HRP20220388T1 - Postupak za dobivanje pegiliranog proteinskog pripravka - Google Patents
Postupak za dobivanje pegiliranog proteinskog pripravka Download PDFInfo
- Publication number
- HRP20220388T1 HRP20220388T1 HRP20220388TT HRP20220388T HRP20220388T1 HR P20220388 T1 HRP20220388 T1 HR P20220388T1 HR P20220388T T HRP20220388T T HR P20220388TT HR P20220388 T HRP20220388 T HR P20220388T HR P20220388 T1 HRP20220388 T1 HR P20220388T1
- Authority
- HR
- Croatia
- Prior art keywords
- pegylated protein
- hic
- iec
- mixture
- mono
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims 24
- 239000000203 mixture Substances 0.000 title claims 21
- 108091006006 PEGylated Proteins Proteins 0.000 title claims 17
- 108090000623 proteins and genes Proteins 0.000 claims 25
- 102000004169 proteins and genes Human genes 0.000 claims 25
- 238000004191 hydrophobic interaction chromatography Methods 0.000 claims 22
- 238000004255 ion exchange chromatography Methods 0.000 claims 20
- 239000000463 material Substances 0.000 claims 12
- 230000006320 pegylation Effects 0.000 claims 9
- 238000005571 anion exchange chromatography Methods 0.000 claims 8
- 239000000243 solution Substances 0.000 claims 7
- 238000002360 preparation method Methods 0.000 claims 6
- 238000010828 elution Methods 0.000 claims 3
- FSVCELGFZIQNCK-UHFFFAOYSA-N N,N-bis(2-hydroxyethyl)glycine Chemical compound OCCN(CCO)CC(O)=O FSVCELGFZIQNCK-UHFFFAOYSA-N 0.000 claims 2
- 239000007832 Na2SO4 Substances 0.000 claims 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims 2
- 239000007998 bicine buffer Substances 0.000 claims 2
- 229910052938 sodium sulfate Inorganic materials 0.000 claims 2
- 235000011152 sodium sulphate Nutrition 0.000 claims 2
- 102000004127 Cytokines Human genes 0.000 claims 1
- 108090000695 Cytokines Proteins 0.000 claims 1
- 102000004190 Enzymes Human genes 0.000 claims 1
- 108090000790 Enzymes Proteins 0.000 claims 1
- 102000003951 Erythropoietin Human genes 0.000 claims 1
- 108090000394 Erythropoietin Proteins 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000012149 elution buffer Substances 0.000 claims 1
- 229940105423 erythropoietin Drugs 0.000 claims 1
- 229940088597 hormone Drugs 0.000 claims 1
- 239000005556 hormone Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/505—Erythropoietin [EPO]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1816—Erythropoietin [EPO]
-
- 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
- A61K47/60—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 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/16—Extraction; Separation; Purification by chromatography
- C07K1/18—Ion-exchange chromatography
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/16—Extraction; Separation; Purification by chromatography
- C07K1/20—Partition-, reverse-phase or hydrophobic interaction chromatography
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/36—Extraction; Separation; Purification by a combination of two or more processes of different types
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Analytical Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Zoology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Toxicology (AREA)
- Immunology (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Claims (21)
1. Postupak za proizvodnju mono-PEGiliranog proteinskog pripravka koji sadrži najmanje oko 90 % mono-PEGiliranog proteina, naznačen time, da postupak uključuje:
a) dobivanje prve smjese koja sadrži ne-PEGilirani protein i PEGilirani protein, pri čemu PEGilirani protein sadrži mono-PEGilirani protein i oligo-PEGilirani protein;
b) podvrgavanje prve smjese koraku ionske izmjenjivačke kromatografije (IEC) kako bi se dobila IEC protočna otopina u kojoj je udio PEGiliranog proteina povećan u odnosu na prvu smjesu; IEC korak uključuje nanošenje prve smjese na IEC materijal pod uvjetima prikladnim za vezanje ne-PEGiliranog proteina;
c) sakupljanje IEC protočne otopine iz koraka b) kako bi se dobila druga smjesa koja sadrži mono-PEGilirani protein i oligo-PEGilirani protein; i
d) podvrgavanje druge smjese koraku hidrofobne interakcijske kromatografije (HIC) kako bi se dobio mono-PEGilirani proteinski pripravak u kojem je udio mono-PEGiliranog proteina povećan u odnosu na drugu smjesu, pri čemu mono-PEGilirani proteinski pripravak sadrži najmanje oko 90 % mono-PEGiliranog proteina.
