IL92122A - Process for making optically active glycid esters - Google Patents
Process for making optically active glycid estersInfo
- Publication number
- IL92122A IL92122A IL9212289A IL9212289A IL92122A IL 92122 A IL92122 A IL 92122A IL 9212289 A IL9212289 A IL 9212289A IL 9212289 A IL9212289 A IL 9212289A IL 92122 A IL92122 A IL 92122A
- Authority
- IL
- Israel
- Prior art keywords
- enzyme
- membrane
- formula
- organic solution
- group
- Prior art date
Links
- OTGHWLKHGCENJV-UHFFFAOYSA-N glycidic acid Chemical class OC(=O)C1CO1 OTGHWLKHGCENJV-UHFFFAOYSA-N 0.000 title claims description 36
- 238000004519 manufacturing process Methods 0.000 title abstract description 29
- 238000000034 method Methods 0.000 claims abstract description 292
- 239000012528 membrane Substances 0.000 claims abstract description 162
- 150000002148 esters Chemical class 0.000 claims abstract description 135
- 238000006243 chemical reaction Methods 0.000 claims abstract description 123
- -1 glycidic acid ester Chemical class 0.000 claims abstract description 112
- 230000008569 process Effects 0.000 claims abstract description 73
- 150000001875 compounds Chemical class 0.000 claims abstract description 61
- 239000006227 byproduct Substances 0.000 claims abstract description 30
- 239000002904 solvent Substances 0.000 claims abstract description 28
- 230000000707 stereoselective effect Effects 0.000 claims abstract description 16
- 238000010931 ester hydrolysis Methods 0.000 claims abstract description 12
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims abstract 16
- 102000004190 Enzymes Human genes 0.000 claims description 261
- 108090000790 Enzymes Proteins 0.000 claims description 260
- 229940088598 enzyme Drugs 0.000 claims description 256
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 229
- 239000000243 solution Substances 0.000 claims description 130
- 108090001060 Lipase Proteins 0.000 claims description 74
- 102000004882 Lipase Human genes 0.000 claims description 74
- 239000004367 Lipase Substances 0.000 claims description 73
- 235000019421 lipase Nutrition 0.000 claims description 73
- 239000000203 mixture Substances 0.000 claims description 72
- 238000006460 hydrolysis reaction Methods 0.000 claims description 67
- 230000007062 hydrolysis Effects 0.000 claims description 66
- 229940040461 lipase Drugs 0.000 claims description 66
- 239000003960 organic solvent Substances 0.000 claims description 55
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 43
- 239000000463 material Substances 0.000 claims description 36
- 125000004432 carbon atom Chemical group C* 0.000 claims description 33
- 230000003301 hydrolyzing effect Effects 0.000 claims description 31
- 230000003287 optical effect Effects 0.000 claims description 31
- 108091005804 Peptidases Proteins 0.000 claims description 30
- 239000004365 Protease Substances 0.000 claims description 30
- 239000003795 chemical substances by application Substances 0.000 claims description 28
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 27
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 25
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims description 23
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- CVZUMGUZDAWOGA-UHFFFAOYSA-N methyl 3-(4-methoxyphenyl)oxirane-2-carboxylate Chemical group COC(=O)C1OC1C1=CC=C(OC)C=C1 CVZUMGUZDAWOGA-UHFFFAOYSA-N 0.000 claims description 20
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 19
- 239000007864 aqueous solution Substances 0.000 claims description 18
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical class OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 claims description 17
- 230000000269 nucleophilic effect Effects 0.000 claims description 17
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 16
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 claims description 16
