EA008777B1 - Способы и продукты, относящиеся к лечению и предупреждению инфекции вируса гепатита c - Google Patents
Способы и продукты, относящиеся к лечению и предупреждению инфекции вируса гепатита c Download PDFInfo
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- EA008777B1 EA008777B1 EA200500733A EA200500733A EA008777B1 EA 008777 B1 EA008777 B1 EA 008777B1 EA 200500733 A EA200500733 A EA 200500733A EA 200500733 A EA200500733 A EA 200500733A EA 008777 B1 EA008777 B1 EA 008777B1
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- EA
- Eurasian Patent Office
- Prior art keywords
- immunostimulatory
- nucleic acid
- cpc
- cpo
- subject
- Prior art date
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- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/576—Immunoassay; Biospecific binding assay; Materials therefor for hepatitis
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Landscapes
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
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| US42198702P | 2002-10-29 | 2002-10-29 | |
| PCT/IB2003/005520 WO2004039829A2 (en) | 2002-10-29 | 2003-10-29 | Use of cpg oligonucleotides in the treatment of hepatitis c virus infection |
Publications (2)
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| EA200500733A1 EA200500733A1 (ru) | 2005-12-29 |
| EA008777B1 true EA008777B1 (ru) | 2007-08-31 |
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| EA200500733A EA008777B1 (ru) | 2002-10-29 | 2003-10-29 | Способы и продукты, относящиеся к лечению и предупреждению инфекции вируса гепатита c |
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| EP (2) | EP2241325B1 (enExample) |
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| BR (1) | BR0315810A (enExample) |
| CA (1) | CA2503693A1 (enExample) |
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| ES (1) | ES2381224T3 (enExample) |
| MX (1) | MXPA05004588A (enExample) |
| NZ (1) | NZ540098A (enExample) |
| PT (1) | PT2241325E (enExample) |
| SI (1) | SI2241325T1 (enExample) |
| WO (1) | WO2004039829A2 (enExample) |
| ZA (1) | ZA200503511B (enExample) |
Families Citing this family (90)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US6727230B1 (en) * | 1994-03-25 | 2004-04-27 | Coley Pharmaceutical Group, Inc. | Immune stimulation by phosphorothioate oligonucleotide analogs |
| US6429199B1 (en) * | 1994-07-15 | 2002-08-06 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules for activating dendritic cells |
| 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 |
| US6207646B1 (en) | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US7935675B1 (en) * | 1994-07-15 | 2011-05-03 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| EP0855184A1 (en) * | 1997-01-23 | 1998-07-29 | Grayson B. Dr. Lipford | Pharmaceutical composition comprising a polynucleotide and an antigen especially for vaccination |
| US6406705B1 (en) * | 1997-03-10 | 2002-06-18 | University Of Iowa Research Foundation | Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant |
| CA2323929C (en) * | 1998-04-03 | 2004-03-09 | University Of Iowa Research Foundation | Methods and products for stimulating the immune system using immunotherapeutic oligonucleotides and cytokines |
| ATE305507T1 (de) * | 1998-05-14 | 2005-10-15 | Coley Pharm Gmbh | Verfahren zur regulierung der hematopoiese mit hilfe von cpg oligonukleotide |
| IL139813A0 (en) * | 1998-05-22 | 2002-02-10 | Loeb Health Res Inst At The Ot | Methods and products for inducing mucosal immunity |
| US6693086B1 (en) * | 1998-06-25 | 2004-02-17 | National Jewish Medical And Research Center | Systemic immune activation method using nucleic acid-lipid complexes |
| US20030022854A1 (en) | 1998-06-25 | 2003-01-30 | Dow Steven W. | Vaccines using nucleic acid-lipid complexes |
| EP2204186B1 (en) | 1999-02-17 | 2016-04-06 | CSL Limited | Immunogenic complexes and methods relating thereto |
| EP1176966B1 (en) * | 1999-04-12 | 2013-04-03 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES | Oligodeoxynucleotide and its use to induce an immune response |
| 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 |
| US6949520B1 (en) * | 1999-09-27 | 2005-09-27 | Coley Pharmaceutical Group, Inc. | Methods related to immunostimulatory nucleic acid-induced interferon |
| HK1047892B (en) * | 1999-11-19 | 2009-01-09 | Csl Limited | HCV vaccine ingredients |
| US7585847B2 (en) * | 2000-02-03 | 2009-09-08 | Coley Pharmaceutical Group, Inc. | Immunostimulatory nucleic acids for the treatment of asthma and allergy |
| US20040131628A1 (en) * | 2000-03-08 | 2004-07-08 | Bratzler Robert L. | Nucleic acids for the treatment of disorders associated with microorganisms |
| US20030129251A1 (en) * | 2000-03-10 | 2003-07-10 | Gary Van Nest | Biodegradable immunomodulatory formulations and methods for use thereof |
| DE60139689D1 (de) | 2000-06-22 | 2009-10-08 | Univ Iowa Res Found | Kombination von CpG und Antikörpern gegen CD19,CD20,CD22 oder CD40 zur Prävention oder Behandlung von Krebs. |
| ATE510850T1 (de) * | 2000-09-15 | 2011-06-15 | Coley Pharm Gmbh | Verfahren zum hochdurchsatzscreening von auf cpg basierenden immunagonisten und -antagonisten |
| ES2307568T3 (es) * | 2000-12-08 | 2008-12-01 | Coley Pharmaceutical Gmbh | Acidos nucleicos de tipo cpg y metodos de uso de los mismos. |
| AU2002345847B2 (en) * | 2001-06-21 | 2008-05-29 | Dynavax Technologies Corporation | Chimeric immunomodulatory compounds and methods of using the same |
| AU2002331643B2 (en) | 2001-08-17 | 2007-10-11 | Coley Pharmaceutical Gmbh | Combination motif immune stimulatory oligonucleotides with improved activity |
| ES2734652T3 (es) | 2002-04-04 | 2019-12-11 | Zoetis Belgium S A | Oligorribonucleótidos inmunoestimulantes que contienen G y U |
| US7569553B2 (en) | 2002-07-03 | 2009-08-04 | Coley Pharmaceutical Group, Inc. | Nucleic acid compositions for stimulating immune responses |
| EP1551221A4 (en) * | 2002-07-03 | 2007-08-01 | Coley Pharm Group Inc | NUCLEIC ACID COMPOSITIONS FOR STIMULATING IMMUNE RESPONSES |
| US20040053880A1 (en) | 2002-07-03 | 2004-03-18 | Coley Pharmaceutical Group, Inc. | Nucleic acid compositions for stimulating immune responses |
