ES2177178T3 - Procedimiento mejorado para la obtencion de precursores de insulina con puentes cistina correctamente unidos. - Google Patents
Procedimiento mejorado para la obtencion de precursores de insulina con puentes cistina correctamente unidos.Info
- Publication number
- ES2177178T3 ES2177178T3 ES99115386T ES99115386T ES2177178T3 ES 2177178 T3 ES2177178 T3 ES 2177178T3 ES 99115386 T ES99115386 T ES 99115386T ES 99115386 T ES99115386 T ES 99115386T ES 2177178 T3 ES2177178 T3 ES 2177178T3
- Authority
- ES
- Spain
- Prior art keywords
- cysteine
- precursor
- insulin
- cystine bridges
- cysteine hydrochloride
- 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.)
- Expired - Lifetime
Links
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 title abstract 12
- 239000002243 precursor Substances 0.000 title abstract 7
- 102000004877 Insulin Human genes 0.000 title abstract 5
- 108090001061 Insulin Proteins 0.000 title abstract 5
- 229940125396 insulin Drugs 0.000 title abstract 4
- 238000000034 method Methods 0.000 title abstract 4
- 229960003067 cystine Drugs 0.000 title abstract 3
- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 abstract 5
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 abstract 5
- 229960002433 cysteine Drugs 0.000 abstract 5
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 abstract 5
- 235000018417 cysteine Nutrition 0.000 abstract 5
- 229960001305 cysteine hydrochloride Drugs 0.000 abstract 5
- 239000004026 insulin derivative Substances 0.000 abstract 5
- 239000002671 adjuvant Substances 0.000 abstract 3
- 230000003196 chaotropic effect Effects 0.000 abstract 3
- 239000000203 mixture Substances 0.000 abstract 3
- 102000003670 Carboxypeptidase B Human genes 0.000 abstract 1
- 108090000087 Carboxypeptidase B Proteins 0.000 abstract 1
- 102000004190 Enzymes Human genes 0.000 abstract 1
- 108090000790 Enzymes Proteins 0.000 abstract 1
- 102000004142 Trypsin Human genes 0.000 abstract 1
- 108090000631 Trypsin Proteins 0.000 abstract 1
- 239000003463 adsorbent Substances 0.000 abstract 1
- 239000007900 aqueous suspension Substances 0.000 abstract 1
- 238000003776 cleavage reaction Methods 0.000 abstract 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 abstract 1
- 238000010790 dilution Methods 0.000 abstract 1
- 239000012895 dilution Substances 0.000 abstract 1
- 230000002255 enzymatic effect Effects 0.000 abstract 1
- 238000010348 incorporation Methods 0.000 abstract 1
- 238000012423 maintenance Methods 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- 238000000746 purification Methods 0.000 abstract 1
- 239000011347 resin Substances 0.000 abstract 1
- 229920005989 resin Polymers 0.000 abstract 1
- 230000007017 scission Effects 0.000 abstract 1
- 239000000243 solution Substances 0.000 abstract 1
- 239000000725 suspension Substances 0.000 abstract 1
- 239000012588 trypsin Substances 0.000 abstract 1
- 230000001810 trypsinlike Effects 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract 1
Classifications
-
- 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
- C07K1/12—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by hydrolysis, i.e. solvolysis in general
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- 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
- C07K1/02—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length in solution
-
- 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
- C07K1/14—Extraction; Separation; Purification
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Diabetes (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Endocrinology (AREA)
