JP2019512498A5 - - Google Patents
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- JP2019512498A5 JP2019512498A5 JP2018548393A JP2018548393A JP2019512498A5 JP 2019512498 A5 JP2019512498 A5 JP 2019512498A5 JP 2018548393 A JP2018548393 A JP 2018548393A JP 2018548393 A JP2018548393 A JP 2018548393A JP 2019512498 A5 JP2019512498 A5 JP 2019512498A5
- Authority
- JP
- Japan
- Prior art keywords
- antisense oligonucleotide
- pharmaceutical composition
- composition according
- conjugate
- oligonucleotide conjugate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 229920000272 Oligonucleotide Polymers 0.000 claims 18
- 108020000948 Antisense Oligonucleotides Proteins 0.000 claims 15
- 239000000074 antisense oligonucleotide Substances 0.000 claims 15
- 239000008194 pharmaceutical composition Substances 0.000 claims 11
- 125000005647 linker group Chemical group 0.000 claims 5
- 239000002777 nucleoside Substances 0.000 claims 5
- 125000003835 nucleoside group Chemical group 0.000 claims 4
- 230000028993 immune response Effects 0.000 claims 3
- 150000003839 salts Chemical class 0.000 claims 3
- 239000011780 sodium chloride Substances 0.000 claims 3
- 102100007290 CD274 Human genes 0.000 claims 2
- 101710012053 CD274 Proteins 0.000 claims 2
- OVRNDRQMDRJTHS-KEWYIRBNSA-N N-[(3R,4R,5R,6R)-2,4,5-trihydroxy-6-(hydroxymethyl)oxan-3-yl]acetamide Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-KEWYIRBNSA-N 0.000 claims 2
- 241000700605 Viruses Species 0.000 claims 2
- 210000004027 cells Anatomy 0.000 claims 2
- 229920003013 deoxyribonucleic acid Polymers 0.000 claims 2
- 239000003085 diluting agent Substances 0.000 claims 2
- 201000009910 diseases by infectious agent Diseases 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims 2
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-Methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims 1
- OPTASPLRGRRNAP-UHFFFAOYSA-N Cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims 1
- 229940104302 Cytosine Drugs 0.000 claims 1
- 210000004185 Liver Anatomy 0.000 claims 1
- OVRNDRQMDRJTHS-CBQIKETKSA-N N-ACETYL-D-GALACTOSAMINE Chemical compound CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 claims 1
- 101700080605 NUC1 Proteins 0.000 claims 1
- 210000001744 T-Lymphocytes Anatomy 0.000 claims 1
- 125000004103 aminoalkyl group Chemical group 0.000 claims 1
- 239000000427 antigen Substances 0.000 claims 1
- 102000038129 antigens Human genes 0.000 claims 1
- 108091007172 antigens Proteins 0.000 claims 1
- 102000005427 asialoglycoprotein receptor family Human genes 0.000 claims 1
- 108010006523 asialoglycoprotein receptor family Proteins 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 230000021615 conjugation Effects 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 101700006494 nucA Proteins 0.000 claims 1
