JP2013537518A - RNA送達に有利なpKa値を有する脂質を含むリポソーム - Google Patents
RNA送達に有利なpKa値を有する脂質を含むリポソーム Download PDFInfo
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Abstract
Description
本発明は、免疫のためのRNAの非ウイルス性送達の分野にある。
動物を免疫するための核酸の送達は、数年間にわたり目標であった。種々のアプローチが、試験されてきており、それらとしては、DNAもしくはRNAの使用、ウイルスもしくは非ウイルス性送達ビヒクルの使用(またはさらには「裸の」ワクチンにおいて、送達ビヒクルなし)、複製もしくは非複製ベクターの使用、またはウイルスもしくは非ウイルス性ベクターの使用が挙げられる。
本発明によれば、免疫原をコードするRNAは、免疫の目的で、リポソーム中で送達される。上記リポソームは、5.0〜7.6の範囲のpKaを有する脂質を含む。理想的には、この範囲のpKaを有する脂質は、三級アミンを有する;このような脂質は、四級アミン基を有する脂質(例えば、DOTAPもしくはDC−Chol)とは異なって挙動する。生理学的pHにおいて、5.0〜7.6の範囲のpKaを有するアミンは、中性のもしくは低下した表面電荷を有するのに対して、DOTAPのような脂質は、強力にカチオン性である。本発明者らは、四級アミン脂質(例えば、DOTAP)から形成されるリポソームが、三級アミン脂質(例えば、DLinDMA)から形成されるリポソームより、免疫原をコードするRNAの送達には適切性において劣ることを見いだした。
本発明は、免疫原をコードするRNAが封入されているリポソームを利用する。従って、上記RNAは、(天然ウイルスにおけるように)上記リポソームの脂質二重層によって任意の外部媒体(external medium)から分離されており、そしてこの方法での封入は、RNase消化からRNAを保護することが見いだされた。上記リポソームは、いくらかの外部RNA(例えば、それらの表面に)を含み得るが、上記RNAのうちの少なくとも半分(および理想的には、そのすべて)は、上記リポソームのコアに封入される。リポソーム内の封入は、例えば、参考文献1で開示される脂質/RNA複合体とは異なる。
上記のように、本発明は、RNA含有リポソームを調製するためのプロセスであって、(a)RNAと、脂質とを、上記脂質のpKa未満であるが、4.5を上回るpHにおいて混合する工程;次いで、(b)上記pHを、上記脂質のpKaを上回るように上昇させる工程を包含するプロセスを提供する。
本発明は、免疫原をコードするRNAのインビボ送達に有用である。上記RNAは、その送達部位において非免疫細胞によって翻訳され、上記免疫原の発現をもたらし、そしてまた、それは、免疫細胞に、I型インターフェロンおよび/もしくは炎症促進性サイトカイン(これらは、局所的なアジュバント効果を提供する)を分泌させる。上記非免疫細胞はまた、上記RNAに応答してI型インターフェロンおよび/もしくは炎症促進性サイトカインを分泌し得る。
本発明で使用されるRNA分子は、ポリペプチド免疫原をコードする。上記リポソームの投与後に、上記RNAは、インビボで翻訳され、そして免疫原は、レシピエントにおける免疫応答を誘発し得る。上記免疫原は、細菌、ウイルス、真菌もしくは寄生生物に対して(あるいは、いくつかの実施形態において、アレルゲンに対して;および他の実施形態において、腫瘍抗原に対して)免疫応答を誘発し得る。上記免疫応答は、抗体応答(通常は、IgGを含む)および/もしくは細胞媒介性免疫応答を含み得る。上記ポリペプチド免疫原は、代表的には、対応する細菌、ウイルス、真菌もしくは寄生生物(またはアレルゲンもしくは腫瘍)ポリペプチドを認識する免疫応答を誘発するが、いくつかの実施形態において、上記ポリペプチドは、細菌、ウイルス、真菌もしくは寄生生物のサッカリドを認識する免疫応答を誘発するように、ミモトープとして作用し得る。上記免疫原は、代表的には、表面ポリペプチド(例えば、アドヘシン、ヘマグルチニン、エンベロープ糖タンパク質、スパイク糖タンパク質など)である。
Neisseria meningitidis:有用な免疫原としては、膜タンパク質、例えば、アドヘシン、オートトランスポーター、毒素、鉄獲得タンパク質、およびH因子結合タンパク質が挙げられるが、これらに限定されない。3種の有用なポリペプチドの組み合わせが、参考文献15に開示される。
Bordetella pertussis:有用な百日咳免疫原としては、百日咳毒素もしくはトキソイド(PT)、線維状ヘマグルチニン(FHA)、ペルタクチン、ならびに凝集原2および3が挙げられるが、これらに限定されない。
Streptococcus agalactiae:有用な免疫原としては、参考文献17に開示されるポリペプチドが挙げられるが、これらに限定されない。
Yersinia pestis:有用な免疫原としては、参考文献31および32に開示されるものが挙げられるが、これらに限定されない。
オルソミクソウイルス:有用な免疫原は、インフルエンザA、BもしくはCウイルスに由来し得る(例えば、ヘマグルチニン、ノイラミニダーゼもしくはマトリクスM2タンパク質)。上記免疫原がインフルエンザAウイルスヘマグルチニンである場合、それは、任意のサブタイプ(例えば、H1、H2、H3、H4、H5、H6、H7、H8、H9、H10、H11、H12、H13、H14、H15もしくはH16)に由来し得る。
本発明のリポソームは、種々の疾患に対して被験体を免疫するための薬学的組成物中の成分として有用である。これらの組成物は、代表的には、上記リポソームに加えて、薬学的に受容可能なキャリアを含む。薬学的に受容可能なキャリアの詳細な考察は、参考文献33において入手可能である。
参考文献14で開示される粒子とは対照的に、本発明のリポソームおよび薬学的組成物は、目的の免疫原に対する免疫応答を誘発するためのインビボでの使用のためのものである。
本発明の粒子は、別段示されなければ、化学、生化学、分子生物学、免疫学および薬理学の、当該分野の技術内の従来の方法を使用する。このような技術は、文献中に十分に説明されている。例えば、参考文献34〜40などを参照のこと。
種々のレプリコンは、以下で使用される。一般に、これらは、ベネズエラウマ脳炎ウイルス(VEEV)に由来する非構造タンパク質、シンドビス・ウイルス由来のパッケージングシグナル、およびシンドビス・ウイルスもしくはVEEV変異体に由来する3’UTRを有するハイブリッドアルファウイルスゲノムに基づく。上記レプリコンは、約10kb長であり、ポリA尾部を有する。
RNAを、参考文献11および42の方法によって作製したリポソーム中に封入した。上記リポソームを、10% DSPC(両性イオン性)、40% DLinDMA(カチオン性)、48% コレステロールおよび2% PEG結合体化DMG(2kDa PEG)から作製した。これら割合は、総リポソーム中の%モルに言及する。
骨髄由来樹状細胞(pDC)を、野生型マウスもしくは「Resq」(rsq1)変異系統から得た。上記変異系統は、そのTLR7レセプターのアミノ末端において点変異を有し、これは、リガンド結合に影響を及ぼさずにTLR7シグナル伝達を破壊する[44]。上記細胞を、DOTAP、リポフェクタミン2000で処方したレプリコンRNAもしくはリポソーム内のレプリコンRNAで刺激した。図19に示されるように、IL−6およびINFαは、WT細胞において誘導されたが、この応答は、変異マウスにおいてほぼ完全に排除された。これらの結果は、TLR7が、免疫細胞におけるRNA認識のために必要とされ、そしてリポソーム封入レプリコンが、免疫細胞に高レベルのインターフェロンおよび炎症促進性(pro−inflammatory)サイトカインの両方を分泌させ得ることを示す。
脂質のpKaを、標準の温度および圧力の水において、以下の技術を使用して測定する:
・エタノール中の脂質の2mM溶液を、上記脂質を秤量し、エタノール中に溶解することによって調製する。エタノール:メタノール 9:1中の蛍光プローブトルエンニトロスルホン酸(TNS)の0.3mM溶液を、最初にメタノール中のTNSの3mM溶液を作製し、次いで、エタノールで0.3mMに希釈することによって調製する。
・それぞれ、濃度20mM、25mM、20mMおよび150mMのリン酸ナトリウム、クエン酸ナトリウム、酢酸ナトリウム、および塩化ナトリウムを含む水性緩衝液を、調製する。上記緩衝液を、8つの部分に分け、そのpHを、12N HClもしくは6N NaOHのいずれかで、4.44〜4.52、5.27、6.15〜6.21、6.57、7.10〜7.20、7.72〜7.80、8.27〜8.33および10.47〜11.12へと調整する。400μLの2mM脂質溶液および800μLの0.3mM TNS溶液を混合する。
・7.5μLのプローブ/脂質混合物を、1mL 96ウェルプレートの中の242.5μLの緩衝液に添加する。これを、8つすべての緩衝液で行う。混合した後、100μLの各プローブ/脂質/緩衝液混合物を、クリアボトム(clear bottom)250μL黒色96ウェルプレート(例えば、モデルCOSTAR 3904, Corning)に移す。この混合を行う便利な方法は、Tecan Genesis RSP150ハイスループット液体ハンドラーおよびGemini Softwareを使用することである。
・各プローブ/脂質/緩衝液混合物の蛍光を、322nm励起、431nm発光(オートカットオフ420nm)で測定する(例えば、SpectraMax M5分光光度計およびSoftMax pro 5.2ソフトウェアで)。
・測定後、上記96ウェルプレートにおける空のウェルのバックグラウンド蛍光値を、各プローブ/脂質/緩衝液混合物から差し引く。次いで、その蛍光強度値を、最低pHにおける値に対して正規化する。次いで、正規化した蛍光強度を、pHに対してプロットし、最適の線を、提供する。
・上記正規化した蛍光強度が0.5に等しい最適の線上の点を、見いだす。0.5に等しい正規化した蛍光強度に対応するpHを見いだし、上記脂質のpKaとみなす。
DlinDMAを使用する代わりとして、参考文献5のカチオン性脂質を使用する。これら脂質を、参考文献5に開示されるように合成しうる。
(RSV免疫原性)
さらなる研究は、RSV Fタンパク質をコードする自己複製レプリコン(vA317)で行った。BALB/cマウス(1群あたり4匹もしくは8匹の動物)に、0日目および21日目に、上記レプリコン(1μg)単独を、あるいは上記RV01脂質もしくはRV05脂質(上記を参照のこと;pKa 5.8もしくは5.85)で、またはRV13でリポソームとして処方されたレプリコンを、両側の筋肉内にワクチン接種(50μL/脚)した。上記RV01リポソームは、40% DLinDMA、10% DSPC、48% コレステロールおよび2% PEG−DMGを有したが、RNAの量は異なった。上記RV05(01)リポソームは、40% カチオン性脂質、48% コレステロール、10% DSPC、および2% PEG−DMGを有した;上記RV05(02)リポソームは、60% カチオン性脂質、38% コレステロール、および2% PEG−DMGを有した。上記RV13リポソームは、40% DOTAP、10% DPE、48% コレステロールおよび2% PEG−DMGを有した。比較のために、同じRSV−F抗原を発現する裸のプラスミドDNA(20μg)を、エレクトロポレーションを使用するか、またはRV01(10)リポソーム(0.1μg DNA)によるかのいずれかで送達した。4匹のマウスを、ナイーブコントロール群として使用した。
RV01リポソームにおけるカチオン性脂質(DLinDMA)は、RV16、RV17、RV18もしくはRV19で置き換えられた。総IgG力価を、図17に示す。最低の結果は、RV19(すなわち、DOTMA四級アミン)で認められる。
異なる脂質を有するリポソームを、BHK細胞とともに一晩インキュベートし、タンパク質発現効力について評価した。RV05脂質発現でのベースラインから、10% 1,2−ジフィタノイル−sn−グリセロ−3−ホスホエタノールアミン(DPyPE)を上記リポソームに添加することによって18×、10% 18:2(cis) ホスファチジルコリンを添加することによって10×、および代わりにRV01を使用することによって900×増大し得た。
レプリコン「vA142」は、RSVの全長野生型表面融合(F)糖タンパク質をコードするが、その融合ペプチドは欠失しており、その3’末端は、リボザイム媒介性切断によって形成される。これを、3種の異なるマウス系統において試験した。
群1には、裸のレプリコン(1μg)を与えた。
群2には、40% DlinDMA、10% DSPC、48% Chol、2% PEG結合体化DMGを有するリポソーム「RV01(37)」中で送達した1μg レプリコンを与えた。
群3には、群2と同じものを与えたが、0.1μg RNAであった。
群4には、「RV17(10)」リポソーム(40% RV17(上記を参照のこと)、10% DSPC、49.5% コレステロール、0.5% PEG−DMG)中において1μg レプリコンを与えた。
群5には、「RV05(11)」リポソーム(40% RV07脂質、30% 18:2 PE(DLoPE)、28% コレステロール、2% PEG−DMG)中において1μg レプリコンを与えた。
群6には、「RV17(10)」リポソーム中において0.1μg レプリコンを与えた。
群7には、水酸化アルミニウムをアジュバント添加した5μg RSV−Fサブユニットタンパク質を与えた。
群8は、ナイーブコントロール(2匹の動物)であった。
DLinDMAをカチオン性脂質として有するRV01リポソームを使用して、サイトメガロウイルス(CMV)糖タンパク質をコードするRNAレプリコンを送達した。「vA160」レプリコンは、全長糖タンパク質HおよびL(gH/gL)をコードするのに対して、「vA322」レプリコンは、可溶性形態(gHsol/gL)をコードする。上記2種のタンパク質は、単一のレプリコン中の別個のサブゲノムプロモーターの制御下にある;2種の別個のベクター(1つは、gHをコードし、1つは、gLをコードする)の共投与は、良好な結果を与えなかった。
Claims (14)
- 水性コアを封入する脂質二重層を有するリポソームであって、ここで:(i)該脂質二重層は、5.0〜7.6の範囲のpKaを有する脂質を含み;そして(ii)該水性コアは、免疫原をコードするRNAを含む、リポソーム。
- 5.0〜7.6の範囲のpKaを有する前記脂質は、三級アミンを有する、請求項1に記載のリポソーム。
- 5.0〜7.6の範囲のpKaは、5.7〜5.9の間である、前記請求項のいずれかに記載のリポソーム。
- 5.0〜7.6の範囲のpKaを有する前記脂質は、RV01、RV02、RV03、RV04、RV05、RV06、RV07、RV08、RV09、RV11、RV12、RV16もしくはRV17について本明細書で示される式を有する、請求項1に記載のリポソーム。
- 20〜220nmの範囲の直径を有する、前記請求項のいずれかに記載のリポソーム。
- 前記RNA分子は、(i)該RNA分子からRNAを転写し得るRNA依存性RNAポリメラーゼ、および(ii)免疫原をコードする、前記請求項のいずれかに記載のリポソーム。
- 前記RNA分子は、2個のオープンリーディングフレームを有し、そのうちの第1のものは、アルファウイルスレプリカーゼをコードし、そのうちの第2のものは、前記免疫原をコードする、請求項5に記載のリポソーム。
- 前記RNA分子は、9000〜12000ヌクレオチド長である、前記請求項のいずれかに記載のリポソーム。
- 前記免疫原は、細菌、ウイルス、真菌もしくは寄生生物に対してインビボで免疫応答を誘発し得る、前記請求項のいずれかに記載のリポソーム。
- 前記免疫原は、呼吸器系合胞体ウイルス糖タンパク質Fに対してインビボで免疫応答を誘発し得る、前記請求項のいずれかに記載のリポソーム。
- 前記請求項のいずれかに記載のリポソームを含む、薬学的組成物。
- 脊椎動物において防御的免疫応答を惹起するための方法であって、該方法は、該脊椎動物に、有効量の、請求項1〜10に記載のリポソーム、または請求項11に記載の薬学的組成物を投与する工程を包含する、方法。
- RNA含有リポソームを調製するためのプロセスであって、該プロセスは、リポソーム処方の間に、(a)RNAと、脂質とを、該脂質のpKa未満であるが4.5を上回るpHにおいて混合する工程;次いで、(b)該pHを、該脂質のpKaを上回るように上昇させる工程、を包含する、プロセス。
- 請求項13に記載のプロセスであって、ここで、工程(a)において使用されるRNAは、前記脂質の有機溶液と混合して、混合物を与える間、水性溶液中に存在し、該混合物は、次いで、希釈されて、リポソームを形成し;そして前記pHは、リポソーム形成後に、工程(b)において上昇させられる、プロセス。
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2016010111A1 (ja) * | 2014-07-17 | 2016-01-21 | 富士フイルム株式会社 | 脂質粒子の製造法および脂質粒子を有する核酸送達キャリア |
WO2016010110A1 (ja) * | 2014-07-17 | 2016-01-21 | 富士フイルム株式会社 | 脂質粒子および核酸送達キャリア |
JP2018016642A (ja) * | 2017-10-20 | 2018-02-01 | 富士フイルム株式会社 | 脂質粒子の製造法および脂質粒子を有する核酸送達キャリア |
JP2018024699A (ja) * | 2017-11-02 | 2018-02-15 | 富士フイルム株式会社 | 脂質粒子および核酸送達キャリア |
Families Citing this family (195)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8530708B2 (en) | 2003-07-25 | 2013-09-10 | Honeywell International Inc. | Processes for selective dehydrohalogenation of halogenated alkanes |
