JP2010509243A5 - - Google Patents
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- JP2010509243A5 JP2010509243A5 JP2009535510A JP2009535510A JP2010509243A5 JP 2010509243 A5 JP2010509243 A5 JP 2010509243A5 JP 2009535510 A JP2009535510 A JP 2009535510A JP 2009535510 A JP2009535510 A JP 2009535510A JP 2010509243 A5 JP2010509243 A5 JP 2010509243A5
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Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050186183A1 (en) * | 2003-12-08 | 2005-08-25 | Deangelo Joseph | Stabilized products, processes and devices for preparing same |
| KR101501780B1 (ko) * | 2006-01-24 | 2015-03-16 | 넥스바이오, 인코퍼레이티드 | 고분자 미소 구체들의 조제를 위한 기술 |
| EP2170283B1 (en) | 2007-06-22 | 2019-01-09 | Board of Regents, The University of Texas System | Formation of stable submicron peptide or protein particles by thin film freezing |
| JP2011505810A (ja) * | 2007-12-13 | 2011-03-03 | シャンハイ グオジアン バイオ−テック インスティチュート | ヒト化抗ヒトｃｄ３４抗体、その調製方法および使用 |
| US8367427B2 (en) * | 2008-08-20 | 2013-02-05 | Baxter International Inc. | Methods of processing compositions containing microparticles |
| US8323685B2 (en) * | 2008-08-20 | 2012-12-04 | Baxter International Inc. | Methods of processing compositions containing microparticles |
| US8323615B2 (en) | 2008-08-20 | 2012-12-04 | Baxter International Inc. | Methods of processing multi-phasic dispersions |
| EP2376522A4 (en) | 2008-11-16 | 2013-12-25 | Univ Texas | LOW VISCOSIS HIGHLY CONCENTRATED SUSPENSIONS |
| WO2010071894A2 (en) | 2008-12-19 | 2010-06-24 | Baxter International Inc. | Tfpi inhibitors and methods of use |
| PL2459171T3 (pl) | 2009-07-31 | 2017-11-30 | Sanofi-Aventis Deutschland Gmbh | Kompozycja insuliny o długim działaniu |
| AU2010277559B2 (en) | 2009-07-31 | 2016-08-11 | Sanofi-Aventis Deutschland Gmbh | Prodrugs comprising an insulin linker conjugate |
| 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 |
| CN103096934A (zh) * | 2010-03-09 | 2013-05-08 | 詹森生物科技公司 | 非水性高浓度低粘度混悬剂 |
| AU2011227714B2 (en) | 2010-03-19 | 2014-09-04 | Takeda Pharmaceutical Company Limited | TFPI inhibitors and methods of use |
| EP2438930A1 (en) | 2010-09-17 | 2012-04-11 | Sanofi-Aventis Deutschland GmbH | Prodrugs comprising an exendin linker conjugate |
| WO2013141965A1 (en) | 2012-03-21 | 2013-09-26 | Baxter International Inc. | Tfpi inhibitors and methods of use |
| EP2866792A4 (en) | 2012-06-28 | 2016-08-17 | Ansun Biopharma Inc | MICROPARTICLE FORMULATIONS FOR DELIVERY TO LOWER AND CENTRAL RESPIRATORY PATHS AND METHOD OF PREPARING THEM |
| US11248040B2 (en) | 2013-09-26 | 2022-02-15 | Trellis Bioscience, Llc | Binding moieties for biofilm remediation |
| US10624934B2 (en) | 2014-03-06 | 2020-04-21 | Research Institute At Nationwide Children's Hospital | Prebiotic formulations |
| AU2015227075A1 (en) | 2014-03-06 | 2016-09-22 | Ohio State Innovation Foundation | Probiotic formulations and methods for use |
| WO2017011588A1 (en) | 2015-07-14 | 2017-01-19 | Research Institute At Nationwide Children's Hospital | Novel formulation for the elimination of cariogenic and opportunistic pathogens within the oral cavity |
| AU2016303688B2 (en) | 2015-07-31 | 2023-06-15 | Research Institute At Nationwide Children's Hospital | Peptides and antibodies for the removal of biofilms |
