DE69630691T2 - Liposomal p-Ethoxy Oligonucleotides - Google Patents
Liposomal p-Ethoxy Oligonucleotides Download PDFInfo
- Publication number
- DE69630691T2 DE69630691T2 DE69630691T DE69630691T DE69630691T2 DE 69630691 T2 DE69630691 T2 DE 69630691T2 DE 69630691 T DE69630691 T DE 69630691T DE 69630691 T DE69630691 T DE 69630691T DE 69630691 T2 DE69630691 T2 DE 69630691T2
- Authority
- DE
- Germany
- Prior art keywords
- oligos
- oligonucleotides
- liposomal
- antisense
- oligonucleotide
- 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
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- 108091034117 Oligonucleotide Proteins 0.000 title claims abstract description 127
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/711—Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
-
- 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
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1135—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against oncogenes or tumor suppressor genes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/312—Phosphonates
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/315—Phosphorothioates
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
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- Public Health (AREA)
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- Organic Chemistry (AREA)
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- Biotechnology (AREA)
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- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
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- Oncology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Dispersion Chemistry (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Silicon Polymers (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/520,385 US5855911A (en) | 1995-08-29 | 1995-08-29 | Liposomal phosphodiester, phosphorothioate, and P-ethoxy oligonucleotides |
| US520385 | 1995-08-29 | ||
| PCT/US1996/014146 WO1997007784A2 (en) | 1995-08-29 | 1996-08-26 | LIPOSOMAL PHOSPHODIESTER, PHOSPHOROTHIOATE, AND p-ETHOXY OLIGONUCLEOTIDES |
Publications (2)
| Publication Number | Publication Date |
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| DE69630691D1 DE69630691D1 (de) | 2003-12-18 |
| DE69630691T2 true DE69630691T2 (de) | 2004-11-25 |
Family
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Family Applications (1)
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| DE69630691T Expired - Lifetime DE69630691T2 (de) | 1995-08-29 | 1996-08-26 | Liposomal p-Ethoxy Oligonucleotides |
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| US (4) | US5855911A (OSRAM) |
| EP (1) | EP0847272B1 (OSRAM) |
| JP (1) | JP4291412B2 (OSRAM) |
| AT (1) | ATE253897T1 (OSRAM) |
| AU (1) | AU6912996A (OSRAM) |
| CA (1) | CA2228944C (OSRAM) |
| DE (1) | DE69630691T2 (OSRAM) |
| DK (1) | DK0847272T3 (OSRAM) |
| ES (1) | ES2210385T3 (OSRAM) |
| PT (1) | PT847272E (OSRAM) |
| WO (1) | WO1997007784A2 (OSRAM) |
Families Citing this family (60)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5855911A (en) * | 1995-08-29 | 1999-01-05 | Board Of Regents, The University Of Texas System | Liposomal phosphodiester, phosphorothioate, and P-ethoxy oligonucleotides |
| US6977244B2 (en) * | 1996-10-04 | 2005-12-20 | Board Of Regents, The University Of Texas Systems | Inhibition of Bcl-2 protein expression by liposomal antisense oligodeoxynucleotides |
| US6894031B1 (en) * | 1996-11-21 | 2005-05-17 | Cedars-Sinai Medical Center | Pituitary tumor transforming gene (PTTG) carboxy-terminal peptides and methods of use thereof to inhibit neoplastic cellular proliferation and/or transformation |
