JP7197464B2 - 結合タンパク質-小分子コンジュゲートのev媒介送達 - Google Patents
結合タンパク質-小分子コンジュゲートのev媒介送達 Download PDFInfo
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Description
特定のインビボ条件下で解離するビオチン-ストレプトアビジン結合などを含む。それにもかかわらず、エステル結合、アミド結合、ジスルフィド結合、チオエーテル結合、ビオチン-ストレプトアビジン相互作用、マレイミド-NHS反応による結合、EDC-NHS反応による結合、ステープリングされた連結(例えば、全炭化水素のステープル)および様々な他の結合のような非限定的な例では、結合タンパク質への小分子薬物の共有結合/結合のために利用可能な複数の戦略が存在する。
材料と方法
実施例1:パーキンソン病のためのアポモルフィンローディングEV
実施例2:癌治療のためのEVへのイマチニブローディング
実施例3:静脈内LPS誘発敗血症を予防するためのイマチニブのEVへのローディング
実施例4:mTOR活性を阻害するためのEVへのラパマイシンローディング
実施例5:脂肪細胞における脂肪分解誘導のためのEVへのアドレノメデュリンローディング
Claims (10)
- 結合タンパク質を含む細胞外小胞(EV)であって、少なくとも1つの小分子剤が結合タンパク質に非共有結合していることを特徴とする、細胞外小胞(EV)であって、
前記結合タンパク質は、結合タンパク質部分およびEVタンパク質を含む融合タンパク質であり、
前記EVタンパク質は、CD9、CD53、CD63、CD81、CD54、CD50、FLOT1、FLOT2、CD49d、CD71、CD133、CD138、CD235a、Lamp2b、TSPAN8、TSPAN14、CD37、CD82、CD151、CD231、CD102、NOTCH1、NOTCH2、NOTCH3、NOTCH4、DLL1、DLL4、JAG1、JAG2、CD49d/ITGA4、ITGB5、ITGB6、ITGB7、CD11a、CD11b、CD11c、CD18/ITGB2、CD41、CD49b、CD49c、CD49e、CD51、CD61、CD104、インターロイキン受容体、CD2、CD3イプシロン、CD3ゼータ、CD13、CD18、CD19、CD30、CD34、CD36、CD40、CD40L、CD44、CD45、CD45RA、CD47、CD86、CD110、CD111、CD115、CD117、CD125、CD135、CD184、CD200、CD279、CD273、CD274、CD362、AGRN、EGFR、GLUR2、GLUR3、HLA-DM、L1CAM、LFA-1、Mac-1アルファ、Mac-1ベータ、STX3、TCRA、TCRB、TCRD、TCRG、VTI1A、VTI1B、およびそれらの任意の組み合わせを含む群から選択される、EV。 - 前記結合タンパク質は、GPCR、ポリクローナルおよびモノクローナル抗体、一本鎖可変断片(scFv)、リポタンパク質、インテグリン、チロシンキナーゼ、DNA-結合タンパク質、RNA-結合タンパク質、ヌクレアーゼ、リガーゼ、プロテアーゼ、インテグラーゼ、イソメラーゼ、ホスファターゼ、GTPアーゼ、アロマターゼ、エステラーゼ、アダプタータンパク質、Gタンパク質、GEF、サイトカイン、インターロイキンおよびインターロイキン受容体、インターフェロンおよびインターフェロン受容体、カスパーゼ、転写因子、神経栄養因子およびそれらの受容体、成長因子およびそれらの受容体、シグナル認識粒子および受容体成分、細胞外マトリックスタンパク質、膜の必須成分、リボソームタンパク質、翻訳伸長因子、翻訳開始因子、GPIアンカー型タンパク質、組織因子、ジストロフィン、ユートロフィン、ジストロブレビン、並びに、その任意の融合物、組み合わせ、サブユニット、誘導体またはドメイン、を含む群から選択される、請求項1に記載のEV。
- 前記少なくとも1つの小分子剤は、抗癌剤、細胞増殖抑制剤、DNAまたはRNAインターカレーター、ヌクレオシド、スプライシングモジュレーター、キナーゼ阻害剤、BTK阻害剤またはBcr-Abl阻害剤などのチロシンキナーゼ阻害剤、スタチン、NSAID、抗生物質、抗真菌剤、抗菌剤、抗炎症剤、抗線維化剤、抗高血圧剤、血管拡張剤、ホルモンおよびその類似体、アロマターゼ阻害剤、エステラーゼ阻害剤、抗コリン剤、SSRis、BKT阻害剤、PPARアゴニスト、ドーパミンアゴニスト、HER阻害剤、AKT阻害剤、BCR-ABL阻害剤、シグナル伝達阻害剤、サイトカイン阻害剤、ILおよびILR阻害剤、TNFおよびTNFR阻害剤、血管形成阻害剤、シンターゼ阻害剤、例えばsiRNA、mRNA、アンチセンスオリゴヌクレオチド、スプライス-スイッチングオリゴヌクレオチドなどのオリゴヌクレオチド、ペプチド、細胞透過性ペプチド、ALK阻害剤、BRAF阻害剤、MEK阻害剤、PI3K阻害剤、ネプリライシン阻害剤、β2-アゴニスト、CRTH2アンタゴニスト、FXRアゴニスト、BACE阻害剤、スフィンゴシン-1-リン酸受容体調節剤、MAPK阻害剤、ヘッジホッグシグナル伝達阻害剤、MDM2アンタゴニスト、LSD1阻害剤、ラクタマーゼ阻害剤、1DO阻害剤、ERK阻害剤、Chk1阻害剤、およびその任意の誘導体、サブユニット、ドメイン、または組み合わせ、を含む群から選択される薬剤である、請求項1または2のいずれか一項に記載のEV。
- 前記少なくとも1つの小分子剤の前記結合は、任意に、結合タンパク質を治療活性化させる、請求項1~3のいずれか一項に記載のEV。
- 前記治療活性化された結合タンパク質は、シグナリング-応答能またはシグナリング-不能である、請求項4に記載のEV。
- 標的部分をさらに含む、請求項1~5のいずれか一項に記載のEV。
- 請求項1~6のいずれか一項に記載のEVおよび薬学的に許容可能な担体を含む、医薬組成物。
- 結合タンパク質-小分子コンジュゲート、結合タンパク質、および/または、小分子剤を送達する方法において使用するための、請求項7に記載の医薬組成物であって、前記方法が標的位置にEVを送達するステップを含む、組成物。
