CA2149212A1 - Production accrue de proteines recombinantes a activite facteur viii:c - Google Patents
Production accrue de proteines recombinantes a activite facteur viii:cInfo
- Publication number
- CA2149212A1 CA2149212A1 CA002149212A CA2149212A CA2149212A1 CA 2149212 A1 CA2149212 A1 CA 2149212A1 CA 002149212 A CA002149212 A CA 002149212A CA 2149212 A CA2149212 A CA 2149212A CA 2149212 A1 CA2149212 A1 CA 2149212A1
- Authority
- CA
- Canada
- Prior art keywords
- factor viii
- heparin
- activity
- fviii
- factor
- 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.)
- Abandoned
Links
- 229960000301 factor viii Drugs 0.000 title claims abstract description 64
- 230000000694 effects Effects 0.000 title claims abstract description 30
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 18
- 102000004169 proteins and genes Human genes 0.000 title claims abstract description 17
- 238000004519 manufacturing process Methods 0.000 title description 10
- 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 claims abstract description 59
- 229920000669 heparin Polymers 0.000 claims abstract description 59
- 229960002897 heparin Drugs 0.000 claims abstract description 59
- 108010054218 Factor VIII Proteins 0.000 claims abstract description 58
- 102000001690 Factor VIII Human genes 0.000 claims abstract description 58
- 238000000034 method Methods 0.000 claims abstract description 22
- 230000001965 increasing effect Effects 0.000 claims abstract description 19
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 claims abstract description 6
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 claims abstract description 6
- 102000004895 Lipoproteins Human genes 0.000 claims description 22
- 108090001030 Lipoproteins Proteins 0.000 claims description 22
- 210000002966 serum Anatomy 0.000 claims description 18
- 239000001963 growth medium Substances 0.000 claims description 11
- 230000010261 cell growth Effects 0.000 claims description 8
- 238000012258 culturing Methods 0.000 claims description 7
- 108010047303 von Willebrand Factor Proteins 0.000 claims description 7
- 239000012679 serum free medium Substances 0.000 claims description 6
- 102100036537 von Willebrand factor Human genes 0.000 claims description 6
- 150000003904 phospholipids Chemical class 0.000 claims description 5
- 229960001134 von willebrand factor Drugs 0.000 claims description 3
- 230000014509 gene expression Effects 0.000 abstract description 23
- 210000004027 cell Anatomy 0.000 description 38
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 28
- 102100026735 Coagulation factor VIII Human genes 0.000 description 24
- 239000002609 medium Substances 0.000 description 18
- 150000001413 amino acids Chemical class 0.000 description 17
- 108090000765 processed proteins & peptides Proteins 0.000 description 16
- 238000007792 addition Methods 0.000 description 14
- 102000004196 processed proteins & peptides Human genes 0.000 description 14
- 210000002969 egg yolk Anatomy 0.000 description 12
- 229920001184 polypeptide Polymers 0.000 description 12
- 102000002322 Egg Proteins Human genes 0.000 description 11
- 108010000912 Egg Proteins Proteins 0.000 description 11
- 235000013345 egg yolk Nutrition 0.000 description 9
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 8
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 239000002953 phosphate buffered saline Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 102000004877 Insulin Human genes 0.000 description 4
- 108090001061 Insulin Proteins 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 235000013601 eggs Nutrition 0.000 description 4
- 102000057593 human F8 Human genes 0.000 description 4
- 229940125396 insulin Drugs 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 230000000087 stabilizing effect Effects 0.000 description 4
- 102100024746 Dihydrofolate reductase Human genes 0.000 description 3
- 208000009292 Hemophilia A Diseases 0.000 description 3
- 239000008118 PEG 6000 Substances 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000000701 coagulant Substances 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 108020001096 dihydrofolate reductase Proteins 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000005194 fractionation Methods 0.000 description 3
- 229960000900 human factor viii Drugs 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 239000013587 production medium Substances 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 241000699800 Cricetinae Species 0.000 description 2
- 108010059378 Endopeptidases Proteins 0.000 description 2
- 102000005593 Endopeptidases Human genes 0.000 description 2
- 208000031220 Hemophilia Diseases 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 101100221606 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) COS7 gene Proteins 0.000 description 2
- 108090000190 Thrombin Proteins 0.000 description 2
- 238000001042 affinity chromatography Methods 0.000 description 2
- 239000007640 basal medium Substances 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 230000023555 blood coagulation Effects 0.000 description 2
- 230000004186 co-expression Effects 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 229940066758 endopeptidases Drugs 0.000 description 2
