SG11201810975UA - Method for stabilizing proteins - Google Patents
Method for stabilizing proteinsInfo
- Publication number
- SG11201810975UA SG11201810975UA SG11201810975UA SG11201810975UA SG11201810975UA SG 11201810975U A SG11201810975U A SG 11201810975UA SG 11201810975U A SG11201810975U A SG 11201810975UA SG 11201810975U A SG11201810975U A SG 11201810975UA SG 11201810975U A SG11201810975U A SG 11201810975UA
- Authority
- SG
- Singapore
- Prior art keywords
- international
- pct
- publication
- product
- date
- Prior art date
Links
- 238000000034 method Methods 0.000 title abstract 3
- 102000004169 proteins and genes Human genes 0.000 title abstract 3
- 108090000623 proteins and genes Proteins 0.000 title abstract 3
- 230000000087 stabilizing effect Effects 0.000 title abstract 2
- 230000019522 cellular metabolic process Effects 0.000 abstract 1
- 238000012258 culturing Methods 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 230000008520 organization Effects 0.000 abstract 1
Classifications
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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
-
- 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
-
- 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
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
-
- 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
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/06—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies from serum
- C07K16/065—Purification, fragmentation
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
- C12M27/02—Stirrer or mobile mixing elements
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/12—Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/28—Means for regulation, monitoring, measurement or control, e.g. flow regulation of redox potential
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/30—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
- C12M41/34—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of gas
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
- C12M47/10—Separation or concentration of fermentation products
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
- C12M47/20—Heating or cooling
-
- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Sustainable Development (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Chemistry (AREA)
- Analytical Chemistry (AREA)
- Biophysics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Thermal Sciences (AREA)
- Physics & Mathematics (AREA)
- Clinical Laboratory Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) CORRECTED VERSION (19) World Intellectual Property Organization International Bureau (43) International Publication Date 111111111111011010101111101011111111101 Oil DID HO HE OWE 11101111 (10) International Publication Number WO 2017/212071 A9 14 December 2017 (14.12.2017) Wi PO I PCT (51) International Patent Classification: C12P 21/00 (2006.01) (21) International Application Number: PCT/EP2017/064313 (22) International Filing Date: 12 June 2017 (12.06.2017) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 62/348,595 10 June 2016 (10.06.2016) US (71) Applicant: LONZA LTD [CH/CH]; Lonzastrasse, 3930 Visp (CH). (72) Inventors: KHAN, Mohsam; 22 Bath Road, Slough SL1 4DX (GB). PORTER, Alison; 228 Bath Road, Slough SL1 4DX (GB). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Published: with international search report (Art. 21(3)) (48) Date of publication of this corrected version: 12 April 2018 (12.04.2018) (15) Information about Correction: 11 see Notice of 12 April 2018 (12.04.2018) O N (54) Title: METHOD FOR STABILIZING PROTEINS O (57) : The present disclosure features methods and compositions for increasing the amount of products of cellular metabolism, e.g., proteins, by lowering the temperature of cells expressing the product at one or more steps while culturing the cells, expressing C the product, and/or recovering the product.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662348595P | 2016-06-10 | 2016-06-10 | |
