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)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (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)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (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 (OSRAM) |
| EP (1) | EP0939655B1 (OSRAM) |
| JP (1) | JP2002513390A (OSRAM) |
| AR (1) | AR008673A1 (OSRAM) |
| AT (1) | ATE218886T1 (OSRAM) |
| AU (1) | AU4821197A (OSRAM) |
| CA (1) | CA2264776C (OSRAM) |
| DE (1) | DE69713378T2 (OSRAM) |
| IN (1) | IN184589B (OSRAM) |
| WO (1) | WO1998016250A1 (OSRAM) |
Families Citing this family (102)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IN184589B (OSRAM) * | 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 |
| DE19940748A1 (de) * | 1999-08-27 | 2001-03-01 | Hugo Seinfeld | Arzneimittel enthaltend xenogene Oligo- oder/und Polyribonukleotide |
| AU2046101A (en) * | 1999-11-22 | 2001-06-04 | Universal Preservation Technologies, Inc. | Preservation and formulation of bioactive materials for storage and delivery in hydrophobic carriers |
| US7456009B2 (en) * | 2000-03-07 | 2008-11-25 | Merck & Co., Inc. | Adenovirus formulations |
| AU4346101A (en) * | 2000-03-07 | 2001-09-17 | Merck & Co., Inc. | Adenovirus formulations |
| US7153472B1 (en) | 2000-11-22 | 2006-12-26 | Quadrant Drug Delivery Limited | Preservation and formulation of bioactive materials for storage and delivery in hydrophobic carriers |
| AU2002361545B2 (en) * | 2001-06-28 | 2007-03-15 | Microchips, Inc. | Methods for hermetically sealing microchip reservoir devices |
| WO2003048665A1 (en) | 2001-12-03 | 2003-06-12 | Massachusetts Institute Of Technology | Microscale lyophilization and drying methods for the stabilization of molecules |
| WO2003077861A2 (en) * | 2002-03-13 | 2003-09-25 | Collagenex Pharmaceuticals, Inc. | Water-based delivery systems |
| WO2004071487A2 (en) * | 2002-08-16 | 2004-08-26 | Microchips, Inc. | Controlled release device and method |
| WO2004022033A1 (en) * | 2002-09-04 | 2004-03-18 | Microchips, Inc. | Method and device for the controlled delivery of parathyroid hormone |
| CN100542605C (zh) * | 2002-09-27 | 2009-09-23 | 磨粉机械研究有限公司 | 核酸包被的颗粒 |
| US7599737B2 (en) | 2002-10-04 | 2009-10-06 | 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 |
| EP2526996B1 (en) | 2002-12-20 | 2019-09-11 | Xeris Pharmaceuticals, Inc. | Formulation for intracutaneous injection |
| AU2004229465B2 (en) * | 2003-04-09 | 2010-04-29 | The United States Of America Department Of Veterans Affairs | Compositions and methods related to production of erythropoietin |
| WO2004096176A2 (en) * | 2003-04-25 | 2004-11-11 | Boston Scientific Scimed Inc. | Solid drug formulation and device for storage and controlled delivery thereof |
| 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 |
| JP2008501037A (ja) * | 2004-06-01 | 2008-01-17 | マイクロチップス・インコーポレーテッド | 医療移植片への／医療移植片からの薬物または分析物の輸送の測定および輸送の増強のためのデバイスおよび方法 |
| WO2006015299A2 (en) * | 2004-07-30 | 2006-02-09 | 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 |
| CA2577709C (en) * | 2004-09-01 | 2013-04-16 | Microchips, Inc. | Multi-cap reservoir devices for controlled release or exposure of reservoir contents |
