JP2010505432A5 - - Google Patents
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- JP2010505432A5 JP2010505432A5 JP2009531824A JP2009531824A JP2010505432A5 JP 2010505432 A5 JP2010505432 A5 JP 2010505432A5 JP 2009531824 A JP2009531824 A JP 2009531824A JP 2009531824 A JP2009531824 A JP 2009531824A JP 2010505432 A5 JP2010505432 A5 JP 2010505432A5
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- Prior art keywords
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- lna
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- 125000003729 nucleotide group Chemical group 0.000 claims 29
- 101001098868 Homo sapiens Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 claims 15
- 239000002773 nucleotide Substances 0.000 claims 14
- 102100038955 Proprotein convertase subtilisin/kexin type 9 Human genes 0.000 claims 13
- 150000007523 nucleic acids Chemical class 0.000 claims 12
- 108020004414 DNA Proteins 0.000 claims 9
- 108020004707 nucleic acids Proteins 0.000 claims 8
- 102000039446 nucleic acids Human genes 0.000 claims 8
- 230000000295 complement effect Effects 0.000 claims 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 6
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims 5
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 4
- 150000001875 compounds Chemical class 0.000 claims 4
- 208000035475 disorder Diseases 0.000 claims 4
- 208000027866 inflammatory disease Diseases 0.000 claims 4
- 208000030159 metabolic disease Diseases 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 102100034343 Integrase Human genes 0.000 claims 3
- 101710203526 Integrase Proteins 0.000 claims 3
- 229910019142 PO4 Inorganic materials 0.000 claims 3
- 239000010452 phosphate Substances 0.000 claims 3
- 150000003839 salts Chemical group 0.000 claims 3
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims 3
- 208000024827 Alzheimer disease Diseases 0.000 claims 2
- 201000001320 Atherosclerosis Diseases 0.000 claims 2
- 208000035150 Hypercholesterolemia Diseases 0.000 claims 2
- 208000001145 Metabolic Syndrome Diseases 0.000 claims 2
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims 2
- 230000000692 anti-sense effect Effects 0.000 claims 2
- 206010003246 arthritis Diseases 0.000 claims 2
- 208000006673 asthma Diseases 0.000 claims 2
- 206010012601 diabetes mellitus Diseases 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 230000002708 enhancing effect Effects 0.000 claims 2
- 102000053786 human PCSK9 Human genes 0.000 claims 2
- 108020004999 messenger RNA Proteins 0.000 claims 2
- PCTMTFRHKVHKIS-BMFZQQSSSA-N (1s,3r,4e,6e,8e,10e,12e,14e,16e,18s,19r,20r,21s,25r,27r,30r,31r,33s,35r,37s,38r)-3-[(2r,3s,4s,5s,6r)-4-amino-3,5-dihydroxy-6-methyloxan-2-yl]oxy-19,25,27,30,31,33,35,37-octahydroxy-18,20,21-trimethyl-23-oxo-22,39-dioxabicyclo[33.3.1]nonatriaconta-4,6,8,10 Chemical compound C1C=C2C[C@@H](OS(O)(=O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2.O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 PCTMTFRHKVHKIS-BMFZQQSSSA-N 0.000 claims 1
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims 1
- RHCSKNNOAZULRK-APZFVMQVSA-N 2,2-dideuterio-2-(3,4,5-trimethoxyphenyl)ethanamine Chemical compound NCC([2H])([2H])C1=CC(OC)=C(OC)C(OC)=C1 RHCSKNNOAZULRK-APZFVMQVSA-N 0.000 claims 1