US9770463B2 (en) | 2010-07-06 | 2017-09-26 | Glaxosmithkline Biologicals Sa | Delivery of RNA to different cell types |
CA2804494A1 (en) | 2010-07-06 | 2012-01-12 | Novartis Ag | Virion-like delivery particles for self-replicating rna molecules |
PL2590626T3 (pl) | 2010-07-06 | 2016-04-29 | Glaxosmithkline Biologicals Sa | Liposomy z lipidami o korzystnej wartości pka do dostarczania rna |
ES2770335T3 (es) | 2010-07-06 | 2020-07-01 | Glaxosmithkline Biologicals Sa | Administración de ARN para desencadenar múltiples vías inmunológicas |
WO2012006369A2 (en) | 2010-07-06 | 2012-01-12 | Novartis Ag | Immunisation of large mammals with low doses of rna |
EP2600901B1 (en) | 2010-08-06 | 2019-03-27 | ModernaTX, Inc. | A pharmaceutical formulation comprising engineered nucleic acids and medical use thereof |
HRP20221048T1 (hr) * | 2010-08-31 | 2022-11-11 | Glaxosmithkline Biologicals Sa | Mali liposomi za isporuku rna koja kodira imunogen |
LT3981427T (lt) | 2010-08-31 | 2022-08-10 | Glaxosmithkline Biologicals S.A. | Pegilintos liposomos, skirtos imunogeną koduojančios rnr pristatymui |
ES2737960T3 (es) | 2010-10-01 | 2020-01-17 | Modernatx Inc | Nucleósidos, nucleótidos y ácidos nucleicos modificados y sus usos |
MX363307B (es) | 2010-10-11 | 2019-03-20 | Novartis Ag Star | Plataformas para suministro de antigenos. |
AU2012236099A1 (en) | 2011-03-31 | 2013-10-03 | Moderna Therapeutics, Inc. | Delivery and formulation of engineered nucleic acids |
TR201910686T4 (tr) | 2011-06-08 | 2019-08-21 | Translate Bio Inc | Mrna iletimine yönelik lipit nanopartikül bileşimleri ve yöntemler. |
EP2729126B1 (en) * | 2011-07-06 | 2020-12-23 | GlaxoSmithKline Biologicals SA | Liposomes having useful n:p ratio for delivery of rna molecules |
CA2840989A1 (en) | 2011-07-06 | 2013-01-10 | Novartis Ag | Immunogenic combination compositions and uses thereof |
RU2628705C2 (ru) | 2011-08-31 | 2017-08-21 | Новартис Аг | Пегилированные липосомы для доставки кодирующей иммуноген рнк |
US9464124B2 (en) | 2011-09-12 | 2016-10-11 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
EP3682905B1 (en) | 2011-10-03 | 2021-12-01 | ModernaTX, Inc. | Modified nucleosides, nucleotides, and nucleic acids, and uses thereof |
EP2791160B1 (en) | 2011-12-16 | 2022-03-02 | ModernaTX, Inc. | Modified mrna compositions |
WO2013143555A1 (en) | 2012-03-26 | 2013-10-03 | Biontech Ag | Rna formulation for immunotherapy |
ME03367B (me) * | 2012-03-26 | 2019-10-20 | Tron Translationale Onkologie An Der Univ Der Johannes Gutenberg Univ Mainz Gemeinnuetzige Gmbh | Formulacija rnk za imunoterapiju |
AU2013243948A1 (en) | 2012-04-02 | 2014-10-30 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of proteins associated with human disease |
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US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
AU2013243949A1 (en) | 2012-04-02 | 2014-10-30 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of biologics and proteins associated with human disease |
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MX2014015041A (es) | 2012-06-08 | 2015-06-17 | Shire Human Genetic Therapies | Administración pulmonar de arnm a células objetivo no pulmonares. |
SG11201408328VA (en) | 2012-07-06 | 2015-02-27 | Novartis Ag | Complexes of cytomegalovirus proteins |
US9512456B2 (en) | 2012-08-14 | 2016-12-06 | Modernatx, Inc. | Enzymes and polymerases for the synthesis of RNA |
EP4074834A1 (en) | 2012-11-26 | 2022-10-19 | ModernaTX, Inc. | Terminally modified rna |
CN109045294A (zh) * | 2013-01-10 | 2018-12-21 | 思齐乐 | 流感病毒免疫原性组合物及其应用 |
EP2946014A2 (en) | 2013-01-17 | 2015-11-25 | Moderna Therapeutics, Inc. | Signal-sensor polynucleotides for the alteration of cellular phenotypes |
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WO2014159813A1 (en) | 2013-03-13 | 2014-10-02 | Moderna Therapeutics, Inc. | Long-lived polynucleotide molecules |
US10258698B2 (en) | 2013-03-14 | 2019-04-16 | Modernatx, Inc. | Formulation and delivery of modified nucleoside, nucleotide, and nucleic acid compositions |
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US20160194625A1 (en) | 2013-09-03 | 2016-07-07 | Moderna Therapeutics, Inc. | Chimeric polynucleotides |
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BR112016024644A2 (pt) | 2014-04-23 | 2017-10-10 | Modernatx Inc | vacinas de ácido nucleico |
EP2974739A1 (en) | 2014-07-15 | 2016-01-20 | Novartis AG | RSVF trimerization domains |
US9738593B2 (en) | 2014-06-25 | 2017-08-22 | Acuitas Therapeutics Inc. | Lipids and lipid nanoparticle formulations for delivery of nucleic acids |
CA2955250A1 (en) | 2014-07-16 | 2016-01-21 | Moderna Therapeutics, Inc. | Chimeric polynucleotides |
EP3171895A1 (en) | 2014-07-23 | 2017-05-31 | Modernatx, Inc. | Modified polynucleotides for the production of intrabodies |
EP3061826A1 (en) | 2015-02-27 | 2016-08-31 | Novartis AG | Flavivirus replicons |
WO2016165825A1 (en) | 2015-04-13 | 2016-10-20 | Curevac Ag | Method for producing rna compositions |
JP2017000667A (ja) | 2015-06-16 | 2017-01-05 | 国立大学法人三重大学 | 無針注射器及びそれを用いた注射対象領域へのdna導入方法 |
IL283545B2 (en) | 2015-06-29 | 2023-09-01 | Acuitas Therapeutics Inc | Lipids and nanoparticulate lipid formulations for delivery of nucleic acids |
EP3324979B1 (en) | 2015-07-21 | 2022-10-12 | ModernaTX, Inc. | Infectious disease vaccines |
US11364292B2 (en) | 2015-07-21 | 2022-06-21 | Modernatx, Inc. | CHIKV RNA vaccines |
WO2017031232A1 (en) | 2015-08-17 | 2017-02-23 | Modernatx, Inc. | Methods for preparing particles and related compositions |
PT3350157T (pt) | 2015-09-17 | 2022-03-18 | Modernatx Inc | Compostos e composições para administração intracelular de agentes terapêuticos |
US10849920B2 (en) | 2015-10-05 | 2020-12-01 | Modernatx, Inc. | Methods for therapeutic administration of messenger ribonucleic acid drugs |
SG10201914006UA (en) * | 2015-10-22 | 2020-03-30 | Modernatx Inc | Respiratory syncytial virus vaccine |
EP3364950A4 (en) | 2015-10-22 | 2019-10-23 | ModernaTX, Inc. | VACCINES AGAINST TROPICAL DISEASES |
CA3002912A1 (en) | 2015-10-22 | 2017-04-27 | Modernatx, Inc. | Nucleic acid vaccines for varicella zoster virus (vzv) |
CA3002819A1 (en) | 2015-10-22 | 2017-04-27 | Modernatx, Inc. | Sexually transmitted disease vaccines |
PL3368507T3 (pl) | 2015-10-28 | 2023-03-27 | Acuitas Therapeutics Inc. | Nowe preparaty lipidów i nanocząstek lipidowych do dostarczania kwasów nukleinowych |
EP3964200A1 (en) | 2015-12-10 | 2022-03-09 | ModernaTX, Inc. | Compositions and methods for delivery of therapeutic agents |
AU2016377681B2 (en) | 2015-12-22 | 2021-05-13 | Modernatx, Inc. | Compounds and compositions for intracellular delivery of agents |
HRP20220525T1 (hr) | 2015-12-23 | 2022-05-27 | Modernatx, Inc. | Postupci uporabe polinukleotida koji kodiraju ligand ox40 |
JP2019500043A (ja) | 2015-12-28 | 2019-01-10 | ノバルティス アーゲー | 異常ヘモグロビン症の治療用組成物および方法 |
WO2017120612A1 (en) | 2016-01-10 | 2017-07-13 | Modernatx, Inc. | Therapeutic mrnas encoding anti ctla-4 antibodies |
WO2017162265A1 (en) | 2016-03-21 | 2017-09-28 | Biontech Rna Pharmaceuticals Gmbh | Trans-replicating rna |
WO2017162266A1 (en) | 2016-03-21 | 2017-09-28 | Biontech Rna Pharmaceuticals Gmbh | Rna replicon for versatile and efficient gene expression |
KR102533456B1 (ko) | 2016-05-18 | 2023-05-17 | 모더나티엑스, 인크. | 릴랙신을 인코딩하는 폴리뉴클레오타이드 |
EP3463445A1 (en) | 2016-06-02 | 2019-04-10 | GlaxoSmithKline Biologicals SA | Zika viral antigen constructs |
CN106176633A (zh) * | 2016-08-17 | 2016-12-07 | 浙江美保龙生物技术有限公司 | 一种猪传染性胃肠炎病毒脂质体稀释液冻干制品及其制备方法 |
CN106176634A (zh) * | 2016-08-17 | 2016-12-07 | 浙江美保龙生物技术有限公司 | 一种猪传染性胃肠炎‑流行性腹泻二联弱毒疫苗脂质体稀释液冻干制品及其制备方法 |
CN106109424A (zh) * | 2016-08-17 | 2016-11-16 | 浙江美保龙生物技术有限公司 | 一种猪圆环病毒2型脂质体稀释液冻干制品及其制备方法 |
WO2018033254A2 (en) | 2016-08-19 | 2018-02-22 | Curevac Ag | Rna for cancer therapy |
EP3518966A1 (en) | 2016-09-29 | 2019-08-07 | GlaxoSmithKline Biologicals S.A. | Compositions and methods of treatment of persistent hpv infection |
GB201616904D0 (en) | 2016-10-05 | 2016-11-16 | Glaxosmithkline Biologicals Sa | Vaccine |
