CO2017012628A2 - Métodos para mejorar la adsorción de conjugados de polisacárido-proteína y una formulación de vacuna multivalente obtenida con los mismos - Google Patents
Métodos para mejorar la adsorción de conjugados de polisacárido-proteína y una formulación de vacuna multivalente obtenida con los mismosInfo
- Publication number
- CO2017012628A2 CO2017012628A2 CONC2017/0012628A CO2017012628A CO2017012628A2 CO 2017012628 A2 CO2017012628 A2 CO 2017012628A2 CO 2017012628 A CO2017012628 A CO 2017012628A CO 2017012628 A2 CO2017012628 A2 CO 2017012628A2
- Authority
- CO
- Colombia
- Prior art keywords
- polysaccharide
- methods
- adsorption
- vaccine formulation
- protein conjugates
- Prior art date
Links
- 238000001179 sorption measurement Methods 0.000 title abstract 5
- 238000009472 formulation Methods 0.000 title abstract 4
- 239000000203 mixture Substances 0.000 title abstract 4
- 238000000034 method Methods 0.000 title abstract 2
- 229940031348 multivalent vaccine Drugs 0.000 title 1
- 230000002378 acidificating effect Effects 0.000 abstract 1
- 238000004220 aggregation Methods 0.000 abstract 1
- 230000002776 aggregation Effects 0.000 abstract 1
- 239000007853 buffer solution Substances 0.000 abstract 1
- 150000004676 glycans Chemical class 0.000 abstract 1
- 230000007935 neutral effect Effects 0.000 abstract 1
- 229960001973 pneumococcal vaccines Drugs 0.000 abstract 1
- 229920001282 polysaccharide Polymers 0.000 abstract 1
- 239000005017 polysaccharide Substances 0.000 abstract 1
- 102000004169 proteins and genes Human genes 0.000 abstract 1
- 108090000623 proteins and genes Proteins 0.000 abstract 1
- 239000001384 succinic acid Substances 0.000 abstract 1
Classifications
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- 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
- A61K47/646—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 the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines
-
- 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
- A61K39/02—Bacterial antigens
- A61K39/09—Lactobacillales, e.g. aerococcus, enterococcus, lactobacillus, lactococcus, streptococcus
- A61K39/092—Streptococcus
-
- 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
- A61K39/02—Bacterial antigens
- A61K39/085—Staphylococcus
-
- 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
- A61K39/02—Bacterial antigens
- A61K39/09—Lactobacillales, e.g. aerococcus, enterococcus, lactobacillus, lactococcus, streptococcus
-
- 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
- A61K39/02—Bacterial antigens
- A61K39/116—Polyvalent bacterial 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
- 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
- A61K47/02—Inorganic compounds
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- A61K47/22—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
- A61K47/50—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
- A61K47/6415—Toxins or lectins, e.g. clostridial toxins or Pseudomonas exotoxins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- 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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55516—Proteins; Peptides
-
- 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
- A61K2039/6037—Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]
-
- 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
- A61K2039/70—Multivalent vaccine
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Inorganic Chemistry (AREA)
- Virology (AREA)
- Toxicology (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)
Abstract
