CA2282841C - A method of purifying factor viii/vwf-complex by means of cation exchange chromatography - Google Patents
A method of purifying factor viii/vwf-complex by means of cation exchange chromatography Download PDFInfo
- Publication number
- CA2282841C CA2282841C CA002282841A CA2282841A CA2282841C CA 2282841 C CA2282841 C CA 2282841C CA 002282841 A CA002282841 A CA 002282841A CA 2282841 A CA2282841 A CA 2282841A CA 2282841 C CA2282841 C CA 2282841C
- Authority
- CA
- Canada
- Prior art keywords
- vwf
- factor viii
- complex
- activity
- molecular
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 229960000301 factor viii Drugs 0.000 title claims abstract description 136
- 238000000034 method Methods 0.000 title claims abstract description 41
- 238000005277 cation exchange chromatography Methods 0.000 title claims abstract description 33
- 108010054218 Factor VIII Proteins 0.000 claims abstract description 133
- 102000001690 Factor VIII Human genes 0.000 claims abstract description 133
- 150000001768 cations Chemical group 0.000 claims abstract description 34
- 238000010828 elution Methods 0.000 claims abstract description 18
- 239000012460 protein solution Substances 0.000 claims abstract description 6
- 108010047303 von Willebrand Factor Proteins 0.000 claims description 116
- 102100036537 von Willebrand factor Human genes 0.000 claims description 114
- 229960001134 von willebrand factor Drugs 0.000 claims description 114
- 230000000694 effects Effects 0.000 claims description 58
- 102100026735 Coagulation factor VIII Human genes 0.000 claims description 40
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 claims description 40
- 238000002360 preparation method Methods 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 26
- 102000004169 proteins and genes Human genes 0.000 claims description 25
- 108090000623 proteins and genes Proteins 0.000 claims description 25
- 239000000243 solution Substances 0.000 claims description 17
- 208000009292 Hemophilia A Diseases 0.000 claims description 9
- 102000039446 nucleic acids Human genes 0.000 claims description 8
- 108020004707 nucleic acids Proteins 0.000 claims description 8
- 150000007523 nucleic acids Chemical class 0.000 claims description 8
- 239000007857 degradation product Substances 0.000 claims description 6
- 208000031220 Hemophilia Diseases 0.000 claims description 5
- 239000000463 material Substances 0.000 claims description 5
- 201000003542 Factor VIII deficiency Diseases 0.000 claims description 4
- 208000015181 infectious disease Diseases 0.000 claims description 4
- 230000002458 infectious effect Effects 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 230000027455 binding Effects 0.000 claims description 3
- 239000007853 buffer solution Substances 0.000 claims description 3
- 238000004113 cell culture Methods 0.000 claims description 3
- 238000005194 fractionation Methods 0.000 claims description 3
- 108010061932 Factor VIIIa Proteins 0.000 claims description 2
- 230000004523 agglutinating effect Effects 0.000 claims description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 229940003169 factor viii / von willebrand factor Drugs 0.000 claims description 2
- 239000006228 supernatant Substances 0.000 claims description 2
- 208000027276 Von Willebrand disease Diseases 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 208000012137 von Willebrand disease (hereditary or acquired) Diseases 0.000 claims 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 77
- 239000011780 sodium chloride Substances 0.000 description 39
- 238000000746 purification Methods 0.000 description 31
- 239000000872 buffer Substances 0.000 description 20
- 150000001450 anions Chemical class 0.000 description 13
- 238000005571 anion exchange chromatography Methods 0.000 description 9
- 239000007858 starting material Substances 0.000 description 9
