CA2223808A1 - Process for making liposome preparation - Google Patents
Process for making liposome preparation Download PDFInfo
- Publication number
- CA2223808A1 CA2223808A1 CA002223808A CA2223808A CA2223808A1 CA 2223808 A1 CA2223808 A1 CA 2223808A1 CA 002223808 A CA002223808 A CA 002223808A CA 2223808 A CA2223808 A CA 2223808A CA 2223808 A1 CA2223808 A1 CA 2223808A1
- Authority
- CA
- Canada
- Prior art keywords
- portions
- liposome
- lipid
- encapsulated
- formulation
- 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
- 239000002502 liposome Substances 0.000 title claims abstract description 153
- 238000000034 method Methods 0.000 title claims abstract description 76
- 238000002360 preparation method Methods 0.000 title claims abstract description 59
- 150000002632 lipids Chemical class 0.000 claims abstract description 73
- 239000000463 material Substances 0.000 claims abstract description 59
- 239000000203 mixture Substances 0.000 claims abstract description 46
- 238000009472 formulation Methods 0.000 claims abstract description 44
- 229960005486 vaccine Drugs 0.000 claims abstract description 20
- 230000000887 hydrating effect Effects 0.000 claims abstract description 9
- 239000000427 antigen Substances 0.000 claims description 26
- 102000036639 antigens Human genes 0.000 claims description 26
- 108091007433 antigens Proteins 0.000 claims description 26
- 239000000725 suspension Substances 0.000 claims description 16
- 229940079593 drug Drugs 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 13
- 239000008188 pellet Substances 0.000 claims description 11
- 238000005406 washing Methods 0.000 claims description 6
- YQDGWZZYGYKDLR-UZVLBLASSA-K sodium stibogluconate Chemical compound O.O.O.O.O.O.O.O.O.[Na+].[Na+].[Na+].O1[C@H]([C@H](O)CO)[C@H](O2)[C@H](C([O-])=O)O[Sb]21([O-])O[Sb]1(O)(O[C@H]2C([O-])=O)O[C@H]([C@H](O)CO)[C@@H]2O1 YQDGWZZYGYKDLR-UZVLBLASSA-K 0.000 claims description 3
- 229960001567 sodium stibogluconate Drugs 0.000 claims description 3
- 238000012377 drug delivery Methods 0.000 abstract description 4
- 239000000243 solution Substances 0.000 description 35
- 238000005538 encapsulation Methods 0.000 description 24
- 239000010408 film Substances 0.000 description 18
- 150000003904 phospholipids Chemical class 0.000 description 15
- 238000004108 freeze drying Methods 0.000 description 12
- 230000036571 hydration Effects 0.000 description 12
- 238000006703 hydration reaction Methods 0.000 description 12
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 10
- 229910052782 aluminium Inorganic materials 0.000 description 10
- 239000002953 phosphate buffered saline Substances 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 8
- 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 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 230000008901 benefit Effects 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 239000005337 ground glass Substances 0.000 description 6
- 230000036512 infertility Effects 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 239000011888 foil Substances 0.000 description 4
- 201000004792 malaria Diseases 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 239000012134 supernatant fraction Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 238000011166 aliquoting Methods 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000011176 pooling Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000002390 rotary evaporation Methods 0.000 description 3
- CITHEXJVPOWHKC-UUWRZZSWSA-N 1,2-di-O-myristoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCC CITHEXJVPOWHKC-UUWRZZSWSA-N 0.000 description 2
