JP6184945B2 - mRNA送達のための脂質ナノ粒子組成物および方法 - Google Patents
mRNA送達のための脂質ナノ粒子組成物および方法 Download PDFInfo
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Description
これまでに、mRNAコード抗原での免疫化等の低レベルの翻訳が制限要素ではなかった適用においてのみ、mRNA遺伝子治療を用いて著しい進歩がもたらされている。ネイキッドまたはプロタミン複合体mRNAの皮内注入による腫瘍抗原に対するワクチン接種を含む臨床試験は、実行可能性、毒性欠如、および有望な結果を実証した。X.Su et al.,Mol.Pharmaceutics 8:774−787(2011)。残念ながら、低レベルの翻訳は、生物学的影響または治療的影響を与えるためにより高いレベルのmRNAコードタンパク質の持続発現を必要とする他の適用におけるmRNAベースの遺伝子治療の活用を大いに制限している。
(項目1)
(a)少なくとも一部が機能的分泌性ポリペプチドをコードする少なくとも1つのmRNA分子と、(b)脂質ナノ粒子を含む移送ビヒクルと、を含む、組成物。
(項目2)
前記mRNAは、リソソーム貯蔵障害を有する個体において異常に欠乏している酵素をコードする、項目1に記載の組成物。
(項目3)
前記mRNAは、機能的エリスロポエチンまたは機能的α−ガラクトシダーゼポリペプチドをコードする、項目1に記載の組成物。
(項目4)
前記RNA分子は、前記RNA分子に安定性を付与する少なくとも1つの修飾を含む、項目1に記載の組成物。
(項目5)
前記RNA分子は、前記RNA分子の5’非翻訳領域の修飾を含む、項目1に記載の組成物。
(項目6)
前記修飾は、Cap1構造の包含を含む、項目5に記載の組成物。
(項目7)
前記RNA分子は、前記RNA分子の3’非翻訳領域の修飾を含む、項目1に記載の組成物。
(項目8)
前記修飾は、ポリA尾部の包含を含む、項目7に記載の組成物。
(項目9)
標的細胞の細胞内コンパートメントへの前記RNA分子の移動を促進するための作用物質をさらに含む、項目1に記載の組成物。
(項目10)
前記脂質ナノ粒子は、1つ以上のカチオン性脂質を含む、項目1に記載の組成物。
(項目11)
前記脂質ナノ粒子は、1つ以上の非カチオン性脂質を含む、項目1に記載の組成物。
(項目12)
前記脂質ナノ粒子は、1つ以上のPEG修飾脂質を含む、項目1に記載の組成物。
(項目13)
前記脂質ナノ粒子は、C12−200を含む、項目1に記載の組成物。
(項目14)
前記脂質ナノ粒子は、DLinKC2DMA、CHOL、DOPE、およびDMG−PEG−2000を含む、項目1に記載の組成物。
(項目15)
前記脂質ナノ粒子は、C12−200、DOPE、CHOL、およびDMGPEG2Kを含む、項目1に記載の組成物。
(項目16)
前記脂質ナノ粒子は、切断可能な脂質を含む、項目1に記載の組成物。
(項目17)
前記組成物は、凍結乾燥される、項目1に記載の組成物。
(項目18)
前記組成物は、凍結乾燥された再構成組成物である、項目1に記載の組成物。
(項目19)
前記標的細胞は、肝細胞、上皮細胞、造血細胞、上皮細胞、内皮細胞、肺細胞、骨細胞、幹細胞、間葉細胞、神経細胞、心臓細胞、含脂肪細胞、血管平滑筋細胞、心筋細胞、骨格筋細胞、β細胞、下垂体細胞、滑膜ライニング細胞、卵巣細胞、精巣細胞、線維芽細胞
、B細胞、T細胞、網状赤血球、白血球、顆粒球、および腫瘍細胞からなる群から選択される、項目10に記載の組成物。
(項目20)
機能的ポリペプチドが欠乏している対象を治療する方法であって、(a)少なくとも一部が前記機能的分泌性ポリペプチドをコードする少なくとも1つのmRNAと、(b)脂質ナノ粒子を含む移送ビヒクルと、を含む組成物を投与することを含み、前記組成物の投与後、前記mRNAは、標的細胞内で発現されて、前記機能的分泌性ポリペプチドを産生する、方法。
(項目21)
前記mRNAは、機能的エリスロポエチン、α−ガラクトシダーゼ、LDL受容体、第VIII因子、第IX因子、α−L−イズロニダーゼ、イズロン酸スルファターゼ、ヘパリン−N−スルファターゼ、α−N−アセチルグルコサミニダーゼ、ガラクトース6−スルファターゼ、β−ガラクトシダーゼ、リソソーム酸リパーゼまたはアリールスルファターゼ−Aポリペプチド、および(b)移送ビヒクルをコードし、前記組成物の投与後、前記mRNAは、標的細胞内で発現されて、機能的分泌性ポリペプチドを産生する、項目21に記載の方法。
(項目22)
前記機能的分泌性ポリペプチドは、リソソーム貯蔵障害を有する個体において異常に欠乏している酵素である、項目21に記載の方法。
(項目23)
前記mRNA分子は、前記mRNA分子に安定性を付与する少なくとも1つの修飾を含む、項目21に記載の方法。
(項目24)
前記mRNA分子は、前記mRNA分子の5’非翻訳領域の修飾を含む、項目21に記載の方法。
(項目25)
前記修飾は、Cap1構造の包含を含む、項目25に記載の方法。
(項目26)
前記mRNA分子は、前記mRNA分子の3’非翻訳領域の修飾を含む、項目21に記載の方法。
(項目27)
前記修飾は、ポリA尾部の包含を含む、項目27に記載の方法。
(項目28)
前記標的細胞の細胞内コンパートメントへの前記mRNA分子の移動を促進するための作用物質をさらに含む、項目21に記載の方法。
(項目29)
前記脂質ナノ粒子は、1つ以上のカチオン性脂質を含む、項目21に記載の方法。
(項目30)
前記脂質ナノ粒子は、1つ以上の非カチオン性脂質を含む、項目21に記載の方法。
(項目31)
前記脂質ナノ粒子は、1つ以上のPEG修飾脂質を含む、項目21に記載の方法。
(項目32)
前記脂質ナノ粒子は、C12−200を含む、項目21に記載の方法。
(項目33)
前記脂質ナノ粒子は、DLinKC2DMA、CHOL、DOPE、およびDMG−PEG−2000を含む、項目21に記載の方法。
(項目34)
前記脂質ナノ粒子は、C12−200、DOPE、CHOL、およびDMGPEG2Kを含む、項目21に記載の方法。
(項目35)
前記脂質ナノ粒子は、切断可能な脂質を含む、項目21に記載の方法。
(項目36)
前記組成物は、凍結乾燥される、項目21に記載の方法。
(項目37)
前記組成物は、凍結乾燥された再構成組成物である、項目21に記載の方法。
(項目38)
前記標的細胞は、肝細胞、上皮細胞、造血細胞、上皮細胞、内皮細胞、肺細胞、骨細胞、幹細胞、間葉細胞、神経細胞、心臓細胞、含脂肪細胞、血管平滑筋細胞、心筋細胞、骨格筋細胞、β細胞、下垂体細胞、滑膜ライニング細胞、卵巣細胞、精巣細胞、線維芽細胞、B細胞、T細胞、網状赤血球、白血球、顆粒球、および腫瘍細胞からなる群から選択される、項目21に記載の方法。
(項目39)
機能的分泌性ポリペプチドが欠乏している対象を治療する方法であって、(a)少なくとも一部が前記機能的分泌性ポリペプチドをコードする少なくとも1つのmRNAと、(b)脂質ナノ粒子を含む移送ビヒクルと、を含む組成物を投与することを含み、前記組成物の投与後、前記mRNAは、標的細胞内で翻訳されて、投与の1時間を超えた後に少なくとも最小治療レベルで前記標的細胞内に前記機能的ポリペプチドを産生する、方法。
(項目40)
標的細胞内で機能的分泌性ポリペプチドを産生する方法であって、(a)少なくとも一部が前記機能的分泌性ポリペプチドをコードする少なくとも1つのmRNAと、(b)脂質ナノ粒子を含む移送ビヒクルと、を含む組成物を投与することを含み、前記組成物の投与後、前記mRNAは、標的細胞内で翻訳されて、投与の1時間を超えた後に少なくとも最小治療レベルで機能的分泌性ポリペプチドを産生する、方法。
上で論じられる特徴および多くの他の特徴ならびに本発明の付随する利点は、添付の実施例と併せて、本発明の以下の詳細な説明を参照することにより、より良好に理解されるであろう。本明細書に記載の様々な実施形態は相補的であり、本明細書に包含される教示を考慮して、当業者によって理解される様式でともに合わせられるか、または使用されてもよい。
本発明は、治療レベルの機能的分泌タンパク質の産生のために1つ以上の標的細胞にリポソーム移送ビヒクル中のmRNAを細胞内送達するための組成物および方法を提供する。
mRNA
移送担体
脂質ナノ粒子
特定の理論によって束縛されることを望むことなく、イミダゾールベースのカチオン性脂質ICEの融合性が、従来のカチオン性脂質と比較してより低いpKaを有するイミダゾール基によって促進されるエンドソーム破壊に関連していることが考えられる。次いで、エンドソーム破壊は、リポソーム膜の浸透圧膨張および破壊を促進し、その後、その中に装填される核酸(複数を含む)含有物の標的細胞へのトランスフェクションまたは細胞内放出が続く。
標的細胞
適用および投与
実施例
実施例1:ポリヌクレオチド組成物の静脈内送達を介するタンパク質産生デポー
ヒトエリスロポエチン(EPO)(配列番号3、図3)、ヒトα−ガラクトシダーゼ(GLA)(配列番号4、図4)、ヒトα−1抗トリプシン(A1AT)(配列番号5、図5)、およびヒト第IX因子(FIX)(配列番号6、図6)を、遺伝子をコードするプラスミドDNA鋳型からの生体外転写によって合成し、その後、5’キャップ構造(Cap1)(Fechter&Brownlee,J.Gen.Virology 86:1239−1249(2005))およびゲル電気泳動によって決定された約200ヌクレオチド長の3’ポリ(A)尾部を付加した。5’および3’非翻訳領域は、以下の実施例におけるそれぞれのmRNA産物において存在し、それぞれ、配列番号:1および2(図1および図2)によって定義される。
脂質ナノ粒子製剤
静脈内送達されたmRNA装填ナノ粒子を介して産生されたタンパク質の分析
注入プロトコル
分析のための臓器組織の単離
分析のための血清の単離
酵素結合イムノソルベントアッセイ(ELISA)分析
ウエスタンブロット分析
結果
1A.生体内ヒトEPOタンパク質産生結果
1B.生体内ヒトGLAタンパク質産生結果
1C.生体内ヒトFIXタンパク質産生結果
1D.生体内ヒトA1ATタンパク質産生結果
実施例2:ポリヌクレオチド組成物の肺送達を介するタンパク質産生デポー
注入プロトコル
結果
Claims (28)
- (a)少なくとも一部が機能的分泌性ポリペプチドをコードする少なくとも1つのmRNA分子と、(b)脂質ナノ粒子を含む移送ビヒクルと、を含む、前記分泌性ポリペプチドの欠陥または欠乏を有する対象の治療方法における使用のための組成物であって、
前記脂質ナノ粒子は、1つ以上のカチオン性脂質、1つ以上の非カチオン性脂質、1つ以上のコレステロールベースの脂質および1つ以上のPEG修飾脂質を含み、
前記移送ビヒクルの寸法は、100nm未満である、
組成物。 - (a)少なくとも一部が機能的分泌性ポリペプチドをコードする少なくとも1つのmRNA分子と、(b)脂質ナノ粒子を含む移送ビヒクルと、を含む、前記分泌性ポリペプチドの欠陥または欠乏を有する対象の治療方法における使用のための組成物であって、
前記機能的分泌性ポリペプチドは、投与後少なくとも1週間にわたって血清中で検出可能なレベルで存在し、
前記脂質ナノ粒子は、1つ以上のカチオン性脂質、1つ以上の非カチオン性脂質、1つ以上のコレステロールベースの脂質および1つ以上のPEG修飾脂質を含み、
前記移送ビヒクルの寸法は、100nm未満である、
組成物。 - (a)少なくとも一部が機能的分泌性ポリペプチドをコードする少なくとも1つのmRNA分子と、(b)脂質ナノ粒子を含む移送ビヒクルと、を含む、前記分泌性ポリペプチドの欠陥または欠乏を有する対象の治療方法における使用のための組成物であって、
前記対象の治療方法は、前記組成物を全身投与することを含み、
前記脂質ナノ粒子は、1つ以上のカチオン性脂質、1つ以上の非カチオン性脂質、1つ以上のコレステロールベースの脂質および1つ以上のPEG修飾脂質を含み、
前記移送ビヒクルの寸法は、100nm未満である、
組成物。 - 前記mRNA分子は、リソソーム貯蔵障害を有する個体において異常に欠乏している酵素をコードする、請求項1〜3のいずれか1項に記載の使用のための組成物。
- 前記mRNA分子によってコードされる前記ポリペプチドは、エリスロポエチン、α−ガラクトシダーゼポリペプチド、LDL受容体、第VIII因子、第IX因子、α−L−イズロニダーゼ、イズロン酸スルファターゼ、ヘパリン−N−スルファターゼ、α−N−アセチルグルコサミニダーゼ、ガラクトース6−スルファターゼ、β−ガラクトシダーゼ、リソソーム酸リパーゼまたはアリールスルファターゼ−Aポリペプチドである、請求項1〜3のいずれか1項に記載の使用のための組成物。
- 前記mRNA分子は、未修飾であるか、または
前記mRNA分子は、
前記mRNA分子に安定性を付与する少なくとも1つの修飾;
その未修飾対応物と比較して、前記mRNA分子の安定性を向上させる少なくとも1つの修飾であって、必要に応じて前記修飾が修飾されたヌクレオチドを含み、必要に応じて前記修飾されたヌクレオチドが偽ウリジンである、修飾;
前記mRNA分子の5’非翻訳領域の修飾であって、必要に応じて前記修飾は、Cap1構造の包含を含む、修飾;または
前記RNA分子の3’非翻訳領域の修飾であって、必要に応じて前記修飾は、ポリA尾部の包含を含む、修飾、
を含む;および/または
前記mRNA分子は、少なくとも30kDaのものである、請求項1〜5のいずれか一項に記載の使用のための組成物。 - 標的細胞の細胞内コンパートメントへの前記mRNA分子の移動を促進するための作用物質をさらに含み、
必要に応じて前記標的細胞は、肝細胞、上皮細胞、造血細胞、上皮細胞、内皮細胞、肺細胞、骨細胞、幹細胞、間葉細胞、神経細胞、心臓細胞、含脂肪細胞、血管平滑筋細胞、心筋細胞、骨格筋細胞、β細胞、下垂体細胞、滑膜ライニング細胞、卵巣細胞、精巣細胞、線維芽細胞、B細胞、T細胞、網状赤血球、白血球、顆粒球、および腫瘍細胞からなる群から選択される、請求項1〜6のいずれか一項に記載の使用のための組成物。 - 前記脂質ナノ粒子は、
C12−200;
DLinKC2DMA、CHOL、DOPE、およびDMG−PEG−2000;または
C12−200、DOPE、CHOL、およびDMGPEG2K
を含む、請求項1〜7のいずれか一項に記載の使用のための組成物。 - 前記脂質ナノ粒子は、切断可能な脂質を含む、請求項1〜8のいずれか一項に記載の使用のための組成物。
- 前記組成物は、凍結乾燥される、請求項1〜9のいずれか一項に記載の使用のための組成物。
- 前記組成物は、凍結乾燥された再構成組成物である、請求項1〜10のいずれか一項に記載の使用のための組成物。
- 前記組成物は、静脈内または肺への送達のためのものである、請求項1〜11のいずれか一項に記載の使用のための組成物。
- 前記組成物は、週2回、週1回、10日毎に、2週間毎に、または3週間毎に前記対象に投与するためのものである、請求項1〜12のいずれか一項に記載の使用のための組成物。
- 前記移送ビヒクルの寸法が、100nm未満、75nm未満、50nm未満、25nm未満または10nm未満であり、必要に応じて前記脂質ナノ粒子は、約100nm未満の寸法を有する、請求項1〜13のいずれか一項に記載の使用のための組成物。
- 前記ポリペプチドが、投与後1時間を超えて、4時間を超えて、6時間を超えて、12時間を超えて、24時間を超えて、48時間を超えて、または72時間を超えて、少なくとも治療レベルで発現され、必要に応じて、分泌されるタンパク質のレベルが、投与後3日目、4日目、5日目、または1週間目以上で検出可能である、請求項1および3〜14のいずれか一項に記載の使用のための組成物。
- 対象への前記組成物の投与後、前記mRNA分子は、生体内で翻訳されて、前記機能的分泌性ポリペプチドを生成し、前記機能的分泌性ポリペプチドは、投与後少なくとも1週間にわたって血清中で検出可能なレベルで存在する、請求項1および3〜14のいずれか一項に記載の使用のための組成物。
- 組成物の投与が、経口、直腸、膣内、経粘膜、腸、筋肉内、皮下、髄内、鞘内、直接脳室内、静脈内、腹腔内、鼻腔内および眼内からなる群より選択される投与経路によって達成される、請求項1〜2および4〜15のいずれか一項に記載の使用のための組成物。
- 前記mRNAが、標的細胞に生体内で送達され、必要に応じて、
(i)前記標的細胞は、肝細胞、上皮細胞、造血細胞、上皮細胞、内皮細胞、肺細胞、骨細胞、幹細胞、間葉細胞、神経細胞、心臓細胞、含脂肪細胞、血管平滑筋細胞、心筋細胞、骨格筋細胞、β細胞、下垂体細胞、滑膜ライニング細胞、卵巣細胞、精巣細胞、線維芽細胞、B細胞、T細胞、網状赤血球、白血球、顆粒球、および腫瘍細胞からなる群から選択される;
(ii)前記標的細胞は、目的とするタンパク質または酵素を欠乏している;ならびに/あるいは
(iii)前記組成物は、1つ以上の標的細胞に対する前記組成物の親和性を高めることができる標的化リガンドを含み、必要に応じて前記標的化リガンドが、アポリポタンパク質Bまたはアポリポタンパク質Eからなる群より選択され、そして前記1つ以上の標的細胞が、低密度のリポタンパク質受容体を発現する、
請求項1〜17のいずれか一項に記載の使用のための組成物。 - 対象の治療方法における使用のための、外因性タンパク質をコードするmRNAを含む組成物であって、
前記対象が、前記外因性タンパク質の欠陥または欠乏を有するか、または前記外因性タンパク質の標的化および/または生物学的標的の不活性化が必要であり、
ここで前記組成物は、肺送達により前記対象に投与され、その結果、前記組成物の投与が、前記対象の肺細胞における前記mRNAによってコードされる前記外因性タンパク質の生体内での発現をもたらし、
前記肺送達は、気管内または噴霧での投与によって達成され、
前記mRNAは、1つ以上のカチオン性脂質、1つ以上の非カチオン性脂質、1つ以上のコレステロールベースの脂質および1つ以上のPEG修飾脂質を含むリポソーム内にカプセル化されており、
前記リポソームの寸法は、100nm未満である、
組成物。 - 前記mRNAが、天然に存在しないヌクレオチドを含み、必要に応じて、前記天然に存在しないヌクレオチドは、偽ウリジンである、請求項19に記載の使用のための組成物。
- 前記mRNAによってコードされる前記外因性タンパク質は、酵素、ホルモン、受容体または抗体である、請求項19に記載の使用のための組成物。
- 前記外因性タンパク質が、
(i)発現後に前記肺細胞の細胞質ゾル内に滞留される;または
(ii)発現後に細胞外に分泌され、必要に応じて、前記外因性タンパク質が、全身的に分布する、
請求項19に記載の使用のための組成物。 - 前記mRNAによってコードされる前記外因性タンパク質の生体内での発現が、投与の少なくとも6時間後に検出可能である、請求項19に記載の使用のための組成物。
- ファブリー病の治療において使用するための、ヒトα−ガラクトシダーゼ(hGLA)タンパク質をコードするmRNAを含む組成物であって、
前記mRNAは、血清hGLAタンパク質レベルが少なくとも72時間にわたって、治療前のベースライン血清hGLAレベルと比較して増大するように静脈内または肺投与によって投与され、
前記mRNAは、1つ以上のカチオン性脂質、1つ以上の非カチオン性脂質、1つ以上のコレステロールベースの脂質および1つ以上のPEG修飾脂質を含むリポソーム内にカプセル化されており、
前記リポソームの寸法は、100nm未満である、
組成物。 - 前記mRNAは、配列番号4を含む、請求項24に記載の使用のための組成物。
- 前記mRNAが、天然に存在しないヌクレオチドを含み、必要に応じて、前記天然に存在しないヌクレオチドが、偽ウリジンである、請求項24に記載の使用のための組成物。
- 前記hGLAタンパク質が、
(i)発現後に細胞外に分泌される;
(ii)全身的に分布する;および/または
(iii)投与の少なくとも6時間後に検出可能である、
請求項24に記載の使用のための組成物。 - 前記mRNAの投与が、前記ヒト対象において治療前のグロボトリアオシルセラミド(Gb3)レベルと比較して、Gb3レベルの低下をもたらす、請求項24に記載の使用のための組成物。
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Families Citing this family (360)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6087504B2 (ja) | 2008-11-07 | 2017-03-01 | 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 |
NZ700688A (en) | 2009-12-01 | 2016-02-26 | Shire Human Genetic Therapies | Delivery of mrna for the augmentation of proteins and enzymes in human genetic diseases |
US8822663B2 (en) | 2010-08-06 | 2014-09-02 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
WO2012027675A2 (en) | 2010-08-26 | 2012-03-01 | Massachusetts Institute Of Technology | Poly(beta-amino alcohols), their preparation, and uses thereof |
HUE058896T2 (hu) | 2010-10-01 | 2022-09-28 | Modernatx Inc | N1-metil-pszeudo-uracilt tartalmazó ribonukleinsavak és azok felhasználásai |
US8853377B2 (en) | 2010-11-30 | 2014-10-07 | Shire Human Genetic Therapies, Inc. | mRNA for use in treatment of human genetic diseases |
EP2691443B1 (en) | 2011-03-28 | 2021-02-17 | Massachusetts Institute of Technology | Conjugated lipomers and uses thereof |
US8710200B2 (en) | 2011-03-31 | 2014-04-29 | Moderna Therapeutics, Inc. | Engineered nucleic acids encoding a modified erythropoietin and their expression |
EP2709590A4 (en) * | 2011-05-11 | 2015-05-13 | Nanovalent Pharmaceuticals Inc | REINFORCED GROWTH INHIBITION OF OSTEOSARCOMS THROUGH CYTOTOXIC POLYMERIZED LIPOSOMAL NANOPARTICLES TO AIM AT THE ALCAM CELL SURFACE RECEPTOR |
AU2012267578B2 (en) | 2011-06-08 | 2017-04-20 | Translate Bio, Inc. | Cleavable lipids |
JP6184945B2 (ja) | 2011-06-08 | 2017-08-23 | 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 | mRNA送達のための脂質ナノ粒子組成物および方法 |
CA2840989A1 (en) | 2011-07-06 | 2013-01-10 | Novartis Ag | Immunogenic combination compositions and uses thereof |
EP3613852A3 (en) | 2011-07-22 | 2020-04-22 | President and Fellows of Harvard College | Evaluation and improvement of nuclease cleavage specificity |
US9464124B2 (en) | 2011-09-12 | 2016-10-11 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
RS62993B1 (sr) | 2011-10-03 | 2022-03-31 | Modernatx Inc | Modifikovani nukleozidi, nukleotidi, i nukleinske kiseline, i njihove upotrebe |
