JP2002514397A - ＣｐＧオリゴヌクレオチドを用いる造血調節の方法 - Google Patents
ＣｐＧオリゴヌクレオチドを用いる造血調節の方法Info
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- JP2002514397A JP2002514397A JP2000547969A JP2000547969A JP2002514397A JP 2002514397 A JP2002514397 A JP 2002514397A JP 2000547969 A JP2000547969 A JP 2000547969A JP 2000547969 A JP2000547969 A JP 2000547969A JP 2002514397 A JP2002514397 A JP 2002514397A
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Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/117—Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
-
- 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
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- 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
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- 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
- A61K2039/55555—Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
-
- 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
-
- 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
- A61K2039/55566—Emulsions, e.g. Freund's adjuvant, MF59
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/315—Phosphorothioates
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/345—Spatial arrangement of the modifications having at least two different backbone modifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- General Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Immunology (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Mycology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Saccharide Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8551698P | 1998-05-14 | 1998-05-14 | |
| US24165399A | 1999-02-02 | 1999-02-02 | |
| US60/085,516 | 1999-02-02 | ||
| US09/241,653 | 1999-02-02 | ||
| PCT/IB1999/001285 WO1999058118A2 (en) | 1998-05-14 | 1999-05-14 | METHODS FOR REGULATING HEMATOPOIESIS USING CpG-OLIGONUCLEOTIDES |
Publications (2)
| Publication Number | Publication Date |
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| JP2002514397A true JP2002514397A (ja) | 2002-05-21 |
| JP2002514397A5 JP2002514397A5 (https=) | 2006-07-13 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2000547969A Pending JP2002514397A (ja) | 1998-05-14 | 1999-05-14 | ＣｐＧオリゴヌクレオチドを用いる造血調節の方法 |
Country Status (10)
| Country | Link |
|---|---|
| US (5) | US20040030118A1 (https=) |
| EP (2) | EP1078053B1 (https=) |
| JP (1) | JP2002514397A (https=) |
| AT (1) | ATE305507T1 (https=) |
| AU (1) | AU760795B2 (https=) |
| CA (1) | CA2328406A1 (https=) |
| DE (1) | DE69927495T2 (https=) |
| IL (3) | IL139646A0 (https=) |
| NZ (1) | NZ508650A (https=) |
| WO (1) | WO1999058118A2 (https=) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007531699A (ja) * | 2003-07-15 | 2007-11-08 | イデラ ファーマシューティカルズ インコーポレイテッド | 免疫刺激性オリゴヌクレオチドおよび／またはイムノマー化合物をサイトカインおよび／または化学療法剤または放射線療法と組み合わせて用いる、免疫系の相乗的刺激 |
| US9617547B2 (en) | 2012-07-13 | 2017-04-11 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant |
| US10428019B2 (en) | 2010-09-24 | 2019-10-01 | Wave Life Sciences Ltd. | Chiral auxiliaries |
Families Citing this family (108)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6727230B1 (en) * | 1994-03-25 | 2004-04-27 | Coley Pharmaceutical Group, Inc. | Immune stimulation by phosphorothioate oligonucleotide analogs |
| US6207646B1 (en) * | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US6429199B1 (en) * | 1994-07-15 | 2002-08-06 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules for activating dendritic cells |
