CA2157902A1 - Ciblage de tumeurs a l'aide de conjugues d'oligonucleotide l-enantiomeres d'immunoreactifs et de radionucleides chelates - Google Patents
Ciblage de tumeurs a l'aide de conjugues d'oligonucleotide l-enantiomeres d'immunoreactifs et de radionucleides chelatesInfo
- Publication number
- CA2157902A1 CA2157902A1 CA002157902A CA2157902A CA2157902A1 CA 2157902 A1 CA2157902 A1 CA 2157902A1 CA 002157902 A CA002157902 A CA 002157902A CA 2157902 A CA2157902 A CA 2157902A CA 2157902 A1 CA2157902 A1 CA 2157902A1
- Authority
- CA
- Canada
- Prior art keywords
- enantiomeric
- residue
- precursor
- reagent
- group
- 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
- 108091034117 Oligonucleotide Proteins 0.000 title claims abstract description 241
- 230000008685 targeting Effects 0.000 title claims abstract description 83
- 206010028980 Neoplasm Diseases 0.000 title claims description 32
- 230000002285 radioactive effect Effects 0.000 claims abstract description 74
- 238000000034 method Methods 0.000 claims abstract description 65
- 230000000295 complement effect Effects 0.000 claims abstract description 59
- 125000005647 linker group Chemical group 0.000 claims abstract description 36
- 239000002738 chelating agent Substances 0.000 claims abstract description 28
- 238000009396 hybridization Methods 0.000 claims abstract description 18
- 238000003384 imaging method Methods 0.000 claims abstract description 12
- 239000012634 fragment Substances 0.000 claims abstract description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 125000003729 nucleotide group Chemical group 0.000 claims description 112
- -1 poly(alkylene glycol Chemical compound 0.000 claims description 111
- 239000002773 nucleotide Substances 0.000 claims description 107
- 239000003153 chemical reaction reagent Substances 0.000 claims description 75
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- 102000004169 proteins and genes Human genes 0.000 claims description 68
- 239000002243 precursor Substances 0.000 claims description 57
- 108020004414 DNA Proteins 0.000 claims description 56
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- 230000000694 effects Effects 0.000 claims description 9
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- CNHYKKNIIGEXAY-UHFFFAOYSA-N thiolan-2-imine Chemical compound N=C1CCCS1 CNHYKKNIIGEXAY-UHFFFAOYSA-N 0.000 claims description 8
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 6
- 108060002716 Exonuclease Proteins 0.000 claims description 4
- 102000013165 exonuclease Human genes 0.000 claims description 4
- FPKVOQKZMBDBKP-UHFFFAOYSA-N 1-[4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexanecarbonyl]oxy-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)C1CCC(CN2C(C=CC2=O)=O)CC1 FPKVOQKZMBDBKP-UHFFFAOYSA-N 0.000 claims description 3
- VHYRLCJMMJQUBY-UHFFFAOYSA-N 1-[4-[4-(2,5-dioxopyrrol-1-yl)phenyl]butanoyloxy]-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound O=C1C(S(=O)(=O)O)CC(=O)N1OC(=O)CCCC1=CC=C(N2C(C=CC2=O)=O)C=C1 VHYRLCJMMJQUBY-UHFFFAOYSA-N 0.000 claims description 3
- 150000005690 diesters Chemical class 0.000 claims description 2
- FLCQLSRLQIPNLM-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 2-acetylsulfanylacetate Chemical compound CC(=O)SCC(=O)ON1C(=O)CCC1=O FLCQLSRLQIPNLM-UHFFFAOYSA-N 0.000 claims 2
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 claims 1
- LAEUQSVCOOXLEE-UHFFFAOYSA-N 4-[(2-iodoacetyl)amino]benzoic acid Chemical compound OC(=O)C1=CC=C(NC(=O)CI)C=C1 LAEUQSVCOOXLEE-UHFFFAOYSA-N 0.000 claims 1
- 229940125877 compound 31 Drugs 0.000 claims 1
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 5