- Analytical Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Procedimiento para la preparación de insulinas o de un derivado de insulina con puentes cistina correctamente unidos a partir de un precursor de insulina o del derivado de insulina, sometiéndose el precursor, en presencia de cisteína o de hidrocloruro de cisteína y de un coadyuvante caótropo, a un proceso de plegado, tras lo cual se obtiene una insulina o un derivado de insulina con puentes cistina correctamente unidos a partir del precursor por escisión enzimática median-te tripsina o una enzima similar a tripsina y, eventualmente, además, por medio de carboxipeptidasa B y subsiguiente puri-ficación en una resina adsorbente, caracterizado porque para la realización del proceso de plegado se ejecutan sucesivamente las siguientes etapas: (a) mezcladura de una suspensión acuosa del precursor de la insulina o del derivado de insulina con una cantidad de cisteína o hidrocloruro de cisteína que da por resultado 1 a 15 restos SH de la cisteína o del hidrocloruro de cisteína por cada resto cisteína del precursor, (b) incorporación de la suspensión del precursor, con contenido en cisteína o hidrocloruro de cisteína, a una solución desde 4 hasta 9 molar del coadyuvante caótropo a un valor del pH desde aproximadamente 8 hasta aproximadamente 11,5 y una temperatura desde aproximadamente 15 hasta aproximadamente 55ºC, mantenimiento de la mezcla obtenida durante aproximadamente 10 a 60 minutos a esta temperatura y (c) incorporación de la mezcla, a un valor del pH desde aproximadamente 8 hasta aproximadamente 11,5 y una temperatura desde aproximadamente 5ºC hasta aproximada mente 30ºC, a una cantidad de agua que da por resultado una dilución de la concentración de la cisteína o del hidrocloruro de cisteína en la mezcla que varía entre aproximadamente 1 y 5 mM, y de la del coadyuvante caótropo que varía entre 0,2 y 1,0 M.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19735711A DE19735711C2 (de) | 1997-08-18 | 1997-08-18 | Verfahren zur Herstellung eines Vorläufers von Insulin oder Insulinderivaten mit korrekt verbundenen Cystinbrücken |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2177178T3 true ES2177178T3 (es) | 2002-12-01 |
Family
ID=7839275
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES98115048T Expired - Lifetime ES2176870T3 (es) | 1997-08-18 | 1998-08-11 | Procedimiento para la obtencion de precusores de la insulina con puentes de cistina correctamente ligados. |
| ES99115386T Expired - Lifetime ES2177178T3 (es) | 1997-08-18 | 1998-08-11 | Procedimiento mejorado para la obtencion de precursores de insulina con puentes cistina correctamente unidos. |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES98115048T Expired - Lifetime ES2176870T3 (es) | 1997-08-18 | 1998-08-11 | Procedimiento para la obtencion de precusores de la insulina con puentes de cistina correctamente ligados. |
Country Status (20)
| Country | Link |
|---|---|
| US (3) | US5986048A (es) |
| EP (2) | EP0906918B1 (es) |
| JP (1) | JP4291900B2 (es) |
| KR (2) | KR100537842B1 (es) |
| CN (3) | CN1132845C (es) |
| AR (1) | AR016821A1 (es) |
| AT (2) | ATE217012T1 (es) |
| AU (1) | AU744824B2 (es) |
| BR (2) | BRPI9816233B8 (es) |
| CA (1) | CA2245151C (es) |
| CZ (1) | CZ295679B6 (es) |
| DE (3) | DE19735711C2 (es) |
| DK (2) | DK0980874T3 (es) |
| ES (2) | ES2176870T3 (es) |
| HU (2) | HU228203B1 (es) |
| ID (1) | ID20717A (es) |
| PL (1) | PL191901B1 (es) |
| PT (2) | PT906918E (es) |
| RU (2) | RU2205836C2 (es) |
| TR (1) | TR199801587A3 (es) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19735711C2 (de) | 1997-08-18 | 2001-04-26 | Aventis Pharma Gmbh | Verfahren zur Herstellung eines Vorläufers von Insulin oder Insulinderivaten mit korrekt verbundenen Cystinbrücken |
| DE19930676B4 (de) * | 1999-07-02 | 2006-01-19 | Sanofi-Aventis Deutschland Gmbh | Verfahren zur Stabilisierung von Insulin, Insulinderivaten und/oder deren Vorläufer in komplexen Mischungen bei deren Lagerung in wäßrigen Lösungsmitteln |
| JP2003530316A (ja) * | 1999-12-22 | 2003-10-14 | ノボ ノルディスク アクティーゼルスカブ | スクランブルした一本鎖ポリペプチドの抽出的再生法 |
| EP1303532A2 (en) * | 2000-07-12 | 2003-04-23 | Eli Lilly And Company | Process to increase protein stability |