| US7935675B1 (en) | 1994-07-15 | 2011-05-03 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US20030026782A1 (en) * | 1995-02-07 | 2003-02-06 | Arthur M. Krieg | Immunomodulatory oligonucleotides |
| US6239116B1 (en) * | 1994-07-15 | 2001-05-29 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| 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 |
| 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 |
| EP1003531B1 (en) | 1997-05-20 | 2007-08-22 | Ottawa Health Research Institute | Processes for preparing nucleic acid constructs |
| AU760549B2 (en) * | 1998-04-03 | 2003-05-15 | University Of Iowa Research Foundation, The | Methods and products for stimulating the immune system using immunotherapeutic oligonucleotides and cytokines |
| JP2002514397A (ja) * | 1998-05-14 | 2002-05-21 | コーリー ファーマシューティカル ゲーエムベーハー | ＣｐＧオリゴヌクレオチドを用いる造血調節の方法 |
| SI1077722T1 (sl) | 1998-05-22 | 2007-02-28 | Ottawa Health Research Inst | Metode in produkti za induciranje sluznicne imunosti |
| 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 |
| PT1104306E (pt) | 1998-08-10 | 2006-05-31 | Antigenics Inc | Composicoes de cpg e adjuvantes de saponina e seus metodos |
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| 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 |
| FR2795963A1 (fr) * | 1999-07-08 | 2001-01-12 | Pasteur Merieux Serums Vacc | Polynucleotide immunostimulant |
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| NZ517929A (en) | 1999-09-25 | 2004-02-27 | Univ Iowa Res Found | Immunostimulatory nucleic acids |
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| AU2001227889A1 (en) | 2000-01-14 | 2001-07-24 | The United States of America, represented by The Secretary, Department of Health & Human Services | Oligodeoxynucleotide and its use to induce an immune response |
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| JP2005500806A (ja) | 2000-09-15 | 2005-01-13 | コーリー ファーマシューティカル ゲーエムベーハー | ＣｐＧに基づく免疫アゴニスト／免疫アンタゴニストの高スループットスクリーニングのためのプロセス |
| ES2307568T3 (es) * | 2000-12-08 | 2008-12-01 | Coley Pharmaceutical Gmbh | Acidos nucleicos de tipo cpg y metodos de uso de los mismos. |
| WO2002053141A2 (en) * | 2000-12-14 | 2002-07-11 | Coley Pharmaceutical Group, Inc. | Inhibition of angiogenesis by nucleic acids |
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| US9777312B2 (en) | 2001-06-30 | 2017-10-03 | Enzo Life Sciences, Inc. | Dual polarity analysis of nucleic acids |
| 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 |
| ATE411054T1 (de) | 2001-08-17 | 2008-10-15 | Coley Pharm Gmbh | Kombinations-motif-immunstimulierende oligonukleotide mit verbesserter wirkung |
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| KR101092043B1 (ko) | 2002-04-22 | 2011-12-12 | 바이오니취 라이프 사이언시즈 인코포레이티드 | 올리고뉴클레오티드 조성물 및 면역 반응 조절시 이의 용도 |
| BR0311995A (pt) * | 2002-06-20 | 2005-04-05 | Cytos Biotechnology Ag | Partìculas semelhantes a vìrus empacotadas para o uso como adjuvantes: método de preparação e uso |
| 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 |
| US7569553B2 (en) * | 2002-07-03 | 2009-08-04 | Coley Pharmaceutical Group, Inc. | Nucleic acid compositions for stimulating immune responses |
| WO2004005476A2 (en) * | 2002-07-03 | 2004-01-15 | 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 |
| US20050209183A1 (en) * | 2002-07-25 | 2005-09-22 | Phenion Gmbh & Co. Kg | Cosmetic or pharmaceutical preparations comprising nucleic acids based on non-methylated CPG motifs |