Métodos para la preparación de formulaciones estables de vacunas antineumocóccicas conjugadas de polisacárido-proteína multivalentes. Las formulaciones estables de la presente presentan un porcentaje óptimo de adsorción para cada conjugado, en donde se puede prevenir la agregación mediante el uso de i) una adsorción individual o separada de conjugados que de lo contrario presentan un porcentaje de adsorción menor con una adsorción combinada ii) un sistema de solución amortiguadora de histidina-ácido succínico junto con un cambio en el pH de pH neutro a pH ácido iii) una relación de polisacárido a proteína de 0,5 a aproximadamente 1,4 iv) un impulsor de turbina tipo Rushton de seis hojas en los recipientes de formulación.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IN2185MU2015 | 2015-06-08 | ||
PCT/IB2016/053265 WO2016199003A1 (en) | 2015-06-08 | 2016-06-03 | Methods for improving the adsorption of polysaccharide-protein conjugates and multivalent vaccine formulation obtained thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
CO2017012628A2 true CO2017012628A2 (es) | 2018-03-28 |
Family
ID=57503115
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CONC2017/0012628A CO2017012628A2 (es) | 2015-06-08 | 2017-12-07 | Métodos para mejorar la adsorción de conjugados de polisacárido-proteína y una formulación de vacuna multivalente obtenida con los mismos |
Country Status (18)
Country | Link |
---|---|
US (1) | US10729780B2 (es) |
EP (1) | EP3302542A4 (es) |
JP (2) | JP7258463B2 (es) |
KR (1) | KR20240007690A (es) |
CN (1) | CN107847571A (es) |
AU (1) | AU2016276269B2 (es) |
BR (1) | BR112017026343A2 (es) |
CA (1) | CA2988366C (es) |
CO (1) | CO2017012628A2 (es) |
EA (1) | EA201792470A1 (es) |
IL (1) | IL256118B (es) |
MX (1) | MX2017015985A (es) |
MY (1) | MY187461A (es) |
PE (1) | PE20180460A1 (es) |
PH (1) | PH12017502244A1 (es) |
SA (1) | SA517390495B1 (es) |
WO (1) | WO2016199003A1 (es) |
ZA (1) | ZA201708325B (es) |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
RU2692923C2 (ru) | 2015-05-04 | 2019-06-28 | Пфайзер Инк. | Конъюгаты полисахарида стрептококка группы В и белка, способы получения конъюгатов, иммуногенные композиции, содержащие конъюгаты, и их применения |
WO2016199003A1 (en) * | 2015-06-08 | 2016-12-15 | Serum Institute Of India Private Ltd. | Methods for improving the adsorption of polysaccharide-protein conjugates and multivalent vaccine formulation obtained thereof |
CN106822884B (zh) * | 2016-12-28 | 2021-04-30 | 北京民海生物科技有限公司 | 一种多价肺炎球菌荚膜多糖结合疫苗的制备方法 |
CA3048981A1 (en) | 2016-12-30 | 2018-07-05 | Sutrovax, Inc. | Polypeptide-antigen conjugates with non-natural amino acids |
US11951165B2 (en) | 2016-12-30 | 2024-04-09 | Vaxcyte, Inc. | Conjugated vaccine carrier proteins |
EP3585803A4 (en) * | 2017-02-24 | 2020-11-11 | Merck Sharp & Dohme Corp. | PNEUMOCOCCIC CONJUGATE VACCINE FORMULATIONS |
US10729763B2 (en) | 2017-06-10 | 2020-08-04 | Inventprise, Llc | Mixtures of polysaccharide-protein pegylated compounds |
WO2019050814A1 (en) * | 2017-09-07 | 2019-03-14 | Merck Sharp & Dohme Corp. | ANTI-PNEUMOCOCCAL POLYSACCHARIDES AND THEIR USE IN IMMUNOGENIC CONJUGATES POLYSACCHARIDE-PROTEIN CARRIER |
JP7369123B2 (ja) | 2017-12-06 | 2023-10-25 | メルク・シャープ・アンド・ドーム・エルエルシー | 肺炎球菌多糖類-タンパク質コンジュゲートを含む組成物およびその使用方法 |
CN108524926B (zh) * | 2018-06-29 | 2021-06-29 | 康希诺生物股份公司 | 一种多价肺炎球菌结合疫苗的制剂组合及其应用 |
AU2019401535B2 (en) | 2018-12-19 | 2023-12-14 | Merck Sharp & Dohme Llc | Compositions comprising Streptococcus pneumoniae polysaccharide-protein conjugates and methods of use thereof |
JP2022535063A (ja) * | 2019-06-05 | 2022-08-04 | メルク・シャープ・アンド・ドーム・コーポレーション | 免疫原性血清型35b肺炎球菌多糖類-タンパク質コンジュゲート及びそれを作成するためのコンジュゲーションプロセス |
US20210070890A1 (en) | 2019-09-06 | 2021-03-11 | Serum Institute Of India Private Limited | Method for obtaining purified bacterial polysaccharides |
CN113607939A (zh) * | 2021-08-05 | 2021-11-05 | 艾美探索者生命科学研发有限公司 | 肺炎球菌多糖结合疫苗各型结合原液吸附率测定方法 |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2059692C (en) * | 1991-01-28 | 2004-11-16 | Peter J. Kniskern | Pneumoccoccal polysaccharide conjugate vaccine |
CN102302776B (zh) * | 2003-01-30 | 2014-06-18 | 诺华疫苗和诊断有限公司 | 抗多种脑膜炎球菌血清组的可注射性疫苗 |
CA2534870C (en) * | 2003-08-06 | 2014-05-06 | Che-Hung Robert Lee | Polysaccharide-protein conjugate vaccines |
