JPWO2021163066A5 - - Google Patents

Download PDF

Info

Publication number
JPWO2021163066A5
JPWO2021163066A5 JP2022548542A JP2022548542A JPWO2021163066A5 JP WO2021163066 A5 JPWO2021163066 A5 JP WO2021163066A5 JP 2022548542 A JP2022548542 A JP 2022548542A JP 2022548542 A JP2022548542 A JP 2022548542A JP WO2021163066 A5 JPWO2021163066 A5 JP WO2021163066A5
Authority
JP
Japan
Prior art keywords
seq
sequence
modifications
strand comprises
nucleotides
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.)
Pending
Application number
JP2022548542A
Other languages
English (en)
Other versions
JP2023514190A (ja
Publication date
Application filed filed Critical
Priority claimed from PCT/US2021/017276 external-priority patent/WO2021163066A1/en
Publication of JP2023514190A publication Critical patent/JP2023514190A/ja
Publication of JPWO2021163066A5 publication Critical patent/JPWO2021163066A5/ja
Pending legal-status Critical Current

Links

Claims (18)

  1. 血管内皮増殖因子Ａ（ＶＥＧＦ－Ａ）の発現を阻害するための二本鎖リボ核酸（ｄｓＲＮＡ）剤であって、ｄｓＲＮＡ剤は、二本鎖領域を形成するセンス鎖およびアンチセンス鎖を含み、アンチセンス鎖は、二本鎖ＡＤ－１３５３４５２、ＡＤ－１３５３４８０、ＡＤ－１０２０５７５、ＡＤ－９０１１１３またはＡＤ－９５３３７０．１からのアンチセンス配列の１つまたは明細書中の［表６］～［表１４５］および［表１８８］～［表１９２］のいずれか１つに列挙されるいずれか１つのアンチセンス配列に由来する、０、１、２または３つのミスマッチを有する、少なくとも１５の連続するヌクレオチドを含むヌクレオチド配列を含み、センス鎖は、アンチセンス配列に対応する、二本鎖ＡＤ－１３５３４５２、ＡＤ－１３５３４８０、ＡＤ－１０２０５７５、ＡＤ－９０１１１３またはＡＤ－９５３３７０．１からのいずれか１つのセンス鎖または明細書中の［表６］～［表１４５］および［表１８８］～［表１９２］のいずれか１つに列挙されたセンス配列に由来する０、１、２または３つのミスマッチを有する、少なくとも１５の連続するヌクレオチドを含むヌクレオチド配列を含む、二本鎖リボ核酸（ｄｓＲＮＡ）剤。
  2. （ａ）センス鎖が、配列番号１のヌクレオチド１８５６－１８７８、１９８６－２００８、２０３５－２０５７、２９４２－２９６４、３０９４－３１１６、１８５５～１８７５、１８５８～１８７８、２１７８～２１９８、２１８１～２２０１、２９４４～２９６４、２９４６～２９６６、２９５２～２９７２、３３６１～３３８１または３３６２～３３８２内の部分である；
    （ｂ）センス鎖が、ＡＤ－１３５３４５２（AGAUUAGAGAGUUUUAUUUCA（配列番号４０２０））、ＡＤ－１３５３４８０（AUUGGAUUCGCCAUUUUAUUA（配列番号４０２８））、ＡＤ－１０２０５７５（CAGAACAGUCCUUAAUCCAGA（配列番号４２０２））、ＡＤ－９０１１１３（GAGAAAGUGUUUUAUAUACGA（配列番号４２０５））、ＡＤ－９５３３７０．１（GCUCUCUUAUUUGUACCGGUA（配列番号７９３）、ＡＤ－１０２０５７４（CGACAGAACAGUCCUUAAUCA（配列番号４２００））、ＡＤ－９０１０９４（CAGAACAGUCCUUAAUCCAGA（配列番号４２０１））、ＡＤ－９０１１００（AACAGUGCUAAUGUUAUUGGA（配列番号４２０３））、ＡＤ－９０１１０１（AGUGCUAAUGUUAUUGGUGUA（配列番号４２０４））、ＡＤ－９０１１２３（AAAAUAGACAUUGCUAUUCUA（配列番号４２０６））、ＡＤ－９０１１２４（AAAUAGACAUUGCUAUUCUGA（配列番号４２０７））、ＡＤ－９０１１５８（GAAAGUGUUUUAUAUACGGUA（配列番号４２０８））、ＡＤ－９０１１５９（GUUUUAUAUACGGUACUUAUA（配列番号４２０９））、ＡＤ－１０２０５７３（AGUGCUAATGTUAUUGGUGUA（配列番号４２１０））、またはＡＤ－１０２３１４３（AAAAUAGACATUGCUAUUCUA（配列番号４２１１））から選択される二重鎖に由来するセンス鎖内の部分である；
    （ｃ）センス鎖が、ＡＤ－１３５３４５２（AGAUUAGAGAGUUUUAUUUCA（配列番号４０２０））、ＡＤ－１３５３４８０（AUUGGAUUCGCCAUUUUAUUA（配列番号４０２８））、ＡＤ－１０２０５７５（CAGAACAGUCCUUAAUCCAGA（配列番号４２０２））、ＡＤ－９０１１１３（GAGAAAGUGUUUUAUAUACGA（配列番号４２０５））、ＡＤ－９５３３７０．１（GCUCUCUUAUUUGUACCGGUA（配列番号７９３）、ＡＤ－１０２０５７４（CGACAGAACAGUCCUUAAUCA（配列番号４２００））、ＡＤ－９０１０９４（CAGAACAGUCCUUAAUCCAGA（配列番号４２０１））、ＡＤ－９０１１００（AACAGUGCUAAUGUUAUUGGA（配列番号４２０３））、ＡＤ－９０１１０１（AGUGCUAAUGUUAUUGGUGUA（配列番号４２０４））、ＡＤ－９０１１２３（AAAAUAGACAUUGCUAUUCUA（配列番号４２０６））、ＡＤ－９０１１２４（AAAUAGACAUUGCUAUUCUGA（配列番号４２０７））、ＡＤ－９０１１５８（GAAAGUGUUUUAUAUACGGUA（配列番号４２０８））、ＡＤ－９０１１５９（GUUUUAUAUACGGUACUUAUA（配列番号４２０９））、ＡＤ－１０２０５７３（AGUGCUAATGTUAUUGGUGUA（配列番号４２１０））、またはＡＤ－１０２３１４３（AAAAUAGACATUGCUAUUCUA（配列番号４２１１））のセンス鎖から選択されるセンス鎖である；
