CA2264776C - Stable protein and nucleic acid formulations using non-aqueous, anhydrous, aprotic, hydrophobic, non-polar vehicles with low reactivity - Google Patents
Stable protein and nucleic acid formulations using non-aqueous, anhydrous, aprotic, hydrophobic, non-polar vehicles with low reactivity Download PDFInfo
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- CA2264776C CA2264776C CA002264776A CA2264776A CA2264776C CA 2264776 C CA2264776 C CA 2264776C CA 002264776 A CA002264776 A CA 002264776A CA 2264776 A CA2264776 A CA 2264776A CA 2264776 C CA2264776 C CA 2264776C
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0026—Blood substitute; Oxygen transporting formulations; Plasma extender
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2816796P | 1996-10-16 | 1996-10-16 | |
| US60/028,167 | 1996-10-16 | ||
| US5292097P | 1997-07-15 | 1997-07-15 | |
| US60/052,920 | 1997-07-15 | ||
| PCT/US1997/018575 WO1998016250A1 (en) | 1996-10-16 | 1997-10-15 | Stable protein and nucleic acid formulations using non-aqueous, anhydrous, aprotic, hydrophobic, non-polar vehicles with low reactivity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2264776A1 CA2264776A1 (en) | 1998-04-23 |
| CA2264776C true CA2264776C (en) | 2008-11-25 |
Family
ID=26703379
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002264776A Expired - Fee Related CA2264776C (en) | 1996-10-16 | 1997-10-15 | Stable protein and nucleic acid formulations using non-aqueous, anhydrous, aprotic, hydrophobic, non-polar vehicles with low reactivity |
Country Status (10)
| Country | Link |
|---|---|
| US (3) | US6264990B1 (en:Method) |
| EP (1) | EP0939655B1 (en:Method) |
| JP (1) | JP2002513390A (en:Method) |
| AR (1) | AR008673A1 (en:Method) |
| AT (1) | ATE218886T1 (en:Method) |
| AU (1) | AU4821197A (en:Method) |
| CA (1) | CA2264776C (en:Method) |
| DE (1) | DE69713378T2 (en:Method) |
| IN (1) | IN184589B (en:Method) |
| WO (1) | WO1998016250A1 (en:Method) |
Families Citing this family (102)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IN184589B (en:Method) * | 1996-10-16 | 2000-09-09 | Alza Corp | |
| US20020182258A1 (en) * | 1997-01-22 | 2002-12-05 | Zycos Inc., A Delaware Corporation | Microparticles for delivery of nucleic acid |
| US7258869B1 (en) | 1999-02-08 | 2007-08-21 | Alza Corporation | Stable non-aqueous single phase viscous vehicles and formulations utilizing such vehicle |
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| US20020041884A1 (en) * | 2000-03-07 | 2002-04-11 | Evans Robert K. | Adenovirus formulations |
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| US6827250B2 (en) * | 2001-06-28 | 2004-12-07 | Microchips, Inc. | Methods for hermetically sealing microchip reservoir devices |
| AU2002353013A1 (en) * | 2001-12-03 | 2003-06-17 | Massachusetts Institute Of Technology | Microscale lyophilization and drying methods for the stabilization of molecules |
| AU2003233396B2 (en) * | 2002-03-13 | 2007-05-24 | Thomas Skold | Water-based delivery systems |
| CA2495327C (en) * | 2002-08-16 | 2008-10-21 | Microchips, Inc. | Controlled release device and method using electrothermal ablation |
| US7497855B2 (en) * | 2002-09-04 | 2009-03-03 | Microchips, Inc. | Method and device for the controlled delivery of parathyroid hormone |
| GB2410497B (en) * | 2002-09-27 | 2006-11-22 | Powderject Res Ltd | Nucleic acid coated particles |
