JP2003526670A - 免疫調節性ポリヌクレオチド配列を使用するヘルペス感染の症候の寛解法 - Google Patents
免疫調節性ポリヌクレオチド配列を使用するヘルペス感染の症候の寛解法Info
- Publication number
- JP2003526670A JP2003526670A JP2001566667A JP2001566667A JP2003526670A JP 2003526670 A JP2003526670 A JP 2003526670A JP 2001566667 A JP2001566667 A JP 2001566667A JP 2001566667 A JP2001566667 A JP 2001566667A JP 2003526670 A JP2003526670 A JP 2003526670A
- Authority
- JP
- Japan
- Prior art keywords
- iss
- sequence
- infection
- symptoms
- herpes simplex
- 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.)
- Pending
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- 238000007619 statistical method Methods 0.000 description 1
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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
- A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
-
- 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
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- 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
- A61K2039/555—Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
- A61K2039/55511—Organic adjuvants
- A61K2039/55561—CpG containing adjuvants; Oligonucleotide containing adjuvants
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Biotechnology (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US18855600P | 2000-03-10 | 2000-03-10 | |
| US60/188,556 | 2000-03-10 | ||
| US09/802,518 US7157437B2 (en) | 2000-03-10 | 2001-03-09 | Methods of ameliorating symptoms of herpes infection using immunomodulatory polynucleotide sequences |
| US09/802,518 | 2001-03-09 | ||
| PCT/US2001/007841 WO2001068103A2 (en) | 2000-03-10 | 2001-03-12 | Treatment of herpes infection using immunomodulatory polynucleotide sequences |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2003526670A true JP2003526670A (ja) | 2003-09-09 |
| JP2003526670A5 JP2003526670A5 (https=) | 2008-05-08 |
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| US (2) | US7157437B2 (https=) |
| EP (1) | EP1265622B1 (https=) |
| JP (1) | JP2003526670A (https=) |
| AT (1) | ATE476984T1 (https=) |
| AU (2) | AU2001281459C1 (https=) |
| CA (1) | CA2402312A1 (https=) |
| DE (1) | DE60142776D1 (https=) |
| WO (1) | WO2001068103A2 (https=) |
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| US6207646B1 (en) * | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US6239116B1 (en) | 1994-07-15 | 2001-05-29 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US20030026782A1 (en) * | 1995-02-07 | 2003-02-06 | Arthur M. Krieg | Immunomodulatory oligonucleotides |
| US6406705B1 (en) | 1997-03-10 | 2002-06-18 | University Of Iowa Research Foundation | Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant |
| PT1077722E (pt) | 1998-05-22 | 2006-12-29 | Coley Pharm Group Inc | Produtos e composições para utilização na indução da imunidade mucosal |
| US6977245B2 (en) | 1999-04-12 | 2005-12-20 | The United States Of America As Represented By The Department Of Health And Human Services | Oligodeoxynucleotide and its use to induce an immune response |
| AU4343700A (en) | 1999-04-12 | 2000-11-14 | Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Oligodeoxynucleotide and its use to induce an immune response |
| US7223398B1 (en) * | 1999-11-15 | 2007-05-29 | Dynavax Technologies Corporation | Immunomodulatory compositions containing an immunostimulatory sequence linked to antigen and methods of use thereof |
| EP1322655B1 (en) | 2000-01-14 | 2007-11-14 | The Government of the United States of America, as represented by the Secretary of the Department of Health and Human Services | Oligodeoxynucleotide and its use to induce an immune response |
| US20030129251A1 (en) * | 2000-03-10 | 2003-07-10 | Gary Van Nest | Biodegradable immunomodulatory formulations and methods for use thereof |