2. Postupak prema patentnom zahtjevu 1, naznačen time, da je protein hormon, citokin, enzim ili protutijelo.
3. Postupak prema patentnom zahtjevu 1 ili patentnom zahtjevu 2, naznačen time, da je protein eritropoetin.
4. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da je korak ionske izmjenjivačke kromatografije (IEC) korak anionske izmjenjivačke kromatografije (AEC).
5. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da IEC materijal ima kapacitet vezanja za PEGilirani protein manji od oko 1,5 g/l.
6. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da:
i. prva smjesa sadrži manje od 25 % oligo-PEGiliranog proteina; i/ili
ii. IEC protočna otopina sadrži najmanje 90 % PEGiliranog proteina; i/ili
iii. mono-PEGilirani proteinski pripravak sadrži najmanje oko 95 %, 98 %, 99 % ili 99,9 % mono-PEGiliranog proteina.
7. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da korak a) nadalje uključuje izvođenje reakcije PEGilacije koja uključuje reakciju ne-PEGiliranog proteina s PEGilacijskim reagensom.
8. Postupak prema patentnom zahtjevu 7, naznačen time, da se reakcija PEGilacije izvodi pri pH vrijednosti od oko 7,0 do 9,0, i naznačen time, da je molarni omjer PEG/protein oko 0,6 – 1,0.
9. Postupak prema patentnom zahtjevu 7 ili patentnom zahtjevu 8, naznačen time, da uključuje
izvođenje prvog ciklusa koji se sastoji od koraka a), b) i c), pri čemu korak b) dalje uključuje eluiranje ne-PEGiliranog proteina iz IEC materijala kako bi se dobio IEC eluat, i
izvođenje drugog ciklusa iz koraka a), b) i c), u kojem se ne-PEGilirani protein eluiran u koraku b) prvog ciklusa dodaje reakciji PEGilacije iz koraka a).
10. Postupak prema patentnom zahtjevu 9, naznačen time, da se za eluiranje ne-PEGiliranog proteina iz IEC materijala koristi pufer za eluiranje koji sadrži količinu koja je manja ili jednaka količini od oko 45 mM soli.
11. Postupak prema patentnom zahtjevu 9 ili patentnom zahtjevu 10, naznačen time, da se postupak sastoji od tri, četiri ili pet ciklusa, i pri čemu korak b) svakog ciklusa uključuje eluiranje ne-PEGiliranog proteina iz IEC materijala kako bi se dobio IEC eluat, i pri čemu se ne-PEGilirani protein eluiran u koraku b) dodaje u reakciju PEGilacije iz koraka a) u sljedećem ciklusu.
12. Postupak prema bilo kojem od patentnih zahtjeva 9 do 11, naznačen time, da se IEC eluat iz koraka b) ciklusa dodaje izravno u reakciju PEGilacije iz koraka a) sljedećeg ciklusa.
13. Postupak prema bilo kojem od patentnih zahtjeva 9 do 12, naznačen time, da se ne-PEGilirani protein eluiran u koraku b) ciklusa dodaje u reakciju PEGilacije iz koraka a) sljedećeg ciklusa, i pri čemu se svježi ne-PEGilirani protein također dodaje u koraku a) kako bi se održavali uglavnom konstantni uvjeti reakcije PEGilacije u koraku a) svakog ciklusa.
14. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da uključuje izvođenje dva ili više ciklusa koraka a), b) i c), pri čemu
korak c) nadalje uključuje združivanje protočne otopine prikupljene iz svakog IEC koraka kako bi se dobila druga smjesa koja je združena druga smjesa, i pri čemu
korak d) uključuje podvrgavanje druge smjese HIC koraku.
15. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da je IEC korak AEC korak i naznačen time, da
i. AEC materijal je Toyopearl Super Q650 M; i/ili
ii. AEC korak se izvodi pri pH vrijednosti od oko 7,0 do 9,0; i/ili
iii. AEC korak se izvodi pri vodljivosti od oko 1,0 do 3,0 mS/cm; i/ili
iv. prva smjesa se nanosi na AEC materijal kao otopina AEC opterećenja koja sadrži oko 10 – 30 mM bicina i oko 1 – 10 mM Na2SO4.
16. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da korak d) uključuje podvrgavanje druge smjese HIC koraku u protočnom načinu kako bi se dobila HIC protočna otopina u kojoj se udio mono-PEGiliranog proteina povećava u odnosu na drugu smjesu,
HIC korak uključuje nanošenje druge smjese na HIC materijal pod uvjetima prikladnim za vezanje oligo-PEGiliranog proteina, pri čemu HIC protok daje mono-PEGilirani proteinski pripravak.