| WO2017066719A2 (en) | 2015-10-14 | 2017-04-20 | Research Institute At Nationwide Children's Hospital | Hu specific interfering agents |
| US11654112B2 (en) | 2016-11-22 | 2023-05-23 | Elektrofi, Inc. | Particles comprising a therapeutic or diagnostic agent and suspensions and methods of use thereof |
| JP7514621B2 (ja) | 2017-01-04 | 2024-07-11 | リサーチ インスティチュート アット ネイションワイド チルドレンズ ホスピタル | Ｄｎａｂｉｉワクチンおよび強化された活性を有する抗体 |
| AU2018306303A1 (en) | 2017-07-25 | 2020-02-20 | Elektrofi, Inc. | Formation of particles including agents |
| WO2019226969A1 (en) | 2018-05-24 | 2019-11-28 | Elektrofi, Inc. | Particles comprising a therapeutic or diagnostic agent and suspensions and methods of use thereof |
| SG11202103001PA (en) | 2018-10-05 | 2021-04-29 | Res Inst Nationwide Childrens Hospital | Hmgb1 protein derivatives for the removal of biofilms cross-reference to related application |
| US12569524B2 (en) | 2018-10-22 | 2026-03-10 | Research Institute At Nationwide Children's Hospital | Compositions and methods for preventing and treating antibiotic induced pathologies using probiotics in the biofilm state |
| WO2020115283A1 (en) | 2018-12-07 | 2020-06-11 | Baxalta GmbH | Bispecific antibodies binding factor ixa and factor x |
| WO2020114615A1 (en) | 2018-12-07 | 2020-06-11 | Baxalta GmbH | Bispecific antibodies binding factor ixa and factor x |
| EP3917500A2 (en) | 2019-01-31 | 2021-12-08 | Elektrofi, Inc. | Particle formation and morphology |
| KR102941878B1 (ko) | 2019-02-05 | 2026-03-23 | 린디 바이오사이언시스, 아이엔씨. | 단리된 세포 배양 성분 및 액체 세포 배양 배지로부터 이를 단리하는 방법 |
| WO2020247536A1 (en) | 2019-06-03 | 2020-12-10 | Research Institute At Nationwide Children's Hospital | Prebiotic formulations for prevention of sepsis and necroenterocolitis induced neurodevelopmental deficiencies |
| WO2021050953A1 (en) | 2019-09-13 | 2021-03-18 | Elektrofi, Inc. | Compositions and methods for the delivery of therapeutic biologics for treatment of disease |
| KR20220083738A (ko) * | 2019-10-16 | 2022-06-20 | 고쿠리쓰다이가쿠호진 규슈다이가쿠 | 경피 흡수형 첩부제 |
| JP2023522627A (ja) | 2020-04-17 | 2023-05-31 | エレクトロフィ，インコーポレイテッド | 連続的な液滴形成及び脱水によって粒子を形成する方法 |
Family Cites Families (150)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2849370A (en) * | 1953-06-04 | 1958-08-26 | Novo Terapeutisk Labortorium A | Injectable insulin preparations with protracted effect and process of producing same |
| DE2010115A1 (de) * | 1970-03-04 | 1971-09-16 | Farbenfabriken Bayer Ag, 5090 Leverkusen | Verfahren zur Herstellung von Mikrogranulaten |
| JPS523342B2 (https=) * | 1972-01-26 | 1977-01-27 | ||
| US4389330A (en) * | 1980-10-06 | 1983-06-21 | Stolle Research And Development Corporation | Microencapsulation process |
| US4530840A (en) * | 1982-07-29 | 1985-07-23 | The Stolle Research And Development Corporation | Injectable, long-acting microparticle formulation for the delivery of anti-inflammatory agents |
| JPS60100516A (ja) * | 1983-11-04 | 1985-06-04 | Takeda Chem Ind Ltd | 徐放型マイクロカプセルの製造法 |
| US4818542A (en) * | 1983-11-14 | 1989-04-04 | The University Of Kentucky Research Foundation | Porous microspheres for drug delivery and methods for making same |
| US4584894A (en) * | 1984-02-29 | 1986-04-29 | Borg-Warner Corporation | Transmission anti-clash and anti-rattle brake |