    （ｄ）アンチセンス鎖が、ＡＤ－１３５３４５２（UGAAAUAAAACUCUCUAAUCUUC（配列番号４１１０））、ＡＤ－１３５３４８０（UAAUAAAAUGGCGAAUCCAAUUC（配列番号４１１８））、ＡＤ－１０２０５７５（UCUGGATUAAGGACUGUUCUGUC（配列番号４２１４））、ＡＤ－９０１１１３（UCGUAUAUAAAACACUUUCUCUU（配列番号４２１７））、ＡＤ－９５３３７０．１（UACCGGUACAAAUAAGAGAGCAA（配列番号９２３）、ＡＤ－１０２０５７４（UGAUUAAGGACUGUUCUGUCGAU（配列番号４２１２））、ＡＤ－９０１０９４（UCUGGAUUAAGGACUGUUCUGUC（配列番号４２１３））、ＡＤ－９０１１００（UCCAAUAACAUUAGCACUGUUAA（配列番号４２１５））、ＡＤ－９０１１０１（UACACCAAUAACAUUAGCACUGU（配列番号４２１６））、ＡＤ－９０１１２３（UAGAAUAGCAAUGUCUAUUUUAU（配列番号４２１８））、ＡＤ－９０１１２４（UCAGAAUAGCAAUGUCUAUUUUA（配列番号４２１９））、ＡＤ－９０１１５８（UACCGUAUAUAAAACACUUUCUC（配列番号４２２０））、ＡＤ－９０１１５９（UAUAAGUACCGUAUAUAAAACAC（配列番号４２２１））、ＡＤ－１０２０５７３（UACACCAAUAACATUAGCACUGU（配列番号４２２２））、またはＡＤ－１０２３１４３（UAGAAUAGCAATGTCTAUUUUAU（配列番号４２２３））から選択される二重鎖に由来するアンチセンス鎖内の部分である；
    （ｅ）アンチセンス鎖が、ＡＤ－１３５３４５２（UGAAAUAAAACUCUCUAAUCUUC（配列番号４１１０））、ＡＤ－１３５３４８０（UAAUAAAAUGGCGAAUCCAAUUC（配列番号４１１８））、ＡＤ－１０２０５７５（UCUGGATUAAGGACUGUUCUGUC（配列番号４２１４））、ＡＤ－９０１１１３（UCGUAUAUAAAACACUUUCUCUU（配列番号４２１７））、ＡＤ－９５３３７０．１（UACCGGUACAAAUAAGAGAGCAA（配列番号９２３）、ＡＤ－１０２０５７４（UGAUUAAGGACUGUUCUGUCGAU（配列番号４２１２））、ＡＤ－９０１０９４（UCUGGAUUAAGGACUGUUCUGUC（配列番号４２１３））、ＡＤ－９０１１００（UCCAAUAACAUUAGCACUGUUAA（配列番号４２１５））、ＡＤ－９０１１０１（UACACCAAUAACAUUAGCACUGU（配列番号４２１６））、ＡＤ－９０１１２３（UAGAAUAGCAAUGUCUAUUUUAU（配列番号４２１８））、ＡＤ－９０１１２４（UCAGAAUAGCAAUGUCUAUUUUA（配列番号４２１９））、ＡＤ－９０１１５８（UACCGUAUAUAAAACACUUUCUC（配列番号４２２０））、ＡＤ－９０１１５９（UAUAAGUACCGUAUAUAAAACAC（配列番号４２２１））、ＡＤ－１０２０５７３（UACACCAAUAACATUAGCACUGU（配列番号４２２２））、またはＡＤ－１０２３１４３（UAGAAUAGCAATGTCTAUUUUAU（配列番号４２２３））のアンチセンス鎖から選択されるアンチセンス鎖である；
    （ｆ）センス鎖およびアンチセンス鎖が、ＡＤ－１３５３４５２（配列番号４０２０および４１１０）、ＡＤ１３５３４８０（配列番号４０２８および４１１８）、ＡＤ－１０２０５７５（配列番号４２０２および４２１４）、ＡＤ－９０１１１３（配列番号４２０５および４２１７）、ＡＤ－９５３３７０．１（配列番号７９３および９２３）、ＡＤ－１０２０５７４（配列番号４２００および４２１２）、ＡＤ－９０１０９４（配列番号４２０１および４２１３）、ＡＤ－９０１１００（配列番号４２０３および４２１５）、ＡＤ－９０１１０１（配列番号４２０４および４２１６）、ＡＤ－９０１１２３（配列番号４２０６および４２１８）、ＡＤ－９０１１２４（配列番号４２０７および４２１９）、ＡＤ－９０１１５８（配列番号４２０８および４２２０）、ＡＤ－９０１１５９（配列番号４２０９および４２２１）、ＡＤ－１０２０５７３（配列番号４２１０および４２２２）、またはＡＤ－１０２３１４３（配列番号４２１１および４２２３）から選択される二重鎖の対形成されたセンス鎖およびアンチセンス鎖のヌクレオチド配列を含む；
    （ｇ）アンチセンス鎖が、明細書中の［表１４４］に列挙されるアンチセンス配列のヌクレオチド配列を含み、センス鎖が、アンチセンス配列に対応する、明細書中の［表１４４］に列挙されるセンス配列のヌクレオチド配列を含む；または
    （ｈ）ｄｓＲＮＡ剤がＡＤ－１３５３４５２、ＡＤ１３５３４８０、ＡＤ－１０２０５７５、ＡＤ－９０１１１３、ＡＤ９５３３７０．１、ＡＤ－１０２０５７４、ＡＤ－９０１０９４、ＡＤ－９０１１００、ＡＤ－９０１１０１、ＡＤ－９０１１２３、ＡＤ－９０１１２４、ＡＤ－９０１１５８、ＡＤ－９０１１５９、ＡＤ－１０２０５７３またはＡＤ－１０２３１４３である、
    請求項１に記載のｄｓＲＮＡ剤。
  3. センス鎖およびアンチセンス鎖の少なくとも一方が、１つまたは複数の親油性部分にコンジュゲートされている、請求項１または２に記載のｄｓＲＮＡ剤。
  4. （ａ）親油性部分が、リンカーまたは担体を介してコンジュゲートされている；
    （ｂ）１つまたは複数の親油性部分が、少なくとも１つの鎖上の１つまたは複数の内部位置にコンジュゲートされている；
    （ｃ）１つまたは複数の親油性部分が、リンカーまたは担体を介して少なくとも１つの鎖上の１つまたは複数の内部位置にコンジュゲートされている；
    （ｄ）親油性部分が、脂肪族、脂環式または多脂環式化合物である；
    （ｅ）親油性部分が、飽和または不飽和Ｃ１６炭化水素鎖を含有する；
    （ｆ）親油性部分、内部位置または二本鎖領域における１つまたは複数のヌクレオチドに置き換わる担体を介してコンジュゲートされている；
    （ｇ）親油性部分が、エーテル、チオエーテル、尿素、カーボネート、アミン、アミド、マレイミド－チオエーテル、ジスルフィド、ホスホジエステル、スルホアミド連結、クリック反応の生成物、またはカルバメートを含有するリンカーを介してセンス鎖またはアンチセンス鎖にコンジュゲートされている；および／または
    （ｈ）親油性部分が、核酸塩基、糖部分、またはヌクレオシド間連結にコンジュゲートされている、
    請求項３に記載のｄｓＲＮＡ剤。
  5. 少なくとも１つの修飾されたヌクレオチドを含む、請求項１～４のいずれか一項に記載のｄｓＲＮＡ剤。
  6. （ａ）センス鎖ヌクレオチドの５つ以下およびアンチセンス鎖のヌクレオチドの５つ以下が、未修飾ヌクレオチドである：
    （ｂ）センス鎖のヌクレオチドの全ておよびアンチセンス鎖のヌクレオチドの全てが、修飾を含む；および／または
    （ｃ）修飾ヌクレオチドのうちの少なくとも１つが、デオキシ－ヌクレオチド、３’－末端デオキシ－チミン（ｄＴ）ヌクレオチド、２’－Ｏ－メチル修飾ヌクレオチド、２’－フルオロ修飾ヌクレオチド、２’－デオキシ－修飾ヌクレオチド、ロックドヌクレオチド、アンロックドヌクレオチド、立体配座制限ヌクレオチド、拘束エチルヌクレオチド、脱塩基ヌクレオチド、２’－アミノ－修飾ヌクレオチド、２’－Ｏ－アリル－修飾ヌクレオチド、２’－Ｃ－アルキル－修飾ヌクレオチド、２’－メトキシエチル修飾ヌクレオチド、２’－Ｏ－アルキル－修飾ヌクレオチド、モルホリノヌクレオチド、ホスホロアミデート、非天然塩基を含むヌクレオチド、テトラヒドロピラン修飾ヌクレオチド、１，５－アンヒドロヘキシトール修飾ヌクレオチド、シクロヘキセニル修飾ヌクレオチド、ホスホロチオエート基を含むヌクレオチド、メチルホスホネート基を含むヌクレオチド、５’－ホスフェートを含むヌクレオチド、５’－ホスフェート模倣物を含むヌクレオチド、グリコール修飾ヌクレオチドおよび２－Ｏ－（Ｎ－メチルアセトアミド）修飾ヌクレオチドおよびそれらの組合せからなる群から選択される、
    請求項５に記載のｄｓＲＮＡ剤。
  7. 少なくとも１つの鎖が、少なくとも２ヌクレオチドの３’オーバーハングを含む、請求項１～６のいずれか一項に記載のｄｓＲＮＡ剤。
  8. （ａ）二本鎖領域が、１５～３０または１７～２３ヌクレオチド対の長さである；
    （ｂ）各鎖が、１９～３０ヌクレオチドを有する；および／または
