CA2160878A1 - Encapsulation d'acides nucleiques a l'aide de conjugues qui ciblent et facilitent l'absorption cellulaire et l'expression genique - Google Patents
Encapsulation d'acides nucleiques a l'aide de conjugues qui ciblent et facilitent l'absorption cellulaire et l'expression geniqueInfo
- Publication number
- CA2160878A1 CA2160878A1 CA002160878A CA2160878A CA2160878A1 CA 2160878 A1 CA2160878 A1 CA 2160878A1 CA 002160878 A CA002160878 A CA 002160878A CA 2160878 A CA2160878 A CA 2160878A CA 2160878 A1 CA2160878 A1 CA 2160878A1
- Authority
- CA
- Canada
- Prior art keywords
- nucleic acid
- acid
- dna
- poly
- microparticle
- 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.)
- Abandoned
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- A61K47/6921—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6923—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6921—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6927—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
- A61K9/1647—Polyesters, e.g. poly(lactide-co-glycolide)
-
- 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
- C07K14/61—Growth hormone [GH], i.e. somatotropin
-
- 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
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/82—Vectors or expression systems specially adapted for eukaryotic hosts for plant cells, e.g. plant artificial chromosomes (PACs)
- C12N15/8201—Methods for introducing genetic material into plant cells, e.g. DNA, RNA, stable or transient incorporation, tissue culture methods adapted for transformation
- C12N15/8206—Methods for introducing genetic material into plant cells, e.g. DNA, RNA, stable or transient incorporation, tissue culture methods adapted for transformation by physical or chemical, i.e. non-biological, means, e.g. electroporation, PEG mediated
-
- 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
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/53—DNA (RNA) vaccination
-
- 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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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Endocrinology (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Toxicology (AREA)
- Ceramic Engineering (AREA)
- Cell Biology (AREA)
- Inorganic Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US4753693A | 1993-04-19 | 1993-04-19 | |
US08/047,536 | 1993-04-19 |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2160878A1 true CA2160878A1 (fr) | 1994-10-27 |
Family
ID=21949539
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002160878A Abandoned CA2160878A1 (fr) | 1993-04-19 | 1994-04-19 | Encapsulation d'acides nucleiques a l'aide de conjugues qui ciblent et facilitent l'absorption cellulaire et l'expression genique |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP0696200A4 (fr) |
JP (1) | JPH08510639A (fr) |
AU (1) | AU6707194A (fr) |
CA (1) | CA2160878A1 (fr) |
NZ (1) | NZ265818A (fr) |
WO (1) | WO1994023738A1 (fr) |
Families Citing this family (77)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0615745B1 (fr) | 1993-02-19 | 1997-05-02 | Howard Green | Compositions contenant des protéines à partir de corneocytes |
US6348449B1 (en) * | 1993-09-21 | 2002-02-19 | The Trustees Of The University Of Pennsylvania | Methods of inducing mucosal immunity |
US6551618B2 (en) * | 1994-03-15 | 2003-04-22 | University Of Birmingham | Compositions and methods for delivery of agents for neuronal regeneration and survival |