17. Postupak prema bilo kojem od patentnih zahtjeva 1 do 15, naznačen time, da korak d) uključuje podvrgavanje druge smjese HIC koraku u načinu vezanja i eluiranja kako bi se dobio HIC eluat u kojem je udio mono-PEGiliranog proteina povećan u odnosu na drugi smjesu, pri čemu HIC korak podrazumijeva
nanošenje druge smjese na HIC materijal pod uvjetima prikladnim za vezanje mono-PEGiliranog proteina i oligo-PEGiliranog proteina,
eluiranje mono-PEGiliranog proteina iz HIC materijala za dobivanje HIC eluata, pri čemu HIC eluat daje mono-PEGilirani proteinski pripravak.
18. Postupak prema patentnom zahtjevu 16, naznačen time, da
i. HIC materijal je Toyopearl Phenyl 650M; i/ili
ii. HIC korak se izvodi pri pH vrijednosti od oko 7,0 do 9,0; i/ili
iii. HIC korak se izvodi pri vodljivosti od oko 30 – 40 mS/cm; i/ili
iv. druga smjesa se nanosi na HIC materijal kao otopina HIC opterećenja koja sadrži oko 25 mM bicina i oko 390 mM Na2SO4.
19. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da
i. IEC korak i HIC korak se izvode pri uglavnom istoj pH vrijednosti; ili
ii. reakcija PEGilacije, IEC korak i HIC korak se izvode pri uglavnom istoj pH vrijednosti.
20. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da mono-PEGilirani protein sadrži PEG ostatak koji ima molekularnu težinu od najmanje oko 20 kDa.
21. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da dalje uključuje formuliranje proteinskog pripravka s farmaceutski prihvatljivim nosačem kako bi se dobio farmaceutski pripravak.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP17211122 | 2017-12-29 | ||
| PCT/EP2018/097125 WO2019129878A1 (en) | 2017-12-29 | 2018-12-28 | Process for providing pegylated protein composition |
| EP18830893.6A EP3731873B1 (en) | 2017-12-29 | 2018-12-28 | Process for providing pegylated protein composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20220388T1 true HRP20220388T1 (hr) | 2022-05-27 |
Family
ID=60856965
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20220388TT HRP20220388T1 (hr) | 2017-12-29 | 2018-12-28 | Postupak za dobivanje pegiliranog proteinskog pripravka |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20200362002A1 (hr) |
| EP (1) | EP3731873B1 (hr) |
| JP (2) | JP7227633B2 (hr) |
| KR (1) | KR102497097B1 (hr) |
| CN (1) | CN111727063A (hr) |
| ES (1) | ES2909454T3 (hr) |
| HR (1) | HRP20220388T1 (hr) |
| PL (1) | PL3731873T3 (hr) |
| SG (1) | SG11202005952TA (hr) |
| SI (1) | SI3731873T1 (hr) |
| WO (1) | WO2019129878A1 (hr) |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2646438B1 (fr) | 1989-03-20 | 2007-11-02 | Pasteur Institut | Procede de remplacement specifique d'une copie d'un gene present dans le genome receveur par l'integration d'un gene different de celui ou se fait l'integration |
| CA2045175C (en) | 1989-11-06 | 2003-03-18 | Arthur I. Skoultchi | Production of proteins using homologous recombination |
| EP0779362B2 (en) | 1989-12-22 | 2012-06-13 | Laboratoires Serono SA | DNA constructs for endogenous gene activation and expression modification |
| JP3051145B2 (ja) | 1990-08-28 | 2000-06-12 | 住友製薬株式会社 | 新規なポリエチレングリコール誘導体修飾ペプチド |
| US5641670A (en) | 1991-11-05 | 1997-06-24 | Transkaryotic Therapies, Inc. | Protein production and protein delivery |
| US5968502A (en) | 1991-11-05 | 1999-10-19 | Transkaryotic Therapies, Inc. | Protein production and protein delivery |
| NZ245015A (en) | 1991-11-05 | 1995-12-21 | Transkaryotic Therapies Inc | Delivery of human growth hormone through the administration of transfected cell lines encoding human growth hormone, which are physically protected from host immune response; the transfected cells and their production |
| AU673190B2 (en) | 1992-07-13 | 1996-10-31 | Bionebraska, Inc. | Method for modification of recombinant polypeptides |
