JP2015509505A - トリアルキルカチオン性脂質およびその使用方法 - Google Patents
トリアルキルカチオン性脂質およびその使用方法 Download PDFInfo
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Classifications
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Abstract
Description
本出願は、2012年2月24日に出願された、米国仮出願第61/602,990号の利益を主張し、これは、参照によりその全体が本明細書に組み込まれる。
本発明は、新規なトリアルキルカチオン性脂質、トリアルキルカチオン性脂質のうちの1つ以上を含む脂質粒子、脂質粒子を作製する方法、ならびに脂質粒子の送達および/または投与の方法(例えば、哺乳動物における疾患の治療のための)に関する。
治療的核酸には、例えば、低分子干渉RNA(siRNA)、マイクロRNA(miRNA)、アンチセンスオリゴヌクレオチド、リボザイム、プラスミド、および免疫賦活核酸が含まれる。これらの核酸は、多様な機序を介して作用する。siRNAおよびmiRNA等の干渉RNA分子の場合、これらの核酸は、RNA干渉(RNAi)と称されるプロセスを通じて特定のタンパク質の細胞内レベルを下方制御し得る。細胞の細胞質内に干渉RNAを導入した後、これらの二本鎖RNA構築物は、RISCと称されるタンパク質に結合することができる。干渉RNAのセンス鎖は、RISC複合体から転位され、結合された干渉RNAのものに相補的な配列を有するmRNAを認識し、それに結合することができる、RISC内の鋳型を提供する。相補的mRNAに結合すると、RISC複合体は、mRNAを切断し、切断された鎖を放出する。RNAiは、タンパク質の合成をコードする、対応するmRNAの特異的な破壊を標的とすることによって、特定のタンパク質の下方制御をもたらすことができる。
これらの発展にもかかわらず、当該技術分野において、一般的な治療上の使用に好適な、改善された脂質−治療的核酸組成物に対する必要性が残る。好ましくは、これらの組成物は、高い効率で核酸をカプセル封入し、薬物:脂質比が高く、カプセル封入された核酸を血清中での分解およびクリアランスから保護し、全身送達に好適であり、カプセル封入された核酸の細胞内送達を提供するものであろう。さらに、これらの核酸−脂質粒子は、核酸の治療有効用量での患者の治療が、患者に対する著しい毒性および/危険性を伴わないように、十分に耐容性であり、適切な治療指標を提供する必要がある。
Xは、アルキルアミノであり、
Aは、C1〜C6の任意に置換されたアルキルであり、前記C1〜C6の任意に置換されたアルキルは、飽和または不飽和であり得、Aは、存在してもしなくてもよく、
Yは、ケタール、エステル、任意に置換されたカルバメート、エーテル、および任意に置換されたアミドからなる群から選択され、
Zは、アルキル鎖のそれぞれがC8〜C11の長さを有する3つのアルキル鎖からなる疎水性部分であり、3つのアルキル鎖のそれぞれは、飽和または不飽和であり得、3つのアルキル鎖のそれぞれは、任意に置換される、カチオン性脂質またはその塩を提供する。
を有し、式中、R1、R2、およびR3は、それぞれ独立して、C8〜C11アルキルからなる群から選択され、R1、R2、およびR3のそれぞれは、独立して、飽和または不飽和であり得、R1、R2、およびR3のそれぞれは、任意に置換される。
本発明は、核酸等の活性剤または治療剤を哺乳動物の細胞にインビボ送達するために脂質粒子において使用する際に利点を提供する、新規なカチオン性(アミノ)脂質の発見に、部分的に基づく。具体的には、本発明は、向上した核酸(例えば、干渉RNA)の活性および改善されたインビボでの組成物の耐容性を提供する、本明細書に記載の新規なカチオン性脂質のうちの1つ以上を含む、核酸−脂質粒子組成物を提供し、結果として以前に記載された核酸−脂質粒子組成物と比較して、治療指標の著しい向上をもたらす。
本明細書に使用される際、以下の用語は、別途示されない限り、それら定められた意味を有する。
本発明は、とりわけ、核酸等の治療剤をインビトロおよび/またはインビボで細胞に送達するために、本明細書に記載の脂質粒子中で有利に使用することができる、新規なカチオン性(アミノ)脂質を提供する。本発明の新規なカチオン性脂質は、本明細書の式Iに記載される構造を有し、それらの(R)および/または(S)エナンチオマーを含む。
Xは、アルキルアミノであり、
Aは、C1〜C6の任意に置換されたアルキルであり、前記C1〜C6の任意に置換されたアルキルは、飽和または不飽和であり得、Aは、存在してもしなくてもよく、
Yは、ケタール、エステル、任意に置換されたカルバメート、エーテル、および任意に置換されたアミドからなる群から選択され、
Zは、アルキル鎖のそれぞれがC8〜C11の長さを有する3つのアルキル鎖からなる疎水性部分であり、3つのアルキル鎖のそれぞれは、独立して、飽和または不飽和であり得、3つのアルキル鎖のそれぞれは、任意に置換される、カチオン性脂質またはその塩を提供する。
を有し、式中、R1、R2、およびR3は、それぞれ独立して、C8〜C11アルキルからなる群から選択され、R1、R2、およびR3のそれぞれは、独立して、飽和または不飽和であり得、R1、R2、およびR3のそれぞれは、任意に置換される。
活性剤(例えば、治療剤)には、細胞、組織、器官、または対象に対して所望の効果を呈することが可能な任意の分子が含まれる。そのような効果は、例えば、生物学的、生理学的、および/または美容的であり得る。活性剤は、核酸、ペプチド、ポリペプチド、小分子、およびそれらの混合物を含むがこれらに限定されない、任意の種類の分子または化合物であり得る。核酸の非限定的な例には、干渉RNA分子(例えば、siRNA、Dicer基質dsRNA、shRNA、aiRNA、および/またはmiRNA)、アンチセンスオリゴヌクレオチド、プラスミド、リボザイム、免疫賦活性オリゴヌクレオチド、およびこれらの混合物が挙げられる。ペプチドまたはポリペプチドの例には、限定することなく、抗体(例えば、ポリクローナル抗体、モノクローナル抗体、抗体フラグメント;ヒト化抗体、組み換え抗体、組み換えヒト抗体、および/またはPrimatized(商標)抗体)、サイトカイン、成長因子、アポトーシス因子、分化誘発因子、細胞表面受容体およびそれらのリガンド、ホルモン、ならびにこれらの組み合わせが挙げられる。小分子の例には、当業者に既知の任意の従来的な薬剤または薬物等の有機小分子または化合物が挙げられるが、これらに限定されない。
ある特定の実施形態において、本発明の脂質粒子は、核酸と会合し、核酸−脂質粒子(例えば、LNP)をもたらす。いくつかの実施形態において、核酸は、脂質粒子に完全にカプセル封入される。本明細書に使用される際、「核酸」という用語には、任意のオリゴヌクレオチドまたはポリヌクレオチドが含まれ、60個までのヌクレオチドを含有するフラグメントは、一般的に、オリゴヌクレオチドと称され、それよりも長いフラグメントは、ポリヌクレオチドと称される。特定の実施形態において、本発明のオリゴヌクレオチドは、約15〜約60ヌクレオチドの長さである。核酸は、本発明の脂質粒子中、単独で投与されてもよく、またはペプチド、ポリペプチド、もしくは従来的な薬物等の小分子を含む本発明の脂質粒子と組み合わせて投与(例えば、共投与)されてもよい。
本発明の核酸−脂質粒子のsiRNA構成成分は、目的の標的遺伝子の発現をサイレンシングすることができる。siRNA二重鎖の各鎖は、典型的に、約15〜約60ヌクレオチドの長さであり、好ましくは、約15〜約30ヌクレオチドの長さである。ある特定の実施形態において、siRNAは、少なくとも1つの修飾ヌクレオチドを含む。修飾siRNAは、通常、対応する非修飾siRNA配列よりも免疫賦活性が低く、目的の標的遺伝子に対するRNAi活性を保持する。いくつかの実施形態において、修飾siRNAは、2’OMe−グアノシン、2’OMe−ウリジン、2’OMe−アデノシン、および/または2’OMe−シトシンヌクレオチドといった、少なくとも1つの2’OMeプリンまたはピリミジンヌクレオチドを含有する。修飾ヌクレオチドは、siRNAの一方の鎖(すなわち、センスもしくはアンチセンス)、または両方の鎖に存在し得る。いくつかの好ましい実施形態において、siRNAの一方の鎖(すなわち、センスもしくはアンチセンス)または両方の鎖において、ウリジンおよび/またはグアノシンヌクレオチドのうちの1つ以上が修飾される(例えば、2’OMe−修飾される)。これらの実施形態において、修飾siRNAは、1つ以上の修飾(例えば、2’OMe−修飾)アデノシンおよび/または修飾(例えば、2’OMe−修飾)シトシンヌクレオチドをさらに含み得る。他の好ましい実施形態において、siRNAの一方の鎖(すなわち、センスもしくはアンチセンス)または両方の鎖において、ウリジンおよび/またはグアノシンヌクレオチドのみが修飾される(例えば、2’OMe−修飾される)。siRNA配列は、オーバーハング(例えば、Elbashir et al.,Genes Dev.,15:188(2001)もしくはNykanen et al.,Cell,107:309(2001)に記載される3’もしくは5’オーバーハング)を有し得るか、またはオーバーハングを欠いてもよい(すなわち、平滑末端を有する)。
好適なsiRNA配列は、当該技術分野で既知の任意の手段を用いて特定することができる。典型的には、Elbashir et al.,Nature,411:494−498(2001)およびElbashir et al.,EMBO J.,20:6877−6888(2001)に記載される方法を、Reynolds et al.,Nature Biotech.,22(3):326−330(2004)に記載される合理的設計規則と組み合わせる。
siRNAは、例えば、1つ以上の単離された低分子干渉RNA(siRNA)二重鎖として、より長い二本鎖RNA(dsRNA)として、またはDNAプラスミドにおいて転写カセットから転写されたsiRNAもしくはdsRNAとしてを含む、複数の形態で提供され得る。いくつかの実施形態において、siRNAは、酵素的に、または部分的/完全な有機合成によって生成することができ、修飾リボヌクレオチドは、インビトロ酵素または有機合成によって導入することができる。ある特定の事例において、各鎖は、化学的に調製される。RNA分子の合成方法は当該技術分野で既知であり、例えば、Verma and Eckstein(1998)に記載されるか、または本明細書に記載される化学合成方法である。
ある特定の態様において、siRNA分子は、2つの鎖と、二本鎖領域に少なくとも1つの修飾ヌクレオチドとを有する二重鎖を含み、ここで、各鎖は、約15〜約60ヌクレオチドの長さである。有利なことに、修飾siRNAは、対応する非修飾siRNA配列よりも免疫賦活性が低いが、標的配列の発現をサイレンシングする能力は保持する。好ましい実施形態において、siRNA分子に導入される化学修飾の程度は、siRNAの免疫賦活特性の低減または無効化と、RNAi活性の保持とをうまく両立させる。非限定的な例として、目的の遺伝子を標的とするsiRNA分子は、siRNAによって生成される免疫応答を排除し、同時に標的遺伝子の発現をサイレンシングするその能力を保持するように、siRNA二重鎖内の選択的なウリジンおよび/またはグアノシンヌクレオチドが最小限に修飾され得る(例えば、約30%未満、25%、20%、15%、10%、または5%修飾される)。
本明細書に記載の核酸−脂質粒子のsiRNA成分を使用して、目的の遺伝子の翻訳(すなわち、発現)を下方制御するか、またはサイレンシングすることができる。目的の遺伝子には、ウイルスの感染および生存と関連する遺伝子、代謝性疾患および障害(例えば、肝臓疾患および障害)と関連する遺伝子、腫瘍形成または細胞形質転換(例えば、癌)と関連する遺伝子、血管形成遺伝子、炎症および自己免疫応答と関連するもの等の免疫調節遺伝子、受容体リガンド遺伝子、ならびに神経変性障害と関連する遺伝子が挙げられるが、これらに限定されない。
いくつかの実施形態において、siRNA分子の各鎖は、約15〜約60ヌクレオチドの長さ(例えば、約15〜60、15〜50、15〜40、15〜30、15〜25、もしくは19〜25ヌクレオチドの長さ、または15、16、17、18、19、20、21、22、23、24、もしくは25ヌクレオチドの長さ)を含む。1つの特定の実施形態において、siRNAは、化学合成される。本発明のsiRNA分子は、インビトロおよび/またはインビボで標的配列の発現をサイレンシングすることができる。
本明細書に使用される際、「Dicer基質dsRNA」または「前駆体RNAi分子」という用語は、インビボでDicerによってプロセシングされて、標的遺伝子のRNA干渉のためにRISC複合体に組み込まれる活性なsiRNAをもたらす、任意の前駆体分子を含むことを意図する。
5’−pXXXXXXXXXXXXXXXXXXXXXXXDD−3’
3’−YXXXXXXXXXXXXXXXXXXXXXXXXXp−5’
式中、「X」=RNAであり、「p」=リン酸基であり、「X」=2’OMe RNAであり、「Y」は、場合によっては2’OMe RNAモノマーである1、2、3、または4個のRNAモノマーから構成されるオーバーハングドメインであり、「D」=DNAである。上の鎖はセンス鎖であり、下の鎖はアンチセンス鎖である。
「低分子ヘアピンRNA」または「短いヘアピンRNA」または「shRNA」には、RNA干渉を介して遺伝子の発現をサイレンシングするために使用可能である、急なヘアピンカーブを生じる短いRNA配列が含まれる。本発明のshRNAは、化学合成され得るか、またはDNAプラスミドにおいて転写カセットから転写され得る。shRNAのヘアピン構造は、細胞機構によってsiRNAに切断され、これが、次いで、RNA誘導型サイレンシング複合体(RISC)に結合する。
siRNAと同様に、非対称干渉RNA(aiRNA)は、RNA誘導型サイレンシング複合体(RISC)を動員し、アンチセンス鎖の5’末端に対するヌクレオチド10と11との間で標的配列の配列特異的切断を媒介することによって、哺乳動物細胞における種々の遺伝子の効果的なサイレンシングをもたらすことができる(Sun et al.,Nat.Biotech.,26:1379−1382(2008))。典型的に、aiRNA分子は、センス鎖およびアンチセンス鎖を有する短いRNA二重鎖を含み、この二重鎖は、アンチセンス鎖の3’および5’末端にオーバーハングを含有する。aiRNAは、一般に、センス鎖が、相補的アンチセンス鎖と比較して、両方の末端で短いため、非対称である。いくつかの態様において、aiRNA分子は、siRNA分子に使用されるものと類似の条件下で、設計、合成、およびアニーリングすることができる。非限定的な例として、aiRNA配列は、siRNA配列を選択するための上述の方法を使用して選択および生成することができる。
一般に、マイクロRNA(miRNA)は、約21〜23ヌクレオチドの長さの一本鎖RNA分子であり、遺伝子発現を制御する。miRNAは、遺伝子によってコードされ、その遺伝子のDNAからmiRNAが転写されるが、miRNAはタンパク質に翻訳されず(非コードRNA)、代わりに、各一次転写産物(pri−miRNA)が、pre−miRNAと称される短いステムのループ構造にプロセシングされ、最終的に機能的な成熟miRNAとなる。成熟miRNA分子は、1つ以上のメッセンジャーRNA(mRNA)分子に部分的または完全にのいずれかで相補的であり、それらの主要な機能は、遺伝子の発現を下方制御することである。miRNA分子の特定は、例えば、Lagos−Quintana et al.,Science,294:853−858、Lau et al.,Science,294:858−862、およびLee et al.,Science,294:862−864に記載されている。
一実施形態において、核酸は、目的の標的遺伝子または配列を対象とするアンチセンスオリゴヌクレオチドである。「アンチセンスオリゴヌクレオチド」または「アンチセンス」という用語には、標的とされるポリヌクレオチド配列に相補的なオリゴヌクレオチドが含まれる。アンチセンスオリゴヌクレオチドは、選択された配列に相補的な一本鎖のDNAまたはRNAである。アンチセンスRNAオリゴヌクレオチドは、相補的RNA鎖の翻訳を、そのRNAに結合することによって阻止する。アンチセンスDNAオリゴヌクレオチドを使用して、特定の相補的(コードまたは非コード)RNAを標的とすることができる。結合が生じると、このDNA/RNAハイブリッドは、酵素RNase Hによって分解され得る。特定の実施形態において、アンチセンスオリゴヌクレオチドは、約10〜約60個のヌクレオチド、より好ましくは約15〜約30個のヌクレオチドを含む。この用語はまた、所望の標的遺伝子に厳密に相補的でない可能性のあるアンチセンスオリゴヌクレオチドを包含する。したがって、本発明は、非標的特異的活性がアンチセンスにみられる場合、または標的配列との1つ以上のミスマッチを含有するアンチセンス配列が特定の使用に最も好ましい場合に、利用可能である。
本発明の実施形態によると、核酸−脂質粒子は、リボザイムと関連する。リボザイムは、エンドヌクレアーゼ活性を有する特定の触媒ドメインを有するRNA−タンパク質複合体である(Kim et al.,Proc.Natl.Acad.Sci.USA.,84:8788−92(1987)およびForster et al.,Cell,49:211−20(1987)を参照されたい)。例えば、多数のリボザイムは、リン酸エステル転移反応を、高度な特異性で加速させ、オリゴヌクレオチド基質において複数のリン酸エステルのうちの1つだけを切断することが多い(Cech et al.,Cell,27:487−96(1981)、Michel et al.,J.Mol.Biol.,216:585−610(1990)、Reinhold−Hurek et al.,Nature,357:173−6(1992)を参照されたい)。この特異性は、基質が、化学反応の前にリボザイムの内部ガイド配列(「IGS」)に特異的な塩基対相互作用を介して結合するという要件に起因している。
本発明の脂質粒子と関連する核酸は、免疫賦活性であり得、ヒト等の哺乳動物であり得る対象に投与した際に、免疫応答を誘発することができる免疫賦活性オリゴヌクレオチド(ISS、一本鎖または二本鎖)を含む。ISSには、例えば、ヘアピン二次構造をもたらす、ある特定のパリンドローム(Yamamoto et al.,J.Immunol.,148:4072−6(1992))、またはCpGモチーフ、ならびに他の既知のISS特徴(多重Gドメイン等、PCT公開第WO 96/11266号を参照されたく、この開示は、あらゆる目的のために参照によりその全体が本明細書に組み込まれる)が含まれる。
