HRP20160490T1 - Pripravak i oblik koji sadrže rekombinantnu humanu iduronat-2-sulfatazu te postupci njihove pripreme - Google Patents
Pripravak i oblik koji sadrže rekombinantnu humanu iduronat-2-sulfatazu te postupci njihove pripreme Download PDFInfo
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- HRP20160490T1 HRP20160490T1 HRP20160490TT HRP20160490T HRP20160490T1 HR P20160490 T1 HRP20160490 T1 HR P20160490T1 HR P20160490T T HRP20160490T T HR P20160490TT HR P20160490 T HRP20160490 T HR P20160490T HR P20160490 T1 HRP20160490 T1 HR P20160490T1
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- exchange chromatography
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- 238000002360 preparation method Methods 0.000 title claims 8
- 239000000203 mixture Substances 0.000 title claims 4
- 238000009472 formulation Methods 0.000 title claims 2
- 101000840540 Homo sapiens Iduronate 2-sulfatase Proteins 0.000 title 1
- 102100029199 Iduronate 2-sulfatase Human genes 0.000 claims 10
- 101710096421 Iduronate 2-sulfatase Proteins 0.000 claims 10
- 238000000034 method Methods 0.000 claims 9
- 210000004027 cell Anatomy 0.000 claims 5
- 239000012149 elution buffer Substances 0.000 claims 4
- 238000001042 affinity chromatography Methods 0.000 claims 3
- 125000003275 alpha amino acid group Chemical group 0.000 claims 3
- 238000005571 anion exchange chromatography Methods 0.000 claims 3
- 238000005277 cation exchange chromatography Methods 0.000 claims 3
- 238000004587 chromatography analysis Methods 0.000 claims 3
- 230000002209 hydrophobic effect Effects 0.000 claims 3
- UGJBHEZMOKVTIM-UHFFFAOYSA-N N-formylglycine Chemical compound OC(=O)CNC=O UGJBHEZMOKVTIM-UHFFFAOYSA-N 0.000 claims 2
- 239000002671 adjuvant Substances 0.000 claims 2
- 239000003963 antioxidant agent Substances 0.000 claims 2
- 230000003078 antioxidant effect Effects 0.000 claims 2
- -1 bacteriostatic Substances 0.000 claims 2
- 230000003385 bacteriostatic effect Effects 0.000 claims 2
- 239000000872 buffer Substances 0.000 claims 2
- 150000001720 carbohydrates Chemical class 0.000 claims 2
- 239000002738 chelating agent Substances 0.000 claims 2
- 239000003755 preservative agent Substances 0.000 claims 2
- 230000002335 preservative effect Effects 0.000 claims 2
- 239000003381 stabilizer Substances 0.000 claims 2
- 239000000126 substance Substances 0.000 claims 2
- 239000000375 suspending agent Substances 0.000 claims 2
- 239000002562 thickening agent Substances 0.000 claims 2
- NBSCHQHZLSJFNQ-QTVWNMPRSA-N D-Mannose-6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@@H]1O NBSCHQHZLSJFNQ-QTVWNMPRSA-N 0.000 claims 1
- 101150110586 IDS gene Proteins 0.000 claims 1
- 241000700605 Viruses Species 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000013604 expression vector Substances 0.000 claims 1
- 230000000415 inactivating effect Effects 0.000 claims 1
- 201000002273 mucopolysaccharidosis II Diseases 0.000 claims 1
- 208000022018 mucopolysaccharidosis type 2 Diseases 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
- 238000000746 purification Methods 0.000 claims 1
- 239000012679 serum free medium Substances 0.000 claims 1
- 230000001131 transforming effect Effects 0.000 claims 1
Classifications
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- 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
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
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- 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
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
-
- 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
-
- 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
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y301/00—Hydrolases acting on ester bonds (3.1)
- C12Y301/06—Sulfuric ester hydrolases (3.1.6)
- C12Y301/06013—Iduronate-2-sulfatase (3.1.6.13)
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biomedical Technology (AREA)
- Physical Education & Sports Medicine (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Pulmonology (AREA)
- Virology (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Claims (14)
1. Pripravak iduronat-2-sulfataze (IDS) čija je aminokiselinska sekvenca SEQ ID broj: 1, gdje je cisteinski ostatak na položaju 59 u IDS aminokiselinskoj sekvenci pretvoren u formilglicin (FGly) u molarnom omjeru od 65% ili više, poželjno u molarnom omjeru od 75% ili više.
