JP2022545055A - PRDM14タンパク質の発現をダウンレギュレートする標的化siRNA製剤を使用する癌処置 - Google Patents
PRDM14タンパク質の発現をダウンレギュレートする標的化siRNA製剤を使用する癌処置 Download PDFInfo
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Abstract
Description
Claims (21)
- 配列番号2~27を含む、癌細胞においてヒトPRDM14遺伝子の発現を阻害するように構成された、単離した二本鎖低分子干渉RNA(siRNA)であって、ここで、ヌクレオチドは、RNA、DNA、およびハイブリッドRNA:DNAの組み合わせであってもよく、かつ鎖は、16-30のヌクレオチド長である、低分子干渉RNA(siRNA)。
- siRNAは、部位特異的な塩基修飾を含む1つ以上の化学修飾を含む、請求項1に記載のsiRNA。
- 前記化学修飾は、以下の
a.糖上の2’位置へのOメチル基の添加と、
b.糖の2’位置へのフッ素原子の添加と、
c.siRNAガイドアンチセンス鎖の3’末端での硫黄原子の酸素への置換と、の少なくとも1つを含む、請求項2に記載のsiRNA。 - 癌細胞においてPRDM14遺伝子の発現を阻害するための医薬組成物であって、該医薬組成物は、
a.PRDM14遺伝子発現をダウンレギュレートする二本鎖siRNAと、
b.siRNAを複合化する担体と、
c.追加の治療薬と、
d.癌細胞特異的な標的化リガンドと、を含む、医薬組成物 - 前記担体はリン酸カルシウムベースのものである、請求項4に記載の医薬組成物。
- 前記標的化リガンドは、タンパク質、ペプチド、およびアプタマーの群から選択される、請求項4に記載の医薬組成物。
- 前記標的化リガンドは、環化ポリペプチドを含む、請求項4に記載の医薬組成物。
- 前記標的化リガンドは、アミノ酸配列DMPGTVLPを含む、請求項4に記載の医薬組成物。
- 前記標的化リガンドは、アミノ酸配列DMPGTVLPを含む環化ポリペプチドを含む、請求項4に記載の医薬組成物。
- 前記担体はリポソーム性である、請求項4に記載の医薬組成物。
- リポソームはペグ化されている、請求項4に記載の医薬組成物。
- 追加の治療薬をさらに含む、請求項4に記載の医薬組成物。
- 前記担体は、エラスチン様タンパク質(ELP)を有するポリペプチド、アセンブリドメイン(AD)、腫瘍特異的細胞標的化ドメイン(CTD)、およびカチオン核酸結合ドメイン(NBD)を含むナノ粒子担体である、請求項4の医薬組成物。
- 前記CTDは、アミノ酸配列DMPGTVLPを含む、請求項11に記載の医薬組成物。
- 結合された治療薬を有する薬物結合ドメイン(DBD)をさらに含む、請求項11に記載の医薬組成物。
- 癌細胞においてPRDM14遺伝子の発現を阻害するための医薬組成物の治療上有効な量を投与することによってヒト癌患者を処置する方法であって、該医薬組成物は、
a.PRDM14遺伝子発現をダウンレギュレートする二本鎖siRNAと、
b.siRNAと追加の治療薬を複合化する担体と、
c.癌細胞特異的な標的化リガンドと、を含み、
d.ここで、癌細胞型は、乳癌、肺癌、食道癌、膵臓癌、卵巣癌、腎臓癌、膀胱癌、腎癌、生殖細胞癌、血液癌、白血病、頭部癌、頚部癌、および子宮頚癌の群から選択される、方法。 - 前記担体はリン酸カルシウムベースのものである、請求項16に記載の方法。
- 前記担体は、
a.エラスチン様タンパク質(ELP)を有するポリペプチドと、
b.アセンブリドメイン(AD)と、
c.腫瘍特異的な細胞標的化ドメイン(CTD)と、
d.カチオン核酸結合ドメイン(NBD)と、を含むナノ粒子担体である、請求項16に記載の方法。 - 前記ナノ粒子担体は、リポソーム性である、請求項16に記載の方法。
- 癌細胞の成長を抑制するために、PRDM14の発現を阻害するためにARIZ siRNAを充填された薬物送達システムを含む医薬組成物。
- 前記ARIZ siRNAは、
a.ARIZ-022と、
b.ARIZ-023と、
c.ARIZ-024と、
d.ARIZ-025と、
e.ARIZ-026と、
f.ARIZ-032と、
g.ARIZ-033と、
h.ARIZ-034と、
i.ARIZ-038と、
j.ARIZ-039と、
k.ARIZ-040と、
l.ARIZ-044と、
m.ARIZ-061を含む群から選択される、請求項20に記載の医薬組成物。
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PCT/US2020/041473 WO2021007465A2 (en) | 2019-07-09 | 2020-07-09 | Cancer treatment using targeted sirna pharmaceutical formulations to downregulate expression of prdm14 protein |
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