| EP1551499A1 (en) | 2002-10-04 | 2005-07-13 | Microchips, Inc. | Medical device for neural stimulation and controlled drug delivery |
| US7731947B2 (en) | 2003-11-17 | 2010-06-08 | Intarcia Therapeutics, Inc. | Composition and dosage form comprising an interferon particle formulation and suspending vehicle |
| US8110209B2 (en) | 2002-12-20 | 2012-02-07 | Xeris Pharmaceuticals Inc. | Intracutaneous injection |
| WO2004091495A2 (en) * | 2003-04-09 | 2004-10-28 | University Of Utah Research Foundation | Compositions and methods related to production of erythropoietin |
| ES2359243T3 (es) * | 2003-04-25 | 2011-05-19 | Boston Scientific Scimed, Inc. | Formulación de fármaco sólida y dispositivo para el almacenamiento y la administración controlada de la misma. |
| US7892205B2 (en) * | 2003-06-06 | 2011-02-22 | Boston Scientific Scimed, Inc. | Device and method for delivering micronized therapeutic agents in the body |
| WO2005041767A2 (en) * | 2003-11-03 | 2005-05-12 | Microchips, Inc. | Medical device for sensing glucose |
| WO2006085908A2 (en) * | 2004-06-01 | 2006-08-17 | Microchips, Inc. | Devices and methods for measuring and enhancing drug or analyte transport to/from medical implant |
| US7537590B2 (en) * | 2004-07-30 | 2009-05-26 | Microchips, Inc. | Multi-reservoir device for transdermal drug delivery and sensing |
| US20060029551A1 (en) * | 2004-08-05 | 2006-02-09 | Kui Liu | Stable particle formulations of erythropoietin receptor agonists |
| US7772182B2 (en) * | 2004-08-05 | 2010-08-10 | Alza Corporation | Stable suspension formulations of erythropoietin receptor agonists |
| US7604628B2 (en) * | 2004-09-01 | 2009-10-20 | Microchips, Inc. | Multi-cap reservoir devices for controlled release or exposure of reservoir contents |
| EP2995331B1 (en) | 2004-09-10 | 2018-09-05 | Becton, Dickinson and Company | Reconstituting infusion device and method of reconstituting medicament |
| CA2595457A1 (en) | 2005-01-25 | 2006-08-03 | Microchips, Inc. | Control of drug release by transient modification of local microenvironments |
| US11246913B2 (en) | 2005-02-03 | 2022-02-15 | Intarcia Therapeutics, Inc. | Suspension formulation comprising an insulinotropic peptide |
| WO2006083761A2 (en) | 2005-02-03 | 2006-08-10 | Alza Corporation | Solvent/polymer solutions as suspension vehicles |
| ES2643140T3 (es) * | 2005-12-22 | 2017-11-21 | Oakwood Laboratories L.L.C. | Sistema de suministro de liberación lenta sublimable y procedimiento de realización del mismo |
| DE602007009377D1 (de) | 2006-05-30 | 2010-11-04 | Intarcia Therapeutics Inc | Zweiteiliger flussmodulator mit einem internen kanal für ein osmotisches ausgabesystem |
| PL2359808T3 (pl) | 2006-08-09 | 2013-10-31 | Intarcia Therapeutics Inc | Osmotyczne systemy dostawcze i zespoły tłokowe |
| US8945529B2 (en) * | 2007-03-30 | 2015-02-03 | Helix Biopharma Corporation | Biphasic lipid-vesicle compositions |
| JP5351884B2 (ja) | 2007-04-23 | 2013-11-27 | インターシア セラピューティクス，インコーポレイティド | インスリン分泌促進性ペプチドの懸濁製剤及び使用 |
| DK2170283T3 (en) | 2007-06-22 | 2019-04-15 | Univ Texas | CREATION OF STABLE SUBMICRON Peptide OR PROTEIN PARTICLES BY THIN FILM FREEZING |
| WO2009102467A2 (en) | 2008-02-13 | 2009-08-20 | Intarcia Therapeutics, Inc. | Devices, formulations, and methods for delivery of multiple beneficial agents |
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| US20110223208A1 (en) * | 2010-03-09 | 2011-09-15 | Beth Hill | Non-Aqueous High Concentration Reduced Viscosity Suspension Formulations |
