HRP20220628T1 - Postupci i međuprodukti za pripremu lijeka - Google Patents
Postupci i međuprodukti za pripremu lijeka Download PDFInfo
- Publication number
- HRP20220628T1 HRP20220628T1 HRP20220628TT HRP20220628T HRP20220628T1 HR P20220628 T1 HRP20220628 T1 HR P20220628T1 HR P20220628T T HRP20220628T T HR P20220628TT HR P20220628 T HRP20220628 T HR P20220628T HR P20220628 T1 HRP20220628 T1 HR P20220628T1
- Authority
- HR
- Croatia
- Prior art keywords
- compound
- formula
- preparation
- ibrutinib
- salt
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims 17
- 239000003814 drug Substances 0.000 title 1
- 239000000543 intermediate Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 15
- 238000006243 chemical reaction Methods 0.000 claims 8
- 239000002177 L01XE27 - Ibrutinib Substances 0.000 claims 7
- XYFPWWZEPKGCCK-GOSISDBHSA-N ibrutinib Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C=C)N=C1C(C=C1)=CC=C1OC1=CC=CC=C1 XYFPWWZEPKGCCK-GOSISDBHSA-N 0.000 claims 7
- 229960001507 ibrutinib Drugs 0.000 claims 7
- 150000003839 salts Chemical class 0.000 claims 7
- 239000012453 solvate Substances 0.000 claims 5
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims 3
- PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical compound NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 claims 3
- -1 carboxybenzyl Chemical group 0.000 claims 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 3
- 239000002671 adjuvant Substances 0.000 claims 2
- 125000000217 alkyl group Chemical group 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 2
- 150000004820 halides Chemical class 0.000 claims 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims 1
- 239000005695 Ammonium acetate Substances 0.000 claims 1
- XPOLVIIHTDKJRY-UHFFFAOYSA-N acetic acid;methanimidamide Chemical compound NC=N.CC(O)=O XPOLVIIHTDKJRY-UHFFFAOYSA-N 0.000 claims 1
- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 claims 1
- 230000010933 acylation Effects 0.000 claims 1
- 238000005917 acylation reaction Methods 0.000 claims 1
- NMVVJCLUYUWBSZ-UHFFFAOYSA-N aminomethylideneazanium;chloride Chemical compound Cl.NC=N NMVVJCLUYUWBSZ-UHFFFAOYSA-N 0.000 claims 1
- 229940043376 ammonium acetate Drugs 0.000 claims 1
- 235000019257 ammonium acetate Nutrition 0.000 claims 1
- 150000001450 anions Chemical class 0.000 claims 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 238000010511 deprotection reaction Methods 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- JPUTTYRVDANTBN-UHFFFAOYSA-N ethyl methanimidate;hydrochloride Chemical compound Cl.CCOC=N JPUTTYRVDANTBN-UHFFFAOYSA-N 0.000 claims 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 238000000926 separation method Methods 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 claims 1
Classifications
-
- 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
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- 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
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Claims (10)
1. Postupak za pripravu spoja formule I,
[image]
ili njegove soli ili solvata, naznačen time što
R1 predstavlja dušikovu zaštitnu skupinu koja je karboksibenzil (Cbz); koji postupak uključuje reakciju spoja formule II,
[image]
ili njegove soli ili solvata, pri čemu
X1 predstavlja prikladnu odlazeću skupinu,
sa spojem formule III,
[image]
ili njegovom soli, solvatom ili zaštićenim derivatom, pri čemu je R1 kao što je gore definirano.
2. Postupak za pripravu spoja formule I prema patentnom zahtjevu 1, naznačen time što:
- u spoju formule (I) i (III) R1 predstavlja dušikovu zaštitnu skupinu koja je Cbz; i
- u spoju formule (II), X1 predstavlja -OR3a, u kojem R3a predstavlja alkil kao što je metil.
3. Postupak za pripravu spoja formule (IVA), naznačen time što postupak obuhvaća postupak za pripravu spoja formule (I) kako je definiran u zahtjevu 1 nakon čega slijedi pretvorba u spoj formule (IVA),
[image]
ili sol ili solvat, pri čemu X2 predstavljaju -OH ili -NH2, i R1 je kako je definiran u zahtjevu 1.
4. Postupak za pripravu spoja formule (IV),
[image]
ili njegove soli ili solvata, pri čemu R1 je kako je definiran u zahtjevu 1, koji postupak uključuje postupak za pripravu spoja formule (I) prema patentnom zahtjevu 1 nakon čega slijedi reakcija s bilo kojim od:
(i) formamidom (HCONH2);
(ii) formamidinom ili soli formamidina H-C(=NH)-NH3+X-, pri čemu X- predstavlja prikladan protuion, kao što je halogenid (npr. Cl-) ili oksi anion (npr. acil-O-), tako da tvori na primjer formamidin HCl ili formamidin acetat ili slično;
(iii) alkil (npr. etil) formimidatom, ili njegovom soli, kao što je etil formimidat HCl;
(iv) etilortoformijatom zatim s amonijevim acetatom.
