CA3012350A1 - Il-6 antagonist formulations and uses thereof - Google Patents
Il-6 antagonist formulations and uses thereof Download PDFInfo
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- CA3012350A1 CA3012350A1 CA3012350A CA3012350A CA3012350A1 CA 3012350 A1 CA3012350 A1 CA 3012350A1 CA 3012350 A CA3012350 A CA 3012350A CA 3012350 A CA3012350 A CA 3012350A CA 3012350 A1 CA3012350 A1 CA 3012350A1
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- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
-
- 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
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/244—Interleukins [IL]
- C07K16/248—IL-6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Ophthalmology & Optometry (AREA)
- Immunology (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Dermatology (AREA)
- Endocrinology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Inorganic Chemistry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662298774P | 2016-02-23 | 2016-02-23 | |
| US62/298,774 | 2016-02-23 | ||
| PCT/US2017/019131 WO2017147293A1 (en) | 2016-02-23 | 2017-02-23 | Il-6 antagonist formulations and uses thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3012350A1 true CA3012350A1 (en) | 2017-08-31 |
Family
ID=59685584
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3012350A Abandoned CA3012350A1 (en) | 2016-02-23 | 2017-02-23 | Il-6 antagonist formulations and uses thereof |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US20190046642A1 (enExample) |
| EP (1) | EP3419599A4 (enExample) |
| JP (2) | JP2019510078A (enExample) |
| KR (1) | KR20180116359A (enExample) |
| CN (1) | CN108718522A (enExample) |
| AR (1) | AR107708A1 (enExample) |
| AU (1) | AU2017223687A1 (enExample) |
| BR (1) | BR112018017031A2 (enExample) |
| CA (1) | CA3012350A1 (enExample) |
| MX (1) | MX2018010032A (enExample) |
| WO (1) | WO2017147293A1 (enExample) |
Families Citing this family (14)
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| BR112020010761A2 (pt) * | 2017-11-30 | 2020-11-24 | Bio-Thera Solutions, Ltd. | formulação líquida de anticorpo humanizado para o tratamento de doenças relacionadas à il-6 |
| CN112739378B (zh) * | 2018-09-14 | 2025-05-06 | 田边三菱制药株式会社 | 含有人抗il-33单克隆抗体的医药用组合物 |
| WO2020088346A1 (en) | 2018-10-31 | 2020-05-07 | Mycenax Biotech Inc. | Aqueous pharmaceutical formulations |
| EP4591885A3 (en) * | 2019-05-01 | 2025-11-19 | Novo Nordisk A/S | Anti-il-6 antibody formulation |
| US20210290732A1 (en) * | 2020-02-21 | 2021-09-23 | Spitfire Pharma Llc | GLP-1R and GCGR Agonists, Formulations, and Methods of Use |
| RU2745814C1 (ru) * | 2020-06-05 | 2021-04-01 | Закрытое Акционерное Общество "Биокад" | Водная фармацевтическая композиция левилимаба и ее применение |
| JP2023532046A (ja) * | 2020-06-26 | 2023-07-26 | トレフォイル セラピューティクス，インク． | 組換え修飾線維芽細胞増殖因子およびそれを使用した治療 |
| CN116234576A (zh) * | 2020-07-31 | 2023-06-06 | 阿拉玛布治疗学股份有限公司 | 抗-连接蛋白抗体制剂 |
| EP4199965A4 (en) * | 2020-08-19 | 2025-03-26 | Bio-Thera Solutions, Ltd. | LIQUID FORMULATIONS CONTAINING HIGHLY CONCENTRATED HUMANIZED ANTIBODIES FOR THE TREATMENT OF IL-6-ASSOCIATED DISEASES |
| KR20220028972A (ko) * | 2020-08-31 | 2022-03-08 | (주)셀트리온 | 안정한 약제학적 제제 |
| US20230073821A1 (en) * | 2021-08-27 | 2023-03-09 | International Business Machines Corporation | Antigen-binding proteins targeting coronavirus (cov) variants |
| JP2023042974A (ja) * | 2021-09-15 | 2023-03-28 | シスメックス株式会社 | 抗サイトカイン抗体の抗原に対する親和性を向上させる方法、抗サイトカイン抗体の製造方法及び抗サイトカイン抗体 |