    （ｃ）ｄｓＲＮＡ剤が少なくとも１つのホスホロチオエートまたはメチルホスホネートヌクレオチド間連結を含む、
    請求項１～７のいずれか一項に記載のｄｓＲＮＡ剤。
  9. （ａ）標的化リガンド、例えば、眼組織を標的化するリガンド；
    （ｂ）眼組織を標的化し、眼組織が、網膜色素上皮（ＲＰＥ）または脈絡膜組織、例えば、脈絡膜血管である標的化リガンド；
    （ｃ）アンチセンス鎖の５’末端にホスフェートまたはホスフェートミミック；および／または
    （ｄ）アンチセンス鎖の５’末端にホスフェートまたはホスフェートミミック、ここでホスフェートミミックが、５’－ビニルホスホネート（ＶＰ）である、
    をさらに含む、請求項１～８のいずれか一項に記載のｄｓＲＮＡ剤。
  10. （ｉ）センス鎖が、配列番号３８４０の配列および全ての修飾を含み、アンチセンス鎖が、配列番号３９３０の配列および全ての修飾を含む、
    （ｉｉ）センス鎖が、配列番号３８４８の配列および全ての修飾を含み、アンチセンス鎖が、配列番号３９３８の配列および全ての修飾を含む、
    （ｉｉｉ）センス鎖が、配列番号４１６６の配列および全ての修飾を含み、アンチセンス鎖が、配列番号４１７８の配列および全ての修飾を含む、
    （ｉｖ）センス鎖が、配列番号４１６９の配列および全ての修飾を含み、アンチセンス鎖が、配列番号４１８１の配列および全ての修飾を含む、
    （ｖ）センス鎖が、配列番号５３３の配列および全ての修飾を含み、アンチセンス鎖が、配列番号６６３の配列および全ての修飾を含む、
    （ｖｉ）センス鎖が、配列番号４１６４の配列および全ての修飾を含み、アンチセンス鎖が、配列番号４１７６の配列および全ての修飾を含む、
    （ｖｉｉ）センス鎖が、配列番号４１６５の配列および全ての修飾を含み、アンチセンス鎖が、配列番号４１７７の配列および全ての修飾を含む、
    （ｖｉｉｉ）センス鎖が、配列番号４１６７の配列および全ての修飾を含み、アンチセンス鎖が、配列番号４１７９の配列および全ての修飾を含む、
    （ｉｘ）センス鎖が、配列番号４１６８の配列および全ての修飾を含み、アンチセンス鎖が、配列番号４１８０の配列および全ての修飾を含む、
    （ｘ）センス鎖が、配列番号４１７０の配列および全ての修飾を含み、アンチセンス鎖が、配列番号４１８２の配列および全ての修飾を含む、
    （ｘｉ）センス鎖が、配列番号４１７１の配列および全ての修飾を含み、アンチセンス鎖が、配列番号４１８３の配列および全ての修飾を含む、
    （ｘｉｉ）センス鎖が、配列番号４１７２の配列および全ての修飾を含み、アンチセンス鎖が、配列番号４１８４の配列および全ての修飾を含む、
    （ｘｉｉｉ）センス鎖が、配列番号４１７３の配列および全ての修飾を含み、アンチセンス鎖が、配列番号４１８５の配列および全ての修飾を含む、
    （ｘｉｖ）センス鎖が、配列番号４１７４の配列および全ての修飾を含み、アンチセンス鎖が、配列番号４１８６の配列および全ての修飾を含む、または
    （ｘｖ）センス鎖が、配列番号４１７５の配列および全ての修飾を含み、アンチセンス鎖が、配列番号４１８７の配列および全ての修飾を含む、
    前記の請求項のいずれか一項に記載のｄｓＲＮＡ剤。
  11. 請求項１～１０のいずれか一項に記載のｄｓＲＮＡ剤を含有する細胞。
  12. ＶＥＧＦ－Ａの発現を阻害するための医薬組成物であって、請求項１～１０のいずれか一項に記載のｄｓＲＮＡ剤を含む医薬組成物。
  13. 細胞におけるＶＥＧＦ－Ａの発現の阻害に使用するための、請求項１～１０のいずれか一項に記載のｄｓＲＮＡ剤または請求項１２に記載の医薬組成物であって、阻害が：
    （ａ）細胞を、ｄｓＲＮＡ剤と接触させること、および
    （ｂ）工程（ａ）において生成された細胞を、ＶＥＧＦ－Ａ ｍＲＮＡ、ＶＥＧＦ－Ａタンパク質またはＶＥＧＦ－Ａ ｍＲＮＡおよびタンパク質の両方のレベルを低減するのに十分な時間維持し、それによって、細胞においてＶＥＧＦ－Ａの発現を阻害すること
    を含む、ｄｓＲＮＡ剤または医薬組成物。
  14. （ａ）細胞が対象内にある；
    （ｂ）細胞が対象内にあり、対象がヒトである；または
    （ｃ）細胞が、ＶＥＧＦ－Ａ関連障害、例えば、滲出性加齢性黄斑変性症（湿性ＡＭＤ）、糖尿病性網膜症（ＤＲ）、糖尿病性黄斑浮腫（ＤＭＥ）、網膜静脈閉塞（ＲＶＯ）、網膜静脈閉塞後黄斑浮腫（ＭＥｆＲＶＯ）、未熟児網膜症（ＲＯＰ）または近視性脈絡膜血管新生（ｍＣＮＶ）と診断されているヒト対象内である、
    請求項１３に記載のｄｓＲＮＡ剤または医薬組成物。
  15. ＶＥＧＦ－Ａ関連障害と診断された対象の処置に使用するための、請求項１～１０のいずれか一項に記載のｄｓＲＮＡ剤または請求項１２に記載の医薬組成物であって、処置が、対象に治療上有効量のｄｓＲＮＡ剤を投与し、それによって、障害を処置することを含む、ｄｓＲＮＡ剤または医薬組成物。
  16. （ａ）ＶＥＧＦ－Ａ関連障害が、血管新生性眼疾患である；
    （ｂ）ＶＥＧＦ－Ａ関連障害が、血管新生性眼疾患であり、血管新生性眼疾患が、ＡＭＤ、ＤＲ、ＤＭＥ、ＲＶＯ、ＭＥｆＲＶＯ、ＲＯＰおよびｍＣＮＶからなる群から選択される；
    （ｃ）処置が、障害の少なくとも１つの兆候または症状の改善を含む；および／または
    （ｄ）処置が、（ｉ）血管新生を阻害すること、（ｉｉ）ＶＥＧＦ－Ａの発現または活性を阻害または低減すること、（ｉｉｉ）脈絡膜の新血管新生を阻害すること、（ｉｖ）脈絡毛細管において新規血管の成長を阻害すること、（ｖ）網膜の厚さを低減すること、（ｖｉ）視力を高めること、または（ｖｉｉ）眼球内炎症を低減することを含む、
    請求項１５に記載のｄｓＲＮＡ剤または医薬組成物。
  17. （ａ）ｄｓＲＮＡ剤が、眼内、静脈内、または局所的投与に適している；または
    （ｂ）ｄｓＲＮＡ剤が、眼球内投与に適しており、眼球内投与が、硝子体内投与（例えば、硝子体内注射）、経強膜投与（例えば、経強膜注射）、結膜下投与（例えば、結膜下注射）、球後投与（例えば、球後注射）、前房内投与（例えば、前房内注射）または網膜下投与（例えば、網膜下注射）を含む、
    請求項１４～１６のいずれか一項に記載のｄｓＲＮＡ剤または医薬組成物。
  18. 処置が、対象に、ＶＥＧＦ－Ａ関連障害の処置または予防にとって好適な追加の薬剤または療法（例えば、光線力学的療法、光血液凝固療法、ステロイド、非ステロイド系抗炎症薬、抗ＶＥＧＦ剤または硝子体切除術のうち１つまたは複数）を投与することをさらに含む、請求項１４～１７のいずれか一項に記載のｄｓＲＮＡ剤または医薬組成物。
JP2022548542A 2020-02-10 2021-02-09 Ｖｅｇｆ－ａ発現をサイレンシングするための組成物および方法 Pending JP2023514190A (ja)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US202062972519P 2020-02-10 2020-02-10
US62/972,519 2020-02-10
US202063055627P 2020-07-23 2020-07-23
US63/055,627 2020-07-23
US202163140714P 2021-01-22 2021-01-22
US63/140,714 2021-01-22
PCT/US2021/017276 WO2021163066A1 (en) 2020-02-10 2021-02-09 Compositions and methods for silencing vegf-a expression

