JPWO2019165067A5 - - Google Patents
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- JPWO2019165067A5 JPWO2019165067A5 JP2020544270A JP2020544270A JPWO2019165067A5 JP WO2019165067 A5 JPWO2019165067 A5 JP WO2019165067A5 JP 2020544270 A JP2020544270 A JP 2020544270A JP 2020544270 A JP2020544270 A JP 2020544270A JP WO2019165067 A5 JPWO2019165067 A5 JP WO2019165067A5
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- Prior art keywords
- aso
- seq
- camk2d
- nucleotides
- conjugate
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- 239000002773 nucleotide Substances 0.000 claims 10
- 125000003729 nucleotide group Chemical group 0.000 claims 10
- 239000002777 nucleoside Substances 0.000 claims 9
- 150000003833 nucleoside derivatives Chemical class 0.000 claims 7
- 239000008194 pharmaceutical composition Substances 0.000 claims 7
- 208000008787 Cardiovascular Disease Diseases 0.000 claims 6
- 229920001850 Nucleic acid sequence Polymers 0.000 claims 6
- 229920000160 (ribonucleotides)n+m Polymers 0.000 claims 5
- 108090000623 proteins and genes Proteins 0.000 claims 5
- 102000004169 proteins and genes Human genes 0.000 claims 5
- 239000000203 mixture Substances 0.000 claims 3
- 150000007523 nucleic acids Chemical group 0.000 claims 3
- 108020000948 Antisense Oligonucleotides Proteins 0.000 claims 2
- 108020004999 Messenger RNA Proteins 0.000 claims 2
- 229920000272 Oligonucleotide Polymers 0.000 claims 2
- 239000000074 antisense oligonucleotide Substances 0.000 claims 2
- -1 bicyclic nucleoside Chemical class 0.000 claims 2
- 230000000295 complement Effects 0.000 claims 2
- 229920003013 deoxyribonucleic acid Polymers 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 229920002106 messenger RNA Polymers 0.000 claims 2
- 208000007474 Aortic Aneurysm Diseases 0.000 claims 1
- 206010003119 Arrhythmia Diseases 0.000 claims 1
- 210000001367 Arteries Anatomy 0.000 claims 1
- 101710038053 CAMK2D Proteins 0.000 claims 1
- 206010007521 Cardiac arrhythmias Diseases 0.000 claims 1
- 206010007554 Cardiac failure Diseases 0.000 claims 1
- 241000083551 Ena Species 0.000 claims 1
- 239000005977 Ethylene Substances 0.000 claims 1
- 101710022695 F40F8.1 Proteins 0.000 claims 1
- 208000002907 Heart Valve Disease Diseases 0.000 claims 1
- 206010019280 Heart failure Diseases 0.000 claims 1
- 210000004165 Myocardium Anatomy 0.000 claims 1
- 208000004124 Rheumatic Heart Disease Diseases 0.000 claims 1
- 208000006011 Stroke Diseases 0.000 claims 1
