CZ287731B6 - Protein selective acylation process - Google Patents
Protein selective acylation process Download PDFInfo
- Publication number
- CZ287731B6 CZ287731B6 CZ19971456A CZ145697A CZ287731B6 CZ 287731 B6 CZ287731 B6 CZ 287731B6 CZ 19971456 A CZ19971456 A CZ 19971456A CZ 145697 A CZ145697 A CZ 145697A CZ 287731 B6 CZ287731 B6 CZ 287731B6
- Authority
- CZ
- Czechia
- Prior art keywords
- insulin
- fatty acid
- amino
- ester
- amino group
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 45
- 230000010933 acylation Effects 0.000 title claims abstract description 34
- 238000005917 acylation reaction Methods 0.000 title claims abstract description 34
- 102000004169 proteins and genes Human genes 0.000 title claims abstract description 21
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 21
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- 239000011356 non-aqueous organic solvent Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000003441 saturated fatty acids Nutrition 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 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
- C07K14/575—Hormones
- C07K14/62—Insulins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
- C07K1/1072—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
- C07K1/1077—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/341,231 US5646242A (en) | 1994-11-17 | 1994-11-17 | Selective acylation of epsilon-amino groups |
| PCT/US1995/014872 WO1996015803A1 (en) | 1994-11-17 | 1995-11-14 | SELECTIVE ACYLATION OF ε-AMINO GROUPS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CZ145697A3 CZ145697A3 (en) | 1997-12-17 |
| CZ287731B6 true CZ287731B6 (en) | 2001-01-17 |
Family
ID=23336740
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CZ19971456A CZ287731B6 (en) | 1994-11-17 | 1995-11-14 | Protein selective acylation process |
Country Status (27)
| Country | Link |
|---|---|
| US (2) | US5646242A (en, 2012) |
| EP (2) | EP1227107A1 (en, 2012) |
| JP (1) | JP4312828B2 (en, 2012) |
| CN (1) | CN1171742A (en, 2012) |
| AR (1) | AR003915A1 (en, 2012) |
| AT (1) | ATE328902T1 (en, 2012) |
| AU (2) | AU691066B2 (en, 2012) |
| BR (1) | BR9509652A (en, 2012) |
| CA (1) | CA2205061A1 (en, 2012) |
| CO (1) | CO4520285A1 (en, 2012) |
| CZ (1) | CZ287731B6 (en, 2012) |
| DE (1) | DE69535031T2 (en, 2012) |
| DK (1) | DK0712862T3 (en, 2012) |
| ES (1) | ES2264124T3 (en, 2012) |
| HU (2) | HU9903007D0 (en, 2012) |
| IL (1) | IL115972A (en, 2012) |
| IN (1) | IN179820B (en, 2012) |
| NO (1) | NO972185D0 (en, 2012) |
| NZ (1) | NZ297256A (en, 2012) |
| PL (1) | PL320556A1 (en, 2012) |
| PT (1) | PT712862E (en, 2012) |
| RU (1) | RU2155773C2 (en, 2012) |
| SI (1) | SI0712862T1 (en, 2012) |
| TR (1) | TR199501421A2 (en, 2012) |
| WO (1) | WO1996015803A1 (en, 2012) |
| YU (1) | YU71495A (en, 2012) |
| ZA (1) | ZA959680B (en, 2012) |
Families Citing this family (76)
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|---|---|---|---|---|
| GB9316895D0 (en) | 1993-08-13 | 1993-09-29 | Guy S And St Thomas Hospitals | Hepatoselective insulin analogues |
| US6869930B1 (en) * | 1993-09-17 | 2005-03-22 | Novo Nordisk A/S | Acylated insulin |