| CN116355825A (zh) * | 2022-02-25 | 2023-06-30 | 南京工业大学 | 一种强化纤维素合成来提高人表皮生长因子分泌生产效率的方法 |
| KR20250071252A (ko) * | 2022-09-30 | 2025-05-21 | 소네트 바이오테라퓨틱스, 인크. | 저 투여량 il-6 제형 및 이의 사용 방법 |
Family Cites Families (85)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US4548990A (en) | 1983-08-15 | 1985-10-22 | Ciba-Geigy Corporation | Crosslinked, porous polymers for controlled drug delivery |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| US5476996A (en) | 1988-06-14 | 1995-12-19 | Lidak Pharmaceuticals | Human immune system in non-human animal |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US6673986B1 (en) | 1990-01-12 | 2004-01-06 | Abgenix, Inc. | Generation of xenogeneic antibodies |
| US6075181A (en) | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| EP1690935A3 (en) | 1990-01-12 | 2008-07-30 | Abgenix, Inc. | Generation of xenogeneic antibodies |
| US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
| GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
| ES2139598T3 (es) | 1990-07-10 | 2000-02-16 | Medical Res Council | Procedimientos para la produccion de miembros de parejas de union especifica. |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| US6300129B1 (en) | 1990-08-29 | 2001-10-09 | Genpharm International | Transgenic non-human animals for producing heterologous antibodies |
| US5789650A (en) | 1990-08-29 | 1998-08-04 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US6255458B1 (en) | 1990-08-29 | 2001-07-03 | Genpharm International | High affinity human antibodies and human antibodies against digoxin |
| WO1993012227A1 (en) | 1991-12-17 | 1993-06-24 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5877397A (en) | 1990-08-29 | 1999-03-02 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5874299A (en) | 1990-08-29 | 1999-02-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| JP2938569B2 (ja) | 1990-08-29 | 1999-08-23 | ジェンファーム インターナショナル，インコーポレイティド | 異種免疫グロブリンを作る方法及びトランスジェニックマウス |
| WO1992009690A2 (en) | 1990-12-03 | 1992-06-11 | Genentech, Inc. | Enrichment method for variant proteins with altered binding properties |
| ATE439435T1 (de) | 1991-03-01 | 2009-08-15 | Dyax Corp | Chimäres protein mit mikroprotein mit zwei oder mehr disulfidbindungen und ausgestaltungen davon |
| EP1471142B1 (en) | 1991-04-10 | 2008-11-19 | The Scripps Research Institute | Heterodimeric receptor libraries using phagemids |
| DE4122599C2 (de) | 1991-07-08 | 1993-11-11 | Deutsches Krebsforsch | Phagemid zum Screenen von Antikörpern |
| EP0605522B1 (en) | 1991-09-23 | 1999-06-23 | Medical Research Council | Methods for the production of humanized antibodies |
| EP1136556B1 (en) | 1991-11-25 | 2005-06-08 | Enzon, Inc. | Method of producing multivalent antigen-binding proteins |
| CA2118508A1 (en) | 1992-04-24 | 1993-11-11 | Elizabeth S. Ward | Recombinant production of immunoglobulin-like domains in prokaryotic cells |
| EP0672142B1 (en) | 1992-12-04 | 2001-02-28 | Medical Research Council | Multivalent and multispecific binding proteins, their manufacture and use |
| CA2161351C (en) | 1993-04-26 | 2010-12-21 | Nils Lonberg | Transgenic non-human animals capable of producing heterologous antibodies |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
| FR2734739B1 (fr) | 1995-06-01 | 1997-07-11 | Gec Alsthom Stein Ind | Dispositif de surveillance d'un broyeur a boulets |
| EP0795743A3 (en) | 1996-03-15 | 1998-02-25 | Japan Tobacco Inc. | Method and apparatus for infra-red moisture measurement |
