HRP20160392T1 - Cjepivo pcsk9 - Google Patents

Cjepivo pcsk9 Download PDF

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Publication number
HRP20160392T1
HRP20160392T1 HRP20160392TT HRP20160392T HRP20160392T1 HR P20160392 T1 HRP20160392 T1 HR P20160392T1 HR P20160392T T HRP20160392T T HR P20160392TT HR P20160392 T HRP20160392 T HR P20160392T HR P20160392 T1 HRP20160392 T1 HR P20160392T1
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Croatia
Prior art keywords
seq
pcsk9
fragments
vaccine according
amino acid
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HRP20160392TT
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English (en)
Inventor
Sylvia Brunner
Gergana Galabova
Bettina Wanko
Markus Windwarder
Gabriele Winsauer
Günther STAFFLER
Claudia Juno
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Affiris Ag
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Publication of HRP20160392T1 publication Critical patent/HRP20160392T1/hr

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/0005Vertebrate antigens
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/0005Vertebrate antigens
    • A61K39/0012Lipids; Lipoproteins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/385Haptens or antigens, bound to carriers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/39Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal 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
    • A61K47/51Medicinal 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
    • A61K47/62Medicinal 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 a protein, peptide or polyamino acid
    • A61K47/64Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/643Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/06Antihyperlipidemics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/40Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/48Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424Serine endopeptidases (3.4.21)
    • C12N9/6454Dibasic site splicing serine proteases, e.g. kexin (3.4.21.61); furin (3.4.21.75) and other proprotein convertases
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/54Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/545Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/555Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55505Inorganic adjuvants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/60Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
    • A61K2039/6031Proteins
    • A61K2039/6081Albumin; Keyhole limpet haemocyanin [KLH]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/30Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/20Fusion polypeptide containing a tag with affinity for a non-protein ligand
    • C07K2319/21Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a His-tag
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/20Fusion polypeptide containing a tag with affinity for a non-protein ligand
    • C07K2319/23Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a GST-tag
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/40Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide
    • C07K2319/50Fusion polypeptide containing protease site
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y304/00Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/21Serine endopeptidases (3.4.21)
    • C12Y304/21061Kexin (3.4.21.61), i.e. proprotein convertase subtilisin/kexin type 9

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Microbiology (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Mycology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biophysics (AREA)
  • General Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biotechnology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Obesity (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Claims (10)

