JP2019505598A5 - - Google Patents
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- JP2019505598A5 JP2019505598A5 JP2018563402A JP2018563402A JP2019505598A5 JP 2019505598 A5 JP2019505598 A5 JP 2019505598A5 JP 2018563402 A JP2018563402 A JP 2018563402A JP 2018563402 A JP2018563402 A JP 2018563402A JP 2019505598 A5 JP2019505598 A5 JP 2019505598A5
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- 108091034117 Oligonucleotide Proteins 0.000 claims description 112
- 239000000074 antisense oligonucleotide Substances 0.000 claims description 101
- 238000012230 antisense oligonucleotides Methods 0.000 claims description 101
- 101700026522 SMAD7 Proteins 0.000 claims description 95
- 206010072877 Intestinal fibrosis Diseases 0.000 claims description 89
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 8
- 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 description 6
- 206010009887 colitis Diseases 0.000 claims description 6
- 102000008186 Collagen Human genes 0.000 claims description 5
- 108010035532 Collagen Proteins 0.000 claims description 5
- 229920001436 collagen Polymers 0.000 claims description 5
- 230000008021 deposition Effects 0.000 claims description 5
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
- 208000011231 Crohn disease Diseases 0.000 claims description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
- 230000001154 acute effect Effects 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 102000007469 Actins Human genes 0.000 claims description 2
- 108010085238 Actins Proteins 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000002702 enteric coating Substances 0.000 claims description 2
- 238000009505 enteric coating Methods 0.000 claims description 2
- GDCRSXZBSIRSFR-UHFFFAOYSA-N ethyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.CCOC(=O)C=C GDCRSXZBSIRSFR-UHFFFAOYSA-N 0.000 claims description 2
- 229920003145 methacrylic acid copolymer Polymers 0.000 claims description 2
- 229940117841 methacrylic acid copolymer Drugs 0.000 claims description 2
- 210000003205 muscle Anatomy 0.000 claims description 2
- 102100030608 Mothers against decapentaplegic homolog 7 Human genes 0.000 claims 5
- 229940123231 SMAD7 inhibitor Drugs 0.000 claims 4
- 210000001842 enterocyte Anatomy 0.000 claims 1
- 230000001131 transforming effect Effects 0.000 claims 1
- 238000000034 method Methods 0.000 description 208
- 102000049873 Smad7 Human genes 0.000 description 90
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 69
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 69
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 69
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 18
- 239000002773 nucleotide Substances 0.000 description 17
- 125000003729 nucleotide group Chemical group 0.000 description 17
- 239000000203 mixture Substances 0.000 description 15
- LUCHPKXVUGJYGU-XLPZGREQSA-N 5-methyl-2'-deoxycytidine Chemical compound O=C1N=C(N)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 LUCHPKXVUGJYGU-XLPZGREQSA-N 0.000 description 6
- 238000002965 ELISA Methods 0.000 description 6
- 101000652166 Homo sapiens Mothers against decapentaplegic homolog 7 Proteins 0.000 description 6
- 102000044356 human SMAD7 Human genes 0.000 description 6
- 231100000682 maximum tolerated dose Toxicity 0.000 description 6
- 238000010276 construction Methods 0.000 description 4
- 230000000968 intestinal effect Effects 0.000 description 4
- CDKIEBFIMCSCBB-UHFFFAOYSA-N 1-(6,7-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)-3-(1-methyl-2-phenylpyrrolo[2,3-b]pyridin-3-yl)prop-2-en-1-one;hydrochloride Chemical class Cl.C1C=2C=C(OC)C(OC)=CC=2CCN1C(=O)C=CC(C1=CC=CN=C1N1C)=C1C1=CC=CC=C1 CDKIEBFIMCSCBB-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 235000006694 eating habits Nutrition 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 210000002381 plasma Anatomy 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 230000000391 smoking effect Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 206010016654 Fibrosis Diseases 0.000 description 2
- 102100025748 Mothers against decapentaplegic homolog 3 Human genes 0.000 description 2
- 101710143111 Mothers against decapentaplegic homolog 3 Proteins 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 230000004761 fibrosis Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662298988P | 2016-02-23 | 2016-02-23 | |
| US62/298,988 | 2016-02-23 | ||