| US7129222B2 (en) | 2000-03-10 | 2006-10-31 | Dynavax Technologies Corporation | Immunomodulatory formulations and methods for use thereof |
| US20020098199A1 (en) * | 2000-03-10 | 2002-07-25 | Gary Van Nest | Methods of suppressing hepatitis virus infection using immunomodulatory polynucleotide sequences |
| US20020107212A1 (en) * | 2000-03-10 | 2002-08-08 | Nest Gary Van | Methods of reducing papillomavirus infection using immunomodulatory polynucleotide sequences |
| US20020028784A1 (en) * | 2000-03-10 | 2002-03-07 | Nest Gary Van | Methods of preventing and treating viral infections using immunomodulatory polynucleotide sequences |
| US20010046967A1 (en) * | 2000-03-10 | 2001-11-29 | Gary Van Nest | Methods of preventing and treating respiratory viral infection using immunomodulatory polynucleotide |
| US7157437B2 (en) | 2000-03-10 | 2007-01-02 | Dynavax Technologies Corporation | Methods of ameliorating symptoms of herpes infection using immunomodulatory polynucleotide sequences |
| JP4188687B2 (ja) | 2000-12-27 | 2008-11-26 | ダイナバックス テクノロジーズ コーポレイション | 免疫変調ポリヌクレオチド及びその使用法 |
| CA2451974C (en) | 2001-06-21 | 2014-10-14 | Karen L. Fearon | Chimeric immunomodulatory compounds and methods of using the same |
| JP4607452B2 (ja) | 2001-08-07 | 2011-01-05 | ダイナバックス テクノロジーズ コーポレイション | 免疫調節性組成物、製剤およびその使用方法 |
| WO2003020884A2 (en) | 2001-08-14 | 2003-03-13 | The Government Of The United States Of America As Represented By The Secretary Of Health And Human Services | Method for rapid generation of mature dendritic cells |
| JP2005508945A (ja) * | 2001-10-06 | 2005-04-07 | メリアル リミテッド | Ｃｐｇ配合物及び関連方法 |
| AU2002366710A1 (en) | 2001-12-20 | 2003-07-09 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of | USE OF CpG OLIGODEOXYNUCLEOTIDES TO INDUCE ANGIOGENESIS |
| PT2241325E (pt) * | 2002-10-29 | 2012-04-12 | Coley Pharm Gmbh | Utilização de oligonucleótidos cpg no tratamento de infecção com vírus da hepatite c |
| AU2003304107B2 (en) | 2002-11-01 | 2008-05-15 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method of preventing infections from bioterrorism agents with immunostimulatory CpG oligonucleotides |
| EP1578954A4 (en) | 2002-12-11 | 2010-08-11 | Coley Pharm Group Inc | 5'-CPG NUCLEIC ACIDS AND USE METHOD |
| US8158768B2 (en) | 2002-12-23 | 2012-04-17 | Dynavax Technologies Corporation | Immunostimulatory sequence oligonucleotides and methods of using the same |
| PT1992635E (pt) | 2002-12-23 | 2012-03-20 | Dynavax Tech Corp | Oligonucleótidos de sequência imunoestimuladora e métodos de utilização dos mesmos |
| AU2004226605A1 (en) * | 2003-04-02 | 2004-10-14 | Coley Pharmaceutical Group, Ltd. | Immunostimulatory nucleic acid oil-in-water formulations for topical application |
| TWI235440B (en) * | 2004-03-31 | 2005-07-01 | Advanced Semiconductor Eng | Method for making leadless semiconductor package |
| AU2006220835B2 (en) | 2005-03-04 | 2012-01-19 | Dynavax Technologies Corporation | Vaccines comprising oligonucleotides having immunostimulatory sequences (ISS) wherein the ISS are conjugated to antigens and stabilized by buffer conditions and further excipients |
| RU2314817C2 (ru) * | 2005-11-22 | 2008-01-20 | Светлана Николаевна Козлова | Способ лечения неврологических повреждений у детей |
| ES2534947T3 (es) | 2009-03-25 | 2015-04-30 | The Board Of Regents Of The University Of Texas System | Composiciones para la estimulación de resistencia inmunitaria innata de mamíferos a patógenos |
| EP3756684A1 (en) | 2009-05-22 | 2020-12-30 | Genocea Biosciences, Inc. | Vaccines against herpes simplex virus type 2: compositions and methods for eliciting an immune response |