| US7605138B2 (en) | 2002-07-03 | 2009-10-20 | Coley Pharmaceutical Group, Inc. | Nucleic acid compositions for stimulating immune responses |
| US7807803B2 (en) | 2002-07-03 | 2010-10-05 | Coley Pharmaceutical Group, Inc. | Nucleic acid compositions for stimulating immune responses |
| US7576066B2 (en) | 2002-07-03 | 2009-08-18 | Coley Pharmaceutical Group, Inc. | Nucleic acid compositions for stimulating immune responses |
| AR040996A1 (es) * | 2002-08-19 | 2005-04-27 | Coley Pharm Group Inc | Acidos nucleicos inmunoestimuladores |
| CN101948835A (zh) * | 2002-10-29 | 2011-01-19 | 科勒制药集团股份有限公司 | Cpg寡核苷酸在治疗丙型肝炎病毒感染中的应用 |
| JP2006512927A (ja) | 2002-12-11 | 2006-04-20 | コーリー ファーマシューティカル グループ，インコーポレイテッド | ５’ｃｐｇ核酸およびその使用方法 |
| US20040235770A1 (en) * | 2003-04-02 | 2004-11-25 | Coley Pharmaceutical Group, Ltd. | Immunostimulatory nucleic acid oil-in-water formulations and related methods of use |
| MXPA05013922A (es) | 2003-06-20 | 2006-02-24 | Coley Pharm Group Inc | Antagonistas de receptor tipo toll de molecula pequena. |
| US20050013812A1 (en) * | 2003-07-14 | 2005-01-20 | Dow Steven W. | Vaccines using pattern recognition receptor-ligand:lipid complexes |
| CA2536139A1 (en) * | 2003-09-25 | 2005-04-07 | Coley Pharmaceutical Group, Inc. | Nucleic acid-lipophilic conjugates |
| GEP20094767B (en) | 2003-10-30 | 2009-09-10 | Coley Pharm Group Inc | C-class oligonucleotide analogs with enhanced immunostimulatory potency |
| US20050239733A1 (en) * | 2003-10-31 | 2005-10-27 | Coley Pharmaceutical Gmbh | Sequence requirements for inhibitory oligonucleotides |
| US20050100983A1 (en) * | 2003-11-06 | 2005-05-12 | Coley Pharmaceutical Gmbh | Cell-free methods for identifying compounds that affect toll-like receptor 9 (TLR9) signaling |
| TW200533750A (en) * | 2004-02-19 | 2005-10-16 | Coley Pharm Group Inc | Immunostimulatory viral RNA oligonucleotides |
| WO2005111057A2 (en) * | 2004-04-02 | 2005-11-24 | Coley Pharmaceutical Group, Inc. | Immunostimulatory nucleic acids for inducing il-10 responses |
| EP1781325A2 (en) * | 2004-07-18 | 2007-05-09 | CSL Limited | Immuno stimulating complex and oligonucleotide formulations for inducing enhanced interferon-gamma responses |
| MY159370A (en) | 2004-10-20 | 2016-12-30 | Coley Pharm Group Inc | Semi-soft-class immunostimulatory oligonucleotides |
| KR20070087624A (ko) * | 2004-12-23 | 2007-08-28 | 노파르티스 아게 | Ｈｃｖ 치료용 조성물 |
| CN101160401A (zh) * | 2005-02-24 | 2008-04-09 | 科勒制药集团公司 | 免疫刺激寡核苷酸 |
| US20060213010A1 (en) * | 2005-03-22 | 2006-09-28 | Davis David T | Mattress sled |
| CA2603976A1 (en) * | 2005-04-08 | 2006-10-19 | Coley Pharmaceutical Group, Inc. | Methods for treating infectious disease exacerbated asthma |
| US20060241076A1 (en) * | 2005-04-26 | 2006-10-26 | Coley Pharmaceutical Gmbh | Modified oligoribonucleotide analogs with enhanced immunostimulatory activity |
| WO2007011777A2 (en) * | 2005-07-18 | 2007-01-25 | Novartis Ag | Small animal model for hcv replication |
| JP2010503608A (ja) * | 2005-09-16 | 2010-02-04 | コーリー ファーマシューティカル ゲーエムベーハー | ホスホジエステルバックボーンを有する免疫刺激性一本鎖リボ核酸 |
| KR20080047463A (ko) * | 2005-09-16 | 2008-05-28 | 콜리 파마슈티칼 게엠베하 | 뉴클레오티드 변형에 의한 짧은 간섭 리보핵산(ｓｉｒｎａ)의 면역자극 특성의 조절 |
| BRPI0622298A8 (pt) | 2005-11-25 | 2016-04-05 | Coley Pharm Gmbh | Oligorribonucleotídeo para estimular a produção de uma citocina pró-inflamatória, uso do mesmo e composição contendo tal oligorribonucleotídeo |
| CA2642152C (en) * | 2006-02-15 | 2016-11-01 | Coley Pharmaceutical Gmbh | Compositions and methods for oligonucleotide formulations |
| CN101460620B (zh) * | 2006-05-31 | 2012-02-15 | 东丽株式会社 | 免疫刺激寡核苷酸及其药物用途 |
| NZ575437A (en) | 2006-09-27 | 2012-02-24 | Coley Pharm Gmbh | Cpg oligonucleotide analogs containing hydrophobic t analogs with enhanced immunostimulatory activity |
| WO2008057529A2 (en) * | 2006-11-06 | 2008-05-15 | Coley Pharmaceutical Group, Inc. | Peptide-based vaccine compositions to endogenous cholesteryl ester transfer protein (cetp) |
| CA2696460A1 (en) | 2007-08-13 | 2009-02-19 | Pfizer Inc. | Combination motif immune stimulatory oligonucleotides with improved activity |
| US20100040576A1 (en) * | 2007-12-18 | 2010-02-18 | The Texas A&M University System | Modified Oligonucleotides For The Treatment Of Hepatitis C Infection |
| CA2744987C (en) | 2008-12-02 | 2018-01-16 | Chiralgen, Ltd. | Method for the synthesis of phosphorus atom modified nucleic acids |
| EP2376107B1 (en) | 2008-12-09 | 2014-05-21 | Coley Pharmaceutical Group, Inc. | Immunostimulatory oligonucleotides |
| US8552165B2 (en) * | 2008-12-09 | 2013-10-08 | Heather Davis | Immunostimulatory oligonucleotides |
| WO2010084100A1 (en) | 2009-01-20 | 2010-07-29 | Transgene Sa | Soluble icam-1 as biomarker for prediction of therapeutic response |
| ES2555858T3 (es) | 2009-03-24 | 2016-01-11 | Transgene Sa | Biomarcador para el control de pacientes |
| CN103800906B (zh) | 2009-03-25 | 2017-09-22 | 德克萨斯大学系统董事会 | 用于刺激哺乳动物对病原体的先天免疫抵抗力的组合物 |
| HRP20140262T1 (hr) | 2009-04-17 | 2014-04-25 | Transgene Sa | Biomarker za praä†enje pacijenata |
| CA2767253A1 (en) | 2009-07-06 | 2011-01-13 | Ontorii, Inc. | Novel nucleic acid prodrugs and methods of use thereof |
| WO2012039448A1 (ja) | 2010-09-24 | 2012-03-29 | 株式会社キラルジェン | 不斉補助基 |
| WO2013012758A1 (en) | 2011-07-19 | 2013-01-24 | Ontorii, Inc. | Methods for the synthesis of functionalized nucleic acids |
| CN104684923B (zh) * | 2012-07-13 | 2018-09-28 | 株式会社新日本科学 | 手性核酸佐剂 |
| JP6268157B2 (ja) | 2012-07-13 | 2018-01-24 | 株式会社Ｗａｖｅ Ｌｉｆｅ Ｓｃｉｅｎｃｅｓ Ｊａｐａｎ | 不斉補助基 |
| KR102712879B1 (ko) | 2012-07-13 | 2024-10-04 | 웨이브 라이프 사이언시스 리미티드 | 키랄 제어 |
| EP2976109B1 (en) | 2013-03-21 | 2018-07-25 | Genisphere, LLC | Cellular delivery of dna intercalating agents |
| WO2015013673A1 (en) | 2013-07-25 | 2015-01-29 | Aurasense Therapeutics, Llc | Spherical nucleic acid-based constructs as immunostimulatory agents for prophylactic and therapeutic use |
| JPWO2015108048A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 抗腫瘍作用を有するキラル核酸アジュバンド及び抗腫瘍剤 |
| JPWO2015108046A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 抗アレルギー作用を有するキラル核酸アジュバンド及び抗アレルギー剤 |