AU2012328570B2 (en) | 2011-10-27 | 2017-08-31 | Massachusetts Institute Of Technology | Amino acid derivatives functionalized on the n-terminus capable of forming drug encapsulating microspheres and uses thereof |
CN104114572A (zh) | 2011-12-16 | 2014-10-22 | 现代治疗公司 | 经修饰的核苷、核苷酸和核酸组合物 |
US9877919B2 (en) | 2012-03-29 | 2018-01-30 | Translate Bio, Inc. | Lipid-derived neutral nanoparticles |
US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
US10501513B2 (en) | 2012-04-02 | 2019-12-10 | Modernatx, Inc. | Modified polynucleotides for the production of oncology-related proteins and peptides |
US9303079B2 (en) | 2012-04-02 | 2016-04-05 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
JP2015518705A (ja) | 2012-04-02 | 2015-07-06 | モデルナ セラピューティクス インコーポレイテッドModerna Therapeutics,Inc. | ヒト疾患に関連する生物製剤およびタンパク質の産生のための修飾ポリヌクレオチド |
US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
DE18200782T1 (de) | 2012-04-02 | 2021-10-21 | Modernatx, Inc. | Modifizierte polynukleotide zur herstellung von proteinen im zusammenhang mit erkrankungen beim menschen |
EP3536787A1 (en) | 2012-06-08 | 2019-09-11 | Translate Bio, 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 |
CA2884870C (en) | 2012-08-13 | 2022-03-29 | Massachusetts Institute Of Technology | Amine-containing lipidoids and uses thereof |
WO2014028429A2 (en) | 2012-08-14 | 2014-02-20 | Moderna Therapeutics, Inc. | Enzymes and polymerases for the synthesis of rna |
EP4074834A1 (en) | 2012-11-26 | 2022-10-19 | ModernaTX, Inc. | Terminally modified rna |
EP2929035A1 (en) * | 2012-12-07 | 2015-10-14 | Shire Human Genetic Therapies, Inc. | Lipidic nanoparticles for mrna delivering |
EP2968391A1 (en) | 2013-03-13 | 2016-01-20 | Moderna Therapeutics, Inc. | Long-lived polynucleotide molecules |
HUE055044T2 (hu) * | 2013-03-14 | 2021-10-28 | Translate Bio Inc | MRNS-kódolt ellenanyagok bejuttatására szolgáló eljárások és készítmények |
ES2647832T3 (es) | 2013-03-14 | 2017-12-26 | Translate Bio, Inc. | Ácidos ribonucleicos con nucleótidos modificados con 4-tio y procedimientos relacionados |
EA037922B1 (ru) | 2013-03-14 | 2021-06-07 | Шир Хьюман Дженетик Терапис, Инк. | мРНК CFTR И КОМПОЗИЦИИ ДЛЯ ЛЕЧЕНИЯ МУКОВИСЦИДОЗА У МЛЕКОПИТАЮЩЕГО |
EP2970955B1 (en) | 2013-03-14 | 2018-11-14 | Translate Bio, Inc. | Methods for purification of messenger rna |
EP2971010B1 (en) | 2013-03-14 | 2020-06-10 | ModernaTX, Inc. | Formulation and delivery of modified nucleoside, nucleotide, and nucleic acid compositions |
ES2795249T3 (es) * | 2013-03-15 | 2020-11-23 | Translate Bio Inc | Mejora sinérgica de la administración de ácidos nucleicos a través de formulaciones mezcladas |
US8980864B2 (en) | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
US9315472B2 (en) | 2013-05-01 | 2016-04-19 | Massachusetts Institute Of Technology | 1,3,5-triazinane-2,4,6-trione derivatives and uses thereof |
JP6620093B2 (ja) * | 2013-07-23 | 2019-12-11 | アービュートゥス バイオファーマ コーポレイションArbutus Biopharma Corporation | メッセンジャーrnaを送達するための組成物及び方法 |
US20150044192A1 (en) | 2013-08-09 | 2015-02-12 | President And Fellows Of Harvard College | Methods for identifying a target site of a cas9 nuclease |
AU2014315287A1 (en) | 2013-09-03 | 2015-03-12 | Moderna Therapeutics, Inc. | Chimeric polynucleotides |
EP3041938A1 (en) | 2013-09-03 | 2016-07-13 | Moderna Therapeutics, Inc. | Circular polynucleotides |
US9228207B2 (en) | 2013-09-06 | 2016-01-05 | President And Fellows Of Harvard College | Switchable gRNAs comprising aptamers |
EP3052106A4 (en) | 2013-09-30 | 2017-07-19 | ModernaTX, Inc. | Polynucleotides encoding immune modulating polypeptides |
MX2016004249A (es) | 2013-10-03 | 2016-11-08 | Moderna Therapeutics Inc | Polinulcleotidos que codifican el receptor de lipoproteina de baja densidad. |
ES2954366T3 (es) | 2013-10-22 | 2023-11-21 | Translate Bio Inc | Terapia de ácido ribonucleico mensajero para la deficiencia de argininosuccinato sintetasa |
EP3060257B1 (en) | 2013-10-22 | 2021-02-24 | Translate Bio, Inc. | Lipid formulations for delivery of messenger rna |
EP4036241A1 (en) * | 2013-10-22 | 2022-08-03 | Translate Bio, Inc. | Cns delivery of mrna and uses thereof |
CA2928186A1 (en) * | 2013-10-22 | 2015-04-30 | Shire Human Genetic Therapies, Inc. | Mrna therapy for phenylketonuria |
JP6621409B2 (ja) | 2013-11-22 | 2019-12-18 | ミナ セラピューティクス リミテッド | C/EBPα小分子活性化RNA組成物 |
HUE051311T2 (hu) | 2014-03-09 | 2021-03-01 | Univ Pennsylvania | Ornitin transzkarbamiláz (TC) deficiencia kezelésében alkalmas készítmények |
TR201900649T4 (tr) | 2014-03-24 | 2019-02-21 | Translate Bio Inc | Oküler hastalıkların tedavisi için mrna tedavisi. |
PT3134131T (pt) | 2014-04-23 | 2022-03-24 | Modernatx Inc | Vacinas de ácidos nucleicos |
ES2750661T3 (es) | 2014-04-25 | 2020-03-26 | Translate Bio Inc | Métodos para la purificación de ARN mensajero |
US10392438B2 (en) | 2014-05-16 | 2019-08-27 | Pfizer Inc. | Bispecific antibodies |
JP6557722B2 (ja) | 2014-05-30 | 2019-08-07 | 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 | 核酸の送達のための生分解性脂質 |
BR112016026980B1 (pt) | 2014-06-10 | 2022-05-03 | Curevac Real Estate Gmbh | Método para sintetizar uma molécula de rna de uma dada sequência |
ES2964588T3 (es) | 2014-06-24 | 2024-04-08 | Translate Bio Inc | Composiciones enriquecidas estereoquímicamente para la administración de ácidos nucleicos |
CN114146063A (zh) | 2014-07-02 | 2022-03-08 | 川斯勒佰尔公司 | 信使rna的包封 |
US9840479B2 (en) | 2014-07-02 | 2017-12-12 | Massachusetts Institute Of Technology | Polyamine-fatty acid derived lipidoids and uses thereof |
WO2016011226A1 (en) | 2014-07-16 | 2016-01-21 | Moderna Therapeutics, Inc. | Chimeric polynucleotides |
US20170210788A1 (en) | 2014-07-23 | 2017-07-27 | Modernatx, Inc. | Modified polynucleotides for the production of intrabodies |
AU2015298571B2 (en) | 2014-07-30 | 2020-09-03 | President And Fellows Of Harvard College | Cas9 proteins including ligand-dependent inteins |
GB201420139D0 (en) | 2014-11-12 | 2014-12-24 | Ucl Business Plc | Factor IX gene therapy |
WO2016090262A1 (en) | 2014-12-05 | 2016-06-09 | Shire Human Genetic Therapies, Inc. | Messenger rna therapy for treatment of articular disease |
BR112017013300A2 (pt) | 2014-12-22 | 2018-02-27 | Codexis Inc | alfa galactosidase a recombinante e/ou fragmento de alfa galactosidase a recombinante biologicamente ativo, composição, sequência de polinucleotídeos recombinantes, vetor de expressão, célula hospedeira, métodos para produzir uma variante de alfa galactosidase a e para tratar e/ou prevenir os sintomas da doença de fabry, composição farmacêutica, e, uso das composições. |
CN107530436B (zh) | 2015-01-21 | 2022-03-29 | 菲泽尔克斯公司 | 用于将治疗剂和诊断剂递送到细胞中的方法、组合物和系统 |
US10676726B2 (en) | 2015-02-09 | 2020-06-09 | Duke University | Compositions and methods for epigenome editing |
US20170151281A1 (en) | 2015-02-19 | 2017-06-01 | Batu Biologics, Inc. | Chimeric antigen receptor dendritic cell (car-dc) for treatment of cancer |
WO2016149508A1 (en) | 2015-03-19 | 2016-09-22 | Shire Human Genetic Therapies, Inc. | Mrna therapy for pompe disease |
JP6851319B2 (ja) | 2015-04-27 | 2021-03-31 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | ヒト疾患のCRISPR/Cas9媒介性の修正のためのデュアルAAVベクター系 |
GB201508025D0 (en) | 2015-05-11 | 2015-06-24 | Ucl Business Plc | Fabry disease gene therapy |
PL3310764T3 (pl) | 2015-06-19 | 2023-11-06 | Massachusetts Institute Of Technology | Podstawione alkenylem 2,5-piperazynodiony i ich zastosowanie w kompozycjach do dostarczania środka do osobnika lub komórki |
US11364292B2 (en) | 2015-07-21 | 2022-06-21 | Modernatx, Inc. | CHIKV RNA vaccines |
TW201718638A (zh) | 2015-07-21 | 2017-06-01 | 現代治療公司 | 傳染病疫苗 |
EP3325018A4 (en) | 2015-07-22 | 2019-04-24 | Duke University | HIGH EFFICIENCY SCREENING OF REGULATORY ELEMENT FUNCTION USING EPIGENOUS EDITING TECHNOLOGIES |
US11564893B2 (en) | 2015-08-17 | 2023-01-31 | Modernatx, Inc. | Methods for preparing particles and related compositions |
CA2996001A1 (en) | 2015-08-25 | 2017-03-02 | Duke University | Compositions and methods of improving specificity in genomic engineering using rna-guided endonucleases |
SI3350157T1 (sl) | 2015-09-17 | 2022-04-29 | Modernatx, Inc. | Sestave za doziranje terapevtskih sredstev v celice |
EP3359670B2 (en) | 2015-10-05 | 2024-02-14 | ModernaTX, Inc. | Methods for therapeutic administration of messenger ribonucleic acid drugs |
EP4089175A1 (en) | 2015-10-13 | 2022-11-16 | Duke University | Genome engineering with type i crispr systems in eukaryotic cells |
WO2017066573A1 (en) | 2015-10-14 | 2017-04-20 | Shire Human Genetic Therapies, Inc. | Modification of rna-related enzymes for enhanced production |
CA3002922A1 (en) | 2015-10-22 | 2017-04-27 | Modernatx, Inc. | Human cytomegalovirus vaccine |
MA46023A (fr) * | 2015-10-22 | 2019-07-03 | Modernatx Inc | Vaccin contre le virus de la grippe à large spectre |
EP3364950A4 (en) | 2015-10-22 | 2019-10-23 | ModernaTX, Inc. | VACCINES AGAINST TROPICAL DISEASES |
CN108513575A (zh) | 2015-10-23 | 2018-09-07 | 哈佛大学的校长及成员们 | 核碱基编辑器及其用途 |
EP3964200A1 (en) | 2015-12-10 | 2022-03-09 | ModernaTX, Inc. | Compositions and methods for delivery of therapeutic agents |
JP7114465B2 (ja) | 2015-12-22 | 2022-08-08 | モデルナティエックス インコーポレイテッド | 薬剤の細胞内送達のための化合物および組成物 |
PT3394093T (pt) | 2015-12-23 | 2022-05-30 | Modernatx Inc | Métodos de utilização de polinucleotídeos que codificam ligandos ox40 |
EP3400023A1 (en) | 2016-01-10 | 2018-11-14 | ModernaTX, Inc. | Therapeutic mrnas encoding anti ctla-4 antibodies |
EP3405579A1 (en) | 2016-01-22 | 2018-11-28 | Modernatx, Inc. | Messenger ribonucleic acids for the production of intracellular binding polypeptides and methods of use thereof |
RU2759737C2 (ru) | 2016-03-31 | 2021-11-17 | Этрис Гмбх | Новые минимальные utr-последовательности |
ES2844180T3 (es) | 2016-04-08 | 2021-07-21 | Translate Bio Inc | Acido nucleico codificante multimérico y usos del mismo |
EP3442590A2 (en) | 2016-04-13 | 2019-02-20 | Modernatx, Inc. | Lipid compositions and their uses for intratumoral polynucleotide delivery |
US20180126003A1 (en) * | 2016-05-04 | 2018-05-10 | Curevac Ag | New targets for rna therapeutics |
MX2018013509A (es) | 2016-05-18 | 2019-03-28 | Modernatx Inc | Polinucleotidos que codifican interleucina-12 (il12) y sus usos de los mismos. |
MA45053A (fr) * | 2016-05-18 | 2019-03-27 | Modernatx Inc | Polynucléotides codant pour un régulateur de conductance transmembranaire de fibrose kystique pour le traitement de la fibrose kystique |
SG11201810256XA (en) | 2016-05-18 | 2018-12-28 | Modernatx Inc | Polynucleotides encoding relaxin |
WO2017201328A1 (en) * | 2016-05-18 | 2017-11-23 | Modernatx, Inc. | POLYNUCLEOTIDES ENCODING α-GALACTOSIDASE A FOR THE TREATMENT OF FABRY DISEASE |
CN109312313A (zh) | 2016-06-13 | 2019-02-05 | 川斯勒佰尔公司 | 用于治疗鸟氨酸转氨甲酰酶缺乏症的信使rna疗法 |
JP7086870B2 (ja) | 2016-06-30 | 2022-06-20 | アルブータス・バイオファーマー・コーポレイション | メッセンジャーrnaを送達するための組成物及び方法 |
WO2018027078A1 (en) | 2016-08-03 | 2018-02-08 | President And Fellows Of Harard College | Adenosine nucleobase editors and uses thereof |
CA3033327A1 (en) | 2016-08-09 | 2018-02-15 | President And Fellows Of Harvard College | Programmable cas9-recombinase fusion proteins and uses thereof |