| US5951974A (en) * | 1993-11-10 | 1999-09-14 | Enzon, Inc. | Interferon polymer conjugates |
| US6251856B1 (en) | 1995-03-17 | 2001-06-26 | Novo Nordisk A/S | Insulin derivatives |
| US5631347A (en) * | 1995-06-07 | 1997-05-20 | Eli Lilly And Company | Reducing gelation of a fatty acid-acylated protein |
| US6451970B1 (en) * | 1996-02-21 | 2002-09-17 | Novo Nordisk A/S | Peptide derivatives |
| AU3255297A (en) * | 1996-07-11 | 1998-02-09 | Novo Nordisk A/S | Selective acylation method |
| US5905140A (en) * | 1996-07-11 | 1999-05-18 | Novo Nordisk A/S, Novo Alle | Selective acylation method |
| US6444641B1 (en) | 1997-10-24 | 2002-09-03 | Eli Lilly Company | Fatty acid-acylated insulin analogs |
| AU747926B2 (en) * | 1997-10-24 | 2002-05-30 | Eli Lilly And Company | Insoluble insulin compositions |
| US5985263A (en) * | 1997-12-19 | 1999-11-16 | Enzon, Inc. | Substantially pure histidine-linked protein polymer conjugates |
| US5981709A (en) * | 1997-12-19 | 1999-11-09 | Enzon, Inc. | α-interferon-polymer-conjugates having enhanced biological activity and methods of preparing the same |
| US6451974B1 (en) | 1999-03-17 | 2002-09-17 | Novo Nordisk A/S | Method of acylating peptides and novel acylating agents |
| WO2000073793A2 (en) * | 1999-05-27 | 2000-12-07 | Cecil Yip | Identification of compounds modulating insulin receptor activity |
| US7169889B1 (en) | 1999-06-19 | 2007-01-30 | Biocon Limited | Insulin prodrugs hydrolyzable in vivo to yield peglylated insulin |
| WO2001085256A2 (en) * | 2000-05-05 | 2001-11-15 | Novo Nordisk A/S | Critical illness neuropathy |
| US7316999B2 (en) | 2000-06-02 | 2008-01-08 | Novo Nordisk A/S | Glucose dependent release of insulin from glucose sensing insulin derivatives |
| WO2002051428A1 (en) * | 2000-12-25 | 2002-07-04 | Shiseido Company, Ltd. | Sympathetic-activating perfume composition |
| US7060675B2 (en) | 2001-02-15 | 2006-06-13 | Nobex Corporation | Methods of treating diabetes mellitus |
| US6867183B2 (en) | 2001-02-15 | 2005-03-15 | Nobex Corporation | Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith |
| US6828305B2 (en) * | 2001-06-04 | 2004-12-07 | Nobex Corporation | Mixtures of growth hormone drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
| US6858580B2 (en) * | 2001-06-04 | 2005-02-22 | Nobex Corporation | Mixtures of drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
| US6835802B2 (en) * | 2001-06-04 | 2004-12-28 | Nobex Corporation | Methods of synthesizing substantially monodispersed mixtures of polymers having polyethylene glycol moieties |
| US6828297B2 (en) | 2001-06-04 | 2004-12-07 | Nobex Corporation | Mixtures of insulin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
| US6713452B2 (en) | 2001-06-04 | 2004-03-30 | Nobex Corporation | Mixtures of calcitonin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same |
| US7713932B2 (en) | 2001-06-04 | 2010-05-11 | Biocon Limited | Calcitonin drug-oligomer conjugates, and uses thereof |
| US7595172B2 (en) | 2001-07-24 | 2009-09-29 | Novo Nordisk A/S | Method for making acylated polypeptides |
| US20030082671A1 (en) * | 2001-07-24 | 2003-05-01 | Thomas Hoeg-Jensen | Method for making acylated polypeptides |