- 230000005587 bubbling Effects 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- BPHQZTVXXXJVHI-UHFFFAOYSA-N dimyristoyl phosphatidylglycerol Chemical compound CCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCCCCCCCC BPHQZTVXXXJVHI-UHFFFAOYSA-N 0.000 description 2
- 229960003724 dimyristoylphosphatidylcholine Drugs 0.000 description 2
- 229960005160 dimyristoylphosphatidylglycerol Drugs 0.000 description 2
- BPHQZTVXXXJVHI-AJQTZOPKSA-N ditetradecanoyl phosphatidylglycerol Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@@H](O)CO)OC(=O)CCCCCCCCCCCCC BPHQZTVXXXJVHI-AJQTZOPKSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 239000003517 fume Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 2
- 229920000515 polycarbonate Polymers 0.000 description 2
- 239000004417 polycarbonate Substances 0.000 description 2
- 239000002510 pyrogen Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000013190 sterility testing Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000008399 tap water Substances 0.000 description 2
- 235000020679 tap water Nutrition 0.000 description 2
- 239000010409 thin film Substances 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 1
- 101710117490 Circumsporozoite protein Proteins 0.000 description 1
- 241000518994 Conta Species 0.000 description 1
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 108010039334 HIV Envelope Protein gp120 Proteins 0.000 description 1
- 208000004554 Leishmaniasis Diseases 0.000 description 1
- 241000223960 Plasmodium falciparum Species 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000002514 anti-leishmanial effect Effects 0.000 description 1
- 239000003012 bilayer membrane Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000013020 final formulation Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 210000003046 sporozoite Anatomy 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K9/1277—Preparation processes; Proliposomes
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
- Y10T428/2984—Microcapsule with fluid core [includes liposome]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Dispersion Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Manufacturing Of Micro-Capsules (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/475,581 US6007838A (en) | 1995-06-07 | 1995-06-07 | Process for making liposome preparation |
| US08/475,581 | 1995-06-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2223808A1 true CA2223808A1 (en) | 1996-12-19 |
Family
ID=23888222
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002223808A Abandoned CA2223808A1 (en) | 1995-06-07 | 1996-06-06 | Process for making liposome preparation |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US6007838A (cg-RX-API-DMAC7.html) |
| EP (1) | EP0831779B2 (cg-RX-API-DMAC7.html) |
| JP (1) | JP2000514035A (cg-RX-API-DMAC7.html) |
| AT (1) | ATE203898T1 (cg-RX-API-DMAC7.html) |
| AU (1) | AU699055B2 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2223808A1 (cg-RX-API-DMAC7.html) |
| DE (1) | DE69614385T3 (cg-RX-API-DMAC7.html) |
| DK (1) | DK0831779T4 (cg-RX-API-DMAC7.html) |
| ES (1) | ES2159358T3 (cg-RX-API-DMAC7.html) |
| IL (1) | IL122486A (cg-RX-API-DMAC7.html) |
| PT (1) | PT831779E (cg-RX-API-DMAC7.html) |
| WO (1) | WO1996040063A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU752802C (en) * | 1997-11-14 | 2006-04-13 | Pacira Pharmaceuticals, Inc. | Production of multivesicular liposomes |
| US7115297B2 (en) | 2000-02-22 | 2006-10-03 | Suzanne Jaffe Stillman | Nutritionally fortified liquid composition with added value delivery systems/elements/additives |
| US7892586B2 (en) | 2001-02-22 | 2011-02-22 | Suzanne Jaffe Stillman | Water containing soluble fiber |
| US8178150B2 (en) | 2000-02-22 | 2012-05-15 | Suzanne Jaffe Stillman | Water containing soluble fiber |