5. Postupak prema patentnom zahtjevu 3 ili zahtjevu 4, naznačen time što je reakcija s(ii) a soli formamidina u kojoj je protuion halogenid ili anion na bazi kisika.
6. Postupak prema bilo kojem od zahtjeva 3 do 5, naznačen time što se reakcija izvodi na temperaturi ispod 160°C, na primjer između 100°C i 140°C.
7. Spoj formule (I) ili (IVA) kako je definiran u bilo kojem od zahtjeva 1, 2 ili 3 i naznačen time što R1 predstavlja dušikovu zaštitnu skupinu koja je Cbz.
8. Postupak za pripremu ibrutiniba:
[image]
koji postupak obuhvaća bilo koji od:
- postupak za pripravu spoja formule (I) kako je definiran u zahtjevu 1 ili zahtjevu 2, nakon čega slijedi pretvorba u ibrutinib;
- postupak za pripravu spoja formule (IVA) ili (IV) kako je definiran u bilo kojem od zahtjeva 3 do 6, nakon čega slijedi pretvorba u ibrutinib, na primjer uklanjanjem zaštite (tj. uklanjanjem skupine R1) nakon čega slijedi acilacija s akril kloridom; i/ili
- postupak razdvajanja za pripravu spoja formule (III) kako je definiran u zahtjevu 1, nakon čega slijedi pretvorba u ibrutinib.
9. Upotreba spoja formule (I), (IVA), (IV) i/ili (III) kako je definiran u bilo kojem zahtjevu 1, 2, 3 ili 7 kao međuprodukta u pripravi ibrutiniba.
10. Postupak za pripremu farmaceutske formulacije koja sadrži ibrutinib, koji obuhvaća korake prema zahtjevu 8, koji se sastoji od povezivanja ibrutiniba (ili njegove farmaceutski prihvatljive soli) s (a) farmaceutski prihvatljivom pomoćnom tvari/tvarima, adjuvantom / adjuvantima, razrjeđivačem/ razrjeđivačima i/ili nosačem/nosačima.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361786842P | 2013-03-15 | 2013-03-15 | |
| EP13159470 | 2013-03-15 | ||
| EP13197813 | 2013-12-17 | ||
| PCT/EP2014/054621 WO2014139970A1 (en) | 2013-03-15 | 2014-03-11 | Processes and intermediates for preparing a medicament |
| EP14708885.0A EP2970291B1 (en) | 2013-03-15 | 2014-03-11 | Processes and intermediates for preparing a medicament |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20220628T1 true HRP20220628T1 (hr) | 2022-06-24 |
Family
ID=51535892
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20220628TT HRP20220628T1 (hr) | 2013-03-15 | 2014-03-11 | Postupci i međuprodukti za pripremu lijeka |
Country Status (19)
| Country | Link |
|---|---|
| EP (1) | EP2970291B1 (hr) |
| JP (1) | JP6777398B2 (hr) |
| KR (2) | KR102377688B1 (hr) |
| CN (2) | CN112608298A (hr) |
| AU (2) | AU2014230935A1 (hr) |
| BR (1) | BR112015021856A2 (hr) |
| CA (1) | CA2901510C (hr) |
| DK (1) | DK2970291T3 (hr) |
| EA (1) | EA201591685A1 (hr) |
| ES (1) | ES2924193T3 (hr) |
| HR (1) | HRP20220628T1 (hr) |
| HU (1) | HUE058914T2 (hr) |
| LT (1) | LT2970291T (hr) |
| MX (2) | MX2015012731A (hr) |
| MY (1) | MY194905A (hr) |
| PE (1) | PE20151652A1 (hr) |
| SG (2) | SG10201809696UA (hr) |
| SI (1) | SI2970291T1 (hr) |
| WO (1) | WO2014139970A1 (hr) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101982475B1 (ko) | 2011-09-02 | 2019-05-27 | 인사이트 홀딩스 코포레이션 | Ｐｉ３ｋ 억제제로서 헤테로시클릴아민 |
| CN105884747B (zh) * | 2014-08-28 | 2021-01-05 | 首药控股(北京)有限公司 | 一种制备布鲁顿酪氨酸激酶(btk)激酶抑制剂的制备方法 |
| CN104447761A (zh) * | 2014-11-27 | 2015-03-25 | 广东东阳光药业有限公司 | 一种吡唑衍生物的制备方法 |