| AU2011258165B2 (en) | 2010-05-26 | 2016-11-17 | Selecta Biosciences, Inc. | Dose selection of adjuvanted synthetic nanocarriers |
| WO2012061717A1 (en) | 2010-11-05 | 2012-05-10 | Selecta Biosciences, Inc. | Modified nicotinic compounds and related methods |
| EP2643014A4 (en) | 2010-11-24 | 2015-11-11 | Genocea Biosciences Inc | HERPES SIMPLEX TYPE 2 VIRUS VACCINES: COMPOSITIONS AND METHODS FOR STIMULATING AN IMMUNE RESPONSE |
| JP2014521687A (ja) | 2011-07-29 | 2014-08-28 | セレクタ バイオサイエンシーズ インコーポレーテッド | 体液性および細胞傷害性ｔリンパ球（ｃｔｌ）免疫応答を生成する合成ナノキャリア |
| EP2782597B1 (en) | 2011-11-23 | 2022-04-13 | Genocea Biosciences, Inc. | Nucleic acid vaccines against herpes simplex virus type 2: compositions and methods for eliciting an immune response |
| US10286065B2 (en) | 2014-09-19 | 2019-05-14 | Board Of Regents, The University Of Texas System | Compositions and methods for treating viral infections through stimulated innate immunity in combination with antiviral compounds |
| JP2019537555A (ja) | 2016-09-28 | 2019-12-26 | ジェノセア バイオサイエンシーズ， インコーポレイテッド | ヘルペスを処置するための方法および組成物 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995026204A1 (en) * | 1994-03-25 | 1995-10-05 | Isis Pharmaceuticals, Inc. | Immune stimulation by phosphorothioate oligonucleotide analogs |
| WO1998040100A1 (en) * | 1997-03-10 | 1998-09-17 | Ottawa Civic Loeb Research Institute | USE OF NUCLEIC ACIDS CONTAINING UNMETHYLATED CpG DINUCLEOTIDE AS AN ADJUVANT |
| WO1998055495A2 (en) * | 1997-06-06 | 1998-12-10 | Dynavax Technologies Corporation | Immunostimulatory oligonucleotides, compositions thereof and methods of use thereof |
| WO1999051259A2 (en) * | 1998-04-03 | 1999-10-14 | University Of Iowa Research Foundation | Methods and products for stimulating the immune system using immunotherapeutic oligonucleotides and cytokines |
Family Cites Families (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4458066A (en) | 1980-02-29 | 1984-07-03 | University Patents, Inc. | Process for preparing polynucleotides |
| US4948882A (en) | 1983-02-22 | 1990-08-14 | Syngene, Inc. | Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis |
| US4650675A (en) | 1983-08-18 | 1987-03-17 | The Children's Medical Center Corporation | Oligonucleotide conjugates |
| US5015733A (en) | 1983-12-20 | 1991-05-14 | California Institute Of Technology | Nucleosides possessing blocked aliphatic amino groups |
| US4849513A (en) | 1983-12-20 | 1989-07-18 | California Institute Of Technology | Deoxyribonucleoside phosphoramidites in which an aliphatic amino group is attached to the sugar ring and their use for the preparation of oligonucleotides containing aliphatic amino groups |
| US5118800A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | Oligonucleotides possessing a primary amino group in the terminal nucleotide |
| US5118802A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | DNA-reporter conjugates linked via the 2' or 5'-primary amino group of the 5'-terminal nucleoside |
| US5093232A (en) | 1985-12-11 | 1992-03-03 | Chiron Corporation | Nucleic acid probes |
| US4910300A (en) | 1985-12-11 | 1990-03-20 | Chiron Corporation | Method for making nucleic acid probes |
| US5124246A (en) | 1987-10-15 | 1992-06-23 | Chiron Corporation | Nucleic acid multimers and amplified nucleic acid hybridization assays using same |
| US5278302A (en) | 1988-05-26 | 1994-01-11 | University Patents, Inc. | Polynucleotide phosphorodithioates |
| EP0468520A3 (en) | 1990-07-27 | 1992-07-01 | Mitsui Toatsu Chemicals, Inc. | Immunostimulatory remedies containing palindromic dna sequences |
| US5616461A (en) | 1992-05-14 | 1997-04-01 | Dana-Farber Cancer Institute | Assay for antiviral activity using complex of herpesvirus origin of replication and cellular protein |