WO1995024929A2 (fr) * | 1994-03-15 | 1995-09-21 | Brown University Research Foundation | Systeme de liberation de genes polymeres |
AUPM747694A0 (en) * | 1994-08-16 | 1994-09-08 | Commonwealth Scientific And Industrial Research Organisation | Delivery of nucleic acids and peptides |
US6143211A (en) * | 1995-07-21 | 2000-11-07 | Brown University Foundation | Process for preparing microparticles through phase inversion phenomena |
US6248720B1 (en) * | 1996-07-03 | 2001-06-19 | Brown University Research Foundation | Method for gene therapy using nucleic acid loaded polymeric microparticles |
JPH11510142A (ja) | 1995-07-21 | 1999-09-07 | ブラウン・ユニバーシティ・リサーチ・ファンデーション | 核酸負荷ポリマー微粒子を使用した遺伝子治療法 |
US6265389B1 (en) | 1995-08-31 | 2001-07-24 | Alkermes Controlled Therapeutics, Inc. | Microencapsulation and sustained release of oligonucleotides |
US6270795B1 (en) | 1995-11-09 | 2001-08-07 | Microbiological Research Authority | Method of making microencapsulated DNA for vaccination and gene therapy |
GB9709900D0 (en) * | 1997-05-15 | 1997-07-09 | Microbiological Res Authority | Microencapsulated DNA for vaccination and gene therapy |
JP2000500744A (ja) * | 1995-11-09 | 2000-01-25 | マイクロバイオロジカル リサーチ オーソリティー | ワクチン接種および遺伝子治療のためのマイクロカプセル化dna |
US20020165183A1 (en) * | 1999-11-29 | 2002-11-07 | Hans Herweijer | Methods for genetic immunization |
GB9619002D0 (en) * | 1996-09-11 | 1996-10-23 | Oxford Biosciences Ltd | Particle delivery |
US6893664B1 (en) * | 1996-06-17 | 2005-05-17 | Powderject Research Limited | Particle delivery techniques |
US6228624B1 (en) | 1996-08-02 | 2001-05-08 | Immunivest Corporation | Method to select and transfect cell subpopulations |
EP0934082B1 (fr) * | 1996-10-23 | 2002-07-17 | SKW Trostberg Aktiengesellschaft | Procede de production de conjugues biologiquement actifs d'acides nucleiques et de nanoparticules polymeres |
DE69837602T2 (de) * | 1997-01-22 | 2008-01-17 | MGI Pharma Biologics, Inc., Cambridge | Mikropartikel zur verabreichung von nukleinsaeuren |
US5783567A (en) * | 1997-01-22 | 1998-07-21 | Pangaea Pharmaceuticals, Inc. | Microparticles for delivery of nucleic acid |
EP2258846A3 (fr) | 1997-07-07 | 2012-03-21 | Medical Research Council | Procédé d'amélioration de la concentration d'une molécule d'acide nucléique |
IT1293088B1 (it) * | 1997-07-10 | 1999-02-11 | Isi Ist Sierovaccinogeno Ital | Microparticelle per il rilascio controllato di molecole biologicamente attive e loro uso in terapia, profilassi e diagnostica in vitro e in |
US6013258A (en) * | 1997-10-09 | 2000-01-11 | Zycos Inc. | Immunogenic peptides from the HPV E7 protein |
US6183746B1 (en) | 1997-10-09 | 2001-02-06 | Zycos Inc. | Immunogenic peptides from the HPV E7 protein |
US6475994B2 (en) * | 1998-01-07 | 2002-11-05 | Donald A. Tomalia | Method and articles for transfection of genetic material |
JP3981525B2 (ja) | 1998-01-20 | 2007-09-26 | ハワード・グリーン | 組織への物質のトランスグルタミナーゼ連結 |
AU2674299A (en) * | 1998-02-11 | 1999-08-30 | Maxygen, Inc. | Targeting of genetic vaccine vectors |
US6328967B1 (en) | 1998-03-12 | 2001-12-11 | Allergenics, Inc. | Delivery system to modulate immune response |
US6395253B2 (en) * | 1998-04-23 | 2002-05-28 | The Regents Of The University Of Michigan | Microspheres containing condensed polyanionic bioactive agents and methods for their production |
GB9810236D0 (en) | 1998-05-13 | 1998-07-08 | Microbiological Res Authority | Improvements relating to encapsulation of bioactive agents |
WO1999058656A2 (fr) * | 1998-05-13 | 1999-11-18 | The Regents Of The University Of Michigan | Liberation prolongee d'adn depuis des matrices structurales |
