PT89802B - Processo para a preparacao de uma composicao farmaceutica, contendo o factor xiii de coagulacao do sangue humano, para a prevencao da hemorragia intraventricular em criancas permaturas - Google Patents
Processo para a preparacao de uma composicao farmaceutica, contendo o factor xiii de coagulacao do sangue humano, para a prevencao da hemorragia intraventricular em criancas permaturas Download PDFInfo
- Publication number
- PT89802B PT89802B PT89802A PT8980289A PT89802B PT 89802 B PT89802 B PT 89802B PT 89802 A PT89802 A PT 89802A PT 8980289 A PT8980289 A PT 8980289A PT 89802 B PT89802 B PT 89802B
- Authority
- PT
- Portugal
- Prior art keywords
- factor xiii
- children
- prevention
- intraventricular hemorrhage
- human blood
- Prior art date
Links
- 206010022840 Intraventricular haemorrhage Diseases 0.000 title claims abstract description 16
- 230000002265 prevention Effects 0.000 title claims abstract description 7
- 229940012444 factor xiii Drugs 0.000 title claims description 32
- 238000000034 method Methods 0.000 title claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 3
- 210000004369 blood Anatomy 0.000 title description 2
- 239000008280 blood Substances 0.000 title description 2
- 230000015271 coagulation Effects 0.000 title 1
- 238000005345 coagulation Methods 0.000 title 1
- 108010071289 Factor XIII Proteins 0.000 claims abstract description 33
- 230000002028 premature Effects 0.000 claims abstract description 9
- 239000002244 precipitate Substances 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 10
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 9
- 241000700605 Viruses Species 0.000 claims description 5
- 210000002826 placenta Anatomy 0.000 claims description 5
- 102000005686 Serum Globulins Human genes 0.000 claims description 4
- 108010045362 Serum Globulins Proteins 0.000 claims description 4
- 238000005194 fractionation Methods 0.000 claims description 4
- 238000010353 genetic engineering Methods 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 238000000605 extraction Methods 0.000 claims 1
- 230000002779 inactivation Effects 0.000 claims 1
- 238000010348 incorporation Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 238000002347 injection Methods 0.000 abstract description 7
- 239000007924 injection Substances 0.000 abstract description 7
- 239000000243 solution Substances 0.000 description 16
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 208000032843 Hemorrhage Diseases 0.000 description 9
- 239000006228 supernatant Substances 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 210000002381 plasma Anatomy 0.000 description 5
- 108010073385 Fibrin Proteins 0.000 description 4
- 102000009123 Fibrin Human genes 0.000 description 4
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 230000000740 bleeding effect Effects 0.000 description 4
- 229950003499 fibrin Drugs 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000002861 ventricular Effects 0.000 description 4
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 3
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 3
- 235000011130 ammonium sulphate Nutrition 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 230000029663 wound healing Effects 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 229960002449 glycine Drugs 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 1
- IYLLULUTZPKQBW-UHFFFAOYSA-N Acrinol Chemical compound CC(O)C(O)=O.C1=C(N)C=CC2=C(N)C3=CC(OCC)=CC=C3N=C21 IYLLULUTZPKQBW-UHFFFAOYSA-N 0.000 description 1
- 206010003497 Asphyxia Diseases 0.000 description 1
- 108010058861 Fibrin Fibrinogen Degradation Products Proteins 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 206010022653 Intestinal haemorrhages Diseases 0.000 description 1
- 206010061249 Intra-abdominal haemorrhage Diseases 0.000 description 1
- 206010036590 Premature baby Diseases 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 102000003929 Transaminases Human genes 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 108060008539 Transglutaminase Proteins 0.000 description 1
- 206010053476 Traumatic haemorrhage Diseases 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000001166 ammonium sulphate Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- YMKDRGPMQRFJGP-UHFFFAOYSA-M cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 210000003017 ductus arteriosus Anatomy 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000208 fibrin degradation product Substances 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000004023 fresh frozen plasma Substances 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 235000013905 glycine and its sodium salt Nutrition 0.000 description 1
- 230000023597 hemostasis Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000003434 inspiratory effect Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 229960002695 phenobarbital Drugs 0.000 description 1
- 230000003169 placental effect Effects 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 102000003601 transglutaminase Human genes 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
- A61K35/16—Blood plasma; Blood serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/45—Transferases (2)
-
- 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