| US5417986A (en) * | 1984-03-16 | 1995-05-23 | The United States Of America As Represented By The Secretary Of The Army | Vaccines against diseases caused by enteropathogenic organisms using antigens encapsulated within biodegradable-biocompatible microspheres |
| CA1279684C (en) * | 1984-10-02 | 1991-01-29 | Takahiro Sakakino | Pressure sensitive switch |
| ATE61935T1 (de) * | 1985-02-07 | 1991-04-15 | Takeda Chemical Industries Ltd | Verfahren zur herstellung von mikrokapseln. |
| JP2551756B2 (ja) * | 1985-05-07 | 1996-11-06 | 武田薬品工業株式会社 | ポリオキシカルボン酸エステルおよびその製造法 |
| US5102872A (en) * | 1985-09-20 | 1992-04-07 | Cetus Corporation | Controlled-release formulations of interleukin-2 |
| GB8601100D0 (en) * | 1986-01-17 | 1986-02-19 | Cosmas Damian Ltd | Drug delivery system |
| EP0257915B1 (en) * | 1986-08-11 | 1993-03-10 | Innovata Biomed Limited | Pharmaceutical formulations comprising microcapsules |
| US5075109A (en) | 1986-10-24 | 1991-12-24 | Southern Research Institute | Method of potentiating an immune response |
| US4861627A (en) * | 1987-05-01 | 1989-08-29 | Massachusetts Institute Of Technology | Preparation of multiwall polymeric microcapsules |
| US4897268A (en) * | 1987-08-03 | 1990-01-30 | Southern Research Institute | Drug delivery system and method of making the same |
| US5422120A (en) * | 1988-05-30 | 1995-06-06 | Depotech Corporation | Heterovesicular liposomes |
| IL92344A0 (en) | 1989-01-04 | 1990-07-26 | Gist Brocades Nv | Microencapsulation of bioactive substances in biocompatible polymers,microcapsules obtained and pharmaceutical preparation comprising said microcapsules |
| GB8903593D0 (en) | 1989-02-16 | 1989-04-05 | Pafra Ltd | Storage of materials |
| USRE38385E1 (en) * | 1989-02-16 | 2004-01-13 | Nektar Therapeutics | Storage of materials |
| JPH0739339B2 (ja) * | 1989-05-01 | 1995-05-01 | アルカーメス コントロールド セラピューティクス，インコーポレイテッド | 生物活性を有する分子の小粒子の製造方法 |
| WO1990013361A1 (en) * | 1989-05-04 | 1990-11-15 | Southern Research Institute | Improved encapsulation process and products therefrom |
| MY107937A (en) * | 1990-02-13 | 1996-06-29 | Takeda Chemical Industries Ltd | Prolonged release microcapsules. |
| DK0528978T3 (da) | 1990-05-16 | 2003-02-17 | Southern Res Inst | Mikrokapsler til reguleret afgivelse og deres anvendelse i stimulering af nervefibervækst |
| GB9016885D0 (en) * | 1990-08-01 | 1990-09-12 | Scras | Sustained release pharmaceutical compositions |
| US5149543A (en) | 1990-10-05 | 1992-09-22 | Massachusetts Institute Of Technology | Ionically cross-linked polymeric microcapsules |
| AU1442592A (en) * | 1991-02-20 | 1992-09-15 | Nova Pharmaceutical Corporation | Controlled release microparticulate delivery system for proteins |
| US5330768A (en) * | 1991-07-05 | 1994-07-19 | Massachusetts Institute Of Technology | Controlled drug delivery using polymer/pluronic blends |
| US6063910A (en) * | 1991-11-14 | 2000-05-16 | The Trustees Of Princeton University | Preparation of protein microparticles by supercritical fluid precipitation |
| US5525519A (en) * | 1992-01-07 | 1996-06-11 | Middlesex Sciences, Inc. | Method for isolating biomolecules from a biological sample with linear polymers |
