CU24483B1 - Método para incrementar los niveles de secreción de la interleucina-2 - Google Patents
Método para incrementar los niveles de secreción de la interleucina-2Info
- Publication number
- CU24483B1 CU24483B1 CU2016000171A CU20160171A CU24483B1 CU 24483 B1 CU24483 B1 CU 24483B1 CU 2016000171 A CU2016000171 A CU 2016000171A CU 20160171 A CU20160171 A CU 20160171A CU 24483 B1 CU24483 B1 CU 24483B1
- Authority
- CU
- Cuba
- Prior art keywords
- human
- mutations
- secretion levels
- secretion
- levels
- Prior art date
Links
- 238000000034 method Methods 0.000 title abstract 4
- 230000028327 secretion Effects 0.000 title abstract 2
- 102000000588 Interleukin-2 Human genes 0.000 title 1
- 108010002350 Interleukin-2 Proteins 0.000 title 1
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 abstract 3
- 102220511387 Proteasome subunit beta type-10_K35E_mutation Human genes 0.000 abstract 2
- 230000035772 mutation Effects 0.000 abstract 2
- 108090000623 proteins and genes Proteins 0.000 abstract 2
- 210000001744 T-lymphocyte Anatomy 0.000 abstract 1
- 150000001413 amino acids Chemical class 0.000 abstract 1
- 230000008827 biological function Effects 0.000 abstract 1
- 102220345545 c.103A>C Human genes 0.000 abstract 1
- 238000000338 in vitro Methods 0.000 abstract 1
- 102000004169 proteins and genes Human genes 0.000 abstract 1
- 238000006467 substitution reaction Methods 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
Classifications
-
- 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
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/54—Interleukins [IL]
- C07K14/55—IL-2
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
- C12N15/01—Preparation of mutants without inserting foreign genetic material therein; Screening processes therefor
-
- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0635—B lymphocytes
-
- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/20—Interleukins [IL]
- A61K38/2013—IL-2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
- C07K2319/735—Fusion polypeptide containing domain for protein-protein interaction containing a domain for self-assembly, e.g. a viral coat protein (includes phage display)
-
- 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
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/20—Cytokines; Chemokines
- C12N2501/23—Interleukins [IL]
- C12N2501/2302—Interleukin-2 (IL-2)
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Hematology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Toxicology (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Epidemiology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
Abstract
<p>La presente invención se relaciona con la rama de la Biotecnología, en particular con un método basado en la introducción de mutaciones únicas en los genes codificantes de la IL-2 humana y de sus muteínas derivadas que conducen al incremento de sus niveles de secreción en distintos hospederos sin afectar sus funciones biológicas. En particular estas mutaciones se basan en un cambio no conservativo en el aminoácido que ocupa la posición 35 en la secuencia primaria de la IL-2 humana, de preferencia las sustituciones son K35E, K35D y K35Q. Dicho método es útil para mejorar la eficiencia de la producción de la IL-2 humana recombinante y de sus muteínas derivadas tanto a escala de laboratorio como industrial. Las proteínas obtenidas al emplear este método se pueden emplear con fines terapéuticos así como en la expansión in vitro de células T para terapias de transferencia adoptiva.</p>
