SK84599A3 - G-rich oligo aptamers and methods of modulating an immune response - Google Patents

G-rich oligo aptamers and methods of modulating an immune response Download PDF

Info

Publication number: SK84599A3
Authority: SK; Slovakia
Prior art keywords: aptamer; ggg; oligonucleotides; regions; seq
Prior art date: 1996-12-27

Application number

SK845-99A

Other languages

English (en)

Slovak (sk)

Inventor

Robert Tam

Original Assignee

Icn Pharmaceuticals

Priority date (The priority date 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 date listed.)

1996-12-27

Filing date

1997-12-19

Publication date

2000-07-11

1997-12-19 Application filed by Icn Pharmaceuticals filed Critical Icn Pharmaceuticals

2000-07-11 Publication of SK84599A3 publication Critical patent/SK84599A3/sk

Links

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SK845-99A 1996-12-27 1997-12-19 G-rich oligo aptamers and methods of modulating an immune response SK84599A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US3450996P	1996-12-27	1996-12-27
PCT/US1997/023927 WO1998029430A1 (en)	1996-12-27	1997-12-19	G-rich oligo aptamers and methods of modulating an immune response

Publications (1)

Publication Number	Publication Date
SK84599A3 true SK84599A3 (en)	2000-07-11

Family

ID=21876859

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK845-99A SK84599A3 (en)	1996-12-27	1997-12-19	G-rich oligo aptamers and methods of modulating an immune response

Country Status (15)

Country	Link
US (1)	US6994959B1 (hu)
EP (1)	EP0968226A4 (hu)
JP (1)	JP2002512599A (hu)
KR (1)	KR20000069658A (hu)
AU (1)	AU5720098A (hu)
BR (1)	BR9714438A (hu)
CA (1)	CA2278031A1 (hu)
CZ (1)	CZ227199A3 (hu)
HU (1)	HU0000769A (hu)
IL (1)	IL130192A0 (hu)
NO (1)	NO993170L (hu)
PL (1)	PL334197A1 (hu)
SI (1)	SI20117A (hu)
SK (1)	SK84599A3 (hu)
WO (1)	WO1998029430A1 (hu)

Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6207646B1 (en)	1994-07-15	2001-03-27	University Of Iowa Research Foundation	Immunostimulatory nucleic acid molecules
WO2000014217A2 (en) *	1998-09-03	2000-03-16	Coley Pharmaceutical Gmbh	G-motif oligonucleotides and uses thereof
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
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
US7585847B2 (en)	2000-02-03	2009-09-08	Coley Pharmaceutical Group, Inc.	Immunostimulatory nucleic acids for the treatment of asthma and allergy
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
AU2002253836A1 (en)	2000-10-20	2002-08-19	Canji, Inc	Aptamer-mediated regulation of gene expression
FR2822156A1 (fr) *	2001-03-16	2002-09-20	Centre Nat Rech Scient	Oligonucleotides pour la regulation du gene codant pour le tnf alpha et/ou de genes sous son controle et leurs applications
US7354909B2 (en)	2001-08-14	2008-04-08	The United States Of America As Represented By Secretary Of The Department Of Health And Human Services	Method for rapid generation of mature dendritic cells
ES2314099T3 (es)	2001-08-17	2009-03-16	Coley Pharmaceutical Gmbh	Oligonucleotidos inmunoestimulantes con motivos combinados con actividad mejorada.
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
EP1625850B1 (en) *	2003-05-15	2012-02-29	Japan Science and Technology Agency	Immunostimulating agents
US20050187176A1 (en) *	2003-10-10	2005-08-25	Bates Paula J.	Method for inhibiting NF-kappa B signaling and use to treat or prevent human diseases
US20050182252A1 (en)	2004-02-13	2005-08-18	Reddy K. R.	Novel 2'-C-methyl nucleoside derivatives
US7482158B2 (en)	2004-07-01	2009-01-27	Mathison Brian H	Composite polynucleic acid therapeutics
KR100998365B1 (ko)	2009-06-29	2010-12-06	압타바이오 주식회사	치료 효능이 있는 변형핵산 및 구아노신을 함유하는 올리고뉴클레오티드 변형체
SG11201500232UA (en)	2012-07-13	2015-04-29	Wave Life Sciences Pte Ltd	Chiral control
EP3105238A4 (en)	2014-02-13	2017-11-08	Ligand Pharmaceuticals, Inc.	Prodrug compounds and their uses
JP2017520545A (ja)	2014-07-02	2017-07-27	リガンド・ファーマシューティカルズ・インコーポレイテッド	プロドラッグ化合物およびそれらの使用
BR112017001311A2 (pt)	2014-09-07	2017-11-14	Selecta Biosciences Inc	métodos e composições para atenuar as respostas imunes do vetor de transferência anti-viral de salto de éxon
JP7427584B2 (ja)	2017-10-13	2024-02-05	セレクタバイオサイエンシーズインコーポレーテッド	抗ウイルス導入ベクターｉｇｍ応答を減弱化するための方法および組成物
KR20190065139A (ko)	2017-12-01	2019-06-11	압타바이오 주식회사	혈액암 치료제
AU2019207625A1 (en)	2018-01-09	2020-07-30	Ligand Pharmaceuticals, Inc.	Acetal compounds and therapeutic uses thereof
WO2020184799A1 (ko) *	2019-03-13	2020-09-17	박동휘	항염증 활성을 갖는 올리고뉴클레오티드
KR20220015425A (ko)	2019-05-28	2022-02-08	셀렉타 바이오사이언시즈, 인크.	약화된 항바이러스 전달 벡터 면역 반응을 위한 방법 및 조성물
US20230322842A1 (en) *	2020-04-14	2023-10-12	Sumitomo Chemical Company, Limited	Composition containing nucleic acid oligomer
WO2023064367A1 (en)	2021-10-12	2023-04-20	Selecta Biosciences, Inc.	Methods and compositions for attenuating anti-viral transfer vector igm responses
WO2023172624A1 (en)	2022-03-09	2023-09-14	Selecta Biosciences, Inc.	Immunosuppressants in combination with anti-igm agents and related dosing