- XQCZBXHVTFVIFE-UHFFFAOYSA-N 2-amino-4-hydroxypyrimidine Chemical compound NC1=NC=CC(O)=N1 XQCZBXHVTFVIFE-UHFFFAOYSA-N 0.000 claims 1
- MWBWWFOAEOYUST-UHFFFAOYSA-N 2-aminopurine Chemical compound NC1=NC=C2N=CNC2=N1 MWBWWFOAEOYUST-UHFFFAOYSA-N 0.000 claims 1
- HBJGQJWNMZDFKL-UHFFFAOYSA-N 2-chloro-7h-purin-6-amine Chemical compound NC1=NC(Cl)=NC2=C1NC=N2 HBJGQJWNMZDFKL-UHFFFAOYSA-N 0.000 claims 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 1
- LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 claims 1
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical group CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims 1
- UJBCLAXPPIDQEE-UHFFFAOYSA-N 5-prop-1-ynyl-1h-pyrimidine-2,4-dione Chemical compound CC#CC1=CNC(=O)NC1=O UJBCLAXPPIDQEE-UHFFFAOYSA-N 0.000 claims 1
- VKKXEIQIGGPMHT-UHFFFAOYSA-N 7h-purine-2,8-diamine Chemical compound NC1=NC=C2NC(N)=NC2=N1 VKKXEIQIGGPMHT-UHFFFAOYSA-N 0.000 claims 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 claims 1
- 229930024421 Adenine Natural products 0.000 claims 1
- 102100030431 Fatty acid-binding protein, adipocyte Human genes 0.000 claims 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims 1
- 101001062864 Homo sapiens Fatty acid-binding protein, adipocyte Proteins 0.000 claims 1
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 claims 1
- 229930010555 Inosine Natural products 0.000 claims 1
- 241000283984 Rodentia Species 0.000 claims 1
- 229940123464 Thiazolidinedione Drugs 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 230000003110 anti-inflammatory effect Effects 0.000 claims 1
- 230000000840 anti-viral effect Effects 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 208000016097 disease of metabolism Diseases 0.000 claims 1
- 229940125753 fibrate Drugs 0.000 claims 1
- 229960003786 inosine Drugs 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- -1 nucleic acid salts Chemical class 0.000 claims 1
- 108091033319 polynucleotide Proteins 0.000 claims 1
- 102000040430 polynucleotide Human genes 0.000 claims 1
- 239000002157 polynucleotide Substances 0.000 claims 1
- 239000000651 prodrug Substances 0.000 claims 1
- 229940002612 prodrug Drugs 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US82873506P | 2006-10-09 | 2006-10-09 | |
| US97293207P | 2007-09-17 | 2007-09-17 | |
| US97740907P | 2007-10-04 | 2007-10-04 | |
| PCT/EP2007/060703 WO2008043753A2 (en) | 2006-10-09 | 2007-10-09 | Rna antagonist compounds for the modulation of pcsk9 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2010505432A JP2010505432A (ja) | 2010-02-25 |
| JP2010505432A5 true JP2010505432A5 (https=) | 2010-12-02 |
Family
ID=39125211
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009531824A Withdrawn JP2010505432A (ja) | 2006-10-09 | 2007-10-09 | Ｐｃｓｋ９を調節するためのｒｎａアンタゴニスト化合物 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US20100216864A1 (https=) |
| EP (2) | EP2444494B1 (https=) |
| JP (1) | JP2010505432A (https=) |
| AU (1) | AU2007306361A1 (https=) |
| CA (1) | CA2666191C (https=) |
| ES (1) | ES2603379T3 (https=) |
| IL (1) | IL197668A0 (https=) |
| MX (1) | MX2009003729A (https=) |
| WO (1) | WO2008043753A2 (https=) |
Families Citing this family (74)
| Publication number | Priority date | Publication date | Assignee | Title |