| MX2007002925A (es) | 2004-09-10 | 2007-08-14 | Becton Dickinson Co | Dispositivo de infusion reconstituyente. |
| WO2006081279A2 (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 |
| US9301919B2 (en) * | 2005-12-22 | 2016-04-05 | Oakwood Laboratories, Llc | Sublimable sustained release delivery system and method of making same |
| DK2020990T3 (da) | 2006-05-30 | 2010-12-13 | Intarcia Therapeutics Inc | Strømningsmodulator med en indre kanal til et todelt osmotisk fremføringssystem |
| DK2049081T3 (da) | 2006-08-09 | 2013-02-25 | Intarcia Therapeutics Inc | Osmotiske leveringssystemer og stempelarrangementer |
| LT2134353T (lt) * | 2007-03-30 | 2017-03-27 | Xisle Pharma Ventures Trust | Dvifazė lipidų vezikulių kompozicija ir gimdos kaklelio displazijos gydymo būdas, skiriant intravaginaliai |
| CA2683610C (en) | 2007-04-23 | 2013-01-08 | Intarcia Therapeutics, Inc. | Suspension formulations of insulinotropic peptides and uses thereof |
| US8968786B2 (en) | 2007-06-22 | 2015-03-03 | Board Of Regents, The University Of Texas System | Formation of stable submicron peptide or protein particles by thin film freezing |
| EP2240155B1 (en) * | 2008-02-13 | 2012-06-06 | Intarcia Therapeutics, Inc | Devices, formulations, and methods for delivery of multiple beneficial agents |
| KR20110103961A (ko) | 2008-11-16 | 2011-09-21 | 보드 오브 리전츠 더 유니버시티 오브 텍사스 시스템 | 저점도 고농축 현탁액 |
| US9283184B2 (en) * | 2008-11-24 | 2016-03-15 | Massachusetts Institute Of Technology | Methods and compositions for localized agent delivery |
| PL2462246T3 (pl) | 2009-09-28 | 2018-02-28 | Intarcia Therapeutics, Inc | Szybkie ustalenie i/lub zakończenie dostarczania leku zasadniczo w stanie równowagi dynamicznej |
| ES2659079T3 (es) * | 2010-03-09 | 2018-03-13 | Janssen Biotech, Inc. | Formulaciones no acuosas en suspensión de viscosidad reducida a concentración elevada |
| US9072668B2 (en) | 2010-03-09 | 2015-07-07 | Janssen Biotech, Inc. | Non-aqueous high concentration reduced viscosity suspension formulations of antibodies |
| US20110223208A1 (en) | 2010-03-09 | 2011-09-15 | Beth Hill | Non-Aqueous High Concentration Reduced Viscosity Suspension Formulations |
| CA2788060C (en) | 2010-03-17 | 2017-07-11 | Novaliq Gmbh | Pharmaceutical composition for treatment of increased intraocular pressure |
| US20120046225A1 (en) | 2010-07-19 | 2012-02-23 | The Regents Of The University Of Colorado, A Body Corporate | Stable glucagon formulations for the treatment of hypoglycemia |
| 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 |
| CN105853348B (zh) | 2011-03-10 | 2019-08-30 | Xeris药物公司 | 肠胃外注射用稳定溶液 |
| CN103596554A (zh) | 2011-05-25 | 2014-02-19 | 诺瓦利克有限责任公司 | 基于半氟化烷烃类的外用药物组合物 |
| AU2012260788B2 (en) | 2011-05-25 | 2017-01-19 | Dermaliq Therapeutics, Inc. | Pharmaceutical composition for administration to nails |
| CN103930096B (zh) | 2011-10-31 | 2017-05-31 | Xeris药物公司 | 用于治疗糖尿病的制剂 |
| US9757460B2 (en) | 2012-01-23 | 2017-09-12 | Novaliq Gmbh | Stabilised protein compositions based on semifluorinated alkanes |
| US9125805B2 (en) | 2012-06-27 | 2015-09-08 | Xeris Pharmaceuticals, Inc. | Stable formulations for parenteral injection of small molecule drugs |