| US5173454A (en) * | 1992-01-09 | 1992-12-22 | Corning Incorporated | Nanocrystalline materials |
| US5912015A (en) * | 1992-03-12 | 1999-06-15 | Alkermes Controlled Therapeutics, Inc. | Modulated release from biocompatible polymers |
| DE4211169C1 (https=) | 1992-03-31 | 1993-06-03 | Klaus Kretzschmar | |
| US5286495A (en) * | 1992-05-11 | 1994-02-15 | University Of Florida | Process for microencapsulating cells |
| JP2651320B2 (ja) | 1992-07-16 | 1997-09-10 | 田辺製薬株式会社 | 徐放性マイクロスフェア製剤の製造方法 |
| JP3277342B2 (ja) * | 1992-09-02 | 2002-04-22 | 武田薬品工業株式会社 | 徐放性マイクロカプセルの製造法 |
| EP0595030A3 (en) * | 1992-10-01 | 1995-06-07 | Tanabe Seiyaku Co | Multi-core microspheres with delayed drug delivery and process for their manufacture. |
| WO1994012158A1 (en) | 1992-12-02 | 1994-06-09 | Alkermes Controlled Therapeutics, Inc. | Controlled release growth hormone containing microspheres |
| US5554730A (en) | 1993-03-09 | 1996-09-10 | Middlesex Sciences, Inc. | Method and kit for making a polysaccharide-protein conjugate |
| ATE163230T1 (de) * | 1993-03-09 | 1998-02-15 | Epic Therapeutics Inc | Makromolekulare mikropartikel und verfahren zu ihrer herstellung |
| US6090925A (en) * | 1993-03-09 | 2000-07-18 | Epic Therapeutics, Inc. | Macromolecular microparticles and methods of production and use |
| US5981719A (en) | 1993-03-09 | 1999-11-09 | Epic Therapeutics, Inc. | Macromolecular microparticles and methods of production and use |
| DE4312970A1 (de) | 1993-04-21 | 1994-10-27 | Juergen Dr Schrezenmeir | Mikrokapsel sowie Verfahren und Vorrichtung zu ihrer Herstellung |
| US5543158A (en) * | 1993-07-23 | 1996-08-06 | Massachusetts Institute Of Technology | Biodegradable injectable nanoparticles |
| DE4333107A1 (de) | 1993-09-29 | 1995-03-30 | Bayer Ag | Auf Trägern angebrachte ein- oder mehrlagige Schichtelemente und ihre Herstellung |
| US5932248A (en) | 1993-11-18 | 1999-08-03 | Paragon Medical Limited | Controlled release preparations for cytotoxic or cytostatic drugs |
| US5650173A (en) * | 1993-11-19 | 1997-07-22 | Alkermes Controlled Therapeutics Inc. Ii | Preparation of biodegradable microparticles containing a biologically active agent |
| CA2474701C (en) | 1993-11-19 | 2009-01-27 | Alkermes Controlled Therapeutics Inc. Ii | Preparation of biodegradeable microparticles containing a biologically active agent |
| US5858973A (en) * | 1994-02-23 | 1999-01-12 | The General Hospital Corporation | Transcription factor and uses therefor |
| US5620883A (en) * | 1994-04-01 | 1997-04-15 | The Johns Hopkins University | Living cells microencapsulated in a polymeric membrane having two layers |
| US6387399B1 (en) * | 1994-12-02 | 2002-05-14 | The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration | Microencapsulated bioactive agents and method of making |
| US6267958B1 (en) * | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
| US6265389B1 (en) * | 1995-08-31 | 2001-07-24 | Alkermes Controlled Therapeutics, Inc. | Microencapsulation and sustained release of oligonucleotides |
| ATE386506T1 (de) | 1995-10-17 | 2008-03-15 | Jagotec Ag | Verabreichung unlöslicher arzneistoffe |
| SE505146C2 (sv) | 1995-10-19 | 1997-06-30 | Biogram Ab | Partiklar för fördröjd frisättning |
| JP2909959B2 (ja) | 1995-10-19 | 1999-06-23 | 三井化学株式会社 | タンパク質超薄膜固定型リアクターの製造方法及び得られたタンパク質超薄膜固定型リアクターを用いた化学反応 |