| US5849719A (en) | 1993-08-26 | 1998-12-15 | The Regents Of The University Of California | Method for treating allergic lung disease |
| ATE509102T1 (de) | 1994-07-15 | 2011-05-15 | Univ Iowa Res Found | Immunomodulatorische oligonukleotide |
| US6207646B1 (en) | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US20030050263A1 (en) | 1994-07-15 | 2003-03-13 | The University Of Iowa Research Foundation | Methods and products for treating HIV infection |
| US6239116B1 (en) * | 1994-07-15 | 2001-05-29 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US5874089A (en) | 1995-10-02 | 1999-02-23 | Georgetown University School Of Medicine | Protecting against canine oral papillomavirus (copy) |
| EP0879284B1 (en) | 1996-01-30 | 2009-07-29 | The Regents of The University of California | Gene expression vectors which generate an antigen specific immune response and methods of using the same |
| ES2241042T3 (es) | 1996-10-11 | 2005-10-16 | The Regents Of The University Of California | Conjugados de polinucleotido inmunoestimulador/ molecula inmunomoduladora. |
| WO1998037919A1 (en) | 1997-02-28 | 1998-09-03 | University Of Iowa Research Foundation | USE OF NUCLEIC ACIDS CONTAINING UNMETHYLATED CpG DINUCLEOTIDE IN THE TREATMENT OF LPS-ASSOCIATED DISORDERS |
| US6406705B1 (en) | 1997-03-10 | 2002-06-18 | University Of Iowa Research Foundation | Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant |
| CA2289741A1 (en) | 1997-05-19 | 1998-11-26 | Merck & Co., Inc. | Oligonucleotide adjuvant |
| AU7690898A (en) | 1997-05-20 | 1998-12-11 | Ottawa Civic Hospital Loeb Research Institute | Vectors and methods for immunization or therapeutic protocols |
| DK1009413T3 (da) * | 1997-09-05 | 2007-06-11 | Univ California | Anvendelse af immunstimulerende oligonukleotider til forebyggelse eller behandling af astma |
| GB9727262D0 (en) | 1997-12-24 | 1998-02-25 | Smithkline Beecham Biolog | Vaccine |
| EP1077708A1 (en) | 1998-05-06 | 2001-02-28 | University Of Iowa Research Foundation | Methods for the prevention and treatment of parasitic infections and related diseases using cpg oligonucleotides |
| ATE305507T1 (de) | 1998-05-14 | 2005-10-15 | Coley Pharm Gmbh | Verfahren zur regulierung der hematopoiese mit hilfe von cpg oligonukleotide |
| US6562798B1 (en) | 1998-06-05 | 2003-05-13 | Dynavax Technologies Corp. | Immunostimulatory oligonucleotides with modified bases and methods of use thereof |
| JP2002521489A (ja) | 1998-07-27 | 2002-07-16 | ユニバーシティ オブ アイオワ リサーチ ファウンデーション | ＣｐＧオリゴヌクレオチドの立体異性体および関連する方法 |
| WO2000016804A1 (en) | 1998-09-18 | 2000-03-30 | Dynavax Technologies Corporation | METHODS OF TREATING IgE-ASSOCIATED DISORDERS AND COMPOSITIONS FOR USE THEREIN |
| EP1117433A1 (en) | 1998-10-09 | 2001-07-25 | Dynavax Technologies Corporation | Anti hiv compositions comprising immunostimulatory polynucleotides and hiv antigens |
| WO2000062802A2 (en) | 1999-04-20 | 2000-10-26 | Smithkline Beecham Biologicals Sa | Vaccine comprising rsv antigen and cpg oligonucleotide |
| WO2000067023A1 (en) | 1999-04-29 | 2000-11-09 | Coley Pharmaceutical Gmbh | Screening for immunostimulatory dna functional modifyers |
| US6514948B1 (en) | 1999-07-02 | 2003-02-04 | The Regents Of The University Of California | Method for enhancing an immune response |
| CA2380947C (en) | 1999-08-19 | 2011-11-01 | Dynavax Technologies Corporation | Methods of modulating an immune response using immunostimulatory sequences and compositions for use therein |
| EP1253947A4 (en) | 2000-01-31 | 2005-01-05 | Univ California | IMMUNOMODULATORY POLYNUCLEOTIDES FOR THE TREATMENT OF INFECTION BY AN INTRACELLULAR PATHOGEN |