- 241000700605 Viruses Species 0.000 description 8
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- 238000011084 recovery Methods 0.000 description 6
- 238000001179 sorption measurement Methods 0.000 description 6
- 238000001042 affinity chromatography Methods 0.000 description 5
- 229960002897 heparin Drugs 0.000 description 5
- 229920000669 heparin Polymers 0.000 description 5
- 230000002779 inactivation Effects 0.000 description 5
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 238000005341 cation exchange Methods 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 238000011097 chromatography purification Methods 0.000 description 4
- 239000004471 Glycine Substances 0.000 description 3
- 208000032843 Hemorrhage Diseases 0.000 description 3
- 229920002684 Sepharose Polymers 0.000 description 3
- 230000004520 agglutination Effects 0.000 description 3
- 239000012620 biological material Substances 0.000 description 3
- 230000000740 bleeding effect Effects 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 229910018626 Al(OH) Inorganic materials 0.000 description 2
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 2
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 238000005349 anion exchange Methods 0.000 description 2
- 239000003114 blood coagulation factor Substances 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000003795 desorption Methods 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 239000012149 elution buffer Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- -1 glycine and lysine Chemical class 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
- STCOOQWBFONSKY-UHFFFAOYSA-N tributyl phosphate Chemical compound CCCCOP(=O)(OCCCC)OCCCC STCOOQWBFONSKY-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- 102000004411 Antithrombin III Human genes 0.000 description 1
- 108090000935 Antithrombin III Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 102000023159 Platelet Glycoprotein GPIb-IX Complex Human genes 0.000 description 1
- 108010045766 Platelet Glycoprotein GPIb-IX Complex Proteins 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229960005348 antithrombin iii Drugs 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 102000023732 binding proteins Human genes 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 229940019700 blood coagulation factors Drugs 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000011026 diafiltration Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 244000000009 viral human pathogen Species 0.000 description 1
- 230000003253 viricidal effect Effects 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
Classifications
-
- 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
- A61K38/36—Blood coagulation or fibrinolysis factors
- A61K38/37—Factors VIII
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- 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
- C07K14/745—Blood coagulation or fibrinolysis factors
- C07K14/755—Factors VIII, e.g. factor VIII C (AHF), factor VIII Ag (VWF)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Toxicology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ATA338/97 | 1997-02-27 | ||
| AT0033897A AT406373B (de) | 1997-02-27 | 1997-02-27 | Verfahren zur reinigung von faktor viii/vwf-komplex mittels kationenaustauscherchromatographie |
| PCT/AT1998/000043 WO1998038220A1 (de) | 1997-02-27 | 1998-02-27 | Verfahren zur reinigung von faktor viii/vwf-komplex mittels kationenaustauscherchromatographie |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2282841A1 CA2282841A1 (en) | 1998-09-03 |
| CA2282841C true CA2282841C (en) | 2008-12-02 |
Family
ID=3487946
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002282841A Expired - Lifetime CA2282841C (en) | 1997-02-27 | 1998-02-27 | A method of purifying factor viii/vwf-complex by means of cation exchange chromatography |
