HRP20230738T1 - Depo sustavi koji sadrže glatiramer acetat - Google Patents
Depo sustavi koji sadrže glatiramer acetat Download PDFInfo
- Publication number
- HRP20230738T1 HRP20230738T1 HRP20230738TT HRP20230738T HRP20230738T1 HR P20230738 T1 HRP20230738 T1 HR P20230738T1 HR P20230738T T HRP20230738T T HR P20230738TT HR P20230738 T HRP20230738 T HR P20230738T HR P20230738 T1 HRP20230738 T1 HR P20230738T1
- Authority
- HR
- Croatia
- Prior art keywords
- depot formulation
- lesions
- rrms
- use according
- pronounced
- Prior art date
Links
- 108010072051 Glatiramer Acetate Proteins 0.000 title claims 22
- FHEAIOHRHQGZPC-KIWGSFCNSA-N acetic acid;(2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-aminopentanedioic acid;(2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound CC(O)=O.C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CCC(O)=O.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 FHEAIOHRHQGZPC-KIWGSFCNSA-N 0.000 title claims 20
- 229960003776 glatiramer acetate Drugs 0.000 title claims 20
- 238000009472 formulation Methods 0.000 claims 15
- 239000000203 mixture Substances 0.000 claims 15
- 230000003902 lesion Effects 0.000 claims 13
- 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 claims 12
- 208000024891 symptom Diseases 0.000 claims 6
- 239000007929 subcutaneous injection Substances 0.000 claims 5
- 238000010254 subcutaneous injection Methods 0.000 claims 5
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N Lactic Acid Natural products CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims 4
- 241001057495 Neda Species 0.000 claims 4
- 230000009266 disease activity Effects 0.000 claims 4
- 238000010255 intramuscular injection Methods 0.000 claims 4
- 239000007927 intramuscular injection Substances 0.000 claims 4
- 229910052688 Gadolinium Inorganic materials 0.000 claims 3
- 210000004556 brain Anatomy 0.000 claims 3
- 229940079593 drug Drugs 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 claims 3
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 claims 3
- YLOCGHYTXIINAI-XKUOMLDTSA-N (2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-aminopentanedioic acid;(2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CCC(O)=O.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 YLOCGHYTXIINAI-XKUOMLDTSA-N 0.000 claims 2
- 229920000954 Polyglycolide Polymers 0.000 claims 2
- 229920001577 copolymer Polymers 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 2
- 229940042385 glatiramer Drugs 0.000 claims 2
- 238000002347 injection Methods 0.000 claims 2
- 239000007924 injection Substances 0.000 claims 2
- 238000002595 magnetic resonance imaging Methods 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 201000006417 multiple sclerosis Diseases 0.000 claims 2
- 239000004633 polyglycolic acid Substances 0.000 claims 2
- 239000000243 solution Substances 0.000 claims 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 2
- 238000013019 agitation Methods 0.000 claims 1
- 238000004945 emulsification Methods 0.000 claims 1
- 239000011859 microparticle Substances 0.000 claims 1
- 239000004626 polylactic acid Substances 0.000 claims 1
- 239000007787 solid Substances 0.000 claims 1
- 238000003756 stirring Methods 0.000 claims 1
- 239000008215 water for injection Substances 0.000 claims 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/02—Peptides of undefined number of amino acids; Derivatives 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- 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
- A61K47/56—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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/593—Polyesters, e.g. PLGA or polylactide-co-glycolide
-
- 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
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Inorganic Chemistry (AREA)
- Neurology (AREA)
- Dermatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Transition And Organic Metals Composition Catalysts For Addition Polymerization (AREA)
- Epoxy Resins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Epoxy Compounds (AREA)
- Chemical Vapour Deposition (AREA)
Claims (12)
1. Depo formulacija koja sadrži dozu od 40 mg glatiramer acetata (GA) za
(i) ublažavanje barem jednog simptoma relapsno-remitirajuće multiple skleroze (RRMS) u osoba s RRMS-om ili osoba koje su doživjele prvu kliničku epizodu i u kojih je utvrđen visok rizik od razvoja klinički jasne multiple skleroze, pri čemu se simptom odabire iz skupine koja uključuje učestalost relapsa, broj izraženijih lezija ili broj novih lezija prema MR snimkama mozga i bolesnikov rezultat prema proširenoj ljestvici statusa onesposobljenosti (engl. Expanded Disability Status Scale, EDSS); ili
(ii) postizanje koncepta NEDA bez znakova aktivnosti bolesti (engl. No Evidence of Disease Activity) u osoba s RRMS-om, pri čemu NEDA podrazumijeva izostanak sljedećeg: relapsa, 12-tjedne potvrđene progresije onesposobljenosti (engl. Confirmed Disability Progression, CDP), novih/rastućih T2 lezija i T1 lezija izraženijih primjenom gadolinija u bolesnika,
pri čemu je depo formulaciju potrebno primijeniti u režimu jedne intramuskularne injekcije svakih 2 do 6 tjedana.
2. Depo formulacija za uporabu prema zahtjevu 1 koja se primjenjuje jednom svaka 4 tjedna.
3. Depo formulacija za uporabu prema zahtjevu 2 koja se primjenjuje jednom svaka 4 tjedna u razdoblju od jedne godine.
4. Depo formulacija za uporabu prema zahtjevu 1 ili 2, pri čemu ublažavanje simptoma uključuje:
smanjenje učestalosti relapsa; ili
smanjenje broja ili veličine izraženijih lezija ili broja novih lezija u mozgu, pri čemu je poželjno da ublažavanje simptoma uključuje smanjenje broja ili veličine lezija izraženijih primjenom gadolinija, smanjenje broja ili veličine izraženijih lezija na T1-ponderiranim snimkama ili smanjenje broja novih lezija na T2-ponderiranim snimkama bolesnika; ili smanjenje bolesnikova rezultata prema ljestvici EDSS.
5. Depo formulacija za uporabu prema zahtjevu 1, pri čemu je bolesnik primao potkožne injekcije od 20 mg GA-a jednom dnevno ili potkožne injekcije od 40 mg GA-a tri puta tjedno prije početka režima.
6. Depo formulacija za uporabu prema bilo kojem od prethodnih zahtjeva, koja nadalje sadrži farmaceutski prihvatljiv biorazgradivi nositelj odabran iz skupine koju čine kopolimer mliječne i glikolne kiseline (PLGA), polilaktična kiselina (PLA), poliglikolna kiselina (PGA) i bilo koja njihova kombinacija, pri čemu je poželjno da je biorazgradivi nositelj PLGA.
7. Depo formulacija za uporabu prema bilo kojem od prethodnih zahtjeva, koja je u obliku mikročestica pripremljenih dvostrukim postupkom emulzije „voda u ulju u vodi” (V-U-V).
8. Depo formulacija za uporabu prema bilo kojem od prethodnih zahtjeva, koja sadrži od 20 % do 30 % krute tvari.
9. Depo formulacija za uporabu prema bilo kojem od zahtjeva 6 do 8, pri čemu je težinski omjer između GA-a i farmaceutski prihvatljivog biorazgradivog nositelja između 1 : 1 i 1 : 100, pri čemu je poželjno da težinski omjer između GA-a i farmaceutski prihvatljivog biorazgradivog nositelja iznosi između 1 : 5 i 1 : 25.
10. Depo formulacija za uporabu prema bilo kojem od prethodnih zahtjeva, koja oslobađa oko 80 % glatiramera unutar 22 dana u otopinu PBS na 37 °C uz kontinuirano miješanje, ili koja oslobađa oko 20 % glatiramera unutar 5 dana u otopinu PBS na 37 °C uz kontinuirano miješanje.
11. Depo formulacija koja sadrži dozu od 40 mg glatiramer acetata (GA) za povećanje podnošljivosti lijeka GA u osoba s relapsno-remitirajućom multiplom sklerozom (RRMS), pri čemu se depo formulacija treba primijeniti u režimu od jedne intramuskularne injekcije svakih 2 do 6 tjedana, pri čemu metoda sadrži smanjenje učestalosti potkožnih injekcija s potkožnih injekcija u dozi od 20 mg GA-a primijenjenih jednom dnevno ili potkožnih injekcija u dozi od 40 mg GA-a tri puta tjedno, uz najmanje jedan dan između svake injekcije, na režim jedne intramuskularne injekcije depo formulacije u dozi od 40 mg GA-a svakih 2 do 6 tjedana, kako bi se time povećala podnošljivost bolesnika na lijek GA.
12. Komplet koji sadrži prvi spremnik koji sadrži lijek GA kapsuliran kopolimerom mliječne i glikolne kiseline (PLGA) i drugi odvojeni spremnik koji sadrži farmaceutski prihvatljiv razrjeđivač za injekciju, pri čemu komplet sadrži 40 mg GA-a i vodu za injekciju, ili pri čemu se miješanjem sadržaja prvog spremnika i drugog spremnika dobiva 40 mg GA-a po 2 ml razrjeđivača, pri čemu je komplet namijenjen za
(i) ublažavanje barem jednog simptoma relapsno-remitirajuće multiple skleroze (RRMS) u osoba s RRMS-om ili osoba koje su doživjele prvu kliničku epizodu i u kojih je utvrđen visok rizik od razvoja klinički jasne multiple skleroze, pri čemu se simptom odabire iz skupine koja uključuje učestalost relapsa, broj izraženijih lezija ili broj novih lezija prema MR snimkama mozga i bolesnikov rezultat prema proširenoj ljestvici statusa onesposobljenosti (engl. Expanded Disability Status Scale, EDSS); ili
(ii) postizanje koncepta NEDA bez znakova aktivnosti bolesti (engl. No Evidence of Disease Activity) u osoba s RRMS-om, pri čemu NEDA podrazumijeva izostanak sljedećeg: relapsa, 12-tjedne potvrđene progresije onesposobljenosti (engl. Confirmed Disability Progression, CDP), novih/rastućih T2 lezija i T1 lezija izraženijih primjenom gadolinija u bolesnika; ili
(iii) povećanje podnošljivosti lijeka GA u bolesnika s relapsno-remitirajućom multiplom sklerozom (RRMS),
metoda koja sadrži jednu intramuskularnu injekciju depo formulacije koja sadrži dozu od 40 mg glatiramer acetata (GA) svakih 2 do 6 tjedana.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201662381598P | 2016-08-31 | 2016-08-31 | |
EP17845658.8A EP3506921B1 (en) | 2016-08-31 | 2017-08-09 | Depot systems comprising glatiramer acetate |
PCT/IL2017/050882 WO2018042415A1 (en) | 2016-08-31 | 2017-08-09 | Depot systems comprising glatiramer acetate |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20230738T1 true HRP20230738T1 (hr) | 2023-10-27 |
Family
ID=61300274
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HRP20230738TT HRP20230738T1 (hr) | 2016-08-31 | 2017-08-09 | Depo sustavi koji sadrže glatiramer acetat |
Country Status (20)
Country | Link |
---|---|
US (1) | US20210283209A1 (hr) |
EP (2) | EP4252849A3 (hr) |
JP (1) | JP7193448B2 (hr) |
CN (1) | CN109982712A (hr) |
AU (1) | AU2017319728A1 (hr) |
BR (1) | BR112019003594A2 (hr) |
CA (1) | CA3035147A1 (hr) |
DK (1) | DK3506921T3 (hr) |
ES (1) | ES2952044T3 (hr) |
FI (1) | FI3506921T3 (hr) |
HR (1) | HRP20230738T1 (hr) |
HU (1) | HUE062393T2 (hr) |
IL (2) | IL301455B2 (hr) |
LT (1) | LT3506921T (hr) |
MX (1) | MX2019002284A (hr) |
PL (1) | PL3506921T3 (hr) |
PT (1) | PT3506921T (hr) |
RS (1) | RS64445B1 (hr) |
SI (1) | SI3506921T1 (hr) |
WO (1) | WO2018042415A1 (hr) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BR112019003131A2 (pt) | 2016-08-28 | 2019-05-21 | Mapi Pharma Ltd. | processo para preparar micropartículas contendo acetato de glatirâmero |
MX2019010174A (es) | 2017-03-26 | 2019-10-15 | Mapi Pharma Ltd | Sistemas de deposito de glatiramer para el tratamiento de formas progresivas de esclerosis multiple. |
US11865213B2 (en) | 2021-07-05 | 2024-01-09 | Mapi Pharma Ltd. | Semaglutide depot systems and use thereof |
WO2023170493A1 (en) * | 2022-03-07 | 2023-09-14 | Hadidi Naghmeh | Drug delivery using a parenteral pharmaceutical composition |
WO2023175598A1 (en) * | 2022-03-17 | 2023-09-21 | Mapi Pharma Ltd. | Depot systems comprising cariprazine or salts thereof |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3773919A (en) | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
US5800808A (en) | 1994-05-24 | 1998-09-01 | Veda Research And Development Co., Ltd. | Copolymer-1 improvements in compositions of copolymers |
US6214791B1 (en) | 1997-01-10 | 2001-04-10 | Yeda Research And Development Co. Ltd. | Treatment of multiple sclerosis through ingestion or inhalation of copolymer-1 |
US8871241B2 (en) | 2002-05-07 | 2014-10-28 | Psivida Us, Inc. | Injectable sustained release delivery devices |
RS52885B (en) | 2009-08-20 | 2014-02-28 | Yeda Research And Development Co. Ltd. | LOW-FREQUENCY GLATIRAMER ACETATOM THERAPY |
JP5916622B2 (ja) | 2010-01-04 | 2016-05-11 | マピ ファーマ リミテッド | グラチラマーまたはその薬理学的に許容される塩を含むデポーシステム |
EA201390144A1 (ru) * | 2010-08-20 | 2013-06-28 | Серулин Фарма Инк. | Конъюгаты терапевтический пептид-полимер, частицы, композиции и связанные с ними способы |
PL2529757T3 (pl) * | 2011-05-31 | 2014-04-30 | Farm Rovi Lab Sa | Formulacja implantu zawierającego paliperydon |
CN103169670B (zh) * | 2013-03-22 | 2016-07-06 | 深圳翰宇药业股份有限公司 | 一种醋酸格拉替雷微球及其制备方法 |
US20210220428A1 (en) * | 2016-06-30 | 2021-07-22 | Stem Cell Medicine Ltd. | Treatment of inflammatory bowel disease with long acting glatiramer and adipose-derived stem cells |
BR112019003131A2 (pt) * | 2016-08-28 | 2019-05-21 | Mapi Pharma Ltd. | processo para preparar micropartículas contendo acetato de glatirâmero |
-
2017
- 2017-08-09 JP JP2019508893A patent/JP7193448B2/ja active Active
- 2017-08-09 US US16/328,582 patent/US20210283209A1/en active Pending
- 2017-08-09 SI SI201731391T patent/SI3506921T1/sl unknown
- 2017-08-09 RS RS20230617A patent/RS64445B1/sr unknown
- 2017-08-09 LT LTEPPCT/IL2017/050882T patent/LT3506921T/lt unknown
- 2017-08-09 HU HUE17845658A patent/HUE062393T2/hu unknown
- 2017-08-09 DK DK17845658.8T patent/DK3506921T3/da active
- 2017-08-09 CA CA3035147A patent/CA3035147A1/en active Pending
- 2017-08-09 WO PCT/IL2017/050882 patent/WO2018042415A1/en active Application Filing
- 2017-08-09 CN CN201780068092.9A patent/CN109982712A/zh active Pending
- 2017-08-09 HR HRP20230738TT patent/HRP20230738T1/hr unknown
- 2017-08-09 AU AU2017319728A patent/AU2017319728A1/en active Pending
- 2017-08-09 PT PT178456588T patent/PT3506921T/pt unknown
- 2017-08-09 MX MX2019002284A patent/MX2019002284A/es unknown
- 2017-08-09 EP EP23173177.9A patent/EP4252849A3/en active Pending
- 2017-08-09 EP EP17845658.8A patent/EP3506921B1/en active Active
- 2017-08-09 IL IL301455A patent/IL301455B2/en unknown
- 2017-08-09 ES ES17845658T patent/ES2952044T3/es active Active
- 2017-08-09 BR BR112019003594-0A patent/BR112019003594A2/pt unknown
- 2017-08-09 FI FIEP17845658.8T patent/FI3506921T3/fi active
- 2017-08-09 PL PL17845658.8T patent/PL3506921T3/pl unknown
-
2019
- 2019-02-19 IL IL264914A patent/IL264914B2/en unknown
Also Published As
Publication number | Publication date |
---|---|
EP4252849A2 (en) | 2023-10-04 |
DK3506921T3 (da) | 2023-07-31 |
CN109982712A (zh) | 2019-07-05 |
SI3506921T1 (sl) | 2023-10-30 |
EP3506921A4 (en) | 2020-05-06 |
BR112019003594A2 (pt) | 2019-05-21 |
EP3506921A1 (en) | 2019-07-10 |
IL264914B1 (en) | 2023-04-01 |
EP4252849A3 (en) | 2023-11-01 |
JP2019530648A (ja) | 2019-10-24 |
LT3506921T (lt) | 2023-08-10 |
IL264914A (hr) | 2019-04-30 |
IL301455A (en) | 2023-05-01 |
MX2019002284A (es) | 2019-09-04 |
FI3506921T3 (fi) | 2023-07-21 |
HUE062393T2 (hu) | 2023-11-28 |
CA3035147A1 (en) | 2018-03-08 |
IL301455B1 (en) | 2023-12-01 |
US20210283209A1 (en) | 2021-09-16 |
RS64445B1 (sr) | 2023-09-29 |
IL264914B2 (en) | 2023-08-01 |
ES2952044T3 (es) | 2023-10-26 |
JP7193448B2 (ja) | 2022-12-20 |
EP3506921B1 (en) | 2023-05-17 |
IL301455B2 (en) | 2024-04-01 |
WO2018042415A1 (en) | 2018-03-08 |
PT3506921T (pt) | 2023-08-07 |
PL3506921T3 (pl) | 2023-08-21 |
AU2017319728A1 (en) | 2019-02-07 |
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