JP2006503914A5 - - Google Patents
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- JP2006503914A5 JP2006503914A5 JP2005501623A JP2005501623A JP2006503914A5 JP 2006503914 A5 JP2006503914 A5 JP 2006503914A5 JP 2005501623 A JP2005501623 A JP 2005501623A JP 2005501623 A JP2005501623 A JP 2005501623A JP 2006503914 A5 JP2006503914 A5 JP 2006503914A5
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- hpv
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| KR101710981B1 (ko) * | 2006-07-28 | 2017-02-28 | 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 | 개선된 백신 및 이의 사용 방법 |
| US8877206B2 (en) | 2007-03-22 | 2014-11-04 | Pds Biotechnology Corporation | Stimulation of an immune response by cationic lipids |
| WO2009129227A1 (en) | 2008-04-17 | 2009-10-22 | Pds Biotechnology Corporation | Stimulation of an immune response by enantiomers of cationic lipids |
| JP5707326B2 (ja) * | 2008-09-02 | 2015-04-30 | アンティジェン・エクスプレス・インコーポレーテッドAntigen Express,Inc. | ヒトパピローマウイルス/Ii−keyのハイブリッドおよびその使用方法 |
| EP2601968A1 (en) | 2011-12-06 | 2013-06-12 | Deutsches Krebsforschungszentrum | HPV derived polynucleic acids for therapy |
| CN105163753B (zh) | 2012-06-15 | 2018-12-21 | Pds生物科技公司 | 阳离子脂质疫苗组合物和使用方法 |
| EP2897639A4 (en) | 2012-09-21 | 2016-05-04 | Frank Bedu-Addo | IMPROVED VACCINATE COMPOSITIONS AND METHODS OF USE |
| CA3005251A1 (en) | 2015-11-13 | 2017-05-18 | Pds Biotechnology Corporation | Lipids as synthetic vectors to enhance antigen processing and presentation ex-vivo in dendritic cell therapy |
| WO2018060288A1 (en) * | 2016-09-29 | 2018-04-05 | Glaxosmithkline Biologicals S.A. | Compositions and methods of treatment of persistent hpv infection |
| MX2019011324A (es) | 2017-03-23 | 2020-01-21 | Massachusetts Gen Hospital | Bloqueo de cxcr4/cxcr7 y tratamiento de enfermedad asociada con el virus del papiloma humano. |
| JP7457642B2 (ja) * | 2017-04-03 | 2024-03-28 | ビオンテック ユーエス インコーポレイテッド | タンパク質抗原およびその使用 |
| JP7558167B2 (ja) | 2018-12-03 | 2024-09-30 | ボード オブ リージェンツ,ザ ユニバーシティ オブ テキサス システム | オリゴベンズアミド類似体およびがん処置におけるそれらの使用 |
| WO2021026335A1 (en) * | 2019-08-08 | 2021-02-11 | The Trustees Of Indiana University | Methods for identifying and treating urinary tract infections |
| CN112957461B (zh) * | 2021-02-02 | 2023-01-10 | 南开大学 | 一种形貌可控自佐剂宫颈癌多肽疫苗的制备及性能表征方法 |
| WO2024180232A1 (en) * | 2023-03-02 | 2024-09-06 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Therapeutic hpv vaccines based on validated target epitopes |
Family Cites Families (60)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE76429T1 (de) * | 1986-03-21 | 1992-06-15 | Pasteur Institut | Bestimmte, von einem papillomavirus-genom abgeleitete dns-sequenzen, deren anwendungen fuer in vitro-diagnostische zwecke und die herstellung von antigenzusammensetzungen. |
| US4741872A (en) * | 1986-05-16 | 1988-05-03 | The University Of Kentucky Research Foundation | Preparation of biodegradable microspheres useful as carriers for macromolecules |
| US4777239A (en) * | 1986-07-10 | 1988-10-11 | The Board Of Trustees Of The Leland Stanford Junior University | Diagnostic peptides of human papilloma virus |
| US6007806A (en) * | 1986-08-13 | 1999-12-28 | Transgene S.A. | Expression of a tumor-specific antigen by a recombinant vector virus and use thereof in preventive or curative treatment of the corresponding tumor |
| US5075109A (en) * | 1986-10-24 | 1991-12-24 | Southern Research Institute | Method of potentiating an immune response |
| DE3907721A1 (de) * | 1989-03-10 | 1990-09-20 | Behringwerke Ag | Immunogene regionen auf dem e7-protein des humanen papillomvierus typ 16 |
| US5703055A (en) * | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
| US5753233A (en) * | 1990-05-10 | 1998-05-19 | Behring Diagnostics Gmbh | Seroreactive epitopes on proteins of human papilloma-virus (HPV) 18 |