Priority Applications (24)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CU2016000171A CU24483B1 (es) | 2016-11-15 | 2016-11-15 | Método para incrementar los niveles de secreción de la interleucina-2 |
| JOP/2019/0087A JOP20190087A1 (ar) | 2016-11-15 | 2017-06-16 | طريقة لزيادة مستويات إفراز الإنترلوكين ? والبروتينات المشتقة منه |
| PCT/CU2017/050007 WO2018091003A1 (es) | 2016-11-15 | 2017-11-10 | Método para incrementar los niveles de secreción de la interleucina 2 y sus proteínas derivadas |
| NZ753820A NZ753820B2 (en) | 2016-11-15 | 2017-11-10 | Method for increasing the secretion levels of interleukin 2 and proteins derived from it |
| MX2019005599A MX2019005599A (es) | 2016-11-15 | 2017-11-10 | Metodo para incrementar los niveles de secrecion de la interleucina-2 y sus proteinas derivadas. |
| EP17817648.3A EP3543252B1 (en) | 2016-11-15 | 2017-11-10 | In vitro method for increasing the secretion levels of interleukin 2 and proteins derived from it |
| ES17817648T ES2906832T3 (es) | 2016-11-15 | 2017-11-10 | Método in vitro para incrementar los niveles de secreción de la interleucina-2 y sus proteínas derivadas |
| BR112019009106A BR112019009106A2 (pt) | 2016-11-15 | 2017-11-10 | método para aumentar os níveis de secreção sem afetar as funções biológicas de il-2 de humano recombinante e suas proteínas mutantes derivadas, proteínas obtidas, e, usos do método e das proteínas obtidas |
| TNP/2019/000122A TN2019000122A1 (en) | 2016-11-15 | 2017-11-10 | Method for increasing the secretion levels of interleukin 2 and proteins derived from it |
| CA3040313A CA3040313A1 (en) | 2016-11-15 | 2017-11-10 | Method for increasing the secretion levels of interleukin 2 and proteins derived from it |
| EA201991093A EA201991093A1 (ru) | 2016-11-15 | 2017-11-10 | Способ повышения уровней секреции интерлейкина-2 и полученных из него белков |
| CN201780070548.5A CN109952311B (zh) | 2016-11-15 | 2017-11-10 | 用于增加白介素-2及其衍生蛋白质的分泌水平的方法 |
| JP2019525840A JP6918405B2 (ja) | 2016-11-15 | 2017-11-10 | インターロイキン２及びそれに由来するタンパク質の分泌レベルを増大させる方法。 |
| MYPI2019002144A MY197059A (en) | 2016-11-15 | 2017-11-10 | Method for increasing the secretion levels of interleukin 2 and proteins derived from it |
| UAA201906701A UA125440C2 (uk) | 2016-11-15 | 2017-11-10 | Спосіб in vitro підвищення рівнів секреції рекомбінантного людського інтерлейкіну-2 та білок, одержаний таким способом |
| KR1020197014646A KR102525674B1 (ko) | 2016-11-15 | 2017-11-10 | 인터류킨 2 및 그로부터 유도된 단백질의 분비 수준을 증가시키는 방법 |
| AU2017359841A AU2017359841B2 (en) | 2016-11-15 | 2017-11-10 | Method for increasing the secretion levels of interleukin 2 and proteins derived from it |
| RS20220217A RS62975B1 (sr) | 2016-11-15 | 2017-11-10 | In vitro postupak za povećanje nivoa izlučivanja interleukina 2 i iz njega izvedenih proteina |
| US16/461,258 US20190315826A1 (en) | 2016-11-15 | 2017-11-10 | Method for Increasing the Secretion Levels of Interleukin 2 and Proteins Derived from it |
| ARP170103167A AR110076A1 (es) | 2016-11-15 | 2017-11-14 | Método para incrementar los niveles de secreción de la interleucina-2 y sus proteínas derivadas |
| TW106139366A TWI713798B (zh) | 2016-11-15 | 2017-11-14 | 增加介白素－２（ｉｌ－２）分泌量之方法和源自該方法之蛋白類 |
| CONC2019/0004006A CO2019004006A2 (es) | 2016-11-15 | 2019-04-23 | Método para incrementar los niveles de secreción de la interleucina 2 y sus proteínas derivadas |
| IL266517A IL266517A (en) | 2016-11-15 | 2019-05-07 | A method for increasing the secretion levels of interleukin 2 and proteins derived from it |