- 125000003118 aryl group Chemical group 0.000 claims description 15
- 241000222120 Candida <Saccharomycetales> Species 0.000 claims description 14
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 14
- 238000002425 crystallisation Methods 0.000 claims description 14
- 230000008025 crystallization Effects 0.000 claims description 14
- YKNYRRVISWJDSR-UHFFFAOYSA-N methyl oxirane-2-carboxylate Chemical compound COC(=O)C1CO1 YKNYRRVISWJDSR-UHFFFAOYSA-N 0.000 claims description 14
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 13
- 239000006185 dispersion Substances 0.000 claims description 13
- 230000007071 enzymatic hydrolysis Effects 0.000 claims description 13
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 13
- 239000012510 hollow fiber Substances 0.000 claims description 12
- 125000003107 substituted aryl group Chemical group 0.000 claims description 12
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 10
- 108090000371 Esterases Proteins 0.000 claims description 10
- 239000003153 chemical reaction reagent Substances 0.000 claims description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 9
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 8
- 229910052783 alkali metal Inorganic materials 0.000 claims description 8
- 244000005700 microbiome Species 0.000 claims description 8
- 102000035195 Peptidases Human genes 0.000 claims description 7
- 230000001965 increasing effect Effects 0.000 claims description 7
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- 239000003849 aromatic solvent Substances 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 238000007142 ring opening reaction Methods 0.000 claims description 6
- 241000235395 Mucor Species 0.000 claims description 5
- 150000001340 alkali metals Chemical class 0.000 claims description 5
- 210000004185 liver Anatomy 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 4
- 108050006759 Pancreatic lipases Proteins 0.000 claims description 4
- 102000019280 Pancreatic lipases Human genes 0.000 claims description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 229940116369 pancreatic lipase Drugs 0.000 claims description 4
- 229920002239 polyacrylonitrile Polymers 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 241000228212 Aspergillus Species 0.000 claims description 3
- 241000193830 Bacillus <bacterium> Species 0.000 claims description 3
- 108090000317 Chymotrypsin Proteins 0.000 claims description 3
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 claims description 3
- 241000179532 [Candida] cylindracea Species 0.000 claims description 3
- 229960002376 chymotrypsin Drugs 0.000 claims description 3
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 239000008096 xylene Substances 0.000 claims description 3
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 claims description 2
- NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- 241000589540 Pseudomonas fluorescens Species 0.000 claims description 2
- 150000007513 acids Chemical class 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 150000001450 anions Chemical class 0.000 claims description 2
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 229940117389 dichlorobenzene Drugs 0.000 claims description 2
- JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 150000002443 hydroxylamines Chemical class 0.000 claims description 2
- 239000007790 solid phase Substances 0.000 claims description 2
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims 3
- RHUYHJGZWVXEHW-UHFFFAOYSA-N 1,1-Dimethyhydrazine Chemical compound CN(C)N RHUYHJGZWVXEHW-UHFFFAOYSA-N 0.000 claims 2
- YSULOORXQBDPCU-UHFFFAOYSA-N 2-(trimethylazaniumyl)ethanehydrazonate;hydrochloride Chemical compound [Cl-].C[N+](C)(C)CC(=O)NN YSULOORXQBDPCU-UHFFFAOYSA-N 0.000 claims 2
- 241000124008 Mammalia Species 0.000 claims 2
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- 108010055297 Sterol Esterase Proteins 0.000 claims 2