| CN105481862B (zh) * | 2015-01-21 | 2018-08-21 | 中国科学院合肥物质科学研究院 | Flt3激酶的新型抑制剂及其用途 |
| WO2016115869A1 (zh) * | 2015-01-21 | 2016-07-28 | 中国科学院合肥物质科学研究院 | Flt3激酶的新型抑制剂及其用途 |
| ES2843522T3 (es) * | 2015-02-27 | 2021-07-19 | Incyte Corp | Sales del inhibidor de PI3K y procesos para su preparación |
| LV15201B (lv) | 2015-08-31 | 2017-07-20 | Latvijas Organiskās Sintēzes Institūts | Ibrutiniba izejvielas iegūšanas paņēmiens |
| CN106608877B (zh) * | 2015-10-21 | 2018-11-13 | 新发药业有限公司 | 一种依鲁替尼中间体4-氨基-3-（4-苯氧基）苯基-1H-吡唑并[3,4-d]嘧啶的制备方法 |
| JO3794B1 (ar) | 2015-12-10 | 2021-01-31 | Janssen Pharmaceutica Nv | المركبات متعددة الحلقات كمثبطات لتيروزين كيناز بروتون |
| JO3793B1 (ar) | 2015-12-10 | 2021-01-31 | Janssen Pharmaceutica Nv | مثبطات تيروزين كاينيز بروتون وأساليب استخدامها |
| WO2018103058A1 (en) * | 2016-12-09 | 2018-06-14 | Janssen Pharmaceutica Nv | Inhibitors of bruton's tyrosine kinase and methods of their use |
| WO2018145280A1 (zh) * | 2017-02-09 | 2018-08-16 | 合肥合源药业有限公司 | Flt3激酶抑制剂或其盐的晶型及其制备方法 |
| CN107383017B (zh) * | 2017-07-20 | 2020-01-14 | 河南师范大学 | 依鲁替尼高效制备方法 |
| WO2019027860A1 (en) * | 2017-08-01 | 2019-02-07 | Boehringer Ingelheim International Gmbh | INTERMEDIATE COMPOUNDS AND METHODS |
| MX2021014246A (es) | 2019-05-21 | 2022-01-06 | Janssen Pharmaceutica Nv | Procedimientos y productos intermedios para preparar un inhibidor de btk. |
| WO2020234379A1 (en) | 2019-05-21 | 2020-11-26 | Janssen Pharmaceutica Nv | Processes and intermediates for preparing a btk inhibitor |
| CN113200987A (zh) * | 2021-04-29 | 2021-08-03 | 湖南华腾制药有限公司 | 一种伊布替尼的制备方法 |
| CN115322226B (zh) * | 2022-08-17 | 2023-08-11 | 厦门大学 | 一种共价靶向砷抑制剂及其制备方法和应用 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CZ2002936A3 (cs) * | 1999-09-17 | 2002-10-16 | Abbott Gmbh & Co. Kg | Pyrazolopyrimidiny jako terapeutické prostředky |
| SI2530083T1 (sl) | 2006-09-22 | 2016-09-30 | Pharmacyclics Llc | Inhibitorji Bruton tirozin kinaze |
| ES2403546T3 (es) * | 2006-11-03 | 2013-05-20 | Pharmacyclics, Inc. | Sonda de actividad de la tirosina-cinasa de Bruton y procedimiento de utilización |
| ES2562215T3 (es) * | 2007-03-28 | 2016-03-03 | Pharmacyclics Llc | Inhibidores de la tirosina quinasa de Bruton |
| UA105362C2 (en) * | 2008-04-02 | 2014-05-12 | Бьорингер Ингельхайм Интернациональ Гмбх | 1-heterocyclyl-1, 5-dihydro-pyrazolo [3, 4-d] pyrimidin-4-one derivatives and their use as pde9a modulators |
| PT2414363E (pt) | 2009-03-31 | 2014-02-26 | Boehringer Ingelheim Int | Derivados de 1-heterociclil-1,5-di-hidro-pirazolo[3,4- d]pirimidin-4-ona e sua utilização como moduladores de pde9a |
| US7741330B1 (en) * | 2009-10-12 | 2010-06-22 | Pharmacyclics, Inc. | Pyrazolo-pyrimidine inhibitors of Bruton's tyrosine kinase |
| CA2804648C (en) * | 2010-07-09 | 2019-01-22 | The Walter And Eliza Hall Institute Of Medical Research | Protein kinase inhibitors and methods of treatment |
| EP2632898A4 (en) * | 2010-10-29 | 2014-04-02 | Biogen Idec Inc | HETEROCYCLIC TYROSINE KINASE HEMMER |
| US9376438B2 (en) * | 2011-05-17 | 2016-06-28 | Principia Biopharma, Inc. | Pyrazolopyrimidine derivatives as tyrosine kinase inhibitors |