- 244000045947 parasites Species 0.000 claims 1
- 239000002953 phosphate buffered saline Substances 0.000 claims 1
- 159000000001 potassium salts Chemical group 0.000 claims 1
- 238000011084 recovery Methods 0.000 claims 1
- 230000001105 regulatory Effects 0.000 claims 1
- 159000000000 sodium salts Chemical group 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
Claims (18)
- CCtatttaacatcAGACのアンチセンスオリゴヌクレオチドであって、大文字がβ−Ｄ−オキシＬＮＡヌクレオシドを表し、小文字がＤＮＡヌクレオシドを表し、すべてのＬＮＡのＣが５−メチルシトシンであり、そしてすべてのヌクレオシド間結合がホスホロチオエート・ヌクレオシド間結合である、アンチセンスオリゴヌクレオチド。
- 請求項１に記載のオリゴヌクレオチドならびに当該オリゴヌクレオチドに共有結合されたコンジュゲート部分を含む、アンチセンスオリゴヌクレオチドコンジュゲートであって、リンカーが当該オリゴヌクレオチドと当該コンジュゲート部分との間に存在する、前記アンチセンスオリゴヌクレオチドコンジュゲート。
- 前記コンジュゲート部分が、３価N-アセチルガラクトサミン（GalNAc）であるアシアロ糖タンパク質受容体標的化結合部分を含む、請求項２に記載のアンチセンスオリゴヌクレオチドコンジュゲート。
- 前記リンカーが、生体開裂性リンカーである、請求項２又は３に記載のアンチセンスオリゴヌクレオチドコンジュゲート。
- 前記生体開裂性なリンカーがヌクレアーゼ感受性リンカーである、請求項４に記載のアンチセンスオリゴヌクレオチドコンジュゲート。
- 前記アンチセンスオリゴヌクレオチドコンジュゲートが、GN2-C6 o c o a o CCtatttaacatcAGACの式であり、式中、C6は６の炭素を有するアミノアルキル基であり、大文字がβ−Ｄ−オキシＬＮＡヌクレオシドを表し、小文字がＤＮＡヌクレオシドを表し、すべてのＬＮＡのＣが５−メチルシトシンであり、下付きの o は、ホスホジエステルヌクレオシド結合を表し、そして他に記載されない場合はヌクレオシド間結合はホスホロチオエート・ヌクレオシド間結合であり、そしてここでGN2は図３に示された３価GalNAcクラスターを表し、さらに図３の波線は前記クラスターのC6アミノリンカーへのコンジュゲート部位を表す、請求項２〜５のいずれか一項に記載のアンチセンスオリゴヌクレオチドコンジュゲート。
- 請求項１に記載のアンチセンスオリゴヌクレオチドコンジュゲート、又は請求項２〜６のいずれか一項に記載のアンチセンスオリゴヌクレオチドコンジュゲート、並びに医薬的に許容される希釈剤、溶媒、担体、塩、および／または補助剤を含む、医薬組成物。
- 前記医薬的に許容される希釈剤が、滅菌リン酸緩衝生理食塩水である、請求項７に記載の医薬組成物。
- 前記医薬的に許容される塩が、ナトリウム塩である、請求項７又は８に記載の医薬組成物。
- 前記医薬的に許容される塩が、カリウム塩である、請求項７又は８に記載の医薬組成物。
- PD-L1を発現する標的細胞におけるPD-L1発現を生体外で調節する方法であって、当該方法が、請求項１に記載のアンチセンスオリゴヌクレオチド、請求項２〜６のいずれか一項に記載のアンチセンスオリゴヌクレオチドコンジュゲート、或いは請求項７〜１０のいずれか一項に記載の医薬組成物の有効量を当該細胞に投与することを含む、を含む方法。
- ウイルスに対する免疫応答の回復に使用するための請求項７〜１０のいずれか一項に記載の医薬組成物。
- 前記ウイルスがHBVである、請求項１２に記載の医薬組成物。
- 寄生虫に対する免疫応答の回復に使用するための請求項７〜１０のいずれか一項に記載の医薬組成物。
- 前記免疫応答の回復が、対照と比較した場合に１又は複数のHBV抗原に特異的なCD8＋T細胞の肝臓における増加である、請求項１２又は１３に記載の医薬組成物。
- 医薬として使用するための請求項７〜１０のいずれか一項に記載の医薬組成物。
- HBV感染の治療において使用するための、請求項７〜１０のいずれか一項に記載の医薬組成物。
- HBV感染の治療用の医薬の製造のための、請求項１に記載のアンチセンスオリゴヌクレオチド、請求項２〜６のいずれか一項に記載のアンチセンスオリゴヌクレオチドコンジュゲート、請求項７〜１０のいずれか一項に記載の医薬組成物の使用。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP16160149 | 2016-03-14 | ||
| EP16160149.7 | 2016-03-14 | ||
| PCT/EP2017/055925 WO2017157899A1 (en) | 2016-03-14 | 2017-03-14 | Oligonucleotides for reduction of pd-l1 expression |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020106728A Division JP7002603B2 (ja) | 2016-03-14 | 2020-06-22 | Ｐｄ－ｌ１発現低減用のオリゴヌクレオチド |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2019512498A JP2019512498A (ja) | 2019-05-16 |
| JP2019512498A5 true JP2019512498A5 (ja) | 2020-04-16 |
