JP2020094063A5 - - Google Patents
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- JP2020094063A5 JP2020094063A5 JP2020046007A JP2020046007A JP2020094063A5 JP 2020094063 A5 JP2020094063 A5 JP 2020094063A5 JP 2020046007 A JP2020046007 A JP 2020046007A JP 2020046007 A JP2020046007 A JP 2020046007A JP 2020094063 A5 JP2020094063 A5 JP 2020094063A5
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- irna agent
- uridine
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- 239000003795 chemical substances by application Substances 0.000 claims 29
- 125000003729 nucleotide group Chemical group 0.000 claims 21
- 239000002773 nucleotide Substances 0.000 claims 16
- 239000008194 pharmaceutical composition Substances 0.000 claims 7
- 230000000692 anti-sense Effects 0.000 claims 5
- 229920000972 Sense strand Polymers 0.000 claims 4
- 102100003617 SCNN1A Human genes 0.000 claims 2
- 108060000361 SCNN1A Proteins 0.000 claims 2
- 238000006011 modification reaction Methods 0.000 claims 2
- 230000002265 prevention Effects 0.000 claims 2
- JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-Dimethylaminophenol Substances CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 claims 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims 1
- 108020005544 Antisense RNA Proteins 0.000 claims 1
- 206010014418 Electrolyte imbalance Diseases 0.000 claims 1
- 206010020772 Hypertension Diseases 0.000 claims 1
- 206010052313 Liddle's syndrome Diseases 0.000 claims 1
- 210000004072 Lung Anatomy 0.000 claims 1
- 206010038435 Renal failure Diseases 0.000 claims 1
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 claims 1
- 229940045145 Uridine Drugs 0.000 claims 1
- DRTQHJPVMGBUCF-UCVXFZOQSA-N Uridine Natural products O[C@H]1[C@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UCVXFZOQSA-N 0.000 claims 1
- 229920002847 antisense RNA Polymers 0.000 claims 1
- 230000027455 binding Effects 0.000 claims 1
- 239000012472 biological sample Substances 0.000 claims 1
- 239000003184 complementary RNA Substances 0.000 claims 1
- 201000003883 cystic fibrosis Diseases 0.000 claims 1
- -1 dimethylaminoethyloxyethyl Chemical group 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 201000006370 kidney failure Diseases 0.000 claims 1
- 239000003446 ligand Substances 0.000 claims 1
- 230000001404 mediated Effects 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 230000004048 modification Effects 0.000 claims 1
- 230000001575 pathological Effects 0.000 claims 1