Country Status (11)
| Country | Link |
|---|---|
| US (3) | US6831159B1 (instruction) |
| EP (1) | EP0971958B2 (instruction) |
| JP (1) | JP4250771B2 (instruction) |
| AR (2) | AR010121A1 (instruction) |
| AT (2) | AT406373B (instruction) |
| AU (1) | AU744919B2 (instruction) |
| CA (1) | CA2282841C (instruction) |
| DE (1) | DE59814211D1 (instruction) |
| ES (1) | ES2306471T5 (instruction) |
| NO (2) | NO324902B1 (instruction) |
| WO (1) | WO1998038220A1 (instruction) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT406373B (de) | 1997-02-27 | 2000-04-25 | Immuno Ag | Verfahren zur reinigung von faktor viii/vwf-komplex mittels kationenaustauscherchromatographie |
| EP1593388A1 (en) * | 2004-05-05 | 2005-11-09 | ZLB Behring GmbH | Therapeutic plasma protein-concentrates containing von willebrand factor as high molecular weight multimers |
| US11197916B2 (en) | 2007-12-28 | 2021-12-14 | Takeda Pharmaceutical Company Limited | Lyophilized recombinant VWF formulations |
| ES2298096B1 (es) | 2008-01-08 | 2009-01-01 | Grifols, S.A. | Procedimiento para la obtencion de un concentrado de factor von willebrand o del complejo de factor viii/factor von willebrand y utilizacionde los mismos. |
| TWI670072B (zh) | 2008-10-21 | 2019-09-01 | 美商巴克斯歐塔公司 | 凍乾的重組ｖｗｆ調配物 |
| NZ598249A (en) * | 2009-08-20 | 2014-04-30 | Baxter Int | Purification of vwf for increased removal of non-lipid enveloped viruses |
| KR101808751B1 (ko) | 2009-11-13 | 2017-12-13 | 그리폴스 테라퓨틱스 인코포레이티드 | 폰 빌레브란트 인자(ｖＷＦ)-함유 제제, 및 그와 관련된 방법, 키트 및 용도 |
| JP2013535683A (ja) * | 2010-07-30 | 2013-09-12 | イー・エム・デイー・ミリポア・コーポレイシヨン | クロマトグラフィー媒体及び方法 |
| SG191186A1 (en) | 2010-12-15 | 2013-07-31 | Baxter Int | Eluate collection using conductivity gradient |
| HRP20180962T1 (hr) * | 2011-06-10 | 2018-10-19 | Baxalta GmbH | Liječenje bolesti zgrušavanja primjenom rekombinantnog vwf |
| US9534037B2 (en) | 2011-08-02 | 2017-01-03 | Baxalta GmbH | Systems and methods to increase protein yield from recombinant manufacturing processes |
| NZ631702A (en) | 2012-06-15 | 2017-01-27 | Grains Res & Dev Corp | Production of long chain polyunsaturated fatty acids in plant cells |
| WO2014083510A1 (en) * | 2012-11-30 | 2014-06-05 | Centre For Bioseparation Technology - Vit | Monolith-based pseudo-bioaffinity purification methods for factor viii and applications thereof |
| US10246485B2 (en) | 2013-11-08 | 2019-04-02 | Csl Limited | Method to concentrate von willebrand factor or complexes thereof |
| PE20170253A1 (es) | 2013-12-18 | 2017-04-14 | Nuseed Pty Ltd | Lipido que comprende acidos grasos poliinsaturados de cadena larga |
| SG11201610596PA (en) | 2014-06-27 | 2017-01-27 | Commw Scient Ind Res Org | Lipid comprising docosapentaenoic acid |
| EP3188816B1 (en) | 2014-09-02 | 2021-06-09 | EMD Millipore Corporation | Chromatography media comprising discrete porous bundles of nanofibrils |
| CA2966515C (en) | 2014-12-08 | 2021-04-27 | Emd Millipore Corporation | Mixed bed ion exchange adsorber |
| CN111436193A (zh) | 2017-07-07 | 2020-07-21 | 百深公司 | 通过施用重组vwf来治疗患有严重冯维勒布兰德病的患者中的胃肠道出血 |
| KR20210134642A (ko) | 2019-02-01 | 2021-11-10 | 다케다 야쿠힌 고교 가부시키가이샤 | 재조합 vwf (rvwf)를 이용한 예방 치료 방법 |
| CN114106145B (zh) * | 2021-10-22 | 2023-09-01 | 山东泰邦生物制品有限公司 | 一种血源人凝血因子ⅷ/血管性血友病因子复合物生产工艺 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4540573A (en) | 1983-07-14 | 1985-09-10 | New York Blood Center, Inc. | Undenatured virus-free biologically active protein derivatives |
| GB8403473D0 (en) * | 1984-02-09 | 1984-03-14 | Special Trustees For St Thomas | Purification of factor viii |
| US5200510A (en) * | 1987-06-16 | 1993-04-06 | Zymogenetics, Inc. | Method for purifying factor viii:c, von willebrand factor and complexes thereof |
| FR2651437A1 (fr) * | 1989-09-05 | 1991-03-08 | Lille Transfusion Sanguine | Procede de preparation de concentre du complexe facteur viii-facteur von willebrand de la coagulation sanguine a partir de plasma total. |
