CN107980001B - 包括硫代磷酸化寡脱氧核苷酸的化合物和组合物及其使用方法 - Google Patents

包括硫代磷酸化寡脱氧核苷酸的化合物和组合物及其使用方法 Download PDF

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CN107980001B
CN107980001B CN201680047408.1A CN201680047408A CN107980001B CN 107980001 B CN107980001 B CN 107980001B CN 201680047408 A CN201680047408 A CN 201680047408A CN 107980001 B CN107980001 B CN 107980001B
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CN107980001A (zh
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M·T·科尔蒂莱夫斯基
P·M·希维德尔斯基
D·F·莫雷拉
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City of Hope
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CN201680047408.1A 2015-07-02 2016-06-30 包括硫代磷酸化寡脱氧核苷酸的化合物和组合物及其使用方法 Active CN107980001B (zh)

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US201562187878P 2015-07-02 2015-07-02
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PCT/US2016/040361 WO2017004357A1 (en) 2015-07-02 2016-06-30 Compounds and compositions including phosphorothioated oligodeoxynucleotide, and methods of use thereof

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Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016115500A1 (en) * 2015-01-16 2016-07-21 City Of Hope Cell penetrating antibodies
CN114525279A (zh) 2015-04-22 2022-05-24 米纳治疗有限公司 C/EBP α SARNA组合物和使用方法
JP7073109B2 (ja) * 2015-07-02 2022-05-23 シティ・オブ・ホープ ホスホロチオエート化オリゴデオキシヌクレオチドを含む化合物及び組成物、ならびにそれらの使用法
WO2018145086A1 (en) 2017-02-06 2018-08-09 Mpeg La, Llc Multimeric oligonucleotides having decreased kidney clearance
WO2018209270A1 (en) 2017-05-11 2018-11-15 Northwestern University Adoptive cell therapy using spherical nucleic acids (snas)
US11554178B2 (en) 2017-06-30 2023-01-17 City Of Hope Compositions and methods of modulating macrophage activity
EP3679139B1 (en) 2017-09-08 2022-11-02 MiNA Therapeutics Limited Stabilized hnf4a sarna compositions and methods of use
CN113584027B (zh) * 2018-04-10 2025-01-10 中美瑞康核酸技术(南通)研究院有限公司 一种激活p21基因表达的方法
WO2019241766A1 (en) * 2018-06-15 2019-12-19 City Of Hope Oligonucleotide-based proteolysis targeting chimera
CN109762042B (zh) * 2018-09-21 2022-04-08 河北艾克美冀生物科技有限公司 一种治疗癌症的药物、其合成方法和应用
CA3132505A1 (en) * 2019-03-04 2020-09-10 Mpeg La, L.L.C. Multimeric oligonucleotides with enhanced bioactivity
EP4003423A4 (en) * 2019-07-26 2024-03-06 MiNA Therapeutics Limited Compositions and methods of using c/ebp alpha sarna
KR102433981B1 (ko) * 2020-12-15 2022-08-19 대구가톨릭대학교산학협력단 HIF-1α 및 STAT5 전사인자를 억제하는 합성 디코이 올리고핵산 및 이를 유효성분으로 함유하는 아토피 피부염의 예방 또는 치료용 약학적 조성물
CN117377764A (zh) * 2021-02-08 2024-01-09 中美瑞康核酸技术(南通)研究院有限公司 多价寡核苷酸试剂及其使用方法
WO2023034853A2 (en) * 2021-08-31 2023-03-09 City Of Hope Oligonucleotides having 6-thio-2'-deoxyguanosine residues and uses thereof
CN114908094B (zh) * 2022-05-31 2024-03-12 中山大学 一类反义寡核苷酸分子及其在制备治疗恶性肿瘤药物中的应用
EP4599065A2 (en) * 2022-10-07 2025-08-13 City of Hope Double-stranded oligonucleotides and methods of use
EP4627086A2 (en) * 2022-11-29 2025-10-08 Lonza Sales AG Methods of using extracellular vesicle-aso targeting stat6
CN118480552B (zh) * 2024-01-18 2024-10-01 成都先衍生物技术有限公司 一种靶向CEBPA基因表达的saRNA及其用途

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030027184A1 (en) * 1998-10-26 2003-02-06 Gorenstein David G. Combinatorial selection of oligonucleotide aptamers
CN102361985A (zh) * 2008-12-04 2012-02-22 欧科库尔纳有限责任公司 通过抑制肿瘤抑制基因的天然反义转录物治疗肿瘤抑制基因相关性疾病