Publications (2)

Publication Number Publication Date
JP2023514190A JP2023514190A (ja) 2023-04-05
JPWO2021163066A5 true JPWO2021163066A5 (ja) 2024-02-20

Family

ID=74853776

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2022548542A Pending JP2023514190A (ja) 2020-02-10 2021-02-09 Ｖｅｇｆ－ａ発現をサイレンシングするための組成物および方法

Country Status (13)

Country Link
US (1) US20230136787A1 (ja)
EP (1) EP4103714A1 (ja)
JP (1) JP2023514190A (ja)
KR (1) KR20220140593A (ja)
CN (1) CN115427571A (ja)
AU (1) AU2021220765A1 (ja)
BR (1) BR112022015770A2 (ja)
CA (1) CA3170377A1 (ja)
CO (1) CO2022012865A2 (ja)
IL (1) IL295445A (ja)
MX (1) MX2022009763A (ja)
TW (1) TW202140786A (ja)
WO (1) WO2021163066A1 (ja)

Family Cites Families (254)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB971700A (en) 1961-02-02 1964-09-30 Boots Pure Drug Co Ltd Anti-Inflammatory Agents
US3904682A (en) 1967-01-13 1975-09-09 Syntex Corp 2-(6{40 -Methoxy-2{40 -naphthyl)acetic acid
US4009197A (en) 1967-01-13 1977-02-22 Syntex Corporation 2-(6-Substituted-2'-naphthyl) acetic acid derivatives and the salts and esters thereof
US3687808A (en) 1969-08-14 1972-08-29 Univ Leland Stanford Junior Synthetic polynucleotides
US4469863A (en) 1980-11-12 1984-09-04 Ts O Paul O P Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof
US4534899A (en) 1981-07-20 1985-08-13 Lipid Specialties, Inc. Synthetic phospholipid compounds
US4426330A (en) 1981-07-20 1984-01-17 Lipid Specialties, Inc. Synthetic phospholipid compounds
US5023243A (en) 1981-10-23 1991-06-11 Molecular Biosystems, Inc. Oligonucleotide therapeutic agent and method of making same
US4476301A (en) 1982-04-29 1984-10-09 Centre National De La Recherche Scientifique Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon
JPS5927900A (ja) 1982-08-09 1984-02-14 Wakunaga Seiyaku Kk 固定化オリゴヌクレオチド
FR2540122B1 (fr) 1983-01-27 1985-11-29 Centre Nat Rech Scient Nouveaux composes comportant une sequence d'oligonucleotide liee a un agent d'intercalation, leur procede de synthese et leur application
US4605735A (en) 1983-02-14 1986-08-12 Wakunaga Seiyaku Kabushiki Kaisha Oligonucleotide derivatives
US4948882A (en) 1983-02-22 1990-08-14 Syngene, Inc. Single-stranded labelled oligonucleotides, reactive monomers and methods of synthesis
US4824941A (en) 1983-03-10 1989-04-25 Julian Gordon Specific antibody to the native form of 2'5'-oligonucleotides, the method of preparation and the use as reagents in immunoassays or for binding 2'5'-oligonucleotides in biological systems
US4587044A (en) 1983-09-01 1986-05-06 The Johns Hopkins University Linkage of proteins to nucleic acids
US5118802A (en) 1983-12-20 1992-06-02 California Institute Of Technology DNA-reporter conjugates linked via the 2' or 5'-primary amino group of the 5'-terminal nucleoside
US5118800A (en) 1983-12-20 1992-06-02 California Institute Of Technology Oligonucleotides possessing a primary amino group in the terminal nucleotide
US5550111A (en) 1984-07-11 1996-08-27 Temple University-Of The Commonwealth System Of Higher Education Dual action 2',5'-oligoadenylate antiviral derivatives and uses thereof
FR2567892B1 (fr) 1984-07-19 1989-02-17 Centre Nat Rech Scient Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons
US5367066A (en) 1984-10-16 1994-11-22 Chiron Corporation Oligonucleotides with selectably cleavable and/or abasic sites
US5430136A (en) 1984-10-16 1995-07-04 Chiron Corporation Oligonucleotides having selectably cleavable and/or abasic sites
US5258506A (en) 1984-10-16 1993-11-02 Chiron Corporation Photolabile reagents for incorporation into oligonucleotide chains
US4828979A (en) 1984-11-08 1989-05-09 Life Technologies, Inc. Nucleotide analogs for nucleic acid labeling and detection
FR2575751B1 (fr) 1985-01-08 1987-04-03 Pasteur Institut Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques
US5166315A (en) 1989-12-20 1992-11-24 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5405938A (en) 1989-12-20 1995-04-11 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
US5185444A (en) 1985-03-15 1993-02-09 Anti-Gene Deveopment Group Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages
US5235033A (en) 1985-03-15 1993-08-10 Anti-Gene Development Group Alpha-morpholino ribonucleoside derivatives and polymers thereof
US4762779A (en) 1985-06-13 1988-08-09 Amgen Inc. Compositions and methods for functionalizing nucleic acids
US5139941A (en) 1985-10-31 1992-08-18 University Of Florida Research Foundation, Inc. AAV transduction vectors
US5317098A (en) 1986-03-17 1994-05-31 Hiroaki Shizuya Non-radioisotope tagging of fragments
JPS638396A (ja) 1986-06-30 1988-01-14 Wakunaga Pharmaceut Co Ltd ポリ標識化オリゴヌクレオチド誘導体
US4920016A (en) 1986-12-24 1990-04-24 Linear Technology, Inc. Liposomes with enhanced circulation time
US4837028A (en) 1986-12-24 1989-06-06 Liposome Technology, Inc. Liposomes with enhanced circulation time
US5276019A (en) 1987-03-25 1994-01-04 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US5264423A (en) 1987-03-25 1993-11-23 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US4904582A (en) 1987-06-11 1990-02-27 Synthetic Genetics Novel amphiphilic nucleic acid conjugates
AU598946B2 (en) 1987-06-24 1990-07-05 Howard Florey Institute Of Experimental Physiology And Medicine Nucleoside derivatives
US5585481A (en) 1987-09-21 1996-12-17 Gen-Probe Incorporated Linking reagents for nucleotide probes
US5188897A (en) 1987-10-22 1993-02-23 Temple University Of The Commonwealth System Of Higher Education Encapsulated 2',5'-phosphorothioate oligoadenylates
US4924624A (en) 1987-10-22 1990-05-15 Temple University-Of The Commonwealth System Of Higher Education 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof
US5525465A (en) 1987-10-28 1996-06-11 Howard Florey Institute Of Experimental Physiology And Medicine Oligonucleotide-polyamide conjugates and methods of production and applications of the same
DE3738460A1 (de) 1987-11-12 1989-05-24 Max Planck Gesellschaft Modifizierte oligonukleotide
US5082830A (en) 1988-02-26 1992-01-21 Enzo Biochem, Inc. End labeled nucleotide probe
JPH03503894A (ja) 1988-03-25 1991-08-29 ユニバーシィティ　オブ　バージニア　アランミ　パテンツ　ファウンデイション オリゴヌクレオチド　ｎ‐アルキルホスホラミデート
US5278302A (en) 1988-05-26 1994-01-11 University Patents, Inc. Polynucleotide phosphorodithioates
US5109124A (en) 1988-06-01 1992-04-28 Biogen, Inc. Nucleic acid probe linked to a label having a terminal cysteine
US5216141A (en) 1988-06-06 1993-06-01 Benner Steven A Oligonucleotide analogs containing sulfur linkages
US5175273A (en) 1988-07-01 1992-12-29 Genentech, Inc. Nucleic acid intercalating agents
US5262536A (en) 1988-09-15 1993-11-16 E. I. Du Pont De Nemours And Company Reagents for the preparation of 5'-tagged oligonucleotides
GB8824593D0 (en) 1988-10-20 1988-11-23 Royal Free Hosp School Med Liposomes
US5512439A (en) 1988-11-21 1996-04-30 Dynal As Oligonucleotide-linked magnetic particles and uses thereof
US5599923A (en) 1989-03-06 1997-02-04 Board Of Regents, University Of Tx Texaphyrin metal complexes having improved functionalization
US5457183A (en) 1989-03-06 1995-10-10 Board Of Regents, The University Of Texas System Hydroxylated texaphyrins
US5391723A (en) 1989-05-31 1995-02-21 Neorx Corporation Oligonucleotide conjugates
US4958013A (en) 1989-06-06 1990-09-18 Northwestern University Cholesteryl modified oligonucleotides
US5032401A (en) 1989-06-15 1991-07-16 Alpha Beta Technology Glucan drug delivery system and adjuvant
US5451463A (en) 1989-08-28 1995-09-19 Clontech Laboratories, Inc. Non-nucleoside 1,3-diol reagents for labeling synthetic oligonucleotides