| PCT/US2017/019094 WO2017147276A1 (en) | 2016-02-23 | 2017-02-23 | Methods of treating intestinal fibrosis using smad7 inhibition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2019505598A JP2019505598A (ja) | 2019-02-28 |
| JP2019505598A5 true JP2019505598A5 (https=) | 2020-04-16 |
Family
ID=59686543
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018563402A Pending JP2019505598A (ja) | 2016-02-23 | 2017-02-23 | Ｓｍａｄ７の阻害を用いて、腸線維症を治療する方法 |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US11162097B2 (https=) |
| EP (1) | EP3420082A4 (https=) |
| JP (1) | JP2019505598A (https=) |
| WO (1) | WO2017147276A1 (https=) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3420082A4 (en) | 2016-02-23 | 2019-10-16 | Celgene Alpine Investment Company II, LLC | METHOD FOR THE TREATMENT OF DARM FIBROSIS USING SMAD7 INHIBITION |
| CN108753791B (zh) * | 2018-07-01 | 2020-10-13 | 中国农业科学院植物保护研究所 | 绿盲蝽decapentaplegic基因及其RNAi在害虫防控中的应用 |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AUPR638101A0 (en) * | 2001-07-13 | 2001-08-09 | Bioa Pty Limited | Composition and method for treatment of disease |
| EP1456380B1 (en) | 2001-11-02 | 2012-04-18 | Giuliani International Limited | Smad7 inhibitors for the treatment of cns diseases |
| ITRM20030149A1 (it) | 2003-04-02 | 2004-10-03 | Giuliani Spa | Oligonucleotidi (odn) antisenso per smad7 e loro usi in campo medico |
| RU2593939C2 (ru) * | 2008-11-13 | 2016-08-10 | Ногра Фарма Лимитед | Антисмысловые композиции и способы их получения и применения |
| JP6389122B2 (ja) | 2011-09-15 | 2018-09-12 | ノグラ ファーマ リミテッド | 抗ｓｍａｄ７治療に対する応答性をモニターするための方法 |
| CN109999017A (zh) * | 2012-02-09 | 2019-07-12 | 诺格拉制药有限公司 | 治疗纤维化的方法 |
| CN107252492A (zh) | 2012-04-18 | 2017-10-17 | 诺格尔制药有限公司 | 治疗糖尿病和/或促进胰岛移植后存活的方法 |
| US9078918B2 (en) * | 2012-05-08 | 2015-07-14 | Northwestern University | Inhibition of fibrosis and AF by TGF-beta inhibition in the posterior left atrium (PLA) |
| EP2948137B1 (en) * | 2013-01-18 | 2018-11-14 | Genfit | Methods of treatment of fibrosis and cancers |
| AU2014229985B2 (en) | 2013-03-15 | 2018-12-13 | Nogra Pharma Limited | Methods of treating colorectal cancer |
| US10006029B2 (en) | 2013-03-15 | 2018-06-26 | Nogra Pharma Limited | Methods of treating colorectal cancer |
| AU2015257589A1 (en) | 2014-05-09 | 2016-11-24 | Nogra Pharma Limited | Methods for treating inflammatory bowel disease |
| EP3213070A2 (en) | 2014-10-17 | 2017-09-06 | Nogra Pharma Limited | Methods for dosing and monitoring smad7 antisense oligonucleotide treatment using biomarker levels |
| EP3207136A1 (en) * | 2014-10-17 | 2017-08-23 | Nogra Pharma Limited | Methods and compositions for treating a subject with a smad7 antisense oligonucleotide |
| EP3207135A2 (en) | 2014-10-17 | 2017-08-23 | Celgene Alpine Investment Company II, LLC | Isotopologues of smad7 antisense oligonucleotides |
| MA41271A (fr) | 2014-12-26 | 2017-10-31 | Celgene Alpine Invest Company Ii Llc | Méthodes d'utilisation d'oligonucléotides antisens ciblant smad7 |
| CA3000569A1 (en) | 2015-09-30 | 2017-04-06 | Nogra Pharma Limited | Methods of using smad7 antisense oligonucleotides based on biomarker expression |
| WO2017059225A1 (en) | 2015-09-30 | 2017-04-06 | Celgene Corporation | Tlr modulators and methods of use |
| PT3380615T (pt) * | 2015-11-25 | 2021-04-01 | Nogra Pharma Ltd | Oligonucleótidos antissentido il-34 e métodos de utilização dos mesmos |
| EP3420082A4 (en) | 2016-02-23 | 2019-10-16 | Celgene Alpine Investment Company II, LLC | METHOD FOR THE TREATMENT OF DARM FIBROSIS USING SMAD7 INHIBITION |
| WO2017144689A1 (en) | 2016-02-24 | 2017-08-31 | Nogra Pharma Limited | Methods of treating celiac disease using smad7 inhibition |
| US20200237801A1 (en) | 2016-05-12 | 2020-07-30 | Nogra Pharma Limited | Methods of using smad7 antisense oligonucleotides based on biomarker expression |
| WO2018122376A1 (en) | 2016-12-30 | 2018-07-05 | Nogra Pharma Limited | Compositions of smad7 antisense oligonucleotide and methods of treating or preventing psoriasis |
| JP2020528910A (ja) | 2017-07-28 | 2020-10-01 | セルジーン コーポレイション | オリゴヌクレオチド化合物の調製方法 |
-
2017
- 2017-02-23 EP EP17757196.5A patent/EP3420082A4/en not_active Withdrawn
- 2017-02-23 US US16/079,059 patent/US11162097B2/en not_active Expired - Fee Related
- 2017-02-23 WO PCT/US2017/019094 patent/WO2017147276A1/en not_active Ceased
- 2017-02-23 JP JP2018563402A patent/JP2019505598A/ja active Pending
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