ある特定の実施形態において、本発明の脂質粒子と関連する活性剤は、1つ以上の治療的タンパク質、ポリペプチド、または有機小分子もしくは化合物を含み得る。このような治療上有効な薬剤または薬物の非限定的な例には、腫瘍学的薬物(例えば、化学療法薬、ホルモン療法剤、免疫療法剤、放射線療法剤等)、脂質低下剤、抗ウイルス薬、抗炎症化合物、抗鬱剤、刺激剤、鎮痛剤、抗生物質、受胎調節薬、解熱剤、血管拡張剤、抗血管形成剤、細胞血管剤(cytovascular agent)、シグナル伝達阻害剤、心血管薬、例えば抗不整脈剤、ホルモン、血管収縮剤、およびステロイドが挙げられる。これらの活性剤は、本発明の脂質粒子中、単独で投与されてもよく、または干渉RNA等の核酸を含む本発明の脂質粒子と組み合わせて投与されてもよい(例えば、共投与)。
ある特定の態様において、本発明は、本明細書に記載のカチオン性(アミノ)脂質またはその塩を含む、脂質粒子を提供する。いくつかの実施形態において、本発明の脂質粒子は、1つ以上の非カチオン性脂質をさらに含む。他の実施形態において、脂質粒子は、粒子の凝集を低減または阻害することができる1つ以上の複合脂質をさらに含む。さらなる実施形態において、脂質粒子は、治療的核酸(例えば、siRNA等の干渉RNA)等の1つ以上の活性剤または治療剤をさらに含む。
本明細書に記載される新規な式Iのカチオン性脂質またはその塩のいずれも、単独または1つ以上の他のカチオン性脂質種もしくは非カチオン性脂質種との組み合わせのいずれかで、本発明の脂質粒子(例えば、LNP)において使用することができる。
本発明の脂質粒子(例えば、LNP)に使用される非カチオン性脂質は、安定な化合物を生成することができる、種々の中性非荷電、双性イオン性、またはアニオン性脂質のいずれかであり得る。
カチオン性および非カチオン性脂質に加えて、本発明の脂質粒子(例えば、LNP)は、脂質複合体をさらに含み得る。複合脂質は、それが粒子の凝集を阻止するという点で、有用である。好適な複合脂質には、PEG−脂質複合体、POZ−脂質複合体、ATTA−脂質複合体、カチオン性−ポリマー−脂質複合体(CPL)、およびこれらの混合物が挙げられるが、これらに限定されない。ある特定の実施形態において、粒子は、PEG−脂質複合体またはATTA−脂質複合体のいずれかを、CPLとともに含む。
本発明での使用に好適なさらなるPEG−脂質には、限定することなく、mPEG2000−1,2−ジ−O−アルキル−sn3−カルボモイルグリセリド(PEG−C−DOMG)が挙げられる。PEG−C−DOMGの合成は、PCT公開第WO 09/086558号に記載され、この開示は、あらゆる目的のために参照によりその全体が本明細書に組み込まれる。なおもさらに好適なPEG−脂質複合体には、限定することなく、1−[8’−(1,2−ジミリストイル−3−プロパノキシ)−カルボキサミド−3’,6’−ジオキサオクタニル]カルバモイル−ω−メチル−ポリ(エチレングリコール)(2KPEG−DMG)が挙げられる。2KPEG−DMGの合成は、米国特許第7,404,969号に記載され、この開示は、あらゆる目的のために参照によりその全体が本明細書に組み込まれる。
干渉RNA(例えば、siRNA)等の活性剤または治療剤が粒子の脂質部分内に封入され、分解から保護される、本発明の脂質粒子、例えば、LNPは、連続混合方法、直接希釈プロセス、および直列(in−line)希釈プロセスを含むが、これらに限定されない、当該技術分野で既知の任意の方法によって形成することができる。
本発明はまた、キット形態での脂質粒子(例えば、LNP)も提供する。いくつかの実施形態において、キットは、脂質粒子の種々の要素(例えば、核酸等の活性剤または治療剤および粒子の個々の脂質構成成分)を保持するために区画化された容器を含む。好ましくは、キットは、本発明の脂質粒子(例えば、LNP)を保持する容器(例えば、バイアルまたはアンプル)を含み、この粒子は、本明細書に記載されるプロセスのうちの1つによって生成される。ある特定の実施形態において、キットは、エンドソーム膜不安定化剤(例えば、カルシウムイオン)をさらに含んでもよい。キットは典型的に、本発明の粒子組成物を、薬学的に許容される担体中の懸濁液または脱水型でのいずれかとして、それらの再水和(凍結乾燥されている場合)および投与のための指示書とともに含有する。
一旦形成されると、本発明の脂質粒子(例えば、LNP)は、活性剤または治療剤(例えば、干渉RNA等の核酸)の細胞内への導入に有用である。したがって、本発明はまた、核酸(例えば、干渉RNA)等の活性剤または治療剤を細胞内に導入するための方法も提供する。いくつかの事例において、細胞は、例えば、肝臓組織内に存在する肝細胞(hepatocyte)等の肝臓細胞(liver cell)である。他の事例において、細胞は、例えば、固形腫瘍中に存在する腫瘍細胞等の腫瘍細胞である。本方法は、上述のように粒子を形成し、次いで活性剤または治療剤の細胞への送達が生じるのに十分な一定期間にわたって粒子を細胞と接触させることによって、インビトロまたはインビボで行われる。
インビボ療法のための全身送達、例えば、循環等の身体のシステムを介した遠位の標的細胞への治療的核酸の送達は、PCT公開第WO 05/007196号、同第WO 05/121348号、同第WO 05/120152号、および同第WO 04/002453号に記載されるもの等の核酸−脂質粒子を使用して達成されてきており、これらの開示は、あらゆる目的のために参照によりその全体が本明細書に組み込まれる。本発明はまた、核酸を血清中のヌクレアーゼ分解から保護し、非免疫原性であり、分包が小さく、かつ反復投薬に好適である、完全にカプセル封入された脂質粒子も提供する。
インビトロ適用のために、核酸(例えば、干渉RNA)等の治療剤の送達は、植物起源または動物起源の細胞、脊椎動物または無脊椎動物、および任意の組織または型の細胞にかかわらず、培養において成長させられる任意の細胞へと行うことができる。好ましい実施形態において、細胞は、動物細胞、より好ましくは哺乳類細胞、および最も好ましくはヒト細胞(例えば、腫瘍細胞または肝細胞)である。
本発明の組成物および方法は、インビボおよびインビトロで、多種多様な細胞型を処理するために使用される。好適な細胞には、肝細胞、細網内皮細胞(例えば、単球、マクロファージ等)、線維芽細胞、内皮細胞、血小板細胞、ウイルスに感染したおよび/またはウイルスに感染しやすい他の細胞型、造血前駆(幹)細胞、角化細胞、骨格筋および平滑筋細胞、骨芽細胞、ニューロン、静止リンパ球、最終分化細胞、分裂速度が遅いまたは分裂していない(noncycling)初代細胞、実質細胞、リンパ系細胞、上皮細胞、骨細胞等が含まれるが、これらに限定されない。
いくつかの実施形態において、本発明の脂質粒子(例えば、LNP)は、対象において、約1、2、3、4、5、6、7、8時間、またはそれを超える時間時点で検出可能である。他の実施形態において、本発明の脂質粒子(例えば、LNP)は、対象において、粒子の投与後の約8、12、24、48、60、72、もしくは96時間、または約6、8、10、12、14、16、18、19、22、24、25、もしくは28日時点で検出可能である。粒子の存在は、対象からの細胞、組織、または他の生体試料内で検出され得る。粒子は、例えば、粒子の直接検出、核酸(例えば、siRNA)配列等の治療的干渉RNAの検出、目的の標的配列の検出(すなわち、目的の配列の発現または低減された発現を検出することによって)、またはそれらの組み合わせによって、検出されてもよい。
LNP等の本発明の脂質粒子は、当該技術分野で既知の任意の方法を使用して検出することができる。例えば、標識が、当該技術分野で既知の方法を使用して脂質粒子の構成成分に直接的または間接的に結合され得る。多種多様な標識を使用することができ、このうち標識の選定は、必要とされる感受性、脂質粒子構成成分との複合体化の容易さ、安定性要件、ならびに利用可能な器具類および自由に使用できる設備に依存する。好適な標識には、蛍光色素等のスペクトル標識(例えば、フルオレセインイソチオシアネート(FITC)およびOregon Green(商標)等のフルオレセインおよび誘導体;テキサスレッド、テトラローダミン(tetrarhodimine)イソチオシアネート(TRITC)等のローダミンおよび誘導体、ジゴキシゲニン、ビオチン、フィコエリトリン、AMCA、CyDyes(商標)等;3H、125I、35S、14C、32P、33P等の放射標識;西洋ワサビペルオキシダーゼ、アルカリホスファターゼ等の酵素;コロイド金もしくは着色ガラスまたはポリスチレン、ポリプロピレン、ラテックス等のプラスチックビーズ等の分光測色スペクトル比色定量標識が含まれるが、これらに限定されない。標識は、当該技術分野で既知の任意の手段を使用して検出することができる。
核酸(例えば、干渉RNA)は、本明細書において、当業者に周知の多数の手段によって検出および定量化される。核酸の検出は、サザン分析、ノーザン分析、ゲル電気泳動、PCR、放射標識、シンチレーション計数、および親和性クロマトグラフィーといった、周知の方法によって処理され得る。分光光度法、放射線撮影法、電気泳動法、キャピラリー電気泳動法、高速液体クロマトグラフィー(HPLC)、薄層クロマトグラフィー(TLC)、および高拡散クロマトグラフィー(hyperdiffusion chromatography)といった追加の分析生化学法もまた、利用可能である。
本発明は、具体的な実施例を用いてより詳細に記載される。次の実施例は、例示説明の目的で提供され、本発明をいかなる様態でも限定することを意図されない。当業者であれば、変更または修正して本質的に同様の結果を得ることができる、多様な重要性の低いパラメータを容易に認識するであろう。
(実施例1)
化合物9のための合成スキーム
化合物3の合成
化合物4の合成
化合物5の合成
化合物6の合成
化合物7の合成
化合物8の合成
化合物9の合成
化合物11および13のための合成スキーム
化合物11の合成
化合物12の合成
化合物13の合成
化合物14のための合成スキーム
化合物14の合成
化合物19および21のための合成スキーム
化合物16の合成
化合物17の合成
化合物18の合成
化合物19の合成
化合物20の合成
化合物21の合成
化合物22のための合成スキーム
化合物22の合成
化合物23、24、および25のための合成スキーム
化合物24の合成
化合物25の合成
化合物26、27、および28のための合成スキーム
化合物27の合成
化合物28の合成
化合物30および31のための合成スキーム
化合物29の合成
化合物30の合成
化合物31の合成
化合物40のための合成スキーム
化合物34の合成
化合物35の合成
化合物36の合成
化合物37の合成
化合物38の合成
化合物39の合成
化合物40の合成
化合物42のための合成スキーム
化合物42の合成
化合物50のための合成スキーム
化合物45の合成
化合物46の合成
化合物47の合成
化合物48の合成
化合物49の合成
化合物50の合成
化合物53のための合成スキーム
化合物51の合成
化合物52の合成
化合物53の合成
(実施例2)
(実施例3)
(実施例4)
化合物62のための合成スキーム
5の合成について記載される手順と類似した手順を使用して、(6Z,16Z)−12−((Z)−デカ−4−エン−1−イル)ドコサ−6,16−ジエン−11−イルメタンスルホネート61(1.18g、90%)を無色の油として、(6Z,16Z)−12−((Z)−デカ−4−エン−1−イル)ドコサ−6,16−ジエン−11−オール8(1.12g、2.43mmol)、トリエチルアミン(8mL)、およびメタンスルホニルクロリド(0.38mL、4.9mmol)から得た。Rf0.91(CH2Cl2)。
化合物62の合成
トルエン(30mL)中のメシル酸塩61(1.09g、2.01mmol)の溶液を、N,N−ジメチルアミノブタノール(1.34mL、10.1mmol)およびNaH(60%の油中分散体として442mg、11.1mmol)で順次に処理した。ガス放散が終止した時点で、反応混合物を還流させ(115°C溶液槽温度)、撹拌した(50時間)。反応混合物を次いで冷却し(室温)、冷水中に注ぎ、次いでEtOAcで抽出した。組み合わせた有機物を水およびブラインで洗浄し、乾燥させ(Na2SO4)、濾過し、濃縮し、クロマトグラフィー(100%EtOAc)を介して精製して、淡黄色の油として4−(((6Z,16Z)−12−((Z)−デカ−4−エン−1−イル)ドコサ−6,16−ジエン−11−イル)オキシ)−N,N−ジメチルブタン−1−アミン62(143mg、13%)を得た。1H NMR(400MHz、CDCl3)δ5.41〜5.30(m、6H)、3.46〜3.35(m、2H)、3.19〜3.14(m、1H)、2.34(t、2H)、2.24(s、6H)、2.10〜1.93(m、12H)、1.60〜1.09(m、35H)、0.90(t、9H)。Rf0.54(10%MeOH−CH2Cl2)。
化合物71のための合成スキーム
5の合成について記載される手順と類似した手順を使用して、3,7−ジメチルオクチルメタンスルホネート63(7.47g、99%超)を無色の油として、3,7−ジメチルオクタン−1−オール(5.0g、31.6mmol)、トリエチルアミン(8mL)、およびメタンスルホニルクロリド(4.89mL、63.2mmol)から得た。Rf0.69(CH2Cl2)。
化合物64の合成
3の合成について記載される手順と類似した手順を使用して、1−ブロモ−3,7−ジメチルオクタン64を無色の油(6.0g、86%)として、3,7−ジメチルオクチルメタンスルホネート63(7.47g、31.6mmol)およびテトラブチルアンモニウムブロミド(13.2g、41.1mmol)から得た。Rf0.92(ヘキサン)。
化合物65の合成
4の合成について記載される手順と類似した手順を使用して、2,6,12,16−テトラメチルヘプタデカン−9−オール65(7.0g、定量)を無色の油として、1−ブロモ−3,7−ジメチルオクタン64(10g、45.2mmol)、削り状マグネシウム(1.21g、49.8mmol)、ギ酸エチル(3.8mL、47.5mmol)、および水酸化カリウム(3.8g、67.8mmol)から得た。Rf0.38(10%EtOAc−ヘキサン)。
化合物66の合成
5の合成について記載される手順と類似した手順を使用して、2,6,12,16−テトラメチルヘプタデカン−9−イルメタンスルホネート66(1.56g、87%)を無色の油として、2,6,12,16−テトラメチルヘプタデカン−9−オール65(1.39g、5.14mmol)、トリエチルアミン(3mL)、およびメタンスルホニルクロリド(0.8mL、10.3mmol)から得た。Rf0.8(CH2Cl2)。
化合物67の合成
6の合成について記載される手順と類似した手順を使用して、2−(3,7−ジメチルオクチル)−5,9−ジメチルデカンニトリル67(0.8g、56%)を無色の油として、2,6,12,16−テトラメチルヘプタデカン−9−イルメタンスルホネート66(1.56g、4.48mmol)およびシアン化ナトリウム(0.55g、11.2mmol)から得た。Rf0.8(10%EtOAc−ヘキサン)。
化合物68の合成
7の合成について記載される手順と類似した手順を使用して、2−(3,7−ジメチルオクチル)−5,9−ジメチルデカナール68(0.63g、78%)を無色の油として、2−(3,7−ジメチルオクチル)−5,9−ジメチルデカンニトリル67(0.8g、2.49mmol)およびDIBAL(ヘキサン中1M溶液として5.74mL、5.74mmol)から得た。Rf0.6(10%EtOAc−ヘキサン)。
化合物69の合成
8の合成について記載される手順と類似した手順を使用して、10−(3,7−ジメチルオクチル)−2,6,13,17−テトラメチルオクタデカン−9−オール69(0.53g、62%)を無色の油として、2−(3,7−ジメチルオクチル)−5,9−ジメチルデカナール68(0.6g、1.85mmol)、1−ブロモ−3,7−ジメチルオクタン64(2.0g、9.0mmol)、および削り状マグネシウム(232mg、9.67mmol)から得た。Rf0.37(10%EtOAc−ヘキサン)。
化合物70の合成
10の合成について記載される手順と類似した手順を使用して、10−(3,7−ジメチルオクチル)−2,6,13,17−テトラメチルオクタデカン−9−イル5−ブロモペンタノエート68(450mg、粗)を黄色の油として、10−(3,7−ジメチルオクチル)−2,6,13,17−テトラメチルオクタデカン−9−オール69(200mg、0.43mmol)、EDC(246mg、1.28mmol)、および5−ブロモ吉草酸(246mg、1.28mmol)から得た。Rf0.49(5%EtOAc−ヘキサン)。
化合物71の合成
11の合成について記載される手順と類似した手順を使用して、10−(3,7−ジメチルオクチル)−2,6,13,17−テトラメチルオクタデカン−9−イル5−(ジメチルアミノ)ペンタノエート71(184mg、72%、2ステップ)を無色の油として、10−(3,7−ジメチルオクチル)−2,6,13,17−テトラメチルオクタデカン−9−イル5−ブロモペンタノエート68(450mg、粗)およびジメチルアミン(EtOH中2.0M溶液として10mL)から得た。1H NMR(400MHz、CDCl3)δ4.95〜4.87(m、1H)、2.33(t、2H)、2.28(t、2H)、2.23(s、6H)、1.74〜1.60(m、4H)、1.58〜0.99(m、37H)、0.93〜0.79(m、27H)。Rf0.43(10%CH3OH−CH2Cl2)。
化合物74のための合成スキーム
化合物72の合成
8の合成について記載される手順と類似した手順を使用して、(Z)−10−((Z)−デカ−4−エン−1−イル)−2,6−ジメチルイコサ−14−エン−9−オール72(0.62g、72%)を無色の油として、(Z)−2−((Z)−デカ−4−エニル)ドデカ−6−エナール7(0.6g、1.87mmol)、1−ブロモ−3,7−ジメチルオクタン64(3.9g、17.5mmol)、および削り状マグネシウム(454mg、18.7mmol)から得た。Rf0.61(10%EtOAc−ヘキサン)。
化合物73の合成
10の合成について記載される手順と類似した手順を使用して、(Z)−10−((Z)−デカ−4−エン−1−イル)−2,6−ジメチルイコサ−14−エン−9−イル5−ブロモペンタノエート73(900mg、粗)を黄色の油として、(Z)−10−((Z)−デカ−4−エン−1−イル)−2,6−ジメチルイコサ−14−エン−9−オール72(620mg、1.34mmol)、EDC(500mg、2.6mmol)、および5−ブロモ吉草酸(500mg、2.56mmol)から得た。Rf0.72(10%EtOAc−ヘキサン)。
化合物74の合成
11の合成について記載される手順と類似した手順を使用して、(Z)−10−((Z)−デカ−4−エン−1−イル)−2,6−ジメチルイコサ−14−エン−9−イル5−(ジメチルアミノ)ペンタノエート74(466mg、58%、2ステップ)を無色の油として、(Z)−10−((Z)−デカ−4−エン−1−イル)−2,6−ジメチルイコサ−14−エン−9−イル5−ブロモペンタノエート73(900mg、粗)およびジメチルアミン(EtOH中2.0M溶液として15mL)。1H NMR(400MHz、CDCl3)δ5.43〜5.29(m、4H)、4.94〜4.88(m、1H)、2.32(t、2H)、2.26(t、2H)、2.15(s、6H)、2.08〜1.93(m、8H)、1.70〜1.00(m、43H)、0.95〜0.83(m、15H)。Rf0.42(10%CH3OH−CH2Cl2)。
化合物76のための合成スキーム