US6406719B1 (en) | 1998-05-13 | 2002-06-18 | Microbiological Research Authority | Encapsulation of bioactive agents |
WO1999065531A1 (fr) * | 1998-06-18 | 1999-12-23 | Johns Hopkins University School Of Medicine | Methodes et reactifs d'administration intramusculaire d'acides nucleiques |
US6818626B1 (en) * | 1998-07-17 | 2004-11-16 | Mirus Corporation | Chelating systems for use in the delivery of compounds to cells |
US6916490B1 (en) | 1998-07-23 | 2005-07-12 | UAB Research Center | Controlled release of bioactive substances |
ES2243082T3 (es) | 1998-10-01 | 2005-11-16 | Powderject Research Limited | Microparticulas con revestimiento aplicado por pulverizacion utilizadaen una jeringa sin aguja. |
CA2276066A1 (fr) * | 1999-03-11 | 2000-09-11 | Zycos Inc. | Microparticules pour diffusion d'un acide nucleique |
US6767928B1 (en) | 1999-03-19 | 2004-07-27 | The Regents Of The University Of Michigan | Mineralization and biological modification of biomaterial surfaces |
CA2370063C (fr) | 1999-03-19 | 2012-10-02 | The Regents Of The University Of Michigan | Mineralisation et developpement cellulaire superficiels sur des biomateriaux |
WO2003045304A2 (fr) | 2001-09-26 | 2003-06-05 | Mayo Foundation For Medical Education And Research | Vaccins mutables |
GB0127564D0 (en) | 2001-11-16 | 2002-01-09 | Medical Res Council | Emulsion compositions |
EP1467711B1 (fr) * | 2002-01-25 | 2007-03-21 | Glaxo Group Limited | Formes posologiques d'adn |
GB0201736D0 (en) * | 2002-01-25 | 2002-03-13 | Glaxo Group Ltd | DNA dosage forms |
US20040048260A1 (en) * | 2002-09-10 | 2004-03-11 | Fu-Hsiung Chang | Transfection of nucleic acid |
JP4473878B2 (ja) | 2003-01-29 | 2010-06-02 | 454 コーポレーション | 核酸を増幅および配列決定する方法 |
US20100022414A1 (en) | 2008-07-18 | 2010-01-28 | Raindance Technologies, Inc. | Droplet Libraries |
US20060078893A1 (en) | 2004-10-12 | 2006-04-13 | Medical Research Council | Compartmentalised combinatorial chemistry by microfluidic control |
GB0307428D0 (en) | 2003-03-31 | 2003-05-07 | Medical Res Council | Compartmentalised combinatorial chemistry |
GB0307403D0 (en) | 2003-03-31 | 2003-05-07 | Medical Res Council | Selection by compartmentalised screening |
EP1641809B2 (fr) | 2003-07-05 | 2018-10-03 | The Johns Hopkins University | Procédé et compositions de détection et d'énumeration de variations génétiques |
US20050221339A1 (en) | 2004-03-31 | 2005-10-06 | Medical Research Council Harvard University | Compartmentalised screening by microfluidic control |
US7968287B2 (en) | 2004-10-08 | 2011-06-28 | Medical Research Council Harvard University | In vitro evolution in microfluidic systems |
EP3913375A1 (fr) | 2006-01-11 | 2021-11-24 | Bio-Rad Laboratories, Inc. | Dispositifs microfluidiques et procédés d'utilisation dans la formation et contrôle de nanoréacteurs |
GB0602637D0 (en) * | 2006-02-09 | 2006-03-22 | Glaxo Group Ltd | Novel process |
US20080003142A1 (en) | 2006-05-11 | 2008-01-03 | Link Darren R | Microfluidic devices |
US9562837B2 (en) | 2006-05-11 | 2017-02-07 | Raindance Technologies, Inc. | Systems for handling microfludic droplets |
EP2077912B1 (fr) | 2006-08-07 | 2019-03-27 | The President and Fellows of Harvard College | Tensioactifs fluorocarbonés stabilisateurs d'émulsions |
US8772046B2 (en) | 2007-02-06 | 2014-07-08 | Brandeis University | Manipulation of fluids and reactions in microfluidic systems |
WO2008130623A1 (fr) | 2007-04-19 | 2008-10-30 | Brandeis University | Manipulation de fluides, composants fluidiques et réactions dans des systèmes microfluidiques |
