ES2306471T5 - Procedimiento para la purificación de un complejo factor VIII/factor von Willebrans(vWF) por cromatografía de intercambio catiónico - Google Patents
Procedimiento para la purificación de un complejo factor VIII/factor von Willebrans(vWF) por cromatografía de intercambio catiónico Download PDFInfo
- Publication number
- ES2306471T5 ES2306471T5 ES98905132T ES98905132T ES2306471T5 ES 2306471 T5 ES2306471 T5 ES 2306471T5 ES 98905132 T ES98905132 T ES 98905132T ES 98905132 T ES98905132 T ES 98905132T ES 2306471 T5 ES2306471 T5 ES 2306471T5
- Authority
- ES
- Spain
- Prior art keywords
- vwf
- factor viii
- complex
- molecular weight
- fraction
- 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
- 108010054218 Factor VIII Proteins 0.000 title claims abstract description 127
- 102000001690 Factor VIII Human genes 0.000 title claims abstract description 127
- 229960000301 factor viii Drugs 0.000 title claims abstract description 127
- 238000000034 method Methods 0.000 title claims abstract description 45
- 238000005277 cation exchange chromatography Methods 0.000 title claims abstract description 28
- 238000000746 purification Methods 0.000 title description 38
- 150000001768 cations Chemical class 0.000 claims abstract description 31
- 239000012460 protein solution Substances 0.000 claims abstract description 5
- 102100036537 von Willebrand factor Human genes 0.000 claims description 183
- 108010047303 von Willebrand Factor Proteins 0.000 claims description 182
- 230000000694 effects Effects 0.000 claims description 54
- 102100026735 Coagulation factor VIII Human genes 0.000 claims description 42
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 claims description 42
- 238000010828 elution Methods 0.000 claims description 32
- 238000002360 preparation method Methods 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 25
- 102000004169 proteins and genes Human genes 0.000 claims description 24
- 108090000623 proteins and genes Proteins 0.000 claims description 24
- 239000000047 product Substances 0.000 claims description 18
- 239000000243 solution Substances 0.000 claims description 13
- 239000000126 substance Substances 0.000 claims description 11
- 208000009292 Hemophilia A Diseases 0.000 claims description 9
- 229960002897 heparin Drugs 0.000 claims description 9
- 229920000669 heparin Polymers 0.000 claims description 9
- 102000039446 nucleic acids Human genes 0.000 claims description 9
- 108020004707 nucleic acids Proteins 0.000 claims description 9
- 150000007523 nucleic acids Chemical class 0.000 claims description 9
- 241000700605 Viruses Species 0.000 claims description 8
- 238000000354 decomposition reaction Methods 0.000 claims description 7
- 239000007853 buffer solution Substances 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 208000031220 Hemophilia Diseases 0.000 claims description 5
- 208000015181 infectious disease Diseases 0.000 claims description 5
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 5
- 201000003542 Factor VIII deficiency Diseases 0.000 claims description 4
- -1 heparin cation Chemical class 0.000 claims description 4
- 230000002458 infectious effect Effects 0.000 claims description 4
- 239000011230 binding agent Substances 0.000 claims description 3
- 238000004113 cell culture Methods 0.000 claims description 3
- 108010061932 Factor VIIIa Proteins 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
- 239000000284 extract Substances 0.000 claims description 2
- 238000005194 fractionation Methods 0.000 claims description 2
- 238000003860 storage Methods 0.000 claims description 2
- 239000006228 supernatant Substances 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 229920001184 polypeptide Polymers 0.000 claims 1
- 102000004196 processed proteins & peptides Human genes 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims 1
- 229960001134 von willebrand factor Drugs 0.000 description 156
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 81
- 239000011780 sodium chloride Substances 0.000 description 41
- 150000001450 anions Chemical class 0.000 description 9
- 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 8
- 239000012928 buffer substance Substances 0.000 description 8
- 238000005571 anion exchange chromatography Methods 0.000 description 7
- 238000005341 cation exchange Methods 0.000 description 7
- 238000001179 sorption measurement Methods 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 230000009849 deactivation Effects 0.000 description 6
- 239000000872 buffer Substances 0.000 description 5