1. Cjepivo, naznačeno time, da obuhvaća najmanje dva fragmenta proproteinske konvertaze subtilizin/keksin tipa 9 (PCSK9), pri čemu barem jedan od navedena najmanje dva fragmenta sadrže najmanje osam uzastopnih aminokiselinskih ostataka od aminokiselinskih ostataka 150 do 170 od PCSK9 u skladu sa SEQ ID NO:9, i gdje barem jedan od navedena najmanje dva fragmenta sadrži najmanje osam uzastopnih aminokiselinskih ostataka od aminokiselinskih ostataka 205 do 225 od PCSK9 u skladu sa SEQ ID NO:9.
2. Cjepivo prema zahtjevu 1, naznačeno time, da su najmanje dva fragmenta odabrana iz skupine sastavljene od peptida koji imaju aminokiselinsku sekvencu SIPWNLERITPPR (SEQ ID NO:2), PEEDGTRFHRQASK (SEQ ID NO:3), PEEDGTRFHRQA (SEQ ID NO:4), EEDGTRFHRQASK (SEQ ID NO:5), EEDGTRFHRQAS (SEQ ID NO:6), SIPWNLERITP (SEQ ID NO:7) i SIPWNLERIT (SEQ ID NO:8).
3. Cjepivo prema zahtjevu 1 ili 2, naznačeno time, da najmanje jedan fragment od PCSK9 ima aminokiselinsku sekvencu odabranu iz skupine koju čine SIPWNLERITPPR (SEQ ID NO:2), SIPWNLERITP (SEQ ID NO:7) i SIPWNLERIT (SEQ ID NO:8), i najmanje jedan fragment od PCSK9 ima aminokiselinsku sekvencu odabranu iz skupine koju čine PEEDGTRFHRQASK (SEQ ID NO:3), PEEDGTRFHRQA (SEQ ID NO:4), EEDGTRFHRQASK (SEQ ID NO:5) i EEDGTRFHRQAS (SEQ ID NO:6).
4. Cjepivo prema bilo kojem od zahtjeva 1 do 3, naznačeno time, da cjepivo obuhvaća SIPWNLERITPPR (SEQ ID NO:2) i PEEDGTRFHRQASK (SEQ ID NO:3), SIPWNLERITPPR (SEQ ID NO:2) i PEEDGTRFHRQA (SEQ ID NO:4), SIPWNLERITPPR (SEQ ID NO:2) i EEDGTRFHRQASK (SEQ ID NO:5), SIPWNLERITPPR (SEQ ID NO:2) i EEDGTRFHRQAS (SEQ ID NO:6), PEEDGTRFHRQASK (SEQ ID NO:3) i SIPWNLERITP (SEQ ID NO:7), PEEDGTRFHRQASK (SEQ ID NO:3) i SIPWNLERIT (SEQ ID NO:8), PEEDGTRFHRQA (SEQ ID NO:4) i SIPWNLERITP (SEQ ID NO:7), PEEDGTRFHRQA (SEQ ID NO:4) i SIPWNLERIT (SEQ ID NO:8), EEDGTRFHRQASK (SEQ ID NO:5) i SIPWNLERITP (SEQ ID NO:7), EEDGTRFHRQASK (SEQ ID NO:5) i SIPWNLERIT (SEQ ID NO:8), EEDGTRFHRQAS (SEQ ID NO:6) i SIPWNLERITP (SEQ ID NO:7), ili EEDGTRFHRQAS (SEQ ID NO:6) i SIPWNLERIT (SEQ ID NO:8).
5. Cjepivo prema bilo kojem od zahtjeva 1 do 4, naznačeno time, da najmanje dva fragmenta od PCSK9 sadrže cisteinski ostatak na C-završnom kraju i/ili na N-završnom kraju.
6. Cjepivo prema bilo kojem od zahtjeva 1 do 5, naznačeno time, da su najmanje dva fragmenta od PCSK9 spojena na farmaceutski prihvatljiv nosač, poželjno na KLH (Keyhole Limpet Hemocyanin).
7. Cjepivo prema bilo kojem od zahtjeva 1 do 6, naznačeno time, da su najmanje dva fragmenta od PCSK9 formulirana za intradermalnu, subkutanu ili intramuskularnu primjenu.
8. Cjepivo prema bilo kojem od zahtjeva 1 do 7, naznačeno time, da cjepivo obuhvaća najmanje jedno pomoćno sredstvo, poželjno aluminijev hidroksid.
9. Cjepivo prema bilo kojem od zahtjeva 1 do 8, naznačeno time, da se upotrebljava u liječenju i/ili u prevenciji kardiovaskularnih bolesti, moždanog udara, perifernih vaskularnih bolesti, periferne arterijske okluzivne bolesti, koronarne srčane bolesti ili apoplektičkog cerebralnog insulta.
10. Cjepivo prema zahtjevu 9, naznačeno time, da se najmanje dva fragmenta od PCSK9 daju pojedincu za jednu dozu u količini od 0,1 ng do 10 mg, poželjno od 1 μg do 500 μg.
HRP20160392TT 2011-09-13 2016-04-15 Cjepivo pcsk9 HRP20160392T1 (hr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP11181090.9A EP2570135B1 (en) 2011-09-13 2011-09-13 PCSK9 Vaccine

Publications (1)

Publication Number Publication Date
HRP20160392T1 true HRP20160392T1 (hr) 2016-05-06

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ID=46851983

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HRP20160392TT HRP20160392T1 (hr) 2011-09-13 2016-04-15 Cjepivo pcsk9
HRP20170328TT HRP20170328T1 (hr) 2011-09-13 2017-02-27 Cjepivo pcsk9