| US10144933B2 (en) | 2014-01-15 | 2018-12-04 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having immunity induction activity, and immunity induction activator |
| EP4137572A1 (en) | 2014-01-16 | 2023-02-22 | Wave Life Sciences Ltd. | Chiral design |
| ES2725948T3 (es) | 2014-06-04 | 2019-09-30 | Exicure Inc | Suministro multivalente de inmunomoduladores mediante ácidos nucleicos esféricos liposomales para aplicaciones profilácticas o terapéuticas |
| WO2016044839A2 (en) | 2014-09-19 | 2016-03-24 | The Board Of Regents Of The University Of Texas System | Compositions and methods for treating viral infections through stimulated innate immunity in combination with antiviral compounds |
| CA2968531A1 (en) | 2014-11-21 | 2016-05-26 | Northwestern University | The sequence-specific cellular uptake of spherical nucleic acid nanoparticle conjugates |
| EP3416691A4 (en) | 2016-02-19 | 2020-02-26 | Genisphere, LLC | SUPPORTS OF NUCLEIC ACIDS AND THEIR THERAPEUTIC METHODS OF USE |
| US12338435B2 (en) | 2016-02-19 | 2025-06-24 | Code Biotherapeutics, Inc. | Nucleic acid carriers and therapeutic methods of use |
| WO2018039629A2 (en) | 2016-08-25 | 2018-03-01 | Northwestern University | Micellar spherical nucleic acids from thermoresponsive, traceless templates |
| US11696954B2 (en) | 2017-04-28 | 2023-07-11 | Exicure Operating Company | Synthesis of spherical nucleic acids using lipophilic moieties |
| CN110869048A (zh) * | 2017-05-03 | 2020-03-06 | 新加坡科技研究局 | 刺激树突细胞(DC)前体细胞群“pre-DC”的方法及其用途 |
| CN109528638B (zh) * | 2018-12-20 | 2021-07-06 | 江西润泽药业有限公司 | 利巴韦林衍生物制剂及其制备方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001022990A2 (en) * | 1999-09-27 | 2001-04-05 | Coley Pharmaceutical Group, Inc. | Methods related to immunostimulatory nucleic acid-induced interferon |
| WO2003002065A2 (en) * | 2001-06-29 | 2003-01-09 | Chiron Corporation | Hcv e1e2 vaccine compositions |
Family Cites Families (232)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3854480A (en) | 1969-04-01 | 1974-12-17 | Alza Corp | Drug-delivery system |
| US4469863A (en) | 1980-11-12 | 1984-09-04 | Ts O Paul O P | Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof |
| US4675189A (en) | 1980-11-18 | 1987-06-23 | Syntex (U.S.A.) Inc. | Microencapsulation of water soluble active polypeptides |
| JP2547714B2 (ja) | 1981-10-23 | 1996-10-23 | モルキユラ− バイオシステムズ インコ−ポレテツド | オリゴヌクレオチド治療剤及びその製法 |
| US5023243A (en) | 1981-10-23 | 1991-06-11 | Molecular Biosystems, Inc. | Oligonucleotide therapeutic agent and method of making same |
| US4452775A (en) | 1982-12-03 | 1984-06-05 | Syntex (U.S.A.) Inc. | Cholesterol matrix delivery system for sustained release of macromolecules |
| US4806463A (en) * | 1986-05-23 | 1989-02-21 | Worcester Foundation For Experimental Biology | Inhibition of HTLV-III by exogenous oligonucleotides |
| US5565354A (en) | 1986-09-05 | 1996-10-15 | Sandoz Ltd. | Production of human monoclonal antibodies specific for hepatitis B surface antigen |
| US5075109A (en) | 1986-10-24 | 1991-12-24 | Southern Research Institute | Method of potentiating an immune response |
| US5264423A (en) | 1987-03-25 | 1993-11-23 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
| US5276019A (en) * | 1987-03-25 | 1994-01-04 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
| CA1339596C (en) | 1987-08-07 | 1997-12-23 | New England Medical Center Hospitals, Inc. | Viral expression inhibitors |
| US5004810A (en) * | 1988-09-30 | 1991-04-02 | Schering Corporation | Antiviral oligomers |
| US5133974A (en) | 1989-05-05 | 1992-07-28 | Kv Pharmaceutical Company | Extended release pharmaceutical formulations |
| US5177198A (en) | 1989-11-30 | 1993-01-05 | University Of N.C. At Chapel Hill | Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates |
| US5457189A (en) | 1989-12-04 | 1995-10-10 | Isis Pharmaceuticals | Antisense oligonucleotide inhibition of papillomavirus |
| US5248670A (en) | 1990-02-26 | 1993-09-28 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotides for inhibiting herpesviruses |
| US5514577A (en) | 1990-02-26 | 1996-05-07 | Isis Pharmaceuticals, Inc. | Oligonucleotide therapies for modulating the effects of herpes viruses |
| US5166195A (en) | 1990-05-11 | 1992-11-24 | Isis Pharmaceuticals, Inc. | Antisense inhibitors of the human immunodeficiency virus phosphorothioate oligonucleotides |
| EP0468520A3 (en) | 1990-07-27 | 1992-07-01 | Mitsui Toatsu Chemicals, Inc. | Immunostimulatory remedies containing palindromic dna sequences |
| EP0544713B1 (en) | 1990-08-16 | 1997-07-02 | Isis Pharmaceuticals, Inc. | Oligonucleotides for modulating the effects of cytomegalovirus infections |
| US5576302A (en) | 1991-10-15 | 1996-11-19 | Isis Pharmaceuticals, Inc. | Oligonucleotides for modulating hepatitis C virus having phosphorothioate linkages of high chiral purity |
| US5407686A (en) | 1991-11-27 | 1995-04-18 | Sidmak Laboratories, Inc. | Sustained release composition for oral administration of active ingredient |
| ATE219522T1 (de) | 1992-02-04 | 2002-07-15 | Chiron Corp | Hepatistherapeutikum |
| US6498147B2 (en) | 1992-05-22 | 2002-12-24 | The Scripps Research Institute | Suppression of nuclear factor-κb dependent processes using oligonucleotides |
| US6107062A (en) | 1992-07-30 | 2000-08-22 | Inpax, Inc. | Antisense viruses and antisense-ribozyme viruses |
| DK0664833T3 (da) | 1992-10-05 | 1997-04-14 | Hybridon Inc | Terapeutisk anti-HIV oligonukletid og lægemiddel |
| US5593972A (en) | 1993-01-26 | 1997-01-14 | The Wistar Institute | Genetic immunization |
| DE69434469T2 (de) | 1993-01-26 | 2006-06-14 | Univ Pennsylvania | Zusammensetzungen und verfahren zur verabreichung von genetischem material |
| US5567604A (en) * | 1993-04-23 | 1996-10-22 | Aronex Pharmaceuticals, Inc. | Anti-viral guanosine-rich oligonucleotides |
| EP0705335A1 (en) * | 1993-06-23 | 1996-04-10 | Genesys Pharma Inc. | Antisense oligonucleotides and therapeutic use thereof in human immunodeficiency virus infection |
| DE4321946A1 (de) | 1993-07-01 | 1995-01-12 | Hoechst Ag | Methylphosphonsäureester, Verfahren zu deren Herstellung und deren Verwendung |
| JPH09501562A (ja) | 1993-07-19 | 1997-02-18 | ジェン−プローブ・インコーポレイテッド | ヒト・免疫不全ウイルスに対する活性を有するオリゴヌクレオチド |