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU1456092A (en) *	1991-02-21	1992-09-15	Gilead Sciences, Inc.	Aptamers specific for thrombin and methods of use
US5567604A (en) *	1993-04-23	1996-10-22	Aronex Pharmaceuticals, Inc.	Anti-viral guanosine-rich oligonucleotides
DE19502912A1 (de) *	1995-01-31	1996-08-01	Hoechst Ag	G-Cap Stabilisierte Oligonucleotide
US5932556A (en) *	1995-09-17	1999-08-03	Tam; Robert C	Methods and compositions for regulation of CD28 expression
WO1996024380A1 (en) *	1995-02-09	1996-08-15	Icn Pharmaceuticals, Inc.	Methods and compositions for regulation of cd28 expression
CA2227867A1 (en) *	1995-07-19	1997-02-06	Michael E. Hogan	Anti-viral guanosine-rich oligonucleotides

1997
- 1997-12-19 EP EP97953460A patent/EP0968226A4/en not_active Withdrawn
- 1997-12-19 HU HU0000769A patent/HU0000769A/hu unknown
- 1997-12-19 CA CA002278031A patent/CA2278031A1/en not_active Abandoned
- 1997-12-19 SI SI9720081A patent/SI20117A/sl unknown
- 1997-12-19 SK SK845-99A patent/SK84599A3/sk unknown
- 1997-12-19 BR BR9714438A patent/BR9714438A/pt not_active Application Discontinuation
- 1997-12-19 PL PL97334197A patent/PL334197A1/xx unknown
- 1997-12-19 KR KR1019997005689A patent/KR20000069658A/ko not_active Withdrawn
- 1997-12-19 WO PCT/US1997/023927 patent/WO1998029430A1/en not_active Ceased
- 1997-12-19 IL IL13019297A patent/IL130192A0/xx unknown
- 1997-12-19 US US09/331,204 patent/US6994959B1/en not_active Expired - Lifetime
- 1997-12-19 CZ CZ992271A patent/CZ227199A3/cs unknown
- 1997-12-19 JP JP53023398A patent/JP2002512599A/ja active Pending
- 1997-12-19 AU AU57200/98A patent/AU5720098A/en not_active Abandoned
1999
- 1999-06-25 NO NO993170A patent/NO993170L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
BR9714438A (pt)	2000-03-21
CA2278031A1 (en)	1998-07-09
KR20000069658A (ko)	2000-11-25
CZ227199A3 (cs)	1999-12-15
NO993170L (no)	1999-08-25
WO1998029430A1 (en)	1998-07-09
EP0968226A1 (en)	2000-01-05
NO993170D0 (no)	1999-06-25
US6994959B1 (en)	2006-02-07
SI20117A (sl)	2000-06-30
EP0968226A4 (en)	2001-02-14
HU0000769A (en)	2000-07-28
IL130192A0 (en)	2000-06-01
PL334197A1 (en)	2000-02-14
JP2002512599A (ja)	2002-04-23
AU5720098A (en)	1998-07-31

Publication	Publication Date	Title
SK84599A3 (en)	2000-07-11	G-rich oligo aptamers and methods of modulating an immune response
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US5932556A (en)	1999-08-03	Methods and compositions for regulation of CD28 expression
JP2732546B2 (ja)	1998-03-30	細胞接着のオリゴヌクレオチド調節
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WO1996024380A9 (en)	1996-10-24	Methods and compositions for regulation of cd28 expression
EP0810882A1 (en)	1997-12-10	Methods and compositions for regulation of cd28 expression
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US20020052331A1 (en)	2002-05-02	Compositions and methods for antisense inhibition of protein translation
Tam et al.	1999	Inhibition of CD28 expression by oligonucleotide decoys to the regulatory element in exon 1 of the CD28 gene
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