HRP20220041T1 - Postupak za dobivanje pegiliranog proteinskog pripravka - Google Patents
Postupak za dobivanje pegiliranog proteinskog pripravka Download PDFInfo
- Publication number
- HRP20220041T1 HRP20220041T1 HRP20220041TT HRP20220041T HRP20220041T1 HR P20220041 T1 HRP20220041 T1 HR P20220041T1 HR P20220041T T HRP20220041T T HR P20220041TT HR P20220041 T HRP20220041 T HR P20220041T HR P20220041 T1 HRP20220041 T1 HR P20220041T1
- Authority
- HR
- Croatia
- Prior art keywords
- hic
- pegylated protein
- mono
- protein
- elution
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims 21
- 239000000203 mixture Substances 0.000 title claims 6
- 108091006006 PEGylated Proteins Proteins 0.000 title claims 4
- 238000004191 hydrophobic interaction chromatography Methods 0.000 claims 42
- 102000004169 proteins and genes Human genes 0.000 claims 30
- 108090000623 proteins and genes Proteins 0.000 claims 30
- 239000000463 material Substances 0.000 claims 24
- 238000010828 elution Methods 0.000 claims 11
- 239000000872 buffer Substances 0.000 claims 7
- 230000002051 biphasic effect Effects 0.000 claims 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 4
- 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 3
- 239000000243 solution Substances 0.000 claims 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 claims 2
- 102100031939 Erythropoietin Human genes 0.000 claims 2
- 239000007995 HEPES buffer Substances 0.000 claims 2
- 229920002684 Sepharose Polymers 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
- 239000007832 Na2SO4 Substances 0.000 claims 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims 1
- 230000000052 comparative effect Effects 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
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 229910052938 sodium sulfate Inorganic materials 0.000 claims 1
- 235000011152 sodium sulphate Nutrition 0.000 claims 1
Classifications
-
- 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
-
- 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
- B01D15/16—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the conditioning of the fluid carrier
- B01D15/166—Fluid composition conditioning, e.g. gradient
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/10—Selective adsorption, e.g. chromatography characterised by constructional or operational features
- B01D15/18—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to flow patterns
- B01D15/1864—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to flow patterns using two or more columns
- B01D15/1871—Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to flow patterns using two or more columns placed in series
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/32—Bonded phase chromatography
- B01D15/325—Reversed phase
- B01D15/327—Reversed phase with hydrophobic interaction
-
- 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
- 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]
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/96—Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Analytical Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Zoology (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Gastroenterology & Hepatology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Toxicology (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Microbiology (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)
- Enzymes And Modification Thereof (AREA)
Claims (17)
1. Postupak za proizvodnju mono-PEGiliranog proteinskog pripravka koji sadrži najmanje oko 90% mono-PEGiliranog proteina, postupak koji uključuje:
a) dobivanje proteinske smjese koja sadrži ne-PEGilirani protein, mono-PEGilirani protein i oligo-PEGilirani protein;
b) podvrgavanje proteinske smjese koraku dvofazne hidrofobne interakcijske kromatografije (HIC), koji uključuje:
nanošenje proteinske smjese na prvi HIC materijal za dobivanje prve HIC protočne otopine; i
nanošenje prve HIC protočne otopine na drugi HIC materijal za dobivanje druge HIC protočne otopine,
pri čemu se drugi HIC materijal razlikuje od prvog HIC materijala; i
pri čemu se dvofazni HIC korak izvodi u dvofaznim HIC uvjetima, gdje su dvofazni HIC uvjeti prikladni za vezanje oligo-PEGiliranog proteina na prvi HIC materijal i vezanje mono-PEGiliranog proteina na drugi HIC materijal; i
c) eluiranje mono-PEGiliranog proteina iz drugog HIC materijala za dobivanje drugog HIC eluata, pri čemu drugi HIC eluat daje mono-PEGilirani proteinski pripravak.
2. Postupak prema patentnom zahtjevu 1, naznačen time, da je protein hormon, citokin, enzim ili protutijelo.
3. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da je protein eritropoetin.
4. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da su prvi HIC materijal i drugi HIC materijal izravno povezani u seriju.
5. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da u dvofaznim HIC uvjetima prvi HIC materijal ne veže ne-PEGilirani protein ili mono-PEGilirani protein, i naznačen time, da drugi HIC materijal ne veže ne-PEGilirani protein.
6. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da u usporednim kromatogramima HIC elucije prvi HIC materijal i drugi HIC materijal imaju dobro razlučene maksimume za mono-PEGilirani protein.
7. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da
a) prvi HIC materijal ima suštinski istu selektivnost kao Phenyl Sepharose HP u dvofaznim HIC uvjetima; i
b) drugi HIC materijal ima suštinski istu selektivnost kao Toyopearl Phenyl 650M u dvofaznim HIC uvjetima.
8. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da
a) prvi HIC materijal je Phenyl Sepharose HP; i/ili
b) drugi HIC materijal je Toyopearl Phenyl 650M.
9. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da uključuje daljnji korak:
d) eluiranje oligo-PEGiliranog proteina iz prvog HIC materijala kako bi se dobio prvi HIC eluat.
10. Postupak prema patentnom zahtjevu 9, naznačen time, da eluiranje oligo-PEGiliranog proteina iz prvog HIC materijala uključuje eluiranje s linearnim gradijentom.
11. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da
i. dvofazni HIC uvjeti su pri vodljivosti od oko 54-55 mS/cm; i/ili
ii. eluiranje mono-PEGiliranog proteina iz drugog HIC materijala je pri vodljivosti od oko 40-41 mS/cm; i/ili
iii. eluiranje oligo-PEGiliranog proteina iz prvog HIC materijala provodi se linearnim gradijentom od oko 54-55 mS/cm do oko 1-5 mS.cm
i pri čemu je izborno protein EPO.
12. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da se postupak provodi upotrebom smjese pufera A i pufera B, pri čemu pufer A sadrži 25 mM HEPES, pH 7,5, 500 mM Na2SO4 i pri čemu pufer B sadrži 25 mM HEPES, pH 7,5, i pri čemu
i. dvije faze HIC uvjeta su na oko 13,5% pufera B; i/ili
ii. eluiranje mono-PEGiliranog proteina iz drugog HIC materijala je na oko 40% pufera B; i/ili
iii. eluiranje oligo-PEGiliranog proteina iz prvog HIC materijala provodi se linearnim gradijentom od oko 13,5% do oko 80% pufera B
i pri čemu je izborno protein EPO.
13. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da eluiranje mono-PEGiliranog proteina iz drugog HIC materijala uključuje korak eluiranja, nakon kojeg po izboru slijedi eluiranje s gradijentom.
14. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da mono-PEGilirani proteinski pripravak sadrži najmanje oko 99% mono-PEGiliranog proteina.
15. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da proteinska smjesa sadrži najmanje 10% oligo-PEGiliranog proteina.
16. 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.
17. Postupak prema bilo kojem od prethodnih patentnih zahtjeva, naznačen time, da je mono-PEGilirani proteinski pripravak farmaceutski pripravak, a proces dalje uključuje formuliranje drugog HIC eluata s farmaceutskim ekscipijensom.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP17211103 | 2017-12-29 | ||
| PCT/EP2018/097124 WO2019129877A1 (en) | 2017-12-29 | 2018-12-28 | Process for providing pegylated protein composition |
| EP18830892.8A EP3731872B1 (en) | 2017-12-29 | 2018-12-28 | Process for providing pegylated protein composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20220041T1 true HRP20220041T1 (hr) | 2022-04-15 |
Family
ID=60954808
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20220041TT HRP20220041T1 (hr) | 2017-12-29 | 2018-12-28 | Postupak za dobivanje pegiliranog proteinskog pripravka |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US11518781B2 (hr) |
| EP (1) | EP3731872B1 (hr) |
| JP (2) | JP7410860B2 (hr) |
| KR (1) | KR102500631B1 (hr) |
| CN (1) | CN111801120A (hr) |
| ES (1) | ES2905105T3 (hr) |
| HR (1) | HRP20220041T1 (hr) |
| PL (1) | PL3731872T3 (hr) |
| SG (1) | SG11202006140TA (hr) |
| SI (1) | SI3731872T1 (hr) |
| WO (1) | WO2019129877A1 (hr) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111727063A (zh) * | 2017-12-29 | 2020-09-29 | 豪夫迈·罗氏有限公司 | 用于提供聚乙二醇化蛋白质组合物的方法 |
| CN115023276A (zh) * | 2020-01-29 | 2022-09-06 | 默沙东有限公司 | 从抗-lag3抗体生产中分离宿主细胞脂肪酶的方法 |
Family Cites Families (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1990008822A1 (en) * | 1989-02-03 | 1990-08-09 | Genetics Institute, Inc. | Erythropoietin receptor |
| 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 |
| ES2090297T5 (es) | 1989-11-06 | 2005-03-01 | Cell Genesys, Inc. | Produccion de proteinas que utilizan recombinacion homologa. |
| DE69031172T2 (de) | 1989-12-22 | 1998-03-12 | Applied Research Systems Ars Holding N.V., Curacao | Modifikation der endogenen genexpression mit hilfe eines regulatorischen elements mittels homologe rekombination |