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| EP2023940B1 (en) | 2006-05-05 | 2011-06-22 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating expression of sglt2 |
| US8093222B2 (en) | 2006-11-27 | 2012-01-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| JP2010510807A (ja) * | 2006-11-27 | 2010-04-08 | アイシス ファーマシューティカルズ， インコーポレーテッド | 高コレステロール血症を治療するための方法 |
| CA2681406A1 (en) | 2007-03-22 | 2008-09-25 | Santaris Pharma A/S | Rna antagonist compounds for the inhibition of apo-b100 expression |
| WO2009027527A2 (en) * | 2007-08-30 | 2009-03-05 | Santaris Pharma A/S | Rna antagonist compounds for the modulation of fabp4/ap2 |
| US20110224280A1 (en) * | 2008-04-16 | 2011-09-15 | Niels Fisker Nielsen | Pharmaceutical Composition Comprising Anti PCSK9 Oligomers |
| WO2009143367A2 (en) * | 2008-05-22 | 2009-11-26 | Schering Corporation | Egf-a domain-mediated modulation of pcsk9 |
| WO2009148605A2 (en) * | 2008-06-04 | 2009-12-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| US8563528B2 (en) | 2009-07-21 | 2013-10-22 | Santaris Pharma A/S | Antisense oligomers targeting PCSK9 |
| EP2490699A1 (en) | 2009-10-20 | 2012-08-29 | Santaris Pharma A/S | Oral delivery of therapeutically effective lna oligonucleotides |
| GB2481373A (en) * | 2010-06-21 | 2011-12-28 | Weiming Xu | Treatment of hypercholesterolaemia by ubiquitination of PCSK9 |
| JP5875006B2 (ja) * | 2010-08-31 | 2016-03-02 | 国立大学法人大阪大学 | オリゴヌクレオチド、およびオリゴヌクレオチドを有効成分として含有する脂質異常症治療剤 |
| EP3260540A1 (en) | 2010-11-12 | 2017-12-27 | The General Hospital Corporation | Polycomb-associated non-coding rnas |
| CA3077910A1 (en) | 2010-11-17 | 2012-05-24 | Ionis Pharmaceuticals, Inc. | Modulation of alpha synuclein expression |
| AU2012205718B2 (en) | 2011-01-10 | 2017-07-06 | The Regents Of The University Of Michigan | Stem cell factor inhibitor |
| WO2013001372A2 (en) | 2011-06-30 | 2013-01-03 | University Of Oslo | Methods and compositions for inhibition of activation of regulatory t cells |
| MX340536B (es) | 2011-07-06 | 2016-07-13 | Sykehuset Sorlandet Hf | Terapia direccionada al receptor del factor de crecimiento epidermico (egfr). |
| HK1200484A1 (zh) | 2011-09-14 | 2015-08-07 | Translate Bio Ma, Inc. | 多聚寡核苷酸化合物 |
| AU2012353330B2 (en) | 2011-12-16 | 2018-04-19 | National University Corporation Tokyo Medical And Dental University | Chimeric double-stranded nucleic acid |
| US9255154B2 (en) | 2012-05-08 | 2016-02-09 | Alderbio Holdings, Llc | Anti-PCSK9 antibodies and use thereof |
| WO2013173652A1 (en) | 2012-05-16 | 2013-11-21 | Rana Therapeutics, Inc. | Compositions and methods for modulating gene expression |
| WO2013184209A1 (en) | 2012-06-04 | 2013-12-12 | Ludwig Institute For Cancer Research Ltd. | Mif for use in methods of treating subjects with a neurodegenerative disorder |
| JP2015165772A (ja) * | 2012-07-04 | 2015-09-24 | 国立大学法人大阪大学 | オリゴヌクレオチド、およびオリゴヌクレオチドを有効成分として含有する脂質異常症治療剤 |
| WO2014062736A1 (en) | 2012-10-15 | 2014-04-24 | Isis Pharmaceuticals, Inc. | Methods for monitoring c9orf72 expression |
| ES2762326T5 (es) | 2012-10-15 | 2023-04-27 | Ionis Pharmaceuticals Inc | Métodos para modular la expresión de C9ORF72 |
| HK1212597A1 (zh) | 2012-10-15 | 2016-06-17 | Isis Pharmaceuticals, Inc. | 用於調節c90rf72表達的組合物 |
