PT1265928E - Anticorpos neutralizantes com afinidade ultra-elevada - Google Patents
Anticorpos neutralizantes com afinidade ultra-elevada Download PDFInfo
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- PT1265928E PT1265928E PT01903352T PT01903352T PT1265928E PT 1265928 E PT1265928 E PT 1265928E PT 01903352 T PT01903352 T PT 01903352T PT 01903352 T PT01903352 T PT 01903352T PT 1265928 E PT1265928 E PT 1265928E
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- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
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- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
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- C07—ORGANIC CHEMISTRY
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
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| US7229619B1 (en) | 2000-11-28 | 2007-06-12 | Medimmune, Inc. | Methods of administering/dosing anti-RSV antibodies for prophylaxis and treatment |
| ATE474854T1 (de) * | 2000-01-27 | 2010-08-15 | Medimmune Llc | Rsv neutralisierende antikörper mit sehr hohen affinität |
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| ES2727425T3 (es) | 2000-12-12 | 2019-10-16 | Medimmune Llc | Moléculas con semividas prolongadas, composiciones y usos de las mismas |
| EP2075256A2 (en) | 2002-01-14 | 2009-07-01 | William Herman | Multispecific binding molecules |
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| US7132100B2 (en) | 2002-06-14 | 2006-11-07 | Medimmune, Inc. | Stabilized liquid anti-RSV antibody formulations |
| JP2005533861A (ja) * | 2002-07-25 | 2005-11-10 | メデュームン，インコーポレーテッド | 抗ＲＳＶ、抗ｈＭＰＶ、および抗ＰＩＶ抗体を使用するＲＳＶ、ｈＭＰＶ、およびＰＩＶの治療法と予防法 |
| AU2004207741B2 (en) * | 2003-01-24 | 2011-02-10 | Applied Molecular Evolution, Inc | Human IL-1 beta antagonists |
| US20050059592A1 (en) * | 2003-04-11 | 2005-03-17 | Kiener Peter A. | EphA2 and hyperproliferative cell disorders |
| WO2004092343A2 (en) * | 2003-04-11 | 2004-10-28 | Medimmune, Inc. | Epha2, hypoproliferative cell disorders and epithelial and endothelial reconstitution |
| AR044388A1 (es) * | 2003-05-20 | 2005-09-07 | Applied Molecular Evolution | Moleculas de union a cd20 |
| US7795404B1 (en) | 2003-08-08 | 2010-09-14 | Five Prime Therapeutics, Inc. | Human soluble notch receptor ligands |
| WO2005035569A2 (en) * | 2003-10-10 | 2005-04-21 | Five Prime Therapeutics, Inc. | Kiaa0779, splice variants thereof, and methods of their use |
| EP1720908A2 (en) * | 2004-02-17 | 2006-11-15 | Absalus, Inc. | Super-humanized antibodies against respiratory syncytial virus |
| DK1716181T3 (da) | 2004-02-19 | 2010-03-01 | Genentech Inc | CDR-reparerede antistoffer |
| AU2005249360B2 (en) | 2004-04-12 | 2011-07-21 | Medimmune, Llc | Anti-IL-9 antibody formulations and uses thereof |
| DK1776384T3 (da) | 2004-08-04 | 2013-09-02 | Mentrik Biotech Llc | VARIANT-Fc-REGIONER |
| WO2006034292A2 (en) | 2004-09-21 | 2006-03-30 | Medimmune, Inc. | Antibodies against and methods for producing vaccines for respiratory syncytial virus |
| EP1812068A4 (en) * | 2004-10-29 | 2010-06-09 | Medimmune Inc | METHODS FOR PREVENTING AND TREATING RSV INFECTIONS AND ASSOCIATED DISEASES |