| JP2005503141A (ja) * | 2001-07-24 | 2005-02-03 | ノボ ノルディスク アクティーゼルスカブ | アシル化ポリペプチドを作出するための方法 |
| CA2452735A1 (en) * | 2001-07-24 | 2003-02-06 | Ivan Diers | Method for making acylated polypeptides |
| US7030082B2 (en) * | 2001-09-07 | 2006-04-18 | Nobex Corporation | Pharmaceutical compositions of drug-oligomer conjugates and methods of treating disease therewith |
| US7166571B2 (en) * | 2001-09-07 | 2007-01-23 | Biocon Limited | Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
| US7196059B2 (en) | 2001-09-07 | 2007-03-27 | Biocon Limited | Pharmaceutical compositions of insulin drug-oligomer conjugates and methods of treating diseases therewith |
| US7312192B2 (en) | 2001-09-07 | 2007-12-25 | Biocon Limited | Insulin polypeptide-oligomer conjugates, proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
| DK1430082T3 (da) | 2001-09-07 | 2010-01-18 | Biocon Ltd | Fremgangsmåde til syntese af insulinpolypeptid-oligomer-konjugater og proinsulinpolypeptid-oligomerkonjugater samt fremgangsmåde til syntese deraf |
| US6770625B2 (en) | 2001-09-07 | 2004-08-03 | Nobex Corporation | Pharmaceutical compositions of calcitonin drug-oligomer conjugates and methods of treating diseases therewith |
| US6913903B2 (en) | 2001-09-07 | 2005-07-05 | Nobex Corporation | Methods of synthesizing insulin polypeptide-oligomer conjugates, and proinsulin polypeptide-oligomer conjugates and methods of synthesizing same |
| US20030199445A1 (en) * | 2002-02-07 | 2003-10-23 | Knudsen Lotte Bjerre | Use of GLP-1 compound for treatment of critically ill patients |
| US7601688B2 (en) | 2002-06-13 | 2009-10-13 | Biocon Limited | Methods of reducing hypoglycemic episodes in the treatment of diabetes mellitus |
| MXPA05003002A (es) * | 2002-09-25 | 2005-06-22 | Novo Nordisk As | Metodo para producir peptidos acilados. |
| US7273921B2 (en) | 2002-09-25 | 2007-09-25 | Novo Nordisk A/S | Method for producing acylated peptides |
| JP4463814B2 (ja) * | 2003-08-05 | 2010-05-19 | ノボ ノルディスク アクティーゼルスカブ | 新規のインスリン誘導体 |
| EP1687428A1 (en) | 2003-11-14 | 2006-08-09 | Novo Nordisk A/S | Processes for making acylated insulin |
| CN105801686B (zh) | 2004-07-19 | 2020-04-07 | 比奥孔有限公司 | 胰岛素-低聚物共轭物、制剂及其用途 |
| ATE513921T1 (de) | 2005-08-16 | 2011-07-15 | Novo Nordisk As | Verfahren zur herstellung reifer insulinpolypeptide |
| PL1969004T3 (pl) | 2005-12-28 | 2012-01-31 | Novo Nordisk As | Kompozycje zawierające acylowaną insulinę i cynk oraz sposób wytwarzania tych kompozycji |
| EP2256129B1 (en) * | 2006-02-27 | 2012-05-09 | Novo Nordisk A/S | Insulin derivatives |
| US8927015B2 (en) * | 2006-04-12 | 2015-01-06 | Emisphere Technologies, Inc. | Formulations for delivering insulin |
| EP2049149B1 (en) | 2006-07-31 | 2015-04-15 | Novo Nordisk A/S | Pegylated extended insulins |
| AU2007298919C1 (en) | 2006-09-22 | 2014-02-06 | Novo Nordisk A/S | Protease resistant insulin analogues |
| WO2008037735A1 (en) | 2006-09-27 | 2008-04-03 | Novo Nordisk A/S | Method for making maturated insulin polypeptides |
| CN101674812B (zh) | 2007-04-30 | 2013-12-11 | 诺沃-诺迪斯克有限公司 | 干燥蛋白组合物的方法、干燥的蛋白组合物和包含干燥的蛋白的药物组合物 |
| EP2167032B1 (en) | 2007-06-13 | 2019-08-07 | Novo Nordisk A/S | Pharmaceutical formulation comprising an insulin derivative |
