KR950704486A - 성분b로 명명된 신규 단백질(new protein from urine named component b) - Google Patents
성분b로 명명된 신규 단백질(new protein from urine named component b)Info
- Publication number
- KR950704486A KR950704486A KR1019950702407A KR19950702407A KR950704486A KR 950704486 A KR950704486 A KR 950704486A KR 1019950702407 A KR1019950702407 A KR 1019950702407A KR 19950702407 A KR19950702407 A KR 19950702407A KR 950704486 A KR950704486 A KR 950704486A
- Authority
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- South Korea
- Prior art keywords
- resin
- component
- acetate buffer
- eluting
- polypeptide
- Prior art date
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- 210000002700 urine Anatomy 0.000 title claims abstract description 7
- 102000004169 proteins and genes Human genes 0.000 title claims abstract 6
- 108090000623 proteins and genes Proteins 0.000 title claims abstract 6
- 230000003110 anti-inflammatory effect Effects 0.000 claims abstract 2
- 230000000259 anti-tumor effect Effects 0.000 claims abstract 2
- 108020004414 DNA Proteins 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 4
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 3
- 239000011347 resin Substances 0.000 claims 16
- 229920005989 resin Polymers 0.000 claims 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 12
- 239000008351 acetate buffer Substances 0.000 claims 12
- 108090000765 processed proteins & peptides Proteins 0.000 claims 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims 8
- 229920001184 polypeptide Polymers 0.000 claims 8
- 102000004196 processed proteins & peptides Human genes 0.000 claims 8
- 239000000203 mixture Substances 0.000 claims 7
- 102000053602 DNA Human genes 0.000 claims 5
- 229910021529 ammonia Inorganic materials 0.000 claims 4
- 229940079593 drug Drugs 0.000 claims 4
- 239000003814 drug Substances 0.000 claims 4
- 238000004128 high performance liquid chromatography Methods 0.000 claims 4
- 150000003839 salts Chemical class 0.000 claims 4
- 239000004480 active ingredient Substances 0.000 claims 3
- 239000012634 fragment Substances 0.000 claims 3
- 239000002243 precursor Substances 0.000 claims 3
- 239000005995 Aluminium silicate Substances 0.000 claims 2
- 229920002271 DEAE-Sepharose Polymers 0.000 claims 2
- 229920002684 Sepharose Polymers 0.000 claims 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims 2
- 230000002378 acidificating effect Effects 0.000 claims 2
- 235000012211 aluminium silicate Nutrition 0.000 claims 2
- 239000003480 eluent Substances 0.000 claims 2
- 239000013604 expression vector Substances 0.000 claims 2
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 claims 2
- 239000002773 nucleotide Substances 0.000 claims 2
- 125000003729 nucleotide group Chemical group 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 2
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 2
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 1
- 239000003146 anticoagulant agent Substances 0.000 claims 1
- 229940127219 anticoagulant drug Drugs 0.000 claims 1
- 239000002299 complementary DNA Substances 0.000 claims 1
- 239000001963 growth medium Substances 0.000 claims 1
- 230000014508 negative regulation of coagulation Effects 0.000 claims 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 claims 1
- 102000006747 Transforming Growth Factor alpha Human genes 0.000 abstract 1
- 101800004564 Transforming growth factor alpha Proteins 0.000 abstract 1
- 230000002744 anti-aggregatory effect Effects 0.000 abstract 1
- 238000004587 chromatography analysis Methods 0.000 abstract 1
- 238000000605 extraction Methods 0.000 abstract 1
- 238000004255 ion exchange chromatography Methods 0.000 abstract 1
- 238000000746 purification Methods 0.000 abstract 1
- 108091035710 E-box Proteins 0.000 description 1
- 108700026226 TATA Box Proteins 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
-
- 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
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4702—Regulators; Modulating activity
- C07K14/4703—Inhibitors; Suppressors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Biomedical Technology (AREA)
- Toxicology (AREA)
- Public Health (AREA)
- Gastroenterology & Hepatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
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- Biotechnology (AREA)
- Immunology (AREA)
- General Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Physics & Mathematics (AREA)
- Hematology (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Pain & Pain Management (AREA)
- Cell Biology (AREA)
- Rheumatology (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
추출과 이온교환 크로마토그래피와 고해상 크로마토그래피에 의한 정제공정을 통하여 뇨로부터 수득가능한 신규 단백질에 관계하며 기술한다. 분자량은 9KDa이고 항염증, 항-응집과 항-종양성질이 있다. 단백질은 TGF-알파가 이의 수용체에 결합하는 것은 저해한다.
