HRP20230474T1 - Postupci za dobivanje stanica izvedenih iz mišića - Google Patents
Postupci za dobivanje stanica izvedenih iz mišića Download PDFInfo
- Publication number
- HRP20230474T1 HRP20230474T1 HRP20230474TT HRP20230474T HRP20230474T1 HR P20230474 T1 HRP20230474 T1 HR P20230474T1 HR P20230474T T HRP20230474T T HR P20230474TT HR P20230474 T HRP20230474 T HR P20230474T HR P20230474 T1 HRP20230474 T1 HR P20230474T1
- Authority
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- Croatia
- Prior art keywords
- smdc
- cell population
- sample
- treatment
- range
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims 15
- 210000003205 muscle Anatomy 0.000 title claims 3
- 210000004027 cell Anatomy 0.000 claims 22
- 238000002347 injection Methods 0.000 claims 9
- 239000007924 injection Substances 0.000 claims 9
- 239000000243 solution Substances 0.000 claims 5
- 230000001464 adherent effect Effects 0.000 claims 4
- 238000001816 cooling Methods 0.000 claims 4
- 210000002027 skeletal muscle Anatomy 0.000 claims 4
- 206010021639 Incontinence Diseases 0.000 claims 3
- 239000006285 cell suspension Substances 0.000 claims 3
- 239000000725 suspension Substances 0.000 claims 3
- 208000034347 Faecal incontinence Diseases 0.000 claims 2
- 208000021642 Muscular disease Diseases 0.000 claims 2
- 201000009623 Myopathy Diseases 0.000 claims 2
- 206010029323 Neuromyopathy Diseases 0.000 claims 2
- 206010046543 Urinary incontinence Diseases 0.000 claims 2
- 230000004064 dysfunction Effects 0.000 claims 2
- 238000011534 incubation Methods 0.000 claims 2
- 230000002265 prevention Effects 0.000 claims 2
- 210000005070 sphincter Anatomy 0.000 claims 2
- 230000002485 urinary effect Effects 0.000 claims 2
- 102000029816 Collagenase Human genes 0.000 claims 1
- 108060005980 Collagenase Proteins 0.000 claims 1
- 102000016911 Deoxyribonucleases Human genes 0.000 claims 1
- 108010053770 Deoxyribonucleases Proteins 0.000 claims 1
- 102100036912 Desmin Human genes 0.000 claims 1
- 108010044052 Desmin Proteins 0.000 claims 1
- 108090000790 Enzymes Proteins 0.000 claims 1
- 102000004190 Enzymes Human genes 0.000 claims 1
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 claims 1
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 claims 1
- 101000581981 Homo sapiens Neural cell adhesion molecule 1 Proteins 0.000 claims 1
- 108010003272 Hyaluronate lyase Proteins 0.000 claims 1
- 102000001974 Hyaluronidases Human genes 0.000 claims 1
- 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 claims 1
- 102000016387 Pancreatic elastase Human genes 0.000 claims 1
- 108010067372 Pancreatic elastase Proteins 0.000 claims 1
- 108090000526 Papain Proteins 0.000 claims 1
- 239000004365 Protease Substances 0.000 claims 1
- 101001023030 Toxoplasma gondii Myosin-D Proteins 0.000 claims 1
- 102000004142 Trypsin Human genes 0.000 claims 1
- 108090000631 Trypsin Proteins 0.000 claims 1
- 239000011324 bead Substances 0.000 claims 1
- 238000005119 centrifugation Methods 0.000 claims 1
- 229960002424 collagenase Drugs 0.000 claims 1
- 210000005045 desmin Anatomy 0.000 claims 1
- 230000002255 enzymatic effect Effects 0.000 claims 1
- 229940088598 enzyme Drugs 0.000 claims 1
- 210000005071 external anal sphincter Anatomy 0.000 claims 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 claims 1
- 238000010438 heat treatment Methods 0.000 claims 1
- 229960002773 hyaluronidase Drugs 0.000 claims 1
- AFCCDDWKHLHPDF-UHFFFAOYSA-M metam-sodium Chemical compound [Na+].CNC([S-])=S AFCCDDWKHLHPDF-UHFFFAOYSA-M 0.000 claims 1
- 230000003287 optical effect Effects 0.000 claims 1
- 229940055729 papain Drugs 0.000 claims 1
- 235000019834 papain Nutrition 0.000 claims 1
- 239000008188 pellet Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 210000002966 serum Anatomy 0.000 claims 1
- 210000001519 tissue Anatomy 0.000 claims 1
- 239000012588 trypsin Substances 0.000 claims 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/34—Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes
-
- 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
- C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
- C12N5/0658—Skeletal muscle cells, e.g. myocytes, myotubes, myoblasts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- 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
- C12N2501/50—Cell markers; Cell surface determinants
- C12N2501/599—Cell markers; Cell surface determinants with CD designations not provided for elsewhere
-
- 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
- C12N2501/70—Enzymes
- C12N2501/71—Oxidoreductases (EC 1.)