| AR040996A1 (es) | 2002-08-19 | 2005-04-27 | Coley Pharm Group Inc | Acidos nucleicos inmunoestimuladores |
| CN1753687A (zh) * | 2002-10-29 | 2006-03-29 | 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 |
| CA2502015A1 (en) * | 2002-12-11 | 2004-06-24 | Coley Pharmaceutical Group, Inc. | 5' cpg nucleic acids and methods of use |
| AU2004224761A1 (en) * | 2003-03-26 | 2004-10-07 | Cytos Biotechnology Ag | HIV-peptide-carrier-conjugates |
| KR100872472B1 (ko) * | 2003-05-15 | 2008-12-05 | 도꾸리쯔교세이호징 가가꾸 기쥬쯔 신꼬 기꼬 | 면역자극제 |
| MXPA05013922A (es) * | 2003-06-20 | 2006-02-24 | Coley Pharm Group Inc | Antagonistas de receptor tipo toll de molecula pequena. |
| RU2375076C2 (ru) * | 2003-07-10 | 2009-12-10 | Цитос Биотехнологи Аг | Укомплектованные вирусоподобные частицы |
| US20050013812A1 (en) * | 2003-07-14 | 2005-01-20 | Dow Steven W. | Vaccines using pattern recognition receptor-ligand:lipid complexes |
| AU2004275876B2 (en) * | 2003-09-25 | 2011-03-31 | Coley Pharmaceutical Gmbh | Nucleic acid-lipophilic conjugates |
| EP1678303A2 (en) * | 2003-10-30 | 2006-07-12 | Coley Pharmaceutical GmbH | 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 |
| JP2007526253A (ja) * | 2004-02-19 | 2007-09-13 | 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 | 免疫刺激性ウイルスｒｎａオリゴヌクレオチド |
| TWI235440B (en) * | 2004-03-31 | 2005-07-01 | Advanced Semiconductor Eng | Method for making leadless semiconductor package |
| US20080113929A1 (en) * | 2004-06-08 | 2008-05-15 | Coley Pharmaceutical Gmbh | Abasic Oligonucleotide as Carrier Platform for Antigen and Immunostimulatory Agonist and Antagonist |
| US20060287263A1 (en) * | 2004-07-18 | 2006-12-21 | Csl Limited | Methods and compositions for inducing antigen-specific immune responses |
| MY159370A (en) * | 2004-10-20 | 2016-12-30 | Coley Pharm Group Inc | Semi-soft-class immunostimulatory oligonucleotides |
| US20080009455A9 (en) * | 2005-02-24 | 2008-01-10 | Coley Pharmaceutical Group, Inc. | Immunostimulatory oligonucleotides |
| JP2008535859A (ja) * | 2005-04-08 | 2008-09-04 | 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 | 感染症によって悪化した喘息を治療するための方法 |
| AU2006241149A1 (en) * | 2005-04-26 | 2006-11-02 | Coley Pharmaceutical Gmbh | Modified oligoribonucleotide analogs with enhanced immunostimulatory activity |
| ATE439135T1 (de) | 2005-07-01 | 2009-08-15 | Index Pharmaceuticals Ab | Modulierung der reaktion auf steroide |
| AU2006266503B2 (en) | 2005-07-01 | 2011-12-08 | Index Pharmaceuticals Ab | Immunostimulatory method |
| KR20080030656A (ko) * | 2005-07-07 | 2008-04-04 | 콜레이 파마시티컬 그룹, 인코포레이티드 | 암 치료를 위한 항-ＣＴＬＡ-4 항체 및 ＣｐＧ-모티프-함유합성 올리고데옥시뉴클레오티드의 조합 요법 |
| CN101321868A (zh) * | 2005-09-16 | 2008-12-10 | 科利制药公司 | 通过核苷酸修饰调节短干扰核糖核酸(siRNA)的免疫刺激特性 |
| US20090214578A1 (en) * | 2005-09-16 | 2009-08-27 | Coley Pharmaceutical Gmbh | Immunostimulatory Single-Stranded Ribonucleic Acid with Phosphodiester Backbone |
| AU2006306805A1 (en) | 2005-10-28 | 2007-05-03 | Index Pharmaceuticals Ab | Composition and method for the prevention, treatment and/or alleviation of an inflammatory disease |
| JP4538522B2 (ja) * | 2005-11-25 | 2010-09-08 | コーリー ファーマシューティカル ゲーエムベーハー | 免疫刺激性オリゴリボヌクレオチド |
| CA2636139A1 (en) | 2005-12-14 | 2007-06-21 | Cytos Biotechnology Ag | Immunostimulatory nucleic acid packaged particles for the treatment of hypersensitivity |