US5134066A (en) 1989-08-29 1992-07-28 Monsanto Company Improved probes using nucleosides containing 3-dezauracil analogs
US5436146A (en) 1989-09-07 1995-07-25 The Trustees Of Princeton University Helper-free stocks of recombinant adeno-associated virus vectors
US5254469A (en) 1989-09-12 1993-10-19 Eastman Kodak Company Oligonucleotide-enzyme conjugate that can be used as a probe in hybridization assays and polymerase chain reaction procedures
US5591722A (en) 1989-09-15 1997-01-07 Southern Research Institute 2'-deoxy-4'-thioribonucleosides and their antiviral activity
US5013556A (en) 1989-10-20 1991-05-07 Liposome Technology, Inc. Liposomes with enhanced circulation time
US5225212A (en) 1989-10-20 1993-07-06 Liposome Technology, Inc. Microreservoir liposome composition and method
US5356633A (en) 1989-10-20 1994-10-18 Liposome Technology, Inc. Method of treatment of inflamed tissues
US5399676A (en) 1989-10-23 1995-03-21 Gilead Sciences Oligonucleotides with inverted polarity
EP0942000B1 (en) 1989-10-24 2004-06-23 Isis Pharmaceuticals, Inc. 2'-Modified oligonucleotides
US5264564A (en) 1989-10-24 1993-11-23 Gilead Sciences Oligonucleotide analogs with novel linkages
US5292873A (en) 1989-11-29 1994-03-08 The Research Foundation Of State University Of New York Nucleic acids labeled with naphthoquinone probe
US5177198A (en) 1989-11-30 1993-01-05 University Of N.C. At Chapel Hill Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates
CA2029273A1 (en) 1989-12-04 1991-06-05 Christine L. Brakel Modified nucleotide compounds
US5486603A (en) 1990-01-08 1996-01-23 Gilead Sciences, Inc. Oligonucleotide having enhanced binding affinity
US5852188A (en) 1990-01-11 1998-12-22 Isis Pharmaceuticals, Inc. Oligonucleotides having chiral phosphorus linkages
US5587361A (en) 1991-10-15 1996-12-24 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity
US5681941A (en) 1990-01-11 1997-10-28 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
US7037646B1 (en) 1990-01-11 2006-05-02 Isis Pharmaceuticals, Inc. Amine-derivatized nucleosides and oligonucleosides
US5670633A (en) 1990-01-11 1997-09-23 Isis Pharmaceuticals, Inc. Sugar modified oligonucleotides that detect and modulate gene expression
US5459255A (en) 1990-01-11 1995-10-17 Isis Pharmaceuticals, Inc. N-2 substituted purines
US5587470A (en) 1990-01-11 1996-12-24 Isis Pharmaceuticals, Inc. 3-deazapurines
US5646265A (en) 1990-01-11 1997-07-08 Isis Pharmceuticals, Inc. Process for the preparation of 2'-O-alkyl purine phosphoramidites
US5578718A (en) 1990-01-11 1996-11-26 Isis Pharmaceuticals, Inc. Thiol-derivatized nucleosides
US6783931B1 (en) 1990-01-11 2004-08-31 Isis Pharmaceuticals, Inc. Amine-derivatized nucleosides and oligonucleosides
AU7579991A (en) 1990-02-20 1991-09-18 Gilead Sciences, Inc. Pseudonucleosides and pseudonucleotides and their polymers
US5214136A (en) 1990-02-20 1993-05-25 Gilead Sciences, Inc. Anthraquinone-derivatives oligonucleotides
US5321131A (en) 1990-03-08 1994-06-14 Hybridon, Inc. Site-specific functionalization of oligodeoxynucleotides for non-radioactive labelling
US5470967A (en) 1990-04-10 1995-11-28 The Dupont Merck Pharmaceutical Company Oligonucleotide analogs with sulfamate linkages
US5665710A (en) 1990-04-30 1997-09-09 Georgetown University Method of making liposomal oligodeoxynucleotide compositions
GB9009980D0 (en) 1990-05-03 1990-06-27 Amersham Int Plc Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides
EP0455905B1 (en) 1990-05-11 1998-06-17 Microprobe Corporation Dipsticks for nucleic acid hybridization assays and methods for covalently immobilizing oligonucleotides
US5981276A (en) 1990-06-20 1999-11-09 Dana-Farber Cancer Institute Vectors containing HIV packaging sequences, packaging defective HIV vectors, and uses thereof
US5688941A (en) 1990-07-27 1997-11-18 Isis Pharmaceuticals, Inc. Methods of making conjugated 4' desmethyl nucleoside analog compounds
US5218105A (en) 1990-07-27 1993-06-08 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5623070A (en) 1990-07-27 1997-04-22 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5677437A (en) 1990-07-27 1997-10-14 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5618704A (en) 1990-07-27 1997-04-08 Isis Pharmacueticals, Inc. Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
BR9106702A (pt) 1990-07-27 1993-06-08 Isis Pharmaceuticals Inc Analogo de oligonucleotideos e processos para modular a producao de uma proteina por um organismo e para tratar um organismo
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
US5138045A (en) 1990-07-27 1992-08-11 Isis Pharmaceuticals Polyamine conjugated oligonucleotides
US5245022A (en) 1990-08-03 1993-09-14 Sterling Drug, Inc. Exonuclease resistant terminally substituted oligonucleotides
IL99066A (en) 1990-08-03 1996-01-31 Sterling Winthrop Inc Nuclease-resistant compounds containing oligonucleotide sequences having either or both of the ends, and preparations containing them
US5512667A (en) 1990-08-28 1996-04-30 Reed; Michael W. Trifunctional intermediates for preparing 3'-tailed oligonucleotides
US5214134A (en) 1990-09-12 1993-05-25 Sterling Winthrop Inc. Process of linking nucleosides with a siloxane bridge
US5561225A (en) 1990-09-19 1996-10-01 Southern Research Institute Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages
JPH06505704A (ja) 1990-09-20 1994-06-30 ギリアド　サイエンシズ，インコーポレイテッド 改変ヌクレオシド間結合
US5432272A (en) 1990-10-09 1995-07-11 Benner; Steven A. Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases
CA2095212A1 (en) 1990-11-08 1992-05-09 Sudhir Agrawal Incorporation of multiple reporter groups on synthetic oligonucleotides
GB9100304D0 (en) 1991-01-08 1991-02-20 Ici Plc Compound
US7015315B1 (en) 1991-12-24 2006-03-21 Isis Pharmaceuticals, Inc. Gapped oligonucleotides
JP3220180B2 (ja) 1991-05-23 2001-10-22 三菱化学株式会社 薬剤含有タンパク質結合リポソーム
US5714331A (en) 1991-05-24 1998-02-03 Buchardt, Deceased; Ole Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility
US5539082A (en) 1993-04-26 1996-07-23 Nielsen; Peter E. Peptide nucleic acids
US5719262A (en) 1993-11-22 1998-02-17 Buchardt, Deceased; Ole Peptide nucleic acids having amino acid side chains
US5371241A (en) 1991-07-19 1994-12-06 Pharmacia P-L Biochemicals Inc. Fluorescein labelled phosphoramidites
US5571799A (en) 1991-08-12 1996-11-05 Basco, Ltd. (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response
DE59208572D1 (de) 1991-10-17 1997-07-10 Ciba Geigy Ag Bicyclische Nukleoside, Oligonukleotide, Verfahren zu deren Herstellung und Zwischenprodukte
US5594121A (en) 1991-11-07 1997-01-14 Gilead Sciences, Inc. Enhanced triple-helix and double-helix formation with oligomers containing modified purines
US5252479A (en) 1991-11-08 1993-10-12 Research Corporation Technologies, Inc. Safe vector for gene therapy
US6235887B1 (en) 1991-11-26 2001-05-22 Isis Pharmaceuticals, Inc. Enhanced triple-helix and double-helix formation directed by oligonucleotides containing modified pyrimidines
US5484908A (en) 1991-11-26 1996-01-16 Gilead Sciences, Inc. Oligonucleotides containing 5-propynyl pyrimidines
US5359044A (en) 1991-12-13 1994-10-25 Isis Pharmaceuticals Cyclobutyl oligonucleotide surrogates
US6277603B1 (en) 1991-12-24 2001-08-21 Isis Pharmaceuticals, Inc. PNA-DNA-PNA chimeric macromolecules
ATE204879T1 (de) 1991-12-24 2001-09-15 Isis Pharmaceuticals Inc Antisense oligonukleotide
US5595726A (en) 1992-01-21 1997-01-21 Pharmacyclics, Inc. Chromophore probe for detection of nucleic acid
US5565552A (en) 1992-01-21 1996-10-15 Pharmacyclics, Inc. Method of expanded porphyrin-oligonucleotide conjugate synthesis
FR2687679B1 (fr) 1992-02-05 1994-10-28 Centre Nat Rech Scient Oligothionucleotides.