| JP4881874B2 (ja) | 2004-12-06 | 2012-02-22 | 協和発酵キリン株式会社 | インフルエンザｍ２タンパク質に対するヒトモノクローナル抗体及びその生産方法及びその使用 |
| CN101171263A (zh) * | 2005-03-04 | 2008-04-30 | 比奥根艾迪克Ma公司 | 通过合理修饰互补决定区残基使免疫球蛋白可变区人源化的方法 |
| WO2007002543A2 (en) | 2005-06-23 | 2007-01-04 | Medimmune, Inc. | Antibody formulations having optimized aggregation and fragmentation profiles |
| BRPI0708636A2 (pt) * | 2006-03-06 | 2011-06-07 | Symphogen As | anticorpo policlonal recombinante para tratamento de infecções por vìrus sinciciais respiratórios |
| WO2008070042A2 (en) * | 2006-12-04 | 2008-06-12 | Medimmune, Inc. | High potency recombinant antibodies, methods for producing them and use in cancer therapy |
| CN101679513A (zh) * | 2007-03-06 | 2010-03-24 | 西福根有限公司 | 用于治疗呼吸道合胞病毒感染的重组抗体 |
| EP1997830A1 (en) | 2007-06-01 | 2008-12-03 | AIMM Therapeutics B.V. | RSV specific binding molecules and means for producing them |
| AU2008304574A1 (en) * | 2007-09-24 | 2009-04-02 | Vanderbilt University | Monoclonal antibodies to respiratory syncytial virus and uses thereof |
| ES2595362T3 (es) | 2008-06-16 | 2016-12-29 | Patrys Limited | Anticuerpos LM, fragmentos funcionales, antígeno diana LM-1 y métodos para prepararlos y usarlos |
| WO2010056893A1 (en) * | 2008-11-13 | 2010-05-20 | Imclone Llc | Humanization and affinity-optimization of antibodies |
| US8775090B2 (en) | 2008-12-12 | 2014-07-08 | Medimmune, Llc | Crystals and structure of a human IgG Fc variant with enhanced FcRn binding |
| AU2009331570C1 (en) * | 2008-12-22 | 2024-04-18 | Novo Nordisk A/S | Antibodies against tissue factor pathway inhibitor |
| WO2010087927A2 (en) | 2009-02-02 | 2010-08-05 | Medimmune, Llc | Antibodies against and methods for producing vaccines for respiratory syncytial virus |
| PL2464664T3 (pl) | 2009-08-13 | 2016-02-29 | Crucell Holland Bv | Przeciwciała przeciwko ludzkiemu syncytialnemu wirusowi oddechowemu (RSV) i sposoby zastosowania |
| US8568726B2 (en) | 2009-10-06 | 2013-10-29 | Medimmune Limited | RSV specific binding molecule |
| NZ718973A (en) | 2010-07-09 | 2019-01-25 | Janssen Vaccines & Prevention Bv | Anti-human respiratory syncytial virus (rsv) antibodies and methods of use |
| CN109776676A (zh) | 2012-11-28 | 2019-05-21 | Cnj控股公司 | 针对艰难梭菌的抗体 |
| TWI659968B (zh) | 2013-03-14 | 2019-05-21 | 再生元醫藥公司 | 針對呼吸道融合病毒ｆ蛋白質的人類抗體及其使用方法 |
| US9682123B2 (en) | 2013-12-20 | 2017-06-20 | The Trustees Of Columbia University In The City Of New York | Methods of treating metabolic disease |
| ES2950426T3 (es) | 2015-08-12 | 2023-10-09 | Univ Columbia | Procedimientos de tratamiento de la depleción de volumen y la lesión renal |
| EP4011919A3 (en) | 2015-12-09 | 2022-10-12 | The Scripps Research Institute | Relaxin immunoglobulin fusion proteins and methods of use |
| AU2017345786A1 (en) | 2016-10-21 | 2019-05-23 | Adimab, Llc | Anti-respiratory syncytial virus antibodies, and methods of their generation and use |
| KR20190103147A (ko) | 2016-10-21 | 2019-09-04 | 아디맵 엘엘씨 | 항-호흡기 세포융합 바이러스 항체, 그리고 이의 생성 방법 및 사용 방법 |
| JP7265984B2 (ja) | 2016-10-21 | 2023-04-27 | アディマブ， エルエルシー | 抗呼吸器合胞体ウイルス抗体、及び、それらの生成及び使用の方法 |
| WO2021202463A1 (en) | 2020-03-30 | 2021-10-07 | Danisco Us Inc | Anti-rsv antibodies |