-
- 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
- C12N2509/00—Methods for the dissociation of cells, e.g. specific use of enzymes
-
- 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
- C12N2509/00—Methods for the dissociation of cells, e.g. specific use of enzymes
- C12N2509/10—Mechanical dissociation
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Cell Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Rheumatology (AREA)
- Wood Science & Technology (AREA)
- Developmental Biology & Embryology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Virology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Compounds Of Unknown Constitution (AREA)
Claims (15)
1. Postupak za dobivanje stanica izvedenih iz skeletnog mišića (SMDC), postupak obuhvaća sljedeće korake:
(a) hlađenje uzorka dobivenog iz tkiva skeletnog mišića u puferu;
(b) obrada uzorka i hlađenje obrađenog uzorka, pri čemu se hlađenje izvodi na temperaturi u opsegu od 1 do 16°C tokom vremena u opsegu od 2 do 48 sati;
(c) resuspendiranje uzorka iz koraka (b) u mediju sa serumom koji sadrži najmanje jedan enzim i zagrijavanje do 25-38°C tokom 1 do 20 sati; peletiranje uzorka i
(d) resuspendiranje peleta uzorka iz koraka (c) da bi se osigurala suspenzija pojedinačnih stanica iz uzorka iz koraka (c), čime se dobivaju SMDC.
2. Postupak prema patentnom zahtjevu 1, pri čemu se korak (a) izvodi na temperaturi nižoj od 16°C, poželjno na temperaturi u opsegu od 1 do 16°C, poželjno 4 do 10°C, posebno poželjno na 7°C; i tokom vremena u opsegu do 96 sati.
3. Postupak prema patentnom zahtjevu 1 ili 2, pri čemu korak (b) obuhvaća upotrebu škara, skalpela, pinceta, filtera, ili mlina sa kuglicama.
4. Postupak prema bilo kojem od patentnih zahtjeva 1 do 3, pri čemu se hlađenje u koraku (b) izvodi na temperaturi u opsegu od 4 do 8°C, posebno poželjno 4 °C i tokom vremena u opsegu od 2 sata do 48 sati.
5. Postupak prema bilo kojem od patentnih zahtjeva 1 do 4, pri čemu korak (c) obuhvaća izvođenje enzimskog tretiranja otopinom koja sadrži bilo koji ili više odabranih iz grupe koju čine tripsin, papain, elastaza, hijaluronidaza, kolagenaza, deoksiribonukleaza, i DNK-aza.
6. Postupak prema bilo kojem od patentnih zahtjeva 1 do 5, pri čemu se korak (c) izvodi na temperaturi u opsegu od 36 do 38°C, posebno poželjno na 37°C.
7. Postupak prema bio kojem od patentnih zahtjeva 1 do 6, pri čemu korak (d) poželjno obuhvaća postupak izabran od najmanje jednog FACS sortiranja, centrifugiranja, elektrokinetičkog sortiranja, sortiranja akustoforezom, sortiranja stanica pomoću kuglica i optičkog sortiranja.