| DK2405002T3 (en) * | 2006-02-15 | 2015-01-05 | Adiutide Pharmaceuticals Gmbh | Compositions and methods for oligonukleotidformuleringer |
| US8541559B2 (en) | 2006-06-12 | 2013-09-24 | Cytos Biotechnology Ag | Process for producing aggregated oligonucleotides |
| PT2078080E (pt) | 2006-09-27 | 2015-09-18 | Coley Pharm Gmbh | Análogos dos oligonucleotídeos cpg que contêm análogos t hidrofóbicos com atividade imunoestimulante potenciada |
| US20090142362A1 (en) * | 2006-11-06 | 2009-06-04 | Avant Immunotherapeutics, Inc. | Peptide-based vaccine compositions to endogenous cholesteryl ester transfer protein (CETP) |
| ES2569907T3 (es) | 2008-06-27 | 2016-05-13 | Zoetis Services Llc | Composiciones adyuvantes novedosas |
| TWI351288B (en) * | 2008-07-04 | 2011-11-01 | Univ Nat Pingtung Sci & Tech | Cpg dna adjuvant in avian vaccines |
| CN102282155B (zh) | 2008-12-02 | 2017-06-09 | 日本波涛生命科学公司 | 磷原子修饰的核酸的合成方法 |
| 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 |
| RU2612521C2 (ru) | 2009-07-06 | 2017-03-09 | Онтории, Инк. | Новые пролекарства нуклеиновых кислот и способы их применения |
| KR101502200B1 (ko) * | 2011-03-03 | 2015-03-13 | 충북대학교 산학협력단 | 쿼르세틴 ３―Ｏ―β―（２＂―갈로일）―람노피란노사이드를 유효성분으로 포함하는 적혈구생성 촉진용 조성물 |
| CN103796657B (zh) | 2011-07-19 | 2017-07-11 | 波涛生命科学有限公司 | 合成官能化核酸的方法 |
| KR102213609B1 (ko) | 2012-07-13 | 2021-02-08 | 웨이브 라이프 사이언시스 리미티드 | 키랄 제어 |
| PL2872485T3 (pl) | 2012-07-13 | 2021-05-31 | Wave Life Sciences Ltd. | Asymetryczna grupa pomocnicza |
| UA130246C2 (uk) | 2013-09-19 | 2025-12-31 | Зоетіс Сервісіз Ллс | Ад'ювант на основі олії |
| 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 |
| JPWO2015108047A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 免疫誘導活性を有するキラル核酸アジュバンド及び免疫誘導活性剤 |
| US10322173B2 (en) | 2014-01-15 | 2019-06-18 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having anti-allergic activity, and anti-allergic agent |
| BR112016016400A2 (pt) | 2014-01-16 | 2017-10-03 | Wave Life Sciences Ltd | Composições de oligonucleotídeos quiralmente controlados, seu uso, sua composição farmacêutica, e métodos |
| 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 |
| CN115317600A (zh) | 2015-01-16 | 2022-11-11 | 硕腾服务有限责任公司 | 口蹄疫疫苗 |
| BR112022001185A2 (pt) * | 2019-08-01 | 2022-03-15 | Acm Biolabs Pte Ltd | Método de eliciamento de uma resposta imune administrando uma população de polimerossomos tendo um antígeno associado com uma população de polimerossomos tendo um adjuvante associado, bem como composições compreendendo as duas populações de polimerossomos |
| CN117462701B (zh) * | 2023-10-31 | 2026-04-07 | 暨南大学 | 一种靶向肝脏的变形红细胞制剂及其制备方法与应用 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996002555A1 (en) * | 1994-07-15 | 1996-02-01 | The University Of Iowa Research Foundation | Immunomodulatory oligonucleotides |
| WO1997040163A1 (en) * | 1996-04-19 | 1997-10-30 | Metin Colpan | Nucleic acid vaccination for parvoviral infections |
| JPH09285291A (ja) * | 1995-11-07 | 1997-11-04 | Ottawa Civic Hospital Loeb Res Inst | 液漬による魚介類のｄｎａベースワクチン |
| WO1998018810A1 (en) * | 1996-10-30 | 1998-05-07 | The University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| JP2002500159A (ja) * | 1997-09-05 | 2002-01-08 | 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 | 抗原刺激顆粒球媒介炎症を予防または軽減するための免疫刺激オリゴヌクレオチドの使用 |
| JP2002513763A (ja) * | 1998-05-06 | 2002-05-14 | 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を使用して寄生生物感染および関連する疾患を予防および処置するための方法 |