| DE60130440D1 (de) | 2000-03-21 | 2007-10-25 | Suzanne Jaffe Stillman | Aufgussbeutel mit dekorativen gebrauchsmitteln, trägerelementen, abgabevorrichtung und verfahren |
| US8642051B2 (en) | 2000-03-21 | 2014-02-04 | Suzanne Jaffe Stillman | Method of hydration; infusion packet system(s), support member(s), delivery system(s), and method(s); with business model(s) and Method(s) |
| US20040022838A1 (en) * | 2001-06-20 | 2004-02-05 | Holick Michael F. | Regulation of cell proliferation and differentiation using topically applied peptides |
| US6852323B2 (en) | 2000-07-21 | 2005-02-08 | The Regents Of The University Of California | Methods and compositions for preventing and treating male erectile dysfunction and female sexual arousal disorder |
| US7223406B2 (en) * | 2000-07-21 | 2007-05-29 | The Regents Of The University Of California | Methods and compositions for preventing and treating male erectile dysfunction and female sexual arousal disorder |
| US20040082521A1 (en) * | 2002-03-29 | 2004-04-29 | Azaya Therapeutics Inc. | Novel formulations of digitalis glycosides for treating cell-proliferative and other diseases |
| US20030219696A1 (en) * | 2002-05-23 | 2003-11-27 | Moreland Gerald W. | Method and apparatus for preventing backflow in dental saliva evacuators |
| EP1519714B1 (en) | 2002-06-28 | 2010-10-20 | Protiva Biotherapeutics Inc. | Method and apparatus for producing liposomes |
| CN1674933B (zh) | 2002-08-02 | 2012-09-26 | 葛兰素史密丝克莱恩生物有限公司 | 疫苗组合物 |
| JP2006508126A (ja) * | 2002-11-06 | 2006-03-09 | アザヤ セラピューティクス インコーポレイティッド | 薬学的製剤のタンパク質安定化されたリポソーム製剤 |
| JP5639338B2 (ja) | 2005-07-27 | 2014-12-10 | プロチバ バイオセラピューティクス インコーポレイティッド | リポソームの製造システムおよび製造方法 |
| WO2007049279A2 (en) * | 2005-10-26 | 2007-05-03 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | A liposomal combination and uses thereof |
| ES2337309T5 (es) | 2006-06-12 | 2013-07-30 | Glaxosmithkline Biologicals S.A. | Vacuna |
| NO329127B1 (no) * | 2006-09-12 | 2010-08-30 | Epitarget As | Sporbart partikulaert materiale for legemiddelavlevering omfattende et matriseeller membranmateriale, et legemiddel, og et T1- og et T2*- magnetisk resonanskontrastmiddel |
| EP2427243A4 (en) | 2009-05-05 | 2012-11-21 | Vapogenix Inc | NEW FORMULATIONS OF VOLATILE ANESTHETICS AND METHOD OF ADMINISTRATION |
| WO2011119920A2 (en) | 2010-03-25 | 2011-09-29 | Oregon Health & Science University | Cmv glycoproteins and recombinant vectors |
| ES2667425T3 (es) | 2011-06-10 | 2018-05-10 | Oregon Health & Science University | Glucoproteínas y vectores recombinantes de CMV |
| EP2586461A1 (en) | 2011-10-27 | 2013-05-01 | Christopher L. Parks | Viral particles derived from an enveloped virus |
| EP2679596B1 (en) | 2012-06-27 | 2017-04-12 | International Aids Vaccine Initiative | HIV-1 env glycoprotein variant |
| PL2968214T3 (pl) | 2013-03-15 | 2021-11-02 | Newvapogen, Inc. | Nowe kompozycje przeciwbólowe |
| US20150065381A1 (en) | 2013-09-05 | 2015-03-05 | International Aids Vaccine Initiative | Methods of identifying novel hiv-1 immunogens |
| EP2873423B1 (en) | 2013-10-07 | 2017-05-31 | International Aids Vaccine Initiative | Soluble hiv-1 envelope glycoprotein trimers |
| US9392814B2 (en) | 2014-06-06 | 2016-07-19 | Nicholas J. Singer | Delivery system for drinks |
| US10174292B2 (en) | 2015-03-20 | 2019-01-08 | International Aids Vaccine Initiative | Soluble HIV-1 envelope glycoprotein trimers |
| EP3072901A1 (en) | 2015-03-23 | 2016-09-28 | International Aids Vaccine Initiative | Soluble hiv-1 envelope glycoprotein trimers |
| USD773313S1 (en) | 2015-06-23 | 2016-12-06 | Nicholas J. Singer | Package |
| PL3615005T3 (pl) | 2017-04-28 | 2025-10-06 | The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. | Kompozycje i sposoby dostarczania szczepionki |