| US10058630B2 (en) | 2012-10-22 | 2018-08-28 | Concievalve, Llc | Methods for inhibiting stenosis, obstruction, or calcification of a stented heart valve or bioprosthesis |
| US10077443B2 (en) | 2012-11-15 | 2018-09-18 | Roche Innovation Center Copenhagen A/S | Oligonucleotide conjugates |
| EP2935333A1 (en) | 2012-12-21 | 2015-10-28 | Sykehuset Sorlandet HF | Egfr targeted therapy of neurological disorders and pain |
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| CA2901983A1 (en) | 2013-03-01 | 2014-09-04 | National University Corporation Tokyo Medical And Dental University | Chimeric single-stranded antisense polynucleotides and double-stranded antisense agent |
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| ES2770667T3 (es) | 2013-06-27 | 2020-07-02 | Roche Innovation Ct Copenhagen As | Oligómeros antisentido y conjugados que se dirigen a PCSK9 |
| WO2015006554A1 (en) | 2013-07-10 | 2015-01-15 | The Regents Of The University Of Michigan | Therapeutic antibodies and uses thereof |
| EP4166667A3 (en) | 2013-10-11 | 2023-08-02 | Ionis Pharmaceuticals, Inc. | Compositions for modulating c9orf72 expression |
| US10301624B2 (en) | 2014-06-25 | 2019-05-28 | The General Hospital Corporation | Targeting human satellite II (HSATII) |
| EP3973958A3 (en) * | 2015-03-20 | 2022-06-22 | Aarhus Universitet | Inhibitors of pcsk9 for treatment of lipoprotein metabolism disorders |
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| RS60230B1 (sr) | 2015-04-16 | 2020-06-30 | Ionis Pharmaceuticals Inc | Kompozicije za moduliranje ekspresije c9orf72 |
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| EP3517610A4 (en) | 2016-09-23 | 2020-05-27 | National University Corporation Tokyo Medical and Dental University | THROUGH HETERODUPLEX NUCLEIC ACID THROUGH BLOOD BRAIN CABINET |
| US11260134B2 (en) | 2016-09-29 | 2022-03-01 | National University Corporation Tokyo Medical And Dental University | Double-stranded nucleic acid complex having overhang |
| CN110337495B (zh) | 2017-02-06 | 2024-03-29 | 日产化学株式会社 | 单链寡核苷酸 |
| US11273222B2 (en) | 2017-05-26 | 2022-03-15 | National Cerebral And Cardiovascular Center | Antisense nucleic acid targeting PCSK9 |
| WO2019004420A1 (ja) | 2017-06-30 | 2019-01-03 | 国立大学法人東京医科歯科大学 | ヘテロ二本鎖型ａｎｔｉｍｉＲ |
| AU2018307294B2 (en) | 2017-07-26 | 2025-04-17 | Nissan Chemical Corporation | Single-stranded oligonucleotide |
| JP7360170B2 (ja) | 2018-02-28 | 2023-10-12 | 国立大学法人 東京医科歯科大学 | 虚血病変部位特異的な遺伝子治療法 |
| EP3766972B1 (en) | 2018-03-14 | 2025-04-23 | Institute of Science Tokyo | Nucleic acid complex |
| US11851654B2 (en) | 2018-03-19 | 2023-12-26 | National University Corporation Tokyo Medical And Dental University | Nucleic acid with reduced toxicity |
| MX2020009765A (es) | 2018-03-20 | 2021-01-08 | Tokyo Inst Tech | Oligonucleotido antisentido reducido en toxicidad. |
| JP7262816B2 (ja) | 2018-03-22 | 2023-04-24 | 国立大学法人 東京医科歯科大学 | ヘテロ核酸のｂｂｂ通過脂質リガンド |
| US20210308170A1 (en) | 2018-07-27 | 2021-10-07 | Osaka University | Composition for suppression of aging, prevention, amelioration, or treatment of an age-related disease or symptom, or extension of lifespan |
| US20220193250A1 (en) | 2018-08-02 | 2022-06-23 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for treating facioscapulohumeral muscular dystrophy |
| JP7530106B2 (ja) | 2019-03-14 | 2024-08-07 | レナセラピューティクス株式会社 | Ｉｈｈ発現を調節するための核酸複合体 |
| EP3954395A4 (en) | 2019-04-08 | 2023-06-28 | National University Corporation Tokyo Medical and Dental University | Pharmaceutical composition for muscle disease treatment |
| US20220370491A1 (en) | 2019-09-18 | 2022-11-24 | National University Corporation Tokyo Medical And Dental University | Nucleic acid complex |
| JP7793144B2 (ja) | 2019-10-11 | 2026-01-05 | 国立大学法人東京科学大学 | 修飾ヘテロ核酸 |
| EP4098747A4 (en) | 2020-01-31 | 2025-03-26 | Sanwa Kagaku Kenkyusho Co., Ltd. | ATN1 ANTISENSE OLIGONUCLEOTIDE |
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| US20240240183A1 (en) | 2021-05-25 | 2024-07-18 | National University Corporation Tokyo Medical And Dental University | Heteronucleic acid containing scpBNA or AmNA |
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| WO2023042876A1 (ja) | 2021-09-15 | 2023-03-23 | 国立大学法人東京医科歯科大学 | ２'－修飾ヌクレオシドを含むヘテロ核酸 |
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| IL318625A (en) | 2022-07-29 | 2025-03-01 | Regeneron Pharma | Compositions and methods for transferrin receptor (TFR)-mediated delivery to brain and muscle |
| JPWO2024071099A1 (https=) | 2022-09-29 | 2024-04-04 | ||
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| FR2848572B1 (fr) * | 2002-12-12 | 2005-12-09 | Univ Joseph Fourier | Molecules inhibitrices de la synthese proteique du virus de l'hepatite c et procede de criblage desdites molecules inhibitrices |
| EP1471152A1 (en) | 2003-04-25 | 2004-10-27 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Mutations in the human PCSK9 gene associated to hypercholesterolemia |
| US7683036B2 (en) * | 2003-07-31 | 2010-03-23 | Regulus Therapeutics Inc. | Oligomeric compounds and compositions for use in modulation of small non-coding RNAs |
| WO2005073378A1 (en) | 2004-01-30 | 2005-08-11 | Santaris Pharma A/S | MODIFIED SHORT INTERFERING RNA (MODIFIED siRNA) |
| PL1786472T3 (pl) * | 2004-08-10 | 2013-06-28 | Kastle Therapeutics Llc | Antysensowna modulacja ekspresji apolipoproteiny B |
| US20060185027A1 (en) * | 2004-12-23 | 2006-08-17 | David Bartel | Systems and methods for identifying miRNA targets and for altering miRNA and target expression |
| AU2007275365A1 (en) * | 2006-07-17 | 2008-01-24 | Sirna Therapeutics Inc. | RNA interference mediated inhibition of Proprotein Convertase Subtilisin Kexin 9 (PCSK9) gene expression using short interfering nucleic acid (siNA) |
-
2007
- 2007-10-09 ES ES11181596.5T patent/ES2603379T3/es active Active
- 2007-10-09 MX MX2009003729A patent/MX2009003729A/es not_active Application Discontinuation
- 2007-10-09 EP EP11181596.5A patent/EP2444494B1/en active Active
- 2007-10-09 CA CA2666191A patent/CA2666191C/en active Active
- 2007-10-09 US US12/444,806 patent/US20100216864A1/en not_active Abandoned
- 2007-10-09 JP JP2009531824A patent/JP2010505432A/ja not_active Withdrawn
- 2007-10-09 AU AU2007306361A patent/AU2007306361A1/en not_active Abandoned
- 2007-10-09 WO PCT/EP2007/060703 patent/WO2008043753A2/en not_active Ceased
- 2007-10-09 EP EP07821072A patent/EP2076597A2/en not_active Withdrawn
-
2009
- 2009-03-18 IL IL197668A patent/IL197668A0/en active IP Right Grant
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