WO2018089540A1 (en) | 2016-11-08 | 2018-05-17 | Modernatx, Inc. | Stabilized formulations of lipid nanoparticles |
US10925958B2 (en) | 2016-11-11 | 2021-02-23 | Modernatx, Inc. | Influenza vaccine |
WO2018091540A1 (en) | 2016-11-17 | 2018-05-24 | Glaxosmithkline Biologicals Sa | Zika viral antigen constructs |
CN110582304A (zh) | 2016-12-08 | 2019-12-17 | 库尔维科公司 | 用于治疗或预防肝脏疾病的rna |
US11103578B2 (en) | 2016-12-08 | 2021-08-31 | Modernatx, Inc. | Respiratory virus nucleic acid vaccines |
WO2018104540A1 (en) | 2016-12-08 | 2018-06-14 | Curevac Ag | Rnas for wound healing |
US11141476B2 (en) | 2016-12-23 | 2021-10-12 | Curevac Ag | MERS coronavirus vaccine |
US11464847B2 (en) | 2016-12-23 | 2022-10-11 | Curevac Ag | Lassa virus vaccine |
TW201839136A (zh) | 2017-02-06 | 2018-11-01 | 瑞士商諾華公司 | 治療血色素異常症之組合物及方法 |
PL3596041T3 (pl) | 2017-03-15 | 2023-03-06 | Modernatx, Inc. | Związek i kompozycje do dokomórkowego dostarczania środków terapeutycznych |
US11045540B2 (en) | 2017-03-15 | 2021-06-29 | Modernatx, Inc. | Varicella zoster virus (VZV) vaccine |
US11752206B2 (en) | 2017-03-15 | 2023-09-12 | Modernatx, Inc. | Herpes simplex virus vaccine |
ES2911186T3 (es) | 2017-03-15 | 2022-05-18 | Modernatx Inc | Formas cristalinas de aminolípidos |
MA47787A (fr) | 2017-03-15 | 2020-01-22 | Modernatx Inc | Vaccin contre le virus respiratoire syncytial |
US11969506B2 (en) | 2017-03-15 | 2024-04-30 | Modernatx, Inc. | Lipid nanoparticle formulation |
MA52262A (fr) | 2017-03-15 | 2020-02-19 | Modernatx Inc | Vaccin à large spectre contre le virus de la grippe |
CN110392577A (zh) | 2017-03-17 | 2019-10-29 | 库尔维科公司 | 用于组合抗癌疗法的rna疫苗和免疫检查点抑制剂 |
AU2018240515A1 (en) | 2017-03-24 | 2019-08-01 | CureVac SE | Nucleic acids encoding CRISPR-associated proteins and uses thereof |
US11905525B2 (en) | 2017-04-05 | 2024-02-20 | Modernatx, Inc. | Reduction of elimination of immune responses to non-intravenous, e.g., subcutaneously administered therapeutic proteins |
WO2018208856A1 (en) | 2017-05-08 | 2018-11-15 | Gritstone Oncology, Inc. | Alphavirus neoantigen vectors |
ES2952779T3 (es) | 2017-05-18 | 2023-11-06 | Modernatx Inc | ARN mensajero modificado que comprende elementos de ARN funcionales |
WO2018213731A1 (en) | 2017-05-18 | 2018-11-22 | Modernatx, Inc. | Polynucleotides encoding tethered interleukin-12 (il12) polypeptides and uses thereof |
US11015204B2 (en) | 2017-05-31 | 2021-05-25 | Arcturus Therapeutics, Inc. | Synthesis and structure of high potency RNA therapeutics |
US20200268666A1 (en) * | 2017-06-14 | 2020-08-27 | Modernatx, Inc. | Polynucleotides encoding coagulation factor viii |
US11786607B2 (en) | 2017-06-15 | 2023-10-17 | Modernatx, Inc. | RNA formulations |
CN111328287A (zh) | 2017-07-04 | 2020-06-23 | 库瑞瓦格股份公司 | 新型核酸分子 |
WO2019046809A1 (en) | 2017-08-31 | 2019-03-07 | Modernatx, Inc. | METHODS OF MANUFACTURING LIPID NANOPARTICLES |
JP7389741B2 (ja) | 2017-09-13 | 2023-11-30 | バイオエヌテック セル アンド ジーン セラピーズ ゲーエムベーハー | T細胞受容体または人工t細胞受容体を発現するためのrnaレプリコン |
EP3681993A1 (en) | 2017-09-13 | 2020-07-22 | BioNTech RNA Pharmaceuticals GmbH | Rna replicon for reprogramming somatic cells |
US10653767B2 (en) | 2017-09-14 | 2020-05-19 | Modernatx, Inc. | Zika virus MRNA vaccines |
EP3461497A1 (en) | 2017-09-27 | 2019-04-03 | GlaxoSmithKline Biologicals S.A. | Viral antigens |
US20220233568A1 (en) | 2017-10-19 | 2022-07-28 | Curevac Ag | Novel artificial nucleic acid molecules |
CA3079543A1 (en) | 2017-11-22 | 2019-05-31 | Modernatx, Inc. | Polynucleotides encoding propionyl-coa carboxylase alpha and beta subunits for the treatment of propionic acidemia |
WO2019104160A2 (en) | 2017-11-22 | 2019-05-31 | Modernatx, Inc. | Polynucleotides encoding phenylalanine hydroxylase for the treatment of phenylketonuria |
EP3714048A1 (en) | 2017-11-22 | 2020-09-30 | Modernatx, Inc. | Polynucleotides encoding ornithine transcarbamylase for the treatment of urea cycle disorders |
KR20200118029A (ko) | 2018-01-04 | 2020-10-14 | 아이코닉 테라퓨틱스, 인코포레이티드 | 항-조직 인자 항체, 항체-약물 결합체, 및 관련 방법 |
WO2019136241A1 (en) | 2018-01-05 | 2019-07-11 | Modernatx, Inc. | Polynucleotides encoding anti-chikungunya virus antibodies |
MA54676A (fr) | 2018-01-29 | 2021-11-17 | Modernatx Inc | Vaccins à base d'arn contre le vrs |
EP3773745A1 (en) | 2018-04-11 | 2021-02-17 | ModernaTX, Inc. | Messenger rna comprising functional rna elements |
WO2019226650A1 (en) | 2018-05-23 | 2019-11-28 | Modernatx, Inc. | Delivery of dna |
US20220184185A1 (en) | 2018-07-25 | 2022-06-16 | Modernatx, Inc. | Mrna based enzyme replacement therapy combined with a pharmacological chaperone for the treatment of lysosomal storage disorders |
WO2020035609A2 (en) | 2018-08-17 | 2020-02-20 | Glaxosmithkline Biologicals Sa | Immunogenic compositions and uses thereof |
WO2020047201A1 (en) | 2018-09-02 | 2020-03-05 | Modernatx, Inc. | Polynucleotides encoding very long-chain acyl-coa dehydrogenase for the treatment of very long-chain acyl-coa dehydrogenase deficiency |
AU2019335055A1 (en) * | 2018-09-04 | 2021-03-25 | The Board Of Regents Of The University Of Texas System | Compositions and methods for organ specific delivery of nucleic acids |
WO2020056155A2 (en) | 2018-09-13 | 2020-03-19 | Modernatx, Inc. | Polynucleotides encoding branched-chain alpha-ketoacid dehydrogenase complex e1-alpha, e1-beta, and e2 subunits for the treatment of maple syrup urine disease |
MX2021003015A (es) | 2018-09-13 | 2021-07-15 | Modernatx Inc | Polinucleotidos que codifican glucosa-6-fosfatasa para el tratamiento de la glucogenosis. |
MA53615A (fr) | 2018-09-14 | 2021-07-21 | Modernatx Inc | Polynucléotides codant pour le polypeptide a1, de la famille de l'uridine diphosphate glycosyltransférase 1, pour le traitement du syndrome de crigler-najjar |
US20220152225A1 (en) | 2018-09-27 | 2022-05-19 | Modernatx, Inc. | Polynucleotides encoding arginase 1 for the treatment of arginase deficiency |
US20220001026A1 (en) | 2018-11-08 | 2022-01-06 | Modernatx, Inc. | Use of mrna encoding ox40l to treat cancer in human patients |
TW202043256A (zh) | 2019-01-10 | 2020-12-01 | 美商健生生物科技公司 | 前列腺新抗原及其用途 |
EP3908328A1 (en) | 2019-01-10 | 2021-11-17 | BioNTech RNA Pharmaceuticals GmbH | Localized administration of rna molecules for therapy |
US11453639B2 (en) | 2019-01-11 | 2022-09-27 | Acuitas Therapeutics, Inc. | Lipids for lipid nanoparticle delivery of active agents |
US11351242B1 (en) | 2019-02-12 | 2022-06-07 | Modernatx, Inc. | HMPV/hPIV3 mRNA vaccine composition |
US20220226438A1 (en) | 2019-05-08 | 2022-07-21 | Astrazeneca Ab | Compositions for skin and wounds and methods of use thereof |
TW202110870A (zh) | 2019-05-30 | 2021-03-16 | 美商葛利史東腫瘤科技公司 | 經修飾之腺病毒 |
WO2020263883A1 (en) | 2019-06-24 | 2020-12-30 | Modernatx, Inc. | Endonuclease-resistant messenger rna and uses thereof |
EP3986480A1 (en) | 2019-06-24 | 2022-04-27 | ModernaTX, Inc. | Messenger rna comprising functional rna elements and uses thereof |
CN112237628A (zh) * | 2019-07-17 | 2021-01-19 | 四川大学华西医院 | 靶向EBV的LMP2-mRNA纳米疫苗 |
WO2021009336A1 (en) | 2019-07-18 | 2021-01-21 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for inducing full ablation of hematopoiesis |
CA3146900A1 (en) | 2019-07-21 | 2021-01-28 | Glaxosmithkline Biologicals Sa | Therapeutic viral vaccine |
AR120080A1 (es) | 2019-09-19 | 2022-02-02 | Modernatx Inc | Compuestos lipídicos de cola ramificada y composiciones para la administración intracelular de agentes terapéuticos |
AU2020352552A1 (en) | 2019-09-23 | 2022-03-17 | Omega Therapeutics, Inc. | Compositions and methods for modulating hepatocyte nuclear factor 4-alpha (HNF4α) gene expression |
EP4048807A1 (en) | 2019-09-23 | 2022-08-31 | Omega Therapeutics, Inc. | Compositions and methods for modulating apolipoprotein b (apob) gene expression |
EP3819377A1 (en) | 2019-11-08 | 2021-05-12 | Justus-Liebig-Universität Gießen | Circular rna and uses thereof for inhibiting rna-binding proteins |
WO2021123920A1 (en) | 2019-12-18 | 2021-06-24 | Novartis Ag | Compositions and methods for the treatment of hemoglobinopathies |
US11576966B2 (en) | 2020-02-04 | 2023-02-14 | CureVac SE | Coronavirus vaccine |