| US6565889B2 (en) * | 1996-12-02 | 2003-05-20 | The Regents Of The University Of California | Bilayer structure which encapsulates multiple containment units and uses thereof |
| US7262173B2 (en) | 1997-03-21 | 2007-08-28 | Georgetown University | Chemosensitizing with liposomes containing oligonucleotides |
| US6126965A (en) * | 1997-03-21 | 2000-10-03 | Georgetown University School Of Medicine | Liposomes containing oligonucleotides |
| US6835395B1 (en) | 1997-05-14 | 2004-12-28 | The University Of British Columbia | Composition containing small multilamellar oligodeoxynucleotide-containing lipid vesicles |
| CA2289702C (en) | 1997-05-14 | 2008-02-19 | Inex Pharmaceuticals Corp. | High efficiency encapsulation of charged therapeutic agents in lipid vesicles |
| EP1017365B1 (en) * | 1997-06-23 | 2003-12-10 | Sequus Pharmaceuticals, Inc. | Liposome-entrapped polynucleotide composition and method |
| JP2002510319A (ja) * | 1997-07-01 | 2002-04-02 | アイシス・ファーマシューティカルス・インコーポレーテッド | オリゴヌクレオチドの消化管を介したデリバリーのための組成物及び方法 |
| DE19740092A1 (de) * | 1997-09-12 | 1999-03-18 | Ulrich Dr Med Hengge | Liposomen und Verfahren zur Transfektion von Zellen |
| US7704962B1 (en) * | 1997-10-03 | 2010-04-27 | Board Of Regents, The University Of Texas System | Small oligonucleotides with anti-tumor activity |
| US7285288B1 (en) * | 1997-10-03 | 2007-10-23 | Board Of Regents, The University Of Texas System | Inhibition of Bcl-2 protein expression by liposomal antisense oligodeoxynucleotides |
| EP1163254B1 (en) | 1999-02-26 | 2008-01-30 | The University of British Columbia | Trpm-2 antisense therapy |
| US7112337B2 (en) | 1999-04-23 | 2006-09-26 | Alza Corporation | Liposome composition for delivery of nucleic acid |
| WO2001026625A2 (en) | 1999-10-08 | 2001-04-19 | Alza Corp | Neutral-cationic lipid for nucleic acid and drug delivery |
| FR2802422B1 (fr) * | 1999-12-21 | 2002-08-09 | Capsulis | Structures mixtes resultant de l'incorporation d'une macromolecule biologique, en particulier d'adn, dans une phase structuree d'amphiphiles et vesicules obtenues a partir de ces structures |
| US7569551B2 (en) | 2000-02-25 | 2009-08-04 | The University Of British Columbia | Chemo- and radiation-sensitization of cancer by antisense TRPM-2 oligodeoxynucleotides |
| NZ524274A (en) | 2000-09-14 | 2004-10-29 | Univ British Columbia | Antisense insulin-like growth factor binding protein (IGFBP)-2-oligodeoxynucleotides for prostate and other endocrine tumor therapy |
| WO2003061386A1 (en) * | 2002-01-03 | 2003-07-31 | Board Of Regents, The University Of Texas System | Wt1 antisense oligos for the inhibition of breast cancer |
| DE60322509D1 (de) * | 2002-01-17 | 2008-09-11 | Univ British Columbia | Bispezifische antisense oligonukleotide die igfbp-2 und igfbp-5 inhibieren und deren verwendung |
| KR101052289B1 (ko) | 2002-08-21 | 2011-07-27 | 더 유니버시티 오브 브리티쉬 콜롬비아 | 클러스테린 양의 감소에 의한 흑색종의 치료 |
| DE60332363D1 (de) | 2002-10-02 | 2010-06-10 | Univ British Columbia | Oligonucleotide zur behandlung von prostatakrebs und anderen krebserkrankungen |
| CA2520864A1 (en) | 2003-03-31 | 2004-10-21 | Alza Corporation | Lipid particles having asymmetric lipid coating and method of preparing same |
| WO2005018493A1 (en) | 2003-08-14 | 2005-03-03 | Boston Scientific Limited | Medical slings |
| EP1667731B1 (en) * | 2003-10-01 | 2013-05-22 | The University Of British Columbia | Bispecific oligonucleotide for the treatment of cns malignancies |
| US20050112130A1 (en) | 2003-11-05 | 2005-05-26 | Bhat Neelima M. | Enhanced B cell cytotoxicity of CDIM binding antibody |
| JP2007512355A (ja) | 2003-11-21 | 2007-05-17 | アルザ コーポレイション | 開裂性のｐｅｇで表面修飾されたリポソーム−ｄｎａ複合体で媒介される遺伝子送達 |