| US20030109469A1 (en) | 1993-08-26 | 2003-06-12 | Carson Dennis A. | Recombinant gene expression vectors and methods for use of same to enhance the immune response of a host to an antigen |
| US5859231A (en) | 1993-09-03 | 1999-01-12 | Duke University | Synthesis of oligonucleotides with boranophosphonate linkages |
| US6133244A (en) | 1993-10-22 | 2000-10-17 | Institut Pasteur | Method for immunization against hepatitis B |
| FR2711670B1 (fr) * | 1993-10-22 | 1996-01-12 | Pasteur Institut | Vecteur nucléotidique, composition le contenant et vaccin pour l'immunisation à l'encontre d'une hépatite. |
| US5712384A (en) | 1994-01-05 | 1998-01-27 | Gene Shears Pty Ltd. | Ribozymes targeting retroviral packaging sequence expression constructs and recombinant retroviruses containing such constructs |
| US5728518A (en) * | 1994-01-12 | 1998-03-17 | The Immune Response Corporation | Antiviral poly-and oligonucleotides |
| US6727230B1 (en) * | 1994-03-25 | 2004-04-27 | Coley Pharmaceutical Group, Inc. | Immune stimulation by phosphorothioate oligonucleotide analogs |
| WO1995026204A1 (en) | 1994-03-25 | 1995-10-05 | Isis Pharmaceuticals, Inc. | Immune stimulation by phosphorothioate oligonucleotide analogs |
| US5658738A (en) | 1994-05-31 | 1997-08-19 | Becton Dickinson And Company | Bi-directional oligonucleotides that bind thrombin |
| US6429199B1 (en) | 1994-07-15 | 2002-08-06 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules for activating dendritic cells |
| US20030050263A1 (en) * | 1994-07-15 | 2003-03-13 | The University Of Iowa Research Foundation | Methods and products for treating HIV infection |
| US7935675B1 (en) | 1994-07-15 | 2011-05-03 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| CA2560114A1 (en) | 1994-07-15 | 1996-02-01 | The University Of Iowa Research Foundation | Immunomodulatory oligonucleotides |
| US6239116B1 (en) | 1994-07-15 | 2001-05-29 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US6207646B1 (en) * | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US20030026782A1 (en) | 1995-02-07 | 2003-02-06 | Arthur M. Krieg | Immunomodulatory oligonucleotides |
| US5646262A (en) * | 1994-07-28 | 1997-07-08 | Georgetown University | Antisense oligonucleotides against hepatitis B viral replication |
| US5858987A (en) * | 1995-05-05 | 1999-01-12 | Mitotix, Inc. | E6AP antisense constructs and methods of use |
| US5856459A (en) * | 1995-06-06 | 1999-01-05 | Hybridon, Inc. | Oligonucleotides specific for hepatitis B virus |
| US5985662A (en) | 1995-07-13 | 1999-11-16 | Isis Pharmaceuticals Inc. | Antisense inhibition of hepatitis B virus replication |
| US6160109A (en) | 1995-10-20 | 2000-12-12 | Isis Pharmaceuticals, Inc. | Preparation of phosphorothioate and boranophosphate oligomers |
| US5736152A (en) | 1995-10-27 | 1998-04-07 | Atrix Laboratories, Inc. | Non-polymeric sustained release delivery system |
| US5780448A (en) | 1995-11-07 | 1998-07-14 | Ottawa Civic Hospital Loeb Research | DNA-based vaccination of fish |
| CA2244946C (en) | 1996-01-30 | 2010-04-13 | The Regents Of The University Of California | Gene expression vectors which generate an antigen specific immune response and methods of using the same |
| US5843770A (en) | 1996-03-11 | 1998-12-01 | The Immune Response Corporation | Antisense constructs directed against viral post-transcriptional regulatory sequences |
| US6030955A (en) * | 1996-03-21 | 2000-02-29 | The Trustees Of Columbia University In The City Of New York And Imclone Systems, Inc. | Methods of affecting intracellular phosphorylation of tyrosine using phosphorothioate oligonucleotides, and antiangiogenic and antiproliferative uses thereof |
| US6136316A (en) | 1996-04-17 | 2000-10-24 | Dabur Research Foundation | Hepatoprotective compositions and composition for treatment of conditions related to hepatitis B and E infection |
| US5854418A (en) | 1996-07-25 | 1998-12-29 | The Trustees Of Columbia University In The City Of New York | Kaposi's sarcoma-associated herpesvirus (KSHV) viral macrophage inflammatory protein-1α II (vMIP-1α II) and uses thereof |
| US5922757A (en) | 1996-09-30 | 1999-07-13 | The Regents Of The University Of California | Treatment and prevention of hepatic disorders |
| US6610661B1 (en) | 1996-10-11 | 2003-08-26 | The Regents Of The University Of California | Immunostimulatory polynucleotide/immunomodulatory molecule conjugates |
| ES2195970T3 (es) | 1996-10-16 | 2003-12-16 | Ribapharm Inc | L-ribavirina y usos de la misma. |
| EP0855184A1 (en) * | 1997-01-23 | 1998-07-29 | Grayson B. Dr. Lipford | Pharmaceutical composition comprising a polynucleotide and an antigen especially for vaccination |
| EP1039935A4 (en) | 1997-02-28 | 2005-04-27 | Univ Iowa Res Found | 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 |
| US6426334B1 (en) | 1997-04-30 | 2002-07-30 | Hybridon, Inc. | Oligonucleotide mediated specific cytokine induction and reduction of tumor growth in a mammal |
| US6835395B1 (en) | 1997-05-14 | 2004-12-28 | The University Of British Columbia | Composition containing small multilamellar oligodeoxynucleotide-containing lipid vesicles |
| ATE370740T1 (de) | 1997-05-20 | 2007-09-15 | Ottawa Health Research Inst | Verfahren zur herstellung von nukleinsäurekonstrukten |
| US6589940B1 (en) | 1997-06-06 | 2003-07-08 | Dynavax Technologies Corporation | Immunostimulatory oligonucleotides, compositions thereof and methods of use thereof |
| US20040006034A1 (en) * | 1998-06-05 | 2004-01-08 | Eyal Raz | Immunostimulatory oligonucleotides, compositions thereof and methods of use thereof |
| EP2085090A3 (en) | 1997-06-06 | 2012-05-02 | The Regents of the University of California | Inhibitors of DNA immunostimulatory sequence activity |
| WO1999001154A1 (en) * | 1997-07-03 | 1999-01-14 | University Of Iowa Research Foundation | Method for inhibiting immunostimulatory dna associated responses |
| AU8771398A (en) | 1997-08-19 | 1999-03-08 | Hybridon, Inc. | Novel hiv-specific synthetic oligonucleotides and methods of their use |
| US7393630B2 (en) * | 1997-12-16 | 2008-07-01 | Novartis Vaccines And Diagnostics, Inc. | Use of microparticles combined with submicron oil-in-water emulsions |