| US5665428A (en) | 1995-10-25 | 1997-09-09 | Macromed, Inc. | Preparation of peptide containing biodegradable microspheres by melt process |
| US6270795B1 (en) | 1995-11-09 | 2001-08-07 | Microbiological Research Authority | Method of making microencapsulated DNA for vaccination and gene therapy |
| CA2192782C (en) | 1995-12-15 | 2008-10-14 | Nobuyuki Takechi | Production of microspheres |
| GB9610992D0 (en) * | 1996-05-24 | 1996-07-31 | Glaxo Group Ltd | Concentrated antibody preparation |
| EP0920339A2 (en) | 1996-07-09 | 1999-06-09 | The Johns Hopkins University | Gene delivery system |
| JP2966795B2 (ja) * | 1996-09-30 | 1999-10-25 | 科学技術振興事業団 | 機能性薄膜とその製造方法 |
| DE69727244T2 (de) * | 1996-10-03 | 2004-11-25 | Hermes Biosciences Inc., San Francisco | Hydrophile Mikroteilchen und Verfahren zu deren Herstellung |
| GB9623051D0 (en) | 1996-11-06 | 1997-01-08 | Schacht Etienne H | Delivery of DNA to target cells in biological systems |
| US6395302B1 (en) * | 1996-11-19 | 2002-05-28 | Octoplus B.V. | Method for the preparation of microspheres which contain colloidal systems |
| US5945126A (en) | 1997-02-13 | 1999-08-31 | Oakwood Laboratories L.L.C. | Continuous microsphere process |
| US6140475A (en) | 1997-04-11 | 2000-10-31 | Altus Biologics Inc. | Controlled dissolution crosslinked protein crystals |
| DE19726282A1 (de) | 1997-06-20 | 1998-12-24 | Inst Neue Mat Gemein Gmbh | Nanoskalige Teilchen mit einem von mindestens zwei Schalen umgebenen eisenoxid-haltigen Kern |
| NZ502358A (en) | 1997-07-18 | 2002-11-26 | Infimed Therapeutics Inc | Hydrogel composition comprising a biologically active substance combined with a macromer |
| US5989463A (en) | 1997-09-24 | 1999-11-23 | Alkermes Controlled Therapeutics, Inc. | Methods for fabricating polymer-based controlled release devices |
| SE512663C2 (sv) * | 1997-10-23 | 2000-04-17 | Biogram Ab | Inkapslingsförfarande för aktiv substans i en bionedbrytbar polymer |
| US6541606B2 (en) | 1997-12-31 | 2003-04-01 | Altus Biologics Inc. | Stabilized protein crystals formulations containing them and methods of making them |
| NZ505877A (en) | 1998-01-16 | 2002-10-25 | Univ Johns Hopkins | Oral delivery of nucleic acid vaccines by particulate complexes |
| JP3629939B2 (ja) * | 1998-03-18 | 2005-03-16 | セイコーエプソン株式会社 | トランジスタ回路、表示パネル及び電子機器 |
| EP0972563A1 (en) | 1998-07-15 | 2000-01-19 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Fabrication of multilayer-coated particles and hollow shells via electrostatic self-assembly of nanocomposite multilayers on decomposable colloidal templates |
| DE19812083A1 (de) | 1998-03-19 | 1999-09-30 | Max Planck Gesellschaft | Herstellung von Nano- und Mikrokapseln durch schichtweise Polyelektrolyt-Selbstassemblierung |
| WO1999047253A1 (en) | 1998-03-19 | 1999-09-23 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Fabrication of multilayer-coated particles and hollow shells via electrostatic self-assembly of nanocomposite multilayers on decomposable colloidal templates |
| US7101575B2 (en) | 1998-03-19 | 2006-09-05 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Production of nanocapsules and microcapsules by layer-wise polyelectrolyte self-assembly |