| PCT/EP2017/064313 WO2017212071A1 (en) | 2016-06-10 | 2017-06-12 | Method for stabilizing proteins |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SG11201810975UA true SG11201810975UA (en) | 2019-01-30 |
Family
ID=59253468
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SG11201810975UA SG11201810975UA (en) | 2016-06-10 | 2017-06-12 | Method for stabilizing proteins |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US10975409B2 (en) |
| EP (1) | EP3469091A1 (en) |
| JP (3) | JP2019517272A (en) |
| KR (2) | KR102451374B1 (en) |
| CN (1) | CN109496237A (en) |
| AU (1) | AU2017277761B2 (en) |
| CA (1) | CA3026589A1 (en) |
| EA (1) | EA201892820A1 (en) |
| IL (1) | IL263342B2 (en) |
| MX (1) | MX2018015298A (en) |
| SG (1) | SG11201810975UA (en) |
| WO (1) | WO2017212071A1 (en) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG11201810975UA (en) | 2016-06-10 | 2019-01-30 | Lonza Ag | Method for stabilizing proteins |
| JP7604222B2 (en) * | 2017-03-22 | 2024-12-23 | ボンチ インコーポレイテッド | Therapeutic Botulinum Neurotoxins |
| CN110621341A (en) * | 2017-04-26 | 2019-12-27 | 百时美施贵宝公司 | Antibody production method that minimizes disulfide bond reduction |
| US10814338B2 (en) * | 2017-08-09 | 2020-10-27 | Delta Separations, Llc | Device, system and methods for separation and purification of organic compounds from botanical material |
| AU2018395215A1 (en) * | 2017-12-28 | 2020-08-13 | Locus Ip Company, Llc | Reactors and submerged fermentation methods for producing microbe-based products |
| US12331320B2 (en) | 2018-10-10 | 2025-06-17 | The Research Foundation For The State University Of New York | Genome edited cancer cell vaccines |
| JP7453151B2 (en) * | 2018-11-02 | 2024-03-19 | 協和キリン株式会社 | How to prepare liquid culture medium |
| CN109932328B (en) * | 2019-03-27 | 2021-06-25 | 西京学院 | A kind of visible spectrophotometric determination method of acrylamide content in instant coffee |
| CN112011514B (en) * | 2019-05-31 | 2024-12-24 | 百济神州(苏州)生物科技有限公司 | Cell culture technology for improving antibody ADCC activity |
| CN114502716A (en) * | 2019-10-11 | 2022-05-13 | 思拓凡瑞典有限公司 | Bioreactor apparatus and method of operating the same |
| KR20230045615A (en) * | 2020-08-14 | 2023-04-04 | 브리스톨-마이어스 스큅 컴퍼니 | how to make protein |
| CN118256580B (en) * | 2022-12-27 | 2025-06-24 | 信立泰(苏州)药业有限公司 | Low-temperature culture method for CHO cells expressing dolastatin |
| CN118240744B (en) * | 2024-03-06 | 2024-11-26 | 上海迈邦生物科技有限公司 | A method for simultaneously regulating cell expression product aggregates, charge heterogeneity and improving yield |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9022545D0 (en) | 1990-10-17 | 1990-11-28 | Wellcome Found | Culture medium |
| IT1258959B (en) | 1992-06-09 | 1996-03-11 | MOBILE MODULES PLANT FOR THE DEVELOPMENT AND PRODUCTION OF BIOTECHNOLOGICAL PRODUCTS ON A PILOT SCALE | |
| DE69839147T2 (en) | 1997-06-12 | 2009-02-19 | Novartis International Pharmaceutical Ltd. | ARTIFICIAL ANTIBODY POLYPEPTIDE |
| WO2003072796A1 (en) * | 2002-02-28 | 2003-09-04 | Yaeta Endo | Reaction solution for cell-free protein synthesis, method of preparing the same and protein synthesis method using the same |
| WO2005076093A1 (en) | 2004-02-03 | 2005-08-18 | Xcellerex, Llc | System and method for manufacturing |
| GB0410118D0 (en) | 2004-05-06 | 2004-06-09 | Glaxo Group Ltd | Novel bioreactor |
| AU2005250500B2 (en) | 2004-06-04 | 2011-06-23 | Global Life Sciences Solutions Usa Llc | Disposable bioreactor systems and methods |