Family Cites Families (82)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2004A (en) * | 1841-03-12 | Improvement in the manner of constructing and propelling steam-vessels | ||
| US3906092A (en) * | 1971-11-26 | 1975-09-16 | Merck & Co Inc | Stimulation of antibody response |
| US5786189A (en) * | 1989-11-29 | 1998-07-28 | Smithkline Beecham Biologicals (S.A.) | Vaccine |
| US5212295A (en) * | 1990-01-11 | 1993-05-18 | Isis Pharmaceuticals | Monomers for preparation of oligonucleotides having chiral phosphorus linkages |
| US5506212A (en) * | 1990-01-11 | 1996-04-09 | Isis Pharmaceuticals, Inc. | Oligonucleotides with substantially chirally pure phosphorothioate linkages |
| US5248670A (en) * | 1990-02-26 | 1993-09-28 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotides for inhibiting herpesviruses |
| US5512668A (en) * | 1991-03-06 | 1996-04-30 | Polish Academy Of Sciences | Solid phase oligonucleotide synthesis using phospholane intermediates |
| US5498410A (en) * | 1991-04-22 | 1996-03-12 | Gleich; Gerald J. | Method for the treatment of eosinophil-associated conditions with anionic polymers |
| US5359052A (en) * | 1991-08-05 | 1994-10-25 | Polish Academy Of Sciences | Chalcophospholanes useful in the synthesis of oligonucleoside phosphorothioates, phosphorodithioates and related selenates |
| US5599797A (en) * | 1991-10-15 | 1997-02-04 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
| US5585479A (en) * | 1992-07-24 | 1996-12-17 | The United States Of America As Represented By The Secretary Of The Navy | Antisense oligonucleotides directed against human ELAM-I RNA |
| US5849719A (en) * | 1993-08-26 | 1998-12-15 | The Regents Of The University Of California | Method for treating allergic lung disease |
| NZ276968A (en) * | 1993-11-16 | 1998-04-27 | Genta Inc | Synthetic oligomers enriched for phosphonate internucleosidyl linkages of preselected chirality and their preparation |
| WO1995026204A1 (en) * | 1994-03-25 | 1995-10-05 | Isis Pharmaceuticals, Inc. | Immune stimulation by phosphorothioate oligonucleotide analogs |
| US6727230B1 (en) * | 1994-03-25 | 2004-04-27 | Coley Pharmaceutical Group, Inc. | Immune stimulation by phosphorothioate oligonucleotide analogs |
| US7935675B1 (en) * | 1994-07-15 | 2011-05-03 | 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 |
| US20030050263A1 (en) * | 1994-07-15 | 2003-03-13 | The University Of Iowa Research Foundation | Methods and products for treating HIV infection |
| US6429199B1 (en) * | 1994-07-15 | 2002-08-06 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules for activating dendritic cells |
| US20030026782A1 (en) * | 1995-02-07 | 2003-02-06 | Arthur M. Krieg | Immunomodulatory oligonucleotides |
| WO1996032138A1 (en) * | 1995-04-13 | 1996-10-17 | Milkhaus Laboratory, Inc. | Methods for treating respiratory disease |
| US5750674A (en) * | 1995-05-23 | 1998-05-12 | Hybridon, Inc. | Methods and compounds for the stereoselective enrichment of oligonucleotide diastereomers and oligonucleotides thereby produced |
| US7034007B1 (en) * | 1995-06-07 | 2006-04-25 | East Carolina University | Low adenosine anti-sense oligonucleotide, compositions, kit & method for treatment of airway disorders associated with bronchoconstriction, lung inflammation, allergy(ies) & surfactant depletion |
| US6025339A (en) * | 1995-06-07 | 2000-02-15 | East Carolina University | Composition, kit and method for treatment of disorders associated with bronchoconstriction and lung inflammation |