8. Postupak prema bilo kojem od patentnih zahtjeva 1 do 7, pri čemu se
dalji korak (e) izvodi nakon koraka (d) koji uključe inkubaciju suspenzije pojedinačne stanice dobivene u koraku (d), pri čemu se inkubacija u koraku (e) poželjno izvodi na temperaturi u opsegu od 25 do 38°C, poželjno 36 do 38°C, posebno poželjno na 37°C, čime se dobivaju adherentne SMDC, i
nakon koraka (e) po izboru se izvodi dalji korak (f) koji obuhvaća odbacivanje neadherentnih stanica iz koraka (e), pri čemu se korak (f) poželjno izvodi nakon najmanje 6 sati do 4 dana, i
nakon koraka (f) po izboru se izvodi dalji korak (g) razmnožavanja adherentnih stanica iz koraka (e), razmnožavanje u koraku (h) obuhvaća uzgoj u kulturi adherentnih stanica za 1 do 5 prolaza do 70 do 80% konfluencije.
9. Stanična populacija SMDC, pri čemu populacija sadrži najmanje 90% CD56 pozitivnih, 90% A2B5 pozitivnih, 90% CD105 pozitivnih i 90% desmin pozitivnih stanica i manje od 10% populacije eksprimira CD34, Sca-1 i MyoD.
10. Stanična populacija SMDC prema patentnom zahtjevu 9 dobivena postupkom prema bilo kojem od patentnih zahtjeva 1 do 8.
11. Stanična populacija SMDC prema patentnom zahtjevu 9 ili 10 za primjenu kao farmaceutska kompozicija.
12. Stanične populacije SMDC prema patentnom zahtjevu 9 ili 10 za primjenu u postupku prevencije i/ili liječenja neuromiopatija i/ili miopatija, poželjno za primjenu u postupku prevencije i/ili liječenja neuromiopatija i/ili miopatija kao što je fekalna inkontinencija i/ili urinarna inkontinencija.
13. Stanična populacija SMDC prema patentnom zahtjevu 9 ili 10 za primjenu u postupku liječenja mišićne disfunkcije, pri čemu je mišićna disfunkcija inkontinencija, posebno urinarna i/ili analna ili fekalna inkontinencija.
14. Stanična populacija SMDC za primjenu prema patentnim zahtjevima 12 ili 13, pri čemu je stanična populacija prema patentnom zahtjevu 9 ili 10 za primjenu u postupku liječenja urinarne inkontinencije a stanična populacija SMDC je osigurana u 50 do 200 µl injekcijske otopine stanične suspenzije sa koncentracijom od 1 × 105 do 6 × 106 stanica na 100 µl injekcijske otopine za injektiranje u urinarni sfinkter.
15. Stanična populacija SMDC za primjenu prema patentnim zahtjevima 12 ili 13, pri čemu je stanična populacija prema patentnom zahtjevu 9 ili 10 za primjenu u postupku liječenja analne inkontinencije i stanična populacija SMDC je osigurana u 50 µl do 1 ml injekcijske otopine stanične suspenzije sa koncentracijom od 1 × 105 to 6 × 106 stanica na 100 µl injekcijske otopine za injektiranje u vanjski analni sfinkter, posebno gdje postupak liječenja analne inkontinencije obuhvaća 20 do 40 injekcija suspenzije stanica izvedenih iz skeletnih mišića, pri čemu se pri svakoj injekciji ubrizgava 50 do 500 µl suspenzije stanice izvedene iz skeletnih mišića i pri čemu se svaka injekcija primjenjuje na drugu regiju analnog sfinktera.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP17207417 | 2017-12-14 | ||
| PCT/EP2018/085015 WO2019115790A1 (en) | 2017-12-14 | 2018-12-14 | Methods for obtaining muscle derived cells |