5−ブロモペンタン−1−オール(1.0g、5.99mmol)の溶液を、密封容器中でジメチルアミン(EtOH中2M溶液として10mL)とともに調製し、加熱した(80°C)。撹拌した後(16時間)、ジメチルアミンおよびEtOHを減圧下で除去して、黄色がかったオレンジ色の固体として5−(ジメチルアミノ)ペンタン−1−オール臭化水素酸塩75(1.26g、定量)を得た。Rf0.25(10%CH3OH−CH2Cl2)。
化合物76の合成
62の合成について記載される手順と類似した手順を使用して、5−(((6Z,16Z)−12−((Z)−デカ−4−エン−1−イル)ドコサ−6,16−ジエン−11−イル)オキシ)−N,N−ジメチルペンタン−1−アミン76(864mg、37%)を淡黄色の油として、(6Z,16Z)−12−((Z)−デカ−4−エン−1−イル)ドコサ−6,16−ジエン−11−イルメタンスルホネート61(1.86g、3.45mmol)、5−(ジメチルアミノ)ペンタン−1−オール臭化水素酸塩75(1.26g、5.99mmol)、およびNaH(60%の油中分散体として288mg、7.2mmol)から得た。1H NMR(400MHz、CDCl3)δ5.43〜5.32(m、6H)、3.46〜3.33(m、2H)、3.18〜3.12(m、1H)、2.30〜2.18(m、8H)、2.07〜1.93(m、12H)、1.61〜1.04(m、37H)、0.89(t、9H)。Rf0.47(10%MeOH−CH2Cl2)。
化合物79のための合成スキーム
化合物77の合成
無水ジクロロメタン(125mL)中の(6Z,16Z)−12−((Z)−デカ−4−エニル)ドコサ−6,16−ジエン−11−オール8(5g、10.9mmol)の冷却した溶液(−15°C)に、ジエチル亜鉛(ヘキサン中1M、82mL、81.8mmol)を窒素下で20分間にわたって滴加した。溶液を0°Cで70分間撹拌し、次いでジヨードメタン(6.6mL、81.8mmol)を注意深く添加した。溶液を一晩撹拌して、室温まで温めさせた。完了すると、溶液を氷水(350mL)中に注ぎ、酢酸エチル(450mL)で希釈した。次いで5%HCl(350mL)を添加して、形成した乳濁液を軽減する一助とした。有機層をNaHCO3(飽和水溶液500mL)、水(500mL)、およびブライン(500mL)で洗浄した。組み合わせた水層を酢酸エチルで逆抽出した。組み合わせた有機抽出物を硫酸マグネシウム上で乾燥させ、濾過し、真空下で濃縮乾固した。残渣をシリカゲル(ヘキサン中2.5%酢酸エチル)上のカラムクロマトグラフィーによって精製して、ピンク色の油を得た。この色(I2)を除去するために、精製した生成物をジクロロメタン(150mL)中に溶解させ、Na2S2O3(飽和水溶液2×40mL)で洗浄して、淡黄色の油(5.54g、96.5%)として1,8−ビス(2−ペンチルシクロプロピル)−5−(3−(2−ペンチルシクロプロピル)プロピル)オクタン−4−オール77を得た。
化合物78の合成
(6Z,16Z)−12−((Z)−デカ−4−エニル)ドコサ−6,16−ジエン−11−イル6ブロモヘキサノエート10の合成について記載される手順と類似した手順を使用して、1,8−ビス(2−ペンチルシクロプロピル)−5−(3−(2−ペンチルシクロプロピル)プロピル)オクタン−4−イル6−ブロモヘキサノエートを粗製の油として、1,8−ビス(2−ペンチルシクロプロピル)−5−(3−(2−ペンチルシクロプロピル)プロピル)オクタン−4−イル6−(ジメチルアミノ)ヘキサノエート(0.75g、1.5mmol)、無水ジクロロメタン(5.2ml)、6−ブロモヘキサン酸(0.88g、4.5mmol)、1−エチル−3−(3−ジメチルアミノプロピル)カルボジイミド塩酸塩(0.87g、4.5mmol)、および4−ジメチルアミノピリジン(5mg)から得た。生成物を次のステップで、さらに精製することなく使用した。
化合物79の合成
(6Z,16Z)−12−((Z)−デカ−4−エニル)ドコサ−6,16−ジエン−11−イル6−(ジメチルアミノ(dimethyamino))ヘキサノエート11の合成について記載する手順と類似した手順を使用して、油(0.56g、59%)として、1,8−ビス(2−ペンチルシクロプロピル)−5−(3−(2−ペンチルシクロプロピル)プロピル)オクタン−4−イル6−ブロモヘキサノエート(1.0g、1.5mmol)およびエタノール中2.0Mジメチルアミン(3.5mL)から得た。Rf0.50(10%MeOH−CH2Cl2)。
化合物83のための合成スキーム
無水ジクロロメタン(500mL)中の2−オクチルドデカン−1−オール(20g、67.0mmol)の溶液に、クロロクロム酸ピリジニウム(43.2g、200mmol)を添加した。溶液を室温で3時間撹拌し、次いでシリカのパッドに通して濾過し、ジクロロメタンで溶出して、無色の油(10.5g、50%)として2−オクチルドデカナール80を得た。
化合物81の合成
(6Z,15Z)−ヘンイコサ−6,15−ジエン−11−オール4の合成について記載される手順と類似した手順を使用して、(Z)−12−オクチルドコサ−6−エン−11−オール81を無色の(cololess)油(0.67g、92%)として、2−オクチルドデカナール80(0.5g、1.6mmol)、(Z)−1−ブロモデセ−4−エン(0.7g、3.1mmol)、マグネシウム(80mg、3.4mmol)、無水テトラヒドロフラン(0.5mL)、水(2mL)、EtOH(2mL)、およびKOH(0.2g、2.8mmol)から得た。
化合物82の合成
(6Z,16Z)−12−((Z)−デカ−4−エニル)ドコサ−6,16−ジエン−11−イル6ブロモヘキサノエート10の合成について記載される手順と類似した手順を使用して、(Z)−12−オクチルドコサ−6−エン−11−イル6−ブロモヘキサノエート82を無色の油(0.78g、85%)として、(Z)−12−オクチルドコサ−6−エン−11−オール81(0.67g、1.5mmol)、無水ジクロロメタン(5mL)、6−ブロモヘキサン酸(0.80g、4.4mmol)、1−エチル−3−(3−ジメチルアミノプロピル)カルボジイミド塩酸塩(0.85g、4.4mmol)、および4−ジメチルアミノピリジン(5mg)から得た。生成物を次のステップで、さらに精製することなく使用した。
化合物83の合成
(6Z,16Z)−12−((Z)−デカ−4−エニル)ドコサ−6,16−ジエン−11−イル6−(ジメチルアミノ(dimethyamino))ヘキサノエート11の合成について記載する手順と類似した手順を使用して、(Z)−12−オクチルドコサ−6−エン−11−イル6−(ジメチルアミノ)ヘキサノエート83を油(103mg、14%)として、(Z)−12−オクチルドコサ−6−エン−11−イル6−ブロモヘキサノエート82(0.78g、1.3mmol)およびエタノール中2.0Mジメチルアミン(3mL)から得た。1H NMR(400MHz、CDCl3)δ5.43〜5.26(m、2H)、4.96〜4.91(m、1H)、2.33(t、4H)、2.26(s、6H)、2.08〜1.93(m、4H)、1.70〜1.60(m、2H)、1.57〜1.43(m、4H)、1.40〜1.15(m、43H)、0.94〜0.85(m、9H)。
化合物89のための合成スキーム
無水ジエチルエーテル(350mL)中の(E)−エチルデカ−4−エノエート(20g、101mmol)の冷却した溶液(0℃)に、水素化アルミニウムリチウム(8.9g、212mmol)を窒素下で添加した。溶液を室温(at room)で1時間撹拌し、次いで0℃まで冷却し、5M NaOH(30mL)で緩徐に反応停止処理し、エチルエーテル(100mL)で希釈した。溶液を30分間撹拌し、硫酸マグネシウム上で乾燥させ、濾過し、真空下で濃縮乾固して、油(16.1g、定量)として(E)−デカ−4−エン−1−オール84を得た。
化合物85の合成
(Z)−デカ−4−エニルメタンスルホネート2の合成について記載される手順と類似した手順を使用して、(E)−デカ−4−エニルメタンスルホネート85をオレンジ色の油(32.7g)として、(E)−デカ−4−エン−1−オール(16.1g、94.7mmol)、トリエチルアミン(15.5mL、111.7mmol)、およびメタンスルホニルクロリド(15.6mL、201.7mmol)から得た。Rf0.65(100%CH2Cl2)。
化合物86の合成
(Z)−1−ブロモデカ−4−エン3の合成について記載される手順と類似した手順を使用して、(E)−1−ブロモデカ−4−エン86を油(17.9g、81%)として、(E)−デカ−4−エニルメタンスルホネート85(23.5g、94.7mmol)、およびテトラブチルアンモニウムブロミド(40.0g、124.1mmol)から得た。Rf0.85(10%EtOAc−ヘキサン)。
化合物87の合成
(6Z,15Z)−ヘンイコサ−6,15−ジエン−11−オール4を得る合成について記載される手順と類似した手順を使用して、(6E,16Z)−12−((Z)−デカ−4−エニル)ドコサ−6,16−ジエン−11−オール87を油(1.28g、71%)として、(E)−1−ブロモデカ−4−エン86(1.7g、7.8mmol)、削り状マグネシウム(0.19g、7.8mmol)、(Z)−2−((Z)−デカ−4−エニル)ドデカ−6−エナール7(1.25g、3.9mmol)、および水酸化カリウム(0.66g、11.7mmol)から得た。Rf0.43(10%EtOAc−ヘキサン)。
化合物88の合成
(6Z,16Z)−12−((Z)−デカ−4−エニル)ドコサ−6,16−ジエン−11−イル6−ブロモヘキサノエート10の合成について記載される手順と類似した手順を使用して、(6E,16Z)−12−((Z)−デカ−4−エニル)ドコサ−6,16−ジエン−11−イル5−ブロモペンタノエート88を油(1.36g、78%)として、(6E,16Z)−12−((Z)−デカ−4−エニル)ドコサ−6,16−ジエン−11−オール87(1.28g、2.8mmol)、および5−ブロモ−n−吉草酸(1.00g、5.6mmol)、1−エチル−3−(3−ジメチルアミノプロピル)カルボジイミド塩酸塩(1.06g、5.6mmol)、ジイソプロピルエチルアミン(1.1g、83.0mmol)、およびジメチルアミノピリジン(10mg)から得た。
化合物89の合成
(6Z,16Z)−12−((Z)−デカ−4−エニル)ドコサ−6,16−ジエン−11−イル6−(ジメチルアミノ)ヘキサノエート11の合成について記載される手順と類似した手順を使用して、(6E,16Z)−12−((Z)−デカ−4−エニル)ドコサ−6,16−ジエン−11−イル5−(ジメチルアミノ)ペンタノエート89を油(0.45g、35%)として、(6E,16Z)−12−((Z)−デカ−4−エニル)ドコサ−6,16−ジエン−11−イル5−ブロモペンタノエート88(1.36g、2.2mmol)、およびエタノール中2Mジメチルアミン(5mL)から得た。1H NMR(400MHz、CDCl3)δ5.45〜5.28(m、6H)、4.96〜4.91(m、1H)、2.34〜2.25(m、2H)、2.06〜1.90(m、12H)、1.68〜1.61(m、2H)、1.55〜1.45(m、5H)、1.45〜1.16(m、28H)、0.95〜0.84(m、9H)。Rf0.46(10%MeOH−CH2Cl2)。
化合物90のための合成スキーム
5の合成について記載される手順と類似した手順を使用して、無色の油として1,8−ビス(2−ペンチルシクロプロピル)−5−(3−(2−ペンチルシクロプロピル)プロピル)オクタン−4−イルメタンスルホネート89を得た。
化合物90の合成
62の合成について記載される手順と類似した手順を使用して、淡黄色の油として5−((1,8−ビス(2−ペンチルシクロプロピル)−5−(3−(2−ペンチルシクロプロピル)プロピル)オクタン−4−イル)オキシ)−N,N−ジメチルペンタン−1−アミン90(580mg)を得た。Rf0.48(10%MeOH−CH2Cl2)。
Claims (39)
- 構造式(I)を有する脂質
Xは、アルキルアミノであり、
Aは、C1〜C6の任意に置換されたアルキルであり、前記C1〜C6の任意に置換されたアルキルは、飽和または不飽和であり得、Aは、存在してもしなくてもよく、
Yは、ケタール、エステル、任意に置換されたカルバメート、エーテル、および任意に置換されたアミドからなる群から選択され、
Zは、アルキル鎖のそれぞれがC8〜C11の長さを有する3つのアルキル鎖からなる疎水性部分であり、前記3つのアルキル鎖のそれぞれは、独立して、飽和または不飽和であり得、前記3つのアルキル鎖のそれぞれは、任意に置換される、脂質またはその塩。 - 前記アルキル鎖のそれぞれが、C9〜C10の長さを有する、請求項1に記載の脂質。
- 前記アルキル鎖のうちの少なくとも1つは、二重結合を有する、請求項1に記載の脂質。
- 前記アルキル鎖のうちの少なくとも1つは、シス二重結合を有する、請求項1に記載の脂質。
- 前記アルキル鎖のうちの少なくとも1つは、シクロアルキル部分を含む、請求項1に記載の脂質。
- Xは、ジメチルアミノ、ジエチルアミノ、およびエチルメチルアミノからなる群から選択される、請求項1に記載の脂質。
- Aが存在する、請求項1に記載の脂質。
- Yは、エステルまたはケタールである、請求項1に記載の脂質。
- Yは、任意に置換されたカルバメートである、請求項1に記載の脂質。
- Yは、エーテルである、請求項1に記載の脂質。
- Yは、任意に置換されたアミドである、請求項1に記載の脂質。
- Zは、式
を有し、式中、R1、R2、およびR3は、それぞれ独立して、C8〜C11アルキルからなる群から選択され、R1、R2、およびR3のそれぞれは、独立して、飽和または不飽和であり得、R1、R2、およびR3のそれぞれは、任意に置換される、請求項1に記載の脂質。 - 前記脂質は、以下からなる群から選択される、請求項1に記載の脂質:
- 請求項1〜13のいずれかに記載の脂質を含む、脂質粒子。
- 前記粒子は、非カチオン性脂質をさらに含む、請求項14に記載の脂質粒子。
- 前記非カチオン性脂質は、リン脂質、コレステロール、またはリン脂質とコレステロールとの混合物からなる群から選択される、請求項15に記載の脂質粒子。
- 前記リン脂質は、ジパルミトイルホスファチジルコリン(DPPC)、ジステアロイルホスファチジルコリン(DSPC)、またはそれらの混合物を含む、請求項16に記載の脂質粒子。
- 前記コレステロールは、コレステロール誘導体である、請求項16に記載の脂質粒子。
- 前記粒子は、粒子の凝集を阻害する、複合脂質をさらに含む、請求項14〜18のいずれかに記載の脂質粒子。
- 粒子の凝集を阻害する前記複合脂質は、ポリエチレングリコール(PEG)−脂質複合体を含む、請求項19に記載の脂質粒子。
- 前記PEG−脂質複合体は、PEG−ジアシルグリセロール(PEG−DAG)複合体、PEG−ジアルキルオキシプロピル(PEG−DAA)複合体、またはそれらの混合物を含む、請求項20に記載の脂質粒子。
- 前記粒子は、治療剤をさらに含む、請求項14〜21のいずれかに記載の脂質粒子。
- 前記治療剤は、核酸である、請求項22に記載の脂質粒子。
- 前記核酸は、干渉RNAである、請求項23に記載の脂質粒子。
- 前記干渉RNAは、低分子干渉RNA(siRNA)、非対称干渉RNA(aiRNA)、マイクロRNA(miRNA)、Dicer基質dsRNA、低分子ヘアピンRNA(shRNA)、およびそれらの混合物からなる群から選択される、請求項24に記載の脂質粒子。
- 前記干渉RNAは、siRNAである、請求項25に記載の脂質粒子。
- 前記治療剤は、37℃で30分間血清中で粒子をインキュベートした後、実質的に分解されない、請求項22に記載の脂質粒子。
- 前記治療剤は、前記粒子に完全にカプセル封入される、請求項22に記載の脂質粒子。
- 前記粒子は、脂質:治療剤の質量比が約5:1〜約15:1である、請求項22に記載の脂質粒子。
- 前記粒子は、約30nm〜約150nmの中位径を有する、請求項14〜29のいずれかに記載の脂質粒子。
- 請求項14〜30のいずれかに記載の脂質粒子と、薬学的に許容される担体とを含む、薬学的組成物。
- 治療剤を細胞に導入するための方法であって、
前記細胞を、請求項14に記載の脂質粒子と接触させることを含む、方法。 - 前記細胞は、哺乳動物におけるものである、請求項32に記載の方法。
- 治療剤をインビボ送達するための方法であって、
哺乳動物に、請求項14に記載の脂質粒子を投与することを含む、方法。 - 前記投与は、経口、鼻腔内、静脈内、腹腔内、筋肉内、関節内、病巣内、気管内、皮下、および皮内からなる群から選択される、請求項34に記載の方法。
- 前記哺乳動物は、ヒトである、請求項34に記載の方法。
- 疾患または障害の治療を、それを必要とする哺乳動物において行うための方法であって、
前記哺乳動物に、請求項14に記載の脂質粒子の治療有効量を投与することを含む、方法。 - 前記疾患または障害は、ウイルス感染症、肝臓疾患または障害、および癌からなる群から選択される、請求項37に記載の方法。
- 前記哺乳動物は、ヒトである、請求項37に記載の方法。
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2018509406A (ja) * | 2015-03-11 | 2018-04-05 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | フィロウイルス感染症の処置のための方法及び医薬組成物 |
WO2019131770A1 (ja) * | 2017-12-27 | 2019-07-04 | 武田薬品工業株式会社 | 核酸含有脂質ナノ粒子及びその用途 |
JP2022506956A (ja) * | 2018-11-09 | 2022-01-17 | アルブータス・バイオファーマー・コーポレイション | 脂質ナノ粒子製剤 |
JP2022506955A (ja) * | 2018-11-09 | 2022-01-17 | アルブータス・バイオファーマー・コーポレイション | 脂質ナノ粒子製剤 |
Families Citing this family (165)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3403647A1 (en) | 2009-12-01 | 2018-11-21 | Translate Bio, Inc. | Delivery of mrna for the augmentation of proteins and enzymes in human genetic diseases |
US8853377B2 (en) | 2010-11-30 | 2014-10-07 | Shire Human Genetic Therapies, Inc. | mRNA for use in treatment of human genetic diseases |
EP2717893B1 (en) | 2011-06-08 | 2019-05-08 | Translate Bio, Inc. | Lipid nanoparticle compositions and methods for mrna delivery |