| US6040296A (en) * | 1995-06-07 | 2000-03-21 | East Carolina University | Specific antisense oligonucleotide composition & method for treatment of disorders associated with bronchoconstriction and lung inflammation |
| US20030078223A1 (en) * | 1996-01-30 | 2003-04-24 | Eyal Raz | Compositions and methods for modulating an immune response |
| 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 |
| US5856465A (en) * | 1996-05-24 | 1999-01-05 | Polska Akademia Nauk Centrum Badan Molekularnych I Makromolekularnych | Compositions and methods for the synthesis of chirally pure organophosphorus nucleoside derivatives |
| US5856462A (en) * | 1996-09-10 | 1999-01-05 | Hybridon Incorporated | Oligonucleotides having modified CpG dinucleosides |
| ATE292980T1 (de) * | 1996-10-11 | 2005-04-15 | Univ California | Immunostimulierende oligonucleotidekonjugate |
| EP0855184A1 (en) * | 1997-01-23 | 1998-07-29 | Grayson B. Dr. Lipford | Pharmaceutical composition comprising a polynucleotide and an antigen especially for vaccination |
| 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 |
| US6426334B1 (en) * | 1997-04-30 | 2002-07-30 | Hybridon, Inc. | Oligonucleotide mediated specific cytokine induction and reduction of tumor growth in a mammal |
| US20030104044A1 (en) * | 1997-05-14 | 2003-06-05 | Semple Sean C. | Compositions for stimulating cytokine secretion and inducing an immune response |
| EP1003531B1 (en) * | 1997-05-20 | 2007-08-22 | Ottawa Health Research Institute | Processes for preparing nucleic acid constructs |
| WO1999001154A1 (en) * | 1997-07-03 | 1999-01-14 | University Of Iowa Research Foundation | Method for inhibiting immunostimulatory dna associated responses |
| US6749856B1 (en) * | 1997-09-11 | 2004-06-15 | The United States Of America, As Represented By The Department Of Health And Human Services | Mucosal cytotoxic T lymphocyte responses |
| US20050031638A1 (en) * | 1997-12-24 | 2005-02-10 | Smithkline Beecham Biologicals S.A. | Vaccine |
| JPH11209289A (ja) * | 1998-01-22 | 1999-08-03 | Taisho Pharmaceut Co Ltd | 粘膜免疫誘起剤 |
| AU760549B2 (en) * | 1998-04-03 | 2003-05-15 | University Of Iowa Research Foundation, The | Methods and products for stimulating the immune system using immunotherapeutic oligonucleotides and cytokines |
| JP2002514397A (ja) * | 1998-05-14 | 2002-05-21 | コーリー ファーマシューティカル ゲーエムベーハー | ＣｐＧオリゴヌクレオチドを用いる造血調節の方法 |
| US6562798B1 (en) * | 1998-06-05 | 2003-05-13 | Dynavax Technologies Corp. | Immunostimulatory oligonucleotides with modified bases and methods of use thereof |
| US20030022854A1 (en) * | 1998-06-25 | 2003-01-30 | Dow Steven W. | Vaccines using nucleic acid-lipid complexes |
| ATE326239T1 (de) * | 1998-09-18 | 2006-06-15 | Dynavax Tech Corp | Verfahren zur behandlung von ig-e assozierten krankheiten und zusammensetzungen zur verwendung in diesen verfahren |
| US6558670B1 (en) * | 1999-04-19 | 2003-05-06 | Smithkline Beechman Biologicals S.A. | Vaccine adjuvants |
| US6514948B1 (en) * | 1999-07-02 | 2003-02-04 | The Regents Of The University Of California | Method for enhancing an immune response |
| US20050249794A1 (en) * | 1999-08-27 | 2005-11-10 | Semple Sean C | Compositions for stimulating cytokine secretion and inducing an immune response |
| NZ517929A (en) * | 1999-09-25 | 2004-02-27 | Univ Iowa Res Found | Immunostimulatory nucleic acids |