| AU4175101A (en) | 2000-02-23 | 2001-09-03 | Univ California | Method for treating inflammatory bowel disease and other forms of gastrointestinal inflammation |
| US20020107212A1 (en) | 2000-03-10 | 2002-08-08 | Nest Gary Van | Methods of reducing papillomavirus infection using immunomodulatory polynucleotide sequences |
| US20010046967A1 (en) | 2000-03-10 | 2001-11-29 | Gary Van Nest | Methods of preventing and treating respiratory viral infection using immunomodulatory polynucleotide |
| US7129222B2 (en) | 2000-03-10 | 2006-10-31 | Dynavax Technologies Corporation | Immunomodulatory formulations and methods for use thereof |
| US20020028784A1 (en) | 2000-03-10 | 2002-03-07 | Nest Gary Van | Methods of preventing and treating viral infections using immunomodulatory polynucleotide sequences |
| US20030129251A1 (en) | 2000-03-10 | 2003-07-10 | Gary Van Nest | Biodegradable immunomodulatory formulations and methods for use thereof |
| US7157437B2 (en) | 2000-03-10 | 2007-01-02 | Dynavax Technologies Corporation | Methods of ameliorating symptoms of herpes infection using immunomodulatory polynucleotide sequences |
| US20020098199A1 (en) | 2000-03-10 | 2002-07-25 | Gary Van Nest | Methods of suppressing hepatitis virus infection using immunomodulatory polynucleotide sequences |
| CA2404041A1 (en) | 2000-03-28 | 2001-10-04 | The Regents Of The University Of California | Methods for increasing a cytotoxic t lymphocyte response in vivo |
| WO2001076642A1 (en) | 2000-04-07 | 2001-10-18 | The Regents Of The University Of California | Synergistic improvements to polynucleotide vaccines |
-
2001
- 2001-03-09 US US09/802,518 patent/US7157437B2/en not_active Expired - Fee Related
- 2001-03-12 WO PCT/US2001/007841 patent/WO2001068103A2/en not_active Ceased
- 2001-03-12 DE DE60142776T patent/DE60142776D1/de not_active Expired - Lifetime
- 2001-03-12 CA CA002402312A patent/CA2402312A1/en not_active Abandoned
- 2001-03-12 AT AT01957594T patent/ATE476984T1/de not_active IP Right Cessation
- 2001-03-12 AU AU2001281459A patent/AU2001281459C1/en not_active Ceased
- 2001-03-12 EP EP01957594A patent/EP1265622B1/en not_active Expired - Lifetime
- 2001-03-12 AU AU8145901A patent/AU8145901A/xx active Pending
- 2001-03-12 JP JP2001566667A patent/JP2003526670A/ja active Pending
-
2006
- 2006-11-10 US US11/595,552 patent/US20070060540A1/en not_active Abandoned
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995026204A1 (en) * | 1994-03-25 | 1995-10-05 | Isis Pharmaceuticals, Inc. | Immune stimulation by phosphorothioate oligonucleotide analogs |
| WO1998040100A1 (en) * | 1997-03-10 | 1998-09-17 | Ottawa Civic Loeb Research Institute | USE OF NUCLEIC ACIDS CONTAINING UNMETHYLATED CpG DINUCLEOTIDE AS AN ADJUVANT |
| WO1998055495A2 (en) * | 1997-06-06 | 1998-12-10 | Dynavax Technologies Corporation | Immunostimulatory oligonucleotides, compositions thereof and methods of use thereof |
| WO1999051259A2 (en) * | 1998-04-03 | 1999-10-14 | University Of Iowa Research Foundation | Methods and products for stimulating the immune system using immunotherapeutic oligonucleotides and cytokines |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2001068103A3 (en) | 2002-08-08 |
| AU8145901A (en) | 2001-09-24 |
| EP1265622A2 (en) | 2002-12-18 |
| EP1265622B1 (en) | 2010-08-11 |
| AU2001281459B2 (en) | 2005-09-15 |
| US7157437B2 (en) | 2007-01-02 |
| US20060264391A1 (en) | 2006-11-23 |
| US20070060540A1 (en) | 2007-03-15 |
| AU2001281459C1 (en) | 2006-08-31 |
| WO2001068103A2 (en) | 2001-09-20 |
| CA2402312A1 (en) | 2001-09-20 |
| AU2001281459B8 (en) | 2005-09-29 |
| ATE476984T1 (de) | 2010-08-15 |
| WO2001068103A9 (en) | 2003-03-06 |
| DE60142776D1 (de) | 2010-09-23 |
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