ES2795110T3 (es) | 2011-06-08 | 2020-11-20 | Translate Bio Inc | Lípidos escindibles |
SG11201405157PA (en) * | 2012-02-24 | 2014-10-30 | Protiva Biotherapeutics Inc | Trialkyl cationic lipids and methods of use thereof |
EP2830595B1 (en) | 2012-03-29 | 2019-10-16 | Translate Bio, Inc. | Ionizable cationic lipids |
EP3865123A1 (en) | 2012-03-29 | 2021-08-18 | Translate Bio, Inc. | Lipid-derived neutral nanoparticles |
US20150267192A1 (en) | 2012-06-08 | 2015-09-24 | Shire Human Genetic Therapies, Inc. | Nuclease resistant polynucleotides and uses thereof |
AU2013271392B2 (en) | 2012-06-08 | 2018-02-15 | Ethris Gmbh | Pulmonary delivery of mRNA to non-lung target cells |
EP3932947A1 (en) | 2013-03-14 | 2022-01-05 | Translate Bio MA, Inc. | Methods and compositions for delivering mrna coded antibodies |
AU2014236396A1 (en) | 2013-03-14 | 2015-08-13 | Shire Human Genetic Therapies, Inc. | Methods for purification of messenger RNA |
US10258698B2 (en) | 2013-03-14 | 2019-04-16 | Modernatx, Inc. | Formulation and delivery of modified nucleoside, nucleotide, and nucleic acid compositions |
CN105142676B (zh) | 2013-03-14 | 2022-06-28 | 夏尔人类遗传性治疗公司 | Cftr mrna组合物以及相关方法和用途 |
DK3388834T3 (da) | 2013-03-15 | 2020-05-04 | Translate Bio Inc | Synergistisk forbedring af levering af nukleinsyrer via blandede formuleringer |
WO2015011633A1 (en) * | 2013-07-23 | 2015-01-29 | Protiva Biotherapeutics, Inc. | Compositions and methods for delivering messenger rna |
WO2015034925A1 (en) | 2013-09-03 | 2015-03-12 | Moderna Therapeutics, Inc. | Circular polynucleotides |
BR112016007255A2 (pt) | 2013-10-03 | 2017-09-12 | Moderna Therapeutics Inc | polinucleotídeos que codificam receptor de lipoproteína de baixa densidade |
MX2016005237A (es) | 2013-10-22 | 2016-08-12 | Shire Human Genetic Therapies | Terapia de acido ribonucleico mensajero para la deficiencia de argininosuccinato sintetasa. |
EA201690588A1 (ru) | 2013-10-22 | 2016-09-30 | Шир Хьюман Дженетик Терапис, Инк. | Доставка мрнк в цнс и ее применение |
EP3060257B1 (en) | 2013-10-22 | 2021-02-24 | Translate Bio, Inc. | Lipid formulations for delivery of messenger rna |
JP6506749B2 (ja) | 2013-10-22 | 2019-04-24 | シャイアー ヒューマン ジェネティック セラピーズ インコーポレイテッド | フェニルケトン尿症のためのmRNA療法 |
PT3134506T (pt) | 2014-04-25 | 2019-10-31 | Translate Bio Inc | Métodos de purificação de rna mensageiro |
US10022455B2 (en) | 2014-05-30 | 2018-07-17 | Translate Bio, Inc. | Biodegradable lipids for delivery of nucleic acids |
ES2964588T3 (es) | 2014-06-24 | 2024-04-08 | Translate Bio Inc | Composiciones enriquecidas estereoquímicamente para la administración de ácidos nucleicos |
IL298516A (en) | 2014-06-25 | 2023-01-01 | Acuitas Therapeutics Inc | Novel lipids and lipid nanoparticle formulations for delivery of nucleic acids |
CA2953265C (en) | 2014-07-02 | 2023-09-26 | Shire Human Genetic Therapies, Inc. | Encapsulation of messenger rna |
EP3169693B1 (en) | 2014-07-16 | 2022-03-09 | ModernaTX, Inc. | Chimeric polynucleotides |
EP3171895A1 (en) | 2014-07-23 | 2017-05-31 | Modernatx, Inc. | Modified polynucleotides for the production of intrabodies |
CA2956554C (en) * | 2014-08-07 | 2022-03-01 | Takeda Pharmaceutical Company Limited | Preparation of cationic lipid compounds and their salts as nucleic acid carriers |
US9339029B2 (en) | 2014-09-04 | 2016-05-17 | Preceres Inc. | Hydrazinyl lipidoids and uses thereof |
AU2015357562B2 (en) | 2014-12-05 | 2021-10-21 | Translate Bio, Inc. | Messenger RNA therapy for treatment of articular disease |
US10172924B2 (en) | 2015-03-19 | 2019-01-08 | Translate Bio, Inc. | MRNA therapy for pompe disease |
IL283545B2 (en) * | 2015-06-29 | 2023-09-01 | Acuitas Therapeutics Inc | Lipids and nanoparticulate lipid formulations for delivery of nucleic acids |
EP3878955A1 (en) | 2015-10-14 | 2021-09-15 | Translate Bio, Inc. | Modification of rna-related enzymes for enhanced production |
EP3364981A4 (en) | 2015-10-22 | 2019-08-07 | ModernaTX, Inc. | VACCINE AGAINST THE HUMAN CYTOMEGALOVIRUS |
CA3003055C (en) | 2015-10-28 | 2023-08-01 | Acuitas Therapeutics, Inc. | Lipids and lipid nanoparticle formulations for delivery of nucleic acids |
RS63135B1 (sr) | 2015-12-23 | 2022-05-31 | Modernatx Inc | Postupci upotrebe polinukleotida koji kodiraju ox40 ligand |
MA43587A (fr) | 2016-01-10 | 2018-11-14 | Modernatx Inc | Arnm thérapeutiques codant pour des anticorps anti-ctla-4 |
KR102369898B1 (ko) | 2016-04-08 | 2022-03-03 | 트랜슬레이트 바이오 인코포레이티드 | 다량체 코딩 핵산 및 그 용도 |
US20190275170A1 (en) | 2016-05-18 | 2019-09-12 | Modernatx, Inc. | Polynucleotides encoding jagged1 for the treatment of alagille syndrome |
EP3469074B1 (en) | 2016-06-13 | 2020-12-09 | Translate Bio, Inc. | Messenger rna therapy for the treatment of ornithine transcarbamylase deficiency |
CA3034681A1 (en) | 2016-06-30 | 2018-01-04 | Arbutus Biopharma Corporation | Compositions and methods for delivering messenger rna |
US11253605B2 (en) | 2017-02-27 | 2022-02-22 | Translate Bio, Inc. | Codon-optimized CFTR MRNA |
US11969506B2 (en) | 2017-03-15 | 2024-04-30 | Modernatx, Inc. | Lipid nanoparticle formulation |
WO2018170256A1 (en) | 2017-03-15 | 2018-09-20 | Modernatx, Inc. | Herpes simplex virus vaccine |
EP3601576A1 (en) | 2017-03-24 | 2020-02-05 | CureVac AG | Nucleic acids encoding crispr-associated proteins and uses thereof |
US11357856B2 (en) | 2017-04-13 | 2022-06-14 | Acuitas Therapeutics, Inc. | Lipids for delivery of active agents |
JP7297676B2 (ja) | 2017-04-28 | 2023-06-26 | アクイタス セラピューティクス インコーポレイテッド | 新規なカルボニル脂質、および核酸を送達するための脂質ナノ粒子製剤 |
US11173190B2 (en) | 2017-05-16 | 2021-11-16 | Translate Bio, Inc. | Treatment of cystic fibrosis by delivery of codon-optimized mRNA encoding CFTR |
US11421011B2 (en) | 2017-05-18 | 2022-08-23 | Modernatx, Inc. | Polynucleotides encoding tethered interleukin-12 (IL12) polypeptides and uses thereof |
MA49395A (fr) | 2017-06-14 | 2020-04-22 | Modernatx Inc | Polynucléotides codant pour le facteur viii de coagulation |
EP3638215A4 (en) | 2017-06-15 | 2021-03-24 | Modernatx, Inc. | RNA FORMULATIONS |
US20210228738A1 (en) | 2017-07-17 | 2021-07-29 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Compositions and methods for increasing or enhancing transduction of gene therapy vectors and for removing or reducing immunoglobulins |
CA3073020A1 (en) | 2017-08-16 | 2019-02-21 | Acuitas Therapeutics, Inc. | Lipids for use in lipid nanoparticle formulations |
CA3073018A1 (en) | 2017-08-17 | 2019-02-21 | Acuitas Therapeutics, Inc. | Lipids for use in lipid nanoparticle formulations |
US11542225B2 (en) | 2017-08-17 | 2023-01-03 | Acuitas Therapeutics, Inc. | Lipids for use in lipid nanoparticle formulations |
US11524932B2 (en) | 2017-08-17 | 2022-12-13 | Acuitas Therapeutics, Inc. | Lipids for use in lipid nanoparticle formulations |
US11866696B2 (en) | 2017-08-18 | 2024-01-09 | Modernatx, Inc. | Analytical HPLC methods |
CN111315359A (zh) | 2017-08-31 | 2020-06-19 | 摩登纳特斯有限公司 | 制备脂质纳米颗粒的方法 |
CA3084061A1 (en) | 2017-12-20 | 2019-06-27 | Translate Bio, Inc. | Improved composition and methods for treatment of ornithine transcarbamylase deficiency |
WO2020041793A1 (en) | 2018-08-24 | 2020-02-27 | Translate Bio, Inc. | Methods for purification of messenger rna |
CN112996854B (zh) | 2018-09-19 | 2024-08-30 | 摩登纳特斯有限公司 | 高纯度peg脂质和其用途 |
WO2020061284A1 (en) | 2018-09-19 | 2020-03-26 | Modernatx, Inc. | Peg lipids and uses thereof |
CA3114699A1 (en) | 2018-10-09 | 2020-04-16 | The University Of British Columbia | Compositions and systems comprising transfection-competent vesicles free of organic-solvents and detergents and methods related thereto |
BR112021007360A2 (pt) | 2018-10-18 | 2021-07-20 | Takeda Pharmaceutical Company Limited | métodos para ativar/proliferar células t, para distribuir um ácido nucleico em células t e para produzir um medicamento, célula t, medicamento, cultura de células, composição, e, kit para distribuir um ácido nucleico em células t |
EP3938379A4 (en) | 2019-03-15 | 2023-02-22 | ModernaTX, Inc. | HIV RNA VACCINE |
CN114340664A (zh) | 2019-06-18 | 2022-04-12 | 爱尔兰詹森科学公司 | 乙型肝炎病毒(HBV)疫苗和靶向HBV的RNAi的组合 |
JP2022537324A (ja) | 2019-06-18 | 2022-08-25 | ヤンセン・サイエンシズ・アイルランド・アンリミテッド・カンパニー | B型肝炎ウイルス(hbv)ワクチンおよび抗pd-1抗体の組合せ |
KR20220041080A (ko) | 2019-06-18 | 2022-03-31 | 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 | B형 간염 바이러스(hbv) 백신 및 항-pd-1 또는 항-pc-l1 항체의 조합 |
CA3141323A1 (en) | 2019-06-18 | 2020-12-24 | Helen Horton | Recombinant interleukin 12 construct and uses thereof |