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- PLDUPXSUYLZYBN-UHFFFAOYSA-N Fluphenazine Chemical compound C1CN(CCO)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 PLDUPXSUYLZYBN-UHFFFAOYSA-N 0.000 description 98
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- 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 49
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
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- UAFBBLZEQSKFBK-UHFFFAOYSA-J tetrasodium;2-[[6-[6-[6-[[bis(carboxylatomethyl)amino]methyl]pyridin-2-yl]-4-(3-isothiocyanato-4-methoxyphenyl)pyridin-2-yl]pyridin-2-yl]methyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(N=C=S)C(OC)=CC=C1C1=CC(C=2N=C(CN(CC([O-])=O)CC([O-])=O)C=CC=2)=NC(C=2N=C(CN(CC([O-])=O)CC([O-])=O)C=CC=2)=C1 UAFBBLZEQSKFBK-UHFFFAOYSA-J 0.000 description 13
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- 235000011803 sesame oil Nutrition 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 238000002603 single-photon emission computed tomography Methods 0.000 description 1
- 238000003998 size exclusion chromatography high performance liquid chromatography Methods 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- VUFNRPJNRFOTGK-UHFFFAOYSA-M sodium;1-[4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexanecarbonyl]oxy-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)C1CCC(CN2C(C=CC2=O)=O)CC1 VUFNRPJNRFOTGK-UHFFFAOYSA-M 0.000 description 1
- HHSGWIABCIVPJT-UHFFFAOYSA-M sodium;1-[4-[(2-iodoacetyl)amino]benzoyl]oxy-2,5-dioxopyrrolidine-3-sulfonate Chemical compound [Na+].O=C1C(S(=O)(=O)[O-])CC(=O)N1OC(=O)C1=CC=C(NC(=O)CI)C=C1 HHSGWIABCIVPJT-UHFFFAOYSA-M 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 108010068698 spleen exonuclease Proteins 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 229910052712 strontium Inorganic materials 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- ACTRVOBWPAIOHC-XIXRPRMCSA-N succimer Chemical compound OC(=O)[C@@H](S)[C@@H](S)C(O)=O ACTRVOBWPAIOHC-XIXRPRMCSA-N 0.000 description 1
- 229960005346 succimer Drugs 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 150000003464 sulfur compounds Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- GKLVYJBZJHMRIY-UHFFFAOYSA-N technetium atom Chemical compound [Tc] GKLVYJBZJHMRIY-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- UWHCKJMYHZGTIT-UHFFFAOYSA-N tetraethylene glycol Chemical compound OCCOCCOCCOCCO UWHCKJMYHZGTIT-UHFFFAOYSA-N 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- YNHJECZULSZAQK-UHFFFAOYSA-N tetraphenylporphyrin Chemical compound C1=CC(C(=C2C=CC(N2)=C(C=2C=CC=CC=2)C=2C=CC(N=2)=C(C=2C=CC=CC=2)C2=CC=C3N2)C=2C=CC=CC=2)=NC1=C3C1=CC=CC=C1 YNHJECZULSZAQK-UHFFFAOYSA-N 0.000 description 1
- 229910052716 thallium Inorganic materials 0.000 description 1
- TXBBUSUXYMIVOS-UHFFFAOYSA-N thenoyltrifluoroacetone Chemical compound FC(F)(F)C(=O)CC(=O)C1=CC=CS1 TXBBUSUXYMIVOS-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 125000004001 thioalkyl group Chemical group 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 125000000101 thioether group Chemical group 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- ATGUDZODTABURZ-UHFFFAOYSA-N thiolan-2-ylideneazanium;chloride Chemical compound Cl.N=C1CCCS1 ATGUDZODTABURZ-UHFFFAOYSA-N 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 238000004846 x-ray emission Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
- A61K51/1093—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody conjugates with carriers being antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2123/00—Preparations for testing in vivo
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Public Health (AREA)