- 206010047249 Venous thrombosis Diseases 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 230000002730 additional Effects 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 230000000240 adjuvant Effects 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 201000003137 congenital heart disease Diseases 0.000 claims 1
- 201000008739 coronary artery disease Diseases 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 229940079593 drugs Drugs 0.000 claims 1
- 201000002053 hypertensive heart disease Diseases 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 108020004707 nucleic acids Proteins 0.000 claims 1
- 230000002093 peripheral Effects 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 229920000023 polynucleotide Polymers 0.000 claims 1
- 239000002157 polynucleotide Substances 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 239000011780 sodium chloride Substances 0.000 claims 1
Claims (22)
- カルシウム／カルモジュリン依存性プロテインキナーゼＩＩ型デルタ(ＣＡＭＫ２Ｄ)転写物内の核酸配列に対して少なくとも約８０％相補的である１０～３０ヌクレオチド長の連続するヌクレオチド配列を含む、アンチセンスオリゴヌクレオチド(ＡＳＯ)。
- ＣＡＭＫ２Ｄ転写物が、配列番号：１および配列番号：２からなる群から選択される、請求項１記載のＡＳＯ。
- ＡＳＯが、ＣＡＭＫ２Ｄタンパク質および／またはＣＡＭＫ２Ｄ転写物（例えば、ｍＲＮＡ）を発現しているヒト細胞における該ＣＡＭＫ２Ｄタンパク質および／またはＣＡＭＫ２Ｄ転写物の発現を低下させることができる、請求項１または２記載のＡＳＯ。
- ＡＳＯがギャップマーである、請求項１～３いずれか１項記載のＡＳＯ。
- ＡＳＯが１以上のヌクレオシドアナログを含み、該ヌクレオシドアナログの１以上が糖修飾ヌクレオシドアナログである、請求項１～４いずれか１項記載のＡＳＯ。
- ヌクレオシドアナログが、２'－Ｏ－アルキル－ＲＮＡ；２'－Ｏ－メチルＲＮＡ(２'－ＯＭｅ)；２'－アルコキシ－ＲＮＡ；２'－Ｏ－メトキシエチル－ＲＮＡ(２'－ＭＯＥ)；２'－アミノ－ＤＮＡ；２'－フルオロ－ＲＮＡ；２'－フルオロ－ＤＮＡ；アラビノ核酸(ＡＮＡ)；２'－フルオロ－ＡＮＡ；または二環式ヌクレオシドアナログ(ＬＮＡ)を含む、請求項５記載のＡＳＯ
- 糖修飾ヌクレオシドが、親和性増強２'糖修飾ヌクレオシドである、請求項５記載のＡＳＯ。
- 親和性増強２'糖修飾ヌクレオシドがＬＮＡであり、ここで、該ＬＮＡが、拘束性エチルヌクレオシド(ｃＥｔ)、２',４'－拘束性２'－Ｏ－メトキシエチル(ｃＭＯＥ)、α－Ｌ－ＬＮＡ、β－Ｄ－ＬＮＡ、２'－Ｏ,４'－Ｃ－エチレン架橋核酸(ＥＮＡ)、アミノ－ＬＮＡ、オキシ－ＬＮＡ、チオ－ＬＮＡまたはそれらの任意の組み合わせ、からなる群から選択される、請求項７記載のＡＳＯ。
- ＡＳＯが、１以上の５'－メチル－シトシン核酸塩基を含む、請求項１～８いずれか１項記載のＡＳＯ。
- 連続するヌクレオチド配列が、(ｉ)配列番号：１のヌクレオチド６２５～８４２；(ｉｉ)配列番号：１のヌクレオチド１,３９８～５９,７５５；(ｉｉｉ)配列番号：１のヌクレオチド６１,８１７～１０４,７２５；(ｉｖ)配列番号：１のヌクレオチド１１２,１６２～１１８,０２１；(ｖ)配列番号：１のヌクレオチド１１９,４４０～１３５,２１９；(ｖｉ)配列番号：１のヌクレオチド１３７,５８７～１５７,８５６；(ｖｉｉ)配列番号：１のヌクレオチド１５９,１９１～２６６,１７４；または(ｖｉｉｉ)配列番号：１のヌクレオチド２７２,７８８～３１０,９４９を含む核酸配列に相補的である、請求項１～９いずれか１項記載のＡＳＯ。
- 連続するヌクレオチド配列が、１つまたは２つのミスマッチを有する配列番号：４～配列番号：１７１３を含む、請求項１～１０いずれか１項記載のＡＳＯ。
- 連続するヌクレオチド配列が、１以上の修飾されたインターヌクレオシド結合を含む、請求項１～１１いずれか１項記載のＡＳＯ。
- １以上の修飾されたインターヌクレオシド結合がホスホロチオエート結合である、請求項１２記載のＡＳＯ。
- ＡＳＯが、少なくとも１つの非ヌクレオチドまたは非ポリヌクレオチド部分に共有結合している、請求項１～１３いずれか１項記載のＡＳＯを含むコンジュゲート。
- 請求項１～１３いずれか１項記載のＡＳＯあるいは請求項１４記載のコンジュゲートと、医薬的に許容される希釈剤、担体、塩またはアジュバントを含む、医薬組成物。
- 請求項１～１３いずれか１項記載のＡＳＯ、請求項１４記載のコンジュゲートまたは請求項１５記載の医薬組成物、および使用説明書を含む、キット。