| DE10235168A1 (de) * | 2002-08-01 | 2004-02-12 | Aventis Pharma Deutschland Gmbh | Verfahren zur Reinigung von Preproinsulin |
| DE102004015965A1 (de) * | 2004-04-01 | 2005-10-20 | Aventis Pharma Gmbh | Verfahren zur Gewinnung von Insulinen durch verbesserte Luftbegasung der Faltung |
| US20080032343A1 (en) | 2005-12-22 | 2008-02-07 | Genentech, Inc. | Recombinant Production of Heparin Binding Proteins |
| SG162834A1 (en) | 2006-07-14 | 2010-07-29 | Genentech Inc | Refolding of recombinant proteins |
| AU2008272762B2 (en) * | 2007-07-03 | 2014-06-19 | Amgen Inc. | Measurement of protein using inclusion body dry weight |
| RU2451750C2 (ru) * | 2007-09-24 | 2012-05-27 | Общество С Ограниченной Ответственностью "Герофарм" | Способ получения рекомбинантного с-пептида проинсулина человека |
| AU2009203809B2 (en) | 2008-01-09 | 2013-07-25 | Sanofi-Aventis Deutschland Gmbh | Novel insulin derivatives having an extremely delayed time-action profile |
| US9296806B2 (en) * | 2008-04-30 | 2016-03-29 | Wockhardt Limited | Processes for refolding of insulin |
| PT3228320T (pt) | 2008-10-17 | 2020-03-26 | Sanofi Aventis Deutschland | Combinação de uma insulina e de um agonista do glp-1 |
| KR101337322B1 (ko) | 2009-11-13 | 2013-12-06 | 사노피-아벤티스 도이칠란트 게엠베하 | Ｇｌｐ-1 효능제 및 메티오닌을 포함하는 약제학적 조성물 |
| DK2498802T3 (en) | 2009-11-13 | 2015-04-13 | Sanofi Aventis Deutschland | Pharmaceutical composition comprising a GLP-1 agonist, insulin and a methionine |
| ES2606554T3 (es) | 2010-08-30 | 2017-03-24 | Sanofi-Aventis Deutschland Gmbh | Uso de AVE0010 para la fabricación de un medicamento para el tratamiento de la diabetes mellitus de tipo 2 |
| US9821032B2 (en) | 2011-05-13 | 2017-11-21 | Sanofi-Aventis Deutschland Gmbh | Pharmaceutical combination for improving glycemic control as add-on therapy to basal insulin |
| AR087744A1 (es) | 2011-09-01 | 2014-04-16 | Sanofi Aventis Deutschland | Composicion farmaceutica para uso en el tratamiento de una enfermedad neurodegenerativa |
| US12157766B2 (en) * | 2012-08-05 | 2024-12-03 | Absci Corporation | Cytoplasmic expression system |
| US10421795B2 (en) | 2012-12-17 | 2019-09-24 | Merck Sharp & Dohme Corp. | Process for purifying insulin and analogues thereof |
| SG10201907106VA (en) * | 2013-02-26 | 2019-09-27 | Hanmi Pharmaceutical Co Ltd | Novel insulin analog and use thereof |
| CN103694339B (zh) * | 2013-12-04 | 2017-10-13 | 珠海联邦制药股份有限公司 | 一种甘精胰岛素前体的复性方法 |
| WO2015138548A1 (en) | 2014-03-14 | 2015-09-17 | Merck Sharp & Dohme Corp. | Purifying insulin using cation exchange and reverse phase chromatography in the presence of an organic modifier and elevated temperature |
| AU2015359376B2 (en) | 2014-12-12 | 2021-09-09 | Sanofi-Aventis Deutschland Gmbh | Insulin glargine/lixisenatide fixed ratio formulation |
| TWI748945B (zh) | 2015-03-13 | 2021-12-11 | 德商賽諾菲阿凡提斯德意志有限公司 | 第２型糖尿病病患治療 |
| TW201705975A (zh) | 2015-03-18 | 2017-02-16 | 賽諾菲阿凡提斯德意志有限公司 | 第２型糖尿病病患之治療 |
| CN104911203A (zh) * | 2015-06-30 | 2015-09-16 | 成都易胜科生物科技有限公司 | 一种重组人胰岛素的工业制备方法 |
| EP3344651B1 (en) | 2015-09-02 | 2022-03-02 | Merck Sharp & Dohme Corp. | A process for obtaining insulin with correctly formed disulfide bonds |
| EP3463413A4 (en) | 2016-05-25 | 2020-03-04 | Merck Sharp & Dohme Corp. | INSULIN RECEPTOR PART AGONISTS |
| WO2018018613A1 (zh) | 2016-07-29 | 2018-02-01 | 广东东阳光药业有限公司 | 一种提高抗体纯度的细胞培养基和培养方法 |
| CN113773391B (zh) * | 2020-06-09 | 2023-10-20 | 宁波鲲鹏生物科技有限公司 | 一种门冬胰岛素的制备方法 |
| CN113773400B (zh) * | 2020-06-09 | 2023-08-18 | 宁波鲲鹏生物科技有限公司 | 一种门冬胰岛素衍生物及其应用 |
| CN113773396A (zh) * | 2020-06-10 | 2021-12-10 | 宁波鲲鹏生物科技有限公司 | 一种地特胰岛素衍生物及其应用 |
| JP7749397B2 (ja) * | 2021-09-30 | 2025-10-06 | キヤノン株式会社 | 超音波ファントム及び超音波ファントムの製造方法 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ199391A (en) * | 1981-01-02 | 1985-12-13 | Genentech Inc | Chimeric polypeptides comprising a proinsulin sequence,and preparation by recombinant dna technique;production of human insulin |