DE4203923A1 (de) 1992-02-11 1993-08-12 Henkel Kgaa Verfahren zur herstellung von polycarboxylaten auf polysaccharid-basis
US5633360A (en) 1992-04-14 1997-05-27 Gilead Sciences, Inc. Oligonucleotide analogs capable of passive cell membrane permeation
US5434257A (en) 1992-06-01 1995-07-18 Gilead Sciences, Inc. Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages
US5587308A (en) 1992-06-02 1996-12-24 The United States Of America As Represented By The Department Of Health & Human Services Modified adeno-associated virus vector capable of expression from a novel promoter
EP0577558A2 (de) 1992-07-01 1994-01-05 Ciba-Geigy Ag Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte
US5272250A (en) 1992-07-10 1993-12-21 Spielvogel Bernard F Boronated phosphoramidate compounds
WO1994002595A1 (en) 1992-07-17 1994-02-03 Ribozyme Pharmaceuticals, Inc. Method and reagent for treatment of animal diseases
US6346614B1 (en) 1992-07-23 2002-02-12 Hybridon, Inc. Hybrid oligonucleotide phosphorothioates
EP0673431A1 (en) 1992-12-03 1995-09-27 Genzyme Corporation Gene therapy for cystic fibrosis
US5478745A (en) 1992-12-04 1995-12-26 University Of Pittsburgh Recombinant viral vector system
US5574142A (en) 1992-12-15 1996-11-12 Microprobe Corporation Peptide linkers for improved oligonucleotide delivery
JP3351476B2 (ja) 1993-01-22 2002-11-25 三菱化学株式会社 リン脂質誘導体及びそれを含有するリポソーム
US5476925A (en) 1993-02-01 1995-12-19 Northwestern University Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups
WO1994018987A1 (en) 1993-02-19 1994-09-01 Nippon Shinyaku Co., Ltd. Drug composition containing nucleic acid copolymer
US5395619A (en) 1993-03-03 1995-03-07 Liposome Technology, Inc. Lipid-polymer conjugates and liposomes
GB9304618D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Chemical compounds
ATE155467T1 (de) 1993-03-30 1997-08-15 Sanofi Sa Acyclische nucleosid analoge und sie enthaltende oligonucleotidsequenzen
AU6412794A (en) 1993-03-31 1994-10-24 Sterling Winthrop Inc. Oligonucleotides with amide linkages replacing phosphodiester linkages
DE4311944A1 (de) 1993-04-10 1994-10-13 Degussa Umhüllte Natriumpercarbonatpartikel, Verfahren zu deren Herstellung und sie enthaltende Wasch-, Reinigungs- und Bleichmittelzusammensetzungen
US6191105B1 (en) 1993-05-10 2001-02-20 Protein Delivery, Inc. Hydrophilic and lipophilic balanced microemulsion formulations of free-form and/or conjugation-stabilized therapeutic agents such as insulin
US5955591A (en) 1993-05-12 1999-09-21 Imbach; Jean-Louis Phosphotriester oligonucleotides, amidites and method of preparation
US6015886A (en) 1993-05-24 2000-01-18 Chemgenes Corporation Oligonucleotide phosphate esters
US6294664B1 (en) 1993-07-29 2001-09-25 Isis Pharmaceuticals, Inc. Synthesis of oligonucleotides
US5502177A (en) 1993-09-17 1996-03-26 Gilead Sciences, Inc. Pyrimidine derivatives for labeled binding partners
EP0729474A4 (en) 1993-11-16 1998-10-21 Genta Inc SYNTHETIC OLIGOMERS THAT HAVE CHIRALITY-PURE PHOSPHONATE INTERNUCLEOSIDYL BINDINGS MIXED WITH NON-PHOSPHONATE INTERNUKLEOSIDYL BINDINGS
US5540935A (en) 1993-12-06 1996-07-30 Nof Corporation Reactive vesicle and functional substance-fixed vesicle
US5457187A (en) 1993-12-08 1995-10-10 Board Of Regents University Of Nebraska Oligonucleotides containing 5-fluorouracil
US5446137B1 (en) 1993-12-09 1998-10-06 Behringwerke Ag Oligonucleotides containing 4'-substituted nucleotides
US5519134A (en) 1994-01-11 1996-05-21 Isis Pharmaceuticals, Inc. Pyrrolidine-containing monomers and oligomers
US5596091A (en) 1994-03-18 1997-01-21 The Regents Of The University Of California Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides
US5599922A (en) 1994-03-18 1997-02-04 Lynx Therapeutics, Inc. Oligonucleotide N3'-P5' phosphoramidates: hybridization and nuclease resistance properties
US5627053A (en) 1994-03-29 1997-05-06 Ribozyme Pharmaceuticals, Inc. 2'deoxy-2'-alkylnucleotide containing nucleic acid
US5625050A (en) 1994-03-31 1997-04-29 Amgen Inc. Modified oligonucleotides and intermediates useful in nucleic acid therapeutics
US6054299A (en) 1994-04-29 2000-04-25 Conrad; Charles A. Stem-loop cloning vector and method
US5525711A (en) 1994-05-18 1996-06-11 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Pteridine nucleotide analogs as fluorescent DNA probes
US5543152A (en) 1994-06-20 1996-08-06 Inex Pharmaceuticals Corporation Sphingosomes for enhanced drug delivery
US5597696A (en) 1994-07-18 1997-01-28 Becton Dickinson And Company Covalent cyanine dye oligonucleotide conjugates
US5597909A (en) 1994-08-25 1997-01-28 Chiron Corporation Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use
US5580731A (en) 1994-08-25 1996-12-03 Chiron Corporation N-4 modified pyrimidine deoxynucleotides and oligonucleotide probes synthesized therewith
US5820873A (en) 1994-09-30 1998-10-13 The University Of British Columbia Polyethylene glycol modified ceramide lipids and liposome uses thereof
US6608035B1 (en) 1994-10-25 2003-08-19 Hybridon, Inc. Method of down-regulating gene expression
US5665557A (en) 1994-11-14 1997-09-09 Systemix, Inc. Method of purifying a population of cells enriched for hematopoietic stem cells populations of cells obtained thereby and methods of use thereof
JP3269301B2 (ja) 1994-12-28 2002-03-25 豊田合成株式会社 ガラスラン用ゴム配合物
US6166197A (en) 1995-03-06 2000-12-26 Isis Pharmaceuticals, Inc. Oligomeric compounds having pyrimidine nucleotide (S) with 2'and 5 substitutions
EP0813539B1 (en) 1995-03-06 2006-05-24 Isis Pharmaceuticals, Inc. Improved process for the synthesis of 2'-o-substituted pyrimidines and oligomeric compounds therefrom
US5981501A (en) 1995-06-07 1999-11-09 Inex Pharmaceuticals Corp. Methods for encapsulating plasmids in lipid bilayers
US7422902B1 (en) 1995-06-07 2008-09-09 The University Of British Columbia Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer
US5756122A (en) 1995-06-07 1998-05-26 Georgetown University Liposomally encapsulated nucleic acids having high entrapment efficiencies, method of manufacturer and use thereof for transfection of targeted cells
IL122290A0 (en) 1995-06-07 1998-04-05 Inex Pharmaceuticals Corp Lipid-nucleic acid complex its preparation and use
DE69629702T2 (de) 1995-08-01 2004-06-17 Isis Pharmaceuticals, Inc., Carlsbad Liposomale oligonukleotidzusammensetzungen
US5858397A (en) 1995-10-11 1999-01-12 University Of British Columbia Liposomal formulations of mitoxantrone
WO1997014809A2 (en) 1995-10-16 1997-04-24 Dana-Farber Cancer Institute Novel expression vectors and methods of use
US6160109A (en) 1995-10-20 2000-12-12 Isis Pharmaceuticals, Inc. Preparation of phosphorothioate and boranophosphate oligomers
US5858401A (en) 1996-01-22 1999-01-12 Sidmak Laboratories, Inc. Pharmaceutical composition for cyclosporines
US5994316A (en) 1996-02-21 1999-11-30 The Immune Response Corporation Method of preparing polynucleotide-carrier complexes for delivery to cells
US6444423B1 (en) 1996-06-07 2002-09-03 Molecular Dynamics, Inc. Nucleosides comprising polydentate ligands
US6172209B1 (en) 1997-02-14 2001-01-09 Isis Pharmaceuticals Inc. Aminooxy-modified oligonucleotides and methods for making same
US6576752B1 (en) 1997-02-14 2003-06-10 Isis Pharmaceuticals, Inc. Aminooxy functionalized oligomers
US6639062B2 (en) 1997-02-14 2003-10-28 Isis Pharmaceuticals, Inc. Aminooxy-modified nucleosidic compounds and oligomeric compounds prepared therefrom
JP3756313B2 (ja) 1997-03-07 2006-03-15 武 今西 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体
DE69841002D1 (de) 1997-05-14 2009-09-03 Univ British Columbia Hochwirksame verkapselung von nukleinsäuren in lipidvesikeln