| NZ237244A (en) | 1990-03-02 | 1992-10-28 | Bio Technology General Corp | Cloning and production of human von willebrand factor analogues and compositions thereof |
| FR2686899B1 (fr) | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
| IT1256622B (it) * | 1992-12-04 | 1995-12-12 | Sclavo Spa | Processo per l'estrazione del complesso fattore viii-fattore von willebrand (fviii:c-fvw) da plasma umano totale. |
| CA2159044A1 (en) | 1994-09-26 | 1996-03-27 | Falko-Guenter Falkner | Method of quantitating nucleic acids |
| AT401270B (de) * | 1994-09-26 | 1996-07-25 | Immuno Ag | Verfahren zur quantifizierung von genomischer dna |
| DE4435485C1 (de) | 1994-10-04 | 1996-03-21 | Immuno Ag | Verfahren zur Gewinnung von hochreinem von Willebrand-Faktor |
| DE4435392B4 (de) * | 1994-10-04 | 2008-02-07 | Immuno Ag | Verfahren zur Trennung von vWF in hochmolekularen vWF und niedermolekularen vWF |
| AT403764B (de) | 1996-03-15 | 1998-05-25 | Immuno Ag | Stabiler faktor viii/vwf-komplex |
| CA2251558C (en) | 1996-04-12 | 2005-11-22 | Immuno Aktiengesellschaft | Highly purified factor viii complex |
| AT403765B (de) | 1996-04-12 | 1998-05-25 | Immuno Ag | Verfahren zur herstellung einer präparation enthaltend einen hochgereinigten komplex |
| AT406373B (de) | 1997-02-27 | 2000-04-25 | Immuno Ag | Verfahren zur reinigung von faktor viii/vwf-komplex mittels kationenaustauscherchromatographie |
| AT405403B (de) | 1997-02-27 | 1999-08-25 | Immuno Ag | Reinigung von von willebrand-faktor durch kationenaustauscherchromatographie |
-
1997
- 1997-02-27 AT AT0033897A patent/AT406373B/de not_active IP Right Cessation
-
1998
- 1998-02-25 AR ARP980100835A patent/AR010121A1/es active IP Right Grant
- 1998-02-27 DE DE59814211T patent/DE59814211D1/de not_active Expired - Lifetime
- 1998-02-27 AT AT98905132T patent/ATE391728T1/de active
- 1998-02-27 CA CA002282841A patent/CA2282841C/en not_active Expired - Lifetime
- 1998-02-27 ES ES98905132T patent/ES2306471T5/es not_active Expired - Lifetime
- 1998-02-27 WO PCT/AT1998/000043 patent/WO1998038220A1/de active IP Right Grant
- 1998-02-27 JP JP53706098A patent/JP4250771B2/ja not_active Expired - Lifetime
- 1998-02-27 AU AU60806/98A patent/AU744919B2/en not_active Expired
- 1998-02-27 US US09/367,459 patent/US6831159B1/en not_active Expired - Lifetime
- 1998-02-27 EP EP98905132A patent/EP0971958B2/de not_active Expired - Lifetime
-
1999
- 1999-08-26 NO NO19994137A patent/NO324902B1/no not_active IP Right Cessation
-
2001
- 2001-11-02 US US10/003,621 patent/US6953837B2/en not_active Expired - Lifetime
-
2004
- 2004-02-27 US US10/789,562 patent/US7648958B2/en not_active Expired - Fee Related
-
2007
- 2007-03-13 NO NO20071357A patent/NO326257B1/no not_active IP Right Cessation
- 2007-03-15 AR ARP070101059A patent/AR059902A2/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AT406373B (de) | 2000-04-25 |
| US7648958B2 (en) | 2010-01-19 |
| EP0971958B1 (de) | 2008-04-09 |
| ATE391728T1 (de) | 2008-04-15 |
| EP0971958A1 (de) | 2000-01-19 |
| ES2306471T5 (es) | 2012-06-07 |
| ES2306471T3 (es) | 2008-11-01 |
| DE59814211D1 (de) | 2008-05-21 |
| NO324902B1 (no) | 2007-12-27 |
| JP4250771B2 (ja) | 2009-04-08 |
| NO994137L (no) | 1999-08-26 |
| EP0971958B2 (de) | 2012-02-08 |
| US20050239171A1 (en) | 2005-10-27 |
| AU6080698A (en) | 1998-09-18 |
| JP2001517212A (ja) | 2001-10-02 |
| US6953837B2 (en) | 2005-10-11 |
| NO994137D0 (no) | 1999-08-26 |
| AR059902A2 (es) | 2008-05-07 |
| US6831159B1 (en) | 2004-12-14 |
| NO326257B1 (no) | 2008-10-27 |
| CA2282841A1 (en) | 1998-09-03 |
| AR010121A1 (es) | 2000-05-17 |
| WO1998038220A1 (de) | 1998-09-03 |
| AU744919B2 (en) | 2002-03-07 |
| US20020058625A1 (en) | 2002-05-16 |
| NO20071357L (no) | 1999-08-26 |
| ATA33897A (de) | 1999-09-15 |
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