Family Cites Families (100)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA814386B (en) | 1980-07-01 | 1982-07-28 | Nat Res Dev | Production of viral antigens |
| JPS58500366A (ja) * | 1981-03-06 | 1983-03-10 | セルテツク リミテツド | 単一クロ−ン抗体 |
| DE3378250D1 (en) * | 1982-04-22 | 1988-11-24 | Ici Plc | Continuous release formulations |
| US5340926A (en) * | 1983-03-25 | 1994-08-23 | Celltech, Limited | Process for the recovery of recombinantly produced protein from insoluble aggregate |
| 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 |
| US5332805A (en) * | 1984-02-03 | 1994-07-26 | Celltech Limited | Process for the recovery of recombinantly produced chymosin from insoluble aggregate |
| US5807715A (en) | 1984-08-27 | 1998-09-15 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin |
| US5128326A (en) * | 1984-12-06 | 1992-07-07 | Biomatrix, Inc. | Drug delivery systems based on hyaluronans derivatives thereof and their salts and methods of producing same |
| FR2590674B1 (fr) * | 1985-11-25 | 1989-03-03 | Inst Nat Sante Rech Med | Nouveaux reactifs de diagnostic |
| US5149650A (en) * | 1986-01-14 | 1992-09-22 | University Of North Carolina At Chapel Hill | Vaccines for human respiratory virus |
| US4659563A (en) * | 1986-01-27 | 1987-04-21 | Miles Laboratories, Inc. | High titer anti-respiratory syncytial virus intravenous immune globulin |
| US4717766A (en) * | 1986-01-27 | 1988-01-05 | Miles Laboratories, Inc. | Method of preparing high titer anti-respiratory syncytial virus intravenous immune globulin |
| US5271927A (en) | 1986-02-13 | 1993-12-21 | Celltech Limited | Antibody conjugates with macrocyclic ligands |
| US5468606A (en) | 1989-09-18 | 1995-11-21 | Biostar, Inc. | Devices for detection of an analyte based upon light interference |
| EP0307434B2 (en) * | 1987-03-18 | 1998-07-29 | Scotgen Biopharmaceuticals, Inc. | Altered antibodies |
| US4800078A (en) * | 1987-05-28 | 1989-01-24 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Immunotherapeutic method of treating respiratory disease by intranasal administration of Igb |
| GB8719041D0 (en) * | 1987-08-12 | 1987-09-16 | Parker D | Conjugate compounds |
| GB8720833D0 (en) * | 1987-09-04 | 1987-10-14 | Celltech Ltd | Recombinant dna product |
| US5223254A (en) * | 1987-09-29 | 1993-06-29 | Praxis Biologics, Inc. | Respiratory syncytial virus: vaccines |
| EP0396563B1 (en) * | 1987-12-23 | 1993-02-10 | The Upjohn Company | Chimeric glycoproteins containing immunogenic segments of the glycoproteins of human respiratory syncytial virus |
| JP3095168B2 (ja) | 1988-02-05 | 2000-10-03 | エル． モリソン，シェリー | ドメイン‐変性不変部を有する抗体 |
| US5183657A (en) * | 1988-03-11 | 1993-02-02 | Celltech Limited | Antibodies for use in antilymphocyte antibody therapy |
| JPH01268646A (ja) | 1988-04-20 | 1989-10-26 | Meiji Milk Prod Co Ltd | 抗腫瘍剤 |
| US5137804A (en) * | 1988-05-10 | 1992-08-11 | E. I. Du Pont De Nemours And Company | Assay device and immunoassay |
| US5223409A (en) * | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| AU634186B2 (en) | 1988-11-11 | 1993-02-18 | Medical Research Council | Single domain ligands, receptors comprising said ligands, methods for their production, and use of said ligands and receptors |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| IL162181A (en) | 1988-12-28 | 2006-04-10 | Pdl Biopharma Inc | A method of producing humanized immunoglubulin, and polynucleotides encoding the same |