| CN114126600B (zh) * | 2020-01-20 | 2024-03-08 | 广州谷森制药有限公司 | 三苯乙酸维兰特罗的脂质体制剂 |
| US11278494B1 (en) | 2021-01-22 | 2022-03-22 | Pacira Pharmaceuticals, Inc. | Manufacturing of bupivacaine multivesicular liposomes |
| US11357727B1 (en) | 2021-01-22 | 2022-06-14 | Pacira Pharmaceuticals, Inc. | Manufacturing of bupivacaine multivesicular liposomes |
| US12151024B2 (en) | 2021-01-22 | 2024-11-26 | Pacira Pharmaceuticals, Inc. | Manufacturing of bupivacaine multivesicular liposomes |
| US11033495B1 (en) | 2021-01-22 | 2021-06-15 | Pacira Pharmaceuticals, Inc. | Manufacturing of bupivacaine multivesicular liposomes |
| US12285419B2 (en) | 2021-10-14 | 2025-04-29 | Pacira Pharmaceuticals, Inc. | Bupivacaine multivesicular liposome formulations and uses thereof |
| US12280149B1 (en) | 2024-05-20 | 2025-04-22 | Pacira Pharmaceuticals, Inc. | Manufacturing of bupivacaine multivesicular liposomes |
| US12251472B1 (en) | 2024-05-20 | 2025-03-18 | Pacira Pharmaceuticals, Inc. | Manufacturing of bupivacaine multivesicular liposomes |
| US12156940B1 (en) | 2024-05-20 | 2024-12-03 | Pacira Pharmaceuticals, Inc. | Manufacturing of bupivacaine multivesicular liposomes |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2408387A2 (fr) † | 1975-06-30 | 1979-06-08 | Oreal | Compositions a base de dispersions aqueuses de spherules lipidiques |
| AU7128887A (en) * | 1986-02-10 | 1987-08-25 | Liposome Technology, Inc. | Controlled-release liposome delivery system |
| US4752425A (en) † | 1986-09-18 | 1988-06-21 | Liposome Technology, Inc. | High-encapsulation liposome processing method |
| DE4124252A1 (de) * | 1991-07-22 | 1993-01-28 | Knoll Ag | Verfahren zur herstellung einer sterilfiltrierbaren wirkstoffloesung |
| US5631237A (en) † | 1992-12-22 | 1997-05-20 | Dzau; Victor J. | Method for producing in vivo delivery of therapeutic agents via liposomes |
| FR2714601B1 (fr) † | 1993-12-30 | 1996-02-09 | Oreal | Composition dépigmentante pour le traitement simultané des couches superficielles et profondes, son utilisation. |
-
1995
- 1995-06-07 US US08/475,581 patent/US6007838A/en not_active Expired - Fee Related
-
1996
- 1996-06-06 PT PT96918002T patent/PT831779E/pt unknown
- 1996-06-06 AT AT96918002T patent/ATE203898T1/de not_active IP Right Cessation
- 1996-06-06 AU AU60365/96A patent/AU699055B2/en not_active Ceased
- 1996-06-06 CA CA002223808A patent/CA2223808A1/en not_active Abandoned
- 1996-06-06 ES ES96918002T patent/ES2159358T3/es not_active Expired - Lifetime
- 1996-06-06 DK DK96918002T patent/DK0831779T4/da active
- 1996-06-06 EP EP96918002A patent/EP0831779B2/en not_active Expired - Lifetime
- 1996-06-06 WO PCT/US1996/008622 patent/WO1996040063A1/en not_active Ceased
- 1996-06-06 DE DE69614385T patent/DE69614385T3/de not_active Expired - Fee Related
- 1996-06-06 IL IL12248696A patent/IL122486A/xx not_active IP Right Cessation
- 1996-06-06 JP JP09501158A patent/JP2000514035A/ja not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| EP0831779B2 (en) | 2005-01-19 |
| EP0831779A1 (en) | 1998-04-01 |
| AU699055B2 (en) | 1998-11-19 |
| WO1996040063A1 (en) | 1996-12-19 |
| IL122486A0 (en) | 1998-06-15 |
| PT831779E (pt) | 2001-11-30 |
| EP0831779B1 (en) | 2001-08-08 |
| ES2159358T3 (es) | 2001-10-01 |
| JP2000514035A (ja) | 2000-10-24 |
| DE69614385T2 (de) | 2002-05-23 |
| IL122486A (en) | 2000-07-16 |
| AU6036596A (en) | 1996-12-30 |
| DE69614385T3 (de) | 2005-05-25 |
| DK0831779T3 (da) | 2001-10-08 |
| US6007838A (en) | 1999-12-28 |
| DK0831779T4 (da) | 2005-06-06 |
| ATE203898T1 (de) | 2001-08-15 |
| DE69614385D1 (de) | 2001-09-13 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |