CN109475568A - Glp-1受体配体部分缀合的寡核苷酸及其用途 - Google Patents

Glp-1受体配体部分缀合的寡核苷酸及其用途 Download PDF

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Publication number
CN109475568A
CN109475568A CN201780040725.5A CN201780040725A CN109475568A CN 109475568 A CN109475568 A CN 109475568A CN 201780040725 A CN201780040725 A CN 201780040725A CN 109475568 A CN109475568 A CN 109475568A
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China
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compound
glp
ser
glu
ala
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Pending
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CN201780040725.5A
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English (en)
Chinese (zh)
Inventor
B.P.莫尼亚
T.P.普拉卡什
G.A.金伯格
R．李
P.P.塞思
S.安德松
E.C.安梅拉
D.L.克内尔
A.M.奥尔维加-哈尔瓦松
W.德鲁里
E.瓦罗伊尔
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AstraZeneca AB
Ionis Pharmaceuticals Inc
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AstraZeneca AB
Ionis Pharmaceuticals Inc
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Publication of CN109475568A publication Critical patent/CN109475568A/zh
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    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
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    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/6425—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the peptide or protein in the drug conjugate being a receptor, e.g. CD4, a cell surface antigen, i.e. not a peptide ligand targeting the antigen, or a cell surface determinant, i.e. a part of the surface of a cell
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    • A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
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CN201780040725.5A 2016-05-06 2017-05-04 Glp-1受体配体部分缀合的寡核苷酸及其用途 Pending CN109475568A (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662333080P 2016-05-06 2016-05-06
US62/333080 2016-05-06
PCT/US2017/031010 WO2017192820A1 (en) 2016-05-06 2017-05-04 Glp-1 receptor ligand moiety conjugated oligonucleotides and uses thereof

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CN109475568A true CN109475568A (zh) 2019-03-15

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US (2) US20190134214A1 (enExample)
EP (1) EP3452049A4 (enExample)
JP (2) JP7091255B2 (enExample)
KR (3) KR102608220B1 (enExample)
CN (1) CN109475568A (enExample)
AU (2) AU2017260003B2 (enExample)
CA (1) CA3021994A1 (enExample)
IL (2) IL262728B2 (enExample)
WO (1) WO2017192820A1 (enExample)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114980916A (zh) * 2020-09-22 2022-08-30 魏洋 用于2型糖尿病的长效glp1类似物药物

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102608220B1 (ko) 2016-05-06 2023-11-29 아이오니스 파마수티컬즈, 인코포레이티드 Glp-1 수용체 리간드 모이어티 컨쥬게이트된 올리고뉴클레오티드 및 이의 용도
US11359200B2 (en) * 2017-04-09 2022-06-14 The Cleveland Clinic Foundation Cancer treatment by MALAT1 inhibition
WO2018202870A1 (en) 2017-05-04 2018-11-08 Follicum Ab Peptides for treatment of diabetes
CN119876131A (zh) * 2017-11-08 2025-04-25 Ionis制药公司 Glp-1受体配体部分缀合的寡核苷酸及其用途
CN107881187A (zh) * 2017-11-20 2018-04-06 珠海联邦制药股份有限公司 将大肠杆菌表达的融合蛋白转化为利拉鲁肽的制备方法及应用
KR20210134686A (ko) * 2019-02-27 2021-11-10 아이오니스 파마수티컬즈, 인코포레이티드 Malat1 발현의 조절인자
KR102193211B1 (ko) * 2019-11-27 2020-12-18 (주)디앤디파마텍 비오틴 모이어티가 결합된 폴리펩티드 및 이를 포함하는 경구 투여용 약학적 조성물

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120295958A1 (en) * 2003-04-28 2012-11-22 Isis Pharmaceuticals, Inc. Modulation of glucagon receptor expression
CN103857408A (zh) * 2011-06-22 2014-06-11 印第安那大学科技研究公司 胰高血糖素/glp-1受体协同激动剂
CN104884618A (zh) * 2012-11-15 2015-09-02 罗氏创新中心哥本哈根有限公司 寡核苷酸缀合物
US20150353930A1 (en) * 2014-06-06 2015-12-10 Berg Llc Methods of treating a metabolic syndrome by modulating heat shock protein (hsp) 90-beta

Family Cites Families (91)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3687808A (en) 1969-08-14 1972-08-29 Univ Leland Stanford Junior Synthetic polynucleotides
US5367066A (en) 1984-10-16 1994-11-22 Chiron Corporation Oligonucleotides with selectably cleavable and/or abasic sites
FR2575751B1 (fr) 1985-01-08 1987-04-03 Pasteur Institut Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques
US5506337A (en) 1985-03-15 1996-04-09 Antivirals Inc. Morpholino-subunit combinatorial library and method
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
US5166315A (en) 1989-12-20 1992-11-24 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5185444A (en) 1985-03-15 1993-02-09 Anti-Gene Deveopment Group Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages
WO1987006941A1 (en) 1986-05-05 1987-11-19 The General Hospital Corporation Insulinotropic hormone
DE3851889T2 (de) 1987-06-24 1995-04-13 Florey Howard Inst Nukleosid-derivate.
US5175273A (en) 1988-07-01 1992-12-29 Genentech, Inc. Nucleic acid intercalating agents
US5134066A (en) 1989-08-29 1992-07-28 Monsanto Company Improved probes using nucleosides containing 3-dezauracil analogs
US5130302A (en) 1989-12-20 1992-07-14 Boron Bilogicals, Inc. Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same
US5457191A (en) 1990-01-11 1995-10-10 Isis Pharmaceuticals, Inc. 3-deazapurines
US5859221A (en) 1990-01-11 1999-01-12 Isis Pharmaceuticals, Inc. 2'-modified oligonucleotides
US6005087A (en) 1995-06-06 1999-12-21 Isis Pharmaceuticals, Inc. 2'-modified oligonucleotides
US5587470A (en) 1990-01-11 1996-12-24 Isis Pharmaceuticals, Inc. 3-deazapurines
US5459255A (en) 1990-01-11 1995-10-17 Isis Pharmaceuticals, Inc. N-2 substituted purines
US5681941A (en) 1990-01-11 1997-10-28 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
CA2088258C (en) 1990-07-27 2004-09-14 Phillip Dan Cook Nuclease resistant, pyrimidine modified oligonucleotides that detect and modulate gene expression
US5432272A (en) 1990-10-09 1995-07-11 Benner; Steven A. Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases
US5948903A (en) 1991-01-11 1999-09-07 Isis Pharmaceuticals, Inc. Synthesis of 3-deazapurines
US5594121A (en) 1991-11-07 1997-01-14 Gilead Sciences, Inc. Enhanced triple-helix and double-helix formation with oligomers containing modified purines
TW393513B (en) 1991-11-26 2000-06-11 Isis Pharmaceuticals Inc Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines
US5484908A (en) 1991-11-26 1996-01-16 Gilead Sciences, Inc. Oligonucleotides containing 5-propynyl pyrimidines
CA2122365C (en) 1991-11-26 2010-05-11 Brian Froehler Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines
US5434257A (en) 1992-06-01 1995-07-18 Gilead Sciences, Inc. Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages
US5502177A (en) 1993-09-17 1996-03-26 Gilead Sciences, Inc. Pyrimidine derivatives for labeled binding partners
US5457187A (en) 1993-12-08 1995-10-10 Board Of Regents University Of Nebraska Oligonucleotides containing 5-fluorouracil
US5596091A (en) 1994-03-18 1997-01-21 The Regents Of The University Of California Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides
US5525711A (en) 1994-05-18 1996-06-11 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Pteridine nucleotide analogs as fluorescent DNA probes
JP3756313B2 (ja) 1997-03-07 2006-03-15 武 今西 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体
USRE44779E1 (en) 1997-03-07 2014-02-25 Santaris Pharma A/S Bicyclonucleoside and oligonucleotide analogues
US6770748B2 (en) 1997-03-07 2004-08-03 Takeshi Imanishi Bicyclonucleoside and oligonucleotide analogue
US6794499B2 (en) 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
US7572582B2 (en) 1997-09-12 2009-08-11 Exiqon A/S Oligonucleotide analogues
KR100414936B1 (ko) 1997-09-12 2004-01-13 엑시콘 에이/에스 이환 및 삼환 뉴클레오시드, 뉴클레오타이드 및올리고뉴클레오타이드 동족체
US7238491B1 (en) 1998-03-27 2007-07-03 Smithkline Beecham Corporation Pregnane X receptor method
PT1178999E (pt) 1999-05-04 2007-06-26 Santaris Pharma As Análogos de l-ribo-lna
US6525191B1 (en) 1999-05-11 2003-02-25 Kanda S. Ramasamy Conformationally constrained L-nucleosides
US20030175906A1 (en) 2001-07-03 2003-09-18 Muthiah Manoharan Nuclease resistant chimeric oligonucleotides
US20030158403A1 (en) 2001-07-03 2003-08-21 Isis Pharmaceuticals, Inc. Nuclease resistant chimeric oligonucleotides
CA2504694C (en) 2002-11-05 2013-10-01 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
EP1560840B1 (en) 2002-11-05 2015-05-06 Isis Pharmaceuticals, Inc. Compositions comprising alternating 2'-modified nucleosides for use in gene modulation
WO2005018536A2 (en) 2003-05-23 2005-03-03 Human Genome Sciences, Inc. Agonist antibodies that specifically bind the glucagon like peptide-1 receptor
WO2004106356A1 (en) 2003-05-27 2004-12-09 Syddansk Universitet Functionalized nucleotide derivatives
JP4731324B2 (ja) 2003-08-28 2011-07-20 武 今西 Ｎ−ｏ結合性架橋構造型新規人工核酸
WO2005027962A1 (en) 2003-09-18 2005-03-31 Isis Pharmaceuticals, Inc. 4’-thionucleosides and oligomeric compounds
US7713944B2 (en) 2004-10-13 2010-05-11 Isis Pharmaceuticals, Inc. Oligomers comprising activated disulfides which bind to plasma proteins and their use for delivery to cells
US20060275288A1 (en) 2005-01-20 2006-12-07 Grihalde Nelson D GLP-1 receptor agonist and allosteric modulator monoclonal antibodies and uses thereof
US7569686B1 (en) 2006-01-27 2009-08-04 Isis Pharmaceuticals, Inc. Compounds and methods for synthesis of bicyclic nucleic acid analogs
ES2516815T3 (es) 2006-01-27 2014-10-31 Isis Pharmaceuticals, Inc. Análogos de ácidos nucleicos bicíclicos modificados en la posición 6
AU2007240313B2 (en) 2006-04-20 2012-02-02 Amgen Inc. GLP-1 compounds
US7666854B2 (en) 2006-05-11 2010-02-23 Isis Pharmaceuticals, Inc. Bis-modified bicyclic nucleic acid analogs
CA2651453C (en) 2006-05-11 2014-10-14 Isis Pharmaceuticals, Inc. 5'-modified bicyclic nucleic acid analogs
JP2010507387A (ja) 2006-10-25 2010-03-11 クアーク・ファーマスーティカルス、インコーポレイテッド 新規のｓｉＲＮＡおよびその使用方法
US20100190837A1 (en) 2007-02-15 2010-07-29 Isis Pharmaceuticals, Inc. 5'-Substituted-2-F' Modified Nucleosides and Oligomeric Compounds Prepared Therefrom
WO2008150729A2 (en) 2007-05-30 2008-12-11 Isis Pharmaceuticals, Inc. N-substituted-aminomethylene bridged bicyclic nucleic acid analogs
EP2173760B2 (en) 2007-06-08 2015-11-04 Isis Pharmaceuticals, Inc. Carbocyclic bicyclic nucleic acid analogs
AU2008272918B2 (en) 2007-07-05 2012-09-13 Isis Pharmaceuticals, Inc. 6-disubstituted bicyclic nucleic acid analogs
EP2188298B1 (en) 2007-08-15 2013-09-18 Isis Pharmaceuticals, Inc. Tetrahydropyran nucleic acid analogs
WO2009030738A1 (en) 2007-09-05 2009-03-12 Novo Nordisk A/S Glucagon-like peptide-1 derivatives and their pharmaceutical use
US8546556B2 (en) 2007-11-21 2013-10-01 Isis Pharmaceuticals, Inc Carbocyclic alpha-L-bicyclic nucleic acid analogs
WO2009089186A2 (en) 2008-01-05 2009-07-16 Sloan-Kettering Institute For Cancer Research Peptide-conjugated oligonucleotide therapeutic and method of making and using same
US8530640B2 (en) 2008-02-07 2013-09-10 Isis Pharmaceuticals, Inc. Bicyclic cyclohexitol nucleic acid analogs
EP2259791A2 (en) * 2008-03-05 2010-12-15 Tel HaShomer Medical Research Infrastructure and Services Ltd. Glp-1 receptor agonists and related active pharmaceutical ingredients for treatment of cancer
WO2009143014A1 (en) 2008-05-23 2009-11-26 Amylin Pharmaceuticals, Inc. Glp-1 receptor agonist bioassays
WO2010036698A1 (en) 2008-09-24 2010-04-01 Isis Pharmaceuticals, Inc. Substituted alpha-l-bicyclic nucleosides
US9012421B2 (en) 2009-08-06 2015-04-21 Isis Pharmaceuticals, Inc. Bicyclic cyclohexose nucleic acid analogs
US8389689B2 (en) 2009-10-28 2013-03-05 Janssen Biotech, Inc. Anti-GLP-1R antibodies and their uses
US9102938B2 (en) 2010-04-01 2015-08-11 Alnylam Pharmaceuticals, Inc. 2′ and 5′ modified monomers and oligonucleotides
WO2011133876A2 (en) 2010-04-22 2011-10-27 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising acyclic and abasic nucleosides and analogs
BR112012027759A2 (pt) * 2010-04-27 2017-08-15 Zealand Pharma As Conjugados de peptídeos de agonistas de receptores glp-1 e gastrina e seu uso
EP2569000B1 (en) 2010-05-13 2017-09-27 Indiana University Research and Technology Corporation Glucagon superfamily peptides exhibiting nuclear hormone receptor activity
CA2839867A1 (en) 2011-06-22 2012-12-27 Indiana University Research And Technology Corporation Glucagon/glp-1 receptor co-agonists
RU2634896C2 (ru) 2011-12-12 2017-11-08 Селджин Интернэшнл Ii Сарл Новые модуляторы рецептора glp-1
CN104968674A (zh) 2012-12-19 2015-10-07 诺和诺德股份有限公司 具有胆固醇流出活性的新颖的glp-1受体激动剂
WO2014140113A1 (en) 2013-03-13 2014-09-18 Biocrine Ab Methods for treating and/or limiting development of diabetes
US20150259416A1 (en) 2014-03-12 2015-09-17 Biocrine Ab Methods for treating and/or limiting development of diabetes
US20160003808A1 (en) 2013-03-14 2016-01-07 Galapagos Nv Molecular targets and compounds, and methods to identify the same, useful in the treatment of diseases associated with epithelial mesenchymal transition
KR102482890B1 (ko) 2013-05-01 2022-12-30 아이오니스 파마수티컬즈, 인코포레이티드 아포지질단백질 (a) 발현을 조절하는 조성물 및 방법
WO2014203518A1 (en) * 2013-06-16 2014-12-24 National University Corporation Tokyo Medical And Dental University Double-stranded antisense nucleic acid with exon-skipping effect
TW202246503A (zh) 2013-07-19 2022-12-01 美商百健Ｍａ公司 用於調節τ蛋白表現之組合物
US10010562B2 (en) 2013-11-06 2018-07-03 Merck Sharp & Dohme Corp. Dual molecular delivery of oligonucleotides and peptide containing conjugates
US10119136B2 (en) 2014-01-09 2018-11-06 Alnylam Pharmaceuticals, Inc. RNAi agents modified at the 4′-C position
WO2016011222A2 (en) 2014-07-16 2016-01-21 Moderna Therapeutics, Inc. Circular polynucleotides
US20170202979A1 (en) 2014-07-17 2017-07-20 Modernatx, Inc. Terminal modifications of polynucleotides
RU2017105342A (ru) * 2014-08-07 2018-09-13 Регулус Терапьютикс Инк. НАЦЕЛИВАНИЕ НА микроРНК ПРИ РАССТРОЙСТВАХ ОБМЕНА ВЕЩЕСТВ
WO2016055610A1 (en) 2014-10-10 2016-04-14 Novo Nordisk A/S Stable glp-1 based glp-1/glucagon receptor co-agonists
EP3328524B8 (en) * 2015-07-29 2020-03-04 DDP Specialty Electronic Materials US, Inc. Filter assembly including spiral wound membrane module and brine seal
US20210052631A1 (en) 2015-09-25 2021-02-25 Ionis Pharmaceuticals, Inc. Conjugated antisense compounds and their use
KR102608220B1 (ko) 2016-05-06 2023-11-29 아이오니스 파마수티컬즈, 인코포레이티드 Glp-1 수용체 리간드 모이어티 컨쥬게이트된 올리고뉴클레오티드 및 이의 용도

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120295958A1 (en) * 2003-04-28 2012-11-22 Isis Pharmaceuticals, Inc. Modulation of glucagon receptor expression
CN103857408A (zh) * 2011-06-22 2014-06-11 印第安那大学科技研究公司 胰高血糖素/glp-1受体协同激动剂
CN104884618A (zh) * 2012-11-15 2015-09-02 罗氏创新中心哥本哈根有限公司 寡核苷酸缀合物
US20150353930A1 (en) * 2014-06-06 2015-12-10 Berg Llc Methods of treating a metabolic syndrome by modulating heat shock protein (hsp) 90-beta

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
GENE HUNG等: "Characterization of Target mRNA Reduction Through In Situ RNA Hybridization in Multiple Organ Systems Following Systemic Antisense Treatment in Animals", 《NUCLEIC ACID THERAPEUTICS》 *
PING WANG等: "GLP-1R–Targeting Magnetic Nanoparticles for Pancreatic Islet Imaging", 《DIABETES》 *
VARMAN T. SAMUEL等: "Targeting Foxo1 in Mice Using Antisense Oligonucleotide Improves Hepatic and Peripheral Insulin Action", 《DIABETES》 *
XIN MING等: "Intracellular delivery of an antisense oligonucleotide via endocytosis of a G protein-coupled receptor", 《NUCLEIC ACIDS RESEARCH》 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114980916A (zh) * 2020-09-22 2022-08-30 魏洋 用于2型糖尿病的长效glp1类似物药物

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