| PT3181119T (pt) | 2012-09-12 | 2019-10-18 | Novaliq Gmbh | Composições de alcano semiflourado para utilização no tratamento de queratoconjuntivite seca |
| 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 |
| EP3712142B1 (en) | 2013-01-11 | 2022-07-06 | 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 |
| TWI683666B (zh) * | 2013-03-15 | 2020-02-01 | 美商百歐維拉提夫治療公司 | 因子ｉｘ多肽調配物 |
| US10273298B2 (en) | 2013-07-23 | 2019-04-30 | Novaliq Gmbh | Stabilized antibody compositions |
| 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 |
| CA3191031A1 (en) | 2013-09-27 | 2015-04-02 | Massachusetts Institute Of Technology | Carrier-free biologically-active protein nanostructures |
| KR102385372B1 (ko) * | 2014-03-24 | 2022-04-11 | 바이오버라티브 테라퓨틱스 인크. | 동결건조된 ix 인자 제형 |
| EP3828160A1 (en) | 2014-07-16 | 2021-06-02 | Corsair Pharma, Inc. | Treprostinil derivative compounds and methods of using same |
| AU2015300944B2 (en) | 2014-08-06 | 2019-07-11 | 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 |
| US11471479B2 (en) | 2014-10-01 | 2022-10-18 | Eagle Biologics, Inc. | Polysaccharide and nucleic acid formulations containing viscosity-lowering agents |
| CN107920884B (zh) | 2015-06-03 | 2021-08-27 | 因塔西亚制药公司 | 植入物放置和移除系统 |
| US9649364B2 (en) | 2015-09-25 | 2017-05-16 | Xeris Pharmaceuticals, Inc. | Methods for producing stable therapeutic formulations in aprotic polar solvents |
| US9643911B2 (en) | 2015-06-17 | 2017-05-09 | Corsair Pharma, Inc. | Treprostinil derivatives and compositions and uses thereof |
| US9394227B1 (en) | 2015-06-17 | 2016-07-19 | Corsair Pharma, Inc. | Treprostinil derivatives and compositions and uses thereof |
| WO2017027843A1 (en) | 2015-08-12 | 2017-02-16 | Massachusetts Institute Of Technology | Cell surface coupling of nanoparticles |
| US11590205B2 (en) | 2015-09-25 | 2023-02-28 | Xeris Pharmaceuticals, Inc. | Methods for producing stable therapeutic glucagon formulations in aprotic polar solvents |
| CN110403923B (zh) | 2015-09-30 | 2021-09-21 | 诺瓦利克有限责任公司 | 半氟化化合物和其组合物 |
| PL3722274T3 (pl) | 2015-09-30 | 2023-12-04 | Novaliq Gmbh | Związki semifluorowane |
| TWI754643B (zh) | 2016-05-16 | 2022-02-11 | 美商因塔希亞治療公司 | 升糖素受體選擇性多肽和彼之使用方法 |
| 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 |
| CN109640900B (zh) | 2016-06-23 | 2020-07-07 | 诺瓦利克有限责任公司 | 一种试剂盒 |
| ES2969758T3 (es) | 2016-09-22 | 2024-05-22 | Novaliq Gmbh | Composiciones farmacéuticas para usar en la terapia de la blefaritis |
| US10813976B2 (en) | 2016-09-23 | 2020-10-27 | Novaliq Gmbh | Ophthalmic compositions comprising ciclosporin |
| MX2019008006A (es) | 2017-01-03 | 2019-08-29 | Intarcia Therapeutics Inc | Metodos que comprenden la administracion continua de un agonista del receptor de glp-1 y la co-administracion de un farmaco. |
| KR102351816B1 (ko) | 2017-04-21 | 2022-01-17 | 노바리크 게엠베하 | 요오드 조성물 |
| 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 |
| CA3063324A1 (en) | 2017-05-16 | 2018-11-22 | Bhami's Research Laboratory, Pvt. Ltd. | High concentration protein formulations with reduced viscosity |