| WO2005094899A1 (en) | 2004-04-02 | 2005-10-13 | The University Of British Columbia | Clusterin antisense therapy for treatment of cancer |
| US8628465B2 (en) * | 2004-06-14 | 2014-01-14 | Boston Scientific Scimed, Inc. | Systems, methods and devices relating to implantable supportive slings |
| EP1814913B1 (en) | 2004-11-05 | 2015-08-19 | IGM Biosciences, Inc. | Antibody induced cell membrane wounding |
| WO2006056054A1 (en) * | 2004-11-23 | 2006-06-01 | The University Of British Columbia | Treatment of cancer with a combination of an agent that perturbs the egf signaling pathway and an oligonucleotide that reduces clusterin levels |
| US8016741B2 (en) * | 2005-04-06 | 2011-09-13 | Boston Scientific Scimed, Inc. | Systems, devices, and methods for sub-urethral support |
| JP2008536874A (ja) * | 2005-04-15 | 2008-09-11 | ボード オブ リージェンツ ザ ユニバーシティー オブ テキサス システム | 中性脂質組成物によるｓｉＲＮＡの送達 |
| WO2007008209A1 (en) | 2005-07-13 | 2007-01-18 | Boston Scientific Scimed Inc. | Snap fit sling anchor system and related methods |
| EP3533416A1 (en) | 2005-07-25 | 2019-09-04 | Boston Scientific Limited | Pelvic floor repair system |
| US7981023B2 (en) * | 2005-07-25 | 2011-07-19 | Boston Scientific Scimed, Inc. | Elastic sling system and related methods |
| US8273429B2 (en) * | 2006-01-19 | 2012-09-25 | Federal-Mogul World Wide, Inc. | Fabric for end fray resistance and protective sleeves formed therewith and methods of construction |
| FR2900576B1 (fr) | 2006-05-03 | 2008-09-19 | Centre Nat Rech Scient | Procede de concentration extemporanee et reversible de liposomes. |
| WO2008106781A1 (en) * | 2007-03-05 | 2008-09-12 | The University Of British Columbia | Treatment of squamous cell carcinoma with hsp27 antisense oligonucleotides and radiotherapy |
| EP2306978A2 (en) * | 2008-06-06 | 2011-04-13 | Mirna Therapeutics, Inc. | Compositions for the in vivo delivery of rnai agents |
| ES2710109T3 (es) | 2010-12-17 | 2019-04-23 | Inst Nat Sante Rech Med | Acidos nucleicos que se dirigen a TCTP para su uso en el tratamiento de cánceres quimiorresistentes u hormonorresistentes |
| WO2012119095A1 (en) | 2011-03-02 | 2012-09-07 | Board Of Regents, The University Of Texas System | Fus1/tusc2 therapies |
| US9113991B2 (en) | 2011-05-12 | 2015-08-25 | Boston Scientific Scimed, Inc. | Anchors for bodily implants and methods for anchoring bodily implants into a patient's body |
| US9636201B2 (en) | 2011-05-12 | 2017-05-02 | Boston Scientific Scimed, Inc. | Delivery members for delivering an implant into a body of a patient |
| JP6335796B2 (ja) | 2012-02-08 | 2018-06-06 | アイジーエム バイオサイエンシズ インク．Ｉｇｍ Ｂｉｏｓｃｉｅｎｃｅｓ Ｉｎｃ． | Ｃｄｉｍ結合タンパク質及びその使用 |
| CN103565745A (zh) | 2012-08-10 | 2014-02-12 | 德克萨斯州大学系统董事会 | 用于治疗中风的神经保护性脂质体组合物和方法 |
| WO2014195755A1 (en) | 2013-06-05 | 2014-12-11 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Hydrophobically modified antisense oligonucleotides comprising a ketal group |
| WO2014195754A1 (en) | 2013-06-05 | 2014-12-11 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Hydrophobically modified antisense oligonucleotides comprising a triple alkyl chain |
| EA038277B1 (ru) * | 2015-10-14 | 2021-08-04 | Байо-Пат Холдингз, Инк. | P-этокси нуклеиновые кислоты для липосомальной лекарственной формы |
| CN108601765A (zh) | 2015-12-18 | 2018-09-28 | 德克萨斯州大学系统董事会 | 用于早产管理的治疗剂 |
| SG10201913501RA (en) * | 2016-09-14 | 2020-03-30 | Univ Nanyang Tech | Liposomal formulations |
| MX2019003070A (es) | 2016-09-16 | 2019-10-14 | Bio Path Holdings Inc | Terapia de combinacion con oligonucleotidos antisentido liposomales. |
| SG11201903283UA (en) | 2016-10-12 | 2019-05-30 | Univ Texas | Methods and compositions for tusc2 immunotherapy |