| US5839430A (en) | 1996-04-26 | 1998-11-24 | Cama; Joseph | Combination inhaler and peak flow rate meter |
| WO1998023289A1 (en) | 1996-11-27 | 1998-06-04 | The General Hospital Corporation | MODULATION OF IgG BINDING TO FcRn |
| US6277375B1 (en) | 1997-03-03 | 2001-08-21 | Board Of Regents, The University Of Texas System | Immunoglobulin-like domains with increased half-lives |
| DK0979281T3 (da) | 1997-05-02 | 2005-11-21 | Genentech Inc | Fremgangsmåde til fremstilling af multispecifikke antistoffer med heteromultimere og fælles bestanddele |
| EP1958962A3 (en) | 1997-06-12 | 2013-05-01 | Novartis International Pharmaceutical Ltd. | Artificial antibody polypeptides |
| US6358058B1 (en) | 1998-01-30 | 2002-03-19 | 1263152 Ontario Inc. | Aerosol dispensing inhaler training device |
| AU775076B2 (en) | 1998-12-10 | 2004-07-15 | Bristol-Myers Squibb Company | Protein scaffolds for antibody mimics and other binding proteins |
| EP1212422B1 (en) | 1999-08-24 | 2007-02-21 | Medarex, Inc. | Human ctla-4 antibodies and their uses |
| KR100857943B1 (ko) | 2000-11-30 | 2008-09-09 | 메다렉스, 인코포레이티드 | 인간 항체의 제조를 위한 형질전환 트랜스염색체 설치류 |
| DK1390535T3 (da) | 2001-04-26 | 2010-12-06 | Amgen Mountain View Inc | Kombinatoriske biblioteker af monomer-domæner |
| US20030157561A1 (en) | 2001-11-19 | 2003-08-21 | Kolkman Joost A. | Combinatorial libraries of monomer domains |
| ATE556591T1 (de) * | 2001-11-08 | 2012-05-15 | Abbott Biotherapeutics Corp | Stabile pharmazeutische flüssigformulierung von igg-antikörpern |
| AU2003234439A1 (en) | 2002-05-07 | 2003-11-11 | Control Delivery Systems, Inc. | Processes for forming a drug delivery device |
| AU2003290682A1 (en) | 2002-11-15 | 2004-06-15 | Centocor, Inc. | Anti-angiogenic uses of il-6 antagonists |
| US20040191243A1 (en) * | 2002-12-13 | 2004-09-30 | Bei Chen | System and method for stabilizing antibodies with histidine |
| WO2005062955A2 (en) | 2003-12-23 | 2005-07-14 | Rinat Neuroscience Corp. | Agonist anti-trkc antibodies and methods using same |
| DK2213683T3 (da) | 2004-08-04 | 2013-09-02 | Mentrik Biotech Llc | VARIANT-Fc-REGIONER |
| EP1789446A2 (en) | 2004-09-02 | 2007-05-30 | Genentech, Inc. | Heteromultimeric molecules |
| US8802820B2 (en) | 2004-11-12 | 2014-08-12 | Xencor, Inc. | Fc variants with altered binding to FcRn |
| BRPI0620797A2 (pt) | 2005-12-30 | 2011-11-22 | Merck Patent Ges Mit Beschonkter Haftung | anticorpos anti-il-6 que previnem a ligação de il-6 complexado com il-6ralfa a gp130 |
| EP2004690A2 (en) | 2006-03-13 | 2008-12-24 | Ablynx N.V. | Amino acid sequences directed against il-6 and polypeptides comprising the same for the treatment of diseases and disorders associated with il-6-mediated signalling |
| AU2007307324B2 (en) | 2006-05-19 | 2013-08-15 | Alder Biopharmaceuticals, Inc. | Culture method for obtaining a clonal population of antigen-specific B cells |
| AU2008216090A1 (en) | 2007-02-16 | 2008-08-21 | Wyeth | Protein formulations containing sorbitol |
| TWI617576B (zh) | 2007-05-21 | 2018-03-11 | 艾爾德生物控股有限責任公司 | 介白素-６（ｉｌ-６）的抗體及其等之用途 |
| CN101855336B (zh) * | 2007-09-14 | 2019-07-30 | 赛诺菲巴斯德生物制剂有限责任公司 | 含艰难梭菌类毒素a和b的药物组合物 |
| CA2705879A1 (en) | 2007-11-21 | 2009-06-04 | Amgen Inc. | Wise binding agents and epitopes |
| US20100187601A1 (en) | 2007-12-12 | 2010-07-29 | Fujio Masuoka | Semiconductor device |
| SG2013054218A (en) | 2008-01-15 | 2014-10-30 | Abbott Gmbh & Co Kg | Powdered protein compositions and methods of making same |