- 230000001605 fetal effect Effects 0.000 description 2
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Chemical compound O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000013049 sediment Substances 0.000 description 2
- 239000004017 serum-free culture medium Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229960004072 thrombin Drugs 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 208000035049 Blood-Borne Infections Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102100023804 Coagulation factor VII Human genes 0.000 description 1
- 101150074155 DHFR gene Proteins 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 101100285518 Drosophila melanogaster how gene Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108010014172 Factor V Proteins 0.000 description 1
- 108010023321 Factor VII Proteins 0.000 description 1
- 201000003542 Factor VIII deficiency Diseases 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 208000028782 Hereditary disease Diseases 0.000 description 1
- 229920000209 Hexadimethrine bromide Polymers 0.000 description 1
- 101710172804 K protein Proteins 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- GXCLGNHLZMTTQJ-ZOULSWATSA-N L-alpha-D-Hepp-(1->3)-L-alpha-D-Hepp Chemical compound O[C@@H]1[C@@H]([C@@H](O)CO)O[C@H](O)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@@H]([C@@H](O)CO)O1 GXCLGNHLZMTTQJ-ZOULSWATSA-N 0.000 description 1
- 208000024556 Mendelian disease Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 101800004937 Protein C Proteins 0.000 description 1
- 102000017975 Protein C Human genes 0.000 description 1
- 101800001700 Saposin-D Proteins 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229920006318 anionic polymer Polymers 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 229920006317 cationic polymer Polymers 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229940012413 factor vii Drugs 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 210000002288 golgi apparatus Anatomy 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 230000031787 nutrient reservoir activity Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 229940012957 plasmin Drugs 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 229960000856 protein c Drugs 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000004114 suspension culture Methods 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/745—Blood coagulation or fibrinolysis factors
- C07K14/755—Factors VIII, e.g. factor VIII C (AHF), factor VIII Ag (VWF)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Biochemistry (AREA)
- Toxicology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Hematology (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US97735692A | 1992-11-17 | 1992-11-17 | |
| US4486593A | 1993-04-08 | 1993-04-08 | |
| US08/044,865 | 1993-04-08 | ||
| US07/977,356 | 1993-04-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2149212A1 true CA2149212A1 (fr) | 1994-05-26 |
Family
ID=26722082
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002149212A Abandoned CA2149212A1 (fr) | 1992-11-17 | 1993-11-17 | Production accrue de proteines recombinantes a activite facteur viii:c |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0679192A1 (fr) |
| JP (1) | JPH08502893A (fr) |
| AU (1) | AU5462694A (fr) |
| CA (1) | CA2149212A1 (fr) |
| WO (1) | WO1994011525A1 (fr) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9303601D0 (sv) * | 1993-11-01 | 1993-11-01 | Kabi Pharmacia Ab | Improved cell cultivation method and medium |
| AU4330597A (en) | 1996-08-30 | 1998-03-19 | Life Technologies, Inc. | Serum-free mammalian cell culture medium, and uses thereof |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0251843A1 (fr) * | 1986-06-06 | 1988-01-07 | Transgene S.A. | Procédé de préparation de facteur VIII à partir de cellules de mammifères |
| ATE63335T1 (de) * | 1986-07-11 | 1991-05-15 | Miles Inc | Herstellung von rekombinantem protein. |
| FR2619314B1 (fr) * | 1987-08-11 | 1990-06-15 | Transgene Sa | Analogue du facteur viii, procede de preparation et composition pharmaceutique le contenant |
| DK18288D0 (da) * | 1988-01-15 | 1988-01-15 | Nordisk Gentofte | Fremgangsmaade til pasteurisering af vandige oploesninger af faktor viii |
| JPH02254436A (ja) * | 1989-03-29 | 1990-10-15 | Mitsubishi Electric Corp | 映画用音声再生装置 |
| FR2657884B1 (fr) * | 1990-02-05 | 1994-09-02 | Tm Innovation | Procede pour la preparation du facteur viii humain et d'analogues du facteur viii. |
-
1993
- 1993-11-17 AU AU54626/94A patent/AU5462694A/en not_active Abandoned
- 1993-11-17 WO PCT/DK1993/000375 patent/WO1994011525A1/fr not_active Application Discontinuation
- 1993-11-17 EP EP94900069A patent/EP0679192A1/fr not_active Withdrawn
- 1993-11-17 JP JP6511619A patent/JPH08502893A/ja active Pending
- 1993-11-17 CA CA002149212A patent/CA2149212A1/fr not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP0679192A1 (fr) | 1995-11-02 |
| AU5462694A (en) | 1994-06-08 |
| WO1994011525A1 (fr) | 1994-05-26 |
| JPH08502893A (ja) | 1996-04-02 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued | ||
| FZDE | Discontinued |
Effective date: 19971117 |