| US5354554A (en) * | 1989-02-10 | 1994-10-11 | Celltech Limited | Crosslinked antibodies and processes for their preparation |
| US6093872A (en) | 1989-05-05 | 2000-07-25 | Systemix, Inc. | Extended human hematopoiesis in a heterologous host |
| FR2650598B1 (fr) | 1989-08-03 | 1994-06-03 | Rhone Poulenc Sante | Derives de l'albumine a fonction therapeutique |
| US5332567A (en) * | 1989-08-24 | 1994-07-26 | Immunomedics | Detection and treatment of infections with immunoconjugates |
| US5518725A (en) * | 1989-09-25 | 1996-05-21 | University Of Utah Research Foundation | Vaccine compositions and method for induction of mucosal immune response via systemic vaccination |
| JP2571874B2 (ja) * | 1989-11-06 | 1997-01-16 | 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 | タンパク質マイクロスフェア組成物 |
| GB8928874D0 (en) * | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
| US5279935A (en) * | 1990-03-01 | 1994-01-18 | Becton, Dickinson And Company | Method of immunossay including deactivation of endogenous alkaline phosphatase |
| DK0481058T3 (da) * | 1990-05-03 | 1996-12-02 | Systemix Inc | Humant, lymfatisk væv i en immunokompromitteret vært |
| US5264563A (en) | 1990-08-24 | 1993-11-23 | Ixsys Inc. | Process for synthesizing oligonucleotides with random codons |
| CA2108259C (en) * | 1991-04-22 | 2003-12-09 | George R. Siber | Process of screening plasma samples for effective antibody titers against respiratory viruses |
| CA2109528A1 (en) * | 1991-05-01 | 1992-11-02 | Gregory A. Prince | A method for treating infectious respiratory diseases |
| CA2044940A1 (en) | 1991-06-10 | 1992-12-11 | Inder M. Verma | Transdominant negative proto-oncogene |
| US5240694A (en) * | 1991-09-23 | 1993-08-31 | University Of Virginia | Combined antiviral and antimediator treatment of common colds |
| US5418136A (en) * | 1991-10-01 | 1995-05-23 | Biostar, Inc. | Devices for detection of an analyte based upon light interference |
| EP0614530B1 (en) * | 1991-11-15 | 1998-03-04 | Cornell Research Foundation, Inc. | Indirect immunoassay for dioxinlike compounds |
| US5824307A (en) * | 1991-12-23 | 1998-10-20 | Medimmune, Inc. | Human-murine chimeric antibodies against respiratory syncytial virus |
| US20020102257A1 (en) * | 1998-09-21 | 2002-08-01 | Leslie Sid Johnson | Human-murine chimeric antibodies against respiratory syncytial virus |
| US5667988A (en) | 1992-01-27 | 1997-09-16 | The Scripps Research Institute | Methods for producing antibody libraries using universal or randomized immunoglobulin light chains |
| US5912015A (en) * | 1992-03-12 | 1999-06-15 | Alkermes Controlled Therapeutics, Inc. | Modulated release from biocompatible polymers |
| ATE231002T1 (de) | 1992-09-16 | 2003-02-15 | Scripps Research Inst | Menschliche, neutralisierende, monoklonale antikörper gegen das respiratorische synzytialvirus |
| US6685942B1 (en) * | 1993-12-10 | 2004-02-03 | The Scripps Research Institute | Human neutralizing monoclonal antibodies to respiratory syncytial virus |