| CN117085022A (zh) | 2017-06-02 | 2023-11-21 | Xeris药物公司 | 抗沉淀的小分子药物制剂 |
| AU2018328209A1 (en) | 2017-09-05 | 2020-04-23 | Torque Therapeutics, Inc. | Therapeutic protein compositions and methods of making and using the same |
| IL273531B2 (en) | 2017-09-27 | 2024-05-01 | Novaliq Gmbh | Ophthalmic preparations containing latanoprost for use in the treatment of eye diseases |
| WO2019068763A1 (en) | 2017-10-04 | 2019-04-11 | Novaliq Gmbh | OPHTHALMIC COMPOSITIONS COMPRISING F6H8 |
| US11576893B2 (en) | 2018-03-02 | 2023-02-14 | Novaliq Gmbh | Pharmaceutical compositions comprising 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 |
| EP4406533A3 (en) | 2018-10-12 | 2024-10-09 | Novaliq GmbH | Ophthalmic composition for treatment of dry eye disease |
| CN113661006A (zh) | 2019-02-05 | 2021-11-16 | 林迪生物科学公司 | 分离的细胞培养物组分以及用于从液体细胞培养基中分离其的方法 |
| WO2020165132A1 (en) | 2019-02-13 | 2020-08-20 | Novaliq Gmbh | Compositions and methods for the treatment of ocular neovascularization |
| WO2021109979A1 (en) | 2019-12-06 | 2021-06-10 | Guangzhou Bioseal Biotech Co., Ltd. | Flowable fibrinogen thrombin paste |
| WO2022109294A2 (en) * | 2020-11-20 | 2022-05-27 | Team Medical Llc | Rna stabilization |
| WO2023044455A2 (en) * | 2021-09-16 | 2023-03-23 | 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 |
| WO1993025673A1 (en) | 1992-06-04 | 1993-12-23 | The Regents Of The University Of California | In vivo gene therapy with intron-free sequence of interest |
| DK0661989T3 (da) | 1992-09-21 | 1998-03-02 | Upjohn Co | Proteinsammensætninger med vedvarende frigivelse |
| US5480914A (en) | 1994-05-06 | 1996-01-02 | Allergan, Inc. | Nonaqueous thixotropic drug delivery suspensions and methods of their use |
| AU5417796A (en) | 1995-03-07 | 1996-09-23 | 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 (OSRAM) * | 1996-10-16 | 2000-09-09 | Alza Corp |
-
1997
- 1997-09-23 IN IN1756CA1997 patent/IN184589B/en unknown
- 1997-10-15 WO PCT/US1997/018575 patent/WO1998016250A1/en active IP Right Grant
- 1997-10-15 AT AT97910959T patent/ATE218886T1/de not_active IP Right Cessation
- 1997-10-15 AR ARP970104744A patent/AR008673A1/es unknown
- 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 CA CA002264776A patent/CA2264776C/en not_active Expired - Fee Related
- 1997-10-15 JP JP51854898A patent/JP2002513390A/ja not_active Ceased
- 1997-10-15 AU AU48211/97A patent/AU4821197A/en not_active Abandoned
- 1997-10-15 EP EP97910959A patent/EP0939655B1/en not_active Expired - Lifetime
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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 |
|---|---|
| AR008673A1 (es) | 2000-02-09 |
| US6264990B1 (en) | 2001-07-24 |
| IN184589B (OSRAM) | 2000-09-09 |
| US20010038859A1 (en) | 2001-11-08 |
| CA2264776A1 (en) | 1998-04-23 |
| US20040151779A1 (en) | 2004-08-05 |
| ATE218886T1 (de) | 2002-06-15 |
| DE69713378D1 (de) | 2002-07-18 |
| AU4821197A (en) | 1998-05-11 |
| US6730328B2 (en) | 2004-05-04 |
| EP0939655B1 (en) | 2002-06-12 |
| DE69713378T2 (de) | 2003-01-30 |
| EP0939655A1 (en) | 1999-09-08 |
| JP2002513390A (ja) | 2002-05-08 |
| WO1998016250A1 (en) | 1998-04-23 |
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