| AU2008313248B2 (en) | 2007-10-16 | 2012-04-26 | Biocon Limited | An orally administerable solid pharmaceutical composition and a process thereof |
| US9260502B2 (en) | 2008-03-14 | 2016-02-16 | Novo Nordisk A/S | Protease-stabilized insulin analogues |
| KR101755434B1 (ko) | 2008-03-18 | 2017-07-10 | 노보 노르디스크 에이/에스 | 프로테아제 안정화되고, 아실화된 인슐린 유사체 |
| CN102149411A (zh) | 2008-09-12 | 2011-08-10 | 诺沃—诺迪斯克有限公司 | 酰化肽或蛋白的方法 |
| CA2738615A1 (en) * | 2008-10-30 | 2010-05-06 | Novo Nordisk A/S | Treating diabetes melitus using insulin injections with less than daily injection frequency |
| CA2751673A1 (en) * | 2009-02-20 | 2010-08-26 | Ipsen Pharma S.A.S | Analogues of neuropeptide y having proline substitution at position 34 |
| BR112012012945A2 (pt) | 2009-11-25 | 2020-12-29 | Arisgen Sa | Composição de liberação mucosal, seu método de produção, complexo de peptídeo pré-formado, kit e uso de um agente ativo de peptídeo |
| DK2632478T3 (da) | 2010-10-27 | 2019-10-07 | Novo Nordisk As | Behandling af diabetes melitus under anvendelse af insulinindsprøjtninger indgivet med varierende indsprøjtningsintervaller |
| ES2594303T3 (es) | 2012-04-11 | 2016-12-19 | Novo Nordisk A/S | Formulaciones de insulina |
| WO2014177623A1 (en) | 2013-04-30 | 2014-11-06 | Novo Nordisk A/S | Novel administration regime |
| PL3055325T3 (pl) | 2013-10-07 | 2018-06-29 | Novo Nordisk A/S | Nowa pochodna analogu insuliny |
| FR3013049B1 (fr) | 2013-11-14 | 2015-11-13 | You-Ping Chan | Analogue de l'insuline glargine |
| AR099569A1 (es) | 2014-02-28 | 2016-08-03 | Novo Nordisk As | Derivados de insulina y los usos médicos de estos |
| CN104558097A (zh) * | 2014-05-20 | 2015-04-29 | 广东东阳光药业有限公司 | 肽的酰化方法 |
| CN105111305B (zh) * | 2015-10-10 | 2018-12-14 | 山东阿华生物药业有限公司 | 酰化胰岛素的色谱纯化方法 |
| CN105440125B (zh) * | 2015-11-25 | 2019-09-24 | 华润昂德生物药业有限公司 | 地特胰岛素或其类似物的制备方法 |
| JP7128519B2 (ja) * | 2016-05-05 | 2022-08-31 | コデクシス， インコーポレイテッド | ペニシリンｇアシラーゼ |
| JP7076442B2 (ja) | 2016-11-07 | 2022-05-27 | ノヴォ ノルディスク アー／エス | Ｐｅｇ化合物のｄｃｈｂｓ活性エステル及びその使用 |
| MY200748A (en) | 2016-12-16 | 2024-01-13 | Novo Nordisk As | Insulin containing pharmaceutical compositions |
| CN107602437A (zh) * | 2017-08-09 | 2018-01-19 | 上海昂德生物科技有限公司 | 活化酯的制备方法 |
| US10335464B1 (en) | 2018-06-26 | 2019-07-02 | Novo Nordisk A/S | Device for titrating basal insulin |
| EP3996679B1 (en) | 2019-07-12 | 2023-09-06 | Novo Nordisk A/S | High concentration insulin formulation |
| CN116874585B (zh) * | 2023-09-06 | 2023-12-15 | 杭州湃肽生化科技有限公司 | 一种地特胰岛素的合成方法 |
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| FR1468831A (fr) * | 1965-10-05 | 1967-02-10 | Roussel Uclaf | Procédé de préparation de nouveaux composés polypeptidiques et produits en résultant |
| DE1902865A1 (de) * | 1968-02-01 | 1969-09-11 | American Home Prod | Substituierte Insulin-Derivate,Verfahren zu ihrer Herstellung und ihre Verwendung in pharmazeutischen Zubereitungen |
| US3591574A (en) * | 1968-05-29 | 1971-07-06 | American Home Prod | Tri-n-phenylglycyl derivatives of insulin |
| US3528960A (en) * | 1968-10-07 | 1970-09-15 | Lilly Co Eli | N-carboxyaroyl insulins |
| US3823125A (en) * | 1969-10-14 | 1974-07-09 | American Home Prod | N-aminoacyl-substituted insulins |