WO2020255010A1 (en) | 2019-06-18 | 2020-12-24 | Janssen Sciences Ireland Unlimited Company | Combination of recombinant interleukin 12 construct and hepatitis b virus (hbv) vaccines |
WO2020255062A1 (en) | 2019-06-20 | 2020-12-24 | Janssen Sciences Ireland Unlimited Company | Lipid nanoparticle or liposome delivery of hepatitis b virus (hbv) vaccines |
CN115279743B (zh) * | 2019-06-29 | 2024-05-14 | 精密纳米系统无限责任公司 | 用于核酸递送的可离子化脂质 |
WO2021016075A1 (en) | 2019-07-19 | 2021-01-28 | Flagship Pioneering Innovations Vi, Llc | Recombinase compositions and methods of use |
AU2020351225A1 (en) * | 2019-09-19 | 2022-04-07 | Modernatx, Inc. | Headgroup lipid compounds and compositions for intracellular delivery of therapeutic agents |
JP2022548320A (ja) | 2019-09-23 | 2022-11-17 | オメガ セラピューティクス, インコーポレイテッド | アポリポタンパク質b(apob)遺伝子発現をモジュレートするための組成物および方法 |
CA3147643A1 (en) | 2019-09-23 | 2021-04-01 | Omega Therapeutics, Inc. | Compositions and methods for modulating hepatocyte nuclear factor 4-alpha (hnf4.alpha.) gene expression |
EP4118207A1 (en) | 2020-03-11 | 2023-01-18 | Omega Therapeutics, Inc. | Compositions and methods for modulating forkhead box p3 (foxp3) gene expression |
JP2023518944A (ja) * | 2020-03-17 | 2023-05-09 | ジェネヴァント サイエンシズ ゲーエムベーハー | 肝星細胞への治療薬の脂質ナノ粒子送達のためのカチオン性脂質 |
IL296660A (en) | 2020-03-24 | 2022-11-01 | Generation Bio Co | Non-viral DNA vectors and their use for therapeutic expression of factor ix |
EP4127186A1 (en) | 2020-03-24 | 2023-02-08 | Generation Bio Co. | Non-viral dna vectors and uses thereof for expressing gaucher therapeutics |
WO2021236930A1 (en) | 2020-05-20 | 2021-11-25 | Flagship Pioneering Innovations Vi, Llc | Immunogenic compositions and uses thereof |
CN116322760A (zh) | 2020-05-20 | 2023-06-23 | 旗舰创业创新第六有限责任公司 | 冠状病毒抗原组合物及其用途 |
US20230203509A1 (en) | 2020-05-29 | 2023-06-29 | Flagship Pioneering Innovations Vi, Llc | Trem compositions and methods relating thereto |
KR20230029685A (ko) | 2020-05-29 | 2023-03-03 | 플래그쉽 파이어니어링 이노베이션스 브이아이, 엘엘씨 | Trem 조성물 및 이에 관련된 방법 |
WO2022008613A1 (en) | 2020-07-08 | 2022-01-13 | Janssen Sciences Ireland Unlimited Company | Rna replicon vaccines against hbv |
BR112023000327A2 (pt) | 2020-07-16 | 2023-01-31 | Acuitas Therapeutics Inc | Lipídeos catiônicos para o uso em nanopartículas lipídicas |
CA3189740A1 (en) | 2020-07-27 | 2022-02-03 | Anjarium Biosciences Ag | Compositions of dna molecules, methods of making therefor, and methods of use thereof |
WO2022032154A2 (en) | 2020-08-06 | 2022-02-10 | Modernatx, Inc. | Compositions for the delivery of payload molecules to airway epithelium |
JP2023542492A (ja) | 2020-09-03 | 2023-10-10 | フラッグシップ パイオニアリング イノベーションズ シックス,エルエルシー | 免疫原性組成物及びその使用 |
WO2022081589A1 (en) * | 2020-10-12 | 2022-04-21 | The Regents Of The University Of California | Endosomal escape domains for delivery of macromolecules into cells |
TW202245809A (zh) | 2020-12-18 | 2022-12-01 | 美商詹森藥物公司 | 用於治療b型肝炎病毒感染之組合療法 |
JP2024501288A (ja) | 2020-12-23 | 2024-01-11 | フラッグシップ パイオニアリング イノベーションズ シックス,エルエルシー | 修飾tremの組成物及びその使用 |
CA3203442A1 (en) | 2020-12-28 | 2022-07-07 | Arcturus Therapeutics, Inc. | Transcription activator-like effector nucleases (talens) targeting hbv |
CA3209032A1 (en) | 2021-02-26 | 2022-09-01 | Ethris Gmbh | Formulations for aerosol formation and aerosols for the delivery of nucleic acid |
US11952461B2 (en) | 2021-03-22 | 2024-04-09 | Sunbio, Inc. | Siloxy polyethylene glycol and derivatives thereof |
US20220325287A1 (en) | 2021-03-31 | 2022-10-13 | Flagship Pioneering Innovations V, Inc. | Thanotransmission polypeptides and their use in treating cancer |
CN115197079A (zh) * | 2021-04-08 | 2022-10-18 | 厦门赛诺邦格生物科技股份有限公司 | 一种聚乙二醇化脂质及其修饰的脂质体、含该脂质体的药物组合物及其制剂和应用 |
JP2024517427A (ja) | 2021-04-20 | 2024-04-22 | アンジャリウム バイオサイエンシズ エージー | アミロ-α-1,6-グルコシダーゼ、4-α-グルカノトランスフェラーゼをコードするDNA分子の組成物、その作製の方法、及びその使用の方法 |
WO2022232289A1 (en) | 2021-04-27 | 2022-11-03 | Generation Bio Co. | Non-viral dna vectors expressing therapeutic antibodies and uses thereof |
WO2022232286A1 (en) | 2021-04-27 | 2022-11-03 | Generation Bio Co. | Non-viral dna vectors expressing anti-coronavirus antibodies and uses thereof |
WO2022229903A1 (en) | 2021-04-28 | 2022-11-03 | Genevant Sciences Gmbh | Mrna delivery constructs and methods of using the same |
CN112979483B (zh) * | 2021-05-14 | 2021-08-06 | 苏州艾博生物科技有限公司 | 一种阳离子脂质化合物、包含其的组合物及应用 |
EP4367242A2 (en) | 2021-07-07 | 2024-05-15 | Omega Therapeutics, Inc. | Compositions and methods for modulating secreted frizzled receptor protein 1 (sfrp1) gene expression |
EP4373506A1 (en) | 2021-07-20 | 2024-05-29 | AGS Therapeutics SAS | Extracellular vesicles from microalgae, their preparation, and uses |
EP4377457A1 (en) | 2021-07-26 | 2024-06-05 | Flagship Pioneering Innovations VI, LLC | Trem compositions and uses thereof |
AR127073A1 (es) | 2021-09-17 | 2023-12-13 | Flagship Pioneering Innovations Vi Llc | Composiciones y métodos para producir polirribonucleótidos circulares |
AU2022370530A1 (en) | 2021-10-18 | 2024-05-02 | Flagship Pioneering Innovations Vi, Llc | Compositions and methods for purifying polyribonucleotides |
AU2022383068A1 (en) | 2021-11-08 | 2024-05-02 | Orna Therapeutics, Inc. | Lipid nanoparticle compositions for delivering circular polynucleotides |
WO2023086465A1 (en) | 2021-11-12 | 2023-05-19 | Modernatx, Inc. | Compositions for the delivery of payload molecules to airway epithelium |
CN118555966A (zh) | 2021-11-24 | 2024-08-27 | 旗舰创业创新六公司 | 免疫原性组合物及其用途 |
KR20240117569A (ko) | 2021-11-24 | 2024-08-01 | 플래그쉽 파이어니어링 이노베이션스 브이아이, 엘엘씨 | 코로나바이러스 면역원 조성물 및 그의 용도 |
WO2023096963A1 (en) | 2021-11-24 | 2023-06-01 | Flagship Pioneering Innovations Vi, Llc | Varicella-zoster virus immunogen compositions and their uses |
CN118510896A (zh) | 2021-12-17 | 2024-08-16 | 旗舰创业创新六公司 | 用于在变性条件下富集环状rna的方法 |
KR20240117149A (ko) | 2021-12-22 | 2024-07-31 | 플래그쉽 파이어니어링 이노베이션스 브이아이, 엘엘씨 | 폴리리보뉴클레오티드를 정제하기 위한 조성물 및 방법 |
AU2022420620A1 (en) | 2021-12-23 | 2024-07-04 | Flagship Pioneering Innovations Vi, Llc | Circular polyribonucleotides encoding antifusogenic polypeptides |
CN114044741B (zh) * | 2022-01-13 | 2022-04-15 | 北京悦康科创医药科技股份有限公司 | 一种阳离子脂质化合物、包含其的组合物及用途 |
WO2023135273A2 (en) | 2022-01-14 | 2023-07-20 | Anjarium Biosciences Ag | Compositions of dna molecules encoding factor viii, methods of making thereof, and methods of use thereof |
WO2023144127A1 (en) | 2022-01-31 | 2023-08-03 | Ags Therapeutics Sas | Extracellular vesicles from microalgae, their biodistribution upon administration, and uses |
TW202345863A (zh) | 2022-02-09 | 2023-12-01 | 美商現代公司 | 黏膜投與方法及調配物 |
WO2023161350A1 (en) | 2022-02-24 | 2023-08-31 | Io Biotech Aps | Nucleotide delivery of cancer therapy |
WO2023160702A1 (zh) * | 2022-02-28 | 2023-08-31 | 深圳深信生物科技有限公司 | 氨基脂质化合物、其制备方法、组合物和应用 |
WO2023177655A1 (en) | 2022-03-14 | 2023-09-21 | Generation Bio Co. | Heterologous prime boost vaccine compositions and methods of use |
CN114380724B (zh) * | 2022-03-23 | 2022-05-24 | 深圳市瑞吉生物科技有限公司 | 用于递送核酸的阳离子脂质化合物和组合物及用途 |
WO2023183616A1 (en) | 2022-03-25 | 2023-09-28 | Senda Biosciences, Inc. | Novel ionizable lipids and lipid nanoparticles and methods of using the same |
WO2023196634A2 (en) | 2022-04-08 | 2023-10-12 | Flagship Pioneering Innovations Vii, Llc | Vaccines and related methods |
CN114685784B (zh) * | 2022-04-26 | 2023-09-15 | 北京清科胜因生物科技有限公司 | 一种用于核酸递送的聚(2-噁唑啉)脂质与脂质纳米颗粒及应用 |
CN115626983A (zh) * | 2022-04-27 | 2023-01-20 | 北京清科胜因生物科技有限公司 | 一种聚(2-噁唑啉)脂质及脂质纳米颗粒 |
WO2023220083A1 (en) | 2022-05-09 | 2023-11-16 | Flagship Pioneering Innovations Vi, Llc | Trem compositions and methods of use for treating proliferative disorders |
WO2023220729A2 (en) | 2022-05-13 | 2023-11-16 | Flagship Pioneering Innovations Vii, Llc | Double stranded dna compositions and related methods |
WO2023218420A1 (en) | 2022-05-13 | 2023-11-16 | Janssen Pharmaceuticals, Inc. | Mrna compositions for inducing latent hiv-1 reversal |
WO2023233290A1 (en) | 2022-05-31 | 2023-12-07 | Janssen Sciences Ireland Unlimited Company | Rnai agents targeting pd-l1 |
CN114940756B (zh) * | 2022-06-02 | 2023-11-07 | 北京清科胜因生物科技有限公司 | 一种聚(2-噁唑啉)脂质与脂质纳米颗粒及应用 |
WO2023232976A1 (en) | 2022-06-03 | 2023-12-07 | Ags Therapeutics Sas | Extracellular vesicles from genetically-modified microalgae containing endogenously-loaded cargo, their preparation, and uses |
WO2023239756A1 (en) | 2022-06-07 | 2023-12-14 | Generation Bio Co. | Lipid nanoparticle compositions and uses thereof |
CN117263818A (zh) * | 2022-06-14 | 2023-12-22 | 杭州高田生物医药有限公司 | 阳离子脂质化合物及其制备方法和应用 |
