HRP20160547T1 - Pegilirani apelin i njegova upotreba - Google Patents
Pegilirani apelin i njegova upotreba Download PDFInfo
- Publication number
- HRP20160547T1 HRP20160547T1 HRP20160547TT HRP20160547T HRP20160547T1 HR P20160547 T1 HRP20160547 T1 HR P20160547T1 HR P20160547T T HRP20160547T T HR P20160547TT HR P20160547 T HRP20160547 T HR P20160547T HR P20160547 T1 HRP20160547 T1 HR P20160547T1
- Authority
- HR
- Croatia
- Prior art keywords
- apelin
- pegylated
- molecule
- amino acid
- peg
- Prior art date
Links
- 102000018746 Apelin Human genes 0.000 title claims 2
- 108010052412 Apelin Proteins 0.000 title claims 2
- BWVPHIKGXQBZPV-QKFDDRBGSA-N apelin Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N1[C@H](C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=2NC=NC=2)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=2NC=NC=2)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CCSC)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(O)=O)CCC1 BWVPHIKGXQBZPV-QKFDDRBGSA-N 0.000 title claims 2
- 102400000251 Apelin-36 Human genes 0.000 claims 19
- 101800001808 Apelin-36 Proteins 0.000 claims 19
- BVTLGARMSLXAHI-VDEROMQGSA-N apelin-36 Chemical compound C([C@@H](C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCSC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)CNC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(C)C)C(C)C)C1=CN=CN1 BVTLGARMSLXAHI-VDEROMQGSA-N 0.000 claims 19
- 239000002202 Polyethylene glycol Substances 0.000 claims 6
- 125000000539 amino acid group Chemical group 0.000 claims 6
- 229920001223 polyethylene glycol Polymers 0.000 claims 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 4
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
- 238000006243 chemical reaction Methods 0.000 claims 2
- 239000003638 chemical reducing agent Substances 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 208000035475 disorder Diseases 0.000 claims 2
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 1
- 206010007556 Cardiac failure acute Diseases 0.000 claims 1
- 206010007558 Cardiac failure chronic Diseases 0.000 claims 1
- 208000031229 Cardiomyopathies Diseases 0.000 claims 1
- 208000024172 Cardiovascular disease Diseases 0.000 claims 1
- 208000017701 Endocrine disease Diseases 0.000 claims 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims 1
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 1
- 206010063837 Reperfusion injury Diseases 0.000 claims 1
- -1 cyanoborohydride Chemical group 0.000 claims 1
- 208000030172 endocrine system disease Diseases 0.000 claims 1
- 230000001747 exhibiting effect Effects 0.000 claims 1
- 230000000297 inotrophic effect Effects 0.000 claims 1
- 208000012947 ischemia reperfusion injury Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 208000030159 metabolic disease Diseases 0.000 claims 1
- 239000000178 monomer Substances 0.000 claims 1
- 208000010125 myocardial infarction Diseases 0.000 claims 1
- 150000007523 nucleic acids Chemical group 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 230000002035 prolonged effect Effects 0.000 claims 1
- 208000002815 pulmonary hypertension Diseases 0.000 claims 1
Classifications
-
- 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
- A61K47/56—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Marine Sciences & Fisheries (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- Organic Chemistry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Claims (14)
1. Pegilirana molekula Apelin 36 koja sadrži jednu ili više molekula polietilen glikola (PEG) funkcionalno vezanu na najmanje jedan aminokiselinski ostatak na N-terminalnom kraju Apelina 36.
2. Molekula prema zahtjevu 1, naznačena time da je navedeni pegilirani Apelin 36 sposoban iskazivati produljeni cirkulirajući vijek ili prošireni inotropni učinak, u odnosu na ne-pegilirani Apelin 36.
3. Molekula prema zahtjevu 1, naznačena time da navedeni pegilirani Apelin 36 je mono-pegilirani ili di-pegilirani Apelin 36.
4. Molekula prema zahtjevu 1, naznačena time da su navedena jedna ili više PEG molekula kovalentno vezane na navedeni najmanje jedan aminokiselinski ostatak, bilo izravno ili preko linkera.
5. Molekula prema zahtjevu 1, naznačena time da svaka PEG molekula ima molekularnu težinu u rasponu od oko 5,000 do oko 50,000 daltona.
6. Molekula prema zahtjevu 1, naznačena time da navedeni pegilirani Apelin 36 sadrži monomerni Apelin 36.
7. Molekula prema zahtjevu 1, naznačena time da navedeni pegilirani Apelin 36 sadrži oligomerni Apelin 36, pri čemu su jedan ili više monomera funkcionalno vezani jedan za drugoga.
8. Molekula prema zahtjevu 1, naznačena time da Apelin 36 sadrži sekvencu aminokiseline od aminokiselinskih ostataka 42-77 iz SEQ ID NO: 1.
9. Molekula prema zahtjevu 8, naznačena time da navedena sekvenca aminokiseline je kodirana sa sekvencom nukleinske kiseline 123-234 bp iz SEQ ID NO: 2.