JP2023519173A (ja) | 2020-03-09 | 2023-05-10 | アークトゥラス・セラピューティクス・インコーポレイテッド | 免疫応答を誘導するための組成物及び方法 |
CA3173528A1 (en) | 2020-03-11 | 2021-09-16 | Omega Therapeutics, Inc. | Compositions and methods for modulating forkhead box p3 (foxp3) gene expression |
EP4135761A1 (en) | 2020-04-16 | 2023-02-22 | GlaxoSmithKline Biologicals S.A. | Sars cov-2 spike protein construct |
US20230235298A1 (en) | 2020-06-01 | 2023-07-27 | Modernatx, Inc. | Phenylalanine hydroxylase variants and uses thereof |
AU2021286169A1 (en) | 2020-06-04 | 2023-01-19 | BioNTech SE | RNA replicon for versatile and efficient gene expression |
US20230234992A1 (en) | 2020-06-05 | 2023-07-27 | Glaxosmithkline Biologicals Sa | Modified betacoronavirus spike proteins |
US20230256090A1 (en) | 2020-06-29 | 2023-08-17 | Glaxosmithkline Biologicals Sa | Adjuvants |
JP2023535365A (ja) | 2020-07-16 | 2023-08-17 | アクイタス セラピューティクス インコーポレイテッド | 脂質ナノ粒子に使用するためのカチオン性脂質 |
CN116438308A (zh) | 2020-08-06 | 2023-07-14 | 磨石生物公司 | 多表位疫苗盒 |
WO2022104131A1 (en) | 2020-11-13 | 2022-05-19 | Modernatx, Inc. | Polynucleotides encoding cystic fibrosis transmembrane conductance regulator for the treatment of cystic fibrosis |
EP4008785A1 (en) | 2020-12-03 | 2022-06-08 | Justus-Liebig-Universität Gießen | Circular nucleic acids and uses thereof for interfering with genome expression and proliferation of coronaviruses |
KR20230164648A (ko) | 2020-12-22 | 2023-12-04 | 큐어백 에스이 | SARS-CoV-2 변이체에 대한 RNA 백신 |
WO2022137128A2 (en) | 2020-12-23 | 2022-06-30 | Glaxosmithkline Biologicals Sa | Self-amplifying messenger rna |
JP2024504614A (ja) * | 2021-01-14 | 2024-02-01 | トランスレイト バイオ, インコーポレイテッド | mRNAがコードする抗体を送達する方法および組成物 |
EP4032546A1 (en) | 2021-01-20 | 2022-07-27 | GlaxoSmithKline Biologicals S.A. | Therapeutic viral vaccine |
US11524023B2 (en) | 2021-02-19 | 2022-12-13 | Modernatx, Inc. | Lipid nanoparticle compositions and methods of formulating the same |
WO2022204371A1 (en) | 2021-03-24 | 2022-09-29 | Modernatx, Inc. | Lipid nanoparticles containing polynucleotides encoding glucose-6-phosphatase and uses thereof |
WO2022204380A1 (en) | 2021-03-24 | 2022-09-29 | Modernatx, Inc. | Lipid nanoparticles containing polynucleotides encoding propionyl-coa carboxylase alpha and beta subunits and uses thereof |
WO2022204369A1 (en) | 2021-03-24 | 2022-09-29 | Modernatx, Inc. | Polynucleotides encoding methylmalonyl-coa mutase for the treatment of methylmalonic acidemia |
JP2024512026A (ja) | 2021-03-24 | 2024-03-18 | モデルナティエックス 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の治療を目的とした脂質ナノ粒子及びオルニチントランスカルバミラーゼをコードするポリヌクレオチド |
WO2022204390A1 (en) | 2021-03-24 | 2022-09-29 | Modernatx, Inc. | Lipid nanoparticles containing polynucleotides encoding phenylalanine hydroxylase and uses thereof |
WO2022200574A1 (en) | 2021-03-26 | 2022-09-29 | Glaxosmithkline Biologicals Sa | Immunogenic compositions |
WO2022248353A1 (en) | 2021-05-24 | 2022-12-01 | Glaxosmithkline Biologicals Sa | Adjuvants |
EP4352247A1 (en) | 2021-06-09 | 2024-04-17 | GlaxoSmithKline Biologicals s.a. | Release assay for determining potency of self-amplifying rna drug product and methods for using |
WO2022266083A2 (en) | 2021-06-15 | 2022-12-22 | Modernatx, Inc. | Engineered polynucleotides for cell-type or microenvironment-specific expression |
WO2022271776A1 (en) | 2021-06-22 | 2022-12-29 | Modernatx, Inc. | Polynucleotides encoding uridine diphosphate glycosyltransferase 1 family, polypeptide a1 for the treatment of crigler-najjar syndrome |
EP4359527A2 (en) | 2021-06-23 | 2024-05-01 | Novartis AG | Compositions and methods for the treatment of hemoglobinopathies |
EP4367242A2 (en) | 2021-07-07 | 2024-05-15 | Omega Therapeutics, Inc. | Compositions and methods for modulating secreted frizzled receptor protein 1 (sfrp1) gene expression |
CA3171750A1 (en) | 2021-07-30 | 2023-02-02 | Tim SONNTAG | Mrnas for treatment or prophylaxis of liver diseases |
WO2023020992A1 (en) | 2021-08-16 | 2023-02-23 | Glaxosmithkline Biologicals Sa | Novel methods |
WO2023020993A1 (en) | 2021-08-16 | 2023-02-23 | Glaxosmithkline Biologicals Sa | Novel methods |
WO2023021421A1 (en) | 2021-08-16 | 2023-02-23 | Glaxosmithkline Biologicals Sa | Low-dose lyophilized rna vaccines and methods for preparing and using the same |
WO2023021427A1 (en) | 2021-08-16 | 2023-02-23 | Glaxosmithkline Biologicals Sa | Freeze-drying of lipid nanoparticles (lnps) encapsulating rna and formulations thereof |
WO2023020994A1 (en) | 2021-08-16 | 2023-02-23 | Glaxosmithkline Biologicals Sa | Novel methods |
WO2023031855A1 (en) | 2021-09-03 | 2023-03-09 | Glaxosmithkline Biologicals Sa | Substitution of nucleotide bases in self-amplifying messenger ribonucleic acids |
WO2023056044A1 (en) | 2021-10-01 | 2023-04-06 | Modernatx, Inc. | Polynucleotides encoding relaxin for the treatment of fibrosis and/or cardiovascular disease |
WO2023066875A1 (en) | 2021-10-18 | 2023-04-27 | BioNTech SE | Modified replicable rna and related compositions and their use |
WO2023066874A1 (en) | 2021-10-18 | 2023-04-27 | BioNTech SE | Methods for determining mutations for increasing modified replicable rna function and related compositions and their use |
WO2023135298A1 (en) | 2022-01-17 | 2023-07-20 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods of inducing cell death of a population of solid tumor cells |
WO2023144193A1 (en) | 2022-01-25 | 2023-08-03 | CureVac SE | Mrnas for treatment of hereditary tyrosinemia type i |
WO2023152365A1 (en) | 2022-02-14 | 2023-08-17 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of the 15-lipoxygenase for the treatment of lymphedema |
WO2023161350A1 (en) | 2022-02-24 | 2023-08-31 | Io Biotech Aps | Nucleotide delivery of cancer therapy |
WO2023183909A2 (en) | 2022-03-25 | 2023-09-28 | Modernatx, Inc. | Polynucleotides encoding fanconi anemia, complementation group proteins for the treatment of fanconi anemia |
WO2023213378A1 (en) | 2022-05-02 | 2023-11-09 | BioNTech SE | Replicon compositions and methods of using same for the treatment of diseases |
WO2023242817A2 (en) | 2022-06-18 | 2023-12-21 | Glaxosmithkline Biologicals Sa | Recombinant rna molecules comprising untranslated regions or segments encoding spike protein from the omicron strain of severe acute respiratory coronavirus-2 |
US11878055B1 (en) | 2022-06-26 | 2024-01-23 | BioNTech SE | Coronavirus vaccine |
WO2024017479A1 (en) | 2022-07-21 | 2024-01-25 | BioNTech SE | Multifunctional cells transiently expressing an immune receptor and one or more cytokines, their use and methods for their production |
WO2024023034A1 (en) | 2022-07-25 | 2024-02-01 | Institut National de la Santé et de la Recherche Médicale | Use of apelin for the treatment of lymphedema |
WO2024026254A1 (en) | 2022-07-26 | 2024-02-01 | Modernatx, Inc. | Engineered polynucleotides for temporal control of expression |
WO2024044147A1 (en) | 2022-08-23 | 2024-02-29 | Modernatx, Inc. | Methods for purification of ionizable lipids |
WO2024047247A1 (en) | 2022-09-02 | 2024-03-07 | Institut National de la Santé et de la Recherche Médicale | Base editing approaches for the treatment of amyotrophic lateral sclerosis |
WO2024056856A1 (en) | 2022-09-15 | 2024-03-21 | BioNTech SE | Systems and compositions comprising trans-amplifying rna vectors with mirna |
WO2024068545A1 (en) | 2022-09-26 | 2024-04-04 | Glaxosmithkline Biologicals Sa | Influenza virus vaccines |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001514857A (ja) * | 1997-09-04 | 2001-09-18 | コノート ラボラトリーズ リミテッド | Rna呼吸合包体ウイルスワクチン |
JP2008501729A (ja) * | 2004-06-07 | 2008-01-24 | 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 | カチオン性脂質および使用方法 |
WO2010042877A1 (en) * | 2008-10-09 | 2010-04-15 | Tekmira Pharmaceuticals Corporation | Improved amino lipids and methods for the delivery of nucleic acids |
Family Cites Families (240)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6090406A (en) | 1984-04-12 | 2000-07-18 | The Liposome Company, Inc. | Potentiation of immune responses with liposomal adjuvants |
US4853228A (en) | 1987-07-28 | 1989-08-01 | Micro-Pak, Inc. | Method of manufacturing unilamellar lipid vesicles |