| DE3501641A1 (de) * | 1985-01-19 | 1986-07-24 | Hoechst Ag, 6230 Frankfurt | Verfahren zur gewinnung von insulin-vorlaeufern aus reaktionsgemischen, die bei der faltung von insulin-vorlaeufern aus den entsprechenden s-sulfonaten anfallen |
| IL95495A (en) * | 1989-08-29 | 1996-10-16 | Hoechst Ag | Fusion proteins their preparation and use |
| RU2045535C1 (ru) * | 1991-06-18 | 1995-10-10 | Институт биоорганической химии им.М.М.Шемякина и Ю.А.Овчинникова РАН | Способ получения проинсулина человека |
| SG46612A1 (en) * | 1992-12-02 | 1998-02-20 | Hoechst Ag | Process for obtaining proinsulin in processing correctly linked cystine bridges |
| DE4405179A1 (de) * | 1994-02-18 | 1995-08-24 | Hoechst Ag | Verfahren zur Gewinnung von Insulin mit korrekt verbundenen Cystinbrücken |
| RU2081122C1 (ru) * | 1994-06-16 | 1997-06-10 | Институт биоорганической химии им.М.М.Шемякина и Ю.А.Овчинникова РАН | Способ выделения и очистки инсулина или его биотехнологических предшественников |
| ATE350053T1 (de) * | 1994-12-29 | 2007-01-15 | Ferring Int Ct Sa | Herstellung von humaninsulin |
| DE19735711C2 (de) * | 1997-08-18 | 2001-04-26 | Aventis Pharma Gmbh | Verfahren zur Herstellung eines Vorläufers von Insulin oder Insulinderivaten mit korrekt verbundenen Cystinbrücken |
-
1997
- 1997-08-18 DE DE19735711A patent/DE19735711C2/de not_active Expired - Lifetime
-
1998
- 1998-08-11 DK DK99115386T patent/DK0980874T3/da active
- 1998-08-11 PT PT98115048T patent/PT906918E/pt unknown
- 1998-08-11 EP EP98115048A patent/EP0906918B1/de not_active Expired - Lifetime
- 1998-08-11 DE DE59803985T patent/DE59803985D1/de not_active Expired - Lifetime
- 1998-08-11 PT PT99115386T patent/PT980874E/pt unknown
- 1998-08-11 EP EP99115386A patent/EP0980874B1/de not_active Expired - Lifetime
- 1998-08-11 AT AT99115386T patent/ATE217012T1/de active
- 1998-08-11 DE DE59804121T patent/DE59804121D1/de not_active Expired - Lifetime
- 1998-08-11 DK DK98115048T patent/DK0906918T3/da active
- 1998-08-11 ES ES98115048T patent/ES2176870T3/es not_active Expired - Lifetime
- 1998-08-11 AT AT98115048T patent/ATE217636T1/de active
- 1998-08-11 ES ES99115386T patent/ES2177178T3/es not_active Expired - Lifetime
- 1998-08-14 ID IDP981136A patent/ID20717A/id unknown
- 1998-08-14 AR ARP980104052A patent/AR016821A1/es active IP Right Grant
- 1998-08-14 CA CA002245151A patent/CA2245151C/en not_active Expired - Lifetime
- 1998-08-17 CN CN98117909A patent/CN1132845C/zh not_active Expired - Lifetime
- 1998-08-17 BR BRPI9816233A patent/BRPI9816233B8/pt not_active IP Right Cessation
- 1998-08-17 CN CN031523307A patent/CN1483831B/zh not_active Expired - Lifetime
- 1998-08-17 AU AU80763/98A patent/AU744824B2/en not_active Expired
- 1998-08-17 CN CN2006101000625A patent/CN101186940B/zh not_active Expired - Lifetime
- 1998-08-17 HU HU0600287A patent/HU228203B1/hu unknown
- 1998-08-17 JP JP23036898A patent/JP4291900B2/ja not_active Expired - Lifetime
- 1998-08-17 TR TR1998/01587A patent/TR199801587A3/tr unknown
- 1998-08-17 BR BR9803755-2A patent/BR9803755A/pt not_active Application Discontinuation
- 1998-08-17 HU HU9801886A patent/HU228161B1/hu unknown
- 1998-08-17 CZ CZ19982598A patent/CZ295679B6/cs not_active IP Right Cessation
- 1998-08-17 US US09/134,836 patent/US5986048A/en not_active Expired - Lifetime
- 1998-08-17 RU RU98116259/04A patent/RU2205836C2/ru active
- 1998-08-18 PL PL328108A patent/PL191901B1/pl unknown
- 1998-08-18 KR KR1019980033384A patent/KR100537842B1/ko not_active Expired - Lifetime
-
1999
- 1999-08-31 US US09/386,303 patent/US6380355B1/en not_active Expired - Lifetime
-
2001
- 2001-09-07 US US09/947,563 patent/US6727346B2/en not_active Expired - Lifetime
-
2002
- 2002-10-07 RU RU2002126598/15A patent/RU2302882C2/ru active
-
2005
- 2005-05-27 KR KR1020050044974A patent/KR100574580B1/ko not_active Expired - Lifetime
Also Published As
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