| US20050031638A1 (en) * | 1997-12-24 | 2005-02-10 | Smithkline Beecham Biologicals S.A. | Vaccine |
| GB9727262D0 (en) | 1997-12-24 | 1998-02-25 | Smithkline Beecham Biolog | Vaccine |
| CA2323929C (en) * | 1998-04-03 | 2004-03-09 | University Of Iowa Research Foundation | Methods and products for stimulating the immune system using immunotherapeutic oligonucleotides and cytokines |
| WO1999052549A1 (en) | 1998-04-09 | 1999-10-21 | Smithkline Beecham Biologicals S.A. | Adjuvant compositions |
| WO1999056755A1 (en) | 1998-05-06 | 1999-11-11 | 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 |
| IL139813A0 (en) | 1998-05-22 | 2002-02-10 | Loeb Health Res Inst At The Ot | Methods and products for inducing mucosal immunity |
| US6562798B1 (en) | 1998-06-05 | 2003-05-13 | Dynavax Technologies Corp. | Immunostimulatory oligonucleotides with modified bases and methods of use thereof |
| US20040247662A1 (en) | 1998-06-25 | 2004-12-09 | Dow Steven W. | Systemic immune activation method using nucleic acid-lipid complexes |
| WO2000006588A1 (en) | 1998-07-27 | 2000-02-10 | University Of Iowa Research Foundation | STEREOISOMERS OF CpG OLIGONUCLEOTIDES AND RELATED METHODS |
| AU777225B2 (en) | 1998-09-03 | 2004-10-07 | Coley Pharmaceutical Gmbh | G-motif oligonucleotides and uses thereof |
| EP1109580A4 (en) | 1998-09-04 | 2004-05-26 | Viropharma Inc | METHOD FOR TREATING OR PREVENTING VIRAL INFECTIONS AND RELATED DISEASES |
| US20020065236A1 (en) | 1998-09-09 | 2002-05-30 | Yew Nelson S. | CpG reduced plasmids and viral vectors |
| FR2783170B1 (fr) | 1998-09-11 | 2004-07-16 | Pasteur Merieux Serums Vacc | Emulsion immunostimulante |
| US6228642B1 (en) * | 1998-10-05 | 2001-05-08 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of tumor necrosis factor-(α) (TNF-α) expression |
| JP2002526425A (ja) | 1998-10-05 | 2002-08-20 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 粘膜免疫を刺激するための方法およびアジュバント |
| AU6425999A (en) | 1998-10-09 | 2000-05-01 | Dynavax Technologies Corporation | Anti hiv compositions comprising immunostimulatory polynucleotides and hiv antigens |
| CA2359110A1 (en) | 1999-01-12 | 2000-07-20 | Ronald James Boon | Combination of hepatitis b vaccine with antiviral agents |
| US6207819B1 (en) | 1999-02-12 | 2001-03-27 | Isis Pharmaceuticals, Inc. | Compounds, processes and intermediates for synthesis of mixed backbone oligomeric compounds |
| WO2000054803A2 (en) | 1999-03-16 | 2000-09-21 | Panacea Pharmaceuticals, Llc | Immunostimulatory nucleic acids and antigens |
| FR2790955B1 (fr) | 1999-03-19 | 2003-01-17 | Assist Publ Hopitaux De Paris | Utilisation d'oligonucleotides stabilises comme principe actif antitumoral |
| EP1176966B1 (en) | 1999-04-12 | 2013-04-03 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES | Oligodeoxynucleotide and its use to induce an immune response |
| 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 |
| WO2000062787A1 (en) | 1999-04-15 | 2000-10-26 | The Regents Of The University Of California | Methods and compositions for use in potentiating antigen presentation by antigen presenting cells |
| US6558670B1 (en) | 1999-04-19 | 2003-05-06 | Smithkline Beechman Biologicals S.A. | Vaccine adjuvants |
| AU4978100A (en) | 1999-04-29 | 2000-11-17 | Coley Pharmaceutical Gmbh | Screening for immunostimulatory dna functional modifyers |
| US6737066B1 (en) | 1999-05-06 | 2004-05-18 | The Immune Response Corporation | HIV immunogenic compositions and methods |
| WO2000067787A2 (en) | 1999-05-06 | 2000-11-16 | The Immune Response Corporation | Hiv immunogenic compositions and methods |
| AU6051800A (en) | 1999-06-16 | 2001-01-02 | University Of Iowa Research Foundation, The | Antagonism of immunostimulatory cpg-oligonucleotides by 4-aminoquinolines and other weak bases |
| CA2376992A1 (en) | 1999-06-29 | 2001-01-04 | Smithkline Beecham Biologicals S.A. | Use of cpg as an adjuvant for hiv vaccine |
| US6514948B1 (en) * | 1999-07-02 | 2003-02-04 | The Regents Of The University Of California | Method for enhancing an immune response |
| DE19935756A1 (de) | 1999-07-27 | 2001-02-08 | Mologen Forschungs Entwicklung | Kovalent geschlossenes Nukleinsäuremolekül zur Immunstimulation |
| DE60041335D1 (de) | 1999-08-19 | 2009-02-26 | Dynavax Tech Corp | Methode zur modulierung eines immunantwortes mit immunstimulierenden sequencen und zusammensetzungen dafür |
| GB9921146D0 (en) | 1999-09-07 | 1999-11-10 | Smithkline Beecham Biolog | Novel composition |
| GB9921147D0 (en) | 1999-09-07 | 1999-11-10 | Smithkline Beecham Biolog | Novel composition |
| UA77152C2 (en) * | 1999-09-25 | 2006-11-15 | Method for stimulation of immune response using nucleic acid-containing immunostimulating compositions, method for treatment of cancer and method for treatment or prophylaxis of allergy or asthma | |
| US6949520B1 (en) | 1999-09-27 | 2005-09-27 | Coley Pharmaceutical Group, Inc. | Methods related to immunostimulatory nucleic acid-induced interferon |
| JP2003512305A (ja) | 1999-09-30 | 2003-04-02 | ユニバーシティ オブ ワシントン | 免疫学的に重要な単純疱疹ウイルス抗原 |
| 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 |
| AU2593701A (en) | 1999-12-21 | 2001-07-03 | Regents Of The University Of California, The | Method for preventing an anaphylactic reaction |
| KR100359753B1 (ko) * | 1999-12-21 | 2002-11-09 | 주식회사 제넥신 | 면역조절능력 및 안전성이 증가되고 ｄＧ 연속서열이결합된 포스포다이에스터 ＣｐＧ올리고데옥시뉴클레오티드 변형체 |
| US20010044416A1 (en) | 2000-01-20 | 2001-11-22 | Mccluskie Michael J. | Immunostimulatory nucleic acids for inducing a Th2 immune response |
| KR20070073987A (ko) | 2000-01-31 | 2007-07-10 | 글락소스미스클라인 바이오로지칼즈 에스.에이. | Ｈｉｖ에 대한 예방 또는 치료용 면역화를 위한 백신 |
| WO2001055341A2 (en) | 2000-01-31 | 2001-08-02 | The Regents Of The University Of California | Immunomodulatory polynucleotides in treatment of an infection by an intracellular pathogen |
| US7585847B2 (en) | 2000-02-03 | 2009-09-08 | Coley Pharmaceutical Group, Inc. | Immunostimulatory nucleic acids for the treatment of asthma and allergy |
| AU2001241751B2 (en) | 2000-02-23 | 2005-09-01 | Tel Aviv Sourasky Medical Center | Method for treating inflammatory bowel disease and other forms of gastrointestinal inflammation |