Family Cites Families (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4911920A (en) 1986-07-30 1990-03-27 Alcon Laboratories, Inc. Sustained release, comfort formulation for glaucoma therapy
FR2588189B1 (fr) 1985-10-03 1988-12-02 Merck Sharp & Dohme Composition pharmaceutique de type a transition de phase liquide-gel
DE69212850T2 (de) 1991-01-15 1997-03-06 Alcon Lab Inc Verwendung von Karrageenan in topischen ophthalmologischen Zusammensetzungen
US5212162A (en) 1991-03-27 1993-05-18 Alcon Laboratories, Inc. Use of combinations gelling polysaccharides and finely divided drug carrier substrates in topical ophthalmic compositions
US6159694A (en) 1999-04-08 2000-12-12 Isis Pharmaceuticals Inc. Antisense modulation of stat3 expression
ITRM20030149A1 (it) * 2003-04-02 2004-10-03 Giuliani Spa Oligonucleotidi (odn) antisenso per smad7 e loro usi in campo medico
US20070265220A1 (en) * 2004-03-15 2007-11-15 City Of Hope Methods and compositions for the specific inhibition of gene expression by double-stranded RNA
AU2005248410B2 (en) * 2004-05-27 2010-04-22 The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Differential expression of molecules associated with acute stroke
CA2604532C (en) * 2005-04-15 2017-03-07 The Regents Of The University Of California Small activating rna molecules and methods of use
US8748405B2 (en) * 2007-01-26 2014-06-10 City Of Hope Methods and compositions for the treatment of cancer or other diseases
WO2008094254A2 (en) 2007-01-26 2008-08-07 City Of Hope Methods and compositions for the treatment of cancer or other diseases
WO2009018332A1 (en) * 2007-08-01 2009-02-05 Alnylam Pharmaceuticals, Inc. Single-stranded and double-stranded oligonucleotides comprising a metal-chelating ligand
WO2012128785A1 (en) 2011-03-22 2012-09-27 City Of Hope Methods and compositions for the treatment of cancer or other diseases
PE20142463A1 (es) * 2011-04-01 2015-01-22 Isis Pharmaceuticals Inc Modulacion de la expresion del transductor de senales y activador de la transcripcion 3 (stat3)
WO2014047649A1 (en) * 2012-09-24 2014-03-27 The Regents Of The University Of California Methods for arranging and packing nucleic acids for unusual resistance to nucleases and targeted delivery for gene therapy
RS58576B1 (sr) * 2012-10-31 2019-05-31 Ionis Pharmaceuticals Inc Tretman raka
AU2014236370C1 (en) * 2013-03-14 2019-01-17 City Of Hope 5-bromo-indirubins
EP3071696B1 (en) 2013-11-22 2019-08-07 Mina Therapeutics Limited C/ebp alpha short activating rna compositions and methods of use
WO2015077657A2 (en) 2013-11-22 2015-05-28 City Of Hope Stat3 inhibitors and uses thereof
JP7073109B2 (ja) * 2015-07-02 2022-05-23 シティ・オブ・ホープ ホスホロチオエート化オリゴデオキシヌクレオチドを含む化合物及び組成物、ならびにそれらの使用法

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030027184A1 (en) * 1998-10-26 2003-02-06 Gorenstein David G. Combinatorial selection of oligonucleotide aptamers
CN102361985A (zh) * 2008-12-04 2012-02-22 欧科库尔纳有限责任公司 通过抑制肿瘤抑制基因的天然反义转录物治疗肿瘤抑制基因相关性疾病

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CpG ODN-mediated regulation of IL-12 p40 transcription;Fumihiko Takeshita et al;《Eur. J. Immunol》;20001231;第30卷;第1967-1976页 *
EB 病毒LMP1在鼻咽癌细胞系中通过NF-κB 、AP-1 促进IL-8 分泌;王承兴等;《中华微生物学和免疫学杂志》;20020331;第22卷(第21期);第198-201页 *
Positive and negative regulatory elements contribute to CpG oligonucleotide-mediated regulation of human IL-6 gene expression;Fumihiko Takeshita et al;《Eur. J. Immunol》;20001231;第30卷;第108-116页 *

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EP3316894A1 (en) 2018-05-09
US20220401563A1 (en) 2022-12-22
EP3316894A4 (en) 2019-06-19
JP2022116006A (ja) 2022-08-09
JP7459168B2 (ja) 2024-04-01
CN114224907A (zh) 2022-03-25
US10758624B2 (en) 2020-09-01
CN107980001A (zh) 2018-05-01
CA2991052A1 (en) 2017-01-05
JP7073109B2 (ja) 2022-05-23
US11464865B2 (en) 2022-10-11
US20210038733A1 (en) 2021-02-11
WO2017004357A1 (en) 2017-01-05
JP2018519831A (ja) 2018-07-26
US20180185497A1 (en) 2018-07-05

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