| WO2018195250A1 (en) * | 2017-04-19 | 2018-10-25 | Bio-Path Holdings, Inc. | P-ethoxy nucleic acids for igf-1r inhibition |
| SG11201909336VA (en) | 2017-04-19 | 2019-11-28 | Bio Path Holdings Inc | P-ethoxy nucleic acids for stat3 inhibition |
| AU2018254485B2 (en) * | 2017-04-19 | 2024-07-11 | Bio-Path Holdings, Inc. | P-ethoxy nucleic acids for IGF-1R inhibition |
| US12234457B2 (en) | 2017-04-19 | 2025-02-25 | Bio-Path Holdings, Inc. | P-ethoxy nucleic acids for BCL2 inhibition |
| IL297450A (en) | 2020-04-20 | 2022-12-01 | Univ Texas | Compositions of biologically active dry powder, methods for production and use |
| WO2022040435A1 (en) | 2020-08-19 | 2022-02-24 | The Board Of Regents Of The University Of Texas System | Nanodrugs for targeted drug delivery and use thereof |
Family Cites Families (82)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH621479A5 (OSRAM) * | 1977-08-05 | 1981-02-13 | Battelle Memorial Institute | |
| US4394448A (en) * | 1978-02-24 | 1983-07-19 | Szoka Jr Francis C | Method of inserting DNA into living cells |
| US4469863A (en) * | 1980-11-12 | 1984-09-04 | Ts O Paul O P | Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof |
| US4480041A (en) * | 1982-07-09 | 1984-10-30 | Collaborative Research, Inc. | Use of phosphotriester intermediates for preparation of functionalized liposomes |
| FR2540122B1 (fr) * | 1983-01-27 | 1985-11-29 | Centre Nat Rech Scient | Nouveaux composes comportant une sequence d'oligonucleotide liee a un agent d'intercalation, leur procede de synthese et leur application |
| US4721612A (en) * | 1984-04-12 | 1988-01-26 | The Liposome Company, Inc. | Steroidal liposomes |
| US5202429A (en) * | 1986-07-09 | 1993-04-13 | The Wistar Institute | DNA molecules having human BCL-2 gene sequences |
| US5049388A (en) * | 1986-11-06 | 1991-09-17 | Research Development Foundation | Small particle aerosol liposome and liposome-drug combinations for medical use |
| US5094785A (en) * | 1986-12-10 | 1992-03-10 | Ciba Corning Diagnostics Corp. | Process for stabilizing liposomes |
| US4837028A (en) * | 1986-12-24 | 1989-06-06 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US4920016A (en) | 1986-12-24 | 1990-04-24 | Linear Technology, Inc. | Liposomes with enhanced circulation time |
| US5030442A (en) * | 1987-03-30 | 1991-07-09 | Liposome Technology, Inc. | Non-crystalline minoxidil composition |
| US4904582A (en) * | 1987-06-11 | 1990-02-27 | Synthetic Genetics | Novel amphiphilic nucleic acid conjugates |
| US4950432A (en) * | 1987-10-16 | 1990-08-21 | Board Of Regents, The University Of Texas System | Polyene microlide pre-liposomal powders |
| US5178875A (en) * | 1991-01-14 | 1993-01-12 | The Board Of Regents, The University Of Texas System | Liposomal-polyene preliposomal powder and method for its preparation |
| US5188897A (en) * | 1987-10-22 | 1993-02-23 | Temple University Of The Commonwealth System Of Higher Education | Encapsulated 2',5'-phosphorothioate oligoadenylates |
| US4924624A (en) * | 1987-10-22 | 1990-05-15 | Temple University-Of The Commonwealth System Of Higher Education | 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof |
| EP0397774A1 (en) * | 1988-02-04 | 1990-11-22 | Board Of Regents, The University Of Texas System | Formulation and use of retinoids in treatment of cancer and other diseases |
| US5098890A (en) * | 1988-11-07 | 1992-03-24 | Temple University-Of The Commonwealth System Of Higher Education | Antisence oligonucleotides to c-myb proto-oncogene and uses thereof |
| US5734033A (en) * | 1988-12-22 | 1998-03-31 | The Trustees Of The University Of Pennsylvania | Antisense oligonucleotides inhibiting human bcl-2 gene expression |