WO1990011092A1 (en) | 1989-03-21 | 1990-10-04 | Vical, Inc. | Expression of exogenous polynucleotide sequences in a vertebrate |
US6867195B1 (en) | 1989-03-21 | 2005-03-15 | Vical Incorporated | Lipid-mediated polynucleotide administration to reduce likelihood of subject's becoming infected |
US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
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 |
FR2676072B1 (fr) | 1991-05-03 | 1994-11-18 | Transgene Sa | Vecteur de delivrance d'arn. |
US5693535A (en) | 1992-05-14 | 1997-12-02 | Ribozyme Pharmaceuticals, Inc. | HIV targeted ribozymes |
US5750390A (en) | 1992-08-26 | 1998-05-12 | Ribozyme Pharmaceuticals, Inc. | Method and reagent for treatment of diseases caused by expression of the bcl-2 gene |
AU4528493A (en) | 1992-06-04 | 1994-01-04 | Regents Of The University Of California, The | In vivo gene therapy with intron-free sequence of interest |
WO1994002595A1 (en) | 1992-07-17 | 1994-02-03 | Ribozyme Pharmaceuticals, Inc. | Method and reagent for treatment of animal diseases |
US5474914A (en) | 1992-07-29 | 1995-12-12 | Chiron Corporation | Method of producing secreted CMV glycoprotein H |
US20020102273A1 (en) | 1995-08-08 | 2002-08-01 | Robert B. Grieve | Use of alphavirus expression vectors to produce parasite anitgens |
WO1994027435A1 (en) | 1993-06-01 | 1994-12-08 | Life Technologies, Inc. | Genetic immunization with cationic lipids |
US6015686A (en) * | 1993-09-15 | 2000-01-18 | Chiron Viagene, Inc. | Eukaryotic layered vector initiation systems |
AU2215995A (en) | 1994-04-07 | 1995-10-30 | Akzo Nobel N.V. | Freeze-dried compositions comprising rna |
US5993850A (en) | 1994-09-13 | 1999-11-30 | Skyepharma Inc. | Preparation of multivesicular liposomes for controlled release of encapsulated biologically active substances |
US5885613A (en) * | 1994-09-30 | 1999-03-23 | The University Of British Columbia | Bilayer stabilizing components and their use in forming programmable fusogenic liposomes |
AU4594996A (en) | 1994-11-30 | 1996-06-19 | Chiron Viagene, Inc. | Recombinant alphavirus vectors |
US5965434A (en) | 1994-12-29 | 1999-10-12 | Wolff; Jon A. | Amphipathic PH sensitive compounds and delivery systems for delivering biologically active compounds |
US5792462A (en) | 1995-05-23 | 1998-08-11 | University Of North Carolina At Chapel Hill | Alphavirus RNA replicon systems |
US5981501A (en) | 1995-06-07 | 1999-11-09 | Inex Pharmaceuticals Corp. | Methods for encapsulating plasmids in lipid bilayers |
US7422902B1 (en) | 1995-06-07 | 2008-09-09 | The University Of British Columbia | Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer |
AU727923B2 (en) | 1995-09-27 | 2001-01-04 | Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Production of infectious respiratory syncytial virus from cloned nucleotide sequences |
CA2244110A1 (en) | 1996-02-12 | 1997-08-14 | Cobra Therapeutics Limited | Novel methods of vaccination and vaccines thereof comprising a nucleic acid encoding a first epitope and a peptide containing a second epitope |
DE19605548A1 (de) | 1996-02-15 | 1997-09-04 | Boehringer Ingelheim Int | Zusammensetzung für die Transfektion höherer eukaryotischer Zellen |
US6451592B1 (en) | 1996-04-05 | 2002-09-17 | Chiron Corporation | Recombinant alphavirus-based vectors with reduced inhibition of cellular macromolecular synthesis |
CA2259179C (en) | 1996-07-03 | 2008-09-23 | University Of Pittsburgh | Emulsion formulations for hydrophilic active agents |
WO1998010748A1 (en) | 1996-09-13 | 1998-03-19 | The School Of Pharmacy | Liposomes |
US7384923B2 (en) | 1999-05-14 | 2008-06-10 | Lipoxen Technologies Limited | Liposomes |
US6395302B1 (en) | 1996-11-19 | 2002-05-28 | Octoplus B.V. | Method for the preparation of microspheres which contain colloidal systems |
DE69841002D1 (de) | 1997-05-14 | 2009-09-03 | Univ British Columbia | Hochwirksame verkapselung von nukleinsäuren in lipidvesikeln |
US6048546A (en) * | 1997-07-31 | 2000-04-11 | Sandia Corporation | Immobilized lipid-bilayer materials |
JP2002500003A (ja) | 1997-11-28 | 2002-01-08 | ザ・クラウン・イン・ザ・ライト・オヴ・ザ・クイーンズランド・デパートメント・オヴ・ヘルス | フラビウイルスの発現および送達のシステム |
US6009406A (en) | 1997-12-05 | 1999-12-28 | Square D Company | Methodology and computer-based tools for re-engineering a custom-engineered product line |
GB9726555D0 (en) | 1997-12-16 | 1998-02-11 | Smithkline Beecham Plc | Vaccine |
US6432925B1 (en) | 1998-04-16 | 2002-08-13 | John Wayne Cancer Institute | RNA cancer vaccine and methods for its use |
EP2311436A1 (en) | 1998-04-27 | 2011-04-20 | Altus Pharmaceuticals Inc. | Stabilized protein crystals, formulations containing them and methods of making them |
US6517842B1 (en) | 1998-06-29 | 2003-02-11 | The United States Of America As Represented By The Secretary Of The Army | Marburg virus vaccines |
CA2335393C (en) | 1998-07-20 | 2008-09-23 | Inex Pharmaceuticals Corporation | Liposomal encapsulated nucleic acid-complexes |
WO2000039302A2 (en) | 1998-12-31 | 2000-07-06 | Chiron Corporation | Improved expression of hiv polypeptides and production of virus-like particles |
EP1541690A3 (en) | 1999-09-09 | 2005-07-27 | CureVac GmbH | Transfer of mRNA using polycationic compounds |
TR200503031T2 (tr) * | 1999-09-25 | 2005-09-21 | University Of Iowa Research Foundation | İmmünostimülatör nükleik asitler |
EP1222289B1 (en) | 1999-10-20 | 2008-04-16 | The Johns Hopkins University School Of Medicine | Chimeric immunogenic compositions and nucleic acids encoding them |
US8541008B2 (en) | 1999-11-19 | 2013-09-24 | Los Angeles Biomedical Research Institute At Harbor-Ucla Medical Center | Pharmaceutical compositions and methods to vaccinate against candidiasis |
US20030212022A1 (en) | 2001-03-23 | 2003-11-13 | Jean-Marie Vogel | Compositions and methods for gene therapy |
EP1287015A1 (en) | 2000-04-18 | 2003-03-05 | Human Genome Sciences, Inc. | Extracellular matrix polynucleotides, polypeptides, and antibodies |
AU2001275423B2 (en) | 2000-06-09 | 2007-01-11 | Regulon, Inc. | Encapsulation of polynucleotides and drugs into targeted liposomes |
ATE440861T1 (de) | 2000-07-03 | 2009-09-15 | Novartis Vaccines & Diagnostic | Immunisierung gegen chlamydia pneumoniae |
AU2001290520A1 (en) | 2000-08-01 | 2002-02-13 | The Johns Hokpins University | Intercellular transport protein linked to an antigen as a molecular vaccine |
US20040142474A1 (en) | 2000-09-14 | 2004-07-22 | Expression Genetics, Inc. | Novel cationic lipopolymer as a biocompatible gene delivery agent |
CA2421683C (en) | 2000-09-28 | 2009-09-15 | Chiron Corporation | Microparticles for delivery of the heterologous nucleic acids |
MXPA03003690A (es) | 2000-10-27 | 2004-05-05 | Chiron Spa | Acidos nucleicos y proteinas de los grupos a y b de estreptococos. |
WO2002079239A2 (en) | 2001-01-31 | 2002-10-10 | U.S. Army Medical Research Institute Of Infectious Diseases | Chimeric filovirus glycoprotein |
WO2002061113A2 (en) | 2001-02-01 | 2002-08-08 | The Johns Hopkins University | Nucleic acid derived vaccine that encodes an antigen linked to a polypeptide that promotes antigen presentation |
US20030040498A1 (en) | 2001-03-14 | 2003-02-27 | Ansardi David Calvert | Oncolytic RNA replicons |
WO2002074920A2 (en) | 2001-03-16 | 2002-09-26 | Johns Hopkins University | A replication-defective alphavirus vaccine linking antigen with an immunogenicity-potentiating polypeptide and a method of delivery the same |
JP2004535388A (ja) * | 2001-04-30 | 2004-11-25 | ターゲティッド ジェネティクス コーポレイション | 脂質含有薬物送達複合体およびそれらの生成方法 |
US20030077251A1 (en) | 2001-05-23 | 2003-04-24 | Nicolas Escriou | Replicons derived from positive strand RNA virus genomes useful for the production of heterologous proteins |
EP2305699B1 (de) | 2001-06-05 | 2014-08-13 | CureVac GmbH | Stabilisierte mRNA mit erhöhtem G/C-Gehalt und optimierter Codon Usage für die Impfung gegen Schlafkrankheit, Leishmaniose und Toxoplasmose |
CA2458854A1 (en) | 2001-08-31 | 2003-03-06 | Chiron Srl | Helicobacter pylori vaccination |
DE60233061D1 (de) | 2001-09-06 | 2009-09-03 | Alphavax Inc | Alphavirus replikon-vektorsysteme |