WO2023250112A1 (en) | 2022-06-22 | 2023-12-28 | Flagship Pioneering Innovations Vi, Llc | Compositions of modified trems and uses thereof |
TW202413424A (zh) | 2022-08-01 | 2024-04-01 | 美商旗艦先鋒創新有限責任(Vii)公司 | 免疫調節蛋白及相關方法 |
WO2024035952A1 (en) | 2022-08-12 | 2024-02-15 | Remix Therapeutics Inc. | Methods and compositions for modulating splicing at alternative splice sites |
WO2024040222A1 (en) | 2022-08-19 | 2024-02-22 | Generation Bio Co. | Cleavable closed-ended dna (cedna) and methods of use thereof |
EP4327829A1 (en) | 2022-08-26 | 2024-02-28 | Ethris GmbH | Stabilization of lipid or lipidoid nanoparticle suspensions |
WO2024042236A1 (en) | 2022-08-26 | 2024-02-29 | Ethris Gmbh | Stable lipid or lipidoid nanoparticle suspensions |
WO2024049979A2 (en) | 2022-08-31 | 2024-03-07 | Senda Biosciences, Inc. | Novel ionizable lipids and lipid nanoparticles and methods of using the same |
US20240174732A1 (en) | 2022-10-05 | 2024-05-30 | Flagship Pioneering Innovations V, Inc. | Nucleic acid molecules encoding trif and additional polypeptides and their use in treating cancer |
WO2024088808A1 (en) | 2022-10-24 | 2024-05-02 | Ags Therapeutics Sas | Extracellular vesicles from microalgae, their biodistribution upon intranasal administration, and uses thereof |
WO2024097664A1 (en) | 2022-10-31 | 2024-05-10 | Flagship Pioneering Innovations Vi, Llc | Compositions and methods for purifying polyribonucleotides |
WO2024102762A1 (en) | 2022-11-08 | 2024-05-16 | Orna Therapeutics, Inc. | Lipids and lipid nanoparticle compositions for delivering polynucleotides |
WO2024102730A1 (en) | 2022-11-08 | 2024-05-16 | Orna Therapeutics, Inc. | Lipids and nanoparticle compositions for delivering polynucleotides |
WO2024102677A1 (en) | 2022-11-08 | 2024-05-16 | Orna Therapeutics, Inc. | Circular rna compositions |
WO2024102799A1 (en) | 2022-11-08 | 2024-05-16 | Flagship Pioneering Innovations Vi, Llc | Compositions and methods for producing circular polyribonucleotides |
WO2024119039A2 (en) | 2022-12-01 | 2024-06-06 | Generation Bio Co. | Stealth lipid nanoparticles and uses thereof |
WO2024119074A1 (en) | 2022-12-01 | 2024-06-06 | Generation Bio Co. | Stealth lipid nanoparticle compositions for cell targeting |
WO2024119051A1 (en) | 2022-12-01 | 2024-06-06 | Generation Bio Co. | Novel polyglycerol-conjugated lipids and lipid nanoparticle compositions comprising the same |
WO2024119103A1 (en) | 2022-12-01 | 2024-06-06 | Generation Bio Co. | Lipid nanoparticles comprising nucleic acids and lipid-anchored polymers |
WO2024121814A1 (en) | 2022-12-09 | 2024-06-13 | Takeda Pharmaceutical Company Limited | Modified immunomodulators |
WO2024129988A1 (en) | 2022-12-14 | 2024-06-20 | Flagship Pioneering Innovations Vii, Llc | Compositions and methods for delivery of therapeutic agents to bone |
US20240269251A1 (en) | 2023-01-09 | 2024-08-15 | Flagship Pioneering Innovations V, Inc. | Genetic switches and their use in treating cancer |
US20240252520A1 (en) | 2023-01-09 | 2024-08-01 | Beth Israel Deaconess Medical Center, Inc. | Therapeutic agents and their use for treating chronic wounds |
WO2024151583A2 (en) | 2023-01-09 | 2024-07-18 | Flagship Pioneering Innovations Vii, Llc | Vaccines and related methods |
US20240238473A1 (en) | 2023-01-09 | 2024-07-18 | Beth Israel Deaconess Medical Center, Inc. | Recombinant nucleic acid molecules and their use in wound healing |
WO2024167885A1 (en) | 2023-02-06 | 2024-08-15 | Flagship Pioneering Innovations Vii, Llc | Immunomodulatory compositions and related methods |
WO2024173307A2 (en) | 2023-02-13 | 2024-08-22 | Flagship Pioneering Innovation Vii, Llc | Cleavable linker-containing ionizable lipids and lipid carriers for therapeutic compositions |
WO2024173836A2 (en) | 2023-02-17 | 2024-08-22 | Flagship Pioneering Innovations Vii, Llc | Dna compositions comprising modified cytosine |
WO2024173828A1 (en) | 2023-02-17 | 2024-08-22 | Flagship Pioneering Innovations Vii, Llc | Dna compositions comprising modified uracil |
CN117482066B (zh) * | 2023-11-02 | 2024-08-13 | 深圳市易瑞生物技术股份有限公司 | 脂质组合物和用于脂质组合物的化合物 |
Citations (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5068120A (en) * | 1990-08-01 | 1991-11-26 | Nabisco Brands, Inc. | Amine ester derivatives as low calorie fat mimetics |
WO1996035760A1 (en) * | 1995-05-12 | 1996-11-14 | Quantum Materials, Inc. | Bleed resistant cyanate ester-containing compositions |
WO2010054401A1 (en) * | 2008-11-10 | 2010-05-14 | Alnylam Pharmaceuticals, Inc. | Novel lipids and compositions for the delivery of therapeutics |
KR100996975B1 (ko) * | 2007-08-24 | 2010-11-29 | 한국화학연구원 | 혈류 내 순환시간 증가를 위한 단백질로 수식된 리포솜 및이의 제조방법 |
US20100324120A1 (en) * | 2009-06-10 | 2010-12-23 | Jianxin Chen | Lipid formulation |
WO2011000106A1 (en) * | 2009-07-01 | 2011-01-06 | Protiva Biotherapeutics, Inc. | Improved cationic lipids and methods for the delivery of therapeutic agents |
WO2011075656A1 (en) * | 2009-12-18 | 2011-06-23 | The University Of British Columbia | Methods and compositions for delivery of nucleic acids |
WO2011143230A1 (en) * | 2010-05-10 | 2011-11-17 | Alnylam Pharmaceuticals | Methods and compositions for delivery of active agents |
WO2011141705A1 (en) * | 2010-05-12 | 2011-11-17 | Protiva Biotherapeutics, Inc. | Novel cationic lipids and methods of use thereof |
WO2011153120A1 (en) * | 2010-06-04 | 2011-12-08 | Merck Sharp & Dohme Corp. | Novel low molecular weight cationic lipids for oligonucleotide delivery |
US8466122B2 (en) * | 2010-09-17 | 2013-06-18 | Protiva Biotherapeutics, Inc. | Trialkyl cationic lipids and methods of use thereof |
JP2013545727A (ja) * | 2010-10-21 | 2013-12-26 | メルク・シャープ・アンド・ドーム・コーポレーション | オリゴヌクレオチド送達用の新規低分子量カチオン性脂質 |
Family Cites Families (135)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NL154598B (nl) | 1970-11-10 | 1977-09-15 | Organon Nv | Werkwijze voor het aantonen en bepalen van laagmoleculire verbindingen en van eiwitten die deze verbindingen specifiek kunnen binden, alsmede testverpakking. |
US3901654A (en) | 1971-06-21 | 1975-08-26 | Biological Developments | Receptor assays of biologically active compounds employing biologically specific receptors |
US3817827A (en) | 1972-03-30 | 1974-06-18 | Scott Paper Co | Soft absorbent fibrous webs containing elastomeric bonding material and formed by creping and embossing |
US3935074A (en) | 1973-12-17 | 1976-01-27 | Syva Company | Antibody steric hindrance immunoassay with two antibodies |
US3996345A (en) | 1974-08-12 | 1976-12-07 | Syva Company | Fluorescence quenching with immunological pairs in immunoassays |
US4034074A (en) | 1974-09-19 | 1977-07-05 | The Board Of Trustees Of Leland Stanford Junior University | Universal reagent 2-site immunoradiometric assay using labelled anti (IgG) |
US3993754A (en) | 1974-10-09 | 1976-11-23 | The United States Of America As Represented By The United States Energy Research And Development Administration | Liposome-encapsulated actinomycin for cancer chemotherapy |
US3984533A (en) | 1975-11-13 | 1976-10-05 | General Electric Company | Electrophoretic method of detecting antigen-antibody reaction |
US4086257A (en) | 1976-10-12 | 1978-04-25 | Sears Barry D | Phosphatidyl quaternary ammonium compounds |
US4098876A (en) | 1976-10-26 | 1978-07-04 | Corning Glass Works | Reverse sandwich immunoassay |
CH624011A5 (ja) | 1977-08-05 | 1981-07-15 | Battelle Memorial Institute | |
US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
US4452901A (en) | 1980-03-20 | 1984-06-05 | Ciba-Geigy Corporation | Electrophoretically transferring electropherograms to nitrocellulose sheets for immuno-assays |
US4376110A (en) | 1980-08-04 | 1983-03-08 | Hybritech, Incorporated | Immunometric assays using monoclonal antibodies |
US4522803A (en) | 1983-02-04 | 1985-06-11 | The Liposome Company, Inc. | Stable plurilamellar vesicles, their preparation and use |
US4588578A (en) | 1983-08-08 | 1986-05-13 | The Liposome Company, Inc. | Lipid vesicles prepared in a monophase |
US5208036A (en) | 1985-01-07 | 1993-05-04 | Syntex (U.S.A.) Inc. | N-(ω, (ω-1)-dialkyloxy)- and N-(ω, (ω-1)-dialkenyloxy)-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
US4737323A (en) | 1986-02-13 | 1988-04-12 | Liposome Technology, Inc. | Liposome extrusion method |
US5453566A (en) | 1986-03-28 | 1995-09-26 | Calgene, Inc. | Antisense regulation of gene expression in plant/cells |
US4987071A (en) | 1986-12-03 | 1991-01-22 | University Patents, Inc. | RNA ribozyme polymerases, dephosphorylases, restriction endoribonucleases and methods |