Description
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 뇨에서 성분B를 얻는 과정의 순서도이다.
제2도는 성분B의 게놈 전사유닛(SEQ ID NO : 2에 보고된 성분B의 게놈 DNA)의 제한효소지도,
제3도는 성분B의 프로모터 부위서열(SEQ ID NO : 2에 보고된 성분B 프로모터부위), AP-1, AP-2, SP-1와 E-박스 전사인자에 대한 결합부위를 나타낸다. TATA박스도 지적하고, GRE도 지적한다.
Claims (16)
- SEQ ID : 1의 펩티드 서열로 구성된 것을 특징으로 하는 폴리펩티드, 이의염, 기능적유도체, 전구체, 그리고 활성단편 또는 이의 혼합물.
- a)카올린으로 산성 pH에서 뇨를 처리하고 암모니아로 추출하고, b)암모니아와 Bio Rex 70수지에서 (a)성분을 용출시키고, c)아세테이트 완충액과 DEAE 세파로스 수지에서 (b)부분을 용출시키고, d)아세테이트 완충액과 CM 세파로스 수지에서 (c)성분을 용출시키고, e)아세테이트 완충액과 아세토니트릴 혼합물과 HPLC C18수지에서 (d)성분을 용출시키고, f)아세테이트 완충액과 DE-52 수지에서 (e)성분을 용출시키고, (g)아세테이트 완충액과 D-제피리 수지에서 (f)성분을 용출시키고, h)수용성 트리플로로아세트산과 아세토니트릴 혼합물의 HPLC C18수지에서 (g)성분을 용출시키고, i)아세테이트 완충액과 D-제피리 수지에서 (h)성분을 용출시키는 단계로 구성된 것을 특징으로 하는 제1항에 따른 폴리펩티드의 생산하는 공정.
- 제2항에 있어서, 뇨는 사람뇨인 것을 특징으로 하는 공정.
- 제1항에 따른 폴리펩티드를 인코드는 DNA 서열로 구성된 것을 특징으로 하는 DNA분자, 이의 돌연변이체 또는 활성단편.
- 제4항에 있어서, DNA 분자의 하이브리드할 수 있고 제1항에 따른 폴리펩티드를 코드할 수 있는 것을 특징으로 하는 DNA 분자, 이의 돌연변이체 또는 활성단편.
- SEQ ID NO : 2의 뉴클레오티드 서열로 구성된 것을 특징으로 하는 게놈 DNA 분자.
- SEQ ID NO : 3의 뉴클레오티드 서열로 구성된 것을 특징으로 하는 게놈 cDNA 분자.
- 제4항 내지 7항중 어느 한 항에 따른 DNA 분자로 구성된 것을 특징으로하는 발현벡터.
- 제8항에 따른 발현벡터로 형질전환된 것을 특징으로 하는 숙주세포.
- 제1항에 있어서, 제7항에 따른 형질전환된 숙주세포를 배양하고 배양배지에서 또는 세포에서 단백질을 회수하는 것을 특징으로 하는 공정.
- a)카올린으로 산성 pH에서 뇨를 처리하고 암모니아로 추출하고, b)암모니아와 Bio Rex 70수지에서 (a)성분을 용출시키고, c)아세테이트 완충액과 DEAE 세파로스 수지에서 (b)부분을 용출시키고, d)아세테이트 완충액과 CM 세파로스 수지에서 (c)성분을 용출시키고, e)아세테이트 완충액과 아세토니트릴 혼합물과 HPLC C18수지에서 (d)성분을 용출시키고, f)아세테이트 완충액과 DE-52 수지에서 (e)성분을 용출시키고, g)아세테이트 완충액과 D-제피리 수지에서 (f)성분을 용출시키고, h)수용성 트리플로로아세트산과 아세토니트릴 혼합물과 HPLC C18수지에서 (g)성분을 용출시키고, i)아세테이트 완충액과 D-제피리 수지에서 (h)성분을 용출시키는 과정으로 구성된 공정을 거쳐서 수득할 수 있는 것을 특징으로 하는 순수단백질, 이의염, 기능적 유도체, 약물, 활성성분.
- 제1항에 있어서, 약물로 사용되는 것을 특징으로 하는 폴리펩티드.
- 제1항에 따른 폴리펩티드를 항-염증성 그리고/또는 항-응고성 그리고/또는 항-종양활성을 가지는 약물에 사용되는 것을 특징으로 하는 용도.