| JP6748219B2 JP6748219B2 (ja) | 2020-08-26 |
Family
ID=58314191
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018548393A Active JP6748219B2 (ja) | 2016-03-14 | 2017-03-14 | Ｐｄ−ｌ１発現低減用のオリゴヌクレオチド |
| JP2020106728A Active JP7002603B2 (ja) | 2016-03-14 | 2020-06-22 | Ｐｄ－ｌ１発現低減用のオリゴヌクレオチド |
| JP2021212541A Active JP7447073B2 (ja) | 2016-03-14 | 2021-12-27 | Ｐｄ－ｌ１発現低減用のオリゴヌクレオチド |
| JP2024000251A Pending JP2024029180A (ja) | 2016-03-14 | 2024-01-04 | Ｐｄ－ｌ１発現低減用のオリゴヌクレオチド |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020106728A Active JP7002603B2 (ja) | 2016-03-14 | 2020-06-22 | Ｐｄ－ｌ１発現低減用のオリゴヌクレオチド |
| JP2021212541A Active JP7447073B2 (ja) | 2016-03-14 | 2021-12-27 | Ｐｄ－ｌ１発現低減用のオリゴヌクレオチド |
| JP2024000251A Pending JP2024029180A (ja) | 2016-03-14 | 2024-01-04 | Ｐｄ－ｌ１発現低減用のオリゴヌクレオチド |
Country Status (31)
| Country | Link |
|---|---|
| US (5) | US20170283496A1 (ja) |
| EP (2) | EP3786297A1 (ja) |
| JP (4) | JP6748219B2 (ja) |
| KR (4) | KR102306797B1 (ja) |
| CN (5) | CN108779465B (ja) |
| AR (2) | AR108038A1 (ja) |
| AU (4) | AU2017235278C1 (ja) |
| BR (1) | BR112018068410A2 (ja) |
| CA (2) | CA3120687A1 (ja) |
| CL (4) | CL2018002570A1 (ja) |
| CO (1) | CO2018007761A2 (ja) |
| CR (2) | CR20200119A (ja) |
| DK (1) | DK3430141T3 (ja) |
| ES (1) | ES2857702T3 (ja) |
| HR (1) | HRP20210315T1 (ja) |
| HU (1) | HUE053172T2 (ja) |
| IL (4) | IL296483B2 (ja) |
| LT (1) | LT3430141T (ja) |
| MX (2) | MX2018010830A (ja) |
| MY (1) | MY194912A (ja) |
| PE (3) | PE20181892A1 (ja) |
| PH (1) | PH12018501964A1 (ja) |
| PL (1) | PL3430141T3 (ja) |
| PT (1) | PT3430141T (ja) |
| RS (1) | RS61528B1 (ja) |
| RU (1) | RU2747822C2 (ja) |
| SG (1) | SG11201807854SA (ja) |
| SI (1) | SI3430141T1 (ja) |
| TW (4) | TWI790485B (ja) |
| UA (1) | UA127432C2 (ja) |
| WO (1) | WO2017157899A1 (ja) |
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| EP3248982A1 (en) | 2011-07-19 | 2017-11-29 | Wave Life Sciences Ltd. | Thiosulfonate reagents for the synthesis of functionalized nucleic acids |
| PL2872147T3 (pl) | 2012-07-13 | 2023-09-25 | Wave Life Sciences Ltd. | Sposób wytwarzania chiralnych oligonukleotydów |
| SG11201500239VA (en) | 2012-07-13 | 2015-03-30 | Wave Life Sciences Japan | Asymmetric auxiliary group |
| JPWO2015108047A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 免疫誘導活性を有するキラル核酸アジュバンド及び免疫誘導活性剤 |
| WO2015108048A1 (ja) | 2014-01-15 | 2015-07-23 | 株式会社新日本科学 | 抗腫瘍作用を有するキラル核酸アジュバンド及び抗腫瘍剤 |
| SG10201912897UA (en) | 2014-01-16 | 2020-02-27 | Wave Life Sciences Ltd | Chiral design |
| JP2018520688A (ja) | 2015-07-21 | 2018-08-02 | ザ チルドレンズ メディカル センター コーポレーション | Ｐｄ−ｌ１発現造血幹細胞およびその使用 |
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