| EP0680337A4 (en) * | 1993-01-12 | 1997-07-30 | Anthony George Gristina | METHODS AND COMPOSITIONS FOR DIRECT APPLICATION WITH HIGH CONCENTRATION OF ANTIBODIES, PRODUCING PASSIVE IMMUNITY. |
| US5934272A (en) * | 1993-01-29 | 1999-08-10 | Aradigm Corporation | Device and method of creating aerosolized mist of respiratory drug |
| US5424189A (en) * | 1993-03-05 | 1995-06-13 | Kansas State University Research Foundation | Bovine respiratory syncytial virus detection and primers |
| AU689489B2 (en) * | 1993-07-30 | 1998-04-02 | Oravax, Inc | Monoclonal IgA antibody against respiratory syncytial virus |
| US5506209A (en) * | 1994-05-26 | 1996-04-09 | Abbott Laboratories | Product for inhibition of infection of mammalian cells by respiratory syncytial virus |
| US5538952A (en) * | 1994-05-26 | 1996-07-23 | Abbott Laboratories | Inhibition of infection of mammalian cells by respiratory syncytial virus |
| US5538733A (en) * | 1994-07-07 | 1996-07-23 | Willmar Poultry Company, Inc. | Method of priming an immune response in a one-day old animal |
| US5792456A (en) | 1994-08-04 | 1998-08-11 | Bristol-Myers Squibb Company | Mutant BR96 antibodies reactive with human carcinomas |
| US6121022A (en) * | 1995-04-14 | 2000-09-19 | Genentech, Inc. | Altered polypeptides with increased half-life |
| US6019968A (en) * | 1995-04-14 | 2000-02-01 | Inhale Therapeutic Systems, Inc. | Dispersible antibody compositions and methods for their preparation and use |
| US5811524A (en) * | 1995-06-07 | 1998-09-22 | Idec Pharmaceuticals Corporation | Neutralizing high affinity human monoclonal antibodies specific to RSV F-protein and methods for their manufacture and therapeutic use thereof |
| WO1997007788A2 (en) * | 1995-08-31 | 1997-03-06 | Alkermes Controlled Therapeutics, Inc. | Composition for sustained release of an agent |
| DK0853487T3 (da) * | 1995-09-18 | 2000-10-23 | Us Health | Neutraliserende monoklonale antistoffer mod respiratorisk syncytial virus |
| ATE508733T1 (de) | 1996-03-04 | 2011-05-15 | Penn State Res Found | Materialien und verfahren zur steigerung der zellulären internalisierung |
| US5985309A (en) | 1996-05-24 | 1999-11-16 | Massachusetts Institute Of Technology | Preparation of particles for inhalation |
| US5855913A (en) * | 1997-01-16 | 1999-01-05 | Massachusetts Instite Of Technology | Particles incorporating surfactants for pulmonary drug delivery |
| US5874064A (en) * | 1996-05-24 | 1999-02-23 | Massachusetts Institute Of Technology | Aerodynamically light particles for pulmonary drug delivery |
| FR2758331B1 (fr) | 1997-01-14 | 1999-03-05 | Univ Bourgogne | Nouveaux moyens pour le diagnostic, la prevention et le traitement vis-a-vis de contaminations ou d'infections par des virus a tropisme muqueux |
| US6117980A (en) * | 1997-02-21 | 2000-09-12 | Genentech, Inc. | Humanized anti-IL-8 monoclonal antibodies |
| US6277375B1 (en) * | 1997-03-03 | 2001-08-21 | Board Of Regents, The University Of Texas System | Immunoglobulin-like domains with increased half-lives |
| US5989463A (en) | 1997-09-24 | 1999-11-23 | Alkermes Controlled Therapeutics, Inc. | Methods for fabricating polymer-based controlled release devices |