US6887906B1 (en) 1997-07-01 2005-05-03 Isispharmaceuticals, Inc. Compositions and methods for the delivery of oligonucleotides via the alimentary canal
CN1273476C (zh) 1997-09-12 2006-09-06 埃克西康有限公司 寡核苷酸类似物
US6794499B2 (en) 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
US6617438B1 (en) 1997-11-05 2003-09-09 Sirna Therapeutics, Inc. Oligoribonucleotides with enzymatic activity
US6528640B1 (en) 1997-11-05 2003-03-04 Ribozyme Pharmaceuticals, Incorporated Synthetic ribonucleic acids with RNAse activity
US6320017B1 (en) 1997-12-23 2001-11-20 Inex Pharmaceuticals Corp. Polyamide oligomers
US7273933B1 (en) 1998-02-26 2007-09-25 Isis Pharmaceuticals, Inc. Methods for synthesis of oligonucleotides
US7045610B2 (en) 1998-04-03 2006-05-16 Epoch Biosciences, Inc. Modified oligonucleotides for mismatch discrimination
US6531590B1 (en) 1998-04-24 2003-03-11 Isis Pharmaceuticals, Inc. Processes for the synthesis of oligonucleotide compounds
US6867294B1 (en) 1998-07-14 2005-03-15 Isis Pharmaceuticals, Inc. Gapped oligomers having site specific chiral phosphorothioate internucleoside linkages
CA2335393C (en) 1998-07-20 2008-09-23 Inex Pharmaceuticals Corporation Liposomal encapsulated nucleic acid-complexes
CA2345936A1 (en) 1998-10-09 2000-04-20 Ingene, Inc. Production of ssdna in a cell
AU6430599A (en) 1998-10-09 2000-05-01 Cytogenix, Inc. Enzymatic synthesis of ssdna
US6465628B1 (en) 1999-02-04 2002-10-15 Isis Pharmaceuticals, Inc. Process for the synthesis of oligomeric compounds
WO2000050050A1 (en) 1999-02-23 2000-08-31 Isis Pharmaceuticals, Inc. Multiparticulate formulation
US7084125B2 (en) 1999-03-18 2006-08-01 Exiqon A/S Xylo-LNA analogues
NZ514348A (en) 1999-05-04 2004-05-28 Exiqon As L-ribo-LNA analogues
US6593466B1 (en) 1999-07-07 2003-07-15 Isis Pharmaceuticals, Inc. Guanidinium functionalized nucleotides and precursors thereof
US6147200A (en) 1999-08-19 2000-11-14 Isis Pharmaceuticals, Inc. 2'-O-acetamido modified monomers and oligomers
WO2001053307A1 (en) 2000-01-21 2001-07-26 Geron Corporation 2'-arabino-fluorooligonucleotide n3'→p5'phosphoramidates: their synthesis and use
IT1318539B1 (it) 2000-05-26 2003-08-27 Italfarmaco Spa Composizioni farmaceutiche a rilascio prolungato per lasomministrazione parenterale di sostanze idrofile biologicamente
DE60119562T2 (de) 2000-10-04 2007-05-10 Santaris Pharma A/S Verbesserte synthese von purin-blockierten nukleinsäure-analoga
US7063860B2 (en) 2001-08-13 2006-06-20 University Of Pittsburgh Application of lipid vehicles and use for drug delivery
US8101348B2 (en) 2002-07-10 2012-01-24 Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften E.V. RNA-interference by single-stranded RNA molecules
US6878805B2 (en) 2002-08-16 2005-04-12 Isis Pharmaceuticals, Inc. Peptide-conjugated oligomeric compounds
EP1562971B1 (en) 2002-11-05 2014-02-12 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
AU2005212433B2 (en) 2003-05-23 2010-12-16 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using multifunctional short interfering nucleic acid (multifunctional sINA)
US8092992B2 (en) 2003-05-29 2012-01-10 Salk Institute For Biological Studies Transcriptional regulation of gene expression by small double-stranded modulatory RNA
EP2567693B1 (en) 2003-07-16 2015-10-21 Protiva Biotherapeutics Inc. Lipid encapsulated interfering RNA
DK1661905T3 (da) 2003-08-28 2012-07-23 Takeshi Imanishi Hidtil ukendte syntetiske nukleinsyrer af N-O-krydsbindingstype
EP1711510A4 (en) * 2004-02-05 2008-11-26 Intradigm Corp THERAPY WITH RNAI AGENTS APPLIED IN THE TREATMENT OF OCULAR DISEASES RESULTING FROM NEOVASCULARIZATION
EP1768998A2 (en) 2004-04-27 2007-04-04 Alnylam Pharmaceuticals Inc. Single-stranded and double-stranded oligonucleotides comprising a 2-arylpropyl moiety
US7740861B2 (en) 2004-06-16 2010-06-22 University Of Massachusetts Drug delivery product and methods
DK1866414T3 (da) 2005-03-31 2012-04-23 Calando Pharmaceuticals Inc Inhibitorer af ribonukleotidreduktase-underenhed 2 og anvendelser deraf.
US8101741B2 (en) 2005-11-02 2012-01-24 Protiva Biotherapeutics, Inc. Modified siRNA molecules and uses thereof
EP2431467A3 (en) 2005-11-17 2012-05-02 Board Of Regents, The University Of Texas Modulation of gene expression by oligomers targeted to chromosomal DNA
PL2314594T3 (pl) 2006-01-27 2014-12-31 Isis Pharmaceuticals Inc Zmodyfikowane w pozycji 6 analogi bicykliczne kwasów nukleinowych
US8362229B2 (en) 2006-02-08 2013-01-29 Quark Pharmaceuticals, Inc. Tandem siRNAS
JP5761911B2 (ja) 2006-04-07 2015-08-12 イデラ ファーマシューティカルズ インコーポレイテッドＩｄｅｒａ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． Ｔｌｒ７およびｔｌｒ８に対する安定化免疫調節ｒｎａ（ｓｉｍｒａ）化合物
MX2009003548A (es) 2006-10-03 2009-04-15 Alnylam Pharmaceuticals Inc Formulaciones que contienen lipidos.
US20100105134A1 (en) 2007-03-02 2010-04-29 Mdrna, Inc. Nucleic acid compounds for inhibiting gene expression and uses thereof
WO2008109362A1 (en) * 2007-03-02 2008-09-12 Mdrna, Inc. Nucleic acid compounds for inhibiting vegf gene expression and uses thereof
MX2009012568A (es) 2007-05-22 2009-12-08 Mdrna Inc Oligonucleotidos de acido ribonucleico sustituidos con hidroximetilo y complejos de acido ribonucleico.
ES2388590T3 (es) 2007-05-30 2012-10-16 Isis Pharmaceuticals, Inc. Análogos de ácidos nucleicos bicíclicos con puente aminometileno N-sustituido.
ES2386492T3 (es) 2007-06-08 2012-08-21 Isis Pharmaceuticals, Inc. Análogos de ácidos nucleicos bicíclicos carbocíclicos
ES2376507T5 (es) 2007-07-05 2015-08-31 Isis Pharmaceuticals, Inc. Análogos de ácidos nucleicos bicíclicos 6-disustituidos
US8188261B2 (en) 2007-07-09 2012-05-29 Idera Pharmaceuticals, Inc. Stabilized immune modulatory RNA (SIMRA) compounds
WO2009082607A2 (en) 2007-12-04 2009-07-02 Alnylam Pharmaceuticals, Inc. Targeting lipids
US9006191B2 (en) 2007-12-27 2015-04-14 Protiva Biotherapeutics, Inc. Silencing of polo-like kinase expression using interfering RNA
WO2009127060A1 (en) 2008-04-15 2009-10-22 Protiva Biotherapeutics, Inc. Novel lipid formulations for nucleic acid delivery
EP2321414B1 (en) 2008-07-25 2018-01-10 Alnylam Pharmaceuticals, Inc. Enhancement of sirna silencing activity using universal bases or mismatches in the sense strand
KR20110097915A (ko) 2008-12-03 2011-08-31 마리나 바이오테크, 인크. ＵｓｉＲＮＡ 복합체
ES2804764T3 (es) 2009-06-01 2021-02-09 Halo Bio Rnai Therapeutics Inc Polinucleótidos para la interferencia de ARN multivalente, composiciones y métodos de uso de los mismos
SI3431076T1 (sl) 2009-06-10 2022-04-29 Arbutus Biopharma Corporation Izboljšana lipidna formulacija
US9512164B2 (en) 2009-07-07 2016-12-06 Alnylam Pharmaceuticals, Inc. Oligonucleotide end caps
WO2011005860A2 (en) 2009-07-07 2011-01-13 Alnylam Pharmaceuticals, Inc. 5' phosphate mimics
ES2646097T3 (es) 2009-08-27 2017-12-12 Idera Pharmaceuticals, Inc. Composición para inhibir la expresión de genes y sus usos
WO2011133876A2 (en) 2010-04-22 2011-10-27 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising acyclic and abasic nucleosides and analogs
WO2011139710A1 (en) 2010-04-26 2011-11-10 Marina Biotech, Inc. Nucleic acid compounds with conformationally restricted monomers and uses thereof
WO2012015775A2 (en) * 2010-07-28 2012-02-02 Dharmacon, Inc. Sirna targeting vegfa and methods for treatment in vivo
CN104136451A (zh) 2011-09-07 2014-11-05 玛瑞纳生物技术有限公司 具有构象限制的单体的核酸化合物的合成和用途
KR20220045091A (ko) 2011-11-18 2022-04-12 알닐람 파마슈티칼스 인코포레이티드 트랜스티레틴（ＴＴＲ） 관련 질병을 치료하기 위한 ＲＮＡｉ 제제, 조성 및 그의 사용방법
IL284593B2 (en) 2013-05-01 2023-02-01 Ionis Pharmaceuticals Inc Compositions and methods for modulation of hbv and ttr expression