| US20020156033A1 (en) | 2000-03-03 | 2002-10-24 | Bratzler Robert L. | Immunostimulatory nucleic acids and cancer medicament combination therapy for the treatment of cancer |
| US20040131628A1 (en) | 2000-03-08 | 2004-07-08 | Bratzler Robert L. | Nucleic acids for the treatment of disorders associated with microorganisms |
| 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 |
| 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 |
| US20020107212A1 (en) | 2000-03-10 | 2002-08-08 | Nest Gary Van | Methods of reducing papillomavirus 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 |
| WO2001072123A1 (en) | 2000-03-28 | 2001-10-04 | The Regents Of The University Of California | Methods for increasing a cytotoxic t lymphocyte response in vivo |
| US6339630B1 (en) * | 2000-05-18 | 2002-01-15 | The United States Of America As Represented By The United States Department Of Energy | Sealed drive screw operator |
| DE60139689D1 (de) * | 2000-06-22 | 2009-10-08 | Univ Iowa Res Found | Kombination von CpG und Antikörpern gegen CD19,CD20,CD22 oder CD40 zur Prävention oder Behandlung von Krebs. |
| US20020165178A1 (en) | 2000-06-28 | 2002-11-07 | Christian Schetter | Immunostimulatory nucleic acids for the treatment of anemia, thrombocytopenia, and neutropenia |
| US20020198165A1 (en) | 2000-08-01 | 2002-12-26 | Bratzler Robert L. | Nucleic acids for the prevention and treatment of gastric ulcers |
| JP2005512499A (ja) * | 2000-09-01 | 2005-05-12 | エピゲノミクス アーゲー | 進行中の疾病または特定の疾病の発病素質の診断 |
| US20020091097A1 (en) | 2000-09-07 | 2002-07-11 | Bratzler Robert L. | Nucleic acids for the prevention and treatment of sexually transmitted diseases |
| ATE510850T1 (de) | 2000-09-15 | 2011-06-15 | Coley Pharm Gmbh | Verfahren zum hochdurchsatzscreening von auf cpg basierenden immunagonisten und -antagonisten |
| FR2814958B1 (fr) | 2000-10-06 | 2003-03-07 | Aventis Pasteur | Composition vaccinale |
| GB0025577D0 (en) * | 2000-10-18 | 2000-12-06 | Smithkline Beecham Biolog | Vaccine |
| ES2307568T3 (es) | 2000-12-08 | 2008-12-01 | Coley Pharmaceutical Gmbh | Acidos nucleicos de tipo cpg y metodos de uso de los mismos. |
| US20030055014A1 (en) * | 2000-12-14 | 2003-03-20 | Bratzler Robert L. | Inhibition of angiogenesis by nucleic acids |
| US20030050268A1 (en) * | 2001-03-29 | 2003-03-13 | Krieg Arthur M. | Immunostimulatory nucleic acid for treatment of non-allergic inflammatory diseases |
| CN1220212C (zh) * | 2001-05-30 | 2005-09-21 | 索尼公司 | 盒式磁带的卷轴锁定机构及盒式磁带 |
| AU2002345847B2 (en) * | 2001-06-21 | 2008-05-29 | Dynavax Technologies Corporation | Chimeric immunomodulatory compounds and methods of using the same |
| US7666674B2 (en) * | 2001-07-27 | 2010-02-23 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Use of sterically stabilized cationic liposomes to efficiently deliver CPG oligonucleotides in vivo |
| AU2002318944A1 (en) | 2001-08-01 | 2003-02-17 | Coley Pharmaceutical Gmbh | Methods and compositions relating to plasmacytoid dendritic cells |
| JP2005518343A (ja) | 2001-08-03 | 2005-06-23 | メダレックス， インク． | 新規なｐｇｃ−１イソフォームおよびその使用媒介型免疫治療を向上させるためのその使用 |
| AU2002331643B2 (en) | 2001-08-17 | 2007-10-11 | Coley Pharmaceutical Gmbh | Combination motif immune stimulatory oligonucleotides with improved activity |
| JP2005501550A (ja) | 2001-08-30 | 2005-01-20 | スリーエム イノベイティブ プロパティズ カンパニー | 免疫反応調整剤分子を用いた形質細胞様樹状細胞を成熟させる方法 |
| EP2196217A1 (en) | 2001-09-14 | 2010-06-16 | Cytos Biotechnology AG | Packaging of immunostimulatory substances into virus-like particles: method of preparation and use |
| WO2003027313A2 (en) * | 2001-09-24 | 2003-04-03 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | SUPPRESSORS OF CpG OLIGONUCLEOTIDES AND METHODS OF USE |
| EP1451581A4 (en) | 2001-10-05 | 2006-01-11 | Coley Pharm Gmbh | AGONISTS AND ANTAGONISTS OF THE SIGNALING OF THE GREAT-SIMILAR RECEPTOR 3 |
| AU2002346960A1 (en) | 2001-10-06 | 2003-04-22 | Merial Limited | Methods and compositions for promoting growth and innate immunity in young animals |
| JP2005519990A (ja) | 2001-10-12 | 2005-07-07 | 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 | イミダゾキノリン化合物を用いて免疫応答を増強するための方法および産物 |
| WO2003035836A2 (en) | 2001-10-24 | 2003-05-01 | Hybridon Inc. | Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5' ends |
| AU2002343728A1 (en) | 2001-11-16 | 2003-06-10 | 3M Innovative Properties Company | Methods and compositions related to irm compounds and toll-like receptor pathways |
| US7615227B2 (en) * | 2001-12-20 | 2009-11-10 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Use of CpG oligodeoxynucleotides to induce angiogenesis |
| ES2734652T3 (es) | 2002-04-04 | 2019-12-11 | Zoetis Belgium S A | Oligorribonucleótidos inmunoestimulantes que contienen G y U |
| JP2005530761A (ja) | 2002-05-10 | 2005-10-13 | イネックス ファーマシューティカルズ コーポレイション | 癌ワクチン及びその使用方法 |
| EP1507850A1 (en) | 2002-05-28 | 2005-02-23 | MERCK PATENT GmbH | A method for generating antigen-presenting cells |
| AU2003243409A1 (en) * | 2002-06-05 | 2003-12-22 | Coley Pharmaceutical Group, Inc. | Method for treating autoimmune or inflammatory diseases with combinations of inhibitory oligonucleotides and small molecule antagonists of immunostimulatory cpg nucleic acids |
| US7569553B2 (en) * | 2002-07-03 | 2009-08-04 | Coley Pharmaceutical Group, Inc. | Nucleic acid compositions for stimulating immune responses |
| US7576066B2 (en) | 2002-07-03 | 2009-08-18 | Coley Pharmaceutical Group, Inc. | Nucleic acid compositions for stimulating immune responses |
| US20040053880A1 (en) * | 2002-07-03 | 2004-03-18 | Coley Pharmaceutical Group, Inc. | Nucleic acid compositions for stimulating immune responses |
| US7807803B2 (en) | 2002-07-03 | 2010-10-05 | Coley Pharmaceutical Group, Inc. | Nucleic acid compositions for stimulating immune responses |
| US7605138B2 (en) | 2002-07-03 | 2009-10-20 | Coley Pharmaceutical Group, Inc. | Nucleic acid compositions for stimulating immune responses |
| AU2003255969A1 (en) | 2002-07-17 | 2004-02-02 | Coley Pharmaceutical Gmbh | Use of cpg nucleic acids in prion-disease |
| CN1468957A (zh) | 2002-07-19 | 2004-01-21 | 中国人民解放军第二军医大学 | 一种用作人用治疗性疫苗佐剂的质粒 |
| AR040996A1 (es) * | 2002-08-19 | 2005-04-27 | Coley Pharm Group Inc | Acidos nucleicos inmunoestimuladores |