US12038438B2 (en) | 2008-07-18 | 2024-07-16 | Bio-Rad Laboratories, Inc. | Enzyme quantification |
EP3415235A1 (fr) | 2009-03-23 | 2018-12-19 | Raindance Technologies Inc. | Manipulation de gouttelettes microfluidiques |
EP2486409A1 (fr) | 2009-10-09 | 2012-08-15 | Universite De Strasbourg | Nanomatériau marqué à base de silice à propriétés améliorées et ses utilisations |
US10837883B2 (en) | 2009-12-23 | 2020-11-17 | Bio-Rad Laboratories, Inc. | Microfluidic systems and methods for reducing the exchange of molecules between droplets |
US10351905B2 (en) | 2010-02-12 | 2019-07-16 | Bio-Rad Laboratories, Inc. | Digital analyte analysis |
EP3392349A1 (fr) | 2010-02-12 | 2018-10-24 | Raindance Technologies, Inc. | Analyse numérique d'analytes |
US9399797B2 (en) | 2010-02-12 | 2016-07-26 | Raindance Technologies, Inc. | Digital analyte analysis |
US9366632B2 (en) | 2010-02-12 | 2016-06-14 | Raindance Technologies, Inc. | Digital analyte analysis |
EP2622103B2 (fr) | 2010-09-30 | 2022-11-16 | Bio-Rad Laboratories, Inc. | Dosages sandwich dans des gouttelettes |
EP3859011A1 (fr) | 2011-02-11 | 2021-08-04 | Bio-Rad Laboratories, Inc. | Procédés permettant de former des gouttelettes mélangées |
EP2675819B1 (fr) | 2011-02-18 | 2020-04-08 | Bio-Rad Laboratories, Inc. | Compositions et méthodes de marquage moléculaire |
DE202012013668U1 (de) | 2011-06-02 | 2019-04-18 | Raindance Technologies, Inc. | Enzymquantifizierung |
US8841071B2 (en) | 2011-06-02 | 2014-09-23 | Raindance Technologies, Inc. | Sample multiplexing |
US8658430B2 (en) | 2011-07-20 | 2014-02-25 | Raindance Technologies, Inc. | Manipulating droplet size |
US11901041B2 (en) | 2013-10-04 | 2024-02-13 | Bio-Rad Laboratories, Inc. | Digital analysis of nucleic acid modification |
US9944977B2 (en) | 2013-12-12 | 2018-04-17 | Raindance Technologies, Inc. | Distinguishing rare variations in a nucleic acid sequence from a sample |
US11193176B2 (en) | 2013-12-31 | 2021-12-07 | Bio-Rad Laboratories, Inc. | Method for detecting and quantifying latent retroviral RNA species |
US10647981B1 (en) | 2015-09-08 | 2020-05-12 | Bio-Rad Laboratories, Inc. | Nucleic acid library generation methods and compositions |
US20220313616A1 (en) * | 2021-03-30 | 2022-10-06 | Celanese Eva Performance Polymers Llc | Implantable Medical Device for the Delivery of Nucleic Acid-Encapsulated Particles |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0248531A3 (fr) * | 1986-05-02 | 1988-09-28 | Southern Research Institute | Acides nucléiques encapsulés |
US4839111A (en) * | 1987-02-02 | 1989-06-13 | The University Of Tennessee Research Corporation | Preparation of solid core liposomes |
ATE104857T1 (de) * | 1989-03-07 | 1994-05-15 | Genentech Inc | Kovalente konjugate von lipiden und oligonukleotiden. |
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1994
- 1994-04-19 CA CA002160878A patent/CA2160878A1/fr not_active Abandoned
- 1994-04-19 WO PCT/US1994/004239 patent/WO1994023738A1/fr not_active Application Discontinuation
- 1994-04-19 EP EP94914823A patent/EP0696200A4/fr not_active Withdrawn
- 1994-04-19 NZ NZ265818A patent/NZ265818A/en unknown
- 1994-04-19 AU AU67071/94A patent/AU6707194A/en not_active Abandoned
- 1994-04-19 JP JP6523517A patent/JPH08510639A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
WO1994023738A1 (fr) | 1994-10-27 |
EP0696200A1 (fr) | 1996-02-14 |
JPH08510639A (ja) | 1996-11-12 |
NZ265818A (en) | 1997-09-22 |
EP0696200A4 (fr) | 1998-04-15 |
AU6707194A (en) | 1994-11-08 |
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