| US9072668B2 (en) | 2010-03-09 | 2015-07-07 | Janssen Biotech, Inc. | Non-aqueous high concentration reduced viscosity suspension formulations of antibodies |
| ES2659079T3 (es) * | 2010-03-09 | 2018-03-13 | Janssen Biotech, Inc. | Formulaciones no acuosas en suspensión de viscosidad reducida a concentración elevada |
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| EP2444063A1 (en) | 2010-10-20 | 2012-04-25 | Novaliq GmbH | Liquid pharmaceutical compositions for the delivery of active ingredients |
| EP2462921A1 (en) | 2010-11-11 | 2012-06-13 | Novaliq GmbH | Liquid pharmaceutical compositions for the treatment of a posterior eye disease |
| US20120208755A1 (en) | 2011-02-16 | 2012-08-16 | Intarcia Therapeutics, Inc. | Compositions, Devices and Methods of Use Thereof for the Treatment of Cancers |
| US8697644B2 (en) | 2011-03-10 | 2014-04-15 | Xeris Pharmaceuticals, Inc. | Stable formulations for parenteral injection of peptide drugs |
| JP6023181B2 (ja) | 2011-05-25 | 2016-11-09 | ノバリック ゲーエムベーハー | 爪に投与するための医薬組成物 |
| EP2714010B1 (en) | 2011-05-25 | 2017-03-01 | Novaliq GmbH | Topical pharmaceutical composition based on semifluorinated alkanes |
| ES2574761T3 (es) | 2011-10-31 | 2016-06-21 | Xeris Pharmaceuticals, Inc. | Formulaciones para el tratamiento de la diabetes |
| MX361681B (es) | 2012-01-23 | 2018-12-13 | Novaliq Gmbh | Composiciones de proteína estabilizadas basadas en alcanos semifluorados. |
| US9125805B2 (en) | 2012-06-27 | 2015-09-08 | Xeris Pharmaceuticals, Inc. | Stable formulations for parenteral injection of small molecule drugs |
| PL3181119T3 (pl) | 2012-09-12 | 2020-01-31 | Novaliq Gmbh | Kompozycje semifluorowanych alkanów do zastosowania w leczeniu suchego zapalenia spojówki i rogówki |
| CN113952321B (zh) | 2012-09-12 | 2023-03-28 | 诺瓦利克有限责任公司 | 包含半氟化烷烃的混合物的组合物 |
| EP2943479B1 (en) | 2013-01-11 | 2020-04-15 | Corsair Pharma, Inc. | Prodrugs of treprostinil |
| US9505737B2 (en) | 2013-01-11 | 2016-11-29 | Corsair Pharma, Inc. | Treprostinil derivative compounds and methods of using same |
| US9018162B2 (en) | 2013-02-06 | 2015-04-28 | Xeris Pharmaceuticals, Inc. | Methods for rapidly treating severe hypoglycemia |
| SG10201913874TA (en) | 2013-03-15 | 2020-03-30 | Biogen Ma Inc | Factor ix polypeptide formulations |
| JP6503349B2 (ja) | 2013-07-23 | 2019-04-17 | ノバリック ゲーエムベーハー | 安定化された抗体組成物 |
| US8986732B2 (en) | 2013-08-12 | 2015-03-24 | Helix Biopharma Corporation | Biphasic lipid-vesicle compositions and methods for treating cervical dysplasia by intravaginal delivery |
| US10159646B2 (en) | 2013-08-12 | 2018-12-25 | Altum-Avro Pharma Partnership | Biphasic lipid-vesicle compositions and methods for treating cervical dysplasia by intravaginal delivery |
| IL312865B2 (en) | 2013-09-11 | 2025-06-01 | Eagle Biologics Inc | Liquid protein formulations containing viscosity-lowering agents |
| JP7097667B2 (ja) | 2013-09-27 | 2022-07-08 | マサチューセッツ インスティテュート オブ テクノロジー | 無担体生物活性タンパク質ナノ構造体 |
| MX387269B (es) * | 2014-03-24 | 2025-03-18 | Bioverativ Therapeutics Inc | Formulaciones de factor ix liofilizadas. |
| WO2016010538A1 (en) | 2014-07-16 | 2016-01-21 | Corsair Pharma, Inc. | Treprostinil derivative compounds and methods of using same |
| CA2957399C (en) | 2014-08-06 | 2023-09-26 | Xeris Pharmaceuticals, Inc. | Syringes, kits, and methods for intracutaneous and/or subcutaneous injection of pastes |