AU2003211103A1 (en) | 2002-02-13 | 2003-09-04 | Northeastern University | Intracellular delivery of therapeutic agents |
DE10207177A1 (de) | 2002-02-19 | 2003-09-04 | Novosom Ag | Fakultativ kationische Lipide |
ATE485031T1 (de) | 2002-06-28 | 2010-11-15 | Protiva Biotherapeutics Inc | Verfahren und vorrichtung zur herstellung von liposomen |
AU2003244855A1 (en) | 2002-07-05 | 2004-01-23 | Lipoxen Technologies Limited | Method to enhance an immune response of nucleic acid vaccination |
EP1530585A2 (en) | 2002-08-22 | 2005-05-18 | Cytos Biotechnology AG | Inducible alphaviral/orip based gene expression system |
CA2498777C (en) | 2002-09-13 | 2015-01-13 | Replicor, Inc. | Non-sequence complementary antiviral oligonucleotides |
ES2618309T3 (es) | 2002-12-13 | 2017-06-21 | Alphavax, Inc. | Partículas de replicón de alfavirus multi-antigénico y métodos |
DE60333035D1 (de) | 2002-12-23 | 2010-07-29 | Vical Inc | Impfstoffe gegen infektionen mit dem humanen zytomegalivirus auf grundlage von codonoptimierten polynukleotiden |
WO2004069148A2 (en) | 2003-02-04 | 2004-08-19 | Bar-Ilan University | Snornai-small nucleolar rna degradation by rna interference in trypanosomatids |
US20040228842A1 (en) | 2003-02-27 | 2004-11-18 | Shan Lu | Compositions and methods for cytomegalovirus treatment |
KR101454842B1 (ko) | 2003-03-20 | 2014-11-04 | 알파벡스, 인크. | 개선된 알파바이러스 레플리콘 및 헬퍼 구축물 |
US7731967B2 (en) | 2003-04-30 | 2010-06-08 | Novartis Vaccines And Diagnostics, Inc. | Compositions for inducing immune responses |
US20070042979A1 (en) | 2003-05-30 | 2007-02-22 | Junichi Yano | Oligonucleic acid-bearing composite and pharmaceutical composition containing the composite |
US20100255002A1 (en) | 2003-06-26 | 2010-10-07 | Chiron Corporation | Immunogenic compositions for chlamydia trachomatis |
AU2004257214B2 (en) | 2003-07-11 | 2010-04-22 | Alphavax, Inc. | Alphavirus-based cytomegalovirus vaccines |
US7368537B2 (en) | 2003-07-15 | 2008-05-06 | Id Biomedical Corporation Of Quebec | Subunit vaccine against respiratory syncytial virus infection |
EP2567693B1 (en) | 2003-07-16 | 2015-10-21 | Protiva Biotherapeutics Inc. | Lipid encapsulated interfering RNA |
EP1648500B1 (en) | 2003-07-31 | 2014-07-09 | Novartis Vaccines and Diagnostics, Inc. | Immunogenic compositions for streptococcus pyogenes |
EP1512393A1 (de) | 2003-09-08 | 2005-03-09 | BOEHRINGER INGELHEIM PHARMA GMBH & CO. KG | Verfahren zur Herstellung von homogenen Liposomen und Lipoplexen |
WO2005046621A2 (en) | 2003-11-12 | 2005-05-26 | The United States Of America As Represented By The Secretary Of The Navy | Enhancement of vaccine-induced immune responses and protection by heterologous boosting with alphavirus replicon vaccines |
US7303881B2 (en) | 2004-04-30 | 2007-12-04 | Pds Biotechnology Corporation | Antigen delivery compositions and methods of use |
GB0410866D0 (en) | 2004-05-14 | 2004-06-16 | Chiron Srl | Haemophilius influenzae |
AU2005248361B2 (en) | 2004-05-18 | 2010-03-11 | Vical Incorporated | Influenza virus vaccine composition and methods of use |
US20050266550A1 (en) | 2004-05-18 | 2005-12-01 | Alphavax, Inc. | TC-83-derived alphavirus vectors, particles and methods |
EP2811027A1 (en) | 2004-05-21 | 2014-12-10 | Novartis Vaccines and Diagnostics, Inc. | Alphavirus vectors for RSV and PIV vaccines |
GB0411428D0 (en) | 2004-05-21 | 2004-06-23 | Got A Gene Ab | Vectors |
US7799565B2 (en) | 2004-06-07 | 2010-09-21 | Protiva Biotherapeutics, Inc. | Lipid encapsulated interfering RNA |
CA2572921C (en) | 2004-07-09 | 2017-01-03 | The University Of North Carolina At Chapel Hill | Replication-competent and propagation-defective venezuelan equine encephalitis (vee) viral adjuvants |
US20060051405A1 (en) | 2004-07-19 | 2006-03-09 | Protiva Biotherapeutics, Inc. | Compositions for the delivery of therapeutic agents and uses thereof |
WO2006038129A2 (en) | 2004-10-01 | 2006-04-13 | Novartis Vaccines And Diagnostics Srl | Hepatitis c virus replication system |
US20060159737A1 (en) | 2004-11-19 | 2006-07-20 | Steffen Panzner | Pharmaceutical compositions for local administration |
GB2421025A (en) | 2004-12-09 | 2006-06-14 | Oxxon Therapeutics Ltd | HSV vaccination vectors |
CA2597724A1 (en) | 2005-02-14 | 2007-08-02 | Sirna Therapeutics, Inc. | Cationic lipids and formulated molecular compositions containing them |
US7404969B2 (en) | 2005-02-14 | 2008-07-29 | Sirna Therapeutics, Inc. | Lipid nanoparticle based compositions and methods for the delivery of biologically active molecules |
CN101203529A (zh) | 2005-02-18 | 2008-06-18 | 诺华疫苗和诊断公司 | 来自脑膜炎/脓毒症相关性大肠杆菌的蛋白质和核酸 |
SG160329A1 (en) | 2005-02-18 | 2010-04-29 | Novartis Vaccines & Diagnostic | Proteins and nucleic acids from meningitis/sepsis-associated escherichia coli |
WO2006092607A1 (en) | 2005-03-02 | 2006-09-08 | The Secretary Of State For Defence | Pharmaceutical composition |
GB0504436D0 (en) | 2005-03-03 | 2005-04-06 | Glaxosmithkline Biolog Sa | Vaccine |
EP1871888A4 (en) | 2005-03-30 | 2013-08-21 | Novartis Vaccines & Diagnostic | HAEMOPHILUS INFLUENZAE TYPE B |
US7618393B2 (en) | 2005-05-03 | 2009-11-17 | Pharmajet, Inc. | Needle-less injector and method of fluid delivery |
WO2006138004A2 (en) | 2005-05-12 | 2006-12-28 | Novartis Vaccines And Diagnostics, Inc. | Immunogenic compositions for chlamydia trachomatis |
US8703095B2 (en) | 2005-07-07 | 2014-04-22 | Sanofi Pasteur S.A. | Immuno-adjuvant emulsion |
WO2007014754A1 (en) | 2005-08-02 | 2007-02-08 | I.D.M. Immuno-Designed Molecules | Process for the preparation of liposomal formulations |
US7951384B2 (en) | 2005-08-05 | 2011-05-31 | University Of Massachusetts | Virus-like particles as vaccines for paramyxovirus |
DK2578685T3 (da) | 2005-08-23 | 2019-06-03 | Univ Pennsylvania | Rna indeholende modificerede nukleosider og fremgangsmåder til anvendelse deraf |
EP1764089A1 (en) | 2005-09-15 | 2007-03-21 | Novosom AG | Serum stable liposomes comprising amphoter II lipid mixtures |
DE102005046490A1 (de) | 2005-09-28 | 2007-03-29 | Johannes-Gutenberg-Universität Mainz | Modifikationen von RNA, die zu einer erhöhten Transkriptstabilität und Translationseffizienz führen |
DK1940826T3 (da) | 2005-09-29 | 2011-04-18 | Elan Pharm Inc | Pyrimidinylamidforbindelser, der inhiberer leukocytadhæsion medieret gennem BLA-4 |
JP2009511636A (ja) | 2005-10-18 | 2009-03-19 | ノバルティス ヴァクシンズ アンド ダイアグノスティクス, インコーポレイテッド | アルファウイルスレプリコン粒子による粘膜免疫および全身免疫 |
JP2007112768A (ja) | 2005-10-24 | 2007-05-10 | Kyoto Univ | 肝指向性リポソーム組成物 |
JP2009515831A (ja) | 2005-10-25 | 2009-04-16 | ノバルティス ヴァクシンズ アンド ダイアグノスティクス エスアールエル | ペスト菌(Yersiniapestis)抗原を含む組成物 |
JP5215865B2 (ja) | 2005-11-22 | 2013-06-19 | ノバルティス ヴァクシンズ アンド ダイアグノスティクス インコーポレイテッド | ノロウイルス抗原およびサポウイルス抗原 |
US9393215B2 (en) | 2005-12-02 | 2016-07-19 | Novartis Ag | Nanoparticles for use in immunogenic compositions |
EP2004141A2 (en) | 2006-03-17 | 2008-12-24 | Novosom AG | An efficient method for loading amphoteric liposomes with nucleic acid active substances |
CA2654563A1 (en) | 2006-06-07 | 2007-12-21 | The Trustees Of Princeton University | Cytomegalovirus surface protein complex for use in vaccines and as a drug target |
US7915399B2 (en) | 2006-06-09 | 2011-03-29 | Protiva Biotherapeutics, Inc. | Modified siRNA molecules and uses thereof |
WO2007149518A2 (en) | 2006-06-21 | 2007-12-27 | The Scripps Research Institute | Dna composition against tumor stromal antigen fap and methods of use thereof |
EP2064230A2 (en) | 2006-08-16 | 2009-06-03 | Novartis AG | Immunogens from uropathogenic escherichia coli |
US20090022760A1 (en) | 2006-09-12 | 2009-01-22 | Alphavax | Alphavirus Replicon Particles Matched to Protein Antigens as Immunological Adjuvants |
DE102007001370A1 (de) | 2007-01-09 | 2008-07-10 | Curevac Gmbh | RNA-kodierte Antikörper |
CA2689042A1 (en) | 2007-02-16 | 2008-08-28 | Merck & Co., Inc. | Compositions and methods for potentiated activity of biologicaly active molecules |
US20100196492A1 (en) | 2007-03-08 | 2010-08-05 | Green Jordan J | Electrostatic coating of particles for drug delivery |
US8877206B2 (en) | 2007-03-22 | 2014-11-04 | Pds Biotechnology Corporation | Stimulation of an immune response by cationic lipids |