| CN101395327A (en) | 2005-12-05 | 2009-03-25 | 欧内斯特·G·霍普 | Pre-approved modular device meeting pharmaceutical manufacturing quality management specifications |
| BRPI0810471A2 (en) | 2007-04-16 | 2014-11-11 | Momenta Pharmaceuticals Inc | DEFINED GLYCOPROTEIN PRODUCTS AND RELATED METHODS |
| SI4365189T1 (en) * | 2007-07-09 | 2025-06-30 | F. Hoffmann-La Roche Ag | Prevention of disulfide bond reduction during recombinant production of polypeptides |
| EP2216395A1 (en) * | 2009-02-09 | 2010-08-11 | Lonza Biologics plc. | Bioreactor for the cultivation of mammalian cells |
| WO2011139708A2 (en) | 2010-04-26 | 2011-11-10 | Toyota Motor Engineering & Manufacturing North America, Inc. | Improved hydrogen release from complex metal hydrides by solvation in ionic liquids |
| US10371394B2 (en) | 2010-09-20 | 2019-08-06 | Biologics Modular Llc | Mobile, modular cleanroom facility |
| US9388373B2 (en) | 2011-03-08 | 2016-07-12 | University Of Maryland Baltimore County | Microscale bioprocessing system and method for protein manufacturing |
| US9422348B2 (en) * | 2011-10-04 | 2016-08-23 | Statens Serum Institut | Production of a cysteine rich protein |
| SG10201805291TA (en) * | 2011-10-27 | 2018-08-30 | Genmab As | Production of heterodimeric proteins |
| AR090340A1 (en) * | 2012-03-27 | 2014-11-05 | Genentech Inc | IMPROVED HARVEST OPERATIONS FOR RECOMBINED PROTEINS |
| JP6063362B2 (en) * | 2013-09-10 | 2017-01-18 | 株式会社日立製作所 | Photosynthesis microorganism separation system and separation method thereof |
| SG11201810975UA (en) | 2016-06-10 | 2019-01-30 | Lonza Ag | Method for stabilizing proteins |
-
2017
- 2017-06-12 SG SG11201810975UA patent/SG11201810975UA/en unknown
- 2017-06-12 EP EP17733993.4A patent/EP3469091A1/en active Pending
- 2017-06-12 JP JP2018564413A patent/JP2019517272A/en active Pending
- 2017-06-12 US US15/619,876 patent/US10975409B2/en active Active
- 2017-06-12 IL IL263342A patent/IL263342B2/en unknown
- 2017-06-12 KR KR1020197000394A patent/KR102451374B1/en active Active
- 2017-06-12 CN CN201780046750.4A patent/CN109496237A/en active Pending
- 2017-06-12 AU AU2017277761A patent/AU2017277761B2/en active Active
- 2017-06-12 MX MX2018015298A patent/MX2018015298A/en unknown
- 2017-06-12 EA EA201892820A patent/EA201892820A1/en unknown
- 2017-06-12 CA CA3026589A patent/CA3026589A1/en not_active Abandoned
- 2017-06-12 KR KR1020227034120A patent/KR102499718B1/en active Active
- 2017-06-12 WO PCT/EP2017/064313 patent/WO2017212071A1/en not_active Ceased
-
2020
- 2020-04-22 US US16/855,714 patent/US11993802B2/en active Active
-
2022
- 2022-09-20 JP JP2022149473A patent/JP7584206B2/en active Active
-
2024
- 2024-07-17 JP JP2024114244A patent/JP2024150571A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| IL263342A (en) | 2018-12-31 |
| KR20190017885A (en) | 2019-02-20 |
| JP2022191246A (en) | 2022-12-27 |
| US10975409B2 (en) | 2021-04-13 |
| MX2018015298A (en) | 2019-04-11 |
| KR102451374B1 (en) | 2022-10-11 |
| WO2017212071A9 (en) | 2018-04-12 |
| BR112018075548A2 (en) | 2019-04-09 |
| KR102499718B1 (en) | 2023-02-13 |
| US20170356022A1 (en) | 2017-12-14 |
| CA3026589A1 (en) | 2017-12-14 |
| JP7584206B2 (en) | 2024-11-15 |
| JP2024150571A (en) | 2024-10-23 |
| AU2017277761B2 (en) | 2021-11-11 |
| WO2017212071A1 (en) | 2017-12-14 |
| US20200248223A1 (en) | 2020-08-06 |
| IL263342B2 (en) | 2023-11-01 |
| US11993802B2 (en) | 2024-05-28 |
| JP2019517272A (en) | 2019-06-24 |
| KR20220139432A (en) | 2022-10-14 |
| EA201892820A1 (en) | 2019-10-31 |
| CN109496237A (en) | 2019-03-19 |
| EP3469091A1 (en) | 2019-04-17 |
| AU2017277761A1 (en) | 2018-12-20 |
| IL263342B1 (en) | 2023-07-01 |
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