| ZA2019/02968A ZA201902968B (en) | 2016-11-15 | 2019-05-13 | Method for increasing the secretion levels of interleukin 2 and proteins derived from it |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CU2016000171A CU24483B1 (es) | 2016-11-15 | 2016-11-15 | Método para incrementar los niveles de secreción de la interleucina-2 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CU20160171A7 CU20160171A7 (es) | 2018-06-05 |
| CU24483B1 true CU24483B1 (es) | 2020-04-02 |
Family
ID=60765569
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CU2016000171A CU24483B1 (es) | 2016-11-15 | 2016-11-15 | Método para incrementar los niveles de secreción de la interleucina-2 |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US20190315826A1 (es) |
| EP (1) | EP3543252B1 (es) |
| JP (1) | JP6918405B2 (es) |
| KR (1) | KR102525674B1 (es) |
| CN (1) | CN109952311B (es) |
| AR (1) | AR110076A1 (es) |
| AU (1) | AU2017359841B2 (es) |
| BR (1) | BR112019009106A2 (es) |
| CA (1) | CA3040313A1 (es) |
| CO (1) | CO2019004006A2 (es) |
| CU (1) | CU24483B1 (es) |
| EA (1) | EA201991093A1 (es) |
| ES (1) | ES2906832T3 (es) |
| IL (1) | IL266517A (es) |
| JO (1) | JOP20190087A1 (es) |
| MX (1) | MX2019005599A (es) |
| MY (1) | MY197059A (es) |
| RS (1) | RS62975B1 (es) |
| TN (1) | TN2019000122A1 (es) |
| TW (1) | TWI713798B (es) |
| UA (1) | UA125440C2 (es) |
| WO (1) | WO2018091003A1 (es) |
| ZA (1) | ZA201902968B (es) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CU24483B1 (es) * | 2016-11-15 | 2020-04-02 | Ct Inmunologia Molecular | Método para incrementar los niveles de secreción de la interleucina-2 |
| SG11202005732XA (en) | 2017-12-19 | 2020-07-29 | Xencor Inc | Engineered il-2 fc fusion proteins |
| JP7490563B2 (ja) * | 2018-03-28 | 2024-05-27 | アセンディス ファーマ オンコロジー ディヴィジョン エー／エス | Ｉｌ－２コンジュゲート |
| EA202092316A1 (ru) | 2018-03-28 | 2021-05-25 | Бристол-Маерс Сквибб Компани | Слитые белки интерлейкина-2/альфа-рецептора интерлейкина-2 и способы применения |
| CN112771072B (zh) * | 2018-07-24 | 2025-01-07 | 生物技术公司 | Il2激动剂 |
| EP3854805A4 (en) * | 2018-09-21 | 2022-08-24 | Innovent Biologics (Suzhou) Co., Ltd. | NOVEL INTERLEUKIN 2 AND ITS USE |
| US11633488B2 (en) | 2020-01-10 | 2023-04-25 | Bright Peak Therapeutics Ag | Modified IL-2 polypeptides and uses thereof |
| WO2021245130A1 (en) | 2020-06-03 | 2021-12-09 | Ascendis Pharma Oncology Division A/S | Il-2 sequences and uses thereof |
| US12024559B2 (en) | 2020-10-23 | 2024-07-02 | Asher Biotherapeutics, Inc. | Fusions with CD8 antigen binding molecules for modulating immune cell function |
| EP4236962A1 (en) | 2020-10-29 | 2023-09-06 | Bristol-Myers Squibb Company | Fusion proteins for the treatment of disease |
| CN112724259B (zh) * | 2020-11-16 | 2022-12-20 | 天津林达生物科技有限公司 | 人血清白蛋白与白介素2的融合蛋白及其用途 |
| CN116854802A (zh) * | 2021-04-13 | 2023-10-10 | 苏州复融生物技术有限公司 | 白介素2突变体及其应用 |
| WO2022260909A1 (en) * | 2021-06-09 | 2022-12-15 | H. Lee Moffitt Cancer Center And Research Institute Inc. | Methods of using anti-cd83 chimeric antigen receptor expressing t cells |
| CU20210104A7 (es) | 2021-12-21 | 2023-07-12 | Ct Inmunologia Molecular | Proteínas de fusión compuestas por un anticuerpo y una muteína agonista de interleucina 2 |
| CU20220020A7 (es) | 2022-03-18 | 2023-12-07 | Ct Inmunologia Molecular | Muteínas derivadas de la interleucina-2 humana con actividad superagonista |
| TW202409069A (zh) * | 2022-07-01 | 2024-03-01 | 大陸商北京星奇原生物科技有限公司 | Ｉｌ－２多肽和使用方法 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3377363D1 (en) * | 1982-03-31 | 1988-08-18 | Ajinomoto Kk | Gene coding for interleukin-2 polypeptide, recombinant dna carrying said gene, cell lines possessing the recombinant dna,and method for producing interleukin-2 using said cells |