- 前記標的位置は、細胞、細胞もしくは細胞下コンパートメント、臓器、組織、および/または血液、胆汁、リンパ液、もしくは間質液である、請求項8に記載の医薬組成物。
- 医薬品における使用のための、請求項1~6のいずれか一項に記載のEV、または請求項9に記載の医薬組成物。
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GB1612110.5 | 2016-07-12 | ||
GB1612110.5A GB2552774A (en) | 2016-07-12 | 2016-07-12 | EV-Mediated delivery of binding protein-small molecule conjugates |
PCT/EP2017/067372 WO2018011191A1 (en) | 2016-07-12 | 2017-07-11 | Ev-mediated delivery of binding protein-small molecule conjugates |
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JP2019521140A JP2019521140A (ja) | 2019-07-25 |
JP2019521140A5 JP2019521140A5 (ja) | 2020-08-13 |
JP7197464B2 true JP7197464B2 (ja) | 2022-12-27 |
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US (1) | US20190290585A1 (ja) |
EP (1) | EP3484522A1 (ja) |
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WO2019197442A1 (en) * | 2018-04-12 | 2019-10-17 | Unicyte Ev Ag | A combination of active ingredients for the treatment of tumor |
GB201809622D0 (en) * | 2018-06-12 | 2018-07-25 | Evox Therapeutics Ltd | Engineering extracellular vesicles for affinity purification |
CN108753822A (zh) * | 2018-06-20 | 2018-11-06 | 中国人民解放军第四军医大学 | 递送融合型rna结合蛋白的表达载体及其制备方法和应用 |
CN108753806A (zh) * | 2018-06-20 | 2018-11-06 | 中国人民解放军第四军医大学 | 增强目标rna装载入外泌体的融合蛋白的表达载体及其构建方法和应用 |
WO2020035532A1 (en) * | 2018-08-14 | 2020-02-20 | Evercyte Gmbh | Target-specific extracellular vesicles |
CN109234237B (zh) * | 2018-09-30 | 2020-08-07 | 中国人民解放军第四军医大学 | 一种装载ABCA1 mRNA的外泌体及其构建方法和应用 |
CN109295081B (zh) * | 2018-10-17 | 2020-06-12 | 中国人民解放军第四军医大学 | 一种LDLR-Lamp2b融合基因、表达载体及其应用 |
EP3950060A4 (en) * | 2019-04-04 | 2023-04-19 | Nissan Chemical Corporation | COMPOSITION TO PROMOTE THE SECRETION OF EXTRACELLULAR VESICLES |
CN111333653A (zh) * | 2019-12-16 | 2020-06-26 | 山东大学 | 一种icd诱导剂-ido抑制剂缀合物及制备方法与应用 |
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KR20220147106A (ko) * | 2020-02-28 | 2022-11-02 | 도쿠리츠다이가쿠호징 가나자와다이가쿠 | 항원 제시 세포 외 소포, 그것을 포함하는 조성물, 및 그들을 제조하기 위한 방법 |
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CN114452266B (zh) * | 2022-02-09 | 2023-05-19 | 南京凯玛生物科技有限公司 | 一种基于重组核糖体蛋白的核酸药物递送系统及其制备方法和应用 |
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KR20190031259A (ko) | 2019-03-25 |
EP3484522A1 (en) | 2019-05-22 |
BR112019000528A2 (pt) | 2019-04-24 |
GB201612110D0 (en) | 2016-08-24 |
SG11201811150WA (en) | 2019-01-30 |
AU2017297728A1 (en) | 2019-02-07 |
US20190290585A1 (en) | 2019-09-26 |
WO2018011191A1 (en) | 2018-01-18 |
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JP2019521140A (ja) | 2019-07-25 |
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