| US6266053B1 (en) * | 1998-04-03 | 2001-07-24 | Synapix, Inc. | Time inheritance scene graph for representation of media content |
| 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 |
| DE59914547D1 (de) * | 1998-07-15 | 2007-12-20 | Max Planck Gesellschaft | Polyelektrolythüllen auf biologischen templaten |
| GB9819272D0 (en) | 1998-09-03 | 1998-10-28 | Andaris Ltd | Microparticles |
| US6270802B1 (en) * | 1998-10-28 | 2001-08-07 | Oakwood Laboratories L.L.C. | Method and apparatus for formulating microspheres and microcapsules |
| DE19852928C1 (de) * | 1998-11-17 | 2000-08-03 | Steffen Panzner | Strukturen in Form von Hohlkugeln |
| US6194006B1 (en) * | 1998-12-30 | 2001-02-27 | Alkermes Controlled Therapeutics Inc. Ii | Preparation of microparticles having a selected release profile |
| US6630169B1 (en) | 1999-03-31 | 2003-10-07 | Nektar Therapeutics | Particulate delivery systems and methods of use |
| AU3957400A (en) | 1999-04-16 | 2000-11-02 | Novo Nordisk A/S | Dry, mouldable drug formulation |
| US20030236214A1 (en) | 1999-06-09 | 2003-12-25 | Wolff Jon A. | Charge reversal of polyion complexes and treatment of peripheral occlusive disease |
| WO2000077281A1 (en) | 1999-06-10 | 2000-12-21 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Encapsulation of crystals via multilayer coatings |
| DE69910987T2 (de) | 1999-06-14 | 2004-05-19 | Baxter International Inc., Deerfield | Mikrosphären mit verzögerter Wirkstoffabgabe |
| US6645525B1 (en) | 1999-06-23 | 2003-11-11 | Sedum Laboratories, Inc. | Ionically formulated biomolecule microcarriers |
| US6458387B1 (en) * | 1999-10-18 | 2002-10-01 | Epic Therapeutics, Inc. | Sustained release microspheres |
| DE10001172A1 (de) | 2000-01-13 | 2001-07-26 | Max Planck Gesellschaft | Templatieren von Feststoffpartikeln mit Polymermultischichten |
| DE10010264A1 (de) | 2000-03-02 | 2001-09-13 | Novosom Gmbh | Stabilisierte Liposomen und Hüllstrukturen |
| US7129222B2 (en) | 2000-03-10 | 2006-10-31 | Dynavax Technologies Corporation | Immunomodulatory formulations and methods for use thereof |
| WO2001078687A1 (en) * | 2000-04-18 | 2001-10-25 | Peptron Inc. | Injectable sustained release pharmaceutical composition and processes for preparing the same |
| CA2408025A1 (en) * | 2000-04-28 | 2001-11-08 | Rainer Pommersheim | Method and facility for producing micromembrane capsules |
| FR2809309B1 (fr) * | 2000-05-23 | 2004-06-11 | Mainelab | Microspheres a liberation prolongee pour administration injectable |
| JP2003534290A (ja) | 2000-05-26 | 2003-11-18 | シムフォゲン アクティーゼルスカブ | アレルギー治療用の組換えまたは精製ポリクロナール抗体 |
| US6849259B2 (en) | 2000-06-16 | 2005-02-01 | Symphogen A/S | Polyclonal antibody composition for treating allergy |
| US6998393B2 (en) * | 2000-06-23 | 2006-02-14 | Biopharm Solutions, Inc. | Aquespheres, their preparation and uses thereof |
| KR100392501B1 (ko) * | 2000-06-28 | 2003-07-22 | 동국제약 주식회사 | 다중 에멀젼법에 의한 서방출성 미립구의 제조방법 |
| DE10031132A1 (de) * | 2000-06-30 | 2002-01-17 | Henkel Kgaa | Verfahren zur Herstellung aktivstoffhaltiger Kapseln mit ultradünner Wandschicht |
| US20040013738A1 (en) * | 2000-08-02 | 2004-01-22 | Andreas Voigt | Encapsulation of liquid template particles |