- 제1항에 있어서, 폴리펩티드 또는 이의염, 기능적유도체, 전구체, 활성성분 또는 이의 혼합물의 제약학적 수용가능한 양과 하나이상의 제약학적 부형제 또는 용출액으로 구성된 것을 특징으로 하는 제약학적 조성물.
- 제11항에 있어서, 약물로 사용되는 것을 특징으로 하는 단백질.
- 제11항에 있어서, 폴리펩티드 또는 이의염, 기능유도체, 전구체, 활성성분 또는 이의 혼합물의 제약학적 수용가능한 양과 하나이상의 제약학적 부형제 또는 용출액으로 구성된 것을 특징으로 하는 제약학적 조성물.※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITRM92A000919 | 1992-12-22 | ||
| ITRM920919A IT1257184B (it) | 1992-12-22 | 1992-12-22 | Preparato ad attivita' antinfiammatoria, anticoagulante e antitumorale |
| PCT/EP1993/003645 WO1994014959A1 (en) | 1992-12-22 | 1993-12-21 | New protein from urine named component b |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR950704486A true KR950704486A (ko) | 1995-11-20 |
| KR100193107B1 KR100193107B1 (ko) | 1999-06-15 |
Family
ID=11401349
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019950702407A KR100193107B1 (ko) | 1992-12-22 | 1993-12-21 | 성분b로 명명된 신규 단백질 |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US5908827A (ko) |
| EP (1) | EP0675956B1 (ko) |
| JP (1) | JP3025014B2 (ko) |
| KR (1) | KR100193107B1 (ko) |
| AT (1) | ATE236976T1 (ko) |
| AU (1) | AU690093B2 (ko) |
| CA (1) | CA2151156A1 (ko) |
| DE (1) | DE69332861T2 (ko) |
| DK (1) | DK0675956T3 (ko) |
| ES (1) | ES2193152T3 (ko) |
| FI (2) | FI114478B (ko) |
| IL (1) | IL108149A (ko) |
| IT (1) | IT1257184B (ko) |
| NO (1) | NO315800B1 (ko) |
| PT (1) | PT675956E (ko) |
| RU (1) | RU2177480C2 (ko) |
| UA (1) | UA46702C2 (ko) |
| WO (1) | WO1994014959A1 (ko) |
| ZA (1) | ZA939621B (ko) |
Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5998364A (en) * | 1996-04-24 | 1999-12-07 | Applied Research Systems Ars Holding N.V. | Component B as cicatrizant |
| WO1998056810A2 (de) * | 1997-06-09 | 1998-12-17 | Forssmann Wolf Georg | Humanes protein lus-i, seine herstellung und verwendung |
| ATE224200T1 (de) * | 1998-07-09 | 2002-10-15 | Applied Research Systems | Komponente b als angiogenes mittel zusammen mit humanen wachstumsfaktoren |
| US6962700B1 (en) * | 2000-09-13 | 2005-11-08 | Atopix Pharmaceuticals Corporation | Method of manufacturing immune globulin |
| WO2004091646A2 (en) * | 2003-04-16 | 2004-10-28 | Applied Research Systems Ars Holding, N.V. | Use of slurp-1 for treating diseases related to acetylcholine receptors dysfunction |
| US7343581B2 (en) * | 2005-06-27 | 2008-03-11 | Tela Innovations, Inc. | Methods for creating primitive constructed standard cells |
| US7590968B1 (en) | 2006-03-01 | 2009-09-15 | Tela Innovations, Inc. | Methods for risk-informed chip layout generation |
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| US8448102B2 (en) | 2006-03-09 | 2013-05-21 | Tela Innovations, Inc. | Optimizing layout of irregular structures in regular layout context |
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| US7908578B2 (en) * | 2007-08-02 | 2011-03-15 | Tela Innovations, Inc. | Methods for designing semiconductor device with dynamic array section |
| US8658542B2 (en) | 2006-03-09 | 2014-02-25 | Tela Innovations, Inc. | Coarse grid design methods and structures |
| US8245180B2 (en) | 2006-03-09 | 2012-08-14 | Tela Innovations, Inc. | Methods for defining and using co-optimized nanopatterns for integrated circuit design and apparatus implementing same |
| US7943967B2 (en) | 2006-03-09 | 2011-05-17 | Tela Innovations, Inc. | Semiconductor device and associated layouts including diffusion contact placement restriction based on relation to linear conductive segments |
| US8247846B2 (en) | 2006-03-09 | 2012-08-21 | Tela Innovations, Inc. | Oversized contacts and vias in semiconductor chip defined by linearly constrained topology |