CA1340323C (en) | 1988-09-20 | 1999-01-19 | Arnold E. Hampel | Rna catalyst for cleaving specific rna sequences |
GB8822492D0 (en) | 1988-09-24 | 1988-10-26 | Considine J | Apparatus for removing tumours from hollow organs of body |
US5725871A (en) | 1989-08-18 | 1998-03-10 | Danbiosyst Uk Limited | Drug delivery compositions comprising lysophosphoglycerolipid |
WO1991003162A1 (en) | 1989-08-31 | 1991-03-21 | City Of Hope | Chimeric dna-rna catalytic sequences |
US5286634A (en) | 1989-09-28 | 1994-02-15 | Stadler Joan K | Synergistic method for host cell transformation |
US5707644A (en) | 1989-11-04 | 1998-01-13 | Danbiosyst Uk Limited | Small particle compositions for intranasal drug delivery |
US6753423B1 (en) | 1990-01-11 | 2004-06-22 | Isis Pharmaceuticals, Inc. | Compositions and methods for enhanced biostability and altered biodistribution of oligonucleotides in mammals |
US5279833A (en) | 1990-04-04 | 1994-01-18 | Yale University | Liposomal transfection of nucleic acids into animal cells |
US5264618A (en) | 1990-04-19 | 1993-11-23 | Vical, Inc. | Cationic lipids for intracellular delivery of biologically active molecules |
US6365730B1 (en) | 1990-06-19 | 2002-04-02 | Gene Shears Pty. Limited | DNA-Armed ribozymes and minizymes |
US5789573A (en) | 1990-08-14 | 1998-08-04 | Isis Pharmaceuticals, Inc. | Antisense inhibition of ICAM-1, E-selectin, and CMV IE1/IE2 |
JP3257675B2 (ja) | 1990-10-12 | 2002-02-18 | マックス−プランク−ゲゼルシャフト ツール フェルデルング デル ビッセンシャフテン エー.ファウ. | 修飾リボザイム |
DE4216134A1 (de) | 1991-06-20 | 1992-12-24 | Europ Lab Molekularbiolog | Synthetische katalytische oligonukleotidstrukturen |
US5283185A (en) | 1991-08-28 | 1994-02-01 | University Of Tennessee Research Corporation | Method for delivering nucleic acids into cells |
US6831166B2 (en) | 1992-10-23 | 2004-12-14 | Isis Pharmaceuticals, Inc. | Derivatized oligonucleotides having improved uptake and other properties |
US5756353A (en) | 1991-12-17 | 1998-05-26 | The Regents Of The University Of California | Expression of cloned genes in the lung by aerosol-and liposome-based delivery |
US5652094A (en) | 1992-01-31 | 1997-07-29 | University Of Montreal | Nucleozymes |
EP0642589A4 (en) | 1992-05-11 | 1997-05-21 | Ribozyme Pharm Inc | METHOD AND REAGENT TO INHIBIT VIRAL REPLICATION. |
ATE155681T1 (de) | 1992-05-18 | 1997-08-15 | Minnesota Mining & Mfg | Einrichtung zur transmucosalen wirkstoffabgabe |
US5792451A (en) | 1994-03-02 | 1998-08-11 | Emisphere Technologies, Inc. | Oral drug delivery compositions and methods |
EP1251170A3 (en) | 1992-07-17 | 2002-10-30 | Ribozyme Pharmaceuticals, Inc. | Method and reagent for treatment of NF-kappaB dependent animal diseases |
IL108367A0 (en) | 1993-01-27 | 1994-04-12 | Hektoen Inst For Medical Resea | Antisense polynzcleotide inhibition of human growth factor-sensitive cancer cells |
US5426039A (en) | 1993-09-08 | 1995-06-20 | Bio-Rad Laboratories, Inc. | Direct molecular cloning of primer extended DNA containing an alkane diol |
US5801154A (en) | 1993-10-18 | 1998-09-01 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of multidrug resistance-associated protein |
US5591317A (en) | 1994-02-16 | 1997-01-07 | Pitts, Jr.; M. Michael | Electrostatic device for water treatment |
US5631359A (en) | 1994-10-11 | 1997-05-20 | Ribozyme Pharmaceuticals, Inc. | Hairpin ribozymes |
US5753613A (en) | 1994-09-30 | 1998-05-19 | Inex Pharmaceuticals Corporation | Compositions for the introduction of polyanionic materials into cells |
CA2200952C (en) | 1994-09-30 | 2006-04-11 | Inex Pharmaceuticals Corp. | Novel compositions comprising quaternary ammonium compounds and neutral lipids for the introduction of polyanionic materials into cells |
US5885613A (en) | 1994-09-30 | 1999-03-23 | The University Of British Columbia | Bilayer stabilizing components and their use in forming programmable fusogenic liposomes |
WO1996011266A2 (en) | 1994-10-05 | 1996-04-18 | Amgen Inc. | Method for inhibiting smooth muscle cell proliferation and oligonucleotides for use therein |
US5783683A (en) | 1995-01-10 | 1998-07-21 | Genta Inc. | Antisense oligonucleotides which reduce expression of the FGFRI gene |
US5580579A (en) | 1995-02-15 | 1996-12-03 | Nano Systems L.L.C. | Site-specific adhesion within the GI tract using nanoparticles stabilized by high molecular weight, linear poly (ethylene oxide) polymers |
IE80468B1 (en) | 1995-04-04 | 1998-07-29 | Elan Corp Plc | Controlled release biodegradable nanoparticles containing insulin |
AU723163B2 (en) | 1995-06-07 | 2000-08-17 | Tekmira Pharmaceuticals Corporation | Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer |
US5705385A (en) | 1995-06-07 | 1998-01-06 | Inex Pharmaceuticals Corporation | Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer |
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 |
US5747470A (en) | 1995-06-07 | 1998-05-05 | Gen-Probe Incorporated | Method for inhibiting cellular proliferation using antisense oligonucleotides to gp130 mRNA |
US5981501A (en) | 1995-06-07 | 1999-11-09 | Inex Pharmaceuticals Corp. | Methods for encapsulating plasmids in lipid bilayers |
US20040142895A1 (en) | 1995-10-26 | 2004-07-22 | Sirna Therapeutics, Inc. | Nucleic acid-based modulation of gene expression in the vascular endothelial growth factor pathway |
US20030216335A1 (en) | 2001-11-30 | 2003-11-20 | Jennifer Lockridge | Method and reagent for the modulation of female reproductive diseases and conditions |
US5998203A (en) | 1996-04-16 | 1999-12-07 | Ribozyme Pharmaceuticals, Inc. | Enzymatic nucleic acids containing 5'-and/or 3'-cap structures |
US6713069B1 (en) | 1996-04-16 | 2004-03-30 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Compositions and methods for detecting, preventing, and treating African Hemorrhagic Fever |
US20050119470A1 (en) | 1996-06-06 | 2005-06-02 | Muthiah Manoharan | Conjugated oligomeric compounds and their use in gene modulation |
US6111085A (en) | 1996-09-13 | 2000-08-29 | Isis Pharmaceuticals, Inc. | Carbamate-derivatized nucleosides and oligonucleosides |
US5739119A (en) | 1996-11-15 | 1998-04-14 | Galli; Rachel L. | Antisense oligonucleotides specific for the muscarinic type 2 acetylcholine receptor MRNA |
US6406705B1 (en) | 1997-03-10 | 2002-06-18 | University Of Iowa Research Foundation | Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant |
JP4656675B2 (ja) | 1997-05-14 | 2011-03-23 | ユニバーシティー オブ ブリティッシュ コロンビア | 脂質小胞への荷電した治療剤の高率封入 |
AU8428998A (en) | 1997-07-24 | 1999-02-16 | Inex Pharmaceuticals Corporation | Preparation of lipid-nucleic acid particles using a solvent extraction and direct hydration method |
US6320017B1 (en) | 1997-12-23 | 2001-11-20 | Inex Pharmaceuticals Corp. | Polyamide oligomers |
WO2000003683A2 (en) | 1998-07-20 | 2000-01-27 | Inex Pharmaceuticals Corporation | Liposomal encapsulated nucleic acid-complexes |
JP5117648B2 (ja) | 1999-04-20 | 2013-01-16 | ザ・ユニバーシティ・オブ・ブリティッシュ・コロンビア | カチオン性peg脂質および使用方法。 |
US6852334B1 (en) | 1999-04-20 | 2005-02-08 | The University Of British Columbia | Cationic peg-lipids and methods of use |
MXPA02002107A (es) | 1999-08-27 | 2003-08-20 | Inex Pharmaceuticals Corp | Composiciones para estimular la secrecion de citoquina e inducir una respuesta inmune. |
US7833992B2 (en) | 2001-05-18 | 2010-11-16 | Merck Sharpe & Dohme | Conjugates and compositions for cellular delivery |
US7491805B2 (en) | 2001-05-18 | 2009-02-17 | Sirna Therapeutics, Inc. | Conjugates and compositions for cellular delivery |
US8202979B2 (en) | 2002-02-20 | 2012-06-19 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid |
US7189705B2 (en) | 2000-04-20 | 2007-03-13 | The University Of British Columbia | Methods of enhancing SPLP-mediated transfection using endosomal membrane destabilizers |
ATE398175T1 (de) | 2000-12-08 | 2008-07-15 | Coley Pharmaceuticals Gmbh | Cpg-artige nukleinsäuren und verfahren zu ihrer verwendung |
TW593427B (en) | 2000-12-18 | 2004-06-21 | Nektar Therapeutics Al Corp | Synthesis of high molecular weight non-peptidic polymer derivatives |
US7053150B2 (en) | 2000-12-18 | 2006-05-30 | Nektar Therapeutics Al, Corporation | Segmented polymers and their conjugates |
US20030077829A1 (en) | 2001-04-30 | 2003-04-24 | Protiva Biotherapeutics Inc.. | Lipid-based formulations |
US20050282188A1 (en) | 2001-05-18 | 2005-12-22 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using short interfering nucleic acid (siNA) |
US20030130186A1 (en) | 2001-07-20 | 2003-07-10 | Chandra Vargeese | Conjugates and compositions for cellular delivery |
