ES2565757T3 - Vacuna de PCSK9 - Google Patents
Vacuna de PCSK9 Download PDFInfo
- Publication number
- ES2565757T3 ES2565757T3 ES11181090.9T ES11181090T ES2565757T3 ES 2565757 T3 ES2565757 T3 ES 2565757T3 ES 11181090 T ES11181090 T ES 11181090T ES 2565757 T3 ES2565757 T3 ES 2565757T3
- Authority
- ES
- Spain
- Prior art keywords
- sec
- pcsk9
- control
- amino acid
- acid residues
- 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.)
- Active
Links
- 101001098868 Homo sapiens Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 title abstract description 5
- 229960005486 vaccine Drugs 0.000 title abstract description 3
- 102100038955 Proprotein convertase subtilisin/kexin type 9 Human genes 0.000 title abstract 5
- 239000012634 fragment Substances 0.000 abstract 5
- 125000000539 amino acid group Chemical group 0.000 abstract 3
- 101710180553 Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 abstract 1
- 101100172879 Caenorhabditis elegans sec-5 gene Proteins 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 101100172886 Caenorhabditis elegans sec-6 gene Proteins 0.000 description 2
- 101100172892 Caenorhabditis elegans sec-8 gene Proteins 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 1
- 102000000853 LDL receptors Human genes 0.000 description 1
- 108010001831 LDL receptors Proteins 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 102000053786 human PCSK9 Human genes 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0012—Lipids; Lipoproteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/385—Haptens or antigens, bound to carriers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- 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
- A61K47/62—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 a protein, peptide or polyamino acid
- A61K47/64—Drug-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
- A61K47/643—Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]
-
- 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
-
- 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
-
- 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
-
- 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
- A61P9/10—Drugs 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6424—Serine endopeptidases (3.4.21)
- C12N9/6454—Dibasic site splicing serine proteases, e.g. kexin (3.4.21.61); furin (3.4.21.75) and other proprotein convertases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55505—Inorganic adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
- A61K2039/6081—Albumin; Keyhole limpet haemocyanin [KLH]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand
- C07K2319/21—Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a His-tag
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand
- C07K2319/23—Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a GST-tag
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/40—Fusion polypeptide containing a tag for immunodetection, or an epitope for immunisation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/50—Fusion polypeptide containing protease site
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
- C12Y304/21—Serine endopeptidases (3.4.21)
- C12Y304/21061—Kexin (3.4.21.61), i.e. proprotein convertase subtilisin/kexin type 9
Landscapes
- 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)
Abstract
Vacuna que comprende por lo menos dos fragmentos de proproteína convertasa subtilisina/kexina de tipo 9 (PCSK9), en la que por lo menos un fragmento de dichos por lo menos dos fragmentos comprende por lo menos 8 residuos aminoácidos consecutivos de los residuos aminoácidos 150 a 170 de PCSK9 según el SEC ID nº 9 y en la que por lo menos un fragmento de dichos por lo menos dos fragmentos comprende por lo menos 8 residuos aminoácidos consecutivos 205 a 225 de PCSK9 según el SEC ID nº 9.
Description
las proteínas siguiendo protocolos estándares.
Se recubrieron placas Nunc-Maxisorb de 96 pocillos con anticuerpo policlonal de cabra anti-RLDL purificado por afinidad para RLDL de ratón (R&D Systems). Se bloqueó la unión no específica mediante incubación con BSA/PBS
5 al 1%. A continuación, los lisados hepáticos se incubaron durante 3 h a temperatura ambiente para capturar el RLDL murino. La detección del RLDL capturado se llevó a cabo con anticuerpo policlonal de pollo anti-RLDL (Abcam), seguido de la incubación con un anticuerpo secundario de cabra biotinilado anti-IgG de pollo (Southern Biotech) y con un conjugado de estreptavidina-HRP. Finalmente, se utilizó TMB como sustrato cromógeno de peroxidasa.
10 La cuantificación del receptor de lipoproteína de baja densidad se llevó a cabo mediante comparación con una curva de calibración de estándares y se normalizó frente a la concentración de proteínas totales de los lisados.
El grupo de control (vacunación de control con péptido irrelevante) se fijó en 100% y se compararon los niveles de los grupos tratados con vacunas anti-PCSK9 a dicho grupo de control.
15 Ejemplo 1. Medianas de valores de proteína contra PCSK9 humano (n=5 ratones en cada grupo).
- ID de secuencia
- Mediana de valor de proteína (DOmax/2)
- sec 1 control
- 0
- sec 4
- 45.000
- sec 7
- 47.000
- sec 5
- 14.000
- sec 7
- 47.000
- sec 5
- 14.000
- sec 8
- 31.000
- sec 6
- 13.000
- sec 8
- 31.000
Ejemplo 2. Valores medios en mg/dl y porcentaje de reducción del colesterol total (n=5 ratones en cada grupo).