WO2018033454A1 (en) | 2016-08-19 | 2018-02-22 | Fundación Para La Investigación Biomédica Del Hospital Universitario Ramón Y Cajal | Mir-127 agents for use in the treatment of renal fibrosis |
WO2018039438A1 (en) | 2016-08-24 | 2018-03-01 | President And Fellows Of Harvard College | Incorporation of unnatural amino acids into proteins using base editing |
KR20240007715A (ko) | 2016-10-14 | 2024-01-16 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 핵염기 에디터의 aav 전달 |
MA46584A (fr) | 2016-10-21 | 2019-08-28 | Modernatx Inc | Vaccin contre le cytomégalovirus humain |
WO2018089540A1 (en) | 2016-11-08 | 2018-05-17 | Modernatx, Inc. | Stabilized formulations of lipid nanoparticles |
MA46762A (fr) | 2016-11-10 | 2019-09-18 | Translate Bio Inc | Procédé amélioré de préparation de nanoparticules lipidiques chargées d'arnm |
EP3538136A1 (en) | 2016-11-10 | 2019-09-18 | Translate Bio, Inc. | Subcutaneous delivery of messenger rna |
CN110114058B (zh) * | 2016-11-10 | 2023-05-26 | 川斯勒佰尔公司 | 用于递送mrna的改进的基于ice的脂质纳米颗粒制剂 |
US20190275071A1 (en) | 2016-11-23 | 2019-09-12 | Mayo Foundation For Medical Education And Research | Particle-mediated delivery of biologics |
US10745677B2 (en) | 2016-12-23 | 2020-08-18 | President And Fellows Of Harvard College | Editing of CCR5 receptor gene to protect against HIV infection |
EP3565605A1 (en) | 2017-01-03 | 2019-11-13 | ethris GmbH | Ornithine transcarbamylase coding polyribonucleotides and formulations thereof |
ES2949801T3 (es) | 2017-01-09 | 2023-10-03 | Whitehead Inst Biomedical Res | Métodos para alterar la expresión génica mediante la perturbación de multímeros de factores de transcripción que estructuran bucles reguladores |
MA47515A (fr) | 2017-02-16 | 2019-12-25 | Modernatx Inc | Compositions immunogènes très puissantes |
MA47605A (fr) | 2017-02-27 | 2020-01-01 | Translate Bio Inc | Procédés de purification d'arn messager |
MA47607A (fr) | 2017-02-27 | 2020-01-01 | Translate Bio Inc | Synthèse à grande échelle d'arn messager |
EP4008783A1 (en) | 2017-02-27 | 2022-06-08 | Translate Bio MA, Inc. | Methods for purification of messenger rna |
MX2019010155A (es) | 2017-02-27 | 2020-12-10 | Translate Bio Inc | Arnm de cftr optimizado por codón novedoso. |
JOP20190200A1 (ar) | 2017-02-28 | 2019-08-27 | Univ Pennsylvania | تركيبات نافعة في معالجة ضمور العضل النخاعي |
HRP20240257T1 (hr) | 2017-02-28 | 2024-05-24 | The Trustees Of The University Of Pennsylvania | Adeno-povezani virusni (aav) clade f vektor i njegova uporaba |
BR112019017327A2 (pt) | 2017-03-01 | 2020-04-14 | Univ Pennsylvania | terapia gênica para distúrbios oculares |
EP3592728A1 (en) | 2017-03-07 | 2020-01-15 | Translate Bio, Inc. | Polyanionic delivery of nucleic acids |
EP3592853A1 (en) | 2017-03-09 | 2020-01-15 | President and Fellows of Harvard College | Suppression of pain by gene editing |
JP2020510439A (ja) | 2017-03-10 | 2020-04-09 | プレジデント アンド フェローズ オブ ハーバード カレッジ | シトシンからグアニンへの塩基編集因子 |
MA52262A (fr) | 2017-03-15 | 2020-02-19 | Modernatx Inc | Vaccin à large spectre contre le virus de la grippe |
ES2911186T3 (es) | 2017-03-15 | 2022-05-18 | Modernatx Inc | Formas cristalinas de aminolípidos |
DK3596041T3 (da) | 2017-03-15 | 2023-01-23 | Modernatx Inc | Forbindelse og sammensætninger til intracellulær afgivelse af terapeutiske midler |
US11969506B2 (en) | 2017-03-15 | 2024-04-30 | Modernatx, Inc. | Lipid nanoparticle formulation |
MA47787A (fr) | 2017-03-15 | 2020-01-22 | Modernatx Inc | Vaccin contre le virus respiratoire syncytial |
SG11201908658TA (en) | 2017-03-23 | 2019-10-30 | Harvard College | Nucleobase editors comprising nucleic acid programmable dna binding proteins |
MA48047A (fr) | 2017-04-05 | 2020-02-12 | Modernatx Inc | Réduction ou élimination de réponses immunitaires à des protéines thérapeutiques administrées par voie non intraveineuse, par exemple par voie sous-cutanée |
US11753434B2 (en) | 2017-04-14 | 2023-09-12 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for transient gene therapy with enhanced stability |
US11879133B2 (en) | 2017-04-24 | 2024-01-23 | The Trustees Of The University Of Pennsylvania | Gene therapy for ocular disorders |
KR20200023280A (ko) | 2017-05-11 | 2020-03-04 | 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 | 신경 세로이드 지질갈색소증에 대한 유전자 요법 |
US11560566B2 (en) | 2017-05-12 | 2023-01-24 | President And Fellows Of Harvard College | Aptazyme-embedded guide RNAs for use with CRISPR-Cas9 in genome editing and transcriptional activation |
IL270631B2 (en) | 2017-05-16 | 2024-03-01 | Translate Bio Inc | Treatment of cystic fibrosis through the administration of mRNA with an optimal codon encoding ctfr |
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 |
US11793887B2 (en) | 2017-05-31 | 2023-10-24 | The Trustees Of The University Of Pennsylvania | Gene therapy for treating peroxisomal disorders |
EP3630964A4 (en) * | 2017-05-31 | 2021-03-03 | Ultragenyx Pharmaceutical Inc. | THERAPEUTIC AGENTS FOR GLYCOGEN STORAGE DISEASE TYPE III |
US20200131498A1 (en) | 2017-06-14 | 2020-04-30 | Modernatx, Inc. | Polynucleotides encoding methylmalonyl-coa mutase |
EP3638292A1 (en) | 2017-06-14 | 2020-04-22 | ModernaTX, Inc. | Polynucleotides encoding coagulation factor viii |
US11786607B2 (en) | 2017-06-15 | 2023-10-17 | Modernatx, Inc. | RNA formulations |
US10034951B1 (en) | 2017-06-21 | 2018-07-31 | New England Biolabs, Inc. | Use of thermostable RNA polymerases to produce RNAs having reduced immunogenicity |
US11732274B2 (en) | 2017-07-28 | 2023-08-22 | President And Fellows Of Harvard College | Methods and compositions for evolving base editors using phage-assisted continuous evolution (PACE) |
US11319532B2 (en) | 2017-08-30 | 2022-05-03 | President And Fellows Of Harvard College | High efficiency base editors comprising Gam |
US11744801B2 (en) | 2017-08-31 | 2023-09-05 | Modernatx, Inc. | Methods of making lipid nanoparticles |
WO2019048632A1 (en) | 2017-09-08 | 2019-03-14 | Mina Therapeutics Limited | STABILIZED COMPOSITIONS OF SMALL ACTIVATORY RNA (PARNA) OF HNF4A AND METHODS OF USE |
US20200208152A1 (en) | 2017-09-08 | 2020-07-02 | Mina Therapeutics Limited | Stabilized sarna compositions and methods of use |
US10653767B2 (en) | 2017-09-14 | 2020-05-19 | Modernatx, Inc. | Zika virus MRNA vaccines |
JP2020537541A (ja) * | 2017-09-29 | 2020-12-24 | インテリア セラピューティクス,インコーポレーテッド | 脂質ナノ粒子を用いるインビトロでのmrnaの送達方法 |
CN111757937A (zh) | 2017-10-16 | 2020-10-09 | 布罗德研究所股份有限公司 | 腺苷碱基编辑器的用途 |
EP3714047A2 (en) | 2017-11-22 | 2020-09-30 | 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 |
EP3714045A1 (en) | 2017-11-22 | 2020-09-30 | Modernatx, Inc. | Polynucleotides encoding propionyl-coa carboxylase alpha and beta subunits for the treatment of propionic acidemia |
CA3083416A1 (en) | 2017-11-30 | 2019-06-06 | The Trustees Of The University Of Pennsylvania | Gene therapy for mucopolysaccharidosis iii a |
EP3717652A4 (en) | 2017-11-30 | 2021-11-24 | The Trustees of the University of Pennsylvania | GENE THERAPY FOR MUCOPOLY SACCHARIDOSIS IIIB |
EP3727428A1 (en) | 2017-12-20 | 2020-10-28 | Translate Bio, Inc. | Improved composition and methods for treatment of ornithine transcarbamylase deficiency |
EP3735270A1 (en) | 2018-01-05 | 2020-11-11 | Modernatx, Inc. | Polynucleotides encoding anti-chikungunya virus antibodies |
CA3088485A1 (en) * | 2018-01-18 | 2019-07-25 | Etherna Immunotherapies Nv | Lipid nanoparticles |
MA54676A (fr) | 2018-01-29 | 2021-11-17 | Modernatx Inc | Vaccins à base d'arn contre le vrs |
WO2019152802A1 (en) | 2018-02-02 | 2019-08-08 | Translate Bio, Inc. | Cationic polymers |
EP3773745A1 (en) | 2018-04-11 | 2021-02-17 | ModernaTX, Inc. | Messenger rna comprising functional rna elements |
EP4242307A3 (en) | 2018-04-12 | 2023-12-27 | MiNA Therapeutics Limited | Sirt1-sarna compositions and methods of use |
EP3784252A4 (en) * | 2018-04-18 | 2022-03-16 | Oisin Biotechnologies, Inc. | FUSOGENIC LIPID DNANOPARTICLES AND METHODS FOR THEIR PRODUCTION AND USE IN TARGET CELL SPECIFIC MANUFACTURE OF A THERAPEUTIC PROTEIN AND TREATMENT OF A TARGET CELL RELATED DISEASE, CONDITION OR DISORDER |
CA3097912A1 (en) * | 2018-05-15 | 2019-11-21 | Translate Bio, Inc. | Subcutaneous delivery of messenger rna |
EP3794008A1 (en) | 2018-05-16 | 2021-03-24 | Translate Bio, Inc. | Ribose cationic lipids |
WO2019226650A1 (en) | 2018-05-23 | 2019-11-28 | Modernatx, Inc. | Delivery of dna |
AU2019277361A1 (en) * | 2018-05-30 | 2020-12-17 | Translate Bio, Inc. | Messenger RNA vaccines and uses thereof |
WO2020023390A1 (en) | 2018-07-25 | 2020-01-30 | Modernatx, Inc. | Mrna based enzyme replacement therapy combined with a pharmacological chaperone for the treatment of lysosomal storage disorders |
IL267923B2 (en) * | 2018-08-02 | 2023-06-01 | Grifols Worldwide Operations Ltd | The composition containing the most concentrated alpha-1 type protein inhibitor and a method for obtaining it |
US10842885B2 (en) | 2018-08-20 | 2020-11-24 | Ucl Business Ltd | Factor IX encoding nucleotides |
CN112739327A (zh) * | 2018-08-24 | 2021-04-30 | 旗舰创业创新六公司 | 修饰的植物信使包及其用途 |
CN112930396B (zh) | 2018-08-24 | 2024-05-24 | 川斯勒佰尔公司 | 用于纯化信使rna的方法 |
KR20210091120A (ko) | 2018-08-29 | 2021-07-21 | 트랜슬레이트 바이오 인코포레이티드 | Mrna-로딩된 지질 나노입자를 제조하는 개선된 공정 |
US20220110966A1 (en) | 2018-09-02 | 2022-04-14 | Modernatx, Inc. | Polynucleotides encoding very long-chain acyl-coa dehydrogenase for the treatment of very long-chain acyl-coa dehydrogenase deficiency |
EP3846822A4 (en) | 2018-09-04 | 2022-07-06 | The Board Of Regents Of The University Of Texas System | COMPOSITIONS AND METHODS FOR ORGAN-SPECIFIC DELIVERY OF NUCLEIC ACIDS |
WO2020051220A1 (en) | 2018-09-04 | 2020-03-12 | The Board of the Regents of the University of Texas System | Compositions and methods for organ specific delivery of nucleic acids |
US20230009009A1 (en) | 2018-09-13 | 2023-01-12 | Modernatx, Inc. | Polynucleotides encoding glucose-6-phosphatase for the treatment of glycogen storage disease |
US20220243182A1 (en) | 2018-09-13 | 2022-08-04 | 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 |
AU2019339430A1 (en) | 2018-09-14 | 2021-04-29 | Modernatx, Inc. | Polynucleotides encoding uridine diphosphate glycosyltransferase 1 family, polypeptide A1 for the treatment of Crigler-Najjar Syndrome |
WO2020069169A1 (en) | 2018-09-27 | 2020-04-02 | Modernatx, Inc. | Polynucleotides encoding arginase 1 for the treatment of arginase deficiency |
AU2019347774A1 (en) | 2018-09-28 | 2021-03-25 | Nutcracker Therapeutics, Inc. | Lipid nanoparticle formulations comprising lipidated cationic peptide compounds for nucleic acid delivery |
US11072808B2 (en) | 2018-10-04 | 2021-07-27 | New England Biolabs, Inc. | Methods and compositions for increasing capping efficiency of transcribed RNA |
WO2020072914A1 (en) | 2018-10-04 | 2020-04-09 | New England Biolabs, Inc. | Methods and compositions for increasing capping efficiency of transcribed rna |
FI3864163T3 (fi) * | 2018-10-09 | 2024-05-03 | Univ British Columbia | Koostumukset ja järjestelmät, joihin sisältyvät transfektiokompetentit vesikkelit, joissa ei ole orgaanisia liuottimia eikä pesuaineita, sekä niihin liittyvät menetelmät |