| US9889085B1 (en) | 2014-09-30 | 2018-02-13 | Intarcia Therapeutics, Inc. | Therapeutic methods for the treatment of diabetes and related conditions for patients with high baseline HbA1c |
| KR102497368B1 (ko) | 2014-10-01 | 2023-02-10 | 이글 바이올로직스 인코포레이티드 | 점도-저하제를 함유하는 폴리삭카라이드 및 핵산 제형 |
| EP4278996A3 (en) | 2015-06-03 | 2024-01-24 | i2o Therapeutics, Inc. | Implant placement systems |
| US9649364B2 (en) | 2015-09-25 | 2017-05-16 | Xeris Pharmaceuticals, Inc. | Methods for producing stable therapeutic formulations in aprotic polar solvents |
| US9394227B1 (en) | 2015-06-17 | 2016-07-19 | Corsair Pharma, Inc. | Treprostinil derivatives and compositions and uses thereof |
| US9643911B2 (en) | 2015-06-17 | 2017-05-09 | Corsair Pharma, Inc. | Treprostinil derivatives and compositions and uses thereof |
| CN108990413A (zh) | 2015-08-12 | 2018-12-11 | 麻省理工学院 | 纳米颗粒的细胞表面偶联 |
| US11590205B2 (en) | 2015-09-25 | 2023-02-28 | Xeris Pharmaceuticals, Inc. | Methods for producing stable therapeutic glucagon formulations in aprotic polar solvents |
| HK1257183B (en) | 2015-09-30 | 2020-06-12 | Novaliq Gmbh | Semifluorinated compounds and their compositions |
| CN108349855B (zh) | 2015-09-30 | 2021-07-20 | 诺瓦利克有限责任公司 | 用于眼部给药的半氟化化合物 |
| BR112018073511A2 (pt) | 2016-05-16 | 2019-03-26 | Intarcia Therapeutics, Inc. | polipeptídeos seletivos do receptor de glucagon e métodos de uso dos mesmos |
| USD840030S1 (en) | 2016-06-02 | 2019-02-05 | Intarcia Therapeutics, Inc. | Implant placement guide |
| USD860451S1 (en) | 2016-06-02 | 2019-09-17 | Intarcia Therapeutics, Inc. | Implant removal tool |
| AU2017283480A1 (en) | 2016-06-13 | 2019-01-24 | Torque Therapeutics, Inc. | Methods and compositions for promoting immune cell function |
| EP3442480B1 (en) | 2016-06-23 | 2019-10-02 | Novaliq GmbH | Topical administration method |
| CN116172987A (zh) | 2016-09-22 | 2023-05-30 | 诺瓦利克有限责任公司 | 用于治疗睑缘炎的药物组合物 |
| US10813976B2 (en) | 2016-09-23 | 2020-10-27 | Novaliq Gmbh | Ophthalmic compositions comprising ciclosporin |
| KR20190104039A (ko) | 2017-01-03 | 2019-09-05 | 인타르시아 세라퓨틱스 인코포레이티드 | Glp-1 수용체 효능제의 연속적인 투여 및 약물의 동시-투여를 포함하는 방법 |
| PL3612228T3 (pl) | 2017-04-21 | 2024-04-08 | Dermaliq Therapeutics, Inc. | Kompozycje jodu |
| CN110650734B (zh) | 2017-05-12 | 2024-11-15 | 诺瓦利克有限责任公司 | 治疗与隐形眼镜有关病症的包含半氟化烷烃的药物组合物 |
| EP3624846B1 (en) | 2017-05-16 | 2024-08-07 | Bhami's Research Laboratory, Pvt. Ltd. | High concentration protein formulations with reduced viscosity including a combination of nicotinic acid and tryoptophan |
| CN117085022A (zh) | 2017-06-02 | 2023-11-21 | Xeris药物公司 | 抗沉淀的小分子药物制剂 |
| JP7285828B2 (ja) | 2017-09-05 | 2023-06-02 | トルク セラピューティクス， インコーポレイテッド | 治療用タンパク質組成物ならびにその作製および使用方法 |
| SG11202002640YA (en) | 2017-09-27 | 2020-04-29 | Novaliq Gmbh | Ophthalmic compositions comprising latanoprost for use in the treatment of ocular diseases |
| CN111182893A (zh) | 2017-10-04 | 2020-05-19 | 诺瓦利克有限责任公司 | 包含f6h8的眼用组合物 |
| MX2020009132A (es) | 2018-03-02 | 2020-12-11 | Novaliq Gmbh | Composiciones farmaceuticas que comprenden nebivolol. |
| EP3784246A1 (en) | 2018-04-27 | 2021-03-03 | Novaliq GmbH | Ophthalmic compositions comprising tafluprost for the treatment of glaucoma |
| WO2019217637A1 (en) * | 2018-05-09 | 2019-11-14 | Biomatrica, Inc. | Stabilization of proteins in biological samples |
| MY206642A (en) | 2018-10-12 | 2024-12-30 | Novaliq Gmbh | Ophthalmic composition for treatment of dry eye disease |