- ID de secuencia
- Valores medios (mg/dl) Stdv % de reducción de CT en comparación con el grupo de control
- Combinación A
- sec 1 control sec 4 sec 7 sec 4 + 7 98 88 78 71 9 12 4 5 10 20 28
- Combinación B
- sec 1 control sec 5 sec 7 sec 5 + 7 86 61 64 51 9 7 5 1 29 26 41
- Combinación C
- sec 1 control sec 5 sec 8 sec 5 + 8 83 60 55 47 7 8 3 7 28 34 43
- Combinación D
- sec 1 control sec 6 sec 8 sec 6 + 8 83 65 55 48 7 4 3 4 22 34 42
8
Claims (1)
-
imagen1
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 |
|---|---|
| ES2565757T3 true ES2565757T3 (es) | 2016-04-06 |
Family
ID=46851983
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES11181090.9T Active ES2565757T3 (es) | 2011-09-13 | 2011-09-13 | Vacuna de PCSK9 |
| ES12759427.3T Active ES2618796T3 (es) | 2011-09-13 | 2012-09-13 | Vacuna de PCSK9 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES12759427.3T Active ES2618796T3 (es) | 2011-09-13 | 2012-09-13 | Vacuna de PCSK9 |
Country Status (24)
| Country | Link |
|---|---|
| US (2) | US9220762B2 (es) |
| EP (2) | EP2570135B1 (es) |
| JP (1) | JP6054400B2 (es) |
| KR (1) | KR101983685B1 (es) |
| CN (1) | CN103874504B (es) |
| AU (1) | AU2012307348B8 (es) |
| BR (1) | BR112014005756A2 (es) |
| CA (1) | CA2848487A1 (es) |
| CY (2) | CY1117335T1 (es) |
| DK (2) | DK2570135T3 (es) |
| ES (2) | ES2565757T3 (es) |
| HR (2) | HRP20160392T1 (es) |
| HU (2) | HUE028583T2 (es) |
| IL (1) | IL231043A (es) |
| LT (1) | LT2755678T (es) |
| MX (1) | MX346883B (es) |
| PL (2) | PL2570135T3 (es) |
| PT (1) | PT2755678T (es) |
| RS (1) | RS54639B1 (es) |
| RU (2) | RU2640258C2 (es) |
| SG (1) | SG11201400086QA (es) |
| SI (2) | SI2570135T1 (es) |
| SM (1) | SMT201600082B (es) |
| WO (1) | WO2013037889A2 (es) |
Families Citing this family (12)
| 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 (es) * | 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)
| 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 |
-
2011
- 2011-09-13 EP EP11181090.9A patent/EP2570135B1/en active Active
- 2011-09-13 SI SI201130773A patent/SI2570135T1/sl unknown
- 2011-09-13 ES ES11181090.9T patent/ES2565757T3/es active Active
- 2011-09-13 DK DK11181090.9T patent/DK2570135T3/en active
- 2011-09-13 HU HUE11181090A patent/HUE028583T2/en unknown
- 2011-09-13 RS RS20160183A patent/RS54639B1/en unknown
- 2011-09-13 PL PL11181090T patent/PL2570135T3/pl unknown
-
2012
- 2012-09-13 DK DK12759427.3T patent/DK2755678T3/en active
- 2012-09-13 US US14/344,879 patent/US9220762B2/en not_active Expired - Fee Related
- 2012-09-13 SG SG11201400086QA patent/SG11201400086QA/en unknown
- 2012-09-13 AU AU2012307348A patent/AU2012307348B8/en not_active Ceased
- 2012-09-13 SI SI201230903A patent/SI2755678T1/sl unknown
- 2012-09-13 ES ES12759427.3T patent/ES2618796T3/es active Active
- 2012-09-13 MX MX2014002879A patent/MX346883B/es active IP Right Grant
- 2012-09-13 RU RU2014114506A patent/RU2640258C2/ru not_active IP Right Cessation
- 2012-09-13 JP JP2014530217A patent/JP6054400B2/ja not_active Expired - Fee Related
- 2012-09-13 RU RU2017139094A patent/RU2017139094A/ru not_active Application Discontinuation
- 2012-09-13 CA CA2848487A patent/CA2848487A1/en not_active Abandoned
- 2012-09-13 EP EP12759427.3A patent/EP2755678B1/en active Active
- 2012-09-13 KR KR1020147009735A patent/KR101983685B1/ko active IP Right Grant
- 2012-09-13 HU HUE12759427A patent/HUE031860T2/en unknown
- 2012-09-13 CN CN201280044571.4A patent/CN103874504B/zh not_active Expired - Fee Related
- 2012-09-13 BR BR112014005756A patent/BR112014005756A2/pt not_active Application Discontinuation
- 2012-09-13 PT PT127594273T patent/PT2755678T/pt unknown
- 2012-09-13 LT LTEP12759427.3T patent/LT2755678T/lt unknown
- 2012-09-13 PL PL12759427T patent/PL2755678T3/pl unknown
- 2012-09-13 WO PCT/EP2012/067950 patent/WO2013037889A2/en active Application Filing
-
2014
- 2014-02-19 IL IL231043A patent/IL231043A/en active IP Right Grant
-
2015
- 2015-10-23 US US14/921,485 patent/US9669079B2/en not_active Expired - Fee Related
-
2016
- 2016-03-22 SM SM201600082T patent/SMT201600082B/xx unknown
- 2016-03-31 CY CY20161100266T patent/CY1117335T1/el unknown
- 2016-04-15 HR HRP20160392TT patent/HRP20160392T1/hr unknown
-
2017
- 2017-02-27 HR HRP20170328TT patent/HRP20170328T1/hr unknown
- 2017-03-16 CY CY20171100333T patent/CY1118856T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
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