- ＣＡＭＫ２Ｄタンパク質および／またはＣＡＭＫ２Ｄ転写物（例えばｍＲＮＡ）の細胞における発現を阻害または低下させる方法であって、ＣＡＭＫ２Ｄタンパク質および／またはＣＡＭＫ２Ｄ転写物を発現する細胞に、請求項１～１３いずれか１項記載のＡＳＯ、請求項１４記載のコンジュゲートまたは請求項１５記載の医薬組成物を接触させることを特徴とし、接触後にＣＡＭＫ２Ｄタンパク質および／またはＣＡＭＫ２Ｄ転写物の細胞における発現が阻害または低下される、方法。
- それが必要な対象における心血管系疾患または障害の１以上の症状を軽減、改善または治療するための、請求項１～１３いずれか１項記載のＡＳＯ、請求項１４記載のコンジュゲートまたは請求項１５記載の医薬組成物。
- 治療における使用のための、請求項１～１３いずれか１項記載のＡＳＯ、請求項１４記載のコンジュゲートまたは請求項１５記載の医薬組成物。
- それが必要な対象における心血管疾患または障害を治療するための医薬品の製造のための、請求項１～１３いずれか１項記載のＡＳＯ、請求項１４記載のコンジュゲートまたは請求項１５記載の医薬組成物の使用。
- 心血管系疾患または障害が、冠動脈疾患、脳卒中、心不全、高血圧性心疾患、リウマチ性心疾患、心筋症、心臓不整脈、先天性心疾患、弁膜症性心疾患、心臓炎、大動脈瘤、末梢動脈疾患、血栓塞栓性疾患、静脈血栓症またはそれらの任意の組み合わせを含む、請求項１８記載のＡＳＯ、コンジュゲートもしくは医薬組成物、または請求項２０記載の使用。
- 対象がヒトである、請求項１８記載のＡＳＯ、コンジュゲートもしくは医薬組成物、または請求項２０記載の使用。
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862633502P | 2018-02-21 | 2018-02-21 | |
| US62/633,502 | 2018-02-21 | ||
| US201862635954P | 2018-02-27 | 2018-02-27 | |
| US62/635,954 | 2018-02-27 | ||
| US201862665998P | 2018-05-02 | 2018-05-02 | |
| US62/665,998 | 2018-05-02 | ||
| US201862778679P | 2018-12-12 | 2018-12-12 | |
| US62/778,679 | 2018-12-12 | ||
| PCT/US2019/018947 WO2019165067A1 (en) | 2018-02-21 | 2019-02-21 | Camk2d antisense oligonucleotides and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2021513861A JP2021513861A (ja) | 2021-06-03 |
| JPWO2019165067A5 true JPWO2019165067A5 (ja) | 2022-03-01 |
Family
ID=65729436
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020544270A Pending JP2021513861A (ja) | 2018-02-21 | 2019-02-21 | Ｃａｍｋ２ｄアンチセンスオリゴヌクレオチドおよびその使用 |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US11083444B2 (ja) |
| EP (1) | EP3755800A1 (ja) |
| JP (1) | JP2021513861A (ja) |
| KR (1) | KR20200140805A (ja) |
| CN (1) | CN112020559A (ja) |
| AU (1) | AU2019226001A1 (ja) |
| BR (1) | BR112020016347A2 (ja) |
| CA (1) | CA3091789A1 (ja) |
| IL (1) | IL276549A (ja) |
| MX (1) | MX2020008581A (ja) |
| SG (1) | SG11202007652UA (ja) |
| WO (1) | WO2019165067A1 (ja) |
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- 2019-02-21 EP EP19710527.3A patent/EP3755800A1/en active Pending
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- 2019-02-21 AU AU2019226001A patent/AU2019226001A1/en active Pending
- 2019-02-21 KR KR1020207026765A patent/KR20200140805A/ko not_active Application Discontinuation
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- 2019-02-21 CA CA3091789A patent/CA3091789A1/en active Pending
- 2019-02-21 CN CN201980025466.8A patent/CN112020559A/zh active Pending
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