| KR20210125032A (ko) | 2019-02-05 | 2021-10-15 | 린디 바이오사이언시스, 아이엔씨. | 세포 배양 성분 및 액체 세포 배양 배지로부터 이를 단리하는 방법 |
| CN113710228A (zh) | 2019-02-13 | 2021-11-26 | 诺瓦利克有限责任公司 | 用于治疗眼部新生血管形成的组合物和方法 |
| EP4069324B1 (en) | 2019-12-06 | 2025-05-21 | Guangzhou Bioseal Biotech Co., Ltd. | Flowable fibrinogen thrombin paste |
| GB2615462A (en) * | 2020-11-20 | 2023-08-09 | Team Medical Llc | RNA stabilization |
| US20230101362A1 (en) * | 2021-09-16 | 2023-03-30 | Team Medical Llc | Rna stabilization |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2342073A1 (fr) * | 1976-02-27 | 1977-09-23 | Merieux Inst | Nouveau vaccin antivariolique sous forme de pate et son dispositif d'application |
| EP0177342A3 (en) * | 1984-10-04 | 1987-12-02 | Genentech, Inc. | Oral formulation of therapeutic proteins |
| IT8922398A0 (it) * | 1989-11-16 | 1989-11-16 | Phidea Spa | Composizioni farmaceutiche ad elevato assorbimento e stabilita', comprendente una calcitonina come sostanza attiva. |
| US5518731A (en) * | 1990-09-27 | 1996-05-21 | Allergan, Inc. | Nonaqueous fluorinated drug delivery vehicle suspensions |
| CA2134773A1 (en) | 1992-06-04 | 1993-12-09 | Robert J. Debs | Methods and compositions for in vivo gene therapy |
| WO1994006452A1 (en) | 1992-09-21 | 1994-03-31 | The Upjohn Company | Sustained-release protein formulations |
| US5480914A (en) | 1994-05-06 | 1996-01-02 | Allergan, Inc. | Nonaqueous thixotropic drug delivery suspensions and methods of their use |
| WO1996027393A1 (en) | 1995-03-07 | 1996-09-12 | University Of Pittsburgh | A dry powder formulation for gene therapy |
| US5811406A (en) | 1995-06-07 | 1998-09-22 | Regents Of The University Of California | Dry powder formulations of polynucleotide complexes |
| IN184589B (en:Method) * | 1996-10-16 | 2000-09-09 | Alza Corp |
-
1997
- 1997-09-23 IN IN1756CA1997 patent/IN184589B/en unknown
- 1997-10-15 AR ARP970104744A patent/AR008673A1/es unknown
- 1997-10-15 CA CA002264776A patent/CA2264776C/en not_active Expired - Fee Related
- 1997-10-15 AT AT97910959T patent/ATE218886T1/de not_active IP Right Cessation
- 1997-10-15 EP EP97910959A patent/EP0939655B1/en not_active Expired - Lifetime
- 1997-10-15 WO PCT/US1997/018575 patent/WO1998016250A1/en active IP Right Grant
- 1997-10-15 AU AU48211/97A patent/AU4821197A/en not_active Abandoned
- 1997-10-15 DE DE69713378T patent/DE69713378T2/de not_active Expired - Fee Related
- 1997-10-15 US US09/269,685 patent/US6264990B1/en not_active Expired - Lifetime
- 1997-10-15 JP JP51854898A patent/JP2002513390A/ja not_active Ceased
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2001
- 2001-05-04 US US09/849,402 patent/US6730328B2/en not_active Expired - Lifetime
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2004
- 2004-01-22 US US10/763,149 patent/US20040151779A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20010038859A1 (en) | 2001-11-08 |
| IN184589B (en:Method) | 2000-09-09 |
| AR008673A1 (es) | 2000-02-09 |
| DE69713378T2 (de) | 2003-01-30 |
| EP0939655A1 (en) | 1999-09-08 |
| US20040151779A1 (en) | 2004-08-05 |
| JP2002513390A (ja) | 2002-05-08 |
| DE69713378D1 (de) | 2002-07-18 |
| WO1998016250A1 (en) | 1998-04-23 |
| US6264990B1 (en) | 2001-07-24 |
| EP0939655B1 (en) | 2002-06-12 |
| AU4821197A (en) | 1998-05-11 |
| US6730328B2 (en) | 2004-05-04 |
| CA2264776A1 (en) | 1998-04-23 |
| ATE218886T1 (de) | 2002-06-15 |
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