| ATE295156T1 (de) * | 2000-08-28 | 2005-05-15 | Max Planck Gesellschaft | Mehrlagige polyelektrolytkapseln mit gesteuerter und verzögerter freisetzung |
| US6471995B1 (en) | 2000-09-27 | 2002-10-29 | Alkermes Controlled Therapeutics, Inc. Ii | Apparatus and method for preparing microparticles using liquid-liquid extraction |
| AU2002213441B2 (en) | 2000-10-12 | 2006-10-26 | Genentech, Inc. | Reduced-viscosity concentrated protein formulations |
| SE518007C2 (sv) | 2000-11-16 | 2002-08-13 | Bioglan Ab | Förfarande för framställning av mikropartiklar |
| DE10157799A1 (de) | 2000-11-27 | 2002-09-05 | Max Delbrueck Centrum | Herstellung und Anwendung von DNA-Polyelektrolyt-Nanopartikeln für den Gentransfer |
| NZ526720A (en) | 2000-12-28 | 2007-11-30 | Altus Pharmaceuticals Inc | Crystallisation of whole antibodies or fragments thereof, on a large scale and a process allowing an alternative route for delivery of therapeutic antibodies |
| EP1801123A3 (en) | 2000-12-28 | 2007-11-21 | Altus Pharmaceuticals Inc. | Crystals of whole antibodies and fragments thereof and methods for making and using them |
| CA2436418A1 (en) * | 2001-01-30 | 2002-08-08 | Board Of Regents, The University Of Texas Systems | Process for production of nanoparticles and microparticles by spray freezing into liquid |
| US6896905B2 (en) * | 2001-02-15 | 2005-05-24 | Rohm And Haas Company | Porous particles, their aqueous dispersions, and method of preparation |
| FR2823675B1 (fr) | 2001-04-19 | 2004-03-12 | Inst Nat Sante Rech Med | Biomateriaux avec recouvrements bioactifs |
| GB0113179D0 (en) * | 2001-05-31 | 2001-07-25 | Novartis Ag | Organic compounds |
| CA2451185A1 (en) | 2001-06-21 | 2003-01-03 | Altus Biologics, Inc. | Spherical protein particles and methods of making and using them |
| ATE395042T1 (de) * | 2001-08-16 | 2008-05-15 | Baxter Int | Darreichungsformen welche mikropartikel und treibgas enthalten |
| US6878693B2 (en) * | 2001-09-28 | 2005-04-12 | Solubest Ltd. | Hydrophilic complexes of lipophilic materials and an apparatus and method for their production |
| AU2002334939A1 (en) * | 2001-10-12 | 2003-04-22 | Eugene R. Cooper | Compositions having a combination of particles for immediate release and for controlled release |
| US7112361B2 (en) * | 2001-10-25 | 2006-09-26 | Massachusetts Institute Of Technology | Methods of making decomposable thin films of polyelectrolytes and uses thereof |
| WO2004001007A2 (en) | 2002-06-21 | 2003-12-31 | Idec Pharmaceuticals Corporation | Buffered formulations for concentrating antibodies and methods of use thereof |
| US20040014698A1 (en) * | 2002-07-18 | 2004-01-22 | Gonzalo Hortelano | Oral administration of therapeutic agent coupled to transporting agent |
| US6896926B2 (en) * | 2002-09-11 | 2005-05-24 | Novartis Ag | Method for applying an LbL coating onto a medical device |
| CN1688275B (zh) | 2002-09-11 | 2012-05-30 | 田边三菱制药株式会社 | 微球的制备方法 |
| US20060002862A1 (en) * | 2002-12-17 | 2006-01-05 | Medimmune Vaccines, Inc. | High pressure spray-dry of bioactive materials |
| KR20050088175A (ko) | 2002-12-17 | 2005-09-02 | 메드이뮨 백신즈 인코포레이티드 | 생물활성 물질의 고압 분무 건조 |
| EP1578394A4 (en) * | 2002-12-31 | 2011-02-23 | Nektar Therapeutics | ANTIBODY PARTICLES AND COMPOSITIONS |
| NZ554885A (en) | 2002-12-31 | 2009-07-31 | Altus Pharmaceuticals Inc | Complexes of hgh crystals and protamine polymers |