US7109165B2 (en) | 2001-05-18 | 2006-09-19 | Sirna Therapeutics, Inc. | Conjugates and compositions for cellular delivery |
US20070173473A1 (en) | 2001-05-18 | 2007-07-26 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of proprotein convertase subtilisin Kexin 9 (PCSK9) gene expression using short interfering nucleic acid (siNA) |
GB0118517D0 (en) * | 2001-07-30 | 2001-09-19 | Mitsubishi Tokyo Pharm Inc | Compound |
DE10163098B4 (de) | 2001-10-12 | 2005-06-02 | Alnylam Europe Ag | Verfahren zur Hemmung der Replikation von Viren |
AU2003207708A1 (en) | 2002-02-20 | 2003-09-09 | Sirna Therapeutics, Inc. | Rna interference mediated inhibition of map kinase genes |
US20050107316A1 (en) | 2002-02-22 | 2005-05-19 | Klaus Strebhardt | Agent for inhibiting development or progress of proliferative diseases and especially cancer diseases and pharmaceutical composition containing said agent |
DK1519714T3 (da) | 2002-06-28 | 2011-01-31 | Protiva Biotherapeutics Inc | Fremgangsmåde og apparat til fremstilling af liposomer |
WO2004011647A1 (en) | 2002-07-26 | 2004-02-05 | Chiron Corporation | Modified small interfering rna molecules and methods of use |
JP2006507841A (ja) | 2002-11-14 | 2006-03-09 | ダーマコン, インコーポレイテッド | 機能的siRNAおよび超機能的siRNA |
WO2006006948A2 (en) | 2002-11-14 | 2006-01-19 | Dharmacon, Inc. | METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY |
US20040167090A1 (en) | 2003-02-21 | 2004-08-26 | Monahan Sean D. | Covalent modification of RNA for in vitro and in vivo delivery |
US20040185559A1 (en) | 2003-03-21 | 2004-09-23 | Isis Pharmaceuticals Inc. | Modulation of diacylglycerol acyltransferase 1 expression |
JP2006522158A (ja) | 2003-04-03 | 2006-09-28 | アルナイラム ファーマシューティカルズ インコーポレイテッド | iRNA複合体 |
AU2004229519B2 (en) | 2003-04-09 | 2011-07-21 | Alnylam Pharmaceuticals, Inc. | iRNA conjugates |
ES2702942T3 (es) | 2003-04-17 | 2019-03-06 | Alnylam Pharmaceuticals Inc | Agentes de ARNi modificados |
AU2004257373B2 (en) | 2003-07-16 | 2011-03-24 | Arbutus Biopharma Corporation | Lipid encapsulated interfering RNA |
US7825235B2 (en) | 2003-08-18 | 2010-11-02 | Isis Pharmaceuticals, Inc. | Modulation of diacylglycerol acyltransferase 2 expression |
NZ592917A (en) | 2003-09-15 | 2012-12-21 | Protiva Biotherapeutics Inc | Stable polyethyleneglycol (PEG) dialkyloxypropyl (DAA) lipid conjugates |
US8084599B2 (en) | 2004-03-15 | 2011-12-27 | City Of Hope | Methods and compositions for the specific inhibition of gene expression by double-stranded RNA |
US20070265220A1 (en) | 2004-03-15 | 2007-11-15 | City Of Hope | Methods and compositions for the specific inhibition of gene expression by double-stranded RNA |
EP1766035B1 (en) | 2004-06-07 | 2011-12-07 | Protiva Biotherapeutics Inc. | Lipid encapsulated interfering rna |
ATE537263T1 (de) | 2004-06-07 | 2011-12-15 | Protiva Biotherapeutics Inc | Kationische lipide und verwendungsverfahren |
US20090170794A1 (en) | 2004-09-10 | 2009-07-02 | Somagenics Inc. | Small interfering rnas that efficiently inhibit viral expression and methods of use thereof |
EP2377873B1 (en) | 2004-09-24 | 2014-08-20 | Alnylam Pharmaceuticals, Inc. | RNAi modulation of ApoB and uses thereof |
CA2587411A1 (en) | 2004-11-17 | 2006-05-26 | Protiva Biotherapeutics, Inc. | Sirna silencing of apolipoprotein b |
US7404969B2 (en) | 2005-02-14 | 2008-07-29 | Sirna Therapeutics, Inc. | Lipid nanoparticle based compositions and methods for the delivery of biologically active molecules |
AU2006336384B2 (en) | 2005-02-14 | 2010-12-16 | Sirna Therapeutics, Inc. | Lipid nanoparticle based compositions and methods for the delivery of biologically active molecules |
WO2007012191A1 (en) | 2005-07-27 | 2007-02-01 | Protiva Biotherapeutics, Inc. | Systems and methods for manufacturing liposomes |
US7838658B2 (en) | 2005-10-20 | 2010-11-23 | Ian Maclachlan | siRNA silencing of filovirus gene expression |
CN101346393B (zh) | 2005-11-02 | 2015-07-22 | 普洛体维生物治疗公司 | 修饰的siRNA分子及其应用 |
WO2007056861A1 (en) | 2005-11-18 | 2007-05-24 | Protiva Biotherapeutics, Inc. | Sirna silencing of influenza virus gene expression |
GB0605900D0 (en) * | 2006-03-23 | 2006-05-03 | Lipigen As | Modulators of nuclear receptors |
EP3872179A1 (en) | 2006-05-11 | 2021-09-01 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the pcsk9 gene |
US8598333B2 (en) | 2006-05-26 | 2013-12-03 | Alnylam Pharmaceuticals, Inc. | SiRNA silencing of genes expressed in cancer |
EP2695608B1 (en) | 2006-10-03 | 2016-11-23 | Arbutus Biopharma Corporation | Lipid containing formulations |
ES2535419T3 (es) | 2007-12-27 | 2015-05-11 | Protiva Biotherapeutics Inc. | Silenciamiento de expresión de quinasa tipo polo usando ARN interferente |
WO2009088891A1 (en) * | 2008-01-02 | 2009-07-16 | Alnylam Pharmaceuticals, Inc. | Screening method for selected amino lipid-containing compositions |
CA3044134A1 (en) | 2008-01-02 | 2009-07-09 | Arbutus Biopharma Corporation | Improved compositions and methods for the delivery of nucleic acids |
JP5475753B2 (ja) * | 2008-04-15 | 2014-04-16 | プロチバ バイオセラピューティクス インコーポレイティッド | 核酸送達用の脂質製剤 |
EP2281041B1 (en) | 2008-04-15 | 2014-07-02 | Protiva Biotherapeutics Inc. | Silencing of csn5 gene expression using interfering rna |
CN102149749B (zh) | 2008-07-10 | 2014-06-25 | 塞瑞纳治疗公司 | 具有惰性端基的聚噁唑啉、由被保护的引发基团制备的聚噁唑啉以及相关化合物 |
KR100996976B1 (ko) | 2008-08-27 | 2010-11-29 | 현대엔지니어링 주식회사 | 장수명 mto 반응용 촉매 및 이의 제조방법 |
PL2350043T3 (pl) | 2008-10-09 | 2014-09-30 | Tekmira Pharmaceuticals Corp | Ulepszone aminolipidy i sposoby dostarczania kwasów nukleinowych |
JP5766188B2 (ja) | 2009-07-01 | 2015-08-19 | プロチバ バイオセラピューティクス インコーポレイティッド | 固形腫瘍に治療剤を送達するための脂質製剤 |
US8865675B2 (en) * | 2010-05-12 | 2014-10-21 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing apolipoprotein B |
WO2011141704A1 (en) * | 2010-05-12 | 2011-11-17 | Protiva Biotherapeutics, Inc | Novel cyclic cationic lipids and methods of use |
SG11201405157PA (en) | 2012-02-24 | 2014-10-30 | Protiva Biotherapeutics Inc | Trialkyl cationic lipids and methods of use thereof |
US9744103B1 (en) | 2013-03-08 | 2017-08-29 | Chad Ricker | Infant teething apparatus |
WO2015011633A1 (en) | 2013-07-23 | 2015-01-29 | Protiva Biotherapeutics, Inc. | Compositions and methods for delivering messenger rna |
US10561723B2 (en) | 2015-07-21 | 2020-02-18 | Theodore C. Marbley | Treatment and prevention of anal conditions |
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Patent Citations (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5068120A (en) * | 1990-08-01 | 1991-11-26 | Nabisco Brands, Inc. | Amine ester derivatives as low calorie fat mimetics |
WO1996035760A1 (en) * | 1995-05-12 | 1996-11-14 | Quantum Materials, Inc. | Bleed resistant cyanate ester-containing compositions |
KR100996975B1 (ko) * | 2007-08-24 | 2010-11-29 | 한국화학연구원 | 혈류 내 순환시간 증가를 위한 단백질로 수식된 리포솜 및이의 제조방법 |
WO2010054401A1 (en) * | 2008-11-10 | 2010-05-14 | Alnylam Pharmaceuticals, Inc. | Novel lipids and compositions for the delivery of therapeutics |
US20100324120A1 (en) * | 2009-06-10 | 2010-12-23 | Jianxin Chen | Lipid formulation |
WO2011000106A1 (en) * | 2009-07-01 | 2011-01-06 | Protiva Biotherapeutics, Inc. | Improved cationic lipids and methods for the delivery of therapeutic agents |
WO2011075656A1 (en) * | 2009-12-18 | 2011-06-23 | The University Of British Columbia | Methods and compositions for delivery of nucleic acids |
WO2011143230A1 (en) * | 2010-05-10 | 2011-11-17 | Alnylam Pharmaceuticals | Methods and compositions for delivery of active agents |
WO2011141705A1 (en) * | 2010-05-12 | 2011-11-17 | Protiva Biotherapeutics, Inc. | Novel cationic lipids and methods of use thereof |
WO2011153120A1 (en) * | 2010-06-04 | 2011-12-08 | Merck Sharp & Dohme Corp. | Novel low molecular weight cationic lipids for oligonucleotide delivery |
US8466122B2 (en) * | 2010-09-17 | 2013-06-18 | Protiva Biotherapeutics, Inc. | Trialkyl cationic lipids and methods of use thereof |
JP2013545727A (ja) * | 2010-10-21 | 2013-12-26 | メルク・シャープ・アンド・ドーム・コーポレーション | オリゴヌクレオチド送達用の新規低分子量カチオン性脂質 |
Non-Patent Citations (1)
Title |
---|
JAYARAMAN, MUTHUSAMY; ANSELL, STEVEN M.; MUI, BARBARA L.; TAM, YING K.; CHEN, JIANXIN; DU, XINYAO; B: "Maximizing the Potency of siRNA Lipid Nanoparticles for Hepatic Gene Silencing In Vivo", ANGEWANDTE CHEMIE, INTERNATIONAL EDITION, vol. 51(34), JPN6016030109, 2012, pages 8533 - 8529, ISSN: 0003704525 * |
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WO2019131770A1 (ja) * | 2017-12-27 | 2019-07-04 | 武田薬品工業株式会社 | 核酸含有脂質ナノ粒子及びその用途 |
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