AP2014007971A0 (en) | 2007-03-29 | 2014-09-30 | Alnylam Pharmaceuticals Inc | Compositions and methods for inhibiting expressionof a gene from the ebola |
US8748591B2 (en) | 2007-04-17 | 2014-06-10 | The Board Of Regents Of The University Of Texas System | Chimeric sindbis-western equine encephalitis virus and uses thereof |
AU2008247488B2 (en) | 2007-05-04 | 2014-02-27 | Marina Biotech, Inc. | Amino acid lipids and uses thereof |
WO2008148068A1 (en) | 2007-05-23 | 2008-12-04 | Mannkind Corporation | Multicistronic vectors and methods for their design |
DE102007029471A1 (de) | 2007-06-20 | 2008-12-24 | Novosom Ag | Neue fakultativ kationische Sterole |
WO2008156829A2 (en) | 2007-06-21 | 2008-12-24 | Alphavax, Inc. | Promoterless cassettes for expression of alphavirus structural proteins |
US8202518B2 (en) | 2007-07-04 | 2012-06-19 | Ribovax Biotechnologies S.A. | Antibodies against human cytomegalovirus (HCMV) |
GB0714963D0 (en) | 2007-08-01 | 2007-09-12 | Novartis Ag | Compositions comprising antigens |
US20110177155A1 (en) | 2007-08-21 | 2011-07-21 | Immune Disease Institute, Inc. | Methods of delivery of agents to leukocytes and endothelial cells |
GB0717187D0 (en) | 2007-09-04 | 2007-10-17 | Novartis Ag | Compositions comprising yersinia pestis antigens |
US20090162395A1 (en) | 2007-09-26 | 2009-06-25 | Crowe Jr James E | Vaccine for rsv and mpv |
EP2042193A1 (en) * | 2007-09-28 | 2009-04-01 | Biomay AG | RNA Vaccines |
WO2009079185A2 (en) | 2007-11-26 | 2009-06-25 | Novartis Vaccines And Diagnostics, Inc. | Methods of generating alphavirus particles |
EP2067749A1 (en) | 2007-11-29 | 2009-06-10 | Total Petrochemicals France | Process for purification of an aqueous phase containing polyaromatics |
WO2009074861A2 (en) | 2007-12-10 | 2009-06-18 | Powderject Research Limited | Improved vaccine |
WO2009086558A1 (en) | 2008-01-02 | 2009-07-09 | Tekmira Pharmaceuticals Corporation | Improved compositions and methods for the delivery of nucleic acids |
WO2009111088A2 (en) | 2008-01-02 | 2009-09-11 | The Johns Hopkins University | Antitumor immunization by liposomal delivery of vaccine to the spleen |
ITMI20081249A1 (it) | 2008-07-09 | 2010-01-09 | Novartis Vaccines & Diagnostic | Immunogeni di escherichia coli con solubilità migliorata. |
US20110110857A1 (en) | 2008-03-06 | 2011-05-12 | Roberto Petracca | Mutant forms of chlamydia htra |
WO2009127060A1 (en) | 2008-04-15 | 2009-10-22 | Protiva Biotherapeutics, Inc. | Novel lipid formulations for nucleic acid delivery |
WO2009127230A1 (en) | 2008-04-16 | 2009-10-22 | Curevac Gmbh | MODIFIED (m)RNA FOR SUPPRESSING OR AVOIDING AN IMMUNOSTIMULATORY RESPONSE AND IMMUNOSUPPRESSIVE COMPOSITION |
WO2009132131A1 (en) | 2008-04-22 | 2009-10-29 | Alnylam Pharmaceuticals, Inc. | Amino lipid based improved lipid formulation |
WO2009132206A1 (en) | 2008-04-25 | 2009-10-29 | Liquidia Technologies, Inc. | Compositions and methods for intracellular delivery and release of cargo |
US20100040650A1 (en) | 2008-05-30 | 2010-02-18 | Crowe Jr James E | Virus-Like paramyxovirus particles and vaccines |
EP2130912A1 (en) | 2008-06-04 | 2009-12-09 | Institut für Viruskrankeiten und Immunprophylaxe | Pestivirus replicons providing an RNA-based viral vector system |
US20110229969A1 (en) | 2008-06-25 | 2011-09-22 | Volker Sandig | Cell Line for Propagation of Highly Attenuated AlphaViruses |
WO2009156852A1 (en) | 2008-06-25 | 2009-12-30 | Novartis Ag | Rapid responses to delayed booster immunisations |
SG10201608381SA (en) | 2008-07-16 | 2016-11-29 | Inst Research In Biomedicine | Human cytomegalovirus neutralizing antibodies and use thereof |
JP5475774B2 (ja) | 2008-07-16 | 2014-04-16 | インスティテュート フォー リサーチ イン バイオメディシン | ヒトサイトメガロウイルス中和抗体およびその使用 |
JP2010025644A (ja) * | 2008-07-16 | 2010-02-04 | Kochi Univ Of Technology | 硝酸イオンの呈色試薬並びにこれを用いた硝酸イオンの検出及び定量方法 |
CA2733147A1 (en) | 2008-08-06 | 2010-02-11 | Novartis Ag | Microparticles for use in immunogenic compositions |
CL2008002322A1 (es) * | 2008-08-07 | 2009-06-05 | Univ Concepcion | Formulacion farmaceutica veterinaria que comprende un sistema vectorial viral constituido por una particula recombinante de arn que codifica una cu/zn superoxido dismutasa de la bacteria patogena de bovinos brucella abortus, y al menos un alfavirus arn perteneciente a la familia del virus semliki forest (sfv), util como vacuna. |
US8557292B2 (en) | 2008-08-13 | 2013-10-15 | California Institute Of Technology | Carrier nanoparticles and related compositions, methods and systems |
WO2010036948A2 (en) | 2008-09-26 | 2010-04-01 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Dna prime/inactivated vaccine boost immunization to influenza virus |
MX2011004859A (es) | 2008-11-07 | 2011-08-03 | Massachusetts Inst Technology | Lipidoides de aminoalcohol y usos de los mismos. |
EP3238738B1 (en) | 2008-11-10 | 2020-09-23 | Arbutus Biopharma Corporation | Novel lipids and compositions for the delivery of therapeutics |
EP2367844A4 (en) | 2008-11-18 | 2012-08-01 | Ligocyte Pharmaceuticals Inc | RSV-F VLP AND MANUFACTURING METHOD AND METHOD OF USE THEREOF |
CA2751342C (en) | 2009-01-29 | 2019-05-07 | Alnylam Pharmaceuticals, Inc. | Lipid formulations comprising cationic lipid and a targeting lipid comprising n-acetyl galactosamine for delivery of nucleic acid |
EP3263128A3 (en) | 2009-04-14 | 2018-01-24 | GlaxoSmithKline Biologicals S.A. | Compositions for immunising against staphylococcus aureus |
EP2416652B1 (en) | 2009-05-05 | 2018-11-07 | Arbutus Biopharma Corporation | Methods of delivering oligonucleotides to immune cells |
SI3431076T1 (sl) | 2009-06-10 | 2022-04-29 | Arbutus Biopharma Corporation | Izboljšana lipidna formulacija |
CA2767127A1 (en) | 2009-07-01 | 2011-01-06 | Protiva Biotherapeutics, Inc. | Novel lipid formulations for delivery of therapeutic agents to solid tumors |
US20120100207A1 (en) | 2009-07-02 | 2012-04-26 | Konica Minolta Holdings, Inc. | Process for producing liposomes by two-step emulsification method utilizing outer aqueous phase containing specific dispersing agent, process for producing liposome dispersion or dry powder thereof using the process for producing liposomes, and liposome dispersion or dry powder thereof produced thereby |
EP2451475A2 (en) | 2009-07-06 | 2012-05-16 | Novartis AG | Self replicating rna molecules and uses thereof |
WO2011008974A2 (en) | 2009-07-15 | 2011-01-20 | Novartis Ag | Rsv f protein compositions and methods for making same |
EP2453914B1 (en) | 2009-07-16 | 2018-09-05 | Vaxil Biotherapeutics Ltd. | Antigen specific multi epitope -based anti-infective vaccines |
CN102695525B (zh) | 2009-07-31 | 2016-01-20 | 埃泽瑞斯公司 | 用于蛋白质表达的具有未修饰和修饰核苷酸的组合的rna |
JO3257B1 (ar) | 2009-09-02 | 2018-09-16 | Novartis Ag | مركبات وتركيبات كمعدلات لفاعلية tlr |
ES2443952T3 (es) | 2009-09-02 | 2014-02-21 | Novartis Ag | Composiciones inmunógenas que incluyen moduladores de la actividad de TLR |
US20110070260A1 (en) | 2009-09-09 | 2011-03-24 | Baric Ralph S | Multivalent Immunogenic Compositions Against Noroviruses and Methods of Use |
SG181488A1 (en) | 2009-11-04 | 2012-07-30 | Marina Biotech Inc | Activity generating delivery molecules |
WO2011140627A1 (en) | 2009-11-04 | 2011-11-17 | The University Of British Columbia | Nucleic acid-containing lipid particles and related methods |
US20110112353A1 (en) | 2009-11-09 | 2011-05-12 | Circulite, Inc. | Bifurcated outflow cannulae |
PT2506857T (pt) | 2009-12-01 | 2018-05-14 | Translate Bio Inc | Entrega de arnm para o acréscimo de proteínas e enzimas em doenças genéticas humanas |
SI3112467T1 (en) | 2009-12-07 | 2018-06-29 | The Trustees Of The University Of Pennsylvania | RNA preparations comprising purified modified RNA for reprogramming cells |
EP3296398A1 (en) | 2009-12-07 | 2018-03-21 | Arbutus Biopharma Corporation | Compositions for nucleic acid delivery |
AU2010330814B2 (en) | 2009-12-18 | 2017-01-12 | Acuitas Therapeutics Inc. | Methods and compositions for delivery of nucleic acids |
SG181904A1 (en) | 2009-12-23 | 2012-07-30 | Novartis Ag | Lipids, lipid compositions, and methods of using them |