| US5831066A (en) * | 1988-12-22 | 1998-11-03 | The Trustees Of The University Of Pennsylvania | Regulation of bcl-2 gene expression |
| US5248671A (en) * | 1989-02-15 | 1993-09-28 | Board Of Regents, The University Of Texas System | Methods and compositions for treatment of cancer using oligonucleotides |
| US5087617A (en) * | 1989-02-15 | 1992-02-11 | Board Of Regents, The University Of Texas System | Methods and compositions for treatment of cancer using oligonucleotides |
| FR2644080A1 (fr) * | 1989-03-13 | 1990-09-14 | Trizac Jacques | Dispositif de filtration et d'evacuation de petites particules, dechets et detritus, de natures diverses |
| AU639925B2 (en) * | 1989-04-18 | 1993-08-12 | Nexstar Pharmaceuticals, Inc. | Liposomal targeting of ischemic tissue |
| US5112962A (en) * | 1989-04-19 | 1992-05-12 | Northwestern University | Labile anchors for solid phase polynucleotide synthesis |
| US5227170A (en) * | 1989-06-22 | 1993-07-13 | Vestar, Inc. | Encapsulation process |
| US5100662A (en) * | 1989-08-23 | 1992-03-31 | The Liposome Company, Inc. | Steroidal liposomes exhibiting enhanced stability |
| US5469854A (en) * | 1989-12-22 | 1995-11-28 | Imarx Pharmaceutical Corp. | Methods of preparing gas-filled liposomes |
| US5542935A (en) | 1989-12-22 | 1996-08-06 | Imarx Pharmaceutical Corp. | Therapeutic delivery systems related applications |
| CA2033725C (en) * | 1990-01-24 | 2001-05-29 | Folker Pittrof | Pharmaceutical and cosmetic compositions containing a salt of cholanic acid |
| US5279833A (en) * | 1990-04-04 | 1994-01-18 | Yale University | Liposomal transfection of nucleic acids into animal cells |
| US5264618A (en) * | 1990-04-19 | 1993-11-23 | Vical, Inc. | Cationic lipids for intracellular delivery of biologically active molecules |
| WO1991016901A1 (en) * | 1990-04-30 | 1991-11-14 | Isis Pharmaceuticals, Inc. | Oligonucleotide modulation of arachidonic acid metabolism |
| US5665710A (en) * | 1990-04-30 | 1997-09-09 | Georgetown University | Method of making liposomal oligodeoxynucleotide compositions |
| DK0464638T3 (da) * | 1990-07-02 | 1997-10-13 | Hoechst Ag | Oligonukleotidanaloge med terminale 3-3- eller 5-5-internukleotidbindinger. |
| US5135917A (en) * | 1990-07-12 | 1992-08-04 | Nova Pharmaceutical Corporation | Interleukin receptor expression inhibiting antisense oligonucleotides |
| US5378825A (en) * | 1990-07-27 | 1995-01-03 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs |
| JPH06501160A (ja) * | 1990-09-17 | 1994-02-10 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 細胞の増殖をコントロールするための方法及び組成物 |
| US5271941A (en) * | 1990-11-02 | 1993-12-21 | Cho Chung Yoon S | Antisense oligonucleotides of human regulatory subunit RI.sub.α of cAMP-dependent protein kinases |
| DE4110085A1 (de) * | 1991-03-27 | 1992-10-01 | Boehringer Ingelheim Int | 2'-o-alkyl-oligoribonukleotide, verfahren zu deren herstellung und deren verwendung als antisense-oligonukleotide |
| FR2677272B1 (fr) * | 1991-06-05 | 1995-03-03 | Biovecteurs As | Vecteur particulaire a tropisme selectif, procede de preparation et composition pharmaceutique. |
| WO1992022303A1 (en) * | 1991-06-18 | 1992-12-23 | Temple University - Of The Commonwealth System Of Higher Education | Selective inhibition of leukemic cell proliferation by bcr-abl antisense oligonucleotides |
| US5525719A (en) * | 1991-08-30 | 1996-06-11 | Chemgenes Corporation | N-protected-2'-O-methyl-and N-protected-3'-O-methyl-ribonucleosides and their phosphoramidite derivatives |
| AU2916292A (en) * | 1991-10-24 | 1993-05-21 | Isis Pharmaceuticals, Inc. | Derivatized oligonucleotides having improved uptake and other properties |