US20210388338A1 (en) | 2018-11-08 | 2021-12-16 | Translate Bio, Inc. | Methods and Compositions for Messenger RNA Purification |
US20220001026A1 (en) | 2018-11-08 | 2022-01-06 | Modernatx, Inc. | Use of mrna encoding ox40l to treat cancer in human patients |
EP3880174A2 (en) | 2018-11-12 | 2021-09-22 | Translate Bio, Inc. | Methods for inducing immune tolerance |
AU2019384557A1 (en) | 2018-11-21 | 2021-06-10 | Translate Bio, Inc. | Treatment of cystic fibrosis by delivery of nebulized mRNA encoding CFTR |
ES2960692T3 (es) | 2018-12-06 | 2024-03-06 | Arcturus Therapeutics Inc | Composiciones y métodos para el tratamiento de la deficiencia de ornitina transcarbamilasa |
BR112021011750A2 (pt) | 2018-12-20 | 2021-08-31 | Codexis, Inc. | Alfa-galactosidase a recombinante e/ou fragmento de alfa-galactosidase a recombinante, composição, sequência de polinucleotídeo recombinante, vetor de expressão, célula hospedeira, métodos para produzir uma variante de alfa-galactosidase a e para tratar e/ou prevenir os sintomas da doença de fabry, composição farmacêutica, e, uso das composições |
BR112021009422A2 (pt) | 2018-12-21 | 2021-10-26 | Curevac Ag | Rna para vacinas contra malária |
CN113365607A (zh) * | 2019-01-25 | 2021-09-07 | 豪夫迈·罗氏有限公司 | 用于口服药物递送的脂质囊泡 |
CA3125511A1 (en) | 2019-02-08 | 2020-08-13 | Curevac Ag | Coding rna administered into the suprachoroidal space in the treatment of ophthalmic diseases |
DE112020001342T5 (de) | 2019-03-19 | 2022-01-13 | President and Fellows of Harvard College | Verfahren und Zusammensetzungen zum Editing von Nukleotidsequenzen |
EP3953473A1 (en) | 2019-04-12 | 2022-02-16 | MiNA Therapeutics Limited | Sirt1-sarna compositions and methods of use |
CN114375190A (zh) | 2019-05-08 | 2022-04-19 | 阿斯利康(瑞典)有限公司 | 用于皮肤和伤口的组合物及其使用方法 |
CA3140423A1 (en) | 2019-05-14 | 2020-11-19 | Translate Bio, Inc. | Improved process of preparing mrna-loaded lipid nanoparticles |
AU2020280105A1 (en) | 2019-05-22 | 2022-01-20 | Massachusetts Institute Of Technology | Circular RNA compositions and methods |
WO2020254535A1 (en) | 2019-06-18 | 2020-12-24 | Curevac Ag | Rotavirus mrna vaccine |
EP3987028A4 (en) * | 2019-06-21 | 2023-07-19 | Kernal Biologics, Inc. | MODIFIED ONCOSELECTIVE PROTEIN EXPRESSION |
US20220387628A1 (en) | 2019-06-24 | 2022-12-08 | Modernatx, Inc. | Messenger rna comprising functional rna elements and uses thereof |
EP3987027A1 (en) | 2019-06-24 | 2022-04-27 | ModernaTX, Inc. | Endonuclease-resistant messenger rna and uses thereof |
WO2020262150A1 (ja) * | 2019-06-24 | 2020-12-30 | 国立大学法人北海道大学 | 脂質ナノ粒子 |
US20220265781A1 (en) | 2019-07-18 | 2022-08-25 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for inducing full ablation of hematopoiesis |
JP2022541586A (ja) * | 2019-07-19 | 2022-09-26 | ユニバーシティ オブ フロリダ リサーチ ファンデーション インコーポレーティッド | 多層rnaナノ粒子 |
EP4003397A1 (en) | 2019-07-30 | 2022-06-01 | Translate Bio, Inc. | Treatment of cystic fibrosis by delivery of nebulized mrna encoding cftr |
WO2021028439A1 (en) | 2019-08-14 | 2021-02-18 | Curevac Ag | Rna combinations and compositions with decreased immunostimulatory properties |
MX2022003269A (es) | 2019-09-19 | 2022-07-04 | Modernatx Inc | Compuestos lipidicos de cola ramificada y composiciones para la administracion intracelular de agentes terapeuticos. |
EP4041400A1 (en) | 2019-10-09 | 2022-08-17 | Translate Bio, Inc. | Compositions, methods and uses of messenger rna |
CA3160739A1 (en) | 2019-12-04 | 2021-06-10 | Brian Goodman | Circular rna compositions and methods |
BR112022013761A2 (pt) * | 2020-01-10 | 2022-11-01 | Andrew Aprikyan Andranik | Nanopartículas para expressão de genes de interesse e/ou regulação de vias de sinalização |
JP2023511633A (ja) | 2020-01-28 | 2023-03-20 | モデルナティエックス インコーポレイテッド | コロナウイルスrnaワクチン |
CA3160511A1 (en) | 2020-02-04 | 2021-08-12 | Susanne RAUCH | Coronavirus vaccine |
CA3170150A1 (en) | 2020-02-07 | 2021-08-12 | Modernatx, Inc. | Sars-cov-2 mrna domain vaccines |
WO2021173840A1 (en) | 2020-02-25 | 2021-09-02 | Translate Bio, Inc. | Improved processes of preparing mrna-loaded lipid nanoparticles |
GB202307565D0 (en) | 2020-04-22 | 2023-07-05 | BioNTech SE | Coronavirus vaccine |
WO2021222304A1 (en) | 2020-04-27 | 2021-11-04 | Modernatx, Inc. | Sars-cov-2 rna vaccines |
EP4146804A1 (en) | 2020-05-08 | 2023-03-15 | The Broad Institute Inc. | Methods and compositions for simultaneous editing of both strands of a target double-stranded nucleotide sequence |
JP2023526310A (ja) | 2020-05-12 | 2023-06-21 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | 導入遺伝子発現のdrg特異的低減のための組成物 |
WO2021159130A2 (en) | 2020-05-15 | 2021-08-12 | Modernatx, Inc. | Coronavirus rna vaccines and methods of use |
CN116322788A (zh) | 2020-05-19 | 2023-06-23 | 奥纳治疗公司 | 环状rna组合物和方法 |
BR112022024248A2 (pt) | 2020-05-29 | 2023-10-10 | CureVac SE | Vacinas de combinação à base de ácido nucleico |
JP2023527875A (ja) | 2020-06-01 | 2023-06-30 | モダーナティエックス・インコーポレイテッド | フェニルアラニンヒドロキシラーゼバリアント及びその使用 |
US20230272378A1 (en) | 2020-06-12 | 2023-08-31 | University Of Rochester | ENCODING AND EXPRESSION OF ACE-tRNAs |
WO2021257668A1 (en) | 2020-06-17 | 2021-12-23 | The Trustees Of The University Of Pennsylvania | Compositions and methods for treatment of gene therapy patients |
IL299762A (en) | 2020-07-13 | 2023-03-01 | Univ Pennsylvania | Useful preparations for the treatment of Charcot-Marietot disease |
EP4179112A2 (en) | 2020-07-13 | 2023-05-17 | The Board of Trustees of the Leland Stanford Junior University | Systems and methods to assess rna stability |
EP4172194A1 (en) | 2020-07-31 | 2023-05-03 | CureVac SE | Nucleic acid encoded antibody mixtures |
US11406703B2 (en) | 2020-08-25 | 2022-08-09 | Modernatx, Inc. | Human cytomegalovirus vaccine |
CA3170743A1 (en) | 2020-08-31 | 2022-03-03 | Susanne RAUCH | Multivalent nucleic acid based coronavirus vaccines |
WO2022047427A2 (en) | 2020-08-31 | 2022-03-03 | The Board Of Trustees Of The Leland Stanford Junior University | Systems and methods for producing rna constructs with increased translation and stability |
US20230355743A1 (en) | 2020-09-25 | 2023-11-09 | Modernatx, Inc. | Multi-proline-substituted coronavirus spike protein vaccines |
CA3197342A1 (en) | 2020-10-07 | 2022-04-14 | Regenxbio Inc. | Gene therapy for ocular manifestations of cln2 disease |
US20230365955A1 (en) | 2020-10-09 | 2023-11-16 | The Trustees Of The University Of Pennsylvania | Compositions and methods for treatment of fabry disease |
EP4240367A2 (en) | 2020-11-04 | 2023-09-13 | Myeloid Therapeutics, Inc. | Engineered chimeric fusion protein compositions and methods of use thereof |
TW202233232A (zh) | 2020-11-06 | 2022-09-01 | 法商賽諾菲公司 | 遞送mRNA疫苗的脂質奈米顆粒 |
US20230406895A1 (en) | 2020-11-13 | 2023-12-21 | Modernatx, Inc. | Polynucleotides encoding cystic fibrosis transmembrane conductance regulator for the treatment of cystic fibrosis |
WO2022119890A1 (en) | 2020-12-01 | 2022-06-09 | The Trustees Of The University Of Pennsylvania | Compositions and uses thereof for treatment of angelman syndrome |
TW202237850A (zh) | 2020-12-01 | 2022-10-01 | 賓州大學委員會 | 具有組織特異性靶向基序的新穎構成物及含有其之組成物 |
EP4255888A2 (en) * | 2020-12-02 | 2023-10-11 | Merck Sharp & Dohme LLC | Lipid nanoparticle compositions containing monoester cationic lipids |
GB2603454A (en) | 2020-12-09 | 2022-08-10 | Ucl Business Ltd | Novel therapeutics for the treatment of neurodegenerative disorders |
WO2022137133A1 (en) | 2020-12-22 | 2022-06-30 | Curevac Ag | Rna vaccine against sars-cov-2 variants |
WO2022135993A2 (en) | 2020-12-22 | 2022-06-30 | Curevac Ag | Pharmaceutical composition comprising lipid-based carriers encapsulating rna for multidose administration |
WO2022150717A1 (en) | 2021-01-11 | 2022-07-14 | Modernatx, Inc. | Seasonal rna influenza virus vaccines |
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 |
AU2022208057A1 (en) | 2021-01-15 | 2023-08-03 | Modernatx, Inc. | Variant strain-based coronavirus vaccines |
AU2022207495A1 (en) | 2021-01-15 | 2023-08-03 | Modernatx, Inc. | Variant strain-based coronavirus vaccines |
CA3170747A1 (en) | 2021-01-27 | 2022-08-04 | Moritz THRAN | Method of reducing the immunostimulatory properties of in vitro transcribed rna |
CA3209779A1 (en) | 2021-02-01 | 2022-08-04 | Regenxbio Inc. | Gene therapy for neuronal ceroid lipofuscinoses |
US11524023B2 (en) | 2021-02-19 | 2022-12-13 | Modernatx, Inc. | Lipid nanoparticle compositions and methods of formulating the same |
JP2024511346A (ja) | 2021-03-15 | 2024-03-13 | モデルナティエックス インコーポレイテッド | Sars-cov-2 mrnaドメインワクチンの治療的使用 |
US20240216515A1 (en) * | 2021-03-22 | 2024-07-04 | Recode Therapeutics, Inc. | Compositions and methods for targeted delivery to cells |
WO2022204369A1 (en) | 2021-03-24 | 2022-09-29 | Modernatx, Inc. | Polynucleotides encoding methylmalonyl-coa mutase for the treatment of methylmalonic acidemia |
US20240216288A1 (en) | 2021-03-24 | 2024-07-04 | Modernatx, Inc. | Lipid nanoparticles containing polynucleotides encoding propionyl-coa carboxylase alpha and beta subunits and uses thereof |
US20240207374A1 (en) | 2021-03-24 | 2024-06-27 | Modernatx, Inc. | Lipid nanoparticles containing polynucleotides encoding glucose-6-phosphatase and uses thereof |
WO2022204390A1 (en) | 2021-03-24 | 2022-09-29 | Modernatx, Inc. | Lipid nanoparticles containing polynucleotides encoding phenylalanine hydroxylase and uses thereof |
US20240189449A1 (en) | 2021-03-24 | 2024-06-13 | Modernatx, Inc. | Lipid nanoparticles and polynucleotides encoding ornithine transcarbamylase for the treatment of ornithine transcarbamylase deficiency |
US20240181037A1 (en) | 2021-03-26 | 2024-06-06 | Glaxosmithkline Biologicals Sa | Immunogenic compositions |
AU2022246144A1 (en) | 2021-03-26 | 2023-09-21 | Mina Therapeutics Limited | Tmem173 sarna compositions and methods of use |
EP4312988A2 (en) | 2021-03-31 | 2024-02-07 | CureVac SE | Syringes containing pharmaceutical compositions comprising rna |
WO2022216536A1 (en) * | 2021-04-06 | 2022-10-13 | Animatus Biosciences, Inc. | Selective expression of mrnas in cardiomyocytes without cardiac fibroblast stimulation |
JP2024515612A (ja) | 2021-04-12 | 2024-04-10 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | 球脊髄性筋萎縮症(sbma)の治療に有用な組成物 |
AU2022258335A1 (en) | 2021-04-13 | 2023-11-23 | Modernatx, Inc. | Respiratory virus combination vaccines |
AU2022258463A1 (en) | 2021-04-14 | 2023-11-23 | Modernatx, Inc. | Influenza-coronavirus combination vaccines |
AR125406A1 (es) | 2021-04-23 | 2023-07-12 | Univ Pennsylvania | Nuevas composiciones con motivos selectivos para el cerebro y composiciones que las contienen |
EP4334446A1 (en) | 2021-05-03 | 2024-03-13 | CureVac SE | Improved nucleic acid sequence for cell type specific expression |
WO2022245888A1 (en) | 2021-05-19 | 2022-11-24 | Modernatx, Inc. | Seasonal flu rna vaccines and methods of use |
EP4355882A2 (en) | 2021-06-15 | 2024-04-24 | Modernatx, Inc. | Engineered polynucleotides for cell-type or microenvironment-specific expression |