| US7569215B2 (en) * | 2003-07-18 | 2009-08-04 | Massachusetts Institute Of Technology | Mutant interleukin-2 (IL-2) polypeptides |
| CA2557677A1 (en) * | 2004-03-05 | 2005-10-06 | Chiron Corporation | In vitro test system for predicting patient tolerability of therapeutic agents |
| MX2007009012A (es) * | 2005-01-27 | 2007-09-14 | Novartis Vaccines & Diagnostic | Metodos para tratar carcinoma de celulas renales. |
| CU23734A1 (es) | 2009-11-27 | 2011-11-15 | Centro Inmunologia Molecular | Polipéptidos inmunomoduladores derivados de la il-2 con actividad antagonista de esta citocina útiles en la terapia del cáncer y enfermedades infecciosas crónicas |
| CU23923B1 (es) * | 2010-11-12 | 2013-07-31 | Ct De Inmunología Molecular | Polipéptidos derivados de la il-2 con actividad agonista |
| RS57767B1 (sr) * | 2011-02-10 | 2018-12-31 | Roche Glycart Ag | Mutantni interleukin-2 polipeptidi |
| CU24483B1 (es) * | 2016-11-15 | 2020-04-02 | Ct Inmunologia Molecular | Método para incrementar los niveles de secreción de la interleucina-2 |
-
2016
- 2016-11-15 CU CU2016000171A patent/CU24483B1/es unknown
-
2017
- 2017-06-16 JO JOP/2019/0087A patent/JOP20190087A1/ar unknown
- 2017-11-10 TN TNP/2019/000122A patent/TN2019000122A1/en unknown
- 2017-11-10 BR BR112019009106A patent/BR112019009106A2/pt unknown
- 2017-11-10 MY MYPI2019002144A patent/MY197059A/en unknown
- 2017-11-10 CA CA3040313A patent/CA3040313A1/en active Pending
- 2017-11-10 EP EP17817648.3A patent/EP3543252B1/en active Active
- 2017-11-10 US US16/461,258 patent/US20190315826A1/en active Pending
- 2017-11-10 RS RS20220217A patent/RS62975B1/sr unknown
- 2017-11-10 JP JP2019525840A patent/JP6918405B2/ja active Active
- 2017-11-10 CN CN201780070548.5A patent/CN109952311B/zh active Active
- 2017-11-10 ES ES17817648T patent/ES2906832T3/es active Active
- 2017-11-10 AU AU2017359841A patent/AU2017359841B2/en active Active
- 2017-11-10 MX MX2019005599A patent/MX2019005599A/es unknown
- 2017-11-10 EA EA201991093A patent/EA201991093A1/ru unknown
- 2017-11-10 KR KR1020197014646A patent/KR102525674B1/ko active IP Right Grant
- 2017-11-10 WO PCT/CU2017/050007 patent/WO2018091003A1/es active Application Filing
- 2017-11-10 UA UAA201906701A patent/UA125440C2/uk unknown
- 2017-11-14 AR ARP170103167A patent/AR110076A1/es unknown
- 2017-11-14 TW TW106139366A patent/TWI713798B/zh active
-
2019
- 2019-04-23 CO CONC2019/0004006A patent/CO2019004006A2/es unknown
- 2019-05-07 IL IL266517A patent/IL266517A/en unknown
- 2019-05-13 ZA ZA2019/02968A patent/ZA201902968B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| IL266517A (en) | 2019-07-31 |
| KR102525674B1 (ko) | 2023-04-25 |
| RS62975B1 (sr) | 2022-03-31 |
| JP6918405B2 (ja) | 2021-08-11 |
| US20190315826A1 (en) | 2019-10-17 |
| MY197059A (en) | 2023-05-23 |
| MX2019005599A (es) | 2019-07-04 |
| WO2018091003A1 (es) | 2018-05-24 |
| BR112019009106A2 (pt) | 2019-07-16 |
| ZA201902968B (en) | 2020-07-29 |
| CN109952311A (zh) | 2019-06-28 |
| NZ753820A (en) | 2021-09-24 |
| EP3543252A1 (en) | 2019-09-25 |
| ES2906832T3 (es) | 2022-04-20 |
| TWI713798B (zh) | 2020-12-21 |
| KR20190079636A (ko) | 2019-07-05 |
| JOP20190087A1 (ar) | 2019-04-18 |
| TW201831688A (zh) | 2018-09-01 |
| AU2017359841A1 (en) | 2019-06-13 |
| EA201991093A1 (ru) | 2019-09-30 |
| CO2019004006A2 (es) | 2019-04-30 |
| CN109952311B (zh) | 2022-07-01 |
| CU20160171A7 (es) | 2018-06-05 |
| AU2017359841B2 (en) | 2020-08-27 |
| AR110076A1 (es) | 2019-02-20 |
| JP2019535269A (ja) | 2019-12-12 |
| TN2019000122A1 (en) | 2020-10-05 |
| EP3543252B1 (en) | 2021-12-29 |
| CA3040313A1 (en) | 2018-05-24 |
| UA125440C2 (uk) | 2022-03-09 |
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