RS61693B1 - 4,6-supstituisani-pirazolo[1,5-a]pirazini kao inhibitori janus kinaze - Google Patents

4,6-supstituisani-pirazolo[1,5-a]pirazini kao inhibitori janus kinaze

Info

Publication number
RS61693B1
RS61693B1 RS20210415A RSP20210415A RS61693B1 RS 61693 B1 RS61693 B1 RS 61693B1 RS 20210415 A RS20210415 A RS 20210415A RS P20210415 A RSP20210415 A RS P20210415A RS 61693 B1 RS61693 B1 RS 61693B1
Authority
RS
Serbia
Prior art keywords
alkyl
pyrazol
mmol
hetcyc
formula
Prior art date
Application number
RS20210415A
Other languages
English (en)
Serbian (sr)
Inventor
Shelley Allen
Mark Laurence Boys
Mark J Chicarelli
Jay Bradford Fell
John P Fischer
John Gaudino
Erik James Hicken
Ronald Jay Hinklin
Christopher F Kraser
Ellen Laird
John E Robinson
Tony P Tang
Laurence E Burgess
Robert Andrew Rieger
Jed Pheneger
Yoshitaka Satoh
Katerina Leftheris
Raj K Raheja
Brydon L Bennett
Original Assignee
Array Biopharma Inc
Celgene Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Array Biopharma Inc, Celgene Corp filed Critical Array Biopharma Inc
Publication of RS61693B1 publication Critical patent/RS61693B1/sr

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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
    • A61K31/495—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
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • 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
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • 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
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • 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
    • 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
    • A61P37/02—Immunomodulators
    • 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
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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
    • A61P37/08—Antiallergic 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
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Diabetes (AREA)
  • Rheumatology (AREA)
  • Hematology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Obesity (AREA)
  • Pain & Pain Management (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Pulmonology (AREA)
  • Dermatology (AREA)
  • Oncology (AREA)
  • Hospice & Palliative Care (AREA)
  • Communicable Diseases (AREA)
  • Endocrinology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Psychiatry (AREA)
  • Transplantation (AREA)
  • Ophthalmology & Optometry (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Emergency Medicine (AREA)
RS20210415A 2014-12-05 2015-12-04 4,6-supstituisani-pirazolo[1,5-a]pirazini kao inhibitori janus kinaze RS61693B1 (sr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201462088068P 2014-12-05 2014-12-05
EP15819933.1A EP3227297B1 (en) 2014-12-05 2015-12-04 4,6-substituted-pyrazolo[1,5-a]pyrazines as janus kinase inhibitors
PCT/US2015/064062 WO2016090285A1 (en) 2014-12-05 2015-12-04 4,6-SUBSTITUTED-PYRAZOLO[1,5-a]PYRAZINES AS JANUS KINASE INHIBITORS

Publications (1)

Publication Number Publication Date
RS61693B1 true RS61693B1 (sr) 2021-05-31

Family

ID=55069089

Family Applications (1)

Application Number Title Priority Date Filing Date
RS20210415A RS61693B1 (sr) 2014-12-05 2015-12-04 4,6-supstituisani-pirazolo[1,5-a]pirazini kao inhibitori janus kinaze

Country Status (29)

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US (3) US10189845B2 (cg-RX-API-DMAC7.html)
EP (2) EP3878451A1 (cg-RX-API-DMAC7.html)
JP (2) JP6641373B2 (cg-RX-API-DMAC7.html)
KR (1) KR20170090476A (cg-RX-API-DMAC7.html)
CN (1) CN107278203B (cg-RX-API-DMAC7.html)
AU (1) AU2015357585B2 (cg-RX-API-DMAC7.html)
BR (1) BR112017011798A2 (cg-RX-API-DMAC7.html)
CA (1) CA2969709A1 (cg-RX-API-DMAC7.html)
CL (1) CL2017001422A1 (cg-RX-API-DMAC7.html)
CO (1) CO2017006674A2 (cg-RX-API-DMAC7.html)
CR (1) CR20170309A (cg-RX-API-DMAC7.html)
DK (1) DK3227297T3 (cg-RX-API-DMAC7.html)
ES (1) ES2865483T3 (cg-RX-API-DMAC7.html)
HR (1) HRP20210501T1 (cg-RX-API-DMAC7.html)
HU (1) HUE054371T2 (cg-RX-API-DMAC7.html)
IL (1) IL252656A0 (cg-RX-API-DMAC7.html)
MX (1) MX386316B (cg-RX-API-DMAC7.html)
MY (1) MY191016A (cg-RX-API-DMAC7.html)
PH (1) PH12017501032A1 (cg-RX-API-DMAC7.html)
PL (1) PL3227297T3 (cg-RX-API-DMAC7.html)
PT (1) PT3227297T (cg-RX-API-DMAC7.html)
RS (1) RS61693B1 (cg-RX-API-DMAC7.html)
RU (2) RU2021102805A (cg-RX-API-DMAC7.html)
SG (1) SG11201704542SA (cg-RX-API-DMAC7.html)
SI (1) SI3227297T1 (cg-RX-API-DMAC7.html)
TW (1) TWI725004B (cg-RX-API-DMAC7.html)
UA (1) UA120065C2 (cg-RX-API-DMAC7.html)
WO (1) WO2016090285A1 (cg-RX-API-DMAC7.html)
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WO2017156493A1 (en) 2016-03-11 2017-09-14 Denali Therapeutics Inc. Compounds, compositions, and methods
RU2021102805A (ru) 2014-12-05 2021-02-12 Эррэй Биофарма Инк. 4,6-ЗАМЕЩЕННЫЕ ПИРАЗОЛО[1,5-a]ПИРАЗИНЫ В КАЧЕСТВЕ ИНГИБИТОРОВ ЯНУС-КИНАЗЫ
AU2017222417B2 (en) 2016-02-24 2020-07-09 Pfizer Inc. Pyrazolo[1,5-a]pyrazin-4-yl derivatives as JAK-inhibitors
SG10201912632YA (en) 2016-06-16 2020-02-27 Denali Therapeutics Inc Pyrimidin-2-ylamino-1h-pyrazols as lrrk2 inhibitors for use in the treatment of neurodegenerative disorders
GB201617758D0 (en) * 2016-10-20 2016-12-07 Almac Discovery Limited Pharmaceutical compounds
CA3049136C (en) 2017-01-18 2022-06-14 Array Biopharma Inc. Substituted pyrazolo[1,5-a]pyrazine compounds as ret kinase inhibitors
US20200157081A1 (en) * 2017-05-24 2020-05-21 Denali Therapeutics Inc. Compounds, compositions and methods
US11254668B2 (en) 2017-08-14 2022-02-22 Pfizer Inc. Pyrazolo[1,5-A]pyrazin-4-yl and related derivatives
EP3740486A1 (en) 2018-01-18 2020-11-25 Array Biopharma, Inc. Substituted pyrazolyl[4,3-c]pyridinecompounds as ret kinase inhibitors
CN111630054B (zh) 2018-01-18 2023-05-09 奥瑞生物药品公司 作为RET激酶抑制剂的取代的吡唑并[3,4-d]嘧啶化合物
EP3740491A1 (en) 2018-01-18 2020-11-25 Array Biopharma, Inc. Substituted pyrrolo[2,3-d]pyrimidines compounds as ret kinase inhibitors
ES2922314T3 (es) 2018-09-10 2022-09-13 Array Biopharma Inc Compuestos heterocíclicos condensados como inhibidores de cinasa RET
ES2981909T3 (es) * 2019-04-12 2024-10-11 Primegene Beijing Co Ltd Compuestos derivados de pirazolopirazina, composición farmacéutica y utilización de los mismos
JOP20210298A1 (ar) 2019-05-14 2023-01-30 Provention Bio Inc طرق وتركيبات للوقاية من مرض السكري من النوع الأول
CN113150012B (zh) * 2020-01-22 2023-03-24 浙江海正药业股份有限公司 吡唑并[1,5-a]吡嗪类衍生物及其制备方法和用途
CA3177852A1 (en) 2020-04-04 2021-10-07 Pfizer Inc. Methods of treating coronavirus disease 2019
KR20230092863A (ko) 2020-06-11 2023-06-26 프로벤션 바이오, 인코포레이티드 제1형 당뇨병을 예방하기 위한 방법 및 조성물
US20250011332A1 (en) * 2021-11-12 2025-01-09 Soter Biopharma Pte. Ltd. Pyrazolo fused ring compound and use thereof
WO2024235167A1 (zh) * 2023-05-12 2024-11-21 海南康哲美丽科技有限公司 一种吡唑并吡嗪类化合物及其晶型的制备方法

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JP6641373B2 (ja) 2020-02-05
RU2017123387A3 (cg-RX-API-DMAC7.html) 2019-06-03
DK3227297T3 (da) 2021-04-06
WO2016090285A1 (en) 2016-06-09
CN107278203B (zh) 2020-05-19
UA120065C2 (uk) 2019-09-25
TWI725004B (zh) 2021-04-21
TW201632523A (zh) 2016-09-16
US10730880B2 (en) 2020-08-04
ZA201704494B (en) 2022-03-30
ES2865483T3 (es) 2021-10-15
MX2017007284A (es) 2017-08-25
MX386316B (es) 2025-03-18
RU2742938C2 (ru) 2021-02-11
HRP20210501T1 (hr) 2021-05-14
US10189845B2 (en) 2019-01-29
EP3227297B1 (en) 2021-01-20
RU2021102805A (ru) 2021-02-12
RU2017123387A (ru) 2019-01-11
IL252656A0 (en) 2017-07-31
US20170362240A1 (en) 2017-12-21
PH12017501032A1 (en) 2017-11-27
JP2018507167A (ja) 2018-03-15
AU2015357585A1 (en) 2017-07-13
CA2969709A1 (en) 2016-06-09
CN107278203A (zh) 2017-10-20
JP2020055859A (ja) 2020-04-09
EP3227297A1 (en) 2017-10-11
KR20170090476A (ko) 2017-08-07
US11028093B2 (en) 2021-06-08
PT3227297T (pt) 2021-04-09
US20190177328A1 (en) 2019-06-13
US20200291039A1 (en) 2020-09-17
BR112017011798A2 (pt) 2017-12-26
CL2017001422A1 (es) 2018-01-05
EP3878451A1 (en) 2021-09-15
PL3227297T3 (pl) 2021-10-25
SI3227297T1 (sl) 2021-04-30
SG11201704542SA (en) 2017-07-28
AU2015357585B2 (en) 2020-07-02
MY191016A (en) 2022-05-28
CO2017006674A2 (es) 2017-10-20
HUE054371T2 (hu) 2021-09-28
CR20170309A (es) 2018-02-02

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