US20230043128A1 (en) | 2021-06-18 | 2023-02-09 | Sanofi | Multivalent influenza vaccines |
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 |
WO2023002509A1 (en) | 2021-07-23 | 2023-01-26 | Institute For Stem Cell Science And Regenerative Medicine | Lipid formulation for delivery of therapeutic agents |
EP4392140A1 (en) | 2021-08-24 | 2024-07-03 | BioNTech SE | In vitro transcription technologies |
IL309505A (en) | 2021-09-03 | 2024-02-01 | CureVac SE | Lipid nanoparticles for nucleic acid delivery |
CN117940158A (zh) | 2021-09-03 | 2024-04-26 | 库瑞瓦格欧洲公司 | 用于核酸递送的包含磷脂酰丝氨酸的新型脂质纳米颗粒 |
CN118043466A (zh) | 2021-09-03 | 2024-05-14 | 葛兰素史克生物有限公司 | 自扩增信使核糖核酸中核苷酸碱基的取代 |
WO2023056044A1 (en) | 2021-10-01 | 2023-04-06 | Modernatx, Inc. | Polynucleotides encoding relaxin for the treatment of fibrosis and/or cardiovascular disease |
WO2023064599A1 (en) * | 2021-10-14 | 2023-04-20 | Kernal Biologics, Inc. | Compositions and methods for delivery of agents |
KR20240090727A (ko) | 2021-10-22 | 2024-06-21 | 세일 바이오메디슨스, 인크. | Mrna 백신 조성물 |
WO2023073228A1 (en) | 2021-10-29 | 2023-05-04 | CureVac SE | Improved circular rna for expressing therapeutic proteins |
IL312452A (en) | 2021-11-01 | 2024-06-01 | Tome Biosciences Inc | A transformant has a single structure for the simultaneous transfer of a gene editing mechanism and a nucleic acid cargo |
AR127585A1 (es) | 2021-11-05 | 2024-02-07 | Sanofi Sa | Vacuna de arn de virus sincicial respiratorio |
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 |
WO2023087019A2 (en) | 2021-11-15 | 2023-05-19 | The Trustees Of The University Of Pennsylvania | Compositions for drg-specific reduction of transgene expression |
WO2023092069A1 (en) | 2021-11-18 | 2023-05-25 | Modernatx, Inc. | Sars-cov-2 mrna domain vaccines and methods of use |
WO2023089183A1 (en) | 2021-11-19 | 2023-05-25 | Branca Bunus Limited | A composition comprising a therapeutically active agent packaged within a drug delivery vehicle |
AU2022398450A1 (en) | 2021-11-23 | 2024-06-06 | Sail Biomedicines, Inc. | A bacteria-derived lipid composition and use thereof |
CA3239417A1 (en) | 2021-11-30 | 2023-06-08 | Yvonne CHAN | Human metapneumovirus vaccines |
WO2023099884A1 (en) | 2021-12-01 | 2023-06-08 | Mina Therapeutics Limited | Pax6 sarna compositions and methods of use |
WO2023102517A1 (en) | 2021-12-02 | 2023-06-08 | The Trustees Of The University Of Pennsylvania | Compositions and methods for treatment of fabry disease |
WO2023107999A2 (en) | 2021-12-08 | 2023-06-15 | Modernatx, Inc. | Herpes simplex virus mrna vaccines |
GB202117758D0 (en) | 2021-12-09 | 2022-01-26 | Ucl Business Ltd | Therapeutics for the treatment of neurodegenerative disorders |
WO2023111262A1 (en) | 2021-12-17 | 2023-06-22 | Sanofi | Lyme disease rna vaccine |
WO2023122080A1 (en) | 2021-12-20 | 2023-06-29 | Senda Biosciences, Inc. | Compositions comprising mrna and lipid reconstructed plant messenger packs |
WO2023122762A1 (en) | 2021-12-22 | 2023-06-29 | Camp4 Therapeutics Corporation | Modulation of gene transcription using antisense oligonucleotides targeting regulatory rnas |
WO2023122764A1 (en) | 2021-12-22 | 2023-06-29 | Tome Biosciences, Inc. | Co-delivery of a gene editor construct and a donor template |
WO2023133574A1 (en) | 2022-01-10 | 2023-07-13 | The Trustees Of The University Of Pennsylvania | Compositions and methods useful for treatment of c9orf72-mediated disorders |
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 |
WO2023141586A1 (en) | 2022-01-21 | 2023-07-27 | Orna Therapeutics, Inc. | Systemic administration of circular rna polynucleotides encoding muscle proteins or protein complexes |
WO2023147090A1 (en) | 2022-01-27 | 2023-08-03 | BioNTech SE | Pharmaceutical compositions for delivery of herpes simplex virus antigens and related methods |
WO2023144330A1 (en) | 2022-01-28 | 2023-08-03 | CureVac SE | Nucleic acid encoded transcription factor inhibitors |
WO2023150753A1 (en) | 2022-02-07 | 2023-08-10 | University Of Rochester | Optimized sequences for enhanced trna expression or/and nonsense mutation suppression |
WO2023161350A1 (en) | 2022-02-24 | 2023-08-31 | Io Biotech Aps | Nucleotide delivery of cancer therapy |
WO2023170435A1 (en) | 2022-03-07 | 2023-09-14 | Mina Therapeutics Limited | Il10 sarna compositions and methods of use |
WO2023177904A1 (en) | 2022-03-18 | 2023-09-21 | Modernatx, Inc. | Sterile filtration of lipid nanoparticles and filtration analysis thereof for biological applications |
WO2023178425A1 (en) | 2022-03-23 | 2023-09-28 | Nanovation Therapeutics Inc. | High sterol-containing lipid nanoparticles |
WO2023183909A2 (en) | 2022-03-25 | 2023-09-28 | Modernatx, Inc. | Polynucleotides encoding fanconi anemia, complementation group proteins for the treatment of fanconi anemia |
WO2023184038A1 (en) | 2022-04-01 | 2023-10-05 | Nanovation Therapeutics Inc. | Mrna delivery method and composition thereof |
WO2023196914A1 (en) | 2022-04-08 | 2023-10-12 | Modernatx, Inc. | Influenza nucleic acid compositions and uses thereof |
US20230346977A1 (en) | 2022-04-13 | 2023-11-02 | Universitat Autònoma De Barcelona | Treatment of neuromuscular diseases via gene therapy that expresses klotho protein |
WO2023205744A1 (en) | 2022-04-20 | 2023-10-26 | Tome Biosciences, Inc. | Programmable gene insertion compositions |
WO2023215831A1 (en) | 2022-05-04 | 2023-11-09 | Tome Biosciences, Inc. | Guide rna compositions for programmable gene insertion |
TW202408567A (zh) | 2022-05-06 | 2024-03-01 | 法商賽諾菲公司 | 用於核酸疫苗之訊息序列 |
WO2023225670A2 (en) | 2022-05-20 | 2023-11-23 | Tome Biosciences, Inc. | Ex vivo programmable gene insertion |
WO2023230481A1 (en) | 2022-05-24 | 2023-11-30 | Modernatx, Inc. | Orthopoxvirus vaccines |
WO2023227608A1 (en) | 2022-05-25 | 2023-11-30 | Glaxosmithkline Biologicals Sa | Nucleic acid based vaccine encoding an escherichia coli fimh antigenic polypeptide |
WO2023231959A2 (en) | 2022-05-30 | 2023-12-07 | Shanghai Circode Biomed Co., Ltd | Synthetic circular rna compositions and methods of use thereof |
WO2023240277A2 (en) | 2022-06-10 | 2023-12-14 | Camp4 Therapeutics Corporation | Methods of modulating progranulin expression using antisense oligonucleotides targeting regulatory rnas |
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 |
WO2024015890A1 (en) | 2022-07-13 | 2024-01-18 | Modernatx, Inc. | Norovirus mrna vaccines |
WO2024017253A1 (zh) * | 2022-07-19 | 2024-01-25 | 深圳深信生物科技有限公司 | 新型冠状病毒S蛋白的mRNA及其应用 |
WO2024020587A2 (en) | 2022-07-22 | 2024-01-25 | Tome Biosciences, Inc. | Pleiopluripotent stem cell programmable gene insertion |
WO2024026254A1 (en) | 2022-07-26 | 2024-02-01 | Modernatx, Inc. | Engineered polynucleotides for temporal control of expression |
WO2024044108A1 (en) | 2022-08-22 | 2024-02-29 | The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. | Vaccines against coronaviruses |
WO2024044147A1 (en) | 2022-08-23 | 2024-02-29 | Modernatx, Inc. | Methods for purification of ionizable lipids |
WO2024050483A1 (en) | 2022-08-31 | 2024-03-07 | Modernatx, Inc. | Variant strain-based coronavirus vaccines and uses thereof |
AU2023274159A1 (en) * | 2022-09-07 | 2024-03-21 | Eyegene Inc. | COMPOSITION FOR IN-VIVO DELIVERING mRNA CONTAINING MODIFIED NUCLEOTIDE |
WO2024064931A1 (en) | 2022-09-23 | 2024-03-28 | BioNTech SE | Compositions for delivery of liver stage antigens and related methods |
WO2024063789A1 (en) | 2022-09-23 | 2024-03-28 | BioNTech SE | Compositions for delivery of malaria antigens and related methods |
WO2024063788A1 (en) | 2022-09-23 | 2024-03-28 | BioNTech SE | Compositions for delivery of malaria antigens and related methods |
WO2024064934A1 (en) | 2022-09-23 | 2024-03-28 | BioNTech SE | Compositions for delivery of plasmodium csp antigens and related methods |
WO2024068545A1 (en) | 2022-09-26 | 2024-04-04 | Glaxosmithkline Biologicals Sa | Influenza virus vaccines |
WO2024072929A1 (en) * | 2022-09-30 | 2024-04-04 | Merck Sharp & Dohme Llc | An analytical method using lc-ms/ms proteomics to characterize proteins translated from mrna |
WO2024083345A1 (en) | 2022-10-21 | 2024-04-25 | BioNTech SE | Methods and uses associated with liquid compositions |
WO2024089638A1 (en) | 2022-10-28 | 2024-05-02 | Glaxosmithkline Biologicals Sa | Nucleic acid based vaccine |
WO2024094881A1 (en) | 2022-11-04 | 2024-05-10 | Sanofi | Respiratory syncytial virus rna vaccination |
WO2024094876A1 (en) | 2022-11-04 | 2024-05-10 | Sanofi | Methods for messenger rna tailing |
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 |
WO2024102954A1 (en) | 2022-11-10 | 2024-05-16 | Massachusetts Institute Of Technology | Activation induced clipping system (aics) |
WO2024102434A1 (en) | 2022-11-10 | 2024-05-16 | Senda Biosciences, Inc. | Rna compositions comprising lipid nanoparticles or lipid reconstructed natural messenger packs |
WO2024119145A1 (en) | 2022-12-01 | 2024-06-06 | Camp4 Therapeutics Corporation | Modulation of syngap1 gene transcription using antisense oligonucleotides targeting regulatory rnas |
WO2024119276A1 (en) * | 2022-12-07 | 2024-06-13 | The University Of British Columbia | Compositions and methods for peptide or protein delivery to the delivery to the central nervous system |
WO2024121378A1 (en) | 2022-12-09 | 2024-06-13 | Institut National de la Santé et de la Recherche Médicale | Novel human antiviral genes related to the eleos and lamassu prokaryotic systems |
WO2024129982A2 (en) | 2022-12-15 | 2024-06-20 | Orna Therapeutics, Inc. | Circular rna compositions and methods |
WO2024126809A1 (en) | 2022-12-15 | 2024-06-20 | Sanofi | Mrna encoding influenza virus-like particle |
WO2024126847A1 (en) | 2022-12-15 | 2024-06-20 | Sanofi | Mrna recombinant capping enzymes |
WO2024130070A2 (en) | 2022-12-17 | 2024-06-20 | The Trustees Of The University Of Pennsylvania | Recombinant aav capsids with cardiac- and skeletal muscle- specific targeting motifs and uses thereof |
WO2024130067A2 (en) | 2022-12-17 | 2024-06-20 | The Trustees Of The University Of Pennsylvania | Recombinant aav mutant vectors with cardiac and skeletal muscle-specific targeting motifs and compositions containing same |
WO2024133160A1 (en) | 2022-12-19 | 2024-06-27 | Glaxosmithkline Biologicals Sa | Hepatitis b compositions |
WO2024134199A1 (en) | 2022-12-22 | 2024-06-27 | Mina Therapeutics Limited | Chemically modified sarna compositions and methods of use |
WO2024138194A1 (en) | 2022-12-22 | 2024-06-27 | Tome Biosciences, Inc. | Platforms, compositions, and methods for in vivo programmable gene insertion |
WO2024133884A2 (en) | 2022-12-23 | 2024-06-27 | Sanofi | Optimized tailing of messenger rna |
GB202404607D0 (en) | 2024-03-29 | 2024-05-15 | Glaxosmithkline Biologicals Sa | RNA formulation |
Family Cites Families (521)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2647121A (en) | 1951-02-02 | 1953-07-28 | Ruth P Jacoby | Diamine-bis-acetamides |
US2819718A (en) | 1953-07-16 | 1958-01-14 | Isidore H Goldman | Drainage tube |
US2717909A (en) | 1953-09-24 | 1955-09-13 | Monsanto Chemicals | Hydroxyethyl-keryl-alkylene-ammonium compounds |