2. IDS pripravak prema zahtjevu 1, gdje IDS čija je aminokiselinska sekvenca SEQ ID broj: 1 sadrži manozu-6-fosfat u količini od 2.0 do 4.0 mola po molu IDS-a, poželjno u količini od 2.5 do 3.0 mola po molu IDS-a.
3. Oblik koji sadrži IDS pripravak prema bilo kojem od zahtjeva 1 i 2.
4. Oblik prema zahtjevu 4 koji dalje sadrži:
farmaceutski prikladan nosač; i po izboru
jednu ili više tvari izabranih iz skupine koju čine pufer, ugljikohidrat, stabilizator, antioksidans, bakteriostatik, sredstvo za keliranje, adjuvans, sredstvo za suspendiranje, zgušnjivač i konzervans.
5. Postupak pripreme pripravka prema bilo kojem od zahtjeva 1 i 2, koji obuhvaća:
(1) uzgoj kulture rekombinantnog staničnog soja transformiranog genom koji kodira IDS predstavljen kao SEQ ID broj: 1 i dobivanje kulture; i
(2) pročišćavanje kulture kroz anionsko izmjenjivačku kromatografiju, hidrofobnu kromatografiju, kationsko izmjenjivačku kromatografiju, i afinitetnu kromatografiju, gdje se kationsko izmjenjivačka kromatografija provodi pomoću eluacijskog pufera čiji je pH od 4.0 do 6.0.
6. Postupak prema zahtjevu 5, koji sadrži:
(1) transformaciju stanice domaćina vektorom ekspresije koji nosi IDS gen radi dobivanja rekombinantnog staničnog soja;
(2) uzgoj kulture rekombinantnog staničnog soja u prisutnosti hidrolizata u mediju bez seruma te dobivanje kulture;
(3) pročišćavanje IDS-a iz kulture kroz anionsko izmjenjivačku kromatografiju, hidrofobnu kromatografiju, kationsko izmjenjivačku kromatografiju, i afinitetnu kromatografiju; i EP 12803297.6
(4) sjedinjavanje pročišćenog IDS-a s farmaceutski prikladnim nosačem.
7. Postupak prema bilo kojem od zahtjeva 5 i 6, gdje je stanica domaćin stanica jajnika kineskog hrčka.
8. Postupak prema bilo kojem od zahtjeva 5 do 7, gdje se hidrofobna kromatografija provodi pomoću eluacijskog pufera čiji je pH 5.0 do 7.0.
9. Postupak prema bilo kojem od zahtjeva 5 do 7, gdje se afinitetna kromatografija provodi pomoću eluacijskog pufera čiji je pH od 6.0 do 8.0.
10. Postupak prema bilo kojem od zahtjeva 5 do 7, gdje se anionska izmjenjivačka kromatografija provodi pomoću eluacijskog pufera čiji je pH od 5.5 do 7.5.
11. Postupak prema bilo kojem od zahtjeva 5 do 10, koji dalje obuhvaća inaktivaciju virusa na pH od 3.0 do 4.0.
12. Pripravak pripremljen postupkom prema bilo kojem od zahtjeva 5 do 11.
13. Postupak pripreme oblika koji obuhvaća oblikovanje pripravaka prema zahtjevima 1 ili 2 s farmaceutski prikladnim nosačem, i po izboru s jednom ili više tvari izabranih iz skupine koju čine pufer, ugljikohidrat, stabilizator, antioksidans, bakteriostatik, sredstvo za keliranje, adjuvans, sredstvo za suspendiranje, zgušnjivač i konzervans.