- 230000003612 virological effect Effects 0.000 description 5
- 238000001042 affinity chromatography Methods 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000004471 Glycine Substances 0.000 description 3
- 208000032843 Hemorrhage Diseases 0.000 description 3
- 230000004520 agglutination Effects 0.000 description 3
- 238000005349 anion exchange Methods 0.000 description 3
- 125000000129 anionic group Chemical group 0.000 description 3
- 238000011097 chromatography purification Methods 0.000 description 3
- 239000007979 citrate buffer Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 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
- 229920002684 Sepharose Polymers 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 230000023555 blood coagulation Effects 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 235000011148 calcium chloride Nutrition 0.000 description 2
- 125000002091 cationic group Chemical group 0.000 description 2
- 238000003795 desorption Methods 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000009472 formulation Methods 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
- 239000000203 mixture Substances 0.000 description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- STCOOQWBFONSKY-UHFFFAOYSA-N tributyl phosphate Chemical compound CCCCOP(=O)(OCCCC)OCCCC STCOOQWBFONSKY-UHFFFAOYSA-N 0.000 description 2
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000004411 Antithrombin III Human genes 0.000 description 1
- 108090000935 Antithrombin III Proteins 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102100023804 Coagulation factor VII Human genes 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 108010023321 Factor VII Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 108010081391 Ristocetin Proteins 0.000 description 1
- 101001059734 Thermococcus litoralis (strain ATCC 51850 / DSM 5473 / JCM 8560 / NS-C) Trehalose/maltose-binding protein MalE Proteins 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 229960005348 antithrombin iii Drugs 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- WDIHJSXYQDMJHN-UHFFFAOYSA-L barium chloride Chemical compound [Cl-].[Cl-].[Ba+2] WDIHJSXYQDMJHN-UHFFFAOYSA-L 0.000 description 1
- 229910001626 barium chloride Inorganic materials 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- BGTFCAQCKWKTRL-YDEUACAXSA-N chembl1095986 Chemical compound C1[C@@H](N)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]([C@H]1C(N[C@H](C2=CC(O)=CC(O[C@@H]3[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)=C2C=2C(O)=CC=C(C=2)[C@@H](NC(=O)[C@@H]2NC(=O)[C@@H]3C=4C=C(C(=C(O)C=4)C)OC=4C(O)=CC=C(C=4)[C@@H](N)C(=O)N[C@@H](C(=O)N3)[C@H](O)C=3C=CC(O4)=CC=3)C(=O)N1)C(O)=O)=O)C(C=C1)=CC=C1OC1=C(O[C@@H]3[C@H]([C@H](O)[C@@H](O)[C@H](CO[C@@H]5[C@H]([C@@H](O)[C@H](O)[C@@H](C)O5)O)O3)O[C@@H]3[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O[C@@H]3[C@H]([C@H](O)[C@@H](CO)O3)O)C4=CC2=C1 BGTFCAQCKWKTRL-YDEUACAXSA-N 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
- 239000012228 culture supernatant Substances 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000012149 elution buffer Substances 0.000 description 1
- 229940012413 factor vii Drugs 0.000 description 1
- 229940003169 factor viii / von willebrand factor Drugs 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000004779 membrane envelope Anatomy 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 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
- 239000011148 porous material Substances 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 229950004257 ristocetin Drugs 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
- 239000002904 solvent Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000005728 strengthening 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
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000007669 thermal treatment 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
- 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)
- Medicinal Chemistry (AREA)
- Hematology (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Toxicology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT338/97 | 1997-02-27 | ||
| AT33897 | 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 |
|---|---|
| ES2306471T3 ES2306471T3 (es) | 2008-11-01 |
| ES2306471T5 true ES2306471T5 (es) | 2012-06-07 |
Family
ID=3487946
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES98905132T Expired - Lifetime ES2306471T5 (es) | 1997-02-27 | 1998-02-27 | Procedimiento para la purificación de un complejo factor VIII/factor von Willebrans(vWF) por cromatografía de intercambio catiónico |
