποιηθούν για θεραπεία νεπλασματικών ασθενειών, ειδικά με υψηλό επίπεδο της πρωτεΐνης HER2. Το φάρμακο για θεραπεία νεοπλασματιών ασθενειών, σύμφωνα με την εφεύρεση, περιέχει τουλάχιστον ένα Ε/Ζ ισομερές των αλειφατικών τριφαινυλοφωσφόνιων παραγώγων της ταμοξιφαίνης με γενικό τύπο I ή/και ΙΑ ή του αντίστοιχου άλατος της τριτοταγούς αμίνης.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CZ2013-308A CZ2013308A3 (cs) | 2013-04-24 | 2013-04-24 | Deriváty tamoxifenu účinné proti nádorům, zejména s vyšší hladinou proteinu HER2 |
| CZ2014-66A CZ305571B6 (cs) | 2014-01-29 | 2014-01-29 | Deriváty tamoxifenu k léčbě neoplastických chorob, zejména s vyšší hladinou proteinu HER2 |
| PCT/CZ2014/000035 WO2014173374A1 (en) | 2013-04-24 | 2014-04-07 | Tamoxifen derivatives for treatment of neoplastic diseases, especially with high her2 protein level |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CY1120821T1 true CY1120821T1 (el) | 2019-12-11 |
Family
ID=50677895
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CY181101155T CY1120821T1 (el) | 2013-04-24 | 2018-11-06 | Παραγωγα ταμοξιφαινης για θεραπεια νεοπλασματικων ασθενειων, ειδικα με υψηλο επιπεδο πρωτεϊνης her2 |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US9896466B2 (el) |
| EP (1) | EP2989110B1 (el) |
| JP (1) | JP6375091B2 (el) |
| KR (1) | KR101764991B1 (el) |
| CN (1) | CN105452265B (el) |
| AU (1) | AU2014256546B2 (el) |
| CA (1) | CA2909994C (el) |
| CY (1) | CY1120821T1 (el) |
| DK (1) | DK2989110T3 (el) |
| EA (1) | EA029881B1 (el) |
| ES (1) | ES2699099T3 (el) |
| GE (1) | GEP20186868B (el) |
| HK (1) | HK1216317A1 (el) |
| HR (1) | HRP20181872T1 (el) |
| HU (1) | HUE042239T2 (el) |
| MD (1) | MD4626C1 (el) |
| NZ (1) | NZ713589A (el) |
| PL (1) | PL2989110T3 (el) |
| PT (1) | PT2989110T (el) |
| SI (1) | SI2989110T1 (el) |
| UA (1) | UA116469C2 (el) |
| WO (1) | WO2014173374A1 (el) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2018000306A (es) * | 2015-07-03 | 2018-03-14 | Bayer Cropscience Ag | Derivados de n-(1,3,4-oxadiazol-2-il)aril carboxamida con accion herbicida. |
| CA2990985A1 (en) * | 2015-07-03 | 2017-01-12 | Bayer Cropscience Aktiengesellschaft | N-(tetrazole-5-yl)- and n-(triazole-5-yl)aryl carboxamide derivatives with herbicidal action |
| EP3368011A4 (en) * | 2016-07-12 | 2019-07-10 | Accutar Biotechnology Inc. | NOVEL CONNECTIONS AND USE THEREOF |
| EP3484463B1 (en) | 2016-08-19 | 2020-02-12 | The United States of America, as Represented by The Secretary, Department of Health and Human Services Office of Technology Transfer | Selective estrogen-receptor modulators (serms) confer protection against photoreceptor degeneration |
| EP3330274A1 (en) * | 2016-12-01 | 2018-06-06 | Springtide Ventures s.r.o. | Compounds for treatment of senescence-related disorders |
| WO2018195446A1 (en) | 2017-04-21 | 2018-10-25 | Lisanti Michael P | Targeting hypoxic cancer stem cells (cscs) with doxycycline: implications for improving anti-angiogenic therapy |
| CA3060510A1 (en) | 2017-04-21 | 2018-10-25 | Lunella Biotech, Inc. | Vitamin c and doxycycline: a synthetic lethal combination therapy for eradicating cancer stem cells (cscs) |
| PE20200605A1 (es) | 2017-05-19 | 2020-03-10 | Lunella Biotech Inc | Antimitoscinas: inhibidores especificos de la biogenesis mitocondrial para erradicar celulas madre cancerosas |
| RU2020116649A (ru) | 2017-10-24 | 2021-11-30 | Лунелла Байотек, Инк. | Митофлавосцины: нацеливание на флавин-содержащие ферменты устраняет злокачественные стволовые клетки (cscs) посредством ингибирования митохондриального дыхания |
| MX2020005311A (es) | 2017-11-24 | 2020-08-17 | Lunella Biotech Inc | Compuestos de derivados de trifenilfosfonio para erradicar celulas madre cancerosas. |
| EP3717015A4 (en) | 2017-12-01 | 2021-07-28 | Lunella Biotech, Inc. | REPURPOSCINS: TARGET MITOCHONDRIAL BIOGENESIS INHIBITORS TO ERADICATE CARCINOUS STEM CELLS |
| US11541120B2 (en) | 2017-12-05 | 2023-01-03 | Anthos Partners, Lp | Phosphonium-based ionic drug conjugates |
| CA3085375A1 (en) | 2017-12-20 | 2019-06-27 | Lunella Biotech, Inc. | Targeting mitochondrial fission through mdivi-1 derivatives |
| CN114025769A (zh) * | 2019-04-16 | 2022-02-08 | 卢内拉生物技术有限公司 | 用于靶向线粒体和抗癌治疗的烷基-tpp化合物 |
| EP3753944A1 (en) | 2019-06-17 | 2020-12-23 | Institute Of Biotechnology Cas, V.V.I. | 3,5-bis(phenyl)-1h-heteroaryl derivatives as medicaments |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1289570C (en) * | 1986-06-16 | 1991-09-24 | Tetsuji Asao | 1,1,2-triaryl-1-alkene derivatives |
| CA2092996A1 (en) * | 1990-10-01 | 1992-04-02 | David Yang | High affinity tamoxifen derivatives and uses thereof |
| JP3635708B2 (ja) * | 1995-03-06 | 2005-04-06 | 出光興産株式会社 | 有機エレクトロルミネッセンス素子 |
| TWI309571B (en) * | 2002-12-31 | 2009-05-11 | Ind Tech Res Inst | Delivery carrier for targeting cells haring over-expressed estrogen |
| ES2541769T3 (es) * | 2003-08-22 | 2015-07-24 | Antipodean Pharmaceuticals, Inc. | Derivados de mitoquinona usados como antioxidantes dirigidos a las mitocondrias |
| RU2007105138A (ru) * | 2004-07-13 | 2008-08-20 | Оридис Биомед Форшунгс-Унд Энтвиклунгс Гмбх (At) | Применение митохондриально направленного антиоксиданта при лечении болезней печени и эпителиальных раковых опухолей |
| US8598145B2 (en) * | 2008-03-14 | 2013-12-03 | Stephen John Ralph | Mitochondrially delivered anti-cancer compounds |
| CN102438615A (zh) * | 2009-04-17 | 2012-05-02 | 科尔比制药公司 | 包含氧化应激调节剂(osm)的药学活性组合物、新的化学实体、组合物和用途 |
| WO2011129837A1 (en) * | 2010-04-16 | 2011-10-20 | Olema Pharmaceuticals, Inc. | Use of a 4-hydroxytoremifene prodrug for treatment of breast cancer |
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2014
- 2014-04-07 WO PCT/CZ2014/000035 patent/WO2014173374A1/en active Application Filing
- 2014-04-07 PL PL14721738T patent/PL2989110T3/pl unknown
- 2014-04-07 UA UAA201510642A patent/UA116469C2/uk unknown
- 2014-04-07 US US14/786,710 patent/US9896466B2/en active Active
- 2014-04-07 PT PT14721738T patent/PT2989110T/pt unknown
- 2014-04-07 AU AU2014256546A patent/AU2014256546B2/en active Active
- 2014-04-07 KR KR1020157030376A patent/KR101764991B1/ko active IP Right Grant
- 2014-04-07 EA EA201591918A patent/EA029881B1/ru unknown
- 2014-04-07 SI SI201430928T patent/SI2989110T1/sl unknown
- 2014-04-07 NZ NZ713589A patent/NZ713589A/en unknown
- 2014-04-07 MD MD20150117A patent/MD4626C1/ro active IP Right Grant
- 2014-04-07 DK DK14721738.4T patent/DK2989110T3/en active
- 2014-04-07 JP JP2016509298A patent/JP6375091B2/ja active Active
- 2014-04-07 EP EP14721738.4A patent/EP2989110B1/en active Active
- 2014-04-07 HU HUE14721738A patent/HUE042239T2/hu unknown
- 2014-04-07 ES ES14721738T patent/ES2699099T3/es active Active
- 2014-04-07 CA CA2909994A patent/CA2909994C/en active Active
- 2014-04-07 CN CN201480033316.9A patent/CN105452265B/zh active Active
-
2015
- 2015-04-07 GE GEAP201513996A patent/GEP20186868B/en unknown
-
2016
- 2016-04-14 HK HK16104277.8A patent/HK1216317A1/zh unknown
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2018
- 2018-11-06 CY CY181101155T patent/CY1120821T1/el unknown
- 2018-11-08 HR HRP20181872TT patent/HRP20181872T1/hr unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NZ713589A (en) | 2017-12-22 |
| KR101764991B1 (ko) | 2017-08-10 |
| UA116469C2 (uk) | 2018-03-26 |
| EP2989110B1 (en) | 2018-08-08 |
| PT2989110T (pt) | 2018-11-15 |
| DK2989110T3 (en) | 2018-12-03 |
| EA029881B1 (ru) | 2018-05-31 |
| MD4626B1 (ro) | 2019-04-30 |
| AU2014256546A1 (en) | 2015-11-12 |
| ES2699099T3 (es) | 2019-02-07 |
| HUE042239T2 (hu) | 2019-06-28 |
| SI2989110T1 (sl) | 2019-01-31 |
| HRP20181872T1 (hr) | 2019-02-08 |
| PL2989110T3 (pl) | 2019-03-29 |
| EP2989110A1 (en) | 2016-03-02 |
| JP6375091B2 (ja) | 2018-08-15 |
| HK1216317A1 (zh) | 2016-11-04 |
| WO2014173374A1 (en) | 2014-10-30 |
| KR20150144756A (ko) | 2015-12-28 |
| MD4626C1 (ro) | 2019-11-30 |
| US9896466B2 (en) | 2018-02-20 |
| CA2909994A1 (en) | 2014-10-30 |
| AU2014256546B2 (en) | 2017-03-30 |
| CN105452265A (zh) | 2016-03-30 |
| CN105452265B (zh) | 2017-05-10 |
| JP2016522179A (ja) | 2016-07-28 |
| US20160075726A1 (en) | 2016-03-17 |
| CA2909994C (en) | 2018-06-26 |
| GEP20186868B (en) | 2018-06-25 |
| MD20150117A2 (ro) | 2016-08-31 |
| EA201591918A1 (ru) | 2016-02-29 |
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