US2844629A (en) | 1956-04-25 | 1958-07-22 | American Home Prod | Fatty acid amides and derivatives thereof |
US3096560A (en) | 1958-11-21 | 1963-07-09 | William J Liebig | Process for synthetic vascular implants |
GB1072118A (en) | 1962-12-01 | 1967-06-14 | Sandoz Ag | Amides of aminopropionic acid |
FR1378382A (fr) | 1962-12-01 | 1964-11-13 | Sandoz Sa | Amides de l'acide amino-propionique, utilisables en particulier pour le traitement des fibres textiles |
JPS5141663B1 (ja) | 1966-03-12 | 1976-11-11 | ||
JPS4822365B1 (ja) | 1968-10-25 | 1973-07-05 | ||
NL143127B (nl) | 1969-02-04 | 1974-09-16 | Rhone Poulenc Sa | Versterkingsorgaan voor een defecte hartklep. |
JPS4822365Y1 (ja) | 1969-11-28 | 1973-06-29 | ||
US3614954A (en) | 1970-02-09 | 1971-10-26 | Medtronic Inc | Electronic standby defibrillator |
US3614955A (en) | 1970-02-09 | 1971-10-26 | Medtronic Inc | Standby defibrillator and method of operation |
JPS5024216Y1 (ja) | 1970-12-29 | 1975-07-21 | ||
JPS5024216B1 (ja) | 1970-12-29 | 1975-08-14 | ||
JPS5012146Y2 (ja) | 1971-07-27 | 1975-04-15 | ||
JPS5123537Y2 (ja) | 1972-01-17 | 1976-06-17 | ||
US3945052A (en) | 1972-05-01 | 1976-03-23 | Meadox Medicals, Inc. | Synthetic vascular graft and method for manufacturing the same |
US3805301A (en) | 1972-07-28 | 1974-04-23 | Meadox Medicals Inc | Tubular grafts having indicia thereon |
JPS5210847Y2 (ja) | 1972-10-11 | 1977-03-09 | ||
JPS49127908A (ja) | 1973-04-20 | 1974-12-07 | ||
JPS5624664B2 (ja) | 1973-06-28 | 1981-06-08 | ||
US4013507A (en) | 1973-09-18 | 1977-03-22 | California Institute Of Technology | Ionene polymers for selectively inhibiting the vitro growth of malignant cells |
JPS5123537A (ja) | 1974-04-26 | 1976-02-25 | Adeka Argus Chemical Co Ltd | Kasozaisoseibutsu |
GB1527592A (en) | 1974-08-05 | 1978-10-04 | Ici Ltd | Wound dressing |
US3995623A (en) | 1974-12-23 | 1976-12-07 | American Hospital Supply Corporation | Multipurpose flow-directed catheter |
JPS5813576B2 (ja) | 1974-12-27 | 1983-03-14 | アデカ ア−ガスカガク カブシキガイシヤ | 安定化された合成高分子組成物 |
JPS5524302Y2 (ja) | 1975-03-31 | 1980-06-10 | ||
DE2520814A1 (de) | 1975-05-09 | 1976-11-18 | Bayer Ag | Lichtstabilisierung von polyurethanen |
US4281669A (en) | 1975-05-09 | 1981-08-04 | Macgregor David C | Pacemaker electrode with porous system |
JPS5210847A (en) | 1975-07-16 | 1977-01-27 | Nippon Steel Corp | Pinch roll |
US4096860A (en) | 1975-10-08 | 1978-06-27 | Mclaughlin William F | Dual flow encatheter |
CA1069652A (en) | 1976-01-09 | 1980-01-15 | Alain F. Carpentier | Supported bioprosthetic heart valve with compliant orifice ring |
US4134402A (en) | 1976-02-11 | 1979-01-16 | Mahurkar Sakharam D | Double lumen hemodialysis catheter |
US4072146A (en) | 1976-09-08 | 1978-02-07 | Howes Randolph M | Venous catheter device |
US4335723A (en) | 1976-11-26 | 1982-06-22 | The Kendall Company | Catheter having inflatable retention means |
US4099528A (en) | 1977-02-17 | 1978-07-11 | Sorenson Research Co., Inc. | Double lumen cannula |
US4140126A (en) | 1977-02-18 | 1979-02-20 | Choudhury M Hasan | Method for performing aneurysm repair |
US4265745A (en) | 1977-05-25 | 1981-05-05 | Teijin Limited | Permselective membrane |
US4182833A (en) | 1977-12-07 | 1980-01-08 | Celanese Polymer Specialties Company | Cationic epoxide-amine reaction products |
US4180068A (en) | 1978-04-13 | 1979-12-25 | Motion Control, Incorporated | Bi-directional flow catheter with retractable trocar/valve structure |
EP0005035B1 (en) | 1978-04-19 | 1981-09-23 | Imperial Chemical Industries Plc | A method of preparing a tubular product by electrostatic spinning |
US4284459A (en) | 1978-07-03 | 1981-08-18 | The Kendall Company | Method for making a molded catheter |
US4227533A (en) | 1978-11-03 | 1980-10-14 | Bristol-Myers Company | Flushable urinary catheter |
US4375817A (en) | 1979-07-19 | 1983-03-08 | Medtronic, Inc. | Implantable cardioverter |
DE3010841A1 (de) | 1980-03-21 | 1981-10-08 | Ulrich Dr.med. 6936 Haag Uthmann | Katheder |
US4308085A (en) | 1980-07-28 | 1981-12-29 | Jenoptik Jena Gmbh | Process for the preparation of high molecular thermoplastic epoxide-amine-polyadducts |
US4339369A (en) | 1981-04-23 | 1982-07-13 | Celanese Corporation | Cationic epoxide-amine reaction products |
US4406656A (en) | 1981-06-01 | 1983-09-27 | Brack Gillium Hattler | Venous catheter having collapsible multi-lumens |
US4475972A (en) | 1981-10-01 | 1984-10-09 | Ontario Research Foundation | Implantable material |
US4401472A (en) | 1982-02-26 | 1983-08-30 | Martin Marietta Corporation | Hydraulic cement mixes and processes for improving hydraulic cement mixes |
US4568329A (en) | 1982-03-08 | 1986-02-04 | Mahurkar Sakharam D | Double lumen catheter |
US4546499A (en) | 1982-12-13 | 1985-10-15 | Possis Medical, Inc. | Method of supplying blood to blood receiving vessels |
US4530113A (en) | 1983-05-20 | 1985-07-23 | Intervascular, Inc. | Vascular grafts with cross-weave patterns |
US4550447A (en) | 1983-08-03 | 1985-11-05 | Shiley Incorporated | Vascular graft prosthesis |
US4647416A (en) | 1983-08-03 | 1987-03-03 | Shiley Incorporated | Method of preparing a vascular graft prosthesis |
US5104399A (en) | 1986-12-10 | 1992-04-14 | Endovascular Technologies, Inc. | Artificial graft and implantation method |
US4710169A (en) | 1983-12-16 | 1987-12-01 | Christopher T Graham | Urinary catheter with collapsible urethral tube |
US4571241A (en) | 1983-12-16 | 1986-02-18 | Christopher T Graham | Urinary catheter with collapsible urethral tube |
US4737518A (en) | 1984-04-03 | 1988-04-12 | Takeda Chemical Industries, Ltd. | Lipid derivatives, their production and use |
US4562596A (en) | 1984-04-25 | 1986-01-07 | Elliot Kornberg | Aortic graft, device and method for performing an intraluminal abdominal aortic aneurysm repair |
US4782836A (en) | 1984-05-24 | 1988-11-08 | Intermedics, Inc. | Rate adaptive cardiac pacemaker responsive to patient activity and temperature |
US4897355A (en) | 1985-01-07 | 1990-01-30 | Syntex (U.S.A.) Inc. | N[ω,(ω-1)-dialkyloxy]- and N-[ω,(ω-1)-dialkenyloxy]-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
US4662382A (en) | 1985-01-16 | 1987-05-05 | Intermedics, Inc. | Pacemaker lead with enhanced sensitivity |
US4762915A (en) | 1985-01-18 | 1988-08-09 | Liposome Technology, Inc. | Protein-liposome conjugates |
US4860751A (en) | 1985-02-04 | 1989-08-29 | Cordis Corporation | Activity sensor for pacemaker control |
US5223263A (en) | 1988-07-07 | 1993-06-29 | Vical, Inc. | Liponucleotide-containing liposomes |
CA1320724C (en) | 1985-07-19 | 1993-07-27 | Koichi Kanehira | Terpene amino alcohols and medicinal uses thereof |
US4701162A (en) | 1985-09-24 | 1987-10-20 | The Kendall Company | Foley catheter assembly |
US4737323A (en) | 1986-02-13 | 1988-04-12 | Liposome Technology, Inc. | Liposome extrusion method |
DE3616824A1 (de) | 1986-05-17 | 1987-11-19 | Schering Ag | Verwendung von haertbaren kunstharzmischungen fuer oberflaechenbeschichtungen und druckfarben und verfahren zu ihrer herstellung |
EP0255899B1 (de) | 1986-07-31 | 1992-07-15 | Werner Prof. Dr.-Ing. Irnich | Frequenzadaptierender Herzschrittmacher |
US4960409A (en) | 1986-09-11 | 1990-10-02 | Catalano Marc L | Method of using bilumen peripheral venous catheter with adapter |
JPH0829776B2 (ja) | 1986-10-29 | 1996-03-27 | 東燃化学株式会社 | 合成樹脂製容器及びその製造用金型 |
US4720517A (en) | 1986-11-24 | 1988-01-19 | Ciba-Geigy Corporation | Compositions stabilized with N-hydroxyiminodiacetic and dipropionic acids and esters thereof |
US4920016A (en) | 1986-12-24 | 1990-04-24 | Linear Technology, Inc. | Liposomes with enhanced circulation time |
JPS63125144U (ja) | 1987-02-09 | 1988-08-16 | ||
JPS63154788U (ja) | 1987-03-31 | 1988-10-11 | ||
WO1988007850A1 (en) | 1987-04-16 | 1988-10-20 | The Liposome Company, Inc. | Liposome continuous size reduction method and apparatus |
JPS63312934A (ja) | 1987-06-16 | 1988-12-21 | Hitachi Cable Ltd | 半導体用リ−ドフレ−ム材 |
DE3728917A1 (de) | 1987-08-29 | 1989-03-09 | Roth Hermann J | Neue lipide mit unsymmetrisch substituierter disulfidbruecke |
US4946683A (en) | 1987-11-18 | 1990-08-07 | Vestar, Inc. | Multiple step entrapment/loading procedure for preparing lipophilic drug-containing liposomes |
US5138067A (en) | 1987-12-17 | 1992-08-11 | Shionogi & Co. Ltd. | Lipid derivatives |
US5047540A (en) | 1987-12-17 | 1991-09-10 | Shionogi & Co., Ltd. | Lipid derivatives |
US4892540A (en) | 1988-04-21 | 1990-01-09 | Sorin Biomedica S.P.A. | Two-leaflet prosthetic heart valve |
US5176661A (en) | 1988-09-06 | 1993-01-05 | Advanced Cardiovascular Systems, Inc. | Composite vascular catheter |
US5024671A (en) | 1988-09-19 | 1991-06-18 | Baxter International Inc. | Microporous vascular graft |
US5200395A (en) | 1988-10-18 | 1993-04-06 | Ajinomoto Company, Inc. | Pharmaceutical composition of BUF-5 for treating anemia |
CA2001401A1 (en) | 1988-10-25 | 1990-04-25 | Claude Piantadosi | Quaternary amine containing ether or ester lipid derivatives and therapeutic compositions |
US5185154A (en) | 1989-02-02 | 1993-02-09 | Liposome Technology, Inc. | Method for instant preparation of a drug containing large unilamellar vesicles |
US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
US6214804B1 (en) | 1989-03-21 | 2001-04-10 | Vical Incorporated | Induction of a protective immune response in a mammal by injecting a DNA sequence |
DE69032284T2 (de) | 1989-03-21 | 1998-10-08 | Vical, Inc., San Diego, Calif. | Expression von exogenen polynukleotidsequenzen in wirbeltieren |
FR2645866B1 (fr) | 1989-04-17 | 1991-07-05 | Centre Nat Rech Scient | Nouvelles lipopolyamines, leur preparation et leur emploi |
US5194654A (en) | 1989-11-22 | 1993-03-16 | Vical, Inc. | Lipid derivatives of phosphonoacids for liposomal incorporation and method of use |
US5279833A (en) | 1990-04-04 | 1994-01-18 | Yale University | Liposomal transfection of nucleic acids into animal cells |
US5101824A (en) | 1990-04-16 | 1992-04-07 | Siemens-Pacesetter, Inc. | Rate-responsive pacemaker with circuitry for processing multiple sensor inputs |
US5264618A (en) | 1990-04-19 | 1993-11-23 | Vical, Inc. | Cationic lipids for intracellular delivery of biologically active molecules |
WO1992001425A1 (en) | 1990-07-26 | 1992-02-06 | Rodney James Lane | Self expanding vascular endoprosthesis for aneurysms |
US5693338A (en) | 1994-09-29 | 1997-12-02 | Emisphere Technologies, Inc. | Diketopiperazine-based delivery systems |
JPH0765267B2 (ja) | 1990-08-22 | 1995-07-12 | 花王株式会社 | 柔軟仕上剤 |
US5206027A (en) | 1990-09-13 | 1993-04-27 | Fuji Photo Film Co., Ltd. | Amphipathic compound and liposome comprising the same |
ES2085435T3 (es) | 1990-10-09 | 1996-06-01 | Cook Inc | Dispositivo dilatador percutaneo. |
EP0491082B1 (de) | 1990-12-19 | 1995-04-12 | Peter Dr. Ing. Osypka | Herzschrittmacherleitung mit einem inneren Kanal und mit einem Elektrodenkopf |
US5116360A (en) | 1990-12-27 | 1992-05-26 | Corvita Corporation | Mesh composite graft |
JP2547524Y2 (ja) | 1991-01-22 | 1997-09-10 | 東洋ラジエーター株式会社 | オイルクーラ |