Country Status (11)
| Country | Link |
|---|---|
| US (3) | US6831159B1 (enExample) |
| EP (1) | EP0971958B2 (enExample) |
| JP (1) | JP4250771B2 (enExample) |
| AR (2) | AR010121A1 (enExample) |
| AT (2) | AT406373B (enExample) |
| AU (1) | AU744919B2 (enExample) |
| CA (1) | CA2282841C (enExample) |
| DE (1) | DE59814211D1 (enExample) |
| ES (1) | ES2306471T5 (enExample) |
| NO (2) | NO324902B1 (enExample) |
| WO (1) | WO1998038220A1 (enExample) |
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. |
| HRP20130414T1 (en) | 2008-10-21 | 2013-06-30 | Baxter International Inc. | Lyophilized recombinant vwf formulations |
| HUE026907T2 (en) * | 2009-08-20 | 2016-07-28 | Baxalta Inc | Clean VWF to enhance removal of non-lipid enveloped viruses |
| RU2579977C2 (ru) | 2009-11-13 | 2016-04-10 | Грифольс Терапьютикс Инк. | СОДЕРЖАЩИЕ ФАКТОР ФОН ВИЛЛЕБРАНДА (vWF) ПРЕПАРАТЫ И СПОСОБЫ, НАБОРЫ И ПРИМЕНЕНИЯ, СВЯЗАННЫЕ С НИМИ |
| KR101997543B1 (ko) | 2010-07-30 | 2019-07-09 | 이엠디 밀리포어 코포레이션 | 크로마토그래피 매질 및 방법 |
| AU2011343813B2 (en) | 2010-12-15 | 2015-05-21 | Takeda Pharmaceutical Company Limited | Eluate collection using conductivity gradient |
| DK3412305T3 (da) * | 2011-06-10 | 2021-03-01 | Baxalta GmbH | Behandling af koagulationssygdom ved administration af rekombinant vwf |
| HRP20171272T4 (hr) | 2011-08-02 | 2020-08-07 | Baxalta GmbH | Sustavi i metode za povećanje prinosa proteina iz postupka rekombinatne proizvodnje |
| NZ631702A (en) | 2012-06-15 | 2017-01-27 | Grains Res & Dev Corp | Production of long chain polyunsaturated fatty acids in plant cells |
| US20150315263A1 (en) * | 2012-11-30 | 2015-11-05 | Centre For Bioseparation Technology - Vit | Monolith-based pseudo-bioaffinity purification methods for factor viii and applications thereof |
| DK3066119T3 (en) * | 2013-11-08 | 2018-11-12 | Csl Ltd | NEW PROCEDURE FOR CONCENTRATION OF THE VON WILLEBRAND FACTOR OR COMPLEXES OF IT |
| EP3082405A4 (en) | 2013-12-18 | 2017-12-13 | Commonwealth Scientific and Industrial Research Organisation | Lipid comprising long chain polyunsaturated fatty acids |
| PH12016502586B1 (en) | 2014-06-27 | 2023-07-19 | 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 |
| JP7307047B2 (ja) | 2017-07-07 | 2023-07-11 | 武田薬品工業株式会社 | 組換えｖｗｆの投与による重度のフォンヴィレブランド病を患う患者における消化管出血の治療 |
| JP2022524291A (ja) | 2019-02-01 | 2022-05-02 | 武田薬品工業株式会社 | 組換えＶＷＦ（ｒＶＷＦ）を使用する予防治療法 |
| 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. |
| AT401270B (de) | 1994-09-26 | 1996-07-25 | Immuno Ag | Verfahren zur quantifizierung von genomischer dna |
| CA2159044A1 (en) * | 1994-09-26 | 1996-03-27 | Falko-Guenter Falkner | Method of quantitating nucleic acids |
| DE4435392B4 (de) * | 1994-10-04 | 2008-02-07 | Immuno Ag | Verfahren zur Trennung von vWF in hochmolekularen vWF und niedermolekularen vWF |
| DE4435485C1 (de) * | 1994-10-04 | 1996-03-21 | Immuno Ag | Verfahren zur Gewinnung von hochreinem von Willebrand-Faktor |
| 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 AT AT98905132T patent/ATE391728T1/de active
- 1998-02-27 AU AU60806/98A patent/AU744919B2/en not_active Expired
- 1998-02-27 CA CA002282841A patent/CA2282841C/en not_active Expired - Lifetime
- 1998-02-27 DE DE59814211T patent/DE59814211D1/de 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 not_active Ceased
- 1998-02-27 US US09/367,459 patent/US6831159B1/en not_active Expired - Lifetime
- 1998-02-27 JP JP53706098A patent/JP4250771B2/ja 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 |
|---|---|
| ES2306471T3 (es) | 2008-11-01 |
| NO994137D0 (no) | 1999-08-26 |
| NO20071357L (no) | 1999-08-26 |
| US6831159B1 (en) | 2004-12-14 |
| AU6080698A (en) | 1998-09-18 |
| NO326257B1 (no) | 2008-10-27 |
| AU744919B2 (en) | 2002-03-07 |
| CA2282841A1 (en) | 1998-09-03 |
| EP0971958A1 (de) | 2000-01-19 |
| JP4250771B2 (ja) | 2009-04-08 |
| US20050239171A1 (en) | 2005-10-27 |
| US20020058625A1 (en) | 2002-05-16 |
| EP0971958B2 (de) | 2012-02-08 |
| DE59814211D1 (de) | 2008-05-21 |
| NO994137L (no) | 1999-08-26 |
| WO1998038220A1 (de) | 1998-09-03 |
| US7648958B2 (en) | 2010-01-19 |
| ATE391728T1 (de) | 2008-04-15 |
| CA2282841C (en) | 2008-12-02 |
| EP0971958B1 (de) | 2008-04-09 |
| US6953837B2 (en) | 2005-10-11 |
| AR010121A1 (es) | 2000-05-17 |
| AT406373B (de) | 2000-04-25 |
| ATA33897A (de) | 1999-09-15 |
| NO324902B1 (no) | 2007-12-27 |
| JP2001517212A (ja) | 2001-10-02 |
| AR059902A2 (es) | 2008-05-07 |
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