| EP2460530A3 (en) | 2002-12-31 | 2012-08-29 | Althea Technologies, Inc. | Human growth hormone crystals and methods for preparing them |
| CN1798575A (zh) | 2003-04-04 | 2006-07-05 | 健泰科生物技术公司 | 高浓度抗体和蛋白制剂 |
| US20050158303A1 (en) * | 2003-04-04 | 2005-07-21 | Genentech, Inc. | Methods of treating IgE-mediated disorders comprising the administration of high concentration anti-IgE antibody formulations |
| EP1628636A1 (de) | 2003-05-09 | 2006-03-01 | Novosom AG | Injizierbare liposomale depots zum wirkstoffdelivery |
| US6959503B2 (en) | 2003-06-13 | 2005-11-01 | P.C.T. Systems, Inc. | Method and apparatus for removing liquid from substrate surfaces using suction |
| US7198777B2 (en) | 2003-06-17 | 2007-04-03 | The Board Of Trustees Of The University Of Illinois | Optical contrast agents for optically modifying incident radiation |
| CN1845938B (zh) * | 2003-06-30 | 2010-05-26 | 杜门蒂斯有限公司 | 多肽 |
| RU2426590C2 (ru) * | 2003-07-18 | 2011-08-20 | Бакстер Интернэшнл Инк. | Способы изготовления, применение и композиции небольших сферических частиц, приготовленных регулируемым фазовым разделением |
| US20050142205A1 (en) * | 2003-07-18 | 2005-06-30 | Julia Rashba-Step | Methods for encapsulating small spherical particles prepared by controlled phase separation |
| US20050048127A1 (en) * | 2003-07-22 | 2005-03-03 | Larry Brown | Small spherical particles of low molecular weight organic molecules and methods of preparation and use thereof |
| DE10355904A1 (de) * | 2003-11-29 | 2005-06-30 | Merck Patent Gmbh | Feste Formen von anti-EGFR-Antikörpern |
| RU2390353C2 (ru) * | 2004-02-12 | 2010-05-27 | Мерк Патент Гмбх | Высококонцентрированные жидкие композиции анти-egfr антител |
| DE102004013637A1 (de) | 2004-03-19 | 2005-10-13 | Capsulution Nanoscience Ag | Verfahren zur Herstellung von CS-Partikeln und Mikrokapseln unter Verwendung poröser Template sowie CS-Partikel und Mikrokapseln |
| US8333995B2 (en) * | 2004-05-12 | 2012-12-18 | Baxter International, Inc. | Protein microspheres having injectable properties at high concentrations |
| DK2072040T3 (da) | 2004-05-12 | 2013-07-29 | Baxter Healthcare Sa | Terapeutisk anvendelse af nukleinsyremikrokugler |
| WO2005112885A2 (en) * | 2004-05-12 | 2005-12-01 | Baxter International Inc. | Oligonucleotide-containing microspheres, their use for the manufacture of a medicament for treating diabetes type 1 |
| JP4595112B2 (ja) | 2005-02-14 | 2010-12-08 | 独立行政法人産業技術総合研究所 | タンパク質の高効率分離または濃縮方法 |
| WO2006112838A1 (en) | 2005-04-18 | 2006-10-26 | Xtl Biopharmaceuticals Ltd. | Stabilized anti-hepatitis b (hbv) antibody formulations |
| RU2303833C2 (ru) * | 2005-07-26 | 2007-07-27 | Самсунг Электро-Меканикс Ко., Лтд. | Осветительное устройство |
| BRPI0620316A2 (pt) * | 2005-12-21 | 2011-11-08 | Wyeth Corp | formulações de proteìnas com viscosidades reduzida e seus usos |
-
2006
- 2006-11-07 US US11/557,486 patent/US8728525B2/en active Active
-
2007
- 2007-11-07 JP JP2009535510A patent/JP2010509243A/ja active Pending
- 2007-11-07 EP EP07871397.1A patent/EP2086572A4/en not_active Withdrawn
- 2007-11-07 WO PCT/US2007/083952 patent/WO2008073642A2/en not_active Ceased
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