- Physics & Mathematics (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Optics & Photonics (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3308393A | 1993-03-10 | 1993-03-10 | |
| US033083 | 1993-03-10 | ||
| PCT/US1994/002610 WO1994020523A1 (fr) | 1993-03-10 | 1994-03-10 | Ciblage de tumeur au moyen de conjugues oligonucleotidiques l-enantiomeres d'immunoreactifs et de radionucleides chelates |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2157902A1 true CA2157902A1 (fr) | 1994-09-15 |
Family
ID=21868470
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002157902A Abandoned CA2157902A1 (fr) | 1993-03-10 | 1994-03-10 | Ciblage de tumeurs a l'aide de conjugues d'oligonucleotide l-enantiomeres d'immunoreactifs et de radionucleides chelates |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0691981A1 (fr) |
| JP (1) | JPH08512019A (fr) |
| AU (1) | AU6402594A (fr) |
| CA (1) | CA2157902A1 (fr) |
| WO (1) | WO1994020523A1 (fr) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU672951B2 (en) * | 1992-05-07 | 1996-10-24 | Ge Healthcare As | Complexing agents and targeting immunoreagents |
| US6444652B1 (en) * | 1998-08-10 | 2002-09-03 | Novirio Pharmaceuticals Limited | β-L-2'-deoxy-nucleosides for the treatment of hepatitis B |
| PT2415776T (pt) * | 1998-08-10 | 2016-07-07 | Novartis Ag | Beta-l-2'-desoxi-nucleosidos para o tratamento da hepatite b |
| US6787526B1 (en) | 2000-05-26 | 2004-09-07 | Idenix Pharmaceuticals, Inc. | Methods of treating hepatitis delta virus infection with β-L-2′-deoxy-nucleosides |
| US6875751B2 (en) | 2000-06-15 | 2005-04-05 | Idenix Pharmaceuticals, Inc. | 3′-prodrugs of 2′-deoxy-β-L-nucleosides |
| EP1264603B8 (fr) * | 2001-06-10 | 2010-03-03 | Noxxon Pharma AG | Utilisation de L-polynucleotides pour l'imagerie diagnostique |
| EP1288309A1 (fr) * | 2001-08-30 | 2003-03-05 | Noxxon Pharma AG | Procédé pour marquer les L-acides nucléiques |
| US6942972B2 (en) * | 2001-10-24 | 2005-09-13 | Beckman Coulter, Inc. | Efficient synthesis of protein-oligonucleotide conjugates |
| EP1306382A1 (fr) * | 2001-10-26 | 2003-05-02 | Noxxon Pharma AG | L-acides nucléiques modifiés |
| ATE469164T1 (de) * | 2001-10-26 | 2010-06-15 | Noxxon Pharma Ag | Modifizierte l-nukleinsäure |
| TWI244393B (en) | 2002-08-06 | 2005-12-01 | Idenix Pharmaceuticals Inc | Crystalline and amorphous forms of beta-L-2'-deoxythymidine |
| EP1572095B1 (fr) | 2002-09-13 | 2015-06-10 | Novartis AG | Beta-l-2'-desoxynucleosides pour l'utilisation dans le traitement de souches du vhb resistantes |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4863713A (en) * | 1986-06-23 | 1989-09-05 | The Board Of Trustees Of Leland Stanford Jr. Univ. | Method and system for administering therapeutic and diagnostic agents |
| US5158880A (en) * | 1988-09-23 | 1992-10-27 | E. I. Du Pont De Nemours And Company | Process for preparing solid perfluorocarbon polymer supports having attached perfluorocarbon-substituted ligand or binder |
| US5367080A (en) * | 1990-11-08 | 1994-11-22 | Sterling Winthrop Inc. | Complexing agents and targeting radioactive immunoreagents useful in therapeutic and diagnostic imaging compositions and methods |
-
1994
- 1994-03-10 JP JP6520313A patent/JPH08512019A/ja active Pending
- 1994-03-10 CA CA002157902A patent/CA2157902A1/fr not_active Abandoned
- 1994-03-10 WO PCT/US1994/002610 patent/WO1994020523A1/fr not_active Ceased
- 1994-03-10 AU AU64025/94A patent/AU6402594A/en not_active Abandoned
- 1994-03-10 EP EP94911542A patent/EP0691981A1/fr not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| WO1994020523A1 (fr) | 1994-09-15 |
| EP0691981A1 (fr) | 1996-01-17 |
| JPH08512019A (ja) | 1996-12-17 |
| AU6402594A (en) | 1994-09-26 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |