HRP20200996T1 - Dualni cistronski bakterijski ekspresijski sustav - Google Patents
Dualni cistronski bakterijski ekspresijski sustav Download PDFInfo
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- HRP20200996T1 HRP20200996T1 HRP20200996TT HRP20200996T HRP20200996T1 HR P20200996 T1 HRP20200996 T1 HR P20200996T1 HR P20200996T T HRP20200996T T HR P20200996TT HR P20200996 T HRP20200996 T HR P20200996T HR P20200996 T1 HRP20200996 T1 HR P20200996T1
- Authority
- HR
- Croatia
- Prior art keywords
- ranibizumab
- antibody
- expression
- fragment
- inclusion
- Prior art date
Links
- 230000001580 bacterial effect Effects 0.000 title claims 4
- 230000009977 dual effect Effects 0.000 title claims 2
- 229960003876 ranibizumab Drugs 0.000 claims 7
- 239000012634 fragment Substances 0.000 claims 6
- 102000004169 proteins and genes Human genes 0.000 claims 6
- 108090000623 proteins and genes Proteins 0.000 claims 6
- 238000000034 method Methods 0.000 claims 5
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 claims 4
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 claims 4
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 claims 4
- 210000004027 cell Anatomy 0.000 claims 4
- 210000003000 inclusion body Anatomy 0.000 claims 4
- 239000002157 polynucleotide Substances 0.000 claims 4
- 102000040430 polynucleotide Human genes 0.000 claims 4
- 108091033319 polynucleotide Proteins 0.000 claims 4
- 241000588724 Escherichia coli Species 0.000 claims 2
- 238000012258 culturing Methods 0.000 claims 2
- BPHPUYQFMNQIOC-NXRLNHOXSA-N isopropyl beta-D-thiogalactopyranoside Chemical compound CC(C)S[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O BPHPUYQFMNQIOC-NXRLNHOXSA-N 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 230000007928 solubilization Effects 0.000 claims 2
- 238000005063 solubilization Methods 0.000 claims 2
- 230000002349 favourable effect Effects 0.000 claims 1
- 239000002773 nucleotide Substances 0.000 claims 1
- 125000003729 nucleotide group Chemical group 0.000 claims 1
- 230000009466 transformation Effects 0.000 claims 1
- 230000001131 transforming effect Effects 0.000 claims 1
Classifications
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01H—NEW PLANTS OR NON-TRANSGENIC PROCESSES FOR OBTAINING THEM; PLANT REPRODUCTION BY TISSUE CULTURE TECHNIQUES
- A01H6/00—Angiosperms, i.e. flowering plants, characterised by their botanic taxonomy
- A01H6/34—Cucurbitaceae, e.g. bitter melon, cucumber or watermelon
- A01H6/342—Citrullus lanatus [watermelon]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
- C07K14/24—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
- C07K14/27—Erwinia (G)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/605—Glucagons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
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- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/67—General methods for enhancing the expression
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/70—Vectors or expression systems specially adapted for E. coli
-
- 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)
- C12N9/52—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from bacteria or Archaea
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
- C12P21/02—Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
-
- 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)
- C12Y304/24—Metalloendopeptidases (3.4.24)
- C12Y304/24029—Aureolysin (3.4.24.29)
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
- C07K2317/14—Specific host cells or culture conditions, e.g. components, pH or temperature
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/51—Complete heavy chain or Fd fragment, i.e. VH + CH1
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/515—Complete light chain, i.e. VL + CL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Endocrinology (AREA)
- Toxicology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Physiology (AREA)
- Botany (AREA)
- Developmental Biology & Embryology (AREA)
- Environmental Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Claims (4)
1. Postupak za proizvodnju antitijela ili njegovog fragmenta koji sadrži korake:
(i) transformacija bakterijske stanice domaćina s jednim vektorom koji se sastoji od dvostrukog cistroničkog ekspresijskog sustava;
(ii) kultiviranje transformiranih bakterijskih stanica u prikladnom mediju da se eksprimira antitijelo ili njegov fragment kao tijela za uključivanje;
(iii) provođenje solubilizacije navedenih tijela za uključivanje;
(iv) provođenje ponovnog sklapanja antitijela ili njegovog fragmenta;
pri čemu sustav dvostruke cistroničke ekspresije sadrži:
a) prvi cistron koji sadrži T7 promotor operativno povezan s polinukleotidnom sekvencom koja kodira tešku lanac antitijela ili njegov fragment;
b) drugi cistron koji sadrži promotor arabinoze operativno povezan s polinukleotidnom sekvencom za
kodiranje lakog lanca antitijela ili njegovog fragmenta;
pri čemu su prvi i drugi cistroni smješteni u jednostrukom vektoru i izražavaju antitijelo ili fragment kao tijela za uključivanje; i
pri čemu ekspresija teškog lanca inducira IPTG dok ekspresiju lakog lanca inducira arabinoza takva da su teški i laki lanac izraženi ekvimolarnim razinama ekspresije.
2. Postupak prema zahtjevu 1, naznačen time da je bakterijska stanica domaćin E.coli.
3. Postupak prema zahtjevu 1, naznačen time da dvostruki cistronski ekspresijski sustav sadrži nukleotidnu sekvencu kako je navedeno u SEQ ID br. 19.
4. Postupak prema zahtjevu 1, naznačen time da je postupak za proizvodnju Ranibizumaba i sadrži korake:
(i) transformiranje E.coli s jednim vektorom koji se sastoji od dualnog cistroničkog ekspresijskog sustava;
(ii) kultiviranje transformirane stanice u prikladnom mediju, pri čemu prvi i drugi cistron izražavaju teške i lake lance Ranibizumaba kao tijela za uključivanje;
(iii) provođenje solubilizacije navedenih tijela za uključivanje;
(iv) obavljanje ponovnog puštanja navedenih inkluzivnih tijela pod pogodnim uvjetima radi dobivanja funkcionalnog Ranibizumaba;
pri čemu se prvi cistron sastoji od T7 promotora koji je operativno povezan s polinukleotidnom sekvencom koja kodira teški lanac ranibizumaba, a drugi cistron se sastoji od Arabinose promotora koji je operativno povezan s polinukleotidnom sekvencom koja kodira laki lanac Ranibizumaba; i
pri čemu se ImM IPTG koristi za induciranje ekspresije teškog lanca Ranibizumaba, dok se 13 mM Arabinose koristi da se inducira ekspresija lakog lanca Ranibizumaba tako da su izraženi teški i laki lanac na ekvimolarnim razinama ekspresije.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN2245MU2014 | 2014-07-09 | ||
| PCT/IB2015/055189 WO2016005931A1 (en) | 2014-07-09 | 2015-07-09 | Dual cistronic bacterial expression system |
| EP15745247.5A EP3167065B1 (en) | 2014-07-09 | 2015-07-09 | Dual cistronic bacterial expression system |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20200996T1 true HRP20200996T1 (hr) | 2021-01-08 |
Family
ID=53773474
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20200996TT HRP20200996T1 (hr) | 2014-07-09 | 2020-06-24 | Dualni cistronski bakterijski ekspresijski sustav |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US10329571B2 (hr) |
| EP (1) | EP3167065B1 (hr) |
| JP (1) | JP6748061B2 (hr) |
| CN (1) | CN106661588B (hr) |
| AU (1) | AU2015287296A1 (hr) |
| BR (1) | BR112017000389A2 (hr) |
| CA (1) | CA2954594A1 (hr) |
| CY (1) | CY1123303T1 (hr) |
| DK (1) | DK3167065T3 (hr) |
| ES (1) | ES2808906T3 (hr) |
| HR (1) | HRP20200996T1 (hr) |
| HU (1) | HUE050300T2 (hr) |
| LT (1) | LT3167065T (hr) |
| MX (1) | MX2017000332A (hr) |
| PH (1) | PH12017500047A1 (hr) |
| PL (1) | PL3167065T3 (hr) |
| PT (1) | PT3167065T (hr) |
| RU (1) | RU2732148C2 (hr) |
| SI (1) | SI3167065T1 (hr) |
| WO (1) | WO2016005931A1 (hr) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6435770B2 (ja) * | 2014-01-21 | 2018-12-12 | 東ソー株式会社 | シグナルペプチドをコードするポリヌクレオチドおよびそれを用いたタンパク質の製造方法 |
| WO2017021819A1 (en) * | 2015-07-31 | 2017-02-09 | Dr. Reddy’S Laboratories Limited | Process for preparation of protein or peptide |
| KR102607655B1 (ko) | 2017-05-19 | 2023-11-28 | 카운슬 오브 사이언티픽 앤드 인더스트리얼 리서치 | 리폴딩된 재조합 인간화 라니비주맙의 제조 방법 |
| EP3673062B1 (en) | 2017-08-23 | 2023-09-06 | Novartis AG | Multi-copy gene protein expression system |
| JP7185006B2 (ja) * | 2018-07-06 | 2022-12-06 | ワッカー ケミー アクチエンゲゼルシャフト | 発酵法で組換えタンパク質を放出する細菌株 |
| JP2020120622A (ja) * | 2019-01-31 | 2020-08-13 | Ｓｐｉｂｅｒ株式会社 | 組換え細胞、発現構築物、及び組換えタンパク質の製造方法 |
| US20220177562A1 (en) * | 2019-04-02 | 2022-06-09 | Council Of Scientific & Industrial Research | Cloning and expression of in vivo refolded antibody fragment |
| CN114774453B (zh) * | 2022-03-14 | 2023-04-21 | 湖北大学 | 一种运动发酵单胞菌基因表达严谨调控系统的构建方法和应用 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0604580A1 (en) | 1991-09-19 | 1994-07-06 | Genentech, Inc. | EXPRESSION IN E. COLI OF ANTIBODY FRAGMENTS HAVING AT LEAST A CYSTEINE PRESENT AS A FREE THIOL, USE FOR THE PRODUCTION OF BIFUNCTIONAL F(ab') 2? ANTIBODIES |
| EP1356052B1 (en) | 2000-12-14 | 2008-08-20 | Genentech, Inc. | Production of full antibodies in procaryotic cells |
| DE60224291T2 (de) | 2001-08-27 | 2008-12-11 | Genentech, Inc., South San Francisco | System zur antikörperexpression und- synthese |
| EP2046382B1 (en) * | 2006-07-10 | 2016-08-17 | ESBATech, an Alcon Biomedical Research Unit LLC | scFv ANTIBODIES WHICH PASS EPITHELIAL AND/OR ENDOTHELIAL LAYERS |
| RU2413769C1 (ru) * | 2009-12-24 | 2011-03-10 | Учреждение Российской академии наук Институт биоорганической химии им. академиков М.М. Шемякина и Ю.А. Овчинникова РАН | РЕКОМБИНАНТНАЯ ПЛАЗМИДНАЯ ДНК pET-32a, КОДИРУЮЩАЯ ГЕН ЛИГАНД-СВЯЗЫВАЮЩЕГО ДОМЕНА РЕЦЕПТОРА II ТИПА ТРАНСФОРМИРУЮЩЕГО ФАКТОРА РОСТА-β ЧЕЛОВЕКА (TβRII), ШТАММ БАКТЕРИЙ Escherichia coli - ПРОДУЦЕНТ СЛИТНОГО БЕЛКА ТИОРЕДОКСИН/TβRII И СПОСОБ РЕНАТУРАЦИИ И ОЧИСТКИ ЦЕЛЕВОГО БЕЛКА TβRII |
| GB201002730D0 (en) * | 2010-02-18 | 2010-04-07 | Uni I Oslo | Product |
| US8853380B2 (en) | 2010-06-04 | 2014-10-07 | Lupin Limited | Modified SAK gene for the production of recombinant proteins |
| MY186731A (en) * | 2013-03-08 | 2021-08-14 | Neuclone Biologics Pty Ltd | A cell expression system |
| MX368142B (es) * | 2013-04-30 | 2019-09-20 | Intas Pharmaceuticals Ltd | Metodo de clonacion, expresion y purificacion novedoso para la preparacion de ranibizumab. |
| TW201534726A (zh) * | 2013-07-03 | 2015-09-16 | Halozyme Inc | 熱穩定ｐｈ２０玻尿酸酶變異體及其用途 |
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2015
- 2015-07-09 US US15/324,105 patent/US10329571B2/en not_active Expired - Fee Related
- 2015-07-09 LT LTEP15745247.5T patent/LT3167065T/lt unknown
- 2015-07-09 SI SI201531263T patent/SI3167065T1/sl unknown
- 2015-07-09 MX MX2017000332A patent/MX2017000332A/es unknown
- 2015-07-09 PL PL15745247T patent/PL3167065T3/pl unknown
- 2015-07-09 RU RU2017102578A patent/RU2732148C2/ru active
- 2015-07-09 PT PT157452475T patent/PT3167065T/pt unknown
- 2015-07-09 DK DK15745247.5T patent/DK3167065T3/da active
- 2015-07-09 CN CN201580037078.3A patent/CN106661588B/zh not_active Expired - Fee Related
- 2015-07-09 AU AU2015287296A patent/AU2015287296A1/en not_active Abandoned
- 2015-07-09 CA CA2954594A patent/CA2954594A1/en not_active Abandoned
- 2015-07-09 HU HUE15745247A patent/HUE050300T2/hu unknown
- 2015-07-09 WO PCT/IB2015/055189 patent/WO2016005931A1/en active Application Filing
- 2015-07-09 ES ES15745247T patent/ES2808906T3/es active Active
- 2015-07-09 BR BR112017000389A patent/BR112017000389A2/pt not_active Application Discontinuation
- 2015-07-09 JP JP2017500849A patent/JP6748061B2/ja active Active
- 2015-07-09 EP EP15745247.5A patent/EP3167065B1/en active Active
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2017
- 2017-01-06 PH PH12017500047A patent/PH12017500047A1/en unknown
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2019
- 2019-04-24 US US16/393,338 patent/US11365418B2/en active Active
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2020
- 2020-06-24 HR HRP20200996TT patent/HRP20200996T1/hr unknown
- 2020-06-25 CY CY20201100580T patent/CY1123303T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP3167065B1 (en) | 2020-03-25 |
| US20190309313A1 (en) | 2019-10-10 |
| RU2732148C2 (ru) | 2020-09-11 |
| SI3167065T1 (sl) | 2020-09-30 |
| BR112017000389A2 (pt) | 2018-01-23 |
| EP3167065A1 (en) | 2017-05-17 |
| HUE050300T2 (hu) | 2020-11-30 |
| LT3167065T (lt) | 2020-07-27 |
| US10329571B2 (en) | 2019-06-25 |
| PH12017500047A1 (en) | 2017-05-22 |
| PT3167065T (pt) | 2020-07-01 |
| WO2016005931A1 (en) | 2016-01-14 |
| ES2808906T3 (es) | 2021-03-02 |
| PL3167065T3 (pl) | 2020-11-16 |
| JP2017520261A (ja) | 2017-07-27 |
| MX2017000332A (es) | 2017-07-28 |
| US11365418B2 (en) | 2022-06-21 |
| CN106661588B (zh) | 2020-11-06 |
| CN106661588A (zh) | 2017-05-10 |
| CA2954594A1 (en) | 2016-01-14 |
| JP6748061B2 (ja) | 2020-08-26 |
| AU2015287296A1 (en) | 2017-02-02 |
| DK3167065T3 (da) | 2020-07-06 |
| US20170159060A1 (en) | 2017-06-08 |
| CY1123303T1 (el) | 2021-12-31 |
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