| EP18815731.7A EP3724319B1 (en) | 2017-12-14 | 2018-12-14 | Methods for obtaining muscle derived cells |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20230474T1 true HRP20230474T1 (hr) | 2023-07-21 |
Family
ID=60923243
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20230474TT HRP20230474T1 (hr) | 2017-12-14 | 2018-12-14 | Postupci za dobivanje stanica izvedenih iz mišića |
Country Status (24)
| Country | Link |
|---|---|
| US (2) | US11617768B2 (hr) |
| EP (2) | EP4223872A3 (hr) |
| JP (2) | JP7361398B2 (hr) |
| KR (1) | KR20200099173A (hr) |
| CN (1) | CN111448307A (hr) |
| AU (1) | AU2018383015A1 (hr) |
| BR (1) | BR112020011853A2 (hr) |
| CA (1) | CA3085483A1 (hr) |
| CL (1) | CL2020001480A1 (hr) |
| CY (1) | CY1126049T1 (hr) |
| DK (1) | DK3724319T3 (hr) |
| ES (1) | ES2948712T3 (hr) |
| FI (1) | FI3724319T3 (hr) |
| HR (1) | HRP20230474T1 (hr) |
| HU (1) | HUE062005T2 (hr) |
| IL (2) | IL309687A (hr) |
| LT (1) | LT3724319T (hr) |
| MX (1) | MX2020005881A (hr) |
| PL (1) | PL3724319T3 (hr) |
| PT (1) | PT3724319T (hr) |
| RS (1) | RS64241B1 (hr) |
| SI (1) | SI3724319T1 (hr) |
| WO (1) | WO2019115790A1 (hr) |
| ZA (1) | ZA202002410B (hr) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114423441B (zh) * | 2019-09-30 | 2024-02-02 | 泰尔茂株式会社 | 用于提高cd56阳性细胞的比率的方法 |
| WO2023012334A1 (en) | 2021-08-06 | 2023-02-09 | Innovacell Ag | Myogenic progenitor cells for use in an optimized method for the prevention and treatment of anal incontinence |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5130141A (en) | 1988-05-24 | 1992-07-14 | Law Peter K | Compositions for and methods of treating muscle degeneration and weakness |
| US5538722A (en) | 1989-06-13 | 1996-07-23 | Stanford University | Isolation, growth, differentiation and genetic engineering of human muscle cells |
| WO2001078754A2 (en) | 2000-04-14 | 2001-10-25 | University Of Pittsburgh | Soft tissue and bone augmentation and bulking utilizing muscle-derived progenitor cells, compositions and treatments thereof |
| CA2461121A1 (en) | 2001-09-20 | 2003-04-03 | Kyowa Hakko Kogyo Co., Ltd. | Multipotent stem cell in the interstitial tissues of skeletal muscle |
| EP1617852B1 (en) * | 2003-04-25 | 2010-09-29 | The University of Pittsburgh | Muscle derived cells (mdcs) for promoting and enhancing nerve repair and regeneration |
| FR2890977A1 (fr) * | 2005-09-19 | 2007-03-23 | Assist Publ Hopitaux De Paris | Procede d'obtention de cellules musculaires lisses humaines et leurs applications |
| US20070264712A1 (en) * | 2006-01-10 | 2007-11-15 | Theradigm, Inc. | Expansion and differentiation of neural stem cells under low oxygen conditions |
| CA2722758C (en) | 2007-05-29 | 2017-04-25 | Thomas Payne | Bone augmentation utilizing muscle-derived progenitor compositions, and treatments thereof |
| EP2206774A1 (en) | 2008-12-23 | 2010-07-14 | Genzyme Corporation | Muscle-derived cells having differentiation capacities |
| CN106350480B (zh) * | 2016-08-26 | 2019-11-08 | 中国农业科学院北京畜牧兽医研究所 | 一种纯化牛胎儿骨骼肌组织来源成肌细胞的方法 |
| CN113614223A (zh) | 2019-03-22 | 2021-11-05 | 伊诺瓦细胞股份有限公司 | 获得诱导性平滑肌细胞的方法 |