| US5932412A (en) * | 1990-05-11 | 1999-08-03 | Euro-Diagnostica Ab | Synthetic peptides in human papillomaviruses 1, 5, 6, 8, 11, 16, 18, 31, 33 and 56, useful in immunoassay for diagnostic purposes |
| US5173414A (en) | 1990-10-30 | 1992-12-22 | Applied Immune Sciences, Inc. | Production of recombinant adeno-associated virus vectors |
| US6183745B1 (en) * | 1990-12-12 | 2001-02-06 | The University Of Queensland | Subunit papilloma virus vaccine and peptides for use therein |
| SE9003978D0 (sv) | 1990-12-13 | 1990-12-13 | Henrik Garoff | Dna expressionssystem baserade paa ett virus replikon |
| GB9105383D0 (en) * | 1991-03-14 | 1991-05-01 | Immunology Ltd | An immunotherapeutic for cervical cancer |
| US5543294A (en) | 1991-07-19 | 1996-08-06 | The Trustees Of Columbia University In The City Of New York | Polymerase chain reaction/restriction fragment length polymorphism method for the detection and typing of myobacteria |
| US5709860A (en) * | 1991-07-25 | 1998-01-20 | Idec Pharmaceuticals Corporation | Induction of cytotoxic T-lymphocyte responses |
| US6037135A (en) * | 1992-08-07 | 2000-03-14 | Epimmune Inc. | Methods for making HLA binding peptides and their uses |
| US5656297A (en) * | 1992-03-12 | 1997-08-12 | Alkermes Controlled Therapeutics, Incorporated | Modulated release from biocompatible polymers |
| AU668384B2 (en) * | 1992-03-12 | 1996-05-02 | Alkermes Controlled Therapeutics, Inc. | Controlled release ACTH containing microspheres |
| CA2142007C (en) * | 1992-08-11 | 2007-10-30 | Robert Glen Urban | Immunomodulatory peptides |
| US5462520A (en) | 1992-08-17 | 1995-10-31 | Genetronics, Inc. | Transsurface drug delivery by electrofusion of microbubbles to the tissue surface |
| US5633234A (en) * | 1993-01-22 | 1997-05-27 | The Johns Hopkins University | Lysosomal targeting of immunogens |
| US5593972A (en) * | 1993-01-26 | 1997-01-14 | The Wistar Institute | Genetic immunization |
| ATE386800T1 (de) * | 1993-03-17 | 2008-03-15 | Us Gov Health & Human Serv | Immunogene chimäre umfassend nucleinsäuresequenzen, die signalsequenzpeptide des endoplasmatischen reticulums und mindestens ein anderes peptid codieren, deren verwendung in impfstoffen und zur behandlung von krankheiten |
| US5993434A (en) | 1993-04-01 | 1999-11-30 | Genetronics, Inc. | Method of treatment using electroporation mediated delivery of drugs and genes |
| US5679647A (en) * | 1993-08-26 | 1997-10-21 | The Regents Of The University Of California | Methods and devices for immunizing a host against tumor-associated antigens through administration of naked polynucleotides which encode tumor-associated antigenic peptides |
| US5679509A (en) * | 1993-09-28 | 1997-10-21 | University Of New Mexico | Methods and a diagnostic aid for distinguishing a subset of HPV that is associated with an increased risk of developing cervical dysplasia and cervical cancer |
| US5643605A (en) * | 1993-10-25 | 1997-07-01 | Genentech, Inc. | Methods and compositions for microencapsulation of adjuvants |
| WO1995024929A2 (en) | 1994-03-15 | 1995-09-21 | Brown University Research Foundation | Polymeric gene delivery system |
| US6239116B1 (en) | 1994-07-15 | 2001-05-29 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US5736524A (en) * | 1994-11-14 | 1998-04-07 | Merck & Co.,. Inc. | Polynucleotide tuberculosis vaccine |
| AUPN015794A0 (en) * | 1994-12-20 | 1995-01-19 | Csl Limited | Variants of human papilloma virus antigens |
| AU5297496A (en) | 1995-02-17 | 1996-09-04 | Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Methods of preparation and use of recombinant adenoviral vectors |
| US5840306A (en) * | 1995-03-22 | 1998-11-24 | Merck & Co., Inc. | DNA encoding human papillomavirus type 18 |
| US5962428A (en) * | 1995-03-30 | 1999-10-05 | Apollon, Inc. | Compositions and methods for delivery of genetic material |
| US5705151A (en) * | 1995-05-18 | 1998-01-06 | National Jewish Center For Immunology & Respiratory Medicine | Gene therapy for T cell regulation |