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Cell Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Cardiology (AREA)
- Virology (AREA)
- Vascular Medicine (AREA)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Developmental Biology & Embryology (AREA)
- Heart & Thoracic Surgery (AREA)
- Zoology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63039646A JPH01216939A (ja) | 1988-02-24 | 1988-02-24 | 末熟児頭蓋内出血阻止剤 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PT89802A PT89802A (pt) | 1989-10-04 |
| PT89802B true PT89802B (pt) | 1994-04-29 |
Family
ID=12558846
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT89802A PT89802B (pt) | 1988-02-24 | 1989-02-23 | Processo para a preparacao de uma composicao farmaceutica, contendo o factor xiii de coagulacao do sangue humano, para a prevencao da hemorragia intraventricular em criancas permaturas |
Country Status (12)
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5612456A (en) * | 1988-11-14 | 1997-03-18 | Zymogenetics, Inc. | Factor XIII compositions |
| WO1993012813A1 (en) * | 1991-12-31 | 1993-07-08 | Zymogenetics, Inc. | Methods and compositions for reducing blood loss |
| EP0598133B1 (en) * | 1992-04-21 | 2000-03-29 | Ajinomoto Co., Inc. | Remedy for wound |
| ES2139729T3 (es) * | 1992-11-12 | 2000-02-16 | Zymogenetics Inc | Uso del factor xiii aplicado topicamente para la inhibicion de hemorragias. |
| JPH07328108A (ja) * | 1994-06-10 | 1995-12-19 | Ajinomoto Co Inc | 生体組織接着剤及び血液凝固剤 |
| CN1896231B (zh) | 1998-08-06 | 2012-09-05 | 山景药品公司 | 分离四聚体尿酸氧化酶的方法 |
| WO2006021584A2 (en) * | 2004-08-27 | 2006-03-02 | Novo Nordisk Health Care Ag | Purification of factor xiii polypeptides from biological materials |
| US8461302B2 (en) * | 2004-11-23 | 2013-06-11 | Zymogenetics, Inc. | Purification of recombinant human factor XIII |
| TWI418564B (zh) * | 2005-04-11 | 2013-12-11 | Savient Pharmaceuticals Inc | 利用陽離子界面活性劑之蛋白質純化 |
| EP2947145A1 (en) | 2005-04-11 | 2015-11-25 | Crealta Pharmaceuticals LLC | Variant forms of urate oxidase and use thereof |
| PL2013225T3 (pl) * | 2006-04-12 | 2015-06-30 | Crealta Pharmaceuticals Llc | Oczyszczanie białek z zastosowaniem kationowego środka powierzchniowo czynnego |
| US9377454B2 (en) | 2009-06-25 | 2016-06-28 | Crealta Pharmaceuticals Llc | Methods and kits for predicting infusion reaction risk and antibody-mediated loss of response by monitoring serum uric acid during pegylated uricase therapy |
| US12121566B2 (en) | 2019-01-30 | 2024-10-22 | Horizon Therapeutics Usa, Inc. | Methods for treating gout |
| US12269875B2 (en) | 2023-08-03 | 2025-04-08 | Jeff R. Peterson | Gout flare prevention methods using IL-1BETA blockers |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3717708A (en) * | 1968-10-24 | 1973-02-20 | Cutter Lab | Blood coagulation complex |
| DE2063070C3 (de) * | 1970-12-22 | 1975-07-24 | Behringwerke Ag, 3550 Marburg | Verfahren zur Herstellung eines Arzneimittels mit fibrinstabilisierender Wirkung |
| DE3622642A1 (de) * | 1986-07-05 | 1988-01-14 | Behringwerke Ag | Einkomponenten-gewebekleber sowie verfahren zu seiner herstellung |
| DK175919B1 (da) * | 1986-09-19 | 2005-06-27 | Univ Washington | Ekspression af biologisk aktiv faktor XIII |
-
1988
- 1988-02-24 JP JP63039646A patent/JPH01216939A/ja active Granted
-
1989
- 1989-02-14 ES ES89102471T patent/ES2059588T3/es not_active Expired - Lifetime
- 1989-02-14 AT AT89102471T patent/ATE94070T1/de not_active IP Right Cessation
- 1989-02-14 EP EP89102471A patent/EP0330049B1/en not_active Expired - Lifetime
- 1989-02-14 DE DE89102471T patent/DE68908913T2/de not_active Expired - Lifetime
- 1989-02-23 AU AU30243/89A patent/AU613154B2/en not_active Expired
- 1989-02-23 IE IE58089A patent/IE63656B1/en not_active IP Right Cessation
- 1989-02-23 CA CA000591929A patent/CA1332352C/en not_active Expired - Lifetime
- 1989-02-23 KR KR1019890002127A patent/KR0137476B1/ko not_active Expired - Lifetime
- 1989-02-23 PT PT89802A patent/PT89802B/pt not_active IP Right Cessation
- 1989-02-23 DK DK198900838A patent/DK174978B1/da not_active IP Right Cessation
-
1990
- 1990-02-14 US US07/480,358 patent/US5114916A/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| PT89802A (pt) | 1989-10-04 |
| DE68908913D1 (de) | 1993-10-14 |
| DE68908913T2 (de) | 1994-01-27 |
| JPH01216939A (ja) | 1989-08-30 |
| KR890012659A (ko) | 1989-09-18 |
| ATE94070T1 (de) | 1993-09-15 |
| DK174978B1 (da) | 2004-04-05 |
| KR0137476B1 (ko) | 1998-06-01 |
| US5114916A (en) | 1992-05-19 |
| DK83889A (da) | 1989-08-25 |
| IE63656B1 (en) | 1995-05-31 |
| AU3024389A (en) | 1989-08-24 |
| EP0330049A2 (en) | 1989-08-30 |
| EP0330049A3 (en) | 1991-01-30 |
| EP0330049B1 (en) | 1993-09-08 |
| DK83889D0 (da) | 1989-02-23 |
| IE890580L (en) | 1989-08-24 |
| CA1332352C (en) | 1994-10-11 |
| AU613154B2 (en) | 1991-07-25 |
| ES2059588T3 (es) | 1994-11-16 |
| JPH0378850B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1991-12-17 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FG3A | Patent granted, date of granting |
Effective date: 19931018 |
|
| MM4A | Annulment/lapse due to non-payment of fees, searched and examined patent |
Free format text: MAXIMUM VALIDITY LIMIT REACHED Effective date: 20090223 |