- 102000000019 Sterol Esterase Human genes 0.000 claims 2
- 108090000631 Trypsin Proteins 0.000 claims 2
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- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
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- 229940055695 pancreatin Drugs 0.000 claims 2
- 125000003944 tolyl group Chemical group 0.000 claims 2
- 239000012588 trypsin Substances 0.000 claims 2
- 229960001322 trypsin Drugs 0.000 claims 2
- FPMXPTIRDWHULR-UHFFFAOYSA-N 2-pyridin-1-ium-1-ylacetate;hydrochloride Chemical compound [Cl-].OC(=O)C[N+]1=CC=CC=C1 FPMXPTIRDWHULR-UHFFFAOYSA-N 0.000 claims 1
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
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- 125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 claims 1
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- 150000003949 imides Chemical class 0.000 claims 1
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- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 1
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- NBVVFGBZGZIQKQ-UHFFFAOYSA-N methyl 3-methoxy-2-phenyloxirane-2-carboxylate Chemical compound COC1OC1(C(=O)OC)C1=CC=CC=C1 NBVVFGBZGZIQKQ-UHFFFAOYSA-N 0.000 description 1
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- RUVINXPYWBROJD-UHFFFAOYSA-N para-methoxyphenyl Natural products COC1=CC=C(C=CC)C=C1 RUVINXPYWBROJD-UHFFFAOYSA-N 0.000 description 1
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- KHDBNRZPFKJRSR-UHFFFAOYSA-N propan-2-yl oxirane-2-carboxylate Chemical compound CC(C)OC(=O)C1CO1 KHDBNRZPFKJRSR-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/48—Compounds containing oxirane rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D281/02—Seven-membered rings
- C07D281/04—Seven-membered rings having the hetero atoms in positions 1 and 4
- C07D281/08—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D281/10—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/02—Oxygen as only ring hetero atoms
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
- C12P41/003—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions
- C12P41/005—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions by esterification of carboxylic acid groups in the enantiomers or the inverse reaction
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Analytical Chemistry (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US26517188A | 1988-10-26 | 1988-10-26 | |
| US07/309,769 US5274300A (en) | 1988-10-26 | 1989-02-10 | Enzymatic hydrolysis of glycidate esters in the presence of bisulfite anion |
| US07/335,636 US6521445B1 (en) | 1988-10-26 | 1989-04-10 | Process for preparing optically active glycidate esters |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL92122A0 IL92122A0 (en) | 1990-07-12 |
| IL92122A true IL92122A (en) | 1996-06-18 |
Family
ID=27401773
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL9212289A IL92122A (en) | 1988-10-26 | 1989-10-26 | Process for making optically active glycid esters |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US6521445B1 (de) |
| EP (2) | EP0657544B1 (de) |
| JP (1) | JP2693248B2 (de) |
| AT (2) | ATE161583T1 (de) |
| AU (1) | AU4497289A (de) |
| CA (1) | CA2001515C (de) |
| DE (2) | DE68928516D1 (de) |
| IL (1) | IL92122A (de) |
| WO (1) | WO1990004643A1 (de) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL8801311A (nl) * | 1988-05-20 | 1989-12-18 | Stamicarbon | Fenylglycidaatstereoisomeren, omzettingsprodukten daarvan met 2-nitrothiofenol en de bereiding van diltiazem. |
| JP2687789B2 (ja) * | 1991-08-13 | 1997-12-08 | 田辺製薬株式会社 | 光学活性３−フェニルグリシッド酸エステル類化合物の製法 |
| FI93833C (fi) * | 1992-05-14 | 1995-06-12 | Orion Yhtymae Oy | Menetelmä propionihappojohdosten valmistamiseksi |
| US5273895A (en) * | 1992-10-26 | 1993-12-28 | Sepracor, Inc. | Enantioselective production of chiral carboxylic acids |
| NL9202208A (nl) * | 1992-12-18 | 1994-07-18 | Dsm Nv | Werkwijze voor de enzymatische bereiding van optisch aktieve glycidezure esters. |
| CA2161849A1 (en) * | 1994-11-01 | 1996-05-02 | Kazuo Nakahama | Production of optically active compounds |
| TW438787B (en) | 1997-02-27 | 2001-06-07 | Tanabe Seiyaku Co | Process for preparing optically active trans-3-substituted glycidic acid ester |
| WO1999037754A2 (en) * | 1998-01-26 | 1999-07-29 | Pharm-Eco Laboratories, Inc. | Enzyme activated supports for enantiomeric separations |
| WO2014030106A2 (en) * | 2012-08-18 | 2014-02-27 | Unimark Remedies Ltd. | Process for preparation of optically active (2r,3s)-3-(4- methoxyphenyl)glycidic acid methyl ester and cis lactam and uses thereof |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3635795A (en) * | 1968-12-27 | 1972-01-18 | Merck & Co Inc | Enzymatic resolution of racemic (cis-1,2-epoxypropyl) phosphonic acid compounds |
| US4585768A (en) * | 1984-04-10 | 1986-04-29 | Tanabe Seiyaku Co., Ltd. | 1,5-benzothiazepine derivatives and processes for preparing the same |
| US4732853A (en) * | 1984-11-21 | 1988-03-22 | President And Fellows Of Harvard College | Method of making chiral epoxy alcohols |
| IT1189069B (it) * | 1986-03-14 | 1988-01-28 | Donegani Guido Ist | Processo per la preparazione biotecnologica della l(-)-carnitina cloruro |
| EP0488999B1 (de) * | 1986-04-16 | 1997-07-09 | Sumitomo Chemical Company Limited | Verfahren zur Herstellung von optisch-aktiven Cyclopropancarbonsäure |
| JPS6315398A (ja) * | 1986-07-07 | 1988-01-22 | 株式会社東芝 | 状態監視用端末装置 |
| US4800162A (en) * | 1987-04-01 | 1989-01-24 | Sepracor, Inc. | Method for resolution of steroisomers in multiphase and extractive membrane reactors |
| JP2627627B2 (ja) * | 1987-11-09 | 1997-07-09 | 昭和飛行機工業株式会社 | 保冷コンテナ |
| NL8801311A (nl) * | 1988-05-20 | 1989-12-18 | Stamicarbon | Fenylglycidaatstereoisomeren, omzettingsprodukten daarvan met 2-nitrothiofenol en de bereiding van diltiazem. |
| IL91453A0 (en) * | 1988-09-02 | 1990-04-29 | Tanabe Seiyaku Co | Preparation of optically active 3-phenyl-glycidic acid esters |
| JPH0678A (ja) * | 1992-06-22 | 1994-01-11 | Fujiwara Techno Art:Kk | 固体培養装置の空気調和装置における加湿方法 |
-
1989
- 1989-04-10 US US07/335,636 patent/US6521445B1/en not_active Expired - Lifetime
- 1989-10-25 CA CA002001515A patent/CA2001515C/en not_active Expired - Lifetime
- 1989-10-26 IL IL9212289A patent/IL92122A/en not_active IP Right Cessation
- 1989-10-26 EP EP95200168A patent/EP0657544B1/de not_active Expired - Lifetime
- 1989-10-26 AT AT95200168T patent/ATE161583T1/de not_active IP Right Cessation
- 1989-10-26 JP JP1511470A patent/JP2693248B2/ja not_active Expired - Lifetime
- 1989-10-26 DE DE68928516T patent/DE68928516D1/de not_active Expired - Lifetime
- 1989-10-26 AT AT89912309T patent/ATE126541T1/de not_active IP Right Cessation
- 1989-10-26 AU AU44972/89A patent/AU4497289A/en not_active Abandoned
- 1989-10-26 DE DE68923883T patent/DE68923883T2/de not_active Expired - Lifetime
- 1989-10-26 WO PCT/US1989/004784 patent/WO1990004643A1/en not_active Ceased
- 1989-10-26 EP EP89912309A patent/EP0440723B1/de not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| EP0440723B1 (de) | 1995-08-16 |
| ATE161583T1 (de) | 1998-01-15 |
| CA2001515A1 (en) | 1990-04-26 |
| US6521445B1 (en) | 2003-02-18 |
| WO1990004643A1 (en) | 1990-05-03 |
| CA2001515C (en) | 2005-05-10 |
| JP2693248B2 (ja) | 1997-12-24 |
| DE68923883T2 (de) | 1995-12-14 |
| EP0440723A1 (de) | 1991-08-14 |
| DE68923883D1 (de) | 1995-09-21 |
| IL92122A0 (en) | 1990-07-12 |
| EP0657544B1 (de) | 1997-12-29 |
| ATE126541T1 (de) | 1995-09-15 |
| DE68928516D1 (de) | 1998-02-05 |
| AU4497289A (en) | 1990-05-14 |
| EP0440723A4 (en) | 1992-05-20 |
| JPH04501360A (ja) | 1992-03-12 |
| EP0657544A1 (de) | 1995-06-14 |
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