JP2020176150A - 脂質組成物 - Google Patents
脂質組成物 Download PDFInfo
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- JP2020176150A JP2020176150A JP2020133109A JP2020133109A JP2020176150A JP 2020176150 A JP2020176150 A JP 2020176150A JP 2020133109 A JP2020133109 A JP 2020133109A JP 2020133109 A JP2020133109 A JP 2020133109A JP 2020176150 A JP2020176150 A JP 2020176150A
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Abstract
Description
本出願は、2009年5月5日に出願された米国特許出願第61/175,770号および2010年1月28日に出願された米国特許出願第61/299,291号に対する優先権を主張し、これらの各内容は参照により本明細書に組み込まれる。
さらに、siRNAおよびmiRNAに関して上で述べたように、治療用核酸が細胞膜を横断する能力が限られていることに関する問題(Vlassov,et al.,Biochim.Biophys.Acta 1197:95−1082(1994)を参照されたい)や、補体媒介性アナフィラキシー、凝固特性の変化、および血球減少症などの全身毒性に関する問題が残る(Galbraith,et al.,Antisense Nucl.Acid Drug Des.4:201−206(1994))。
式(I)中、
各々のXaおよびXbは、各存在において、独立に、C1−6アルキレンであり、
nは、0、1、2、3、4、または5であり、
Aは、各存在において、NR2または1〜3個のRで任意に置換された環状部分であり、
Bは、NRまたは1〜2個のRで任意に置換された環状部分であり、
各々のRは独立に、H、アルキル、
R1は、各存在において、独立に、H、R3、
R2は、各存在において、独立に、アルキル、アルケニル、アルキニル、ヘテロアルキル、ヘテロアルケニル、またはヘテロアルキニルであり、これらは各々、1つ以上の置換基で任意に置換されており、
R3は、各存在において、独立に、アルキル、アルケニル、アルキニル、ヘテロアルキル、ヘテロアルケニル、またはヘテロアルキニルであり、これらは各々、1つ以上の置換基(例えば、親水性置換基)で任意に置換されており、
Yは、各存在において、独立に、O、NR4、またはSであり、
R4は、各存在において、独立に、H、アルキル、アルケニル、アルキニル、ヘテロアルキル、ヘテロアルケニル、またはヘテロアルキニルであり、これらは各々、1つ以上の置換基で任意に置換されており、
各々のRは独立に、H、アルキル、
R2は、各存在において、独立に、アルキル、アルケニル、アルキニル、ヘテロアルキル、ヘテロアルケニル、またはヘテロアルキニルであり、これらは各々、1つ以上の置換基で任意に置換されており、
R3は、各存在において、独立に、アルキル、アルケニル、アルキニル、ヘテロアルキル、ヘテロアルケニル、またはヘテロアルキニルであり、これらは各々、1つ以上の置換基で任意に置換されており、
Yは、各存在において、独立に、O、NR4、またはSであり、
R4は、各存在において、独立に、H、アルキル、アルケニル、アルキニル、ヘテロアルキル、ヘテロアルケニル、またはヘテロアルキニルであり、これらは各々、1つ以上の置換基で任意に置換されている
の化合物を作製する方法であって、β−ヒドロキシアルキル基が1つ以上の置換基で任意に置換されている、エナンチオマーが豊富なβ−ヒドロキシアルキル合成等価物を、式(VIII)
の化合物と接触させることを含む、方法。
各々のXaおよびXbは、各存在において、独立にC1−6アルキレンであり、
nは、0、1、2、3、4、または5であり、
Aは、各存在において、NR2または1〜3個のRで任意に置換された環状部分であり、
Bは、NRまたは1〜2個のRで任意に置換された環状部分であり、
各々のRは独立に、H、アルキル、
R2は、各存在において、独立に、アルキル、アルケニル、アルキニル、ヘテロアルキル、ヘテロアルケニル、またはヘテロアルキニルであり、これらは各々、1つ以上の置換基で任意に置換されており、
R3は、各存在において、独立に、アルキル、アルケニル、アルキニル、ヘテロアルキル、ヘテロアルケニル、またはヘテロアルキニルであり、これらは各々、1つ以上の置換基(例えば、親水性置換基)で任意に置換されており、
Yは、各存在において、独立に、O、NR4、またはSであり、
R4は、各存在において、独立に、H、アルキル、アルケニル、アルキニル、ヘテロアルキル、ヘテロアルケニル、またはヘテロアルキニルであり、これらは各々、1つ以上の置換基で任意に置換されている、の化合物と、
ステロールと、
PEGまたはPEG修飾脂質と
を含む組成物を提供する。
各々のXaおよびXbは、各存在において、独立にC1−6アルキレンであり、nは、0、1、2、3、4、または5であり、
各々のRは独立に、H、アルキル、
R1は、各存在において、独立に、H、R3、
R2は、各存在において、独立に、アルキル、アルケニル、アルキニル、ヘテロアルキル、ヘテロアルケニル、またはヘテロアルキニルであり、これらは各々、1つ以上の置換基で任意に置換されており、
R3は、各存在において、独立に、アルキル、アルケニル、アルキニル、ヘテロアルキル、ヘテロアルケニル、またはヘテロアルキニルであり、これらは各々、1つ以上の置換基で任意に置換されており、
Yは、各存在において、独立に、O、NR4、またはSであり、
R4は、各存在において、独立に、H、アルキル、アルケニル、アルキニル、ヘテロアルキル、ヘテロアルケニル、またはヘテロアルキニルであり、これらは各々、1つ以上の置換基で任意に置換されている、の化合物と、
ステロールと、
PEGまたはPEG修飾脂質と、を含む。
各々のRは独立に、H、アルキル、
R1は、各存在において、独立に、H、R3、
R2は、各存在において、独立に、アルキル、アルケニル、アルキニル、ヘテロアルキル、ヘテロアルケニル、またはヘテロアルキニルであり、これらは各々、1つ以上の置換基で任意に置換されており、
R3は、各存在において、独立に、アルキル、アルケニル、アルキニル、ヘテロアルキル、ヘテロアルケニル、またはヘテロアルキニルであり、これらは各々、1つ以上の置換基(例えば、親水性置換基)で任意に置換されており、
Yは、各存在において、独立に、O、NR4、またはSであり、
R4は、各存在において、独立に、H、アルキル、アルケニル、アルキニル、ヘテロアルキル、ヘテロアルケニル、またはヘテロアルキニルであり、これらは各々、1つ以上の置換基で任意に置換されている、の化合物またはそれらの混合物と、
ステロールと、
PEGまたはPEG修飾脂質と、を含む組成物。
(ターゲッティング基)n−L−脂質
式L
式中、
ターゲッティング基は、当業者に公知のおよび/または本明細書に記載の任意のターゲッティング基(例えば、細胞表面受容体)であり、
nは1〜5の整数(例えば、3)であり、
Lは結合基であり、かつ
脂質は、本明細書に記載の脂質(例えば、DSGなどの中性脂質)などの脂質である。
本発明の化合物を既知の有機合成技術により調製し得る。一般に、式(I)、(II)、(III)、(IV)および(V)の脂質は、アミン化合物を様々なエポキシドと反応させることによって調製することができる。1つの例では、式(V)および(VI)の脂質を以下の反応スキーム1によって作製することができ、その場合、置換基は全て、別途指示しない限り、上で定義されたものである。
本明細書で取り上げられる肝臓または内皮(例えば、心臓、肝臓、肺、腎臓、視床下部もしくは骨格筋)スクリーニングモデルで試験するための作用剤および/またはアミノ脂質を脂質粒子中に製剤化することができる。脂質粒子としては、リポソームが挙げられるが、これに限定されない。本明細書で使用されるとき、リポソームは、水性内部を封入する脂質含有膜を有する構造である。リポソームは1つ以上の脂質膜を有し得る。本発明は、単一膜と呼ばれる単層リポソームと、多重膜と呼ばれる多層リポソームの両方を企図している。核酸と複合体を形成する場合、脂質粒子は、例えば、Feigner,Scientific Americanに記載されているような、DNA層とDNA層の間に挟まれたカチオン性脂質二重層から構成されるリポプレックスでもあり得る。
本発明は、本発明の脂質粒子と活性剤とを含む組成物を含み、その場合、この活性剤は、脂質粒子と関連している。特定の実施形態では、活性剤は治療剤である。特定の実施形態では、活性剤は、脂質粒子の水性内部に封入されている。他の実施形態では、活性剤は、脂質粒子の1つ以上の脂質層の内部に存在する。他の実施形態では、活性剤は、脂質粒子の外部または内部脂質表面に結合している。
特定の実施形態では、本発明の脂質粒子は核酸と関連して、核酸−脂質粒子を生じさせる。特定の実施形態では、核酸は、脂質粒子中に完全に封入されている。本明細書で使用されるとき、「核酸」という用語は、任意のオリゴヌクレオチドまたはポリヌクレオチドを含むことが意図されている。最大50個のヌクレオチドを含む断片を通常オリゴヌクレオチドと呼び、それよりも長い断片をポリヌクレオチドと呼ぶ。特定の実施形態では、本発明のオリゴヌクレオチドは20〜50ヌクレオチド長である。
特定の実施形態では、本発明の核酸−脂質粒子は、RNA干渉(RNAi)分子と関連している。RNAi分子を用いたRNA干渉法を用いて、目的の遺伝子またはポリヌクレオチドの発現を妨害し得る。この5年の間に、低分子干渉RNA(siRNA)は、基本的には、開発中の次世代の標的化オリゴヌクレオチド薬物としてアンチセンスODNやリボザイムに取って代わった。siRNAは、RNAi誘導型サイレンシング複合体(RISC)として知られる細胞質の多タンパク質複合体と会合することができる通常21〜30ヌクレオチド 長のRNA二重鎖である。siRNAを搭載したRISCは、相同なmRNA転写産物の分解を仲介し、それゆえ、高い特異性をもってタンパク質発現をノックダウンするよう、siRNAを設計することができる。他のアンチセンス技術とは異なり、自然な機構によるsiRNA機能は、非コードRNAを介して遺伝子発現を制御するよう進化した。これは、その活性が、アンチセンスODNまたはリボザイムよりもインビトロおよびインビボで強力である理由であると一般に考えられている。臨床的に意義のある標的を標的とするsiRNAをはじめとする種々のRNAi試薬は現在、例えば、de Fougerolles,A.et al.,Nature Reviews 6:443−453(2007)に記載されているように、医薬品として開発されているところである。
マイクロRNA(miRNA)は、植物および動物のゲノム中のDNAから転写されるが、タンパク質には翻訳されない高度に保存された小RNA分子群である。プロセッシングされたmiRNAは、RNA誘導型サイレンシング複合体(RISC)に取り込まれるようになる約17〜25ヌクレオチド(nt)の一本鎖RNA分子であり、発生、細胞増殖、アポトーシスおよび分化の重要な調節因子として同定されている。これらは、特定のmRNAの3’−非翻訳領域に結合することによって、遺伝子発現の調節に役割を果たしていると考えられている。RISCは、翻訳阻害、転写産物切断、またはその両方によって、遺伝子発現の下方調節を仲介する。RISCは、広範囲にわたる真核生物の核内での転写サイレンシングにも関与する。
一実施形態では、核酸は、標的ポリヌクレオチドに対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」または単に「アンチセンス」という用語は、標的化ポリヌクレオチド配列に相補的なオリゴヌクレオチドを含むことが意図される。アンチセンスオリゴヌクレオチドは、選ば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の場合、相補的なRNA鎖に結合することによって、その翻訳を妨げる。アンチセンスDNAは、特異的で、相補的な(コードまたは非コード)RNAを標的するために用いることができる。結合が起こる場合、このDNA/RNAハイブリッドを酵素のRNアーゼHで分解することができる。特定の実施形態では、アンチセンスオリゴヌクレオチドは、約10〜約50ヌクレオチド、より好ましくは約15〜約30ヌクレオチドを含む。この用語は、所望の標的遺伝子と正確には相補的ではない場合があるアンチセンスオリゴヌクレオチドも包含する。したがって、本発明は、非標的特異的活性がアンチセンスで見られる場合に、または標的配列との1つ以上のミスマッチを含むアンチセンス配列が特定の用途で最も好ましい場合に利用することができる。
本発明の別の実施形態によれば、核酸−脂質粒子は、リボザイムと会合する。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 and Cech,Proc Natl Acad Sci USA.1987 Dec;84(24):8788−92;Forster and Symons,Cell.1987 Apr 24;49(2):211−20)。例えば、多数のリボザイムが、しばしばオリゴヌクレオチド基質内のいくつかのリン酸エステルのうちの1つだけを切断する高度の特異性によって、リン酸エステル転移反応を加速させる(Cech et al.,Cell.1981 Dec;27(3 Pt 2):487−96;Michel and Westhof,J Mol Biol.1990 Dec 5;216(3):585−610;Reinhold−Hurek and Shub,Nature.1992 May 14;357(6374):173−6)。この特異性は、基質が化学反応前に特異的な塩基対形成相互作用を介してリボザイムの内部のガイド配列(「IGS」)に結合する必要があることに起因している。
1990年代、DNAベースのアンチセンスオリゴデオキシヌクレオチド(ODN)およびリボザイム(RNA)が、薬物のデザインおよび開発に対して興奮させる新しいパラダイムをもたらしたが、それらのインビボでの適用は、エンド−およびエキソ−ヌクレアーゼ活性ならびに首尾よい細胞内送達の欠如によって妨げられた。この分解の問題は、オリゴヌクレオチド(オリゴ)薬物がヌクレアーゼ酵素によって認識されるのを妨げるが、それらの作用機構を阻害しない化学修飾に対する大規模な研究の後、効果的に克服された。この研究は非常に成功したので、現在開発過程のアンチセンスODN薬物は、未修飾分子の場合の数分間と比較して、インビボで数日間インタクトな状態である(Kurreck,J.2003.Antisense technologies.Improvement through novel chemical modifications.Eur J Biochem 270:1628−44)。しかしながら、細胞内送達および作用機序の問題は、これまで、アンチセンスODNおよびリボザイムが臨床的な製品になることを制限している。
本発明において有用なアンチセンス、siRNAおよび他のオリゴヌクレオチドとしては、修飾された骨格または非天然のヌクレオシド間結合を含むオリゴヌクレオチドが挙げられるが、これに限定されない。修飾された骨格を有するオリゴヌクレオチドには、骨格内にリン原子を保持するオリゴヌクレオチドと骨格内にリン原子を有さないオリゴヌクレオチドが含まれる。ヌクレオシド間骨格内にリン原子を有さない修飾されたオリゴヌクレオチドもまた、オリゴヌクレオシドと考えることができる。修飾されたオリゴヌクレオチド骨格としては、例えば、ホスホロチオアート、キラルホスホロチオアート、ホスホロジチオアート、ホスホトリエステル、アミノアルキルホスホトリ−エステル、メチルホスホナートおよび他のアルキルホスホナート(3’−アルキレンホスホナートおよびキラルホスホナートを含む)、ホスフィナート、ホスホルアミダート(3’−アミノホスホルアミダートおよびアミノアルキルホスホルアミダートを含む)、チオノホスホルアミダート、チオノアルキルホスホナート、チオノアルキルホスホトリエステル、ホスホロセレナート、メチルホスホナートまたはO−アルキルホスホトリエステル結合、ならびに通常の3’−5’結合を有するボラノホスファート、これらの2’−5’結合類似体、および反転した極性を有するもの(ヌクレオシド単位の隣接する対では、3’−5’と5’−3’または2’−5’と5’−2’とが結合する)が挙げられる。本発明による核酸内に存在し得る特定の修飾の特定の非限定的な例を表2に示す。
塩基修飾は、骨格および糖に対する修飾よりも一般的ではない。0.3−6に示す修飾の全てが、ヌクレアーゼに対してsiRNAを安定化させ、活性に対してほとんど効果がないようである(Zhang,H.Y.,Du,Q.,Wahlestedt,C,Liang,Z.2006.RNA Interference with chemically modified siRNA.Curr Top Med Chem 6:893−900)。
糖基におけるほとんどの修飾は、好都合に化学的に反応性の部位を提供する、RNA糖環の2’−OHにおいて生じる。(Manoharan,M.2004.RNA interference and chemically modified small interfering RNAs.Curr Opin Chem Biol 8:570−9;Zhang,H.Y.,Du,Q.,Wahlestedt,C,Liang,Z.2006.RNA Interference with chemically modified siRNA.Curr Top Med Chem 6:893−900)。2’−Fおよび2’−OME(0.7および8)が、一般的であり、その両方が、安定性を高め、2’−OME修飾は、1本の鎖あたり4ヌクレオチド未満に制限される限り、活性を低下させない(Holen,T.,Amarzguioui,M.,Babaie,E.,Prydz,H.2003.Similar behaviour of single−strand and double−strand siRNAs suggests they act through a common RNAi pathway.Nucleic Acids Res 31:2401−7)。修飾塩基がその分子の中央領域に限定されるとき、2’−O−MOE(0.9)は、siRNAにおいて最も有効である(Prakash,T.P.,Allerson,C.R.,Dande,P.,Vickers,T.A.,Sioufi,N.,Jarres,R.,Baker,B.F.,Swayze,E.E.,Griffey,R.H.,Bhat,B.2005.Positional effect of chemical modifications on short interference RNA activity in mammalian cells.J Med Chem 48:4247−53)。活性を失わせることなくsiRNAを安定化させることが見出されている他の修飾を、0.10−14に示す。
所与の化合物における全ての位置が均一に修飾される必要はなく、実際に、上述の修飾のうちの2つ以上が、1つの化合物、またはオリゴヌクレオチド内の1つのヌクレオシドにさえ組み込まれ得る。本発明の特定の好ましいオリゴヌクレオチドは、キメラオリゴヌクレオチドである。「キメラオリゴヌクレオチド」または「キメラ」は、本発明との関連において、各々が少なくとも1つのヌクレオチドで構成されている2つ以上の化学的に異なる領域を含むオリゴヌクレオチドである。これらのオリゴヌクレオチドは、通常、1つ以上の有利な特性(例えば、高いヌクレアーゼ耐性、細胞への高い取り込み、RNA標的に対する高い結合親和性)を付与する修飾ヌクレオチドの少なくとも1つの領域、およびRNaseH切断に対する基質である領域を含む。
便宜のため、本明細書、実施例、および付随する特許請求の範囲で使用される特定の用語および語句の意味が、以下に提供される。本明細書の他の部分におけるある用語の用法と本節で示されるその定義との間に明白な矛盾がある場合には、本節の定義が優先されるものとする。
特定の実施形態では、本発明は、脂質に封入された核酸粒子を生成するための方法および組成物に関し、この粒子中で、核酸は脂質層内に封入される。siRNAオリゴヌクレオチドを組み込んでいるこのような核酸−脂質粒子は:(1)薬物対脂質比;(2)封入効率;および(3)粒径をはじめとする種々の生物物理学的パラメータを用いて特徴付けられる。高い薬物対脂質比、高い封入効率、良好なヌクレアーゼ耐性および血清安定性、ならびに調節可能な粒径(通常、直径200nm未満)が望ましい。さらに、ヌクレアーゼ耐性を付与するための核酸の修飾が、治療薬のコストに加えられるが、多くの場合、限られた耐性しか提供しないので、核酸ポリマーの性質が重要である。特に記述されない限り、これらの基準は、本明細書中で以下の通りに計算される。
本発明の方法および組成物は、特定のカチオン性脂質を利用し、その脂質の合成、調製および特徴づけは、以下および添付の実施例において説明される。さらに、本発明は、治療剤(例えば、核酸)と会合した脂質粒子をはじめとする脂質粒子を調製する方法を提供する。本明細書で記載される方法において、脂質の混合物は、核酸の緩衝水溶液と組み合わされて、脂質粒子内に封入された核酸を含む中間体混合物を生成し、その場合、この封入された核酸は、約3重量%〜約25重量%、好ましくは5〜15重量%という核酸/脂質比で存在する。この中間体混合物は、脂質に封入された核酸粒子を得るために、場合によって大きさが揃えられてもよく、その場合、この脂質部分は、好ましくは30〜150nmの直径、より好ましくは約40〜90nmの直径を有する単層小胞である。次に、pHを上げて、脂質−核酸粒子上の表面電荷の少なくとも一部を中和し、それにより、少なくとも部分的に表面が中和された、脂質に封入された核酸組成物が提供される。
本発明の脂質粒子は、インビトロまたはインビボで治療剤を細胞に送達するために使用され得る。特定の実施形態では、治療剤は、本発明の核酸−脂質粒子を用いて細胞に送達される核酸である。本発明の脂質粒子および関連する薬学的組成物を使用する様々な方法の以下の説明は、核酸−脂質粒子に関する説明によって例証されるが、これらの方法および組成物が、そのような治療の恩恵を受ける任意の疾患または障害を治療するための任意の治療剤を送達するために容易に適応され得ることが理解される。
一実施形態では、本発明は、本明細書に記載の肝臓スクリーニングモデルで同定された核酸剤を含む薬学的組成物を提供する。組成物は、作用剤(例えば、dsRNA)と薬学的に許容される担体とを含む。薬学的組成物は、遺伝子の発現または活性と関連する疾患または障害を治療するのに有用である。このような薬学的組成物は、送達の様式に基づいて製剤化される。1つの例は、非経口送達を介する全身投与用に製剤化される組成物である。
C57BL/6マウスで静脈内(ボーラス)注射した24時間後、FVII活性をFVII siRNA処理動物で評価した。マイクロプレートスケールで、製造元の指示に従って、血清または組織中のタンパク質レベルを決定するための市販キットを用いてFVIIを測定した。FVIIの低下を未処理の対照マウスに対して決定し、結果を残存FVII%として表した。4つの用量レベル(2、5、12.5、25mg/kg FVII siRNA)を各々の新規リポソーム組成物の初期スクリーンで用い、初期スクリーンで得られた結果を基にして、この用量を後の研究で拡大した。
体重変化、臨床観察、臨床化学検査および、場合によって、血液検査をモニタリングすることにより、各々の新規リポソームsiRNA組成物の認容性を評価した。処理前および処理24時間後に、動物の体重を記録した。データを体重変化%として記録した。体重測定に加えて、肝機能マーカーを含む、完全な臨床化学検査パネルを、FVII解析用に採取された血清のアリコートを用いて、注射24時間後に、各用量レベル(2、5、12.5および25mg/kg siRNA)で得た。解析のために、試料をCentral Laboratory for Veterinarians(Langley,BC)に送付した。場合によっては、血液検査解析用の全血の採取が行えるように、治療群に追加のマウスを含めた。
脂質(脂質(I)、(II)、(III)、(IV)、(V)または(VI):DSPC:コレステロール:DMG−PEG)を可溶化し、所望のモル比に従ってエタノール中で混合する。混合した脂質をpH5.2の酢酸ナトリウム緩衝液に添加するエタノール注入法によって、リポソームを形成させる。これにより、35%エタノール中でリポソームが自然に形成される。リポソームを0.08μmポリカーボネート膜に少なくとも2回通して押し出す。ストックsiRNA溶液を酢酸ナトリウムおよび35%エタノール中に調製し、リポソームに添加して、充填(load)した。siRNA−リポソーム溶液を37℃で30分間インキュベートし、その後、希釈した。エタノールを除去し、透析または接線流濾過でPBS緩衝液に交換した。
一方は脂質を含み、もう一方はsiRNAを含む、個々別々のストックを調製する。脂質(I)、(II)、(III)、(IV)、(V)または(VI);DSPC:コレステロール:PEG脂質を含む脂質ストックを90%エタノールに可溶化して調製する。残りの10%は低pHクエン酸緩衝液である。脂質ストックの濃度は4mg/mLである。このクエン酸緩衝液のpHの範囲は、利用される融合原性脂質の種類によって、pH3〜5であることができる。siRNAを4mg/mLの濃度でクエン酸緩衝液にも可溶化する。小規模用に、5mLの各ストック溶液を調製する。
様々な脂質比を、下記の表に示すように試験した。脂質T(「T」)、コレステロール(「C」)およびPEG−脂質(PEG−DMG)が含まれる。これらの成分の相対モルパーセンテージを以下に記載する。それゆえ、「T50−C40−P10」は、50mol%の脂質Tと、40mol%のコレステロールと、10mol%のPEG−DMGを含む。使用したsiRNA二重鎖は、第VII因子遺伝子(FVII)を標的とするAD−1661であった。
PEG鎖長または中性脂質を修飾する効果を調べた。中性脂質については、DOPC(ジオレオイル−ホスファチジルコリン)またはDMPC(ジミリストイル−ホスファチジルコリン)を試験した。C10またはC18鎖長のmPEG2000コンジュゲート脂質も1.5mol%で試験した。下に「IL」で示されている場合は、粒子をインライン混合法を用いて作製した。
C57BL/6マウス(Charles River Labs,MA)およびSprague−Dawleyラット(Charles River Labs,MA)に、尾静脈注射によって、0.01mL/gの容量で、食塩水または製剤化したsiRNAのいずれかを投与した。投与後の様々な時点で、後眼窩採血によって、血清試料を採取した。第VII因子タンパク質の血清レベルを、発色アッセイ(Biophen FVII,Aniara Corporation,OH)を用いて試料中で決定した。第VII因子の肝臓mRNAレベルを決定するために、動物を屠殺し、肝臓を摘出し、液体窒素中で瞬間凍結した。凍結した組織から組織ライセートを調製し、分岐DNAアッセイ(QuantiGene Assay,Panomics,CA)を用いて、第VII因子の肝臓mRNAレベルを定量した。
様々なAF12リポソーム組成物の効力におけるApoEの役割をさらに調べるために、AD−1661 siRNA組成物を含むものを、様々な濃度で投与した。
様々なAF12リポソーム組成物のApoE依存性を調べるために、LDLR(LDL受容体)欠損マウスにおけるこれらのリポソーム組成物の効力を評価した。LDLR欠損マウスにおけるリポソーム組成物の効力の減少により、ApoE依存性が示唆された。以下に示すような様々な濃度で、AD−1661 siRNA組成物を含むAF12リポソーム組成物を野生型マウスおよびLDLR KOマウスに投与した。第1の群には陰性対照としてのPBSを投与した。
ApoE欠損マウスに対するAF12組成物の効果を調べるために、ApoEまたは以下に詳述するようなGalNAcターゲッティング脂質の存在下で、様々な濃度のAF12を投与した。
本明細書に記載の製剤を用いた核酸の送達を試験するために、内皮特異的マーカーのTEKチロシンキナーゼを選んだ。Tie2またはルシフェラーゼ(「Luc」)を標的とする、以下の配列を有するsiRNA二重鎖AD−27430をAF−012またはAF−011とともに製剤化した。
本明細書に記載の製剤によって与えられる比較的広範な治療域の結果として、単回i.v.投与で肝臓における多数の遺伝子をサイレンシングする可能性が試験された。多数の遺伝子を調節する能力は、多数の遺伝子標的が既に同定されている疾患に対して強力な治療的アプローチを提供し得ると想定することができる。このアプローチの実行可能性を調べるために、潜在的な治療的関心のある肝臓の標的である、第VII因子、ApoB、PCSK9、Xbp1、SORT1、TTR1、TTC39B、ITGb1、ApoC3、およびRab5cに対するsiRNA配列をプールし、TechG1脂質を含む粒子とともに製剤化した。
Claims (20)
- 式(I)
各々のXaおよびXbは、各存在において、独立にC1−6アルキレンであり、
nは、0、1、2、3、4、または5であり、
Aは、各存在において、NR2または1〜3個のRで任意に置換された環状部分であり、
Bは、NRまたは1〜2個のRで任意に置換された環状部分であり、
各々のRは独立に、H、アルキル、
R1は、各存在において、独立に、H、R3、
R2は、各存在において、独立に、アルキル、アルケニル、アルキニル、ヘテロアルキル、ヘテロアルケニル、またはヘテロアルキニルであり、
R3は、各存在において、独立に、アルキル、アルケニル、アルキニル、ヘテロアルキル、ヘテロアルケニル、またはヘテロアルキニルであり、
Yは、各存在において、独立に、O、NR4、またはSであり、
R4は、各存在において、独立に、H、アルキル、アルケニル、アルキニル、ヘテロアルキル、ヘテロアルケニル、またはヘテロアルキニルである)
の脂質またはその塩。 - nが、1または2である、請求項1に記載の脂質。
- Aが、各存在において、NR2である、請求項1に記載の脂質。
- Bが、環状部分である、請求項1に記載の脂質。
- Bが、窒素含有環状部分である、請求項1に記載の脂質。
- Bが、ピペリジニルまたはピペリジニル部分である、請求項1に記載の脂質。
- R1が、各存在において、Hである、請求項1に記載の脂質。
- R2が、各存在において、独立してアルキルである、請求項1に記載の脂質。
- R2が、各存在において、独立してアルケニルである、請求項1に記載の脂質。
- Yが、Oである、請求項1に記載の脂質。
- ステロール、中性脂質、PEGまたはPEG修飾脂質および請求項1に記載の脂質を含む、組成物。
- ステロールが、コレステロールである、請求項14に記載の組成物。
- PEGまたはPEG修飾脂質が、PEG修飾脂質である、請求項14に記載の組成物。
- リポソームである、請求項14に記載の組成物。
- 核酸剤を更に含む、請求項14に記載の組成物。
- 核酸剤が、siRNAである、請求項18に記載の組成物。
- 核酸剤が、mRNAである、請求項18に記載の組成物。
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Publication number | Priority date | Publication date | Assignee | Title |
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US9228186B2 (en) | 2002-11-14 | 2016-01-05 | Thermo Fisher Scientific Inc. | Methods and compositions for selecting siRNA of improved functionality |
ES2423060T3 (es) | 2004-03-12 | 2013-09-17 | Alnylam Pharmaceuticals, Inc. | Agentes iRNA que tienen como diana al VEGF |
US9006487B2 (en) | 2005-06-15 | 2015-04-14 | Massachusetts Institute Of Technology | Amine-containing lipids and uses thereof |
JP5570806B2 (ja) | 2006-05-11 | 2014-08-13 | 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 | Pcsk9遺伝子の発現を阻害するための組成物および方法 |
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EA020312B1 (ru) | 2008-10-20 | 2014-10-30 | Элнилэм Фармасьютикалз, Инк. | Композиции и способы для ингибирования экспрессии транстиретина |
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AU2009324534B2 (en) | 2008-12-10 | 2015-07-30 | Alnylam Pharmaceuticals, Inc. | GNAQ targeted dsRNA compositions and methods for inhibiting expression |
SG10201402054UA (en) | 2009-05-05 | 2014-09-26 | Muthiah Manoharan | Lipid compositions |
US9051567B2 (en) | 2009-06-15 | 2015-06-09 | Tekmira Pharmaceuticals Corporation | Methods for increasing efficacy of lipid formulated siRNA |
NZ597504A (en) | 2009-06-15 | 2013-10-25 | Alnylam Pharmaceuticals Inc | Lipid formulated dsrna targeting the pcsk9 gene |
EP2810643A3 (en) | 2009-08-14 | 2015-03-11 | Alnylam Pharmaceuticals Inc. | Lipid formulated compositions and mehods for inhibiting expression of a gene from the ebola virus |
WO2011038031A1 (en) | 2009-09-22 | 2011-03-31 | Alnylam Pharmaceuticals, Inc. | Dual targeting sirna agents |
EP2496238A4 (en) | 2009-11-03 | 2013-10-02 | Alnylam Pharmaceuticals Inc | FORMULATED LIPID COMPOSITIONS AND METHODS FOR INHIBITING TRANSTHYRETIN EXPRESSION (TTR) |
NZ600616A (en) | 2009-12-01 | 2014-11-28 | Shire Human Genetic Therapies | Delivery of mrna for the augmentation of proteins and enzymes in human genetic diseases |
CN103096875B (zh) | 2010-06-03 | 2016-08-17 | 阿尔尼拉姆医药品有限公司 | 用于递送活性剂的生物可降解脂质 |
CA2807552A1 (en) | 2010-08-06 | 2012-02-09 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
EP2609135A4 (en) | 2010-08-26 | 2015-05-20 | Massachusetts Inst Technology | POLY (BETA-AMINO ALCOHOLS), THEIR PREPARATION AND USES THEREOF |
CN104531812A (zh) | 2010-10-01 | 2015-04-22 | 现代治疗公司 | 设计核酸及其使用方法 |
WO2012075040A2 (en) | 2010-11-30 | 2012-06-07 | Shire Human Genetic Therapies, Inc. | mRNA FOR USE IN TREATMENT OF HUMAN GENETIC DISEASES |
WO2012135025A2 (en) | 2011-03-28 | 2012-10-04 | Massachusetts Institute Of Technology | Conjugated lipomers and uses thereof |
WO2012135805A2 (en) | 2011-03-31 | 2012-10-04 | modeRNA Therapeutics | Delivery and formulation of engineered nucleic acids |
KR102128248B1 (ko) | 2011-06-08 | 2020-07-01 | 샤이어 휴먼 지네틱 테라피즈 인크. | Mrna 전달을 위한 지질 나노입자 조성물 및 방법 |
EP3640332A1 (en) | 2011-08-29 | 2020-04-22 | Ionis Pharmaceuticals, Inc. | Oligomer-conjugate complexes and their use |
US9464124B2 (en) | 2011-09-12 | 2016-10-11 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
RU2707251C2 (ru) | 2011-10-03 | 2019-11-25 | Модерна Терапьютикс, Инк. | Модифицированные нуклеозиды, нуклеотиды и нуклеиновые кислоты и их применение |
KR102272498B1 (ko) | 2011-10-27 | 2021-07-06 | 메사추세츠 인스티튜트 오브 테크놀로지 | 약물 캡슐화 마이크로스피어를 형성할 수 있는, n-말단 상에 관능화된 아미노산 유도체 |
KR102095699B1 (ko) | 2011-11-18 | 2020-04-02 | 알닐람 파마슈티칼스 인코포레이티드 | 트랜스티레틴(TTR) 관련 질병을 치료하기 위한 RNAi 제제, 조성 및 그의 사용방법 |
US20140308304A1 (en) | 2011-12-07 | 2014-10-16 | Alnylam Pharmaceuticals, Inc. | Lipids for the delivery of active agents |
US9463247B2 (en) | 2011-12-07 | 2016-10-11 | Alnylam Pharmaceuticals, Inc. | Branched alkyl and cycloalkyl terminated biodegradable lipids for the delivery of active agents |
AU2012347637B2 (en) | 2011-12-07 | 2017-09-14 | Alnylam Pharmaceuticals, Inc. | Biodegradable lipids for the delivery of active agents |
US10557136B2 (en) | 2011-12-12 | 2020-02-11 | Oncolmmunin Inc. | In vivo delivery of oligonucleotides |
KR20140102759A (ko) | 2011-12-16 | 2014-08-22 | 모더나 세라퓨틱스, 인코포레이티드 | 변형된 뉴클레오사이드, 뉴클레오타이드 및 핵산 조성물 |
EP3620447B1 (en) | 2012-03-29 | 2021-02-17 | Translate Bio, Inc. | Ionizable cationic lipids |
EP2833892A4 (en) | 2012-04-02 | 2016-07-20 | Moderna Therapeutics Inc | MODIFIED POLYNUCLEOTIDES FOR THE PRODUCTION OF PROTEINS AND PEPTIDES ASSOCIATED WITH ONCOLOGY |
WO2013151666A2 (en) | 2012-04-02 | 2013-10-10 | modeRNA Therapeutics | Modified polynucleotides for the production of biologics and proteins associated with human disease |
US9878056B2 (en) | 2012-04-02 | 2018-01-30 | Modernatx, Inc. | Modified polynucleotides for the production of cosmetic proteins and peptides |
US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
US20150267192A1 (en) | 2012-06-08 | 2015-09-24 | Shire Human Genetic Therapies, Inc. | Nuclease resistant polynucleotides and uses thereof |
EA201492055A1 (ru) | 2012-06-08 | 2015-11-30 | Шир Хьюман Дженетик Терапис, Инк. | ИНГАЛЯЦИОННАЯ ДОСТАВКА мРНК В НЕЛЕГОЧНЫЕ КЛЕТКИ-МИШЕНИ |
US9415109B2 (en) | 2012-07-06 | 2016-08-16 | Alnylam Pharmaceuticals, Inc. | Stable non-aggregating nucleic acid lipid particle formulations |
CA2884870C (en) * | 2012-08-13 | 2022-03-29 | Massachusetts Institute Of Technology | Amine-containing lipidoids and uses thereof |
US9512456B2 (en) | 2012-08-14 | 2016-12-06 | Modernatx, Inc. | Enzymes and polymerases for the synthesis of RNA |
JP6144355B2 (ja) | 2012-11-26 | 2017-06-07 | モデルナティエックス インコーポレイテッドModernaTX,Inc. | 化学修飾mRNA |
US20140271820A1 (en) * | 2013-03-13 | 2014-09-18 | Mallinckrodt Llc | Liposome oxaliplatin compositions for cancer therapy |
DK2968586T3 (en) | 2013-03-14 | 2018-10-08 | Translate Bio Inc | CFTR MRNA COMPOSITIONS AND RELATED PROCEDURES AND APPLICATIONS |
WO2014152211A1 (en) | 2013-03-14 | 2014-09-25 | Moderna Therapeutics, Inc. | Formulation and delivery of modified nucleoside, nucleotide, and nucleic acid compositions |
AU2014236396A1 (en) | 2013-03-14 | 2015-08-13 | Shire Human Genetic Therapies, Inc. | Methods for purification of messenger RNA |
AU2014239184B2 (en) | 2013-03-14 | 2018-11-08 | Translate Bio, Inc. | Methods and compositions for delivering mRNA coded antibodies |
EP3757570B1 (en) | 2013-03-15 | 2023-10-11 | Translate Bio, Inc. | Synergistic enhancement of the delivery of nucleic acids via blended formulations |
US8980864B2 (en) | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
EP2992009B1 (en) | 2013-05-01 | 2020-06-24 | Ionis Pharmaceuticals, Inc. | Compositions and methods for modulating apolipoprotein (a) expression |
WO2014179562A1 (en) | 2013-05-01 | 2014-11-06 | Massachusetts Institute Of Technology | 1,3,5-triazinane-2,4,6-trione derivatives and uses thereof |
US9895443B2 (en) | 2013-06-26 | 2018-02-20 | Massachusetts Institute Of Technology | Multi-tailed lipids and uses thereof |
EP3971287A1 (en) | 2013-07-11 | 2022-03-23 | ModernaTX, Inc. | Compositions comprising synthetic polynucleotides encoding crispr related proteins and synthetic sgrnas and methods of use |
AU2014315287A1 (en) | 2013-09-03 | 2015-03-12 | Moderna Therapeutics, Inc. | Chimeric polynucleotides |
US20160194368A1 (en) | 2013-09-03 | 2016-07-07 | Moderna Therapeutics, Inc. | Circular polynucleotides |
WO2015048020A2 (en) * | 2013-09-24 | 2015-04-02 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for the manufacture of lipid nanoparticles |
WO2015048744A2 (en) | 2013-09-30 | 2015-04-02 | Moderna Therapeutics, Inc. | Polynucleotides encoding immune modulating polypeptides |
US10323076B2 (en) | 2013-10-03 | 2019-06-18 | Modernatx, Inc. | Polynucleotides encoding low density lipoprotein receptor |
EA201690576A1 (ru) | 2013-10-22 | 2016-10-31 | Шир Хьюман Дженетик Терапис, Инк. | Липидные композиции для доставки матричной рнк |
WO2015061500A1 (en) | 2013-10-22 | 2015-04-30 | Shire Human Genetic Therapies, Inc. | Mrna therapy for argininosuccinate synthetase deficiency |
BR112016008832A2 (pt) | 2013-10-22 | 2017-10-03 | Shire Human Genetic Therapies | Distribuição de mrna no snc e suas utilizações |
MX2016005239A (es) | 2013-10-22 | 2016-08-12 | Shire Human Genetic Therapies | Tratamiento con acido ribonucleico mensajero para la fenilcetonuria. |
KR102507624B1 (ko) | 2013-11-22 | 2023-03-09 | 미나 테라퓨틱스 리미티드 | C/ebp 알파 짧은 활성화 rna 조성물 및 사용 방법 |
BR112016024644A2 (pt) | 2014-04-23 | 2017-10-10 | Modernatx Inc | vacinas de ácido nucleico |
JP6571679B2 (ja) | 2014-04-25 | 2019-09-04 | トランスレイト バイオ, インコーポレイテッド | メッセンジャーrnaの精製方法 |
WO2015168172A1 (en) | 2014-04-28 | 2015-11-05 | Isis Pharmaceuticals, Inc. | Linkage modified oligomeric compounds |
EP3137091B1 (en) | 2014-05-01 | 2020-12-02 | Ionis Pharmaceuticals, Inc. | Conjugates of modified antisense oligonucleotides and their use for modulating pkk expression |
CN110903337A (zh) | 2014-05-01 | 2020-03-24 | Ionis制药公司 | 用于调节生长激素受体表达的组合物和方法 |
WO2015168589A2 (en) | 2014-05-01 | 2015-11-05 | Isis Pharmaceuticals, Inc. | Compositions and methods for modulating angiopoietin-like 3 expression |
ES2745825T3 (es) | 2014-05-01 | 2020-03-03 | Ionis Pharmaceuticals Inc | Composiciones y métodos para modular la expresión del factor B del complemento |
WO2015179693A1 (en) | 2014-05-22 | 2015-11-26 | Isis Pharmaceuticals, Inc. | Conjugated antisense compounds and their use |
EP3587409B8 (en) | 2014-05-30 | 2022-07-13 | Translate Bio, Inc. | Biodegradable lipids for delivery of nucleic acids |
WO2015200465A1 (en) | 2014-06-24 | 2015-12-30 | Shire Human Genetic Therapies, Inc. | Stereochemically enriched compositions for delivery of nucleic acids |
ES2834556T3 (es) | 2014-06-25 | 2021-06-17 | Acuitas Therapeutics Inc | Lípidos y formulaciones de nanopartículas lipídicas novedosos para la entrega de ácidos nucleicos |
JP6782171B2 (ja) | 2014-07-02 | 2020-11-11 | 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 | メッセンジャーrnaのカプセル化 |
EP3164379A1 (en) | 2014-07-02 | 2017-05-10 | Massachusetts Institute of Technology | Polyamine-fatty acid derived lipidoids and uses thereof |
CA2955250A1 (en) | 2014-07-16 | 2016-01-21 | Moderna Therapeutics, Inc. | Chimeric polynucleotides |
US11406742B2 (en) | 2014-07-18 | 2022-08-09 | M.A. Med Alliance SA | Coating for intraluminal expandable catheter providing contact transfer of drug micro-reservoirs |
US9492594B2 (en) | 2014-07-18 | 2016-11-15 | M.A. Med Alliance SA | Coating for intraluminal expandable catheter providing contact transfer of drug micro-reservoirs |
US20170210788A1 (en) | 2014-07-23 | 2017-07-27 | Modernatx, Inc. | Modified polynucleotides for the production of intrabodies |
WO2016025643A1 (en) * | 2014-08-12 | 2016-02-18 | Massachusetts Institute Of Technology | Brush-poly(glycoamidoamine)-lipids and uses thereof |
KR102631505B1 (ko) | 2014-08-29 | 2024-02-01 | 알닐람 파마슈티칼스 인코포레이티드 | 트랜스타이레틴(ttr) 매개 아밀로이드증의 치료 방법 |
WO2016040748A1 (en) | 2014-09-12 | 2016-03-17 | Ionis Pharmaceuticals, Inc. | Compositions and methods for detection of smn protein in a subject and treatment of a subject |
JOP20200092A1 (ar) | 2014-11-10 | 2017-06-16 | Alnylam Pharmaceuticals Inc | تركيبات iRNA لفيروس الكبد B (HBV) وطرق لاستخدامها |
EP3226912B1 (en) | 2014-12-05 | 2021-01-20 | Translate Bio, Inc. | Messenger rna therapy for treatment of articular disease |
CA2979695A1 (en) | 2015-03-19 | 2016-09-22 | Translate Bio, Inc. | Mrna therapy for pompe disease |
US10207919B2 (en) * | 2015-06-12 | 2019-02-19 | Rhodia Operations | Hybrid nanoparticles containing dendrons, methods of producing such hybrid nanoparticles, and uses thereof |
AU2016278970B2 (en) | 2015-06-19 | 2020-10-29 | Massachusetts Institute Of Technology | Alkenyl substituted 2,5-piperazinediones and their use in compositions for delivering an agent to a subject or cell |
WO2016209862A1 (en) | 2015-06-23 | 2016-12-29 | Alnylam Pharmaceuticals, Inc. | Glucokinase (gck) irna compositions and methods of use thereof |
JP7072386B2 (ja) | 2015-06-29 | 2022-05-20 | アクイタス セラピューティクス インコーポレイテッド | 核酸の送達のための脂質および脂質ナノ粒子製剤 |
WO2017011286A1 (en) | 2015-07-10 | 2017-01-19 | Alnylam Pharmaceuticals, Inc. | Insulin-like growth factor binding protein, acid labile subunit (igfals) and insulin-like growth factor 1 (igf-1) irna compositions and methods of use thereof |
AU2016294347B2 (en) | 2015-07-10 | 2022-07-28 | Ionis Pharmaceuticals, Inc. | Modulators of diacyglycerol acyltransferase 2 (DGAT2) |
SG10201912341SA (en) | 2015-07-31 | 2020-02-27 | Alnylam Pharmaceuticals Inc | TRANSTHYRETIN (TTR) iRNA COMPOSITIONS AND METHODS OF USE THEREOF FOR TREATING OR PREVENTING TTR-ASSOCIATED DISEASES |
JP7028764B2 (ja) | 2015-09-02 | 2022-03-02 | 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 | プログラム細胞死1リガンド1(PD-L1)iRNA組成物およびその使用方法 |
HRP20220156T1 (hr) | 2015-09-17 | 2022-04-15 | Modernatx, Inc. | Spojevi i pripravci za unutarstaničnu isporuku terapeutskih sredstava |
EP3353328A4 (en) | 2015-09-24 | 2019-06-12 | Ionis Pharmaceuticals, Inc. | MODULATORS OF KRAS EXPRESSION |
AU2016336344A1 (en) | 2015-10-05 | 2018-04-19 | Modernatx, Inc. | Methods for therapeutic administration of messenger ribonucleic acid drugs |
ES2862412T3 (es) | 2015-10-14 | 2021-10-07 | Translate Bio Inc | Modificación de enzimas relacionados con el ARN para producción mejorada |
MA47016A (fr) | 2015-10-22 | 2018-08-29 | Modernatx Inc | Vaccins contre les virus respiratoires |
CN108368028B (zh) | 2015-10-28 | 2021-09-03 | 爱康泰生治疗公司 | 用于递送核酸的新型脂质和脂质纳米颗粒制剂 |
US20190046555A1 (en) | 2015-11-06 | 2019-02-14 | Ionis Pharmaceuticals, Inc. | Conjugated antisense compounds for use in therapy |
WO2017079739A1 (en) | 2015-11-06 | 2017-05-11 | Ionis Pharmaceuticals, Inc. | MODULATING APOLIPOPROTEIN (a) EXPRESSION |
JP7080172B2 (ja) | 2015-12-10 | 2022-06-03 | モデルナティエックス インコーポレイテッド | 治療薬の送達のための組成物及び方法 |
DK3394030T3 (da) | 2015-12-22 | 2022-03-28 | Modernatx Inc | Forbindelser og sammensætninger til intracellulær afgivelse af midler |
CN113797348A (zh) | 2016-03-07 | 2021-12-17 | 箭头药业股份有限公司 | 用于治疗性化合物的靶向配体 |
KR102475301B1 (ko) | 2016-04-08 | 2022-12-09 | 트랜슬레이트 바이오 인코포레이티드 | 다량체 코딩 핵산 및 그 용도 |
JP2019522047A (ja) | 2016-06-13 | 2019-08-08 | トランスレイト バイオ, インコーポレイテッド | オルニチントランスカルバミラーゼ欠損症治療のためのメッセンジャーrna療法 |
JP6976277B2 (ja) | 2016-06-22 | 2021-12-08 | ドルビー・インターナショナル・アーベー | 第一の周波数領域から第二の周波数領域にデジタル・オーディオ信号を変換するためのオーディオ・デコーダおよび方法 |
KR102556825B1 (ko) | 2016-07-15 | 2023-07-17 | 아이오니스 파마수티컬즈, 인코포레이티드 | Smn2 조정을 위한 조성물 및 방법 |
WO2018033254A2 (en) | 2016-08-19 | 2018-02-22 | Curevac Ag | Rna for cancer therapy |
AU2017320582B2 (en) | 2016-09-02 | 2023-11-16 | Arrowhead Pharmaceuticals, Inc | Targeting ligands |
AU2017326253B2 (en) | 2016-09-13 | 2021-10-21 | Allergan, Inc. | Stabilized non-protein clostridial toxin compositions |
US11400161B2 (en) | 2016-10-06 | 2022-08-02 | Ionis Pharmaceuticals, Inc. | Method of conjugating oligomeric compounds |
US11583504B2 (en) | 2016-11-08 | 2023-02-21 | Modernatx, Inc. | Stabilized formulations of lipid nanoparticles |
US11542490B2 (en) | 2016-12-08 | 2023-01-03 | CureVac SE | RNAs for wound healing |
JP2020501545A (ja) | 2016-12-08 | 2020-01-23 | キュアバック アーゲー | 肝疾患の処置または予防のためのrna |
WO2018115507A2 (en) | 2016-12-23 | 2018-06-28 | Curevac Ag | Henipavirus vaccine |
WO2018115525A1 (en) | 2016-12-23 | 2018-06-28 | Curevac Ag | Lassa virus vaccine |
WO2018115527A2 (en) | 2016-12-23 | 2018-06-28 | Curevac Ag | Mers coronavirus vaccine |
AU2018224326B2 (en) | 2017-02-27 | 2024-01-04 | Translate Bio, Inc. | Novel codon-optimized CFTR mRNA |
AU2018234814B2 (en) | 2017-03-15 | 2022-06-30 | Modernatx, Inc. | Crystal forms of amino lipids |
KR20190132405A (ko) | 2017-03-15 | 2019-11-27 | 모더나티엑스, 인크. | 치료제의 세포내 전달을 위한 화합물 및 조성물 |
AU2018234828A1 (en) | 2017-03-15 | 2019-09-19 | Modernatx, Inc. | Lipid nanoparticle formulation |
US20200085944A1 (en) | 2017-03-17 | 2020-03-19 | Curevac Ag | Rna vaccine and immune checkpoint inhibitors for combined anticancer therapy |
SG11201906297QA (en) | 2017-03-24 | 2019-10-30 | Curevac Ag | Nucleic acids encoding crispr-associated proteins and uses thereof |
JOP20190215A1 (ar) | 2017-03-24 | 2019-09-19 | Ionis Pharmaceuticals Inc | مُعدّلات التعبير الوراثي عن pcsk9 |
US11357856B2 (en) | 2017-04-13 | 2022-06-14 | Acuitas Therapeutics, Inc. | Lipids for delivery of active agents |
KR20200015895A (ko) | 2017-04-18 | 2020-02-13 | 알닐람 파마슈티칼스 인코포레이티드 | B형 간염 바이러스 (hbv)에 감염된 대상체의 치료 방법 |
IL301115A (en) | 2017-04-28 | 2023-05-01 | Acuitas Therapeutics Inc | New lipid carbonyl and lipid nanoparticle formulations for delivery of nucleic acids |
MA49138A (fr) | 2017-05-16 | 2020-03-25 | Translate Bio Inc | Traitement de la fibrose kystique par administration d'arnm à codons optimisés codant pour la cftr |
MX2019014412A (es) | 2017-05-31 | 2020-02-10 | Ultragenyx Pharmaceutical Inc | Productos terapeuticos para la enfermedad de almacenamiento de glucogeno de tipo iii. |
WO2018222925A1 (en) | 2017-05-31 | 2018-12-06 | Ultragenyx Pharmaceutical Inc. | Therapeutics for phenylketonuria |
US11015204B2 (en) | 2017-05-31 | 2021-05-25 | Arcturus Therapeutics, Inc. | Synthesis and structure of high potency RNA therapeutics |
MA49421A (fr) | 2017-06-15 | 2020-04-22 | Modernatx Inc | Formulations d'arn |
SG11201911430PA (en) | 2017-07-04 | 2020-01-30 | Curevac Ag | Novel nucleic acid molecules |
CA3073020A1 (en) | 2017-08-16 | 2019-02-21 | Acuitas Therapeutics, Inc. | Lipids for use in lipid nanoparticle formulations |
WO2019036028A1 (en) | 2017-08-17 | 2019-02-21 | Acuitas Therapeutics, Inc. | LIPIDS FOR USE IN LIPID NANOPARTICULAR FORMULATIONS |
WO2019036030A1 (en) | 2017-08-17 | 2019-02-21 | Acuitas Therapeutics, Inc. | LIPIDS FOR USE IN LIPID NANOPARTICLE FORMULATIONS |
US11602557B2 (en) | 2017-08-22 | 2023-03-14 | Cure Vac SE | Bunyavirales vaccine |
WO2019046809A1 (en) | 2017-08-31 | 2019-03-07 | Modernatx, Inc. | METHODS OF MANUFACTURING LIPID NANOPARTICLES |
CA3075205A1 (en) | 2017-09-08 | 2019-03-14 | Mina Therapeutics Limited | Stabilized hnf4a sarna compositions and methods of use |
EP4219715A3 (en) | 2017-09-08 | 2023-09-06 | MiNA Therapeutics Limited | Stabilized cebpa sarna compositions and methods of use |
BR112020005230A2 (pt) | 2017-09-19 | 2020-09-24 | Alnylam Pharmaceuticals, Inc. | composições e métodos para o tratamento da amiloidose mediada por transtiretina (ttr) |
BR112020004351A2 (pt) | 2017-10-19 | 2020-09-08 | Curevac Ag | moléculas de ácido nucleico artificial |
EP3707271A1 (en) | 2017-11-08 | 2020-09-16 | CureVac AG | Rna sequence adaptation |
US20210236644A1 (en) | 2017-11-10 | 2021-08-05 | Cocoon Biotech Inc. | Ocular applications of silk-based products |
EP3714054A1 (en) | 2017-11-20 | 2020-09-30 | Alnylam Pharmaceuticals, Inc. | Serum amyloid p component (apcs) irna compositions and methods of use thereof |
US11931406B2 (en) | 2017-12-13 | 2024-03-19 | CureVac SE | Flavivirus vaccine |
EP3727428A1 (en) | 2017-12-20 | 2020-10-28 | Translate Bio, Inc. | Improved composition and methods for treatment of ornithine transcarbamylase deficiency |
EP3740575A1 (en) | 2018-01-15 | 2020-11-25 | Ionis Pharmaceuticals, Inc. | Modulators of dnm2 expression |
EP3752612A4 (en) | 2018-02-12 | 2021-11-10 | Ionis Pharmaceuticals, Inc. | MODIFIED COMPOUNDS AND USES THEREOF |
JP7153460B2 (ja) * | 2018-03-30 | 2022-10-14 | シスメックス株式会社 | リポタンパク質の取り込み能を測定する方法及び試薬 |
US20210361761A1 (en) | 2018-04-05 | 2021-11-25 | Curevac Ag | Novel yellow fever nucleic acid molecules for vaccination |
EP3775211B1 (en) | 2018-04-12 | 2023-04-05 | MiNA Therapeutics Limited | Sirt1-sarna compositions and methods of use |
SG11202008225PA (en) | 2018-04-17 | 2020-11-27 | Curevac Ag | Novel rsv rna molecules and compositions for vaccination |
EP3799604A4 (en) | 2018-05-09 | 2022-09-07 | Ionis Pharmaceuticals, Inc. | COMPOUNDS AND METHODS FOR REDUCING FXI EXPRESSION |
WO2020002525A1 (en) | 2018-06-27 | 2020-01-02 | Curevac Ag | Novel lassa virus rna molecules and compositions for vaccination |
EP3833397A4 (en) | 2018-08-08 | 2023-06-14 | Arcturus Therapeutics, Inc. | COMPOSITIONS AND AGENTS AGAINST NON-ALCOHOLIC STEATOHEPATITIS |
AU2019325702A1 (en) | 2018-08-24 | 2021-02-25 | Translate Bio, Inc. | Methods for purification of messenger RNA |
CN109406790B (zh) * | 2018-09-19 | 2022-05-17 | 深圳市新产业生物医学工程股份有限公司 | 辅酶q10和/或pcsk9作为检测动脉粥样硬化的标志物在制备试剂或试剂盒中的应用 |
TW202023573A (zh) | 2018-09-19 | 2020-07-01 | 美商Ionis製藥公司 | Pnpla3表現之調節劑 |
JP7387745B2 (ja) | 2018-10-01 | 2023-11-28 | アルニラム・ファーマシューティカルズ・インコーポレーテッド | 活性物質の送達のための生分解性脂質 |
JP2022512578A (ja) | 2018-10-09 | 2022-02-07 | ザ ユニヴァーシティ オブ ブリティッシュ コロンビア | 有機溶媒不含かつ劣化剤不含のトランスフェクション・コンピテント・ベシクルを含む組成物及びシステム並びにそれらに関連する方法 |
PL3891274T3 (pl) | 2018-12-06 | 2024-03-25 | Arcturus Therapeutics, Inc. | Kompozycje i sposoby leczenia niedoboru transkarbamylazy ornityny |
TW202039534A (zh) | 2018-12-14 | 2020-11-01 | 美商美國禮來大藥廠 | KRAS變體mRNA分子 |
US20220040281A1 (en) | 2018-12-21 | 2022-02-10 | Curevac Ag | Rna for malaria vaccines |
CN113474328A (zh) | 2019-01-11 | 2021-10-01 | 爱康泰生治疗公司 | 用于脂质纳米颗粒递送活性剂的脂质 |
WO2020161342A1 (en) | 2019-02-08 | 2020-08-13 | Curevac Ag | Coding rna administered into the suprachoroidal space in the treatment of ophtalmic diseases |
WO2020208361A1 (en) | 2019-04-12 | 2020-10-15 | Mina Therapeutics Limited | Sirt1-sarna compositions and methods of use |
WO2020254535A1 (en) | 2019-06-18 | 2020-12-24 | Curevac Ag | Rotavirus mrna vaccine |
EP4013870A1 (en) | 2019-08-13 | 2022-06-22 | Alnylam Pharmaceuticals, Inc. | Small ribosomal protein subunit 25 (rps25) irna agent compositions and methods of use thereof |
BR112022001947A2 (pt) | 2019-08-14 | 2022-09-20 | Curevac Ag | Combinações e composições de rna com propriedades imunoestimuladoras reduzidas |
EP4031524A1 (en) | 2019-09-19 | 2022-07-27 | ModernaTX, Inc. | Branched tail lipid compounds and compositions for intracellular delivery of therapeutic agents |
AU2020355000A1 (en) | 2019-09-23 | 2022-03-17 | Omega Therapeutics, Inc. | Compositions and methods for modulating apolipoprotein B (APOB) gene expression |
EP4041894A1 (en) | 2019-09-23 | 2022-08-17 | Omega Therapeutics, Inc. | COMPOSITIONS AND METHODS FOR MODULATING HEPATOCYTE NUCLEAR FACTOR 4-ALPHA (HNF4a) GENE EXPRESSION |
CN114728017A (zh) | 2019-10-14 | 2022-07-08 | 阿斯利康(瑞典)有限公司 | Pnpla3表达的调节剂 |
AU2020376840A1 (en) | 2019-11-01 | 2022-04-07 | Alnylam Pharmaceuticals, Inc. | Huntingtin (HTT) iRNA agent compositions and methods of use thereof |
US20230056569A1 (en) | 2019-11-22 | 2023-02-23 | Alnylam Pharmaceuticals, Inc. | Ataxin3 (atxn3) rnai agent compositions and methods of use thereof |
MX2022006433A (es) | 2019-12-13 | 2022-06-23 | Alnylam Pharmaceuticals Inc | Composiciones de agentes de acido ribonucleico de interferencia (arni) del marco de lectura abierto 72 del cromosoma 9 humano (c9orf72) y metodos de uso de los mismos. |
MX2022007680A (es) | 2019-12-20 | 2022-09-26 | Curevac Ag | Nanoparticulas lipidicas para administracion de acidos nucleicos. |
KR102198736B1 (ko) * | 2020-01-15 | 2021-01-05 | 이화여자대학교 산학협력단 | 생체 내 약물 전달을 위한 지질 나노입자 및 이의 용도 |
CN116113430A (zh) | 2020-02-04 | 2023-05-12 | 奎尔法克股份有限公司 | 冠状病毒疫苗 |
CA3173034A1 (en) | 2020-02-28 | 2021-09-02 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating smn2 |
WO2021178607A1 (en) | 2020-03-05 | 2021-09-10 | Alnylam Pharmaceuticals, Inc. | Complement component c3 irna compositions and methods of use thereof for treating or preventing complement component c3-associated diseases |
AU2021233816A1 (en) | 2020-03-09 | 2022-10-06 | Arcturus Therapeutics, Inc. | Coronavirus vaccine compositions and methods |
EP4118207A1 (en) | 2020-03-11 | 2023-01-18 | Omega Therapeutics, Inc. | Compositions and methods for modulating forkhead box p3 (foxp3) gene expression |
KR20230003478A (ko) | 2020-03-24 | 2023-01-06 | 제너레이션 바이오 컴퍼니 | 비-바이러스성 dna 벡터 및 고셰 치료제 발현을 위한 이의 용도 |
CN115667530A (zh) | 2020-03-24 | 2023-01-31 | 世代生物公司 | 非病毒dna载体和其用于表达因子ix治疗剂的用途 |
WO2021195307A1 (en) | 2020-03-26 | 2021-09-30 | Alnylam Pharmaceuticals, Inc. | Coronavirus irna compositions and methods of use thereof |
EP4133076A1 (en) | 2020-04-07 | 2023-02-15 | Alnylam Pharmaceuticals, Inc. | Angiotensin-converting enzyme 2 (ace2) irna compositions and methods of use thereof |
WO2021206922A1 (en) | 2020-04-07 | 2021-10-14 | Alnylam Pharmaceuticals, Inc. | Transmembrane serine protease 2 (tmprss2) irna compositions and methods of use thereof |
AU2021263554A1 (en) | 2020-04-27 | 2022-12-08 | Alnylam Pharmaceuticals, Inc. | Apolipoprotein E (APOE) iRNA agent compositions and methods of use thereof |
CN116322758A (zh) | 2020-05-29 | 2023-06-23 | 库尔维科欧洲股份公司 | 基于核酸的组合疫苗 |
EP4162050A1 (en) | 2020-06-09 | 2023-04-12 | Alnylam Pharmaceuticals, Inc. | Rnai compositions and methods of use thereof for delivery by inhalation |
WO2022008613A1 (en) | 2020-07-08 | 2022-01-13 | Janssen Sciences Ireland Unlimited Company | Rna replicon vaccines against hbv |
WO2022016070A1 (en) | 2020-07-16 | 2022-01-20 | Acuitas Therapeutics, Inc. | Cationic lipids for use in lipid nanoparticles |
JP2023535632A (ja) | 2020-07-27 | 2023-08-18 | アンジャリウム バイオサイエンシズ エージー | Dna分子の組成物、その作製方法、及びその使用方法 |
EP4172194A1 (en) | 2020-07-31 | 2023-05-03 | CureVac SE | Nucleic acid encoded antibody mixtures |
EP4157344A2 (en) | 2020-08-31 | 2023-04-05 | CureVac SE | Multivalent nucleic acid based coronavirus vaccines |
WO2022066847A1 (en) | 2020-09-24 | 2022-03-31 | Alnylam Pharmaceuticals, Inc. | Dipeptidyl peptidase 4 (dpp4) irna compositions and methods of use thereof |
EP4225917A1 (en) | 2020-10-05 | 2023-08-16 | Alnylam Pharmaceuticals, Inc. | G protein-coupled receptor 75 (gpr75) irna compositions and methods of use thereof |
WO2022087329A1 (en) | 2020-10-23 | 2022-04-28 | Alnylam Pharmaceuticals, Inc. | Mucin 5b (muc5b) irna compositions and methods of use thereof |
CA3201661A1 (en) | 2020-11-18 | 2022-05-27 | Ionis Pharmaceuticals, Inc. | Compounds and methods for modulating angiotensinogen expression |
CA3200234A1 (en) | 2020-11-25 | 2022-06-02 | Daryl C. Drummond | Lipid nanoparticles for delivery of nucleic acids, and related methods of use |
JP2023552555A (ja) * | 2020-12-07 | 2023-12-18 | トラスティーズ オブ タフツ カレッジ | リピドイド組成物およびその使用方法 |
WO2022137133A1 (en) | 2020-12-22 | 2022-06-30 | Curevac Ag | Rna vaccine against sars-cov-2 variants |
CA3171051A1 (en) | 2020-12-22 | 2022-06-30 | Curevac Ag | Pharmaceutical composition comprising lipid-based carriers encapsulating rna for multidose administration |
JP2024501022A (ja) | 2020-12-28 | 2024-01-10 | アークトゥルス セラピューティクス, インコーポレイテッド | Hbvを標的とする転写活性化因子様エフェクターヌクレアーゼ(talen) |
WO2022162027A2 (en) | 2021-01-27 | 2022-08-04 | Curevac Ag | Method of reducing the immunostimulatory properties of in vitro transcribed rna |
IL304880A (en) | 2021-02-12 | 2023-10-01 | Alnylam Pharmaceuticals Inc | Superoxide dismutase 1 (SOD1) IRNA compositions and methods of using them to treat or prevent superoxide dismutase 1- (SOD1-) associated neurodegenerative diseases |
US11524023B2 (en) | 2021-02-19 | 2022-12-13 | Modernatx, Inc. | Lipid nanoparticle compositions and methods of formulating the same |
EP4298220A1 (en) | 2021-02-25 | 2024-01-03 | Alnylam Pharmaceuticals, Inc. | Prion protein (prnp) irna compositions and methods of use thereof |
WO2022192519A1 (en) | 2021-03-12 | 2022-09-15 | Alnylam Pharmaceuticals, Inc. | Glycogen synthase kinase 3 alpha (gsk3a) irna compositions and methods of use thereof |
KR20230160872A (ko) | 2021-03-26 | 2023-11-24 | 미나 테라퓨틱스 리미티드 | Tmem173 sarna 조성물 및 사용 방법 |
CA3212653A1 (en) | 2021-03-26 | 2022-09-29 | Glaxosmithkline Biologicals Sa | Immunogenic compositions |
IL307239A (en) | 2021-03-29 | 2023-11-01 | Alnylam Pharmaceuticals Inc | Preparations containing Huntingtin IRNA factor (HTT) and methods of using them |
CA3171429A1 (en) | 2021-03-31 | 2022-09-30 | Alexander SCHWENGER | Syringes containing pharmaceutical compositions comprising rna |
EP4326860A1 (en) | 2021-04-20 | 2024-02-28 | Anjarium Biosciences AG | Compositions of dna molecules encoding amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase, methods of making thereof, and methods of use thereof |
WO2022232286A1 (en) | 2021-04-27 | 2022-11-03 | Generation Bio Co. | Non-viral dna vectors expressing anti-coronavirus antibodies and uses thereof |
KR20240011714A (ko) | 2021-04-27 | 2024-01-26 | 제너레이션 바이오 컴퍼니 | 치료용 항체를 발현하는 비바이러스성 dna 벡터 및 이의 용도 |
JP2024519293A (ja) | 2021-04-29 | 2024-05-10 | 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 | シグナル伝達兼転写活性化因子6(STAT6)iRNA組成物およびその使用方法 |
WO2022233880A1 (en) | 2021-05-03 | 2022-11-10 | Curevac Ag | Improved nucleic acid sequence for cell type specific expression |
CN113018449B (zh) * | 2021-05-14 | 2021-09-07 | 苏州艾博生物科技有限公司 | 阳离子脂质化合物、包含其的组合物及应用 |
JP2024522068A (ja) | 2021-05-18 | 2024-06-11 | 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 | ナトリウム-グルコース共輸送体2(sglt2)irna組成物およびその使用方法 |
BR112023025224A2 (pt) | 2021-06-04 | 2024-02-27 | Alnylam Pharmaceuticals Inc | Quadro de leitura aberto 72 do cromossomo humano 9 (c9orf72) composições de agente de irna e métodos de uso dos mesmos |
EP4367242A2 (en) | 2021-07-07 | 2024-05-15 | Omega Therapeutics, Inc. | Compositions and methods for modulating secreted frizzled receptor protein 1 (sfrp1) gene expression |
EP4377331A2 (en) | 2021-07-30 | 2024-06-05 | CureVac SE | Mrnas for treatment or prophylaxis of liver diseases |
CN117795074A (zh) | 2021-08-03 | 2024-03-29 | 阿尔尼拉姆医药品有限公司 | 转甲状腺素蛋白(TTR)iRNA组合物和其使用方法 |
CN115724806A (zh) * | 2021-08-25 | 2023-03-03 | 广州谷森制药有限公司 | 新型阳离子脂质化合物(二) |
AU2022336209A1 (en) | 2021-09-03 | 2024-01-18 | CureVac SE | Novel lipid nanoparticles for delivery of nucleic acids |
AU2022336664A1 (en) | 2021-09-03 | 2024-01-18 | CureVac SE | Novel lipid nanoparticles for delivery of nucleic acids comprising phosphatidylserine |
WO2023036311A1 (zh) * | 2021-09-10 | 2023-03-16 | 浙江吉量科技有限公司 | 可离子化脂质体、其制备及在基因递送中的应用 |
TW202334418A (zh) | 2021-10-29 | 2023-09-01 | 美商艾拉倫製藥股份有限公司 | 杭丁頓(HTT)iRNA劑組成物及其使用方法 |
WO2023073228A1 (en) | 2021-10-29 | 2023-05-04 | CureVac SE | Improved circular rna for expressing therapeutic proteins |
TW202334080A (zh) | 2021-11-08 | 2023-09-01 | 美商歐納醫療公司 | 用於遞送環狀聚核苷酸之脂質奈米粒子組合物 |
KR20230068047A (ko) | 2021-11-10 | 2023-05-17 | 주식회사 에스엠엘바이오팜 | 트레할로즈 유도체 및 신규 구조 유지 화합물을 포함하는 핵산 의약품 전달용 지질나노입자의 약학 조성물 |
WO2023099884A1 (en) | 2021-12-01 | 2023-06-08 | Mina Therapeutics Limited | Pax6 sarna compositions and methods of use |
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 |
WO2023141314A2 (en) | 2022-01-24 | 2023-07-27 | Alnylam Pharmaceuticals, Inc. | Heparin sulfate biosynthesis pathway enzyme irna agent compositions and methods of use thereof |
WO2023144193A1 (en) | 2022-01-25 | 2023-08-03 | CureVac SE | Mrnas for treatment of hereditary tyrosinemia type i |
WO2023144330A1 (en) | 2022-01-28 | 2023-08-03 | CureVac SE | Nucleic acid encoded transcription factor inhibitors |
WO2023170435A1 (en) | 2022-03-07 | 2023-09-14 | Mina Therapeutics Limited | Il10 sarna compositions and methods of use |
WO2023177655A1 (en) | 2022-03-14 | 2023-09-21 | Generation Bio Co. | Heterologous prime boost vaccine compositions and methods of use |
WO2023218420A1 (en) | 2022-05-13 | 2023-11-16 | Janssen Pharmaceuticals, Inc. | Mrna compositions for inducing latent hiv-1 reversal |
WO2023227608A1 (en) | 2022-05-25 | 2023-11-30 | Glaxosmithkline Biologicals Sa | Nucleic acid based vaccine encoding an escherichia coli fimh antigenic polypeptide |
WO2023239756A1 (en) | 2022-06-07 | 2023-12-14 | Generation Bio Co. | Lipid nanoparticle compositions and uses thereof |
WO2024040222A1 (en) | 2022-08-19 | 2024-02-22 | Generation Bio Co. | Cleavable closed-ended dna (cedna) and methods of use thereof |
WO2024068545A1 (en) | 2022-09-26 | 2024-04-04 | Glaxosmithkline Biologicals Sa | Influenza virus vaccines |
WO2024089638A1 (en) | 2022-10-28 | 2024-05-02 | Glaxosmithkline Biologicals Sa | Nucleic acid based vaccine |
WO2024102677A1 (en) | 2022-11-08 | 2024-05-16 | Orna Therapeutics, Inc. | Circular rna compositions |
WO2024102730A1 (en) | 2022-11-08 | 2024-05-16 | Orna Therapeutics, Inc. | Lipids and nanoparticle compositions for delivering polynucleotides |
WO2024102762A1 (en) | 2022-11-08 | 2024-05-16 | Orna Therapeutics, Inc. | Lipids and lipid nanoparticle compositions for delivering polynucleotides |
CN118125994A (zh) * | 2022-11-25 | 2024-06-04 | 艾斯拓康医药科技(北京)有限公司 | 可离子化脂质及其应用 |
WO2024119074A1 (en) | 2022-12-01 | 2024-06-06 | Generation Bio Co. | Stealth lipid nanoparticle compositions for cell targeting |
WO2024119039A2 (en) | 2022-12-01 | 2024-06-06 | Generation Bio Co. | Stealth lipid nanoparticles and uses thereof |
WO2024119103A1 (en) | 2022-12-01 | 2024-06-06 | Generation Bio Co. | Lipid nanoparticles comprising nucleic acids and lipid-anchored polymers |
WO2024119051A1 (en) | 2022-12-01 | 2024-06-06 | Generation Bio Co. | Novel polyglycerol-conjugated lipids and lipid nanoparticle compositions comprising the same |
GB202404607D0 (en) | 2024-03-29 | 2024-05-15 | Glaxosmithkline Biologicals Sa | RNA formulation |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3931430A (en) * | 1972-11-11 | 1976-01-06 | Kanzaki Paper Mfg. Co. Ltd. | Method of desensitizing a pressure sensitive recording sheet and the product thereof |
US4743304A (en) * | 1983-12-14 | 1988-05-10 | Morton Thiokol, Inc. | Asphalt antistripping agents containing organic amines and Portland cement |
JPH01301364A (ja) * | 1988-05-31 | 1989-12-05 | Daio Paper Corp | 感圧複写紙用減感剤組成物 |
JP2002537492A (ja) * | 1999-02-19 | 2002-11-05 | ザ、プロクター、エンド、ギャンブル、カンパニー | 布地改良組成物 |
US20030175966A1 (en) * | 2002-03-14 | 2003-09-18 | Genteric, Inc. | Cationic sugar derivatives for gene transfer |
WO2007130073A2 (en) * | 2006-05-05 | 2007-11-15 | Molecular Transfer, Inc. | Novel reagents for transfection of eukaryotic cells |
WO2008113364A2 (en) * | 2007-03-20 | 2008-09-25 | Recepticon Aps | Amino derivatives to prevent nephrotoxicity and cancer |
JP2012508235A (ja) * | 2008-11-07 | 2012-04-05 | マサチューセッツ インスティテュート オブ テクノロジー | アミノアルコールリピドイドおよびその使用 |
Family Cites Families (159)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US533471A (en) | 1895-02-05 | Greene kendrick | ||
SE379044B (ja) | 1969-03-28 | 1975-09-22 | Ciba Geigy Ag | |
US3687808A (en) | 1969-08-14 | 1972-08-29 | Univ Leland Stanford Junior | Synthetic polynucleotides |
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 |
US4086257A (en) | 1976-10-12 | 1978-04-25 | Sears Barry D | Phosphatidyl quaternary ammonium compounds |
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 |
JPS6032780B2 (ja) | 1978-03-30 | 1985-07-30 | 株式会社新潟鐵工所 | 管式加熱炉 |
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 |
US5023243A (en) | 1981-10-23 | 1991-06-11 | Molecular Biosystems, Inc. | Oligonucleotide therapeutic agent and method of making same |
US4522803A (en) | 1983-02-04 | 1985-06-11 | The Liposome Company, Inc. | Stable plurilamellar vesicles, their preparation and use |
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 |
US4603044A (en) | 1983-01-06 | 1986-07-29 | Technology Unlimited, Inc. | Hepatocyte Directed Vesicle delivery system |
US4588578A (en) | 1983-08-08 | 1986-05-13 | The Liposome Company, Inc. | Lipid vesicles prepared in a monophase |
JPS6032780A (ja) | 1983-08-02 | 1985-02-19 | Toyo Soda Mfg Co Ltd | ポリアミンの製造方法 |
US5118800A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | Oligonucleotides possessing a primary amino group in the terminal nucleotide |
US5008050A (en) | 1984-06-20 | 1991-04-16 | The Liposome Company, Inc. | Extrusion technique for producing unilamellar vesicles |
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 |
AU587989B2 (en) | 1984-10-16 | 1989-09-07 | Mitsubishi Chemical Corporation | DMA fragments, expression vectors, proteins, hosts, and process for production of the proteins |
FR2575751B1 (fr) | 1985-01-08 | 1987-04-03 | Pasteur Institut | Nouveaux nucleosides de derives de l'adenosine, leur preparation et leurs applications biologiques |
DE3688418T2 (de) | 1985-02-13 | 1993-08-26 | Scios Nova Inc | Menschlicher metallothionein ii-promotor in saeugetierexpressionssystemen. |
US5235033A (en) | 1985-03-15 | 1993-08-10 | Anti-Gene Development Group | Alpha-morpholino ribonucleoside derivatives and polymers thereof |
US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
US5405938A (en) | 1989-12-20 | 1995-04-11 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
US5185444A (en) | 1985-03-15 | 1993-02-09 | Anti-Gene Deveopment Group | Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages |
US5166315A (en) | 1989-12-20 | 1992-11-24 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
AU6522486A (en) | 1985-10-04 | 1987-04-24 | Biotechnology Research Partners Limited | Recombinant apolipoproteins and methods |
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 |
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 |
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 |
GB8712540D0 (en) | 1987-05-28 | 1987-07-01 | Ucb Sa | Expression of human proapolipoprotein a-i |
AU598946B2 (en) | 1987-06-24 | 1990-07-05 | Howard Florey Institute Of Experimental Physiology And Medicine | Nucleoside derivatives |
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 |
EP0406309A4 (en) | 1988-03-25 | 1992-08-19 | The University Of Virginia Alumni Patents Foundation | Oligonucleotide n-alkylphosphoramidates |
US5278302A (en) | 1988-05-26 | 1994-01-11 | University Patents, Inc. | Polynucleotide phosphorodithioates |
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 |
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 |
US4927637A (en) | 1989-01-17 | 1990-05-22 | Liposome Technology, Inc. | Liposome extrusion method |
US4957773A (en) | 1989-02-13 | 1990-09-18 | Syracuse University | Deposition of boron-containing films from decaborane |
US5182364A (en) | 1990-02-26 | 1993-01-26 | The Scripps Research Institute | Polypeptide analogs of apolipoprotein E |
US5168045A (en) | 1989-08-18 | 1992-12-01 | The Scripps Research Institute | Diagnostic systems and methods using polypeptide analogs of apolipoprotein e |
US5177189A (en) | 1989-08-18 | 1993-01-05 | The Scripps Research Institute | Polypeptide analogs of Apolipoprotein E |
US5473039A (en) | 1989-08-18 | 1995-12-05 | The Scripps Research Institute | Polypeptide analogs of apolipoprotein E, diagnostic systems and methods using the analogs |
US5134066A (en) | 1989-08-29 | 1992-07-28 | Monsanto Company | Improved probes using nucleosides containing 3-dezauracil analogs |
JP3058686B2 (ja) | 1989-08-31 | 2000-07-04 | シティ・オブ・ホープ | キメラdna―rna触媒活性配列 |
US5591722A (en) | 1989-09-15 | 1997-01-07 | Southern Research Institute | 2'-deoxy-4'-thioribonucleosides and their antiviral activity |
US5286634A (en) | 1989-09-28 | 1994-02-15 | Stadler Joan K | Synergistic method for host cell transformation |
US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
US5399676A (en) | 1989-10-23 | 1995-03-21 | Gilead Sciences | Oligonucleotides with inverted polarity |
US5264562A (en) | 1989-10-24 | 1993-11-23 | Gilead Sciences, Inc. | Oligonucleotide analogs with novel linkages |
WO1991006556A1 (en) | 1989-10-24 | 1991-05-16 | Gilead Sciences, Inc. | 2' modified oligonucleotides |
US5264564A (en) | 1989-10-24 | 1993-11-23 | Gilead Sciences | Oligonucleotide analogs with novel linkages |
US5177198A (en) | 1989-11-30 | 1993-01-05 | University Of N.C. At Chapel Hill | Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates |
US5130302A (en) | 1989-12-20 | 1992-07-14 | Boron Bilogicals, Inc. | Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same |
US5587361A (en) | 1991-10-15 | 1996-12-24 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
US5670633A (en) | 1990-01-11 | 1997-09-23 | Isis Pharmaceuticals, Inc. | Sugar modified oligonucleotides that detect and modulate gene expression |
US5646265A (en) | 1990-01-11 | 1997-07-08 | Isis Pharmceuticals, Inc. | Process for the preparation of 2'-O-alkyl purine phosphoramidites |
US5459255A (en) | 1990-01-11 | 1995-10-17 | Isis Pharmaceuticals, Inc. | N-2 substituted purines |
US5681941A (en) | 1990-01-11 | 1997-10-28 | Isis Pharmaceuticals, Inc. | Substituted purines and oligonucleotide cross-linking |
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 |
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 |
DE69032425T2 (de) | 1990-05-11 | 1998-11-26 | Microprobe Corp., Bothell, Wash. | Teststreifen zum Eintauchen für Nukleinsäure-Hybridisierungsassays und Verfahren zur kovalenten Immobilisierung von Oligonucleotiden |
US6365730B1 (en) | 1990-06-19 | 2002-04-02 | Gene Shears Pty. Limited | DNA-Armed ribozymes and minizymes |
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 |
ATE154246T1 (de) | 1990-07-27 | 1997-06-15 | Isis Pharmaceuticals Inc | Nuklease resistente, pyrimidin modifizierte oligonukleotide, die die gen-expression detektieren und modulieren |
US5677437A (en) | 1990-07-27 | 1997-10-14 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
US5608046A (en) | 1990-07-27 | 1997-03-04 | Isis Pharmaceuticals, Inc. | Conjugated 4'-desmethyl nucleoside analog compounds |
US5618704A (en) | 1990-07-27 | 1997-04-08 | Isis Pharmacueticals, Inc. | Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling |
US5541307A (en) | 1990-07-27 | 1996-07-30 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs and solid phase synthesis thereof |
US5610289A (en) | 1990-07-27 | 1997-03-11 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogues |
US5623070A (en) | 1990-07-27 | 1997-04-22 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
HU217036B (hu) | 1990-08-03 | 1999-11-29 | Sanofi | Eljárás génexpresszió gátlására alkalmas vegyületek előállítására |
US5789573A (en) | 1990-08-14 | 1998-08-04 | Isis Pharmaceuticals, Inc. | Antisense inhibition of ICAM-1, E-selectin, and CMV IE1/IE2 |
US5177196A (en) | 1990-08-16 | 1993-01-05 | Microprobe Corporation | Oligo (α-arabinofuranosyl nucleotides) and α-arabinofuranosyl precursors thereof |
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 |
EP0549686A4 (en) | 1990-09-20 | 1995-01-18 | Gilead Sciences Inc | Modified internucleoside linkages |
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 |
CA2093664C (en) | 1990-10-12 | 2003-07-29 | Fritz Eckstein | Modified ribozymes |
US5539082A (en) | 1993-04-26 | 1996-07-23 | Nielsen; Peter E. | Peptide nucleic acids |
US5714331A (en) | 1991-05-24 | 1998-02-03 | Buchardt, Deceased; Ole | Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility |
US5719262A (en) | 1993-11-22 | 1998-02-17 | Buchardt, Deceased; Ole | Peptide nucleic acids having amino acid side chains |
DE4216134A1 (de) | 1991-06-20 | 1992-12-24 | Europ Lab Molekularbiolog | Synthetische katalytische oligonukleotidstrukturen |
WO1993000443A1 (en) | 1991-06-26 | 1993-01-07 | Bio-Technology General Corp. | Purification of recombinant apolipoprotein e from bacteria |
US5571799A (en) | 1991-08-12 | 1996-11-05 | Basco, Ltd. | (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response |
ES2103918T3 (es) | 1991-10-17 | 1997-10-01 | Ciba Geigy Ag | Nucleosidos biciclicos, oligonucleotidos, procedimiento para su obtencion y productos intermedios. |
US5594121A (en) | 1991-11-07 | 1997-01-14 | Gilead Sciences, Inc. | Enhanced triple-helix and double-helix formation with oligomers containing modified purines |
US5484908A (en) | 1991-11-26 | 1996-01-16 | Gilead Sciences, Inc. | Oligonucleotides containing 5-propynyl pyrimidines |
SE9103701D0 (sv) | 1991-12-13 | 1991-12-13 | Kabi Pharmacia Ab | Apolipoprotein |
US5359044A (en) | 1991-12-13 | 1994-10-25 | Isis Pharmaceuticals | Cyclobutyl oligonucleotide surrogates |
US5652094A (en) | 1992-01-31 | 1997-07-29 | University Of Montreal | Nucleozymes |
FR2687679B1 (fr) | 1992-02-05 | 1994-10-28 | Centre Nat Rech Scient | Oligothionucleotides. |
US5256786A (en) | 1992-03-02 | 1993-10-26 | The Dow Chemical Company | Catalytic reforming of cyclic alkyleneamines |
US5633360A (en) | 1992-04-14 | 1997-05-27 | Gilead Sciences, Inc. | Oligonucleotide analogs capable of passive cell membrane permeation |
CA2135646A1 (en) | 1992-05-11 | 1993-11-25 | Kenneth G. Draper | Method and reagent for inhibiting viral replication |
US5434257A (en) | 1992-06-01 | 1995-07-18 | Gilead Sciences, Inc. | Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages |
US6372886B1 (en) | 1992-06-23 | 2002-04-16 | Arch Development Corp. | Expression and purification of kringle domains of human apolipoprotein (a) in E. coli |
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 |
EP0786522A2 (en) | 1992-07-17 | 1997-07-30 | Ribozyme Pharmaceuticals, Inc. | Enzymatic RNA molecules for treatment of stenotic conditions |
SE9203753D0 (sv) | 1992-12-11 | 1992-12-11 | Kabi Pharmacia Ab | Expression system for producing apolipoprotein ai-m |
IL108367A0 (en) | 1993-01-27 | 1994-04-12 | Hektoen Inst For Medical Resea | Antisense polynzcleotide inhibition of human growth factor-sensitive cancer cells |
US5476925A (en) | 1993-02-01 | 1995-12-19 | Northwestern University | Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups |
GB9304618D0 (en) | 1993-03-06 | 1993-04-21 | Ciba Geigy Ag | Chemical compounds |
AU6449394A (en) | 1993-03-30 | 1994-10-24 | Sterling Winthrop Inc. | Acyclic nucleoside analogs and oligonucleotide sequences containing them |
HU9501974D0 (en) | 1993-03-31 | 1995-09-28 | 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 |
US5532130A (en) | 1993-07-20 | 1996-07-02 | Dyad Pharmaceutical Corporation | Methods and compositions for sequence-specific hybridization of RNA by 2'-5' oligonucleotides |
US5502177A (en) | 1993-09-17 | 1996-03-26 | Gilead Sciences, Inc. | Pyrimidine derivatives for labeled binding partners |
US5801154A (en) | 1993-10-18 | 1998-09-01 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of multidrug resistance-associated protein |
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 |
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 |
US5596091A (en) | 1994-03-18 | 1997-01-21 | The Regents Of The University Of California | Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides |
JP3754072B2 (ja) | 1994-03-22 | 2006-03-08 | リサーチ・コーポレーション・テクノロジーズ・インコーポレーテッド | 摂食抑制ペプチド |
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 |
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 |
US5534499A (en) | 1994-05-19 | 1996-07-09 | The University Of British Columbia | Lipophilic drug derivatives for use in liposomes |
US5597909A (en) | 1994-08-25 | 1997-01-28 | Chiron Corporation | Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use |
AU3559695A (en) | 1994-09-30 | 1996-04-26 | Inex Pharmaceuticals Corp. | Glycosylated protein-liposome conjugates and methods for their preparation |
US5885613A (en) | 1994-09-30 | 1999-03-23 | The University Of British Columbia | Bilayer stabilizing components and their use in forming programmable fusogenic liposomes |
US5820873A (en) | 1994-09-30 | 1998-10-13 | The University Of British Columbia | Polyethylene glycol modified ceramide lipids and liposome uses thereof |
US5783683A (en) | 1995-01-10 | 1998-07-21 | Genta Inc. | Antisense oligonucleotides which reduce expression of the FGFRI gene |
SE9500778D0 (sv) | 1995-03-03 | 1995-03-03 | Pharmacia Ab | Process for producing a protein |
US5747470A (en) | 1995-06-07 | 1998-05-05 | Gen-Probe Incorporated | Method for inhibiting cellular proliferation using antisense oligonucleotides to gp130 mRNA |
ATE285477T1 (de) | 1995-06-07 | 2005-01-15 | Inex Pharmaceutical Corp | Herstellung von lipid-nukleinsäure partikeln duch ein hydrophobische lipid-nukleinsäuree komplexe zwischenprodukt und zur verwendung in der gentransfer |
US5672685A (en) | 1995-10-04 | 1997-09-30 | Duke University | Source of apolipoprotein E and method of isolating apolipoprotein E |
US5861397A (en) | 1996-10-03 | 1999-01-19 | Vical Incorporated | Piperazine based cytofectins |
TW520297B (en) * | 1996-10-11 | 2003-02-11 | Sequus Pharm Inc | Fusogenic liposome composition and method |
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 |
US6287591B1 (en) | 1997-05-14 | 2001-09-11 | Inex Pharmaceuticals Corp. | Charged therapeutic agents encapsulated in lipid particles containing four lipid components |
US6835395B1 (en) | 1997-05-14 | 2004-12-28 | The University Of British Columbia | Composition containing small multilamellar oligodeoxynucleotide-containing lipid vesicles |
EP0956050A1 (fr) * | 1997-06-12 | 1999-11-17 | Transgene S.A. | Nouveaux complexes lipidiques pour le transfert d'au moins une substance therapeutiquement active, notamment un polynucleotide, dans une cellule cible et utilisation en therapie genique |
US6037323A (en) | 1997-09-29 | 2000-03-14 | Jean-Louis Dasseux | Apolipoprotein A-I agonists and their use to treat dyslipidemic disorders |
US6004925A (en) | 1997-09-29 | 1999-12-21 | J. L. Dasseux | Apolipoprotein A-I agonists and their use to treat dyslipidemic disorders |
US6046166A (en) | 1997-09-29 | 2000-04-04 | Jean-Louis Dasseux | Apolipoprotein A-I agonists and their use to treat dyslipidemic disorders |
US6320017B1 (en) | 1997-12-23 | 2001-11-20 | Inex Pharmaceuticals Corp. | Polyamide oligomers |
AU756196B2 (en) | 1998-11-13 | 2003-01-09 | Optime Therapeutics, Inc. | Method and apparatus for liposome production |
MXPA02002107A (es) | 1999-08-27 | 2003-08-20 | Inex Pharmaceuticals Corp | Composiciones para estimular la secrecion de citoquina e inducir una respuesta inmune. |
NZ526226A (en) | 2000-11-30 | 2004-05-28 | Ranbaxy Lab Ltd | 1,4-disubstituted piperazine derivatives useful as uro-selective alpha1-adrenoceptor blockers |
EP1985702A3 (en) | 2000-12-08 | 2010-08-18 | Coley Pharmaceutical GmbH | CPG-like nucleic acids and methods of use thereof |
US20040009216A1 (en) | 2002-04-05 | 2004-01-15 | Rodrigueza Wendi V. | Compositions and methods for dosing liposomes of certain sizes to treat or prevent disease |
US7887431B2 (en) | 2008-05-16 | 2011-02-15 | Taylor Made Golf Company, Inc. | Golf club |
AU2006274413B2 (en) | 2005-07-27 | 2013-01-10 | Arbutus Biopharma Corporation | Systems and methods for manufacturing liposomes |
AU2007303205A1 (en) * | 2006-10-03 | 2008-04-10 | Tekmira Pharmaceuticals Corporation | Lipid containing formulations |
SG10201402054UA (en) | 2009-05-05 | 2014-09-26 | Muthiah Manoharan | Lipid compositions |
US10867398B2 (en) | 2017-11-21 | 2020-12-15 | Reliance Core Consulting LLC | Methods, systems, apparatuses and devices for facilitating motion analysis in an environment |
-
2010
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Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3931430A (en) * | 1972-11-11 | 1976-01-06 | Kanzaki Paper Mfg. Co. Ltd. | Method of desensitizing a pressure sensitive recording sheet and the product thereof |
US4743304A (en) * | 1983-12-14 | 1988-05-10 | Morton Thiokol, Inc. | Asphalt antistripping agents containing organic amines and Portland cement |
JPH01301364A (ja) * | 1988-05-31 | 1989-12-05 | Daio Paper Corp | 感圧複写紙用減感剤組成物 |
JP2002537492A (ja) * | 1999-02-19 | 2002-11-05 | ザ、プロクター、エンド、ギャンブル、カンパニー | 布地改良組成物 |
US20030175966A1 (en) * | 2002-03-14 | 2003-09-18 | Genteric, Inc. | Cationic sugar derivatives for gene transfer |
WO2007130073A2 (en) * | 2006-05-05 | 2007-11-15 | Molecular Transfer, Inc. | Novel reagents for transfection of eukaryotic cells |
WO2008113364A2 (en) * | 2007-03-20 | 2008-09-25 | Recepticon Aps | Amino derivatives to prevent nephrotoxicity and cancer |
JP2012508235A (ja) * | 2008-11-07 | 2012-04-05 | マサチューセッツ インスティテュート オブ テクノロジー | アミノアルコールリピドイドおよびその使用 |
Non-Patent Citations (1)
Title |
---|
JOURNAL OF CONTROLLED RELEASE, vol. 66, no. 2, JPN6021033267, 15 May 2000 (2000-05-15), pages 115 - 126, ISSN: 0004822035 * |
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