US5405363A (en) | 1991-03-15 | 1995-04-11 | Angelon Corporation | Implantable cardioverter defibrillator having a smaller displacement volume |
US5330768A (en) | 1991-07-05 | 1994-07-19 | Massachusetts Institute Of Technology | Controlled drug delivery using polymer/pluronic blends |
US5545449A (en) | 1991-10-02 | 1996-08-13 | Weyerhaeuser Company | Polyether-reinforced fiber-based materials |
US5151105A (en) | 1991-10-07 | 1992-09-29 | Kwan Gett Clifford | Collapsible vessel sleeve implant |
US5284491A (en) | 1992-02-27 | 1994-02-08 | Medtronic, Inc. | Cardiac pacemaker with hysteresis behavior |
US5352461A (en) | 1992-03-11 | 1994-10-04 | Pharmaceutical Discovery Corporation | Self assembling diketopiperazine drug delivery system |
SE9200951D0 (sv) | 1992-03-27 | 1992-03-27 | Kabi Pharmacia Ab | Pharmaceutical composition containing a defined lipid system |
CA2132342A1 (en) | 1992-04-06 | 1993-10-14 | Kenneth F. Buechler | Novel opiate derivatives and protein and polypeptide opiate derivative conjugates and labels |
US6670178B1 (en) | 1992-07-10 | 2003-12-30 | Transkaryotic Therapies, Inc. | In Vivo production and delivery of insulinotropin for gene therapy |
CA2141685A1 (en) | 1992-08-04 | 1994-02-17 | Koji Naito | Antiallergic composition |
US5334761A (en) | 1992-08-28 | 1994-08-02 | Life Technologies, Inc. | Cationic lipids |
US5461223A (en) | 1992-10-09 | 1995-10-24 | Eastman Kodak Company | Bar code detecting circuitry |
US5300022A (en) | 1992-11-12 | 1994-04-05 | Martin Klapper | Urinary catheter and bladder irrigation system |
US5496362A (en) | 1992-11-24 | 1996-03-05 | Cardiac Pacemakers, Inc. | Implantable conformal coil patch electrode with multiple conductive elements for cardioversion and defibrillation |
US5552155A (en) | 1992-12-04 | 1996-09-03 | The Liposome Company, Inc. | Fusogenic lipsomes and methods for making and using same |
US5716395A (en) | 1992-12-11 | 1998-02-10 | W.L. Gore & Associates, Inc. | Prosthetic vascular graft |
CA2156288C (en) | 1993-02-19 | 2005-10-18 | Junichi Yano | Glycerol derivative, device and pharmaceutical composition |
US5395619A (en) | 1993-03-03 | 1995-03-07 | Liposome Technology, Inc. | Lipid-polymer conjugates and liposomes |
US5697953A (en) | 1993-03-13 | 1997-12-16 | Angeion Corporation | Implantable cardioverter defibrillator having a smaller displacement volume |
JPH0753535Y2 (ja) | 1993-03-16 | 1995-12-13 | 株式会社ハンズ | リュックサック |
US5624976A (en) | 1994-03-25 | 1997-04-29 | Dentsply Gmbh | Dental filling composition and method |
EP1624068A1 (en) | 1993-06-01 | 2006-02-08 | Life Technologies Inc. | Genetic immunization with cationic lipids |
US5314430A (en) | 1993-06-24 | 1994-05-24 | Medtronic, Inc. | Atrial defibrillator employing transvenous and subcutaneous electrodes and method of use |
DE4325848A1 (de) | 1993-07-31 | 1995-02-02 | Basf Ag | Verfahren zur Herstellung von N-(2-Hydroxyethyl)-piperazin |
EP0875280B1 (en) | 1993-10-06 | 2001-08-22 | The Kansai Electric Power Co., Inc. | Method for removing carbon dioxide from combustion exhaust gas |
US5609624A (en) | 1993-10-08 | 1997-03-11 | Impra, Inc. | Reinforced vascular graft and method of making same |
SE9303481L (sv) | 1993-10-22 | 1995-04-23 | Berol Nobel Ab | Hygienkomposition |
WO1995013033A1 (en) | 1993-11-08 | 1995-05-18 | Lazarus Harrison M | Intraluminal vascular graft and method |
CA2176714A1 (en) | 1993-11-24 | 1995-06-01 | Timothy D. Heath | Amphiphilic derivatives of piperazine |
US5595756A (en) | 1993-12-22 | 1997-01-21 | Inex Pharmaceuticals Corporation | Liposomal compositions for enhanced retention of bioactive agents |
US5464924A (en) | 1994-01-07 | 1995-11-07 | The Dow Chemical Company | Flexible poly(amino ethers) for barrier packaging |
US5844107A (en) | 1994-03-23 | 1998-12-01 | Case Western Reserve University | Compacted nucleic acids and their delivery to cells |
US6077835A (en) | 1994-03-23 | 2000-06-20 | Case Western Reserve University | Delivery of compacted nucleic acid to cells |
DK0758883T3 (da) | 1994-04-12 | 2003-06-02 | Liposome Co Inc | Fusogene liposomer og fremgangsmåder til fremstilling af og anvendelse af disse |
US5833979A (en) | 1994-07-20 | 1998-11-10 | Cytotherapeutics, Inc. | Methods and compositions of growth control for cells encapsulated within bioartificial organs |
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 |
US5641665A (en) | 1994-11-28 | 1997-06-24 | Vical Incorporated | Plasmids suitable for IL-2 expression |
US6071890A (en) | 1994-12-09 | 2000-06-06 | Genzyme Corporation | Organ-specific targeting of cationic amphiphile/DNA complexes for gene therapy |
US5965434A (en) | 1994-12-29 | 1999-10-12 | Wolff; Jon A. | Amphipathic PH sensitive compounds and delivery systems for delivering biologically active compounds |
US6485726B1 (en) | 1995-01-17 | 2002-11-26 | The Brigham And Women's Hospital, Inc. | Receptor specific transepithelial transport of therapeutics |
US5830430A (en) | 1995-02-21 | 1998-11-03 | Imarx Pharmaceutical Corp. | Cationic lipids and the use thereof |
JP2001523215A (ja) | 1995-04-17 | 2001-11-20 | イマークス ファーマシューティカル コーポレーション | ハイブリッド磁気共鳴造影剤 |
US5772694A (en) | 1995-05-16 | 1998-06-30 | Medical Carbon Research Institute L.L.C. | Prosthetic heart valve with improved blood flow |
US5783383A (en) | 1995-05-23 | 1998-07-21 | The Board Of Trustees Of The Leland Stanford Junior University | Method of detecting cytomegalovirus (CMV) |
US5981501A (en) | 1995-06-07 | 1999-11-09 | Inex Pharmaceuticals Corp. | Methods for encapsulating plasmids in lipid bilayers |
US5609629A (en) | 1995-06-07 | 1997-03-11 | Med Institute, Inc. | Coated implantable medical device |
US5705385A (en) | 1995-06-07 | 1998-01-06 | Inex Pharmaceuticals Corporation | Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer |
US7422902B1 (en) | 1995-06-07 | 2008-09-09 | The University Of British Columbia | Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer |
IL122290A0 (en) | 1995-06-07 | 1998-04-05 | Inex Pharmaceuticals Corp | Lipid-nucleic acid complex its preparation and use |
US5607385A (en) | 1995-08-17 | 1997-03-04 | Medtronic, Inc. | Device and algorithm for a combined cardiomyostimulator and a cardiac pacer-carioverter-defibrillator |
US5744335A (en) | 1995-09-19 | 1998-04-28 | Mirus Corporation | Process of transfecting a cell with a polynucleotide mixed with an amphipathic compound and a DNA-binding protein |
FR2740978B1 (fr) | 1995-11-10 | 1998-01-02 | Ela Medical Sa | Dispositif medical actif du type defibrillateur/cardioverteur implantable |
US6183774B1 (en) | 1996-01-31 | 2001-02-06 | Collaborative Laboratories, Inc. | Stabilizing vitamin A derivatives by encapsulation in lipid vesicles formed with alkylammonium fatty acid salts |
US5874105A (en) | 1996-01-31 | 1999-02-23 | Collaborative Laboratories, Inc. | Lipid vesicles formed with alkylammonium fatty acid salts |
US5783566A (en) * | 1996-05-10 | 1998-07-21 | California Institute Of Technology | Method for increasing or decreasing transfection efficiency |
ATE273320T1 (de) | 1996-04-11 | 2004-08-15 | Univ British Columbia | Fusogene liposomen |
US5935936A (en) | 1996-06-03 | 1999-08-10 | Genzyme Corporation | Compositions comprising cationic amphiphiles and co-lipids for intracellular delivery of therapeutic molecules |
US5913848A (en) | 1996-06-06 | 1999-06-22 | Luther Medical Products, Inc. | Hard tip over-the-needle catheter and method of manufacturing the same |
US5677124A (en) | 1996-07-03 | 1997-10-14 | Ambion, Inc. | Ribonuclease resistant viral RNA standards |
US5736573A (en) | 1996-07-31 | 1998-04-07 | Galat; Alexander | Lipid and water soluble derivatives of drugs |
US7288266B2 (en) | 1996-08-19 | 2007-10-30 | United States Of America As Represented By The Secretary, Department Of Health And Human Services | Liposome complexes for increased systemic delivery |
AU729077B2 (en) | 1996-08-26 | 2001-01-25 | Transgene S.A. | Cationic lipid-nucleic acid complexes |
US6458574B1 (en) | 1996-09-12 | 2002-10-01 | Transkaryotic Therapies, Inc. | Treatment of a α-galactosidase a deficiency |
EP0938298B1 (en) | 1996-09-13 | 2002-12-04 | Lipoxen Technologies Limited | Liposome-based composition |
TW520297B (en) | 1996-10-11 | 2003-02-11 | Sequus Pharm Inc | Fusogenic liposome composition and method |
WO1998019709A2 (en) | 1996-11-04 | 1998-05-14 | Qiagen Gmbh | Cationic reagents for transfection |
US6887665B2 (en) | 1996-11-14 | 2005-05-03 | Affymetrix, Inc. | Methods of array synthesis |
US5985930A (en) | 1996-11-21 | 1999-11-16 | Pasinetti; Giulio M. | Treatment of neurodegenerative conditions with nimesulide |
US6204297B1 (en) | 1996-11-26 | 2001-03-20 | Rhodia Inc. | Nonionic gemini surfactants |
JPH10197978A (ja) | 1997-01-09 | 1998-07-31 | Mitsubishi Paper Mills Ltd | ハロゲン化銀写真感光材料 |
EP0853123A1 (de) | 1997-01-10 | 1998-07-15 | Roche Diagnostics GmbH | Reinigung von DNA durch Cross-Flow-Filtration |
FR2760193B1 (fr) | 1997-02-28 | 1999-05-28 | Transgene Sa | Lipides et complexes de lipides cationiques et de substances actives, notamment pour la transfection de cellules |
US5837283A (en) | 1997-03-12 | 1998-11-17 | The Regents Of The University Of California | Cationic lipid compositions targeting angiogenic endothelial cells |
ATE486614T1 (de) * | 1997-03-14 | 2010-11-15 | Philadelphia Children Hospital | Zusammensetzungen zum einsatz in einer gentherapie zur behandlung von hämophilie |
US5945326A (en) | 1997-03-20 | 1999-08-31 | New England Biolabs, Inc. | Method for cloning and producing the Spel restriction endonuclease |
US6060082A (en) | 1997-04-18 | 2000-05-09 | Massachusetts Institute Of Technology | Polymerized liposomes targeted to M cells and useful for oral or mucosal drug delivery |
EP1027033B1 (en) | 1997-05-14 | 2009-07-22 | The University Of British Columbia | High efficiency encapsulation of nucleic acids in lipid vesicles |
US20030104044A1 (en) | 1997-05-14 | 2003-06-05 | Semple Sean C. | Compositions for stimulating cytokine secretion and inducing an immune response |
US6835395B1 (en) | 1997-05-14 | 2004-12-28 | The University Of British Columbia | Composition containing small multilamellar oligodeoxynucleotide-containing lipid vesicles |
JPH115786A (ja) | 1997-06-13 | 1999-01-12 | Pola Chem Ind Inc | 新規アミノヒドロキシプロピルピペラジン誘導体 |
US6067471A (en) | 1998-08-07 | 2000-05-23 | Cardiac Pacemakers, Inc. | Atrial and ventricular implantable cardioverter-defibrillator and lead system |
WO1999009997A1 (en) | 1997-08-26 | 1999-03-04 | Board Of Regents, The University Of Texas System | Edta and other chelators with or without antifungal antimicrobial agents for the prevention and treatment of fungal infections |
US6060308A (en) | 1997-09-04 | 2000-05-09 | Connaught Laboratories Limited | RNA respiratory syncytial virus vaccines |
JPH1180142A (ja) | 1997-09-05 | 1999-03-26 | Pola Chem Ind Inc | ジフェニルアルキル化合物の製造法 |
EP1021549A2 (en) | 1997-09-19 | 2000-07-26 | Sequitur, Inc. | SENSE mRNA THERAPY |
US6734171B1 (en) | 1997-10-10 | 2004-05-11 | Inex Pharmaceuticals Corp. | Methods for encapsulating nucleic acids in lipid bilayers |
WO1999018933A2 (en) | 1997-10-10 | 1999-04-22 | Inex Pharmaceuticals Corporation | Methods for encapsulating nucleic acids in lipid bilayers |