| BRPI0916668B1 (pt) | 2008-08-05 | 2021-12-28 | Novartis Ag | Anticorpo monoclonal isolado, composição farmacêutica, ácido nucleico isolado e vetor |
| DK2324930T3 (da) | 2008-09-12 | 2012-12-10 | Kdf Co Ltd | Vandsprøjteindretning |
| US20120005773A1 (en) * | 2008-10-01 | 2012-01-05 | Aasen Eric D | Transgenic plants with enhanced agronomic traits |
| US8992920B2 (en) * | 2008-11-25 | 2015-03-31 | Alderbio Holdings Llc | Anti-IL-6 antibodies for the treatment of arthritis |
| CN102224169A (zh) | 2008-11-26 | 2011-10-19 | 葛兰素集团有限公司 | 多肽、抗体可变结构域和拮抗剂 |
| WO2010088444A1 (en) | 2009-01-29 | 2010-08-05 | Medimmune, Llc | Human anti-il-6 antibodies with extended in vivo half-life and their use in treatment of oncology, autoimmune diseases and inflammatory diseases |
| JO3417B1 (ar) * | 2010-01-08 | 2019-10-20 | Regeneron Pharma | الصيغ المستقرة التي تحتوي على الأجسام المضادة لمضاد مستقبل( interleukin-6 (il-6r |
| PE20130643A1 (es) * | 2010-07-12 | 2013-06-07 | Covx Technologies Ireland Ltd | Conjugados de anticuerpos multifuncionales |
| AU2012347545A1 (en) | 2011-12-07 | 2014-06-12 | Amgen Inc. | IgG2 disulfide isoform separation |
| EP2854844A4 (en) | 2012-06-01 | 2016-11-23 | Ophthotech Corp | COMPOSITIONS COMPRISING AN ANTI-PDGF APTAMER AND A VEGF ANTAGONIST |
| PE20150361A1 (es) | 2012-07-13 | 2015-03-14 | Roche Glycart Ag | Anticuerpos biespecificos anti-vegf/anti-ang-2 y su utilizacion en el tratamiento de enfermedades vasculares oculares |
| SG11201501715QA (en) * | 2012-09-07 | 2015-05-28 | Coherus Biosciences Inc | Stable aqueous formulations of adalimumab |
| AU2013334740A1 (en) * | 2012-10-25 | 2015-04-02 | Medimmune, Llc | Stable, low viscosity antibody formulation |
| RU2670943C9 (ru) * | 2012-11-08 | 2018-11-26 | Илэвэн Байотерапьютикс, Инк. | Антагонисты ил-6 и их применение |
| EP3019243A4 (en) * | 2013-07-12 | 2017-03-15 | Ophthotech Corporation | Methods for treating or preventing ophthalmological conditions |
| EP2898896A1 (en) | 2014-01-22 | 2015-07-29 | Université Pierre et Marie Curie (Paris 6) | Agents for use in the treatment of retinal inflammation |
| WO2016073894A1 (en) | 2014-11-07 | 2016-05-12 | Eleven Biotherapeutics, Inc. | Therapeutic agents with increased ocular retention |
| MY185114A (en) * | 2014-11-07 | 2021-04-30 | Sesen Bio Inc | Improved il-6 antibodies |
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2017
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- 2017-02-23 JP JP2018563405A patent/JP2019510078A/ja active Pending
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- 2017-02-23 US US16/078,671 patent/US20190046642A1/en not_active Abandoned
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2021
- 2021-08-31 US US17/462,654 patent/US12048746B2/en active Active
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2022
- 2022-03-31 JP JP2022058898A patent/JP2022084922A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP3419599A4 (en) | 2019-09-11 |
| BR112018017031A2 (pt) | 2019-01-22 |
| WO2017147293A1 (en) | 2017-08-31 |
| US20220241414A1 (en) | 2022-08-04 |
| EP3419599A1 (en) | 2019-01-02 |
| MX2018010032A (es) | 2019-03-11 |
| CN108718522A (zh) | 2018-10-30 |
| US20190046642A1 (en) | 2019-02-14 |
| JP2022084922A (ja) | 2022-06-07 |
| US12048746B2 (en) | 2024-07-30 |
| AU2017223687A1 (en) | 2018-08-09 |
| KR20180116359A (ko) | 2018-10-24 |
| AR107708A1 (es) | 2018-05-23 |
| JP2019510078A (ja) | 2019-04-11 |
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