| US8263091B2 (en) | 2002-09-18 | 2012-09-11 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method of treating and preventing infections in immunocompromised subjects with immunostimulatory CpG oligonucleotides |
| WO2004026888A2 (en) | 2002-09-19 | 2004-04-01 | Coley Pharmaceutical Gmbh | Toll-like receptor 9 (tlr9) from various mammalian species |
| US20040132063A1 (en) | 2002-09-25 | 2004-07-08 | Gierse James K. | Antisense modulation of microsomal prostaglandin E2 synthase expression |
| GB0222953D0 (en) | 2002-10-03 | 2002-11-13 | Glaxo Group Ltd | Novel Compounds |
| US8043622B2 (en) * | 2002-10-08 | 2011-10-25 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method of treating inflammatory lung disease with suppressors of CpG oligonucleotides |
| CN101948835A (zh) * | 2002-10-29 | 2011-01-19 | 科勒制药集团股份有限公司 | Cpg寡核苷酸在治疗丙型肝炎病毒感染中的应用 |
| CA2504493C (en) * | 2002-11-01 | 2015-12-29 | 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 |
| JP2006512927A (ja) | 2002-12-11 | 2006-04-20 | コーリー ファーマシューティカル グループ，インコーポレイテッド | ５’ｃｐｇ核酸およびその使用方法 |
| KR100525321B1 (ko) | 2002-12-13 | 2005-11-02 | 안웅식 | 파필로마바이러스 항원 단백질 및ＣｐＧ-올리고데옥시뉴클레오타이드를 포함하는파필로마바이러스 유발 질환의 예방 또는 치료용 약제학적조성물 |
| US8158768B2 (en) * | 2002-12-23 | 2012-04-17 | Dynavax Technologies Corporation | Immunostimulatory sequence oligonucleotides and methods of using the same |
| EP1625140A4 (en) | 2002-12-23 | 2008-06-18 | Dynavax Tech Corp | BRANCHED IMMUNOMODULAR COMPOUNDS AND METHOD OF USE THEREOF |
| US20040191833A1 (en) | 2003-03-25 | 2004-09-30 | 3M Innovative Properties Company | Selective activation of cellular activities mediated through a common toll-like receptor |
| CN100560719C (zh) | 2003-03-26 | 2009-11-18 | 赛托斯生物技术公司 | Melan-a肽类似物-病毒样颗粒偶联物 |
| US20040235770A1 (en) | 2003-04-02 | 2004-11-25 | Coley Pharmaceutical Group, Ltd. | Immunostimulatory nucleic acid oil-in-water formulations and related methods of use |
| US20050004144A1 (en) | 2003-04-14 | 2005-01-06 | Regents Of The University Of California | Combined use of IMPDH inhibitors with toll-like receptor agonists |
| EP1631687A2 (en) | 2003-04-22 | 2006-03-08 | Coley Pharmaceutical GmbH | Methods and products for identification and assessment of tlr ligands |
| CA2529057A1 (en) * | 2003-06-17 | 2005-01-13 | Mannkind Corporation | Methods to elicit, enhance and sustain immune responses against mhc class i-restricted epitopes, for prophylactic or therapeutic purposes |
| MXPA05013922A (es) | 2003-06-20 | 2006-02-24 | Coley Pharm Group Inc | Antagonistas de receptor tipo toll de molecula pequena. |
| AU2004255470B2 (en) | 2003-07-10 | 2010-08-19 | Cytos Biotechnology Ag | Packaged virus-like particles |
| ATE489967T1 (de) | 2003-07-11 | 2010-12-15 | Intercell Ag | Hcv-vakzin |
| US20050013812A1 (en) * | 2003-07-14 | 2005-01-20 | Dow Steven W. | Vaccines using pattern recognition receptor-ligand:lipid complexes |
| US20070253979A1 (en) | 2003-08-28 | 2007-11-01 | Moss Ronald B | Immunogenic Hiv Compositions and Related Methods |
| ES2342069T4 (es) * | 2003-09-05 | 2011-01-26 | Anadys Pharmaceuticals, Inc. | Ligandos de tlr7 para el tratamiento de la hepatitis c. |
| WO2005023289A1 (ja) | 2003-09-08 | 2005-03-17 | Intellectual Property Consulting Incorporated | 慢性ｃ型肝炎を治療するための医薬組成物 |
| CA2536139A1 (en) | 2003-09-25 | 2005-04-07 | Coley Pharmaceutical Group, Inc. | Nucleic acid-lipophilic conjugates |
| US20050215501A1 (en) | 2003-10-24 | 2005-09-29 | Coley Pharmaceutical Group, Inc. | Methods and products for enhancing epitope spreading |
| GEP20094767B (en) | 2003-10-30 | 2009-09-10 | Coley Pharm Group Inc | C-class oligonucleotide analogs with enhanced immunostimulatory potency |
| US20050239733A1 (en) | 2003-10-31 | 2005-10-27 | Coley Pharmaceutical Gmbh | Sequence requirements for inhibitory oligonucleotides |
| US20050100983A1 (en) | 2003-11-06 | 2005-05-12 | Coley Pharmaceutical Gmbh | Cell-free methods for identifying compounds that affect toll-like receptor 9 (TLR9) signaling |
| WO2005079419A2 (en) | 2004-02-17 | 2005-09-01 | The Regents Of The University Of California | Methods of treating immunopathological disorders |
| TW200533750A (en) | 2004-02-19 | 2005-10-16 | Coley Pharm Group Inc | Immunostimulatory viral RNA oligonucleotides |
| WO2005089231A2 (en) | 2004-03-12 | 2005-09-29 | Hybridon, Inc. | Enhanced activity of hiv vaccine using a second generation immunomodulatory oligonucleotide |
| WO2005111057A2 (en) * | 2004-04-02 | 2005-11-24 | Coley Pharmaceutical Group, Inc. | Immunostimulatory nucleic acids for inducing il-10 responses |
| US7622125B2 (en) | 2004-05-05 | 2009-11-24 | Novartis Vaccines And Diagnostics, Inc. | Polycistronic HIV vector constructs |
| US20080113929A1 (en) | 2004-06-08 | 2008-05-15 | Coley Pharmaceutical Gmbh | Abasic Oligonucleotide as Carrier Platform for Antigen and Immunostimulatory Agonist and Antagonist |
| AU2005333126A1 (en) * | 2004-07-18 | 2006-12-21 | Csl Limited | Methods and compositions for inducing innate immune responses |
| EP1781325A2 (en) | 2004-07-18 | 2007-05-09 | CSL Limited | Immuno stimulating complex and oligonucleotide formulations for inducing enhanced interferon-gamma responses |
| MX2007003171A (es) | 2004-09-21 | 2007-05-23 | Cytos Biotechnology Ag | Particulas tipo virus que comprenden una proteina de fusion de la proteina de cubierta de ap205 y un polipeptido antigenico. |
| MY159370A (en) | 2004-10-20 | 2016-12-30 | Coley Pharm Group Inc | Semi-soft-class immunostimulatory oligonucleotides |
| CN101160401A (zh) * | 2005-02-24 | 2008-04-09 | 科勒制药集团公司 | 免疫刺激寡核苷酸 |
| CA2603976A1 (en) | 2005-04-08 | 2006-10-19 | Coley Pharmaceutical Group, Inc. | Methods for treating infectious disease exacerbated asthma |
| CN1847256B (zh) | 2005-04-13 | 2011-06-15 | 长春华普生物技术有限公司 | 含CpG单链脱氧寡核苷酸和利巴韦林联合应用产生的抗病毒作用 |
| US20060241076A1 (en) | 2005-04-26 | 2006-10-26 | Coley Pharmaceutical Gmbh | Modified oligoribonucleotide analogs with enhanced immunostimulatory activity |
| KR20080047463A (ko) | 2005-09-16 | 2008-05-28 | 콜리 파마슈티칼 게엠베하 | 뉴클레오티드 변형에 의한 짧은 간섭 리보핵산(ｓｉｒｎａ)의 면역자극 특성의 조절 |
| JP2010503608A (ja) | 2005-09-16 | 2010-02-04 | コーリー ファーマシューティカル ゲーエムベーハー | ホスホジエステルバックボーンを有する免疫刺激性一本鎖リボ核酸 |