RU2442825C2 (ru) * | 2005-04-18 | 2012-02-20 | Новартис Вэксинес Энд Дайэгностикс Инк. | Иммуногенные композиции, способы получения таких композиций и плазмида, включенная в такие композиции |
MY150719A (en) * | 2005-12-22 | 2014-02-28 | Glaxosmithkline Biolog Sa | Pneumococcal polysaccharide conjugate vaccine |
WO2007071786A2 (en) * | 2005-12-23 | 2007-06-28 | Glaxosmithkline Biologicals Sa | Conjugate vaccines |
TW200806315A (en) * | 2006-04-26 | 2008-02-01 | Wyeth Corp | Novel formulations which stabilize and inhibit precipitation of immunogenic compositions |
US9610340B2 (en) * | 2007-06-26 | 2017-04-04 | Glaxosmithkline Biologicals, S.A. | Vaccine comprising Streptococcus pneumoniae capsular polysaccharide conjugates |
TW201136603A (en) | 2010-02-09 | 2011-11-01 | Merck Sharp & Amp Dohme Corp | 15-valent pneumococcal polysaccharide-protein conjugate vaccine composition |
CA2819366A1 (en) * | 2010-12-10 | 2012-06-14 | Merck Sharp & Dohme Corp. | Novel formulations which mitigate agitation-induced aggregation of immunogenic compositions |
HUE040914T4 (hu) | 2012-01-30 | 2019-05-28 | Serum Institute Of India Pvt Ltd | Immunogén készítmény |
KR102057217B1 (ko) | 2012-06-20 | 2020-01-22 | 에스케이바이오사이언스 주식회사 | 다가 폐렴구균 다당류-단백질 접합체 조성물 |
CN104661684B (zh) * | 2012-08-16 | 2018-03-20 | 辉瑞公司 | 糖缀合方法和组合物 |
CN103893751B (zh) * | 2014-03-26 | 2016-04-20 | 天津康希诺生物技术有限公司 | 一种肺炎球菌多糖蛋白缀合疫苗及其制备方法 |
WO2016199003A1 (en) * | 2015-06-08 | 2016-12-15 | Serum Institute Of India Private Ltd. | Methods for improving the adsorption of polysaccharide-protein conjugates and multivalent vaccine formulation obtained thereof |
-
2016
- 2016-06-03 WO PCT/IB2016/053265 patent/WO2016199003A1/en active Application Filing
- 2016-06-03 BR BR112017026343-2A patent/BR112017026343A2/pt active Search and Examination
- 2016-06-03 JP JP2017564108A patent/JP7258463B2/ja active Active
- 2016-06-03 AU AU2016276269A patent/AU2016276269B2/en active Active
- 2016-06-03 KR KR1020237045298A patent/KR20240007690A/ko active Application Filing
- 2016-06-03 PE PE2017002539A patent/PE20180460A1/es unknown
- 2016-06-03 MY MYPI2017704714A patent/MY187461A/en unknown
- 2016-06-03 US US15/580,653 patent/US10729780B2/en active Active
- 2016-06-03 EA EA201792470A patent/EA201792470A1/ru unknown
- 2016-06-03 EP EP16806975.5A patent/EP3302542A4/en active Pending
- 2016-06-03 MX MX2017015985A patent/MX2017015985A/es unknown
- 2016-06-03 CN CN201680040596.5A patent/CN107847571A/zh active Pending
- 2016-06-03 CA CA2988366A patent/CA2988366C/en active Active
-
2017
- 2017-12-05 IL IL256118A patent/IL256118B/en unknown
- 2017-12-07 CO CONC2017/0012628A patent/CO2017012628A2/es unknown
- 2017-12-07 PH PH12017502244A patent/PH12017502244A1/en unknown
- 2017-12-07 ZA ZA2017/08325A patent/ZA201708325B/en unknown
- 2017-12-10 SA SA517390495A patent/SA517390495B1/ar unknown
-
2021
- 2021-08-06 JP JP2021129726A patent/JP2021185152A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
ZA201708325B (en) | 2019-05-29 |
NZ738090A (en) | 2023-09-29 |
PH12017502244A1 (en) | 2018-06-11 |
EP3302542A1 (en) | 2018-04-11 |
EA201792470A1 (ru) | 2018-10-31 |
MX2017015985A (es) | 2018-08-15 |
AU2016276269A1 (en) | 2018-01-18 |
CA2988366A1 (en) | 2016-12-15 |
KR20180030498A (ko) | 2018-03-23 |
BR112017026343A2 (pt) | 2019-11-19 |
SA517390495B1 (ar) | 2023-03-23 |
IL256118B (en) | 2021-12-01 |
KR20240007690A (ko) | 2024-01-16 |
EP3302542A4 (en) | 2019-04-10 |
JP2018516962A (ja) | 2018-06-28 |
US20180161445A1 (en) | 2018-06-14 |
US10729780B2 (en) | 2020-08-04 |
CN107847571A (zh) | 2018-03-27 |
WO2016199003A1 (en) | 2016-12-15 |
CA2988366C (en) | 2021-12-07 |
PE20180460A1 (es) | 2018-03-06 |
JP2021185152A (ja) | 2021-12-09 |
IL256118A (en) | 2018-02-28 |
JP7258463B2 (ja) | 2023-04-17 |
MY187461A (en) | 2021-09-23 |
AU2016276269B2 (en) | 2021-01-28 |
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