14. Pripravak prema bilo kojem od zahtjeva 1, 2 i 12, ili oblik prema bilo kojem od zahtjeva 3 i 4, za uporabu u liječenju Hunterovog sindroma.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161500994P | 2011-06-24 | 2011-06-24 | |
| KR1020120012718A KR101158673B1 (ko) | 2011-06-24 | 2012-02-08 | 재조합 인간 이듀로네이트-2-설파타아제를 포함하는 조성물, 제제 및 이의 제조방법 |
| EP12803297.6A EP2723369B2 (en) | 2011-06-24 | 2012-06-15 | Composition and formulation comprising recombinant human iduronate-2-sulfatase and preparation method thereof |
| PCT/KR2012/004734 WO2012177020A2 (en) | 2011-06-24 | 2012-06-15 | Composition and formulation comprising recombinant human iduronate-2-sulfatase and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HRP20160490T1 true HRP20160490T1 (hr) | 2016-08-12 |
| HRP20160490T4 HRP20160490T4 (hr) | 2023-09-15 |
Family
ID=46716009
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20160490TT HRP20160490T4 (hr) | 2011-06-24 | 2012-06-15 | Pripravak i oblik koji sadrže rekombinantnu humanu iduronat-2-sulfatazu te postupci njihove pripreme |
Country Status (28)
| Country | Link |
|---|---|
| US (2) | US9206402B2 (hr) |
| EP (1) | EP2723369B2 (hr) |
| JP (2) | JP5844459B2 (hr) |
| KR (2) | KR101158673B1 (hr) |
| CN (1) | CN103635203B (hr) |
| AU (2) | AU2012274215B2 (hr) |
| BR (1) | BR112013032193A2 (hr) |
| CA (1) | CA2839674C (hr) |
| CO (1) | CO6862105A2 (hr) |
| CY (1) | CY1117861T1 (hr) |
| DK (1) | DK2723369T4 (hr) |
| EA (1) | EA026499B1 (hr) |
| ES (1) | ES2575377T5 (hr) |
| FI (1) | FI2723369T4 (hr) |
| HK (1) | HK1195731A1 (hr) |
| HR (1) | HRP20160490T4 (hr) |
| HU (1) | HUE027431T2 (hr) |
| IL (1) | IL230120B (hr) |
| MX (1) | MX341946B (hr) |
| MY (1) | MY166647A (hr) |
| PE (1) | PE20140734A1 (hr) |
| PL (1) | PL2723369T5 (hr) |
| PT (1) | PT2723369E (hr) |
| RS (1) | RS54822B2 (hr) |
| SI (1) | SI2723369T2 (hr) |
| SM (1) | SMT201600194B (hr) |
| UA (1) | UA109949C2 (hr) |
| WO (1) | WO2012177020A2 (hr) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012101671A1 (en) * | 2011-01-25 | 2012-08-02 | Jcr Pharmaceuticals Co., Ltd. | Method for production of human recombinant iduronate 2-sulfatase |
| US20160145589A1 (en) | 2011-06-24 | 2016-05-26 | Green Cross Corporation | Composition and formulation comprising recombinant human iduronate-2-sulfatase and preparation method thereof |
| KR101158673B1 (ko) * | 2011-06-24 | 2012-07-03 | 주식회사 지씨바이오 | 재조합 인간 이듀로네이트-2-설파타아제를 포함하는 조성물, 제제 및 이의 제조방법 |
| US9150841B2 (en) | 2012-06-29 | 2015-10-06 | Shire Human Genetic Therapies, Inc. | Cells for producing recombinant iduronate-2-sulfatase |
| US20140004097A1 (en) * | 2012-06-29 | 2014-01-02 | Shire Human Genetic Therapies, Inc. | Method of producing recombinant iduronate-2-sulfatase |
| KR101380740B1 (ko) * | 2012-06-29 | 2014-04-11 | 쉐어 휴먼 제네텍 세러피스, 인코포레이티드 | 이듀로네이트-2-설파타제의 정제 |
| CN106153746B (zh) * | 2015-03-31 | 2020-11-06 | 三生国健药业（上海）股份有限公司 | IgG2型单抗二硫键配对分析方法 |
| CN106153744B (zh) * | 2015-03-31 | 2020-11-10 | 三生国健药业（上海）股份有限公司 | 融合蛋白二硫键配对分析方法 |
| CN106153745B (zh) * | 2015-03-31 | 2020-11-10 | 三生国健药业（上海）股份有限公司 | 抗体蛋白二硫键配对分析方法 |
| WO2017003270A1 (ko) * | 2015-07-02 | 2017-01-05 | 주식회사 녹십자 | 헌터증후군 치료제 및 치료방법 |
| KR20170004814A (ko) | 2015-07-02 | 2017-01-11 | 주식회사 녹십자 | 헌터증후군 치료제 |
| DK3397270T3 (da) | 2015-12-30 | 2024-05-06 | Green Cross Corp | Sammensætninger til anvendelse i behandlingen af hunters syndrom |