| AUPN443995A0 (en) * | 1995-07-27 | 1995-08-17 | Csl Limited | Papillomavirus polyprotein |
| US6270795B1 (en) | 1995-11-09 | 2001-08-07 | Microbiological Research Authority | Method of making microencapsulated DNA for vaccination and gene therapy |
| US5626161A (en) * | 1996-04-29 | 1997-05-06 | Fu Tai Umbrella Works, Ltd. | Multiple-fold automatic umbrella with simplified reliable control means |
| AU733719B2 (en) * | 1996-10-23 | 2001-05-24 | Trustees Of The University Of Pennsylvania, The | Improved vaccines |
| US20020103145A1 (en) * | 1999-05-19 | 2002-08-01 | Adrian Bot | Immunization of infants |
| JP2001507352A (ja) * | 1996-12-20 | 2001-06-05 | メルク エンド カンパニー インコーポレーテッド | 組換えパピローマウイルスワクチンの組成物 |
| US5783567A (en) | 1997-01-22 | 1998-07-21 | Pangaea Pharmaceuticals, Inc. | Microparticles for delivery of nucleic acid |
| US6261281B1 (en) | 1997-04-03 | 2001-07-17 | Electrofect As | Method for genetic immunization and introduction of molecules into skeletal muscle and immune cells |
| US6183746B1 (en) * | 1997-10-09 | 2001-02-06 | Zycos Inc. | Immunogenic peptides from the HPV E7 protein |
| US6013258A (en) * | 1997-10-09 | 2000-01-11 | Zycos Inc. | Immunogenic peptides from the HPV E7 protein |
| GB9722766D0 (en) | 1997-10-28 | 1997-12-24 | British Telecomm | Portable computers |
| JP2002508190A (ja) | 1997-12-12 | 2002-03-19 | ダイジーン・コーポレーション | 万能収集媒質 |
| US6406719B1 (en) | 1998-05-13 | 2002-06-18 | Microbiological Research Authority | Encapsulation of bioactive agents |
| GB9810236D0 (en) | 1998-05-13 | 1998-07-08 | Microbiological Res Authority | Improvements relating to encapsulation of bioactive agents |
| EP1078092B1 (en) * | 1998-05-13 | 2011-08-03 | Epimmune Inc. | Expression vectors for stimulating an immune response and methods of using the same |
| CA2339817A1 (en) | 1998-08-12 | 2000-02-24 | Zycos Inc. | Profiling and cataloging expressed protein tags |
| ES2291039T3 (es) * | 1998-09-04 | 2008-02-16 | Sanofi Pasteur Limited | Tratamiento del cancer cervical. |
| CA2276066A1 (en) | 1999-03-11 | 2000-09-11 | Zycos Inc. | Microparticles for delivery of nucleic acid |
| US20050100928A1 (en) * | 1999-09-16 | 2005-05-12 | Zycos Inc., A Delaware Corporation | Nucleic acids encoding polyepitope polypeptides |
| AU785319B2 (en) * | 1999-09-16 | 2007-01-11 | Eisai Inc. | Nucleic acids encoding polyepitope polypeptides |
| WO2001027291A1 (en) * | 1999-10-12 | 2001-04-19 | Institut Pasteur | Design of a polyepitopic construct for the induction of hla-a2.1 restricted hiv 1 specific ctl responses using hhd mice |
| ES2260070T3 (es) | 1999-11-19 | 2006-11-01 | Mgi Pharma Biologics, Inc. | Metodo en flujo continuo para preparar microparticulas. |
| CA2410208A1 (en) | 2000-06-22 | 2001-12-27 | 3M Innovative Properties Company | Systems and methods for treating a mucosal surface |
| KR100919266B1 (ko) * | 2000-06-26 | 2009-09-30 | 엔벤타 바이오파마슈티컬스 코포레이션 | 인간 파필로마 바이러스 치료법 |
| GB0017990D0 (en) * | 2000-07-21 | 2000-09-13 | Glaxo Group Ltd | Papilloma virus sequences |
-
2003
- 2003-10-16 WO PCT/US2003/032705 patent/WO2004037175A2/en not_active Ceased
- 2003-10-16 EP EP03776419A patent/EP1556513B1/en not_active Expired - Lifetime
- 2003-10-16 AT AT03776419T patent/ATE465753T1/de not_active IP Right Cessation
- 2003-10-16 US US10/532,168 patent/US20060247190A1/en not_active Abandoned
- 2003-10-16 CA CA002502696A patent/CA2502696A1/en not_active Abandoned
- 2003-10-16 AU AU2003284239A patent/AU2003284239B2/en not_active Ceased
- 2003-10-16 JP JP2005501623A patent/JP2006503914A/ja active Pending
- 2003-10-16 DE DE60332377T patent/DE60332377D1/de not_active Expired - Lifetime
-
2008
- 2008-11-21 AU AU2008249148A patent/AU2008249148A1/en not_active Abandoned
-
2010
- 2010-06-07 US US12/795,483 patent/US20110158952A1/en not_active Abandoned
- 2010-12-10 JP JP2010275323A patent/JP2011121946A/ja active Pending
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