- ZXDUPDQEFOYLOM-UHFFFAOYSA-O propylideneazanium Chemical group [CH2-]CC=[NH2+] ZXDUPDQEFOYLOM-UHFFFAOYSA-O 0.000 claims 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims 1
- 210000001519 tissues Anatomy 0.000 claims 1
Claims (20)
- 表１Ａ〜１Ｄに示される薬剤(ＮＤ８２８５〜ＮＤ１０７８８と呼称される薬剤)のいずれか１つのセンス鎖列と１個、２個または３個のヌクレオチドだけが異なる少なくとも１５個の連続するヌクレオチドを含むセンス鎖と、
配列番号１９３の配列を有するアンチセンス配列と１、２または３個のヌクレオチドだけが異なる少なくとも１５個の連続するヌクレオチドを含むアンチセンス鎖とを含む、ｉＲＮＡ剤。 - 表１Ａ〜１Ｄに示される薬剤(ＮＤ８２８５〜ＮＤ１０７８８と呼称される薬剤)のいずれか１つのセンス鎖配列と１個、２個または３個のヌクレオチドだけが異なる少なくとも１５個の連続するヌクレオチドを含むセンス鎖と、配列番号１９３の配列を有するアンチセンス配列の少なくとも１５個の連続するヌクレオチドを含むアンチセンス鎖とを含み、ｉＲＮＡ剤とともにインキュベートされていない細胞に比べてα−ＥＮａＣの発現を２０％、３０％、４０％、５０％、６０％、７０％または８０％を超えて低下させる、ｉＲＮＡ剤。
- 前記薬剤がND-8381である、請求項１又は２に記載のｉＲＮＡ剤。
- 前記アンチセンスＲＮＡ鎖が３０以下のヌクレオチド長であり、ｉＲＮＡ剤の二本鎖領域が１５〜３０ヌクレオチド対の長さである、請求項１又は２に記載のｉＲＮＡ剤。
- ｉＲＮＡ剤に生体サンプルにおいて高い安定性を持たせる修飾を含む、請求項１又は２に記載のｉＲＮＡ剤。
- ホスホロチオエートまたは２'−修飾ヌクレオチドを含む、請求項１又は２に記載のｉＲＮＡ剤。
- 少なくとも１つの５'−ウリジン−アデニン−３'(５'−ｕａ−３')ジヌクレオチド(ここで、ウリジンは２'−修飾ヌクレオチドである)；少なくとも１つの５'−ウリジン−グアニン−３'(５'−ｕｇ−３')ジヌクレオチド(ここで、５'−ウリジンは２'−修飾ヌクレオチドである)；少なくとも１つの５'−シチジン−アデニン−３'(５'−ｃａ−３')ジヌクレオチド(ここで、５'−シチジンは２'−修飾ヌクレオチドである)；または少なくとも１つの５'−ウリジン−ウリジン−３'(５'−ｕｕ−３')ジヌクレオチド(ここで、５'−ウリジンは２'−修飾ヌクレオチドである)を含む、請求項１又は２に記載のｉＲＮＡ剤。
- 前記２'−修飾が、２'−デオキシ、２'−デオキシ−２'−フルオロ、２'−Ｏ−メチル、２'−Ｏ−メトキシエチル(２'−Ｏ−ＭＯＥ)、２'−Ｏ−アミノプロピル(２'−Ｏ−ＡＰ)、２'−Ｏ−ジメチルアミノエチル(２'−Ｏ−ＤＭＡＯＥ)、２'−Ｏ−ジメチルアミノプロピル(２'−Ｏ−ＤＭＡＰ)、２'−Ｏ−ジメチルアミノエチルオキシエチル(２'−Ｏ−ＤＭＡＥＯＥ)および２'−Ｏ−Ｎ−メチルアセトアミド(２'−Ｏ−ＮＭＡ)からなる群から選択される、請求項１又は２に記載のｉＲＮＡ剤。
- １〜４個の不対ヌクレオチドを有するヌクレオチドオーバーハングを含む、請求項１又は２に記載のｉＲＮＡ剤。
- 前記ヌクレオチドオーバーハングが２個または３個の不対ヌクレオチドを有する、請求項９に記載のｉＲＮＡ剤。
- 前記ヌクレオチドオーバーハングがｉＲＮＡ剤のアンチセンス鎖の３'末端にある、請求項９に記載のｉＲＮＡ剤。
- 上皮受容体リガンドを含む、請求項１〜３のいずれかに記載のｉＲＮＡ剤。
- 肺の細胞による取り込みに関して標的化される、請求項１〜３のいずれかに記載のｉＲＮＡ剤。
- 請求項１〜３のいずれか一項に提供される薬剤のいずれかひとつのセンス鎖配列と１個、２個または３個のヌクレオチドだけが異なる少なくとも１５個の連続するヌクレオチドを含むセンス鎖を含む、ｉＲＮＡ剤を含む医薬組成物であって、α−ＥＮａＣ発現により少なくとも部分的に媒介される病理プロセスを有するヒト対象の治療において使用するための、前記医薬組成物。
- ｉＲＮＡ剤が対象の細胞または組織におけるα−ＥＮａＣ発現のレベルを低下させるのに十分な量で投与される、請求項１４に記載の医薬組成物。
- ａ)請求項１〜３のいずれか一項に記載のｉＲＮＡ剤と、
ｂ)薬学上許容される担体
を含む、医薬組成物。 - 嚢胞性繊維症に罹患しているヒト対象の治療において使用するための、請求項１〜３のいずれか一項に記載のｉＲＮＡ剤を含む、医薬組成物。
- リドル症候群に罹患しているヒト対象の治療において使用するための、請求項１〜３のいずれか一項に記載のｉＲＮＡ剤を含む、医薬組成物。
- ヒト対象において高血圧症および／または腎不全の治療および／または予防において使用するための、請求項１〜３のいずれか一項に記載のｉＲＮＡ剤を含む、医薬組成物。
- ヒト対象において電解質平衡異常の治療および／または予防において使用するための、請求項１〜３のいずれか一項に記載のｉＲＮＡ剤を含む、医薬組成物。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2022162309A JP2022188234A (ja) | 2007-06-15 | 2022-10-07 | α－ＥＮａＣ発現のＲＮＡｉ阻害 |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP07110376.6 | 2007-06-15 | ||
| EP07110376 | 2007-06-15 | ||
| EP07114265 | 2007-08-13 | ||