| 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 |
| US5968502A (en) | 1991-11-05 | 1999-10-19 | Transkaryotic Therapies, Inc. | Protein production and protein delivery |
| US5641670A (en) | 1991-11-05 | 1997-06-24 | 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 |
| EP0651761B1 (en) | 1992-07-13 | 2002-10-09 | 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 |
| US5886155A (en) * | 1997-06-18 | 1999-03-23 | Bioresources International Inc. | Purification of miraculin glycoprotein using tandem hydrophobic interaction chromatography |
| CZ300546B6 (cs) | 1999-01-29 | 2009-06-10 | Amgen, Inc. | Fyziologicky aktivní konjugát, prostredek a zpusob prípravy |
| 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 |
| JP3108767B1 (ja) | 1999-10-20 | 2000-11-13 | 農林水産省食品総合研究所長 | ｃｈｉｂ２型キチナーゼの製造法 |
| CA2498886C (en) * | 2002-09-20 | 2013-06-25 | Pharmacia Corporation | Process for decreasing aggregate levels of pegylated protein |
| 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 |
| EP1789092A2 (en) | 2004-08-31 | 2007-05-30 | Pharmacia & Upjohn Company LLC | Glycerol branched polyethylene glycol human growth hormone conjugates, process for their preparation, and methods of use thereof |
| WO2007010552A2 (en) | 2005-03-17 | 2007-01-25 | Serum Institute Of India Limited | N- terminal peg conjugate of erythropoietin |
| US8969532B2 (en) * | 2006-10-03 | 2015-03-03 | Novo Nordisk A/S | Methods for the purification of polypeptide conjugates comprising polyalkylene oxide using hydrophobic interaction chromatography |
| AR067537A1 (es) | 2007-07-17 | 2009-10-14 | Hoffmann La Roche | Purificacion de polipeptidos pegilados |
| WO2011018515A1 (en) * | 2009-08-14 | 2011-02-17 | Novo Nordisk Health Care Ag | Method of purifying pegylated proteins |
| JP5827955B2 (ja) | 2009-11-24 | 2015-12-02 | ノヴォ・ノルディスク・ヘルス・ケア・アーゲー | Ｐｅｇ化タンパク質の精製方法 |
| 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 |
| SI2616101T1 (sl) | 2010-09-14 | 2014-10-30 | F. Hoffmann-La Roche Ag | Postopek za čiščenje pegiliranega eritropoetina |
| 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 |
| JP2015512368A (ja) | 2012-03-16 | 2015-04-27 | ベルローズ ファーマ，インコーポレーテッド | Ｃ１阻害剤のポリマーコンジュゲート |
| CN104513306B (zh) | 2014-12-15 | 2016-08-17 | 山西瑞亚力科技有限公司 | 载脂蛋白A1的纯化方法和ApoAI蛋白注射抗原 |
| CN105037523B (zh) * | 2015-06-25 | 2019-02-19 | 北京三元基因药业股份有限公司 | 干扰素突变体及其聚乙二醇衍生物 |
| EP3337819B1 (en) * | 2015-08-20 | 2024-02-21 | F. Hoffmann-La Roche AG | Method of purifying for producing recombinant polypeptides using fkpa |
-
2018
- 2018-12-28 KR KR1020207021890A patent/KR102500631B1/ko active IP Right Grant
- 2018-12-28 WO PCT/EP2018/097124 patent/WO2019129877A1/en unknown
- 2018-12-28 PL PL18830892T patent/PL3731872T3/pl unknown
- 2018-12-28 JP JP2020536134A patent/JP7410860B2/ja active Active
- 2018-12-28 CN CN201880090112.7A patent/CN111801120A/zh active Pending
- 2018-12-28 US US16/957,160 patent/US11518781B2/en active Active
- 2018-12-28 SG SG11202006140TA patent/SG11202006140TA/en unknown
- 2018-12-28 SI SI201830545T patent/SI3731872T1/sl unknown
- 2018-12-28 HR HRP20220041TT patent/HRP20220041T1/hr unknown
- 2018-12-28 EP EP18830892.8A patent/EP3731872B1/en active Active
- 2018-12-28 ES ES18830892T patent/ES2905105T3/es active Active
-
2022
- 2022-08-12 JP JP2022128594A patent/JP7464660B2/ja active Active
Also Published As
| Publication number | Publication date |
|---|---|
| JP7464660B2 (ja) | 2024-04-09 |
| CN111801120A (zh) | 2020-10-20 |
| KR102500631B1 (ko) | 2023-02-15 |
| JP7410860B2 (ja) | 2024-01-10 |
| JP2021508710A (ja) | 2021-03-11 |
| JP2022160686A (ja) | 2022-10-19 |
| US20210238223A1 (en) | 2021-08-05 |
| US11518781B2 (en) | 2022-12-06 |
| SI3731872T1 (sl) | 2022-04-29 |
| KR20200104381A (ko) | 2020-09-03 |
| EP3731872A1 (en) | 2020-11-04 |
| WO2019129877A1 (en) | 2019-07-04 |
| SG11202006140TA (en) | 2020-07-29 |
| PL3731872T3 (pl) | 2022-03-21 |
| ES2905105T3 (es) | 2022-04-07 |
| EP3731872B1 (en) | 2021-11-24 |
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