| KR20140048968A (ko) * | 2011-07-13 | 2014-04-24 | 파마시클릭스, 인코포레이티드 | 브루톤형 티로신 키나제의 억제제 |
| MX2015001802A (es) * | 2012-08-10 | 2015-05-07 | Boehringer Ingelheim Int | Compuestos heteroaromaticos como inhibidores de btk. |
| GEP201606597B (en) * | 2012-11-02 | 2017-01-10 | Pfizer | Bruton's tyrosine kinase inhibitors |
| CN103848810A (zh) * | 2012-11-30 | 2014-06-11 | 北京赛林泰医药技术有限公司 | 鲁顿酪氨酸激酶抑制剂 |
-
2014
- 2014-03-11 HU HUE14708885A patent/HUE058914T2/hu unknown
- 2014-03-11 CA CA2901510A patent/CA2901510C/en active Active
- 2014-03-11 KR KR1020217031854A patent/KR102377688B1/ko active IP Right Grant
- 2014-03-11 PE PE2015001956A patent/PE20151652A1/es unknown
- 2014-03-11 DK DK14708885.0T patent/DK2970291T3/da active
- 2014-03-11 JP JP2015562078A patent/JP6777398B2/ja active Active
- 2014-03-11 SG SG10201809696UA patent/SG10201809696UA/en unknown
- 2014-03-11 SI SI201431956T patent/SI2970291T1/sl unknown
- 2014-03-11 WO PCT/EP2014/054621 patent/WO2014139970A1/en active Application Filing
- 2014-03-11 LT LTEPPCT/EP2014/054621T patent/LT2970291T/lt unknown
- 2014-03-11 HR HRP20220628TT patent/HRP20220628T1/hr unknown
- 2014-03-11 KR KR1020157025525A patent/KR102311329B1/ko active IP Right Grant
- 2014-03-11 EP EP14708885.0A patent/EP2970291B1/en active Active
- 2014-03-11 BR BR112015021856A patent/BR112015021856A2/pt not_active Application Discontinuation
- 2014-03-11 SG SG11201507595XA patent/SG11201507595XA/en unknown
- 2014-03-11 CN CN202011305518.8A patent/CN112608298A/zh active Pending
- 2014-03-11 CN CN201480015131.5A patent/CN105026400A/zh active Pending
- 2014-03-11 MX MX2015012731A patent/MX2015012731A/es unknown
- 2014-03-11 EA EA201591685A patent/EA201591685A1/ru unknown
- 2014-03-11 AU AU2014230935A patent/AU2014230935A1/en not_active Abandoned
- 2014-03-11 MY MYPI2015002280A patent/MY194905A/en unknown
- 2014-03-11 ES ES14708885T patent/ES2924193T3/es active Active
-
2015
- 2015-09-14 MX MX2020012596A patent/MX2020012596A/es unknown
-
2018
- 2018-06-08 AU AU2018204086A patent/AU2018204086B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| SI2970291T1 (sl) | 2022-07-29 |
| KR102377688B1 (ko) | 2022-03-22 |
| KR20150132172A (ko) | 2015-11-25 |
| KR20210123429A (ko) | 2021-10-13 |
| MY194905A (en) | 2022-12-22 |
| CA2901510A1 (en) | 2014-09-18 |
| JP2016510779A (ja) | 2016-04-11 |
| AU2018204086A1 (en) | 2018-06-28 |
| BR112015021856A2 (pt) | 2017-07-18 |
| MX2015012731A (es) | 2016-02-18 |
| WO2014139970A1 (en) | 2014-09-18 |
| DK2970291T3 (da) | 2022-08-01 |
| SG10201809696UA (en) | 2018-11-29 |
| AU2018204086B2 (en) | 2020-03-12 |
| SG11201507595XA (en) | 2015-10-29 |
| KR102311329B1 (ko) | 2021-10-14 |
| EP2970291A1 (en) | 2016-01-20 |
| EA201591685A1 (ru) | 2016-01-29 |
| CA2901510C (en) | 2022-11-29 |
| AU2014230935A1 (en) | 2015-09-03 |
| EP2970291B1 (en) | 2022-05-11 |
| PE20151652A1 (es) | 2015-11-12 |
| LT2970291T (lt) | 2022-06-10 |
| CN105026400A (zh) | 2015-11-04 |
| CN112608298A (zh) | 2021-04-06 |
| ES2924193T3 (es) | 2022-10-05 |
| JP6777398B2 (ja) | 2020-10-28 |
| HUE058914T2 (hu) | 2022-09-28 |
| MX2020012596A (es) | 2021-02-09 |
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