| EP07114265.7 | 2007-08-13 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017149211A Division JP6680728B2 (ja) | 2007-06-15 | 2017-08-01 | α−ＥＮａＣ発現のＲＮＡｉ阻害 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022162309A Division JP2022188234A (ja) | 2007-06-15 | 2022-10-07 | α－ＥＮａＣ発現のＲＮＡｉ阻害 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2020094063A JP2020094063A (ja) | 2020-06-18 |
| JP2020094063A5 true JP2020094063A5 (ja) | 2020-08-06 |
| JP7157775B2 JP7157775B2 (ja) | 2022-10-20 |
Family
ID=40130244
Family Applications (6)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010511658A Active JP5485146B2 (ja) | 2007-06-15 | 2008-06-13 | α−ＥＮａＣ発現のＲＮＡｉ阻害 |
| JP2014029519A Active JP5719047B2 (ja) | 2007-06-15 | 2014-02-19 | α−ＥＮａＣ発現のＲＮＡｉ阻害 |
| JP2015055783A Active JP6193906B2 (ja) | 2007-06-15 | 2015-03-19 | α−ＥＮａＣ発現のＲＮＡｉ阻害 |
| JP2017149211A Active JP6680728B2 (ja) | 2007-06-15 | 2017-08-01 | α−ＥＮａＣ発現のＲＮＡｉ阻害 |
| JP2020046007A Active JP7157775B2 (ja) | 2007-06-15 | 2020-03-17 | α－ＥＮａＣ発現のＲＮＡｉ阻害 |
| JP2022162309A Pending JP2022188234A (ja) | 2007-06-15 | 2022-10-07 | α－ＥＮａＣ発現のＲＮＡｉ阻害 |
Family Applications Before (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010511658A Active JP5485146B2 (ja) | 2007-06-15 | 2008-06-13 | α−ＥＮａＣ発現のＲＮＡｉ阻害 |
| JP2014029519A Active JP5719047B2 (ja) | 2007-06-15 | 2014-02-19 | α−ＥＮａＣ発現のＲＮＡｉ阻害 |
| JP2015055783A Active JP6193906B2 (ja) | 2007-06-15 | 2015-03-19 | α−ＥＮａＣ発現のＲＮＡｉ阻害 |
| JP2017149211A Active JP6680728B2 (ja) | 2007-06-15 | 2017-08-01 | α−ＥＮａＣ発現のＲＮＡｉ阻害 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022162309A Pending JP2022188234A (ja) | 2007-06-15 | 2022-10-07 | α－ＥＮａＣ発現のＲＮＡｉ阻害 |
Country Status (26)
| Country | Link |
|---|---|
| US (12) | US7718632B2 (ja) |
| EP (7) | EP2171059A2 (ja) |
| JP (6) | JP5485146B2 (ja) |
| KR (2) | KR101821081B1 (ja) |
| CN (1) | CN101778941B (ja) |
| AR (1) | AR066984A1 (ja) |
| AU (1) | AU2008263876B2 (ja) |
| BR (1) | BRPI0813680A8 (ja) |
| CA (1) | CA2690674C (ja) |
| CL (1) | CL2008001756A1 (ja) |
| CO (1) | CO6251331A2 (ja) |
| CR (1) | CR11136A (ja) |
| CU (1) | CU23774A3 (ja) |
| EA (1) | EA200901653A1 (ja) |
| EC (1) | ECSP099794A (ja) |
| ES (6) | ES2432643T3 (ja) |
| GT (1) | GT200900315A (ja) |
| IL (1) | IL202366A0 (ja) |
| MA (1) | MA31564B1 (ja) |
| MX (1) | MX2009013609A (ja) |
| PE (1) | PE20090942A1 (ja) |
| SG (3) | SG10201404955RA (ja) |
| SV (1) | SV2009003434A (ja) |
| TN (1) | TN2009000521A1 (ja) |
| TW (3) | TWI629063B (ja) |
| WO (1) | WO2008152131A2 (ja) |
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