| AU760120B2 (en) * | 1997-12-01 | 2003-05-08 | Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Antibodies, including Fv molecules, and immunoconjugates having high binding affinity for mesothelin and methods for their use |
| US6528624B1 (en) * | 1998-04-02 | 2003-03-04 | Genentech, Inc. | Polypeptide variants |
| US6194551B1 (en) * | 1998-04-02 | 2001-02-27 | Genentech, Inc. | Polypeptide variants |
| US6572856B1 (en) * | 1998-09-10 | 2003-06-03 | The University Of Virginia Patent Foundation | Methods for the prevention and treatment of cancer using anti-C3b(i) antibodies |
| ATE384792T1 (de) | 1998-11-18 | 2008-02-15 | Genentech Inc | Antikörpervarianten mit höheren bindungsaffinitäten im vergleich zu parentalen antikörpern |
| US6737056B1 (en) * | 1999-01-15 | 2004-05-18 | Genentech, Inc. | Polypeptide variants with altered effector function |
| AR022952A1 (es) * | 1999-03-19 | 2002-09-04 | Smithkline Beecham Corp | ANTICUERPO MONOCLONAL DE ROEDOR ESPECIFICAMENTE NEUTRALIZANTE PARA LA INTERLEUQUINA-18 HUMANA , UN FRAGMENTO FAB NEUTRALIZANTE o FRAGMENTO F(AB')2, UNA REGION DE COMPLEMENTARIEDAD DE CADENA LIGERA DE INMONOGLOBULINA(CDR), UNA MOLECULA DE ACIDO NUCLEICO, COMPOSICION FARMACEUTICA QUE LO COMPRENDE, EL |
| CA2374398C (en) * | 1999-05-27 | 2011-03-15 | Ira Pastan | Immunoconjugates having high binding affinity |
| ATE474854T1 (de) | 2000-01-27 | 2010-08-15 | Medimmune Llc | Rsv neutralisierende antikörper mit sehr hohen affinität |
| US7229619B1 (en) * | 2000-11-28 | 2007-06-12 | Medimmune, Inc. | Methods of administering/dosing anti-RSV antibodies for prophylaxis and treatment |
| US20010034062A1 (en) | 2000-02-09 | 2001-10-25 | Scott Koenig | Antibody gene therapy with adeno-associated viral vectors |
| EP2341075A1 (en) * | 2000-03-01 | 2011-07-06 | MedImmune, LLC | Antibodies binding to the f protein of a respiratory syncytial virus (rsv) |
| AU2001241918A1 (en) * | 2000-03-02 | 2001-09-12 | Med Immune, Inc. | Methods of enhancing activity of vaccines and vaccine compositions |
| IL151348A0 (en) * | 2000-04-13 | 2003-04-10 | Univ Rockefeller | Enhancement of antibody-mediated immune responses |
| US20020004046A1 (en) * | 2000-05-03 | 2002-01-10 | Johnson Leslie S. | Combination therapy of respiratory diseases using antibodies |
| ATE300713T1 (de) * | 2000-05-03 | 2005-08-15 | Ipv Inheidener Produktions Und | Thermobehälter |
| ES2338098T3 (es) * | 2000-05-03 | 2010-05-04 | Medimmune, Llc | Terapia de combinacion de enfermedades respiratorias usando anticuerpos y agentes antiinflamatorios. |
| AU2001263443A1 (en) * | 2000-05-25 | 2001-12-03 | Med Immune, Inc. | F-protein epitope-based vaccine for respiratory syncytial virus infection |
| US6565888B1 (en) * | 2000-08-23 | 2003-05-20 | Alkermes Controlled Therapeutics, Inc. | Methods and compositions for the targeted delivery of biologically active agents |
| US7179900B2 (en) * | 2000-11-28 | 2007-02-20 | Medimmune, Inc. | Methods of administering/dosing anti-RSV antibodies for prophylaxis and treatment |
| US6855493B2 (en) * | 2000-11-28 | 2005-02-15 | Medimmune, Inc. | Methods of administering/dosing anti-RSV antibodies for prophylaxis and treatment |
| US6818216B2 (en) | 2000-11-28 | 2004-11-16 | Medimmune, Inc. | Anti-RSV antibodies |