| EP1928500A2 (en) | 2005-09-27 | 2008-06-11 | Coley Pharmaceutical GmbH | Modulation of tlr-mediated immune responses using adaptor oligonucleotides |
| BRPI0622298A8 (pt) | 2005-11-25 | 2016-04-05 | Coley Pharm Gmbh | Oligorribonucleotídeo para estimular a produção de uma citocina pró-inflamatória, uso do mesmo e composição contendo tal oligorribonucleotídeo |
| JP5484732B2 (ja) | 2005-12-14 | 2014-05-07 | サイトス バイオテクノロジー アーゲー | 過敏症の治療のための免疫賦活性核酸パッケージ粒子 |
| CA2642152C (en) * | 2006-02-15 | 2016-11-01 | Coley Pharmaceutical Gmbh | Compositions and methods for oligonucleotide formulations |
| US8027888B2 (en) | 2006-08-31 | 2011-09-27 | Experian Interactive Innovation Center, Llc | Online credit card prescreen systems and methods |
| WO2008033432A2 (en) | 2006-09-12 | 2008-03-20 | Coley Pharmaceutical Group, Inc. | Immune modulation by chemically modified ribonucleosides and oligoribonucleotides |
| NZ575437A (en) | 2006-09-27 | 2012-02-24 | Coley Pharm Gmbh | Cpg oligonucleotide analogs containing hydrophobic t analogs with enhanced immunostimulatory activity |
| JP2010504982A (ja) | 2006-09-27 | 2010-02-18 | コーリー ファーマシューティカル グループ，インコーポレイテッド | Ｔｌｒのリガンドと抗ウイルス剤との組成物 |
| MX2009004510A (es) | 2006-10-26 | 2009-05-12 | Coley Pharm Gmbh | Oligorribonucleotidos y sus usos. |
| WO2008057529A2 (en) | 2006-11-06 | 2008-05-15 | Coley Pharmaceutical Group, Inc. | Peptide-based vaccine compositions to endogenous cholesteryl ester transfer protein (cetp) |
| BRPI0718360A2 (pt) * | 2006-12-04 | 2013-11-12 | Univ Illinois | "composições e métodos para o tratamento do câncer com cupredoxinas e dna rico em cpg" |
| BRPI0811621A2 (pt) | 2007-05-17 | 2014-10-21 | Coley Pharm Group Inc | Oligonucleotídeos de classe a com potência imunoestimuladora, composição contendo os mesmos e uso da referida composição |
| CA2687535C (en) * | 2007-05-18 | 2017-08-22 | Coley Pharmaceutical Gmbh | Phosphate-modified oligonucleotide analogs with enhanced immunostimulatory activity |
| EP2278979A4 (en) * | 2008-05-21 | 2012-09-26 | Us Gov Health & Human Serv | PROCESS FOR TREATING PNEUMOCONIOSIS WITH OLIGODEOXYNUCLEOTIDES |
| US8053422B2 (en) * | 2008-12-04 | 2011-11-08 | The United States Of America As Represented By The Department Of Health And Human Services | Anti-cancer oligodeoxynucleotides |
| US9501570B2 (en) | 2014-07-14 | 2016-11-22 | Verizon Patent And Licensing Inc. | Dynamic routing system |
| US9719791B2 (en) | 2014-12-10 | 2017-08-01 | Mapquest, Inc. | Computerized systems and methods for providing travel information and/or content to users |
-
2003
- 2003-10-29 CN CN2010102626914A patent/CN101948835A/zh active Pending
- 2003-10-29 AU AU2003283647A patent/AU2003283647B2/en not_active Ceased
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- 2003-10-29 US US10/532,746 patent/US7998492B2/en not_active Expired - Fee Related
- 2003-10-29 CA CA002503693A patent/CA2503693A1/en not_active Abandoned
- 2003-10-29 JP JP2004547932A patent/JP2006515277A/ja not_active Ceased
- 2003-10-29 MX MXPA05004588A patent/MXPA05004588A/es active IP Right Grant
- 2003-10-29 PT PT10166710T patent/PT2241325E/pt unknown
- 2003-10-29 EP EP10166710A patent/EP2241325B1/en not_active Expired - Lifetime
- 2003-10-29 EP EP03775627A patent/EP1556077A2/en not_active Withdrawn
- 2003-10-29 CN CNA200380105159XA patent/CN1753687A/zh active Pending
-
2005
- 2005-07-15 US US11/183,253 patent/US20060003962A1/en not_active Abandoned
-
2010
- 2010-07-15 AU AU2010203015A patent/AU2010203015B2/en not_active Ceased
- 2010-11-15 US US12/946,806 patent/US20110135605A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001022990A2 (en) * | 1999-09-27 | 2001-04-05 | Coley Pharmaceutical Group, Inc. | Methods related to immunostimulatory nucleic acid-induced interferon |
| WO2003002065A2 (en) * | 2001-06-29 | 2003-01-09 | Chiron Corporation | Hcv e1e2 vaccine compositions |
Non-Patent Citations (4)
| Title |
|---|
| DATABASE WPI Section Ch, Week 200203 Derwent Publications Ltd., London, GB; Class B04, AN 2002-023500 XP002285703 & KR 2001 063 153 A (GENEXINE INC) 9 July 2001 (2001-07-09) the whole document * |
| DAVIS H.L. ET AL.: "CpG DNA overcomes hyporesponsiveness to hepatitis B vaccine in orangutans" VACCINE, BUTTERWORTH SCIENTIFIC. GUILDFORD, GB, vol. 18, no. 18, March 2000 (2000-03), pages 1920-1924, XP004190074 ISSN: 0264-410X page 1923, left-hand column, paragraph 3 - right-hand column, paragraph 1 * |
| MALANCHERE-BRES E. ET AL.: "CpG oligodeoxynucleotides with hepatitis B surface antigen (HBsAg) for vaccination in HBsAg-transgenic mice" JOURNAL OF VIROLOGY, vol. 75, no. 14, July 2001 (2001-07), pages 6482-6491, XP002285701 ISSN: 0022-538X page 6482, left-hand column, paragraph 2 page 6489, last paragraph - page 6490 * |
| WEERATNA RISINI D. ET AL.: "CpG ODN can re-direct the Th bias of established Th2 immune responses in adult and young mice" FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY, vol. 32, no. 1, December 2001 (2001-12), pages 65-71, XP002285702 ISSN: 0928-8244 the whole document * |
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| ATE544466T1 (de) | 2012-02-15 |
| US20110135605A1 (en) | 2011-06-09 |
| CN1753687A (zh) | 2006-03-29 |
| AU2010203015A2 (en) | 2010-09-23 |
| KR20050089799A (ko) | 2005-09-08 |
| ZA200503511B (en) | 2006-10-25 |
| DK2241325T3 (da) | 2012-04-10 |
| US20060003962A1 (en) | 2006-01-05 |
| CN101948835A (zh) | 2011-01-19 |
| AU2010203015B2 (en) | 2011-08-25 |
| EA200500733A1 (ru) | 2005-12-29 |
| ES2381224T3 (es) | 2012-05-24 |
| US7998492B2 (en) | 2011-08-16 |
| JP2006515277A (ja) | 2006-05-25 |
| EP1556077A2 (en) | 2005-07-27 |
| WO2004039829A3 (en) | 2004-09-10 |
| HK1149894A1 (en) | 2011-10-21 |
| WO2004039829A2 (en) | 2004-05-13 |
| AU2003283647B2 (en) | 2010-04-15 |
| EP2241325B1 (en) | 2012-02-08 |
| SI2241325T1 (sl) | 2012-05-31 |
| CA2503693A1 (en) | 2004-05-13 |
| EP2241325A1 (en) | 2010-10-20 |
| AU2010203015A1 (en) | 2010-08-05 |
| US20060246035A1 (en) | 2006-11-02 |
| PT2241325E (pt) | 2012-04-12 |
| NZ540098A (en) | 2008-09-26 |
| BR0315810A (pt) | 2005-09-13 |
| MXPA05004588A (es) | 2005-12-14 |
| AU2003283647A1 (en) | 2004-05-25 |
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