| US8225261B2 (en) | 2006-03-09 | 2012-07-17 | Tela Innovations, Inc. | Methods for defining contact grid in dynamic array architecture |
| US7446352B2 (en) | 2006-03-09 | 2008-11-04 | Tela Innovations, Inc. | Dynamic array architecture |
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Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4359415A (en) * | 1981-06-03 | 1982-11-16 | University Of Tennessee Research Corporation | Isolation of an antineoplastic protein fraction and an antineoplastic peptide fraction from human urine |
| US4470970A (en) * | 1981-07-02 | 1984-09-11 | Burzynski Stanislaw R | Purified antineoplaston fractions and methods of treating neoplastic disease |
| US5298604A (en) * | 1992-07-27 | 1994-03-29 | Sloane Nathan H | Parital primary amino acid sequence of the antineoplastic protein (ANUP); a cytokine present in granulocytes |
-
1992
- 1992-12-22 IT ITRM920919A patent/IT1257184B/it active IP Right Grant
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1993
- 1993-12-21 EP EP94904167A patent/EP0675956B1/en not_active Expired - Lifetime
- 1993-12-21 JP JP6514813A patent/JP3025014B2/ja not_active Expired - Fee Related
- 1993-12-21 DK DK94904167T patent/DK0675956T3/da active
- 1993-12-21 KR KR1019950702407A patent/KR100193107B1/ko not_active IP Right Cessation
- 1993-12-21 DE DE69332861T patent/DE69332861T2/de not_active Expired - Fee Related
- 1993-12-21 WO PCT/EP1993/003645 patent/WO1994014959A1/en active IP Right Grant
- 1993-12-21 UA UA95062918A patent/UA46702C2/uk unknown
- 1993-12-21 CA CA002151156A patent/CA2151156A1/en not_active Abandoned
- 1993-12-21 AT AT94904167T patent/ATE236976T1/de not_active IP Right Cessation
- 1993-12-21 AU AU58335/94A patent/AU690093B2/en not_active Ceased
- 1993-12-21 PT PT94904167T patent/PT675956E/pt unknown
- 1993-12-21 ES ES94904167T patent/ES2193152T3/es not_active Expired - Lifetime
- 1993-12-21 US US08/448,561 patent/US5908827A/en not_active Expired - Fee Related
- 1993-12-22 RU RU95113418/13A patent/RU2177480C2/ru not_active IP Right Cessation
- 1993-12-22 IL IL10814993A patent/IL108149A/xx not_active IP Right Cessation
- 1993-12-22 ZA ZA939621A patent/ZA939621B/xx unknown
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1995
- 1995-06-21 FI FI953091A patent/FI114478B/fi active IP Right Grant
- 1995-06-21 NO NO19952494A patent/NO315800B1/no not_active IP Right Cessation
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Also Published As
| Publication number | Publication date |
|---|---|
| FI116059B (fi) | 2005-09-15 |
| US5908827A (en) | 1999-06-01 |
| DE69332861D1 (de) | 2003-05-15 |
| ITRM920919A1 (it) | 1994-06-22 |
| IL108149A (en) | 2005-05-17 |
| NO952494L (no) | 1995-08-21 |
| FI114478B (fi) | 2004-10-29 |
| UA46702C2 (uk) | 2002-06-17 |
| IT1257184B (it) | 1996-01-10 |
| AU5833594A (en) | 1994-07-19 |
| ES2193152T3 (es) | 2003-11-01 |
| ZA939621B (en) | 1995-06-22 |
| KR100193107B1 (ko) | 1999-06-15 |
| FI953091A0 (fi) | 1995-06-21 |
| FI953091A (fi) | 1995-06-21 |
| CA2151156A1 (en) | 1994-07-07 |
| AU690093B2 (en) | 1998-04-23 |
| JP3025014B2 (ja) | 2000-03-27 |
| ITRM920919A0 (it) | 1992-12-22 |
| EP0675956B1 (en) | 2003-04-09 |
| RU2177480C2 (ru) | 2001-12-27 |
| ATE236976T1 (de) | 2003-04-15 |
| DK0675956T3 (da) | 2003-07-07 |
| NO315800B1 (no) | 2003-10-27 |
| EP0675956A1 (en) | 1995-10-11 |
| WO1994014959A1 (en) | 1994-07-07 |
| DE69332861T2 (de) | 2004-01-29 |
| FI20040608A (fi) | 2004-04-29 |
| NO952494D0 (no) | 1995-06-21 |
| IL108149A0 (en) | 1994-04-12 |
| PT675956E (pt) | 2003-07-31 |
| JPH08509359A (ja) | 1996-10-08 |
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