| US3752798A (en) * | 1969-12-02 | 1973-08-14 | G Amird | Tris-na1,nb1,nepsilonb29 - (3-x-3-oxo - 1-y-prop-1-en-1-yl)(ndelta-(4-z-6-r-pyrimidin - 2 - yl) ornithine b22)-insulins and their preparation |
| US3869437A (en) * | 1970-05-08 | 1975-03-04 | Nat Res Dev | Mono-, di, and N{HD A1{B , N{HU B1{B , N{HU B29{B -tri-acylated insulin |
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| GB1381273A (en) * | 1971-01-28 | 1975-01-22 | Nat Res Dev | Insulin derivatives |
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| DE2439296A1 (de) * | 1974-08-16 | 1976-02-26 | Hoechst Ag | Verfahren zur herstellung von insulin, insulin-analogen und -derivaten |
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| US5905140A (en) | 1996-07-11 | 1999-05-18 | Novo Nordisk A/S, Novo Alle | Selective acylation method |
-
1994
- 1994-11-17 US US08/341,231 patent/US5646242A/en not_active Ceased
-
1995
- 1995-11-14 HU HU9903007A patent/HU9903007D0/hu unknown
- 1995-11-14 CO CO95053590A patent/CO4520285A1/es unknown
- 1995-11-14 YU YU71495A patent/YU71495A/sh unknown
- 1995-11-14 BR BR9509652A patent/BR9509652A/pt not_active Application Discontinuation
- 1995-11-14 NZ NZ297256A patent/NZ297256A/xx active IP Right Revival
- 1995-11-14 CN CN95197224A patent/CN1171742A/zh active Pending
- 1995-11-14 PT PT95308167T patent/PT712862E/pt unknown
- 1995-11-14 ZA ZA959680A patent/ZA959680B/xx unknown
- 1995-11-14 CZ CZ19971456A patent/CZ287731B6/cs not_active IP Right Cessation
- 1995-11-14 AT AT95308167T patent/ATE328902T1/de active
- 1995-11-14 ES ES95308167T patent/ES2264124T3/es not_active Expired - Lifetime
- 1995-11-14 IN IN1452CA1995 patent/IN179820B/en unknown
- 1995-11-14 DE DE69535031T patent/DE69535031T2/de not_active Expired - Lifetime
- 1995-11-14 PL PL95320556A patent/PL320556A1/xx unknown
- 1995-11-14 CA CA002205061A patent/CA2205061A1/en not_active Abandoned
- 1995-11-14 TR TR95/01421A patent/TR199501421A2/xx unknown
- 1995-11-14 DK DK95308167T patent/DK0712862T3/da active
- 1995-11-14 IL IL11597295A patent/IL115972A/xx unknown
- 1995-11-14 EP EP02000258A patent/EP1227107A1/en not_active Ceased
- 1995-11-14 HU HU9800566A patent/HU217585B/hu not_active IP Right Cessation
- 1995-11-14 SI SI9530727T patent/SI0712862T1/sl unknown
- 1995-11-14 EP EP95308167A patent/EP0712862B1/en not_active Expired - Lifetime
- 1995-11-14 WO PCT/US1995/014872 patent/WO1996015803A1/en not_active Application Discontinuation
- 1995-11-14 AR ARP950100165A patent/AR003915A1/es not_active Application Discontinuation
- 1995-11-14 RU RU97110075/04A patent/RU2155773C2/ru active
- 1995-11-14 AU AU42372/96A patent/AU691066B2/en not_active Revoked
- 1995-11-14 JP JP51696396A patent/JP4312828B2/ja not_active Expired - Lifetime
-
1997
- 1997-05-13 NO NO972185A patent/NO972185D0/no not_active Application Discontinuation
-
1998
- 1998-08-07 AU AU78854/98A patent/AU720820B2/en not_active Ceased
-
1999
- 1999-07-08 US US09/351,103 patent/USRE37971E1/en not_active Expired - Lifetime
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PD00 | Pending as of 2000-06-30 in czech republic | ||
| MM4A | Patent lapsed due to non-payment of fee |
Effective date: 19951114 |