| US6949520B1 (en) * | 1999-09-27 | 2005-09-27 | Coley Pharmaceutical Group, Inc. | Methods related to immunostimulatory nucleic acid-induced interferon |
| 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 |
| US7585847B2 (en) * | 2000-02-03 | 2009-09-08 | Coley Pharmaceutical Group, Inc. | Immunostimulatory nucleic acids for the treatment of asthma and allergy |
| EP1296714B1 (en) * | 2000-06-22 | 2009-08-26 | University Of Iowa Research Foundation | Combination of CpG and antibodies directed against CD19,CD20, CD22 or CD40 for the treatment or prevention of cancer. |
| 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 |
| US20020091097A1 (en) * | 2000-09-07 | 2002-07-11 | Bratzler Robert L. | Nucleic acids for the prevention and treatment of sexually transmitted diseases |
| JP2005500806A (ja) * | 2000-09-15 | 2005-01-13 | コーリー ファーマシューティカル ゲーエムベーハー | ＣｐＧに基づく免疫アゴニスト／免疫アンタゴニストの高スループットスクリーニングのためのプロセス |
| ES2307568T3 (es) * | 2000-12-08 | 2008-12-01 | Coley Pharmaceutical Gmbh | Acidos nucleicos de tipo cpg y metodos de uso de los mismos. |
| WO2002053141A2 (en) * | 2000-12-14 | 2002-07-11 | Coley Pharmaceutical Group, Inc. | 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 |
| US20030148316A1 (en) * | 2001-08-01 | 2003-08-07 | Lipford Grayson B. | Methods and compositions relating to plasmacytoid dendritic cells |
| CN1633598A (zh) * | 2001-10-05 | 2005-06-29 | 科勒制药股份公司 | Toll样受体3信号传导的激动剂和拮抗剂 |
| US20030139364A1 (en) * | 2001-10-12 | 2003-07-24 | University Of Iowa Research Foundation | Methods and products for enhancing immune responses using imidazoquinoline compounds |
| EP3006043B1 (en) * | 2002-04-04 | 2019-05-29 | Zoetis Belgium S.A. | Immunostimulatory g,u-containing oligoribonucleotides |
| US20040009949A1 (en) * | 2002-06-05 | 2004-01-15 | 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 |
| US20040053880A1 (en) * | 2002-07-03 | 2004-03-18 | 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 |
| US7569553B2 (en) * | 2002-07-03 | 2009-08-04 | 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 |
| CN1753687A (zh) * | 2002-10-29 | 2006-03-29 | 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 |
| WO2004098491A2 (en) * | 2002-11-01 | 2004-11-18 | 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 |
| MXPA05013922A (es) * | 2003-06-20 | 2006-02-24 | Coley Pharm Group Inc | Antagonistas de receptor tipo toll de molecula pequena. |
| AU2004275876B2 (en) * | 2003-09-25 | 2011-03-31 | Coley Pharmaceutical Gmbh | Nucleic acid-lipophilic conjugates |
| 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 |
| JP2007531746A (ja) * | 2004-04-02 | 2007-11-08 | 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 | Ｉｌ−１０応答を誘導するための免疫活性化核酸 |
| US20080113929A1 (en) * | 2004-06-08 | 2008-05-15 | Coley Pharmaceutical Gmbh | Abasic Oligonucleotide as Carrier Platform for Antigen and Immunostimulatory Agonist and Antagonist |
| EP1776105A2 (en) * | 2004-07-18 | 2007-04-25 | Coley Pharmaceutical Group, Ltd | Methods and compositions for inducing innate immune responses |
| MY159370A (en) * | 2004-10-20 | 2016-12-30 | Coley Pharm Group Inc | Semi-soft-class immunostimulatory oligonucleotides |
| US20080009455A9 (en) * | 2005-02-24 | 2008-01-10 | Coley Pharmaceutical Group, Inc. | Immunostimulatory oligonucleotides |
| KR20080030656A (ko) * | 2005-07-07 | 2008-04-04 | 콜레이 파마시티컬 그룹, 인코포레이티드 | 암 치료를 위한 항-ＣＴＬＡ-4 항체 및 ＣｐＧ-모티프-함유합성 올리고데옥시뉴클레오티드의 조합 요법 |