| EP2412384A1 (en) | 2000-11-28 | 2012-02-01 | MedImmune, LLC | Methods of administering/dosing anti-RSV antibodies for prophylaxis and treatment |
| ES2727425T3 (es) * | 2000-12-12 | 2019-10-16 | Medimmune Llc | Moléculas con semividas prolongadas, composiciones y usos de las mismas |
| US20040002587A1 (en) * | 2002-02-20 | 2004-01-01 | Watkins Jeffry D. | Fc region variants |
| US7425618B2 (en) * | 2002-06-14 | 2008-09-16 | Medimmune, Inc. | Stabilized anti-respiratory syncytial virus (RSV) antibody formulations |
| US7132100B2 (en) | 2002-06-14 | 2006-11-07 | Medimmune, Inc. | Stabilized liquid anti-RSV antibody formulations |
| WO2006034292A2 (en) * | 2004-09-21 | 2006-03-30 | Medimmune, Inc. | Antibodies against and methods for producing vaccines for respiratory syncytial virus |
| EP1812068A4 (en) * | 2004-10-29 | 2010-06-09 | Medimmune Inc | METHODS FOR PREVENTING AND TREATING RSV INFECTIONS AND ASSOCIATED DISEASES |
-
2001
- 2001-01-26 AT AT01903352T patent/ATE474854T1/de active
- 2001-01-26 WO PCT/US2001/002618 patent/WO2001055217A1/en active Application Filing
- 2001-01-26 EP EP01903352A patent/EP1265928B1/en not_active Expired - Lifetime
- 2001-01-26 US US09/771,415 patent/US6656467B2/en not_active Expired - Fee Related
- 2001-01-26 PT PT01903352T patent/PT1265928E/pt unknown
- 2001-01-26 ES ES01903352T patent/ES2349348T3/es not_active Expired - Lifetime
- 2001-01-26 AU AU31180/01A patent/AU785038B2/en not_active Ceased
- 2001-01-26 DE DE60142614T patent/DE60142614D1/de not_active Expired - Lifetime
- 2001-01-26 DK DK01903352.1T patent/DK1265928T3/da active
- 2001-01-26 CA CA002398466A patent/CA2398466A1/en not_active Abandoned
- 2001-01-26 EP EP10007381A patent/EP2289550A3/en not_active Withdrawn
- 2001-01-26 JP JP2001561064A patent/JP4992068B2/ja not_active Expired - Fee Related
-
2003
- 2003-09-08 US US10/657,363 patent/US7740851B2/en not_active Expired - Fee Related
-
2010
- 2010-02-09 JP JP2010026299A patent/JP2010180207A/ja active Pending
- 2010-03-19 AU AU2010201090A patent/AU2010201090B2/en not_active Ceased
- 2010-05-11 US US12/777,814 patent/US20100266614A1/en not_active Abandoned
- 2010-10-21 CY CY20101100947T patent/CY1111542T1/el unknown
-
2011
- 2011-10-24 US US13/279,592 patent/US20120135006A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2001055217A1 (en) | 2001-08-02 |
| DK1265928T3 (da) | 2010-11-15 |
| JP4992068B2 (ja) | 2012-08-08 |
| ATE474854T1 (de) | 2010-08-15 |
| JP2010180207A (ja) | 2010-08-19 |
| AU785038B2 (en) | 2006-08-31 |
| AU785038C (en) | 2001-08-07 |
| JP2003528052A (ja) | 2003-09-24 |
| AU2010201090A1 (en) | 2010-04-15 |
| EP1265928A1 (en) | 2002-12-18 |
| EP2289550A2 (en) | 2011-03-02 |
| AU3118001A (en) | 2001-08-07 |
| AU2010201090B2 (en) | 2012-05-17 |
| CY1111542T1 (el) | 2015-08-05 |
| US20020164326A1 (en) | 2002-11-07 |
| US20040131609A1 (en) | 2004-07-08 |
| US20100266614A1 (en) | 2010-10-21 |
| US6656467B2 (en) | 2003-12-02 |
| EP2289550A3 (en) | 2012-02-15 |
| US7740851B2 (en) | 2010-06-22 |
| US20120135006A1 (en) | 2012-05-31 |
| CA2398466A1 (en) | 2001-08-02 |
| EP1265928B1 (en) | 2010-07-21 |
| ES2349348T3 (es) | 2010-12-30 |
| DE60142614D1 (de) | 2010-09-02 |
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