| SG11201806335RA (en) * | 2016-02-22 | 2018-09-27 | Agency Science Tech & Res | Cell culture medium |
| CA3059441A1 (en) | 2017-04-14 | 2018-10-18 | Stephen YOO | Treatment of mucopolysaccharidosis ii with recombinant human iduronate-2-sulfatase (ids) produced by human neural or glial cells |
| KR20190013615A (ko) * | 2017-07-28 | 2019-02-11 | 한미약품 주식회사 | 이두로네이트 2-설파타제 결합체 |
| CR20200129A (es) | 2017-10-02 | 2020-08-22 | Denali Therapeutics Inc | Proteínas de fusión que comprenden enzimas de terapia de reemplazo de enzimas |
| KR20190136271A (ko) | 2018-05-30 | 2019-12-10 | 주식회사 녹십자 | 대뇌 측뇌실 투여에 의해 헌터증후군을 치료하기 위한 방법 및 조성물 |
| WO2020050947A2 (en) * | 2018-09-05 | 2020-03-12 | Sangamo Therapeutics, Inc. | Enzymatic assays for quantifying therapy in subjects with mucopolysaccharidosis type i or ii |
| CN112805026A (zh) | 2019-02-06 | 2021-05-14 | 桑格摩生物治疗股份有限公司 | 用于治疗i型黏多糖贮积症的方法 |
| BR112023016075A2 (pt) | 2021-02-10 | 2023-11-21 | Regenxbio Inc | Método para tratar hepatoesplenomegalia, método de distribuição de um raav que codifica hids, método para tratar um sujeito humano, método de tratamento de um sujeito humano, método para determinar a eficácia do tratamento, método para identificar um sujeito como tendo mps ii |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5932211A (en) | 1991-11-12 | 1999-08-03 | Women's And Children's Hospital | Glycosylation variants of iduronate 2-sulfatase |
| IL155588A0 (en) * | 2003-04-27 | 2003-11-23 | Metabogal Ltd | Methods for expression of enzymatically active recombinant lysosomal enzymes in transgenic plant root cells and vectors used thereby |
| ATE534730T1 (de) * | 2003-02-11 | 2011-12-15 | Shire Human Genetic Therapies | Diagnose und behandlung von multiplen sulfatase- erkrankungen und anderen mit hilfe eines formylglycin bildenden enzyms |
| WO2005113765A2 (en) * | 2004-05-06 | 2005-12-01 | Biomarin Pharmaceutical Inc. | Methods of activation of sulfatases and methods and compositions of using the same |
| KR101158673B1 (ko) * | 2011-06-24 | 2012-07-03 | 주식회사 지씨바이오 | 재조합 인간 이듀로네이트-2-설파타아제를 포함하는 조성물, 제제 및 이의 제조방법 |
| KR101380740B1 (ko) | 2012-06-29 | 2014-04-11 | 쉐어 휴먼 제네텍 세러피스, 인코포레이티드 | 이듀로네이트-2-설파타제의 정제 |
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2012
- 2012-02-08 KR KR1020120012718A patent/KR101158673B1/ko active IP Right Grant
- 2012-05-24 KR KR1020120055450A patent/KR101910124B1/ko active IP Right Grant
- 2012-06-15 MX MX2013015127A patent/MX341946B/es active IP Right Grant
- 2012-06-15 EP EP12803297.6A patent/EP2723369B2/en active Active
- 2012-06-15 EA EA201490149A patent/EA026499B1/ru not_active IP Right Cessation
- 2012-06-15 BR BR112013032193A patent/BR112013032193A2/pt not_active Application Discontinuation
- 2012-06-15 PT PT128032976T patent/PT2723369E/pt unknown
- 2012-06-15 WO PCT/KR2012/004734 patent/WO2012177020A2/en active Application Filing
- 2012-06-15 US US14/128,918 patent/US9206402B2/en active Active
- 2012-06-15 PE PE2013002881A patent/PE20140734A1/es active IP Right Grant
- 2012-06-15 JP JP2014516901A patent/JP5844459B2/ja active Active
- 2012-06-15 MY MYPI2013004575A patent/MY166647A/en unknown
- 2012-06-15 HU HUE12803297A patent/HUE027431T2/en unknown
- 2012-06-15 ES ES12803297T patent/ES2575377T5/es active Active
- 2012-06-15 PL PL12803297.6T patent/PL2723369T5/pl unknown
- 2012-06-15 UA UAA201400664A patent/UA109949C2/ru unknown
- 2012-06-15 DK DK12803297.6T patent/DK2723369T4/da active
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