JP7065030B2 - Ｒｓｖの処置のための組合せ製品 - Google Patents

Ｒｓｖの処置のための組合せ製品 Download PDF

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JP7065030B2
JP7065030B2 JP2018540796A JP2018540796A JP7065030B2 JP 7065030 B2 JP7065030 B2 JP 7065030B2 JP 2018540796 A JP2018540796 A JP 2018540796A JP 2018540796 A JP2018540796 A JP 2018540796A JP 7065030 B2 JP7065030 B2 JP 7065030B2
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compound
pharmaceutical composition
methyl
rsv
combination
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JP2019504102A (ja
JP2019504102A5 (enExample
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イセバート，ニーナ
イーサ イー． ゴーイバーツ，ネレ
アンドレ イー． ロイマンズ，ダーク
コール，アニル
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ヤンセン・サイエンシズ・アイルランド・アンリミテッド・カンパニー
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
    • 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
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • 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
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/42—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum viral
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • 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
    • A61P31/12—Antivirals
    • 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
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/08—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from viruses
    • C07K16/10—RNA viruses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/08—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from viruses
    • C07K16/10—RNA viruses
    • C07K16/11—Paramyxoviridae (F); Pneumoviridae (F), e.g. respiratory syncytial virus [RSV]
    • 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
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Virology (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
JP2018540796A 2016-02-03 2017-02-02 Ｒｓｖの処置のための組合せ製品 Expired - Fee Related JP7065030B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP16154035.6 2016-02-03
EP16154035 2016-02-03
PCT/EP2017/052201 WO2017134133A1 (en) 2016-02-03 2017-02-02 Combination products for the treatment of rsv

Publications (3)

Publication Number Publication Date
JP2019504102A JP2019504102A (ja) 2019-02-14
JP2019504102A5 JP2019504102A5 (enExample) 2020-03-12
JP7065030B2 true JP7065030B2 (ja) 2022-05-11

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JP2018540796A Expired - Fee Related JP7065030B2 (ja) 2016-02-03 2017-02-02 Ｒｓｖの処置のための組合せ製品

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US (1) US10363253B2 (enExample)
EP (2) EP3411028B1 (enExample)
JP (1) JP7065030B2 (enExample)
KR (1) KR20180108598A (enExample)
CN (2) CN108601774B (enExample)
AU (2) AU2017214246B2 (enExample)
BR (1) BR112018014958A2 (enExample)
CA (1) CA3006488A1 (enExample)
CL (3) CL2018001808A1 (enExample)
EA (3) EA202092250A1 (enExample)
ES (1) ES2877808T3 (enExample)
IL (2) IL259669B (enExample)
MX (2) MX2020012592A (enExample)
MY (1) MY197217A (enExample)
PH (2) PH12020551598B1 (enExample)
SG (1) SG11201806581TA (enExample)
UA (1) UA124099C2 (enExample)
WO (1) WO2017134133A1 (enExample)
ZA (1) ZA201805205B (enExample)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2957868C (en) 2014-10-10 2023-02-28 Pulmocide Limited Novel 5,6-dihydro-4h-benzo[b]thieno-[2,3-d]azepine derivative
US10160772B2 (en) 2014-12-18 2018-12-25 Pulmocide Limited 5,6-dihydro-4H-benzo[b]thieno-[2,3-d]azepine derivatives
US10626126B2 (en) 2016-04-08 2020-04-21 Pulmocide Limited Compounds
TW201936193A (zh) 2017-12-05 2019-09-16 愛爾蘭商健生科學愛爾蘭無限公司 使用組合產品治療ｒｓｖ
PH12022551042A1 (en) * 2019-10-30 2023-05-29 Janssen Sciences Ireland Unlimited Co Synthesis of 3-({5-chloro-1-[3-(methylsulfonyl)propyl]-1h-indol-2 yl} methyl)-1-(2,2,2-trifluoroethyl)-1,3-dihydro-2h-imidazo[4,5-c]pyridin-2-one
CN114014856B (zh) * 2021-11-26 2023-12-22 嘉兴安谛康生物科技有限公司 作为呼吸道合胞病毒抗病毒剂的咪唑并吡啶类衍生物
CN116077494A (zh) * 2023-01-11 2023-05-09 黑龙江中医药大学 一种治疗呼吸道合胞病毒的药物组合物及其制备方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2014503525A (ja) 2010-12-16 2014-02-13 ヤンセン・アールアンドデイ・アイルランド 呼吸合胞体ウイルスの抗ウイルス剤としてのインドール
WO2014174018A1 (en) 2013-04-25 2014-10-30 Crucell Holland B.V. Stabilized soluble prefusion rsv f polypeptides
WO2015026792A1 (en) 2013-08-21 2015-02-26 Alios Biopharma, Inc. Antiviral compounds
WO2016055791A1 (en) 2014-10-10 2016-04-14 Pulmocide Limited Novel 5,6-dihydro-4H-benzo[b]thieno-[2,3-d]azepine derivative

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2014503525A (ja) 2010-12-16 2014-02-13 ヤンセン・アールアンドデイ・アイルランド 呼吸合胞体ウイルスの抗ウイルス剤としてのインドール
WO2014174018A1 (en) 2013-04-25 2014-10-30 Crucell Holland B.V. Stabilized soluble prefusion rsv f polypeptides
WO2015026792A1 (en) 2013-08-21 2015-02-26 Alios Biopharma, Inc. Antiviral compounds
WO2016055791A1 (en) 2014-10-10 2016-04-14 Pulmocide Limited Novel 5,6-dihydro-4H-benzo[b]thieno-[2,3-d]azepine derivative

Non-Patent Citations (8)

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Title
Antimicrobial Agents and Chemotherapy，2015年12月14日，Vol.60, No.3，p.1264-1273
Antiviral Research，2003年，Vol.60, No.1，p.51-59
DRUGS OF THE FUTURE，2015年，Vol.40, No.11，p.765-766
JOURNAL OF VIROLOGY，2005年，Vol.79, No.20，p.13105-13115
MEJIAS ASUNCION，NEW OPTIONS IN THE TREATMENT OF RESPIRATORY SYNCYTIAL VIRUS DISEASE，JOURNAL OF INFECTION，2015年04月25日，VOL:71，PAGE(S):S80-S87，http://dx.doi.org/10.1016/j.jinf.2015.04.025
The NEW ENGLAND JOURNAL of MEDICINE，2014年，Vol.371, No.8，p.711-722
WORLD JOURNAL OF PEDIATRICS，2010年，Vol.6, No.4，p.296-300
XIONG HUI; FOULK MELINDA; ET AL，DISCOVERY OF A POTENT RESPIRATORY SYNCYTIAL VIRUS RNA POLYMERASE INHIBITOR，BIOORGANIC & MEDICINAL CHEMISTRY LETTERS，NL，PERGAMON，2013年10月16日，VOL:23, NR:24，PAGE(S):6789 - 6793，http://dx.doi.org/10.1016/j.bmcl.2013.10.018

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IL277281B (en) 2021-04-29
EA201891655A1 (ru) 2018-12-28
AU2017214246A1 (en) 2018-06-21
PH12020551598B1 (en) 2024-05-17
CN108601774B (zh) 2021-09-21
UA124099C2 (uk) 2021-07-21
EP3892273A2 (en) 2021-10-13
CN112245429A (zh) 2021-01-22
MX381654B (es) 2025-03-13
EP3411028A1 (en) 2018-12-12
CA3006488A1 (en) 2017-08-10
MY197217A (en) 2023-06-01
MX2018009422A (es) 2018-12-19
PH12020551598A1 (en) 2021-05-10
AU2022202070A1 (en) 2022-04-14
EA037206B1 (ru) 2021-02-19
KR20180108598A (ko) 2018-10-04
PH12018501649A1 (en) 2019-06-03
BR112018014958A2 (pt) 2019-01-08
US10363253B2 (en) 2019-07-30
MX2020012592A (es) 2022-10-27
SG11201806581TA (en) 2018-09-27
ZA201805205B (en) 2020-10-28
ES2877808T3 (es) 2021-11-17
EA202092251A1 (ru) 2020-12-11
WO2017134133A1 (en) 2017-08-10
JP2019504102A (ja) 2019-02-14
US20190054084A1 (en) 2019-02-21
CL2019001455A1 (es) 2019-08-16
IL259669A (en) 2018-07-31
IL259669B (en) 2021-03-25
CL2018001808A1 (es) 2018-08-31
AU2017214246B2 (en) 2022-03-31
EP3892273A3 (en) 2021-12-22
IL277281A (en) 2020-10-29
CL2019001454A1 (es) 2019-08-16
EA202092250A1 (ru) 2020-12-11
CN108601774A (zh) 2018-09-28
PH12018501649B1 (en) 2021-10-13
EP3411028B1 (en) 2021-05-05

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