CA2787598A1 (en) | 2010-01-24 | 2012-06-21 | Novartis Ag | Irradiated biodegradable polymer microparticles |
DK2544693T3 (en) | 2010-03-09 | 2017-12-04 | Biomedical Res Models Inc | Hitherto UNKNOWN ACCESS TO VACCINATION THROUGH MILKHINDER AGAINST HERPES SIMPLEX VIRUS TYPE-2 |
WO2011127316A1 (en) | 2010-04-07 | 2011-10-13 | Novartis Ag | Method for generating a parvovirus b19 virus-like particle |
ES2770335T3 (es) | 2010-07-06 | 2020-07-01 | Glaxosmithkline Biologicals Sa | Administración de ARN para desencadenar múltiples vías inmunológicas |
WO2012006369A2 (en) | 2010-07-06 | 2012-01-12 | Novartis Ag | Immunisation of large mammals with low doses of rna |
CA2804494A1 (en) | 2010-07-06 | 2012-01-12 | Novartis Ag | Virion-like delivery particles for self-replicating rna molecules |
US9192661B2 (en) | 2010-07-06 | 2015-11-24 | Novartis Ag | Delivery of self-replicating RNA using biodegradable polymer particles |
US9770463B2 (en) | 2010-07-06 | 2017-09-26 | Glaxosmithkline Biologicals Sa | Delivery of RNA to different cell types |
PL2590626T3 (pl) | 2010-07-06 | 2016-04-29 | Glaxosmithkline Biologicals Sa | Liposomy z lipidami o korzystnej wartości pka do dostarczania rna |
MX343410B (es) | 2010-07-06 | 2016-11-04 | Novartis Ag * | Emulsiones cationicas de agua en aceite. |
EP3153578A1 (en) | 2010-07-06 | 2017-04-12 | Novartis Ag | Norovirus derived immunogenic compositions and methods |
US8898852B2 (en) | 2010-08-04 | 2014-12-02 | Honeywell International Inc. | Air burst to clear detection window |
EP2600901B1 (en) | 2010-08-06 | 2019-03-27 | ModernaTX, Inc. | A pharmaceutical formulation comprising engineered nucleic acids and medical use thereof |
LT3981427T (lt) | 2010-08-31 | 2022-08-10 | Glaxosmithkline Biologicals S.A. | Pegilintos liposomos, skirtos imunogeną koduojančios rnr pristatymui |
HRP20221048T1 (hr) | 2010-08-31 | 2022-11-11 | Glaxosmithkline Biologicals Sa | Mali liposomi za isporuku rna koja kodira imunogen |
ES2727583T3 (es) | 2010-08-31 | 2019-10-17 | Glaxosmithkline Biologicals Sa | Lípidos adecuados para la administración liposómica de ARN que codifica proteínas |
EP2614072A4 (en) | 2010-09-09 | 2014-03-19 | Univ Virginia Commonwealth | VACCINE AGAINST THE HUMAN CYTOMEGALOVIRUS |
ES2737960T3 (es) | 2010-10-01 | 2020-01-17 | Modernatx Inc | Nucleósidos, nucleótidos y ácidos nucleicos modificados y sus usos |
MX363307B (es) | 2010-10-11 | 2019-03-20 | Novartis Ag Star | Plataformas para suministro de antigenos. |
SG189990A1 (en) | 2010-10-25 | 2013-06-28 | Stepan Co | Quaternized fatty amines, amidoamines, and their derivatives from natural oil metathesis |
HUE043879T2 (hu) | 2011-01-26 | 2019-09-30 | Glaxosmithkline Biologicals Sa | RSV-immunizálási rend |
KR20140007404A (ko) | 2011-01-31 | 2014-01-17 | 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 | 신규 허피스 항원을 암호화하는 핵산 분자, 이것을 포함하는 백신 및 이것의 사용 방법 |
WO2012116714A1 (en) | 2011-03-02 | 2012-09-07 | Curevac Gmbh | Vaccination in elderly patients |
AU2012236099A1 (en) | 2011-03-31 | 2013-10-03 | Moderna Therapeutics, Inc. | Delivery and formulation of engineered nucleic acids |
DK3275892T3 (da) | 2011-05-13 | 2020-04-06 | Glaxosmithkline Biologicals Sa | Præfusions-rsv-f-antigener |
WO2012158736A1 (en) | 2011-05-17 | 2012-11-22 | modeRNA Therapeutics | Engineered nucleic acids and methods of use thereof for non-human vertebrates |
CA2838063C (en) | 2011-06-08 | 2023-07-11 | Shire Human Genetic Therapies, Inc. | Cleavable lipids |
US11058762B2 (en) | 2011-07-06 | 2021-07-13 | Glaxosmithkline Biologicals Sa | Immunogenic compositions and uses thereof |
CA2840989A1 (en) | 2011-07-06 | 2013-01-10 | Novartis Ag | Immunogenic combination compositions and uses thereof |
WO2013006837A1 (en) | 2011-07-06 | 2013-01-10 | Novartis Ag | Cationic oil-in-water emulsions |
EP3424495A1 (en) | 2011-07-06 | 2019-01-09 | GlaxoSmithKline Biologicals S.A. | Oil-in-water emulsions that contain nucleic acids |
EP2729126B1 (en) | 2011-07-06 | 2020-12-23 | GlaxoSmithKline Biologicals SA | Liposomes having useful n:p ratio for delivery of rna molecules |
RU2628705C2 (ru) | 2011-08-31 | 2017-08-21 | Новартис Аг | Пегилированные липосомы для доставки кодирующей иммуноген рнк |
EP3384938A1 (en) | 2011-09-12 | 2018-10-10 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
EP3682905B1 (en) | 2011-10-03 | 2021-12-01 | ModernaTX, Inc. | Modified nucleosides, nucleotides, and nucleic acids, and uses thereof |
BR112014008694A2 (pt) | 2011-10-11 | 2017-06-20 | Novartis Ag | moléculas de ácido nucleico policistrônico recombinante |
EP2766385A2 (en) | 2011-10-12 | 2014-08-20 | Novartis AG | Cmv antigens and uses thereof |
WO2013130161A1 (en) | 2011-12-14 | 2013-09-06 | modeRNA Therapeutics | Methods of responding to a biothreat |
EP2791160B1 (en) | 2011-12-16 | 2022-03-02 | ModernaTX, Inc. | Modified mrna compositions |
RU2014129863A (ru) | 2011-12-21 | 2016-02-10 | Модерна Терапьютикс, Инк. | Способы повышения жизнеспособности или увеличения продолжительности жизни органа или экспланта органа |
AU2013243948A1 (en) | 2012-04-02 | 2014-10-30 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of proteins associated with human disease |
AU2013243949A1 (en) | 2012-04-02 | 2014-10-30 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of biologics and proteins associated with human disease |
EP4074834A1 (en) | 2012-11-26 | 2022-10-19 | ModernaTX, Inc. | Terminally modified rna |
CN109045294A (zh) | 2013-01-10 | 2018-12-21 | 思齐乐 | 流感病毒免疫原性组合物及其应用 |
US9504747B2 (en) | 2013-03-08 | 2016-11-29 | Novartis Ag | Lipids and lipid compositions for the delivery of active agents |
WO2014160243A1 (en) | 2013-03-14 | 2014-10-02 | The Trustees Of The University Of Pennsylvania | Purification and purity assessment of rna molecules synthesized with modified nucleosides |
US10258698B2 (en) | 2013-03-14 | 2019-04-16 | Modernatx, Inc. | Formulation and delivery of modified nucleoside, nucleotide, and nucleic acid compositions |
US8980864B2 (en) | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
PL3083556T3 (pl) | 2013-12-19 | 2020-06-29 | Novartis Ag | Lipidy i kompozycje lipidowe dla dostarczania środków czynnych |
PT3350157T (pt) | 2015-09-17 | 2022-03-18 | Modernatx Inc | Compostos e composições para administração intracelular de agentes terapêuticos |
PL3368507T3 (pl) | 2015-10-28 | 2023-03-27 | Acuitas Therapeutics Inc. | Nowe preparaty lipidów i nanocząstek lipidowych do dostarczania kwasów nukleinowych |
WO2018089790A1 (en) | 2016-11-10 | 2018-05-17 | Translate Bio, Inc. | Improved ice-based lipid nanoparticle formulation for delivery of mrna |
US11045540B2 (en) | 2017-03-15 | 2021-06-29 | Modernatx, Inc. | Varicella zoster virus (VZV) vaccine |
EP3883592A1 (en) | 2018-11-21 | 2021-09-29 | Translate Bio, Inc. | Treatment of cystic fibrosis by delivery of nebulized mrna encoding cftr |
US20230172858A1 (en) | 2019-08-30 | 2023-06-08 | Glaxosmithkline Biologicals Sa | Jet mixing lipid nanoparticle manufacturing process |
WO2022137133A1 (en) | 2020-12-22 | 2022-06-30 | Curevac Ag | Rna vaccine against sars-cov-2 variants |
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001514857A (ja) * | 1997-09-04 | 2001-09-18 | コノート ラボラトリーズ リミテッド | Rna呼吸合包体ウイルスワクチン |
JP2008501729A (ja) * | 2004-06-07 | 2008-01-24 | 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 | カチオン性脂質および使用方法 |
WO2010042877A1 (en) * | 2008-10-09 | 2010-04-15 | Tekmira Pharmaceuticals Corporation | Improved amino lipids and methods for the delivery of nucleic acids |
Non-Patent Citations (1)
Title |
---|
MARTINON F, ET AL.: "Induction of virus-specific cytotoxic T lymphocytes in vivo by liposome-entrapped mRNA", EUROPIAN JOURNNAL OF IMMUNOLOGY, vol. 23, no. 7, JPN7015001530, July 1993 (1993-07-01), pages 1719 - 1722, XP002660045, ISSN: 0003087882 * |
Cited By (6)
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WO2016010110A1 (ja) * | 2014-07-17 | 2016-01-21 | 富士フイルム株式会社 | 脂質粒子および核酸送達キャリア |
JP2016023147A (ja) * | 2014-07-17 | 2016-02-08 | 富士フイルム株式会社 | 脂質粒子および核酸送達キャリア |
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