CS251766B2 - Method of interferon production - Google Patents
Method of interferon production Download PDFInfo
- Publication number
- CS251766B2 CS251766B2 CS834518A CS451883A CS251766B2 CS 251766 B2 CS251766 B2 CS 251766B2 CS 834518 A CS834518 A CS 834518A CS 451883 A CS451883 A CS 451883A CS 251766 B2 CS251766 B2 CS 251766B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- cells
- interferon
- induction
- potentiating agent
- concentration
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 26
- 230000016396 cytokine production Effects 0.000 title description 7
- 229940079322 interferon Drugs 0.000 claims abstract description 65
- 102000014150 Interferons Human genes 0.000 claims abstract description 64
- 108010050904 Interferons Proteins 0.000 claims abstract description 64
- 230000006698 induction Effects 0.000 claims abstract description 43
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 42
- 238000004519 manufacturing process Methods 0.000 claims abstract description 14
- 239000000411 inducer Substances 0.000 claims abstract description 8
- 230000008569 process Effects 0.000 claims abstract description 8
- 230000003389 potentiating effect Effects 0.000 claims description 33
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 26
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 22
- AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 claims description 10
- FZERHIULMFGESH-UHFFFAOYSA-N N-phenylacetamide Chemical compound CC(=O)NC1=CC=CC=C1 FZERHIULMFGESH-UHFFFAOYSA-N 0.000 claims description 8
- CPJSUEIXXCENMM-UHFFFAOYSA-N phenacetin Chemical compound CCOC1=CC=C(NC(C)=O)C=C1 CPJSUEIXXCENMM-UHFFFAOYSA-N 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 7
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 230000015572 biosynthetic process Effects 0.000 claims description 6
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims description 6
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 5
- GGYVTHJIUNGKFZ-UHFFFAOYSA-N 1-methylpiperidin-2-one Chemical compound CN1CCCCC1=O GGYVTHJIUNGKFZ-UHFFFAOYSA-N 0.000 claims description 4
- 229960001413 acetanilide Drugs 0.000 claims description 4
- 230000001939 inductive effect Effects 0.000 claims description 4
- 150000003672 ureas Chemical class 0.000 claims description 4
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 claims description 3
- BNQSTAOJRULKNX-UHFFFAOYSA-N N-(6-acetamidohexyl)acetamide Chemical compound CC(=O)NCCCCCCNC(C)=O BNQSTAOJRULKNX-UHFFFAOYSA-N 0.000 claims description 2
- 150000003869 acetamides Chemical class 0.000 claims description 2
- 150000008061 acetanilides Chemical class 0.000 claims description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 150000008625 2-imidazolidinones Chemical class 0.000 claims 1
- 230000002708 enhancing effect Effects 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 91
- 239000002609 medium Substances 0.000 description 11
- SWEYNHYBJHPVJL-UHFFFAOYSA-N butanoic acid;sodium Chemical compound [Na].CCCC(O)=O SWEYNHYBJHPVJL-UHFFFAOYSA-N 0.000 description 9
- -1 Virology Chemical class 0.000 description 8
- 241000711408 Murine respirovirus Species 0.000 description 7
- 239000012737 fresh medium Substances 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 238000011534 incubation Methods 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 210000000265 leukocyte Anatomy 0.000 description 5
- 159000000000 sodium salts Chemical class 0.000 description 5
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 239000006285 cell suspension Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 229940047124 interferons Drugs 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 3
- 244000309466 calf Species 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- PMDCZENCAXMSOU-UHFFFAOYSA-N N-ethylacetamide Chemical compound CCNC(C)=O PMDCZENCAXMSOU-UHFFFAOYSA-N 0.000 description 2
- XGEGHDBEHXKFPX-UHFFFAOYSA-N N-methyl urea Chemical compound CNC(N)=O XGEGHDBEHXKFPX-UHFFFAOYSA-N 0.000 description 2
- OHLUUHNLEMFGTQ-UHFFFAOYSA-N N-methylacetamide Chemical compound CNC(C)=O OHLUUHNLEMFGTQ-UHFFFAOYSA-N 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000012888 bovine serum Substances 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 230000035931 haemagglutination Effects 0.000 description 2
- 230000002452 interceptive effect Effects 0.000 description 2