10. Postupak za proizvodnju molekula prema zahtjevu 1, naznačen time da sadrži korak:
reakcije Apelina 36 s aktiviranim PEG-aldehidnim linkerom u prisutnosti redukcijskog sredstva da se dobije navedeni pegilirani Apelin 36 pod uvjetima u kojima je linker kovalentno vezan na ostatak Leucina na N-terminalnom kraju Apelina 36.
11. Postupak prema zahtjevu 10, naznačen time da redukcijsko sredstvo je cijanoborohidrid i reakcijski korak se izvodi kod pH od 5.0 do 7.5.
12. Farmaceutski pripravak koji sadrži terapijski učinkovitu količinu pegiliranog Apelina 36 koji sadrži jednu ili više molekula polietilen glikola (PEG) funkcionalno vezane na najmanje jedan aminokiselinski ostatak na N-terminalnom kraju od Apelina 36, naznačen time da navedeni najmanje jedan aminokiselinski ostatak je Leucin.
13. Terapijski učinkovita količina pegilirane molekule Apelina 36 prema zahtjevu 1 naznačena time da je za upotrebu u liječenju bolesti ili poremećaja povezanih sa Apelinom, pri čemu bolest ili poremećaj je kardiovaskularna bolest, ishemijsko-reperfuzijska ozljeda, infarkt miokarda, akutno dekompenzacijsko zatajenje srca, kronično zatajenje srca, kardiomiopatija, endokrini poremećaj, metabolički poremećaj ili plućna hipertenzija.
14. Pegilirana molekula Apelin 36 za uporabu prema zahtjevu 13, naznačena time da navedeni najmanje jedan aminokiselinski ostatak na N-terminalnom kraju od Apelina 36 je Leucin.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161451623P | 2011-03-11 | 2011-03-11 | |
| EP12757055.4A EP2683360B1 (en) | 2011-03-11 | 2012-03-08 | Pegylated apelin and uses thereof |
| PCT/US2012/028298 WO2012125408A1 (en) | 2011-03-11 | 2012-03-08 | Pegylated apelin and uses thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20160547T1 true HRP20160547T1 (hr) | 2016-06-17 |
Family
ID=46831054
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20160547TT HRP20160547T1 (hr) | 2011-03-11 | 2016-05-23 | Pegilirani apelin i njegova upotreba |
| HRP20181589TT HRP20181589T1 (hr) | 2011-03-11 | 2018-10-03 | Pegilirani apelin i njegova upotreba |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20181589TT HRP20181589T1 (hr) | 2011-03-11 | 2018-10-03 | Pegilirani apelin i njegova upotreba |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US20140142049A1 (hr) |
| EP (2) | EP3045183B1 (hr) |
| AU (2) | AU2012229336B2 (hr) |
| CA (1) | CA2829693C (hr) |
| CY (1) | CY1117654T1 (hr) |
| DK (2) | DK3045183T3 (hr) |
| ES (2) | ES2690147T3 (hr) |
| HR (2) | HRP20160547T1 (hr) |
| HU (1) | HUE027579T2 (hr) |
| LT (1) | LT3045183T (hr) |
| PL (2) | PL3045183T3 (hr) |
| PT (1) | PT3045183T (hr) |
| SI (2) | SI2683360T1 (hr) |
| WO (1) | WO2012125408A1 (hr) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2690147T3 (es) | 2011-03-11 | 2018-11-19 | Genzyme Corporation | Apelina pegilada y usos de la misma |
| JP6426107B2 (ja) * | 2012-12-20 | 2018-11-21 | アムジエン・インコーポレーテツド | Ａｐｊ受容体アゴニストおよびその使用 |
| ES2708957T3 (es) | 2013-03-14 | 2019-04-12 | Regeneron Pharma | Proteínas de fusión de apelina y usos de las mismas |
| WO2015013169A2 (en) * | 2013-07-25 | 2015-01-29 | Novartis Ag | Bioconjugates of synthetic apelin polypeptides |
| US9908919B2 (en) * | 2013-07-25 | 2018-03-06 | Novartis Ag | Cyclic apelin derivatives for the treatment of heart failure |
| WO2015013168A1 (en) * | 2013-07-25 | 2015-01-29 | Novartis Ag | Cyclic polypeptides for the treatment of heart failure |
| US9683018B2 (en) * | 2013-07-25 | 2017-06-20 | Novartis Ag | Disulfide cyclic polypeptides for the treatment of heart failure |
| MA39061A1 (fr) | 2013-11-20 | 2017-10-31 | Regeneron Pharma | Modulateurs d'aplnr et leurs utilisations |
| ES2719137T3 (es) | 2014-03-25 | 2019-07-08 | Lanthiopep Bv | Análogos de apelina cíclica |
| WO2015191781A2 (en) | 2014-06-10 | 2015-12-17 | Amgen Inc. | Apelin polypeptides |
| CA2972871A1 (en) | 2015-01-23 | 2016-07-28 | Novartis Ag | Synthetic apelin fatty acid conjugates with improved half-life |
| US11400049B2 (en) | 2016-10-19 | 2022-08-02 | Avive, Inc. | Pegylated liposomal formulations of apelin for treatment of cardiovascular-related diseases |
| WO2021255282A1 (en) * | 2020-06-18 | 2021-12-23 | Universite D'aix Marseille | Conjugated and labelled apelin, preparation and uses thereof |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6420339B1 (en) * | 1998-10-14 | 2002-07-16 | Amgen Inc. | Site-directed dual pegylation of proteins for improved bioactivity and biocompatibility |
| US20020102208A1 (en) | 1999-03-01 | 2002-08-01 | Paul Chinn | Radiolabeling kit and binding assay |
| EP1613348B1 (en) * | 2003-03-12 | 2010-06-23 | The Arizona Board of Regents on Behalf of the University of Arizona | Methods for modulating angiogenesis with apelin compositions |
| US7947280B2 (en) * | 2003-05-22 | 2011-05-24 | The Board Of Trustees Of The Leland Stanford Junior University | Apelin and uses thereof |
| CA2617649A1 (en) * | 2005-08-11 | 2007-02-22 | Amylin Pharmaceuticals, Inc. | Hybrid polypeptides with selectable properties |
| US20090252703A1 (en) * | 2006-10-19 | 2009-10-08 | Gegg Jr Colin V | Use of alcohol co-solvents to improve pegylation reaction yields |
| ES2690147T3 (es) | 2011-03-11 | 2018-11-19 | Genzyme Corporation | Apelina pegilada y usos de la misma |
-
2012
- 2012-03-08 ES ES16155181.7T patent/ES2690147T3/es active Active
- 2012-03-08 WO PCT/US2012/028298 patent/WO2012125408A1/en active Application Filing
- 2012-03-08 LT LTEP16155181.7T patent/LT3045183T/lt unknown
- 2012-03-08 CA CA2829693A patent/CA2829693C/en not_active Expired - Fee Related
- 2012-03-08 PT PT16155181T patent/PT3045183T/pt unknown
- 2012-03-08 DK DK16155181.7T patent/DK3045183T3/en active
- 2012-03-08 EP EP16155181.7A patent/EP3045183B1/en active Active
- 2012-03-08 DK DK12757055.4T patent/DK2683360T3/en active
- 2012-03-08 SI SI201230560A patent/SI2683360T1/sl unknown
- 2012-03-08 PL PL16155181T patent/PL3045183T3/pl unknown
- 2012-03-08 PL PL12757055.4T patent/PL2683360T3/pl unknown
- 2012-03-08 US US14/004,377 patent/US20140142049A1/en active Pending
- 2012-03-08 AU AU2012229336A patent/AU2012229336B2/en not_active Ceased
- 2012-03-08 SI SI201231407T patent/SI3045183T1/sl unknown
- 2012-03-08 ES ES12757055.4T patent/ES2573337T3/es active Active
- 2012-03-08 HU HUE12757055A patent/HUE027579T2/en unknown
- 2012-03-08 EP EP12757055.4A patent/EP2683360B1/en active Active
-
2016
- 2016-05-23 HR HRP20160547TT patent/HRP20160547T1/hr unknown
- 2016-05-24 CY CY20161100447T patent/CY1117654T1/el unknown
-
2017
- 2017-05-02 AU AU2017202919A patent/AU2017202919B2/en not_active Ceased
-
2018
- 2018-10-03 HR HRP20181589TT patent/HRP20181589T1/hr unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2012125408A1 (en) | 2012-09-20 |
| AU2012229336B2 (en) | 2017-02-02 |
| PL3045183T3 (pl) | 2018-12-31 |
| AU2017202919A1 (en) | 2017-05-25 |
| CY1117654T1 (el) | 2018-03-07 |
| CA2829693C (en) | 2020-04-21 |
| CA2829693A1 (en) | 2012-09-20 |
| WO2012125408A8 (en) | 2018-01-25 |
| SI3045183T1 (sl) | 2018-11-30 |
| EP2683360A1 (en) | 2014-01-15 |
| EP3045183B1 (en) | 2018-07-04 |
| EP2683360A4 (en) | 2014-09-03 |
| DK3045183T3 (en) | 2018-10-22 |
| HUE027579T2 (en) | 2016-10-28 |
| LT3045183T (lt) | 2018-10-25 |
| EP3045183A1 (en) | 2016-07-20 |
| SI2683360T1 (sl) | 2016-06-30 |
| AU2012229336A1 (en) | 2013-10-10 |
| PT3045183T (pt) | 2018-11-02 |
| DK2683360T3 (en) | 2016-05-30 |
| AU2017202919B2 (en) | 2019-03-14 |
| ES2690147T3 (es) | 2018-11-19 |
| US20140142049A1 (en) | 2014-05-22 |
| EP2683360B1 (en) | 2016-02-24 |
| ES2573337T3 (es) | 2016-06-07 |
| PL2683360T3 (pl) | 2016-09-30 |
| HRP20181589T1 (hr) | 2018-12-28 |
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