| AU675923B2 (en) * | 1991-12-04 | 1997-02-27 | E.I. Du Pont De Nemours And Company | Fatty acid desaturase genes from plants |
| US5279957A (en) * | 1992-04-30 | 1994-01-18 | Washington University | cDNA encoding human phospholipase A2 polypeptide |
| EP0646178A1 (en) * | 1992-06-04 | 1995-04-05 | The Regents Of The University Of California | expression cassette with regularoty regions functional in the mammmlian host |
| US5320962A (en) * | 1992-07-22 | 1994-06-14 | Duke University | DNA encoding the human A1 adenosine receptor |
| NL9201440A (nl) * | 1992-08-11 | 1994-03-01 | Univ Leiden | Triantennaire clusterglycosiden, hun bereiding en toepassing. |
| WO1994005259A1 (en) * | 1992-09-02 | 1994-03-17 | Georgetown University | Method of encapsulating anthracycline glycosides in liposomes |
| US6001992A (en) | 1999-01-07 | 1999-12-14 | Isis Pharmaceuticals Inc. | Antisense modulation of novel anti-apoptotic bcl-2-related proteins |
| DE69330137T2 (de) | 1992-10-21 | 2001-11-15 | Temple University Of The Commonwealth System Of Higher Education, Philadelphia | Die kombination von antineoplastischen mitteln und antisense-oligonukleotiden bei der behandlung von krebs |
| US6015886A (en) * | 1993-05-24 | 2000-01-18 | Chemgenes Corporation | Oligonucleotide phosphate esters |
| US5417978A (en) * | 1993-07-29 | 1995-05-23 | Board Of Regents, The University Of Texas System | Liposomal antisense methyl phosphonate oligonucleotides and methods for their preparation and use |
| FR2710074B1 (fr) * | 1993-09-15 | 1995-12-08 | Rhone Poulenc Rorer Sa | Gène GRB3-3, ses variants et leurs utilisations. |
| AU683957B2 (en) * | 1993-11-05 | 1997-11-27 | Amgen, Inc. | Liposome preparation and material encapsulation method |
| US5651981A (en) * | 1994-03-29 | 1997-07-29 | Northwestern University | Cationic phospholipids for transfection |
| US5696248A (en) * | 1994-06-15 | 1997-12-09 | Hoechst Aktiengesellschaft | 3'-modified oligonucleotide derivatives |
| US5908635A (en) * | 1994-08-05 | 1999-06-01 | The United States Of America As Represented By The Department Of Health And Human Services | Method for the liposomal delivery of nucleic acids |
| IT1275862B1 (it) * | 1995-03-03 | 1997-10-24 | Consiglio Nazionale Ricerche | Trascritto antisenso associato ad alcuni tipi di cellule tumorali ed oligodeossinucleotidi sintetici utili nella diagnosi e nel trattamento |
| DE59607750D1 (de) * | 1995-03-13 | 2001-10-31 | Aventis Pharma Gmbh | Phosphonomonoesternnukleinsäuren, Verfahren zu ihrer Herstellung und ihre Verwendung |
| ES2268705T3 (es) * | 1995-06-01 | 2007-03-16 | Kishimoto, Tadamitsu | Inhibidor del crecimiento de celulas leucemicas que contienen un derivado oligonucleotidico antisentido frente al gen del tumor de wiloms (wt1). |
| US6326487B1 (en) * | 1995-06-05 | 2001-12-04 | Aventis Pharma Deutschland Gmbh | 3 modified oligonucleotide derivatives |
| US5705385A (en) * | 1995-06-07 | 1998-01-06 | Inex Pharmaceuticals Corporation | Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer |
| US5756122A (en) * | 1995-06-07 | 1998-05-26 | Georgetown University | Liposomally encapsulated nucleic acids having high entrapment efficiencies, method of manufacturer and use thereof for transfection of targeted cells |
| CA2222328C (en) * | 1995-06-07 | 2012-01-10 | Inex Pharmaceuticals Corporation | Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer |
| EP0843555B1 (en) * | 1995-08-01 | 2003-08-27 | Isis Pharmaceuticals, Inc. | Liposomal oligonucleotide compositions |
| US5855911A (en) * | 1995-08-29 | 1999-01-05 | Board Of Regents, The University Of Texas System | Liposomal phosphodiester, phosphorothioate, and P-ethoxy oligonucleotides |