| JP4538522B2 (ja) * | 2005-11-25 | 2010-09-08 | コーリー ファーマシューティカル ゲーエムベーハー | 免疫刺激性オリゴリボヌクレオチド |
| DK2405002T3 (en) * | 2006-02-15 | 2015-01-05 | Adiutide Pharmaceuticals Gmbh | Compositions and methods for oligonukleotidformuleringer |
-
1999
- 1999-05-14 JP JP2000547969A patent/JP2002514397A/ja active Pending
- 1999-05-14 AT AT99928176T patent/ATE305507T1/de not_active IP Right Cessation
- 1999-05-14 AU AU45288/99A patent/AU760795B2/en not_active Ceased
- 1999-05-14 DE DE69927495T patent/DE69927495T2/de not_active Expired - Lifetime
- 1999-05-14 WO PCT/IB1999/001285 patent/WO1999058118A2/en not_active Ceased
- 1999-05-14 EP EP99928176A patent/EP1078053B1/en not_active Expired - Lifetime
- 1999-05-14 CA CA002328406A patent/CA2328406A1/en not_active Abandoned
- 1999-05-14 EP EP05108933A patent/EP1674574A1/en not_active Withdrawn
- 1999-05-14 IL IL13964699A patent/IL139646A0/xx active IP Right Grant
- 1999-05-14 NZ NZ508650A patent/NZ508650A/en unknown
-
2000
- 2000-11-13 IL IL139646A patent/IL139646A/en not_active IP Right Cessation
-
2003
- 2003-02-24 US US10/373,381 patent/US20040030118A1/en not_active Abandoned
-
2004
- 2004-06-25 US US10/877,369 patent/US20040234512A1/en not_active Abandoned
- 2004-06-25 US US10/876,892 patent/US20040235777A1/en not_active Abandoned
- 2004-06-25 US US10/876,965 patent/US20040235778A1/en not_active Abandoned
-
2006
- 2006-11-10 US US11/595,823 patent/US20070184465A1/en not_active Abandoned
-
2007
- 2007-12-06 IL IL187987A patent/IL187987A0/en unknown
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1996002555A1 (en) * | 1994-07-15 | 1996-02-01 | The University Of Iowa Research Foundation | Immunomodulatory oligonucleotides |
| JPH09285291A (ja) * | 1995-11-07 | 1997-11-04 | Ottawa Civic Hospital Loeb Res Inst | 液漬による魚介類のｄｎａベースワクチン |
| WO1997040163A1 (en) * | 1996-04-19 | 1997-10-30 | Metin Colpan | Nucleic acid vaccination for parvoviral infections |
| WO1998018810A1 (en) * | 1996-10-30 | 1998-05-07 | The University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| JP2002500159A (ja) * | 1997-09-05 | 2002-01-08 | 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 | 抗原刺激顆粒球媒介炎症を予防または軽減するための免疫刺激オリゴヌクレオチドの使用 |
| JP2002513763A (ja) * | 1998-05-06 | 2002-05-14 | 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を使用して寄生生物感染および関連する疾患を予防および処置するための方法 |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007531699A (ja) * | 2003-07-15 | 2007-11-08 | イデラ ファーマシューティカルズ インコーポレイテッド | 免疫刺激性オリゴヌクレオチドおよび／またはイムノマー化合物をサイトカインおよび／または化学療法剤または放射線療法と組み合わせて用いる、免疫系の相乗的刺激 |
| US10428019B2 (en) | 2010-09-24 | 2019-10-01 | Wave Life Sciences Ltd. | Chiral auxiliaries |
| US9617547B2 (en) | 2012-07-13 | 2017-04-11 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1999058118A3 (en) | 2000-01-13 |
| EP1078053B1 (en) | 2005-09-28 |
| AU4528899A (en) | 1999-11-29 |
| AU760795B2 (en) | 2003-05-22 |
| IL187987A0 (en) | 2008-03-20 |
| US20040234512A1 (en) | 2004-11-25 |
| NZ508650A (en) | 2003-05-30 |
| US20040030118A1 (en) | 2004-02-12 |
| IL139646A (en) | 2008-03-20 |
| US20040235778A1 (en) | 2004-11-25 |
| CA2328406A1 (en) | 1999-11-18 |
| WO1999058118A2 (en) | 1999-11-18 |
| ATE305507T1 (de) | 2005-10-15 |
| US20070184465A1 (en) | 2007-08-09 |
| EP1078053A2 (en) | 2001-02-28 |
| DE69927495D1 (de) | 2006-02-09 |
| EP1674574A1 (en) | 2006-06-28 |
| US20040235777A1 (en) | 2004-11-25 |
| DE69927495T2 (de) | 2006-07-06 |
| IL139646A0 (en) | 2002-02-10 |
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