Similar Documents

Publication Publication Date Title
US5814620A (en) Inhibition of neovascularization using vegf-specific oligonucleotides
US5641756A (en) Modified VEGF oligonucleotides
JP4177455B2 (ja) 逆キメラおよびハイブリッドオリゴヌクレオチド
US5639872A (en) Human VEGF-specific oligonucleotides
JP2023103244A5 (ja)
JP6752151B2 (ja) 遺伝子サイレンシングにおいて低下したｏｆｆ−ｔａｒｇｅｔ効果を有するｕｎａオリゴマー
US20170314025A1 (en) Modified tgf-beta oligonucleotide for use in a method of preventing and/or treating an ophthalmic disease
US6306829B1 (en) Modified VEGF oligonucleotides for treatment of skin disorders
EP0859636A1 (en) Hyaluronic acid as dna carrier for gene therapy and vegf antisense dna to treat abnormal retinal vascularization
JP2000501941A (ja) 修飾ｖｅｇｆアンチセンスオリゴヌクレオチド
JPWO2020206350A5 (ja)
JPWO2021163066A5 (ja)
JP7394815B2 (ja) ＮＲＡＲＰ遺伝子の発現を阻害するためのｓｉＲＮＡ、並びにそのための方法及び組成物におけるそれらの使用
US10570394B2 (en) Double-stranded RNA compounds to CASP2 and uses thereof
IL295445A (en) Preparations and methods for silencing vegf-a expression
AU2012389270B2 (en) siRNA and their use in methods and compositions for the treatment and/or prevention of eye conditions
KR20180015268A (ko) 마이크로rna-328 안티-센스 조성물 및 치료 용도
CA2214431C (en) Human vegf-specific antisense oligonucleotides