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Country Link
US (2) US9220762B2 (hr)
EP (2) EP2570135B1 (hr)
JP (1) JP6054400B2 (hr)
KR (1) KR101983685B1 (hr)
CN (1) CN103874504B (hr)
AU (1) AU2012307348B8 (hr)
BR (1) BR112014005756A2 (hr)
CA (1) CA2848487A1 (hr)
CY (2) CY1117335T1 (hr)
DK (2) DK2570135T3 (hr)
ES (2) ES2565757T3 (hr)
HR (2) HRP20160392T1 (hr)
HU (2) HUE028583T2 (hr)
IL (1) IL231043A (hr)
LT (1) LT2755678T (hr)
MX (1) MX346883B (hr)
PL (2) PL2570135T3 (hr)
PT (1) PT2755678T (hr)
RS (1) RS54639B1 (hr)
RU (2) RU2640258C2 (hr)
SG (1) SG11201400086QA (hr)
SI (2) SI2570135T1 (hr)
SM (1) SMT201600082B (hr)
WO (1) WO2013037889A2 (hr)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9255154B2 (en) 2012-05-08 2016-02-09 Alderbio Holdings, Llc Anti-PCSK9 antibodies and use thereof
EP2703483A1 (en) 2012-08-29 2014-03-05 Affiris AG PCSK9 peptide vaccine
WO2015123291A1 (en) 2014-02-11 2015-08-20 The Usa, As Represented By The Secretary, Dept. Of Health And Human Services Pcsk9 vaccine and methods of using the same
US10004791B2 (en) * 2014-02-28 2018-06-26 Affiris Ag Peptide vaccines against PCSK9
CN105085684B (zh) * 2014-05-14 2020-04-17 上海亨臻实业有限公司 Pcsk9靶向重组疫苗设计及其应用
CN106822881A (zh) * 2016-12-09 2017-06-13 四川大学 一种针对pcsk9的抗高血脂蛋白疫苗
CA3058567A1 (en) 2017-04-13 2018-10-18 Cadila Healthcare Limited Novel peptide based pcsk9 vaccine
CN107488215A (zh) * 2017-07-19 2017-12-19 邱志华 人前蛋白转化酶枯草溶菌素9免疫原性肽段及其载体疫苗
WO2021154947A1 (en) * 2020-01-28 2021-08-05 Ubi Ip Holdings Peptide immunogens targeting pcsk9 and formulations thereof for prevention and treatment of pcsk9-mediated disorders
KR20210158693A (ko) * 2020-06-24 2021-12-31 바이오스트림테크놀러지스(주) 항 pcsk9 항체 및 이의 용도
JPWO2022244845A1 (hr) * 2021-05-19 2022-11-24
WO2023161526A1 (en) 2022-02-28 2023-08-31 Tridem Bioscience Gmbh & Co Kg A CONJUGATE CONSISTING OF OR COMPRISING AT LEAST A ß-GLUCAN OR A MANNAN

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP5570806B2 (ja) * 2006-05-11 2014-08-13 アルナイラム ファーマシューティカルズ, インコーポレイテッド Pcsk9遺伝子の発現を阻害するための組成物および方法
AR066042A1 (es) * 2007-04-13 2009-07-22 Novartis Ag Moleculas y metodos para modular la proteina convertasa-subtilisina /quexina tipo 9 (pcsk9)
AR070316A1 (es) * 2008-02-07 2010-03-31 Merck & Co Inc Antagonistas de pcsk9 (proproteina subtilisina-kexina tipo 9)
AT507604A1 (de) * 2008-11-19 2010-06-15 Affiris Forschungs & Entwicklungs Gmbh Behandlung von atherosklerose
PE20161560A1 (es) * 2009-09-03 2017-01-11 Pfizer Vaccines Llc Vacuna de pcsk9

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Publication number Publication date
KR101983685B1 (ko) 2019-05-29
SI2755678T1 (sl) 2017-04-26
AU2012307348A8 (en) 2017-04-06
HRP20170328T1 (hr) 2017-05-19
CY1118856T1 (el) 2018-01-10
SMT201600082B (it) 2016-04-29
HUE028583T2 (en) 2016-12-28
EP2755678B1 (en) 2016-12-21
ES2618796T3 (es) 2017-06-22
EP2755678A2 (en) 2014-07-23
MX346883B (es) 2017-04-05
KR20140067118A (ko) 2014-06-03
CN103874504A (zh) 2014-06-18
SI2570135T1 (sl) 2016-05-31
EP2570135B1 (en) 2016-01-27
US9669079B2 (en) 2017-06-06
WO2013037889A2 (en) 2013-03-21
US20160106822A1 (en) 2016-04-21
AU2012307348A1 (en) 2014-03-20
CN103874504B (zh) 2017-05-31
BR112014005756A2 (pt) 2017-03-28
CY1117335T1 (el) 2017-04-26
AU2012307348B2 (en) 2017-03-02
IL231043A (en) 2017-05-29
MX2014002879A (es) 2014-04-10
IL231043A0 (en) 2014-03-31
DK2755678T3 (en) 2017-03-13
LT2755678T (lt) 2017-03-27
RU2017139094A (ru) 2019-02-12
RU2017139094A3 (hr) 2019-02-12
US20150071951A1 (en) 2015-03-12
DK2570135T3 (en) 2016-02-15
WO2013037889A3 (en) 2013-05-10
RU2014114506A (ru) 2015-10-20
AU2012307348B8 (en) 2017-04-06
JP2014527078A (ja) 2014-10-09
PL2570135T3 (pl) 2016-07-29
NZ621439A (en) 2015-06-26
HUE031860T2 (en) 2017-08-28
RU2640258C2 (ru) 2017-12-27
SG11201400086QA (en) 2014-03-28
ES2565757T3 (es) 2016-04-06
EP2570135A1 (en) 2013-03-20
PL2755678T3 (pl) 2017-08-31
JP6054400B2 (ja) 2016-12-27
PT2755678T (pt) 2017-03-24
CA2848487A1 (en) 2013-03-21
RS54639B1 (en) 2016-08-31
US9220762B2 (en) 2015-12-29

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