| DE19532553A1 (de) * | 1995-09-04 | 1997-03-06 | Hoechst Ag | Verfahren zur Herstellung substituierter N-Ethyl-Glycinderivate |
| US6120794A (en) * | 1995-09-26 | 2000-09-19 | University Of Pittsburgh | Emulsion and micellar formulations for the delivery of biologically active substances to cells |
| US6977244B2 (en) * | 1996-10-04 | 2005-12-20 | Board Of Regents, The University Of Texas Systems | Inhibition of Bcl-2 protein expression by liposomal antisense oligodeoxynucleotides |
| US5874224A (en) * | 1997-03-11 | 1999-02-23 | Incyte Pharmaceuticals, Inc. | Growth factor receptor binding protein |
| US6126965A (en) * | 1997-03-21 | 2000-10-03 | Georgetown University School Of Medicine | Liposomes containing oligonucleotides |
| GB9711919D0 (en) * | 1997-06-09 | 1997-08-06 | Ciba Geigy Ag | Oligonucleotide derivatives |
| EP1017365B1 (en) * | 1997-06-23 | 2003-12-10 | Sequus Pharmaceuticals, Inc. | Liposome-entrapped polynucleotide composition and method |
| WO1999001139A1 (en) * | 1997-07-03 | 1999-01-14 | Thomas Jefferson University | An improved method for design and selection of efficacious antisense oligonucleotides |
| US7285288B1 (en) * | 1997-10-03 | 2007-10-23 | Board Of Regents, The University Of Texas System | Inhibition of Bcl-2 protein expression by liposomal antisense oligodeoxynucleotides |
| US6136965A (en) * | 1998-07-02 | 2000-10-24 | The Regents Of The University Of California | Deoxynucleic alkyl and alkoxy thiourea compounds |
| US6211349B1 (en) * | 1998-12-30 | 2001-04-03 | Oligos Etc., Inc. | Protonated/acidified nucleic acids and methods of use |
| US6211162B1 (en) * | 1998-12-30 | 2001-04-03 | Oligos Etc. Inc. | Pulmonary delivery of protonated/acidified nucleic acids |
| US7795232B1 (en) | 2000-08-25 | 2010-09-14 | Genta Incorporated | Methods of treatment of a bcl-2 disorder using bcl-2 antisense oligomers |
-
1995
- 1995-08-29 US US08/520,385 patent/US5855911A/en not_active Expired - Lifetime
-
1996
- 1996-08-26 AU AU69129/96A patent/AU6912996A/en not_active Abandoned
- 1996-08-26 DE DE69630691T patent/DE69630691T2/de not_active Expired - Lifetime
- 1996-08-26 JP JP51064297A patent/JP4291412B2/ja not_active Expired - Fee Related
- 1996-08-26 CA CA2228944A patent/CA2228944C/en not_active Expired - Fee Related
- 1996-08-26 ES ES96929888T patent/ES2210385T3/es not_active Expired - Lifetime
- 1996-08-26 EP EP96929888A patent/EP0847272B1/en not_active Expired - Lifetime
- 1996-08-26 DK DK96929888T patent/DK0847272T3/da active
- 1996-08-26 AT AT96929888T patent/ATE253897T1/de not_active IP Right Cessation
- 1996-08-26 PT PT96929888T patent/PT847272E/pt unknown
- 1996-08-26 WO PCT/US1996/014146 patent/WO1997007784A2/en not_active Ceased
-
1998
- 1998-07-09 US US09/112,869 patent/US6042846A/en not_active Expired - Lifetime
-
2003
- 2003-06-16 US US10/462,172 patent/US7176302B2/en not_active Expired - Fee Related
-
2007
- 2007-02-13 US US11/674,563 patent/US7754872B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| WO1997007784A2 (en) | 1997-03-06 |
| CA2228944A1 (en) | 1997-03-06 |
| AU6912996A (en) | 1997-03-19 |
| US20070202157A1 (en) | 2007-08-30 |
| ES2210385T3 (es) | 2004-07-01 |
| US5855911A (en) | 1999-01-05 |
| JP4291412B2 (ja) | 2009-07-08 |
| PT847272E (pt) | 2004-04-30 |
| ATE253897T1 (de) | 2003-11-15 |
| US7754872B2 (en) | 2010-07-13 |
| JPH11512099A (ja) | 1999-10-19 |
| EP0847272A2 (en) | 1998-06-17 |
| EP0847272B1 (en) | 2003-11-12 |
| US20040005353A1 (en) | 2004-01-08 |
| DE69630691D1 (de) | 2003-12-18 |
| DK0847272T3 (da) | 2004-03-22 |
| US7176302B2 (en) | 2007-02-13 |
| WO1997007784A3 (en) | 1997-04-24 |
| CA2228944C (en) | 2011-10-18 |
| US6042846A (en) | 2000-03-28 |
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