- OAERLTPBKQBWHJ-UHFFFAOYSA-N n,n-dimethylhexanamide Chemical compound CCCCCC(=O)N(C)C OAERLTPBKQBWHJ-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 239000000021 stimulant Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- WEKQSZQVVIURQD-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C.CN(C)C(=O)N(C)C WEKQSZQVVIURQD-UHFFFAOYSA-N 0.000 description 1
- YBBLOADPFWKNGS-UHFFFAOYSA-N 1,1-dimethylurea Chemical compound CN(C)C(N)=O YBBLOADPFWKNGS-UHFFFAOYSA-N 0.000 description 1
- ZWAVGZYKJNOTPX-UHFFFAOYSA-N 1,3-diethylurea Chemical compound CCNC(=O)NCC ZWAVGZYKJNOTPX-UHFFFAOYSA-N 0.000 description 1
- ZFPGARUNNKGOBB-UHFFFAOYSA-N 1-Ethyl-2-pyrrolidinone Chemical compound CCN1CCCC1=O ZFPGARUNNKGOBB-UHFFFAOYSA-N 0.000 description 1
- 208000011691 Burkitt lymphomas Diseases 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- RYECOJGRJDOGPP-UHFFFAOYSA-N Ethylurea Chemical compound CCNC(N)=O RYECOJGRJDOGPP-UHFFFAOYSA-N 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 206010028470 Mycoplasma infections Diseases 0.000 description 1
- FQKKPLXFGDCBJT-UHFFFAOYSA-N N-(5-Acetamidopentyl)acetamide Chemical compound CC(=O)NCCCCCNC(C)=O FQKKPLXFGDCBJT-UHFFFAOYSA-N 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 108010040201 Polymyxins Proteins 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 101100528457 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) RMP1 gene Proteins 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- MNOILHPDHOHILI-UHFFFAOYSA-N Tetramethylthiourea Chemical compound CN(C)C(=S)N(C)C MNOILHPDHOHILI-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000002269 analeptic agent Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940054066 benzamide antipsychotics Drugs 0.000 description 1
- 150000003936 benzamides Chemical class 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 description 1
- 235000013877 carbamide Nutrition 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 239000002799 interferon inducing agent Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- VJPODIJDERZHMG-UHFFFAOYSA-N n-(6-hydroxyhexyl)acetamide Chemical compound CC(=O)NCCCCCCO VJPODIJDERZHMG-UHFFFAOYSA-N 0.000 description 1
- ZQMWGNLDKKJHFU-UHFFFAOYSA-N n-(7-acetamidoheptyl)acetamide Chemical compound CC(=O)NCCCCCCCNC(C)=O ZQMWGNLDKKJHFU-UHFFFAOYSA-N 0.000 description 1
- GYLDXXLJMRTVSS-UHFFFAOYSA-N n-butylacetamide Chemical compound CCCCNC(C)=O GYLDXXLJMRTVSS-UHFFFAOYSA-N 0.000 description 1
- NCCHARWOCKOHIH-UHFFFAOYSA-N n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC=C1 NCCHARWOCKOHIH-UHFFFAOYSA-N 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 229940080818 propionamide Drugs 0.000 description 1
- ZQZJKHIIQFPZCS-UHFFFAOYSA-N propylurea Chemical compound CCCNC(N)=O ZQZJKHIIQFPZCS-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- MFBOGIVSZKQAPD-UHFFFAOYSA-M sodium butyrate Chemical compound [Na+].CCCC([O-])=O MFBOGIVSZKQAPD-UHFFFAOYSA-M 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 210000002700 urine Anatomy 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
- C07K14/52—Cytokines; Lymphokines; Interferons
- C07K14/555—Interferons [IFN]
-
- 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
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/811—Interferon
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8217884 | 1982-06-21 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS451883A2 CS451883A2 (en) | 1986-12-18 |
| CS251766B2 true CS251766B2 (en) | 1987-08-13 |
Family
ID=10531183
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS834518A CS251766B2 (en) | 1982-06-21 | 1983-06-20 | Method of interferon production |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US4780413A (es) |
| EP (1) | EP0097353B1 (es) |
| JP (1) | JPH0636751B2 (es) |
| AT (1) | ATE55620T1 (es) |
| AU (1) | AU572783B2 (es) |
| CA (1) | CA1211397A (es) |
| CS (1) | CS251766B2 (es) |
| DE (1) | DE3381805D1 (es) |
| DK (1) | DK283683A (es) |
| ES (1) | ES8504934A1 (es) |
| FI (1) | FI832252L (es) |
| GB (1) | GB2122207B (es) |
| HU (1) | HU189706B (es) |
| IL (1) | IL69027A (es) |
| IT (1) | IT1172270B (es) |
| PL (1) | PL141593B1 (es) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2572093A1 (fr) * | 1984-10-22 | 1986-04-25 | Anda Biolog | Nouveau milieu de culture cellulaire contenant des cellules de rate humaine, procede de culture utilisant ce milieu de culture, lignees de cellules lymphoblastoides obtenues, application a la production d'interferon, procede de preparation d'interferon et interferon ainsi produit |
| US5681718A (en) * | 1986-03-14 | 1997-10-28 | Celltech Limited | Methods for enhanced production of tissue plasminogen activator in cell culture using alkanoic acids or salts thereof |
| US6656466B1 (en) | 1995-06-06 | 2003-12-02 | Genetech, Inc. | Human tumor necrosis factor—immunoglobulin(TNFR1-IgG1) chimera composition |
| US5721121A (en) * | 1995-06-06 | 1998-02-24 | Genentech, Inc. | Mammalian cell culture process for producing a tumor necrosis factor receptor immunoglobulin chimeric protein |
| US5705364A (en) | 1995-06-06 | 1998-01-06 | Genentech, Inc. | Mammalian cell culture process |
| US6855519B2 (en) * | 1995-08-22 | 2005-02-15 | The Regents Of The University Of California | Methods for enhancing the production of interferon in cell culture |
| US5840565A (en) | 1995-08-22 | 1998-11-24 | The Regents Of The University Of California | Methods for enhancing the production of viral vaccines in PKR-deficient cell culture |
| SE513313C2 (sv) * | 1998-12-29 | 2000-08-21 | Bionative Ab | Modifierad interferonproduktion |
| AU2004234377A1 (en) * | 2003-04-25 | 2004-11-11 | Immunex Corporation | Inducers of recombinant protein expression |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3773924A (en) * | 1970-12-24 | 1973-11-20 | M Ho | Interferon production |
| CS215108B2 (en) * | 1977-07-15 | 1982-07-30 | Wellcome Found | Method of making the interferrone |
| DE2961658D1 (en) * | 1978-05-17 | 1982-02-18 | Thomae Gmbh Dr K | Process for preparing human interferon |
| DE2821466A1 (de) * | 1978-05-17 | 1979-11-29 | Thomae Gmbh Dr K | Verbessertes verfahren zur herstellung von humaninterferon |
| ES482789A0 (es) * | 1978-08-25 | 1980-12-01 | Thomae Gmbh Dr K | Procedimiento para la preparacion de nuevos bencimidazoles sustituidos en posicion 5 o 6 con un anillo de piridazinona |
| EP0014050A3 (en) * | 1979-01-16 | 1980-10-01 | Beecham Group Plc | Interferon production |
| EP0030094A1 (en) * | 1979-11-30 | 1981-06-10 | Beecham Group Plc | Calcium enhanced interferon production process |
-
1983
- 1983-06-20 GB GB08316758A patent/GB2122207B/en not_active Expired
- 1983-06-20 DK DK283683A patent/DK283683A/da not_active Application Discontinuation
- 1983-06-20 PL PL1983242612A patent/PL141593B1/pl unknown
- 1983-06-20 EP EP83106006A patent/EP0097353B1/en not_active Expired - Lifetime
- 1983-06-20 IL IL69027A patent/IL69027A/xx unknown
- 1983-06-20 AU AU15935/83A patent/AU572783B2/en not_active Expired - Fee Related
- 1983-06-20 ES ES523424A patent/ES8504934A1/es not_active Expired
- 1983-06-20 IT IT48536/83A patent/IT1172270B/it active
- 1983-06-20 AT AT83106006T patent/ATE55620T1/de not_active IP Right Cessation
- 1983-06-20 DE DE8383106006T patent/DE3381805D1/de not_active Expired - Fee Related
- 1983-06-20 HU HU832194A patent/HU189706B/hu unknown
- 1983-06-20 CA CA000430775A patent/CA1211397A/en not_active Expired
- 1983-06-20 JP JP58110756A patent/JPH0636751B2/ja not_active Expired - Lifetime
- 1983-06-20 FI FI832252A patent/FI832252L/fi not_active Application Discontinuation
- 1983-06-20 CS CS834518A patent/CS251766B2/cs unknown
-
1985
- 1985-08-26 US US06/769,670 patent/US4780413A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| PL242612A1 (en) | 1984-08-13 |
| GB2122207A (en) | 1984-01-11 |
| DE3381805D1 (de) | 1990-09-20 |
| FI832252L (fi) | 1983-12-22 |
| PL141593B1 (en) | 1987-08-31 |
| AU572783B2 (en) | 1988-05-19 |
| GB2122207B (en) | 1986-02-12 |
| ES523424A0 (es) | 1985-04-16 |
| HU189706B (en) | 1986-07-28 |
| IT8348536A0 (it) | 1983-06-20 |
| CS451883A2 (en) | 1986-12-18 |
| IL69027A (en) | 1988-08-31 |
| JPS596896A (ja) | 1984-01-13 |
| ATE55620T1 (de) | 1990-09-15 |
| DK283683A (da) | 1983-12-22 |
| AU1593583A (en) | 1984-01-05 |
| FI832252A0 (fi) | 1983-06-20 |
| IT1172270B (it) | 1987-06-18 |
| EP0097353A3 (en) | 1987-08-05 |
| DK283683D0 (da) | 1983-06-20 |
| ES8504934A1 (es) | 1985-04-16 |
| IL69027A0 (en) | 1983-10-31 |
| EP0097353A2 (en) | 1984-01-04 |
| CA1211397A (en) | 1986-09-16 |
| GB8316758D0 (en) | 1983-07-20 |
| EP0097353B1 (en) | 1990-08-16 |
| US4780413A (en) | 1988-10-25 |
| JPH0636751B2 (ja) | 1994-05-18 |
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