-
2018
- 2018-12-14 AU AU2018383015A patent/AU2018383015A1/en active Pending
- 2018-12-14 RS RS20230376A patent/RS64241B1/sr unknown
- 2018-12-14 BR BR112020011853-2A patent/BR112020011853A2/pt unknown
- 2018-12-14 EP EP23166320.4A patent/EP4223872A3/en active Pending
- 2018-12-14 IL IL309687A patent/IL309687A/en unknown
- 2018-12-14 SI SI201830915T patent/SI3724319T1/sl unknown
- 2018-12-14 CA CA3085483A patent/CA3085483A1/en active Pending
- 2018-12-14 CN CN201880079500.5A patent/CN111448307A/zh active Pending
- 2018-12-14 HR HRP20230474TT patent/HRP20230474T1/hr unknown
- 2018-12-14 LT LTEPPCT/EP2018/085015T patent/LT3724319T/lt unknown
- 2018-12-14 EP EP18815731.7A patent/EP3724319B1/en active Active
- 2018-12-14 KR KR1020207020127A patent/KR20200099173A/ko not_active Application Discontinuation
- 2018-12-14 MX MX2020005881A patent/MX2020005881A/es unknown
- 2018-12-14 DK DK18815731.7T patent/DK3724319T3/da active
- 2018-12-14 US US16/772,666 patent/US11617768B2/en active Active
- 2018-12-14 ES ES18815731T patent/ES2948712T3/es active Active
- 2018-12-14 JP JP2020533052A patent/JP7361398B2/ja active Active
- 2018-12-14 WO PCT/EP2018/085015 patent/WO2019115790A1/en unknown
- 2018-12-14 PL PL18815731.7T patent/PL3724319T3/pl unknown
- 2018-12-14 PT PT188157317T patent/PT3724319T/pt unknown
- 2018-12-14 HU HUE18815731A patent/HUE062005T2/hu unknown
- 2018-12-14 FI FIEP18815731.7T patent/FI3724319T3/fi active
-
2020
- 2020-05-04 ZA ZA2020/02410A patent/ZA202002410B/en unknown
- 2020-06-03 CL CL2020001480A patent/CL2020001480A1/es unknown
- 2020-06-10 IL IL275288A patent/IL275288A/en unknown
-
2023
- 2023-03-08 US US18/180,377 patent/US20230285467A1/en active Pending
- 2023-04-07 JP JP2023062671A patent/JP2023085507A/ja active Pending
- 2023-05-18 CY CY20231100235T patent/CY1126049T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US11617768B2 (en) | 2023-04-04 |
| CL2020001480A1 (es) | 2020-10-30 |
| KR20200099173A (ko) | 2020-08-21 |
| WO2019115790A1 (en) | 2019-06-20 |
| DK3724319T3 (da) | 2023-05-01 |
| JP7361398B2 (ja) | 2023-10-16 |
| MX2020005881A (es) | 2020-08-13 |
| CN111448307A (zh) | 2020-07-24 |
| JP2023085507A (ja) | 2023-06-20 |
| CA3085483A1 (en) | 2019-06-20 |
| RS64241B1 (sr) | 2023-06-30 |
| FI3724319T3 (fi) | 2023-05-04 |
| BR112020011853A2 (pt) | 2020-11-24 |
| LT3724319T (lt) | 2023-06-12 |
| EP4223872A3 (en) | 2023-08-23 |
| ZA202002410B (en) | 2021-09-29 |
| PT3724319T (pt) | 2023-06-07 |
| EP4223872A2 (en) | 2023-08-09 |
| CY1126049T1 (el) | 2023-11-15 |
| ES2948712T3 (es) | 2023-09-18 |
| US20230285467A1 (en) | 2023-09-14 |
| EP3724319B1 (en) | 2023-04-05 |
| PL3724319T3 (pl) | 2023-07-24 |
| IL309687A (en) | 2024-02-01 |
| JP2021506285A (ja) | 2021-02-22 |
| SI3724319T1 (sl) | 2023-07-31 |
| IL275288A (en) | 2020-07-30 |
| HUE062005T2 (hu) | 2023-09-28 |
| US20210069255A1 (en) | 2021-03-11 |
| AU2018383015A1 (en) | 2020-05-28 |
| RU2020120580A (ru) | 2022-01-14 |
| EP3724319A1 (en) | 2020-10-21 |
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