| TW402639B (en) | 1992-12-03 | 2000-08-21 | Transkaryotic Therapies Inc | Protein production and protein delivery |
| US5932462A (en) | 1995-01-10 | 1999-08-03 | Shearwater Polymers, Inc. | Multiarmed, monofunctional, polymer for coupling to molecules and surfaces |
| KR100689212B1 (ko) | 1999-01-29 | 2007-03-09 | 암겐 인코포레이티드 | Ｇｃｓｆ 결합체 |
| JO2291B1 (en) * | 1999-07-02 | 2005-09-12 | اف . هوفمان لاروش ايه جي | Erythropoietin derivatives |
| CZ299516B6 (cs) | 1999-07-02 | 2008-08-20 | F. Hoffmann-La Roche Ag | Konjugát erythropoetinového glykoproteinu, zpusobjeho výroby a použití a farmaceutická kompozice sjeho obsahem |
| EP1311285B2 (en) * | 2000-05-15 | 2017-04-12 | F. Hoffmann-La Roche AG | Liquid pharmaceutical composition containing an erythropoietin derivative |
| JP2006517400A (ja) | 2002-12-19 | 2006-07-27 | ネクター セラピューティクス アラバマ，コーポレイション | シアノビリン変異体−ポリマー接合体 |
| MX2007002441A (es) | 2004-08-31 | 2007-05-04 | Pharmacia & Upjohn Co Llc | Conjugados de hormona del crecimiento humana y polietilenglicol ramificado con glicerol, proceso para su preparacion y metodos de uso de los mismos. |
| WO2007010552A2 (en) * | 2005-03-17 | 2007-01-25 | Serum Institute Of India Limited | N- terminal peg conjugate of erythropoietin |
| JP2010505874A (ja) | 2006-10-03 | 2010-02-25 | ノヴォ ノルディスク アー／エス | ポリペプチドコンジュゲートの精製方法 |
| CL2008002053A1 (es) | 2007-07-17 | 2009-05-22 | Hoffmann La Roche | Metodo para la purificacion de una eritropoyetina monopeguilada (epompeg) que consiste en proporcionar una solucion que contiene eritropoyetina mono, poli y no peguilada y hacerla pasar por dos pasos de cromatografia de intercambio cationico y metodo para producir epo mpeg que incluye metodo de purificacion. |
| CN102639553A (zh) | 2009-11-24 | 2012-08-15 | 诺沃—诺迪斯克保健股份有限公司 | 纯化聚乙二醇化蛋白质的方法 |
| BR112012020254A2 (pt) * | 2010-02-12 | 2016-05-03 | Dsm Ip Assets Bv | método para a purificação de anticorpos a partir de uma mistura de proteína e, unidade operacional única. |
| CN102234310B (zh) * | 2010-04-30 | 2017-02-08 | 杭州九源基因工程有限公司 | 一种聚乙二醇修饰蛋白的分离纯化方法 |
| WO2012035037A1 (en) | 2010-09-14 | 2012-03-22 | F. Hoffmann-La Roche Ag | Method for purifying pegylated erythropoietin |
| CN102453087B (zh) * | 2010-10-22 | 2013-12-25 | 广东赛保尔生物医药技术有限公司 | 一种单取代peg-epo的纯化及制备方法 |
| ES2905105T3 (es) * | 2017-12-29 | 2022-04-07 | Hoffmann La Roche | Procedimiento para proporcionar una composición de proteína PEGilada |
-
2018
- 2018-12-28 SI SI201830617T patent/SI3731873T1/sl unknown
- 2018-12-28 CN CN201880089659.5A patent/CN111727063A/zh active Pending
- 2018-12-28 HR HRP20220388TT patent/HRP20220388T1/hr unknown
- 2018-12-28 US US16/958,114 patent/US20200362002A1/en active Pending
- 2018-12-28 SG SG11202005952TA patent/SG11202005952TA/en unknown
- 2018-12-28 ES ES18830893T patent/ES2909454T3/es active Active
- 2018-12-28 KR KR1020207021891A patent/KR102497097B1/ko active IP Right Grant
- 2018-12-28 WO PCT/EP2018/097125 patent/WO2019129878A1/en unknown
- 2018-12-28 EP EP18830893.6A patent/EP3731873B1/en active Active
- 2018-12-28 JP JP2020536096A patent/JP7227633B2/ja active Active
- 2018-12-28 PL PL18830893T patent/PL3731873T3/pl unknown
-
2023
- 2023-02-03 JP JP2023014951A patent/JP2023055876A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| SI3731873T1 (sl) | 2022-05-31 |
| CN111727063A (zh) | 2020-09-29 |
| JP2021508706A (ja) | 2021-03-11 |
| JP2023055876A (ja) | 2023-04-18 |
| EP3731873B1 (en) | 2022-01-26 |
| PL3731873T3 (pl) | 2022-04-25 |
| ES2909454T3 (es) | 2022-05-06 |
| KR20200104382A (ko) | 2020-09-03 |
| KR102497097B1 (ko) | 2023-02-06 |
| JP7227633B2 (ja) | 2023-02-22 |
| US20200362002A1 (en) | 2020-11-19 |
| SG11202005952TA (en) | 2020-07-29 |
| EP3731873A1 (en) | 2020-11-04 |
| WO2019129878A1 (en) | 2019-07-04 |
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