IL135578A0 (en) | 1997-10-29 | 2001-05-20 | Genzyme Corp | Compositions and methods for treating lysosomal storage disease |
US6165763A (en) | 1997-10-30 | 2000-12-26 | Smithkline Beecham Corporation | Ornithine carbamoyltransferase |
US6096075A (en) | 1998-01-22 | 2000-08-01 | Medical Carbon Research Institute, Llc | Prosthetic heart valve |
US6617171B2 (en) | 1998-02-27 | 2003-09-09 | The General Hospital Corporation | Methods for diagnosing and treating autoimmune disease |
US6271209B1 (en) | 1998-04-03 | 2001-08-07 | Valentis, Inc. | Cationic lipid formulation delivering nucleic acid to peritoneal tumors |
US6176877B1 (en) | 1998-04-20 | 2001-01-23 | St. Jude Medical, Inc. | Two piece prosthetic heart valve |
DE19822602A1 (de) | 1998-05-20 | 1999-11-25 | Goldschmidt Ag Th | Verfahren zur Herstellung von Polyaminosäureestern durch Veresterung von sauren Polyaminosäuren oder Umesterung von Polyaminosäureestern |
NO313244B1 (no) | 1998-07-08 | 2002-09-02 | Crew Dev Corp | Fremgangsmåte for isolering og produksjon av magnesitt eller magnesiumklorid |
US6055454A (en) | 1998-07-27 | 2000-04-25 | Cardiac Pacemakers, Inc. | Cardiac pacemaker with automatic response optimization of a physiologic sensor based on a second sensor |
WO2000006120A1 (en) | 1998-07-31 | 2000-02-10 | Korea Institute Of Science And Technology | Lipid emulsion and solid lipid nanoparticle as a gene or drug carrier |
KR20010072816A (ko) | 1998-08-20 | 2001-07-31 | 쿡 인코포레이티드 | 피복된 삽입용 의료 장치 |
US6210892B1 (en) | 1998-10-07 | 2001-04-03 | Isis Pharmaceuticals, Inc. | Alteration of cellular behavior by antisense modulation of mRNA processing |
AU1830200A (en) | 1998-11-25 | 2000-06-13 | Vanderbilt University | Cationic liposomes for gene transfer |
US6248725B1 (en) | 1999-02-23 | 2001-06-19 | Amgen, Inc. | Combinations and methods for promoting in vivo liver cell proliferation and enhancing in vivo liver-directed gene transduction |
JP2003503011A (ja) | 1999-04-02 | 2003-01-28 | エムティー テクノロジー,インコーポレイテッド | 固定プローブを使用する微生物の検出方法 |
US6379698B1 (en) | 1999-04-06 | 2002-04-30 | Isis Pharmaceuticals, Inc. | Fusogenic lipids and vesicles |
US8647864B2 (en) | 1999-04-14 | 2014-02-11 | Novartis Ag | Compositions and methods for generating an immune response utilizing alphavirus-based vector systems |
AU783647B2 (en) | 1999-04-20 | 2005-11-17 | University Of British Columbia, The | Cationic peg-lipids and methods of use |
IL146055A0 (en) | 1999-04-23 | 2002-07-25 | Alza Corp | Conjugate having a cleavable linkage for use in a liposome |
US6169923B1 (en) | 1999-04-23 | 2001-01-02 | Pacesetter, Inc. | Implantable cardioverter-defibrillator with automatic arrhythmia detection criteria adjustment |
DE60035871T2 (de) | 1999-05-19 | 2008-06-05 | Merck Patent Gmbh | Expression und export von interferon-alpha proteinen als fc fusionsproteine |
US6696424B1 (en) | 1999-05-28 | 2004-02-24 | Vical Incorporated | Cytofectin dimers and methods of use thereof |
US6346382B1 (en) | 1999-06-01 | 2002-02-12 | Vanderbilt University | Human carbamyl phosphate synthetase I polymorphism and diagnostic methods related thereto |
US7094423B1 (en) | 1999-07-15 | 2006-08-22 | Inex Pharmaceuticals Corp. | Methods for preparation of lipid-encapsulated therapeutic agents |
WO2001005375A1 (en) | 1999-07-16 | 2001-01-25 | Purdue Research Foundation | Vinyl ether lipids with cleavable hydrophilic headgroups |
CA2378944A1 (en) | 1999-07-23 | 2001-02-01 | Genentech, Inc. | Method for rnase- and organic solvent-free plasmid dna purification using tangential flow filtration |
US6358278B1 (en) | 1999-09-24 | 2002-03-19 | St. Jude Medical, Inc. | Heart valve prosthesis with rotatable cuff |
WO2001023002A1 (en) | 1999-09-30 | 2001-04-05 | National Jewish Medical And Research Center | Method for inhibition of pathogenic microorganisms |
US6371983B1 (en) | 1999-10-04 | 2002-04-16 | Ernest Lane | Bioprosthetic heart valve |
AU7868400A (en) | 1999-10-08 | 2001-04-23 | Alza Corporation | Neutral-cationic lipid for nucleic acid and drug delivery |
US7060291B1 (en) | 1999-11-24 | 2006-06-13 | Transave, Inc. | Modular targeted liposomal delivery system |
EP1242609A2 (en) | 1999-12-30 | 2002-09-25 | Novartis AG | Novel colloid synthetic vectors for gene therapy |
CA2400634A1 (en) | 2000-02-17 | 2001-08-23 | Chester Li | Genetic modification of the lung as a portal for gene delivery |
US6370434B1 (en) | 2000-02-28 | 2002-04-09 | Cardiac Pacemakers, Inc. | Cardiac lead and method for lead implantation |
US6565960B2 (en) | 2000-06-01 | 2003-05-20 | Shriners Hospital Of Children | Polymer composite compositions |
EP1297169B1 (en) | 2000-06-26 | 2012-08-08 | Ethris Gmbh | Method for transfecting cells using a magnetic field |
IL138474A0 (en) | 2000-09-14 | 2001-10-31 | Epox Ltd | Highly branched water-soluble polyamine oligomers, process for their preparation and applications thereof |
USRE43612E1 (en) | 2000-10-10 | 2012-08-28 | Massachusetts Institute Of Technology | Biodegradable poly(β-amino esters) and uses thereof |
US7427394B2 (en) | 2000-10-10 | 2008-09-23 | Massachusetts Institute Of Technology | Biodegradable poly(β-amino esters) and uses thereof |
US6998115B2 (en) | 2000-10-10 | 2006-02-14 | Massachusetts Institute Of Technology | Biodegradable poly(β-amino esters) and uses thereof |
JP2004511572A (ja) | 2000-10-25 | 2004-04-15 | ザ ユニバーシティ オブ ブリティッシュ コロンビア | 標的化送達のための脂質製剤 |
GB0028361D0 (en) | 2000-11-21 | 2001-01-03 | Glaxo Group Ltd | Method of separating extra chromosomal dna from other cellular components |
US20020094528A1 (en) | 2000-11-29 | 2002-07-18 | Salafsky Joshua S. | Method and apparatus using a surface-selective nonlinear optical technique for detection of probe-target interations |
JP2002167368A (ja) | 2000-12-01 | 2002-06-11 | Nitto Denko Corp | アルキル置換デンドリマーおよびその製造法 |
US20050004058A1 (en) | 2000-12-07 | 2005-01-06 | Patrick Benoit | Sequences upstream of the carp gene, vectors containing them and uses thereof |
DE10109897A1 (de) | 2001-02-21 | 2002-11-07 | Novosom Ag | Fakultativ kationische Liposomen und Verwendung dieser |
US20020192721A1 (en) | 2001-03-28 | 2002-12-19 | Engeneos, Inc. | Modular molecular clasps and uses thereof |
TW588032B (en) | 2001-04-23 | 2004-05-21 | Shinetsu Chemical Co | New tertiary amine compound having ester structure and method for producing the same |
US6585410B1 (en) | 2001-05-03 | 2003-07-01 | The United States Of America As Represented By The Administrator Of The National Aeronautics And Space Administration | Radiant temperature nulling radiometer |
DE50214200D1 (de) | 2001-06-05 | 2010-03-25 | Curevac Gmbh | Stabilisierte Tumorantigen-mRNA mit erhöhtem G/C-Gehalt |
EP2428568B1 (en) | 2001-09-28 | 2018-04-25 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Microrna molecules |
EP1446665A2 (de) | 2001-11-09 | 2004-08-18 | Bayer HealthCare AG | Isotopencodierte affinitätsmarker 3 |
DE10162480A1 (de) | 2001-12-19 | 2003-08-07 | Ingmar Hoerr | Die Applikation von mRNA für den Einsatz als Therapeutikum gegen Tumorerkrankungen |
DE10207178A1 (de) | 2002-02-19 | 2003-09-04 | Novosom Ag | Komponenten für die Herstellung amphoterer Liposomen |
DE10214983A1 (de) * | 2002-04-04 | 2004-04-08 | TransMIT Gesellschaft für Technologietransfer mbH | Vernebelbare Liposomen und ihre Verwendung zur pulmonalen Applikation von Wirkstoffen |
US20030215395A1 (en) | 2002-05-14 | 2003-11-20 | Lei Yu | Controllably degradable polymeric biomolecule or drug carrier and method of synthesizing said carrier |
US7601367B2 (en) | 2002-05-28 | 2009-10-13 | Mirus Bio Llc | Compositions and processes using siRNA, amphipathic compounds and polycations |
US7901708B2 (en) | 2002-06-28 | 2011-03-08 | Protiva Biotherapeutics, Inc. | Liposomal apparatus and manufacturing methods |
DE10229872A1 (de) | 2002-07-03 | 2004-01-29 | Curevac Gmbh | Immunstimulation durch chemisch modifizierte RNA |
US20040028804A1 (en) | 2002-08-07 | 2004-02-12 | Anderson Daniel G. | Production of polymeric microarrays |
EP1539936A2 (en) | 2002-08-22 | 2005-06-15 | Celltran Limited | Cell culture surface |
US7563857B2 (en) | 2002-11-04 | 2009-07-21 | Momentive Performance Materials Gmbh | Linear polyamino and/or polyammonium polysiloxane copolymers I |
EP1572669A2 (en) | 2002-11-22 | 2005-09-14 | Novo Nordisk A/S | 2,5-diketopiperazines for the treatment of obesity |
EP1578193A4 (en) | 2002-12-23 | 2011-06-15 | Vical Inc | FREEZING PROCESS FOR NUCLEIC ACID / BLOCK COPOLYMER / CATION SIDE COMPLEXES |
WO2004060363A1 (en) | 2002-12-23 | 2004-07-22 | Vical Incorporated | Method for producing sterile polynucleotide based medicaments |
EP1587816B1 (en) | 2002-12-23 | 2010-06-16 | Vical Incorporated | Codon-optimized polynucleotide-based vaccines against human cytomegalovirus infection |
US7169892B2 (en) | 2003-01-10 | 2007-01-30 | Astellas Pharma Inc. | Lipid-peptide-polymer conjugates for long blood circulation and tumor specific drug delivery systems |
WO2004066138A1 (ja) | 2003-01-20 | 2004-08-05 | Asahi Kasei Emd Corporation | ポインティングデバイス |
NZ542665A (en) | 2003-03-05 | 2008-05-30 | Senesco Technologies Inc | Use of antisense oligonucleotides or siRNA to suppress expression of eIF-5A1 |
US20040224912A1 (en) | 2003-05-07 | 2004-11-11 | Isis Pharmaceuticals Inc. | Modulation of PAI-1 mRNA-binding protein expression |
US7619017B2 (en) | 2003-05-19 | 2009-11-17 | Wacker Chemical Corporation | Polymer emulsions resistant to biodeterioration |
WO2005007810A2 (en) | 2003-06-16 | 2005-01-27 | Grinstaff Mark W | Functional synthetic molecules and macromolecules for gene delivery |
WO2005079185A2 (en) | 2003-09-02 | 2005-09-01 | Board Of Regents, The University Of Texas System | Neutral liposome-encapsulated compounds and methods of making and using thereof |
US7803397B2 (en) | 2003-09-15 | 2010-09-28 | Protiva Biotherapeutics, Inc. | Polyethyleneglycol-modified lipid compounds and uses thereof |
CA2539670A1 (en) | 2003-09-15 | 2005-03-31 | Massachusetts Institute Of Technology | Nanoliter-scale synthesis of arrayed biomaterials and screening thereof |
US20050069590A1 (en) | 2003-09-30 | 2005-03-31 | Buehler Gail K. | Stable suspensions for medicinal dosages |
AU2004279991B2 (en) | 2003-10-10 | 2010-11-25 | Powderject Vaccines, Inc. | Nucleic acid constructs |
WO2005037226A2 (en) | 2003-10-17 | 2005-04-28 | Georgia Tech Research Corporation | Genetically engineered enteroendocrine cells for treating glucose-related metabolic disorders |
EP1683784A4 (en) | 2003-11-10 | 2007-08-22 | Nippon Kayaku Kk | DIIMONIUM SALT CONNECTION AND ITS USE |
CN1906308B (zh) * | 2003-12-19 | 2011-09-14 | 诺华疫苗和诊断公司 | 小干扰rna的细胞转染制剂、相关组合物以及制备和使用方法 |
US7022214B2 (en) | 2004-01-21 | 2006-04-04 | Bio-Rad Laboratories, Inc. | Carrier ampholytes of high pH range |
US7556684B2 (en) | 2004-02-26 | 2009-07-07 | Construction Research & Technology Gmbh | Amine containing strength improvement admixture |
US20060228404A1 (en) | 2004-03-04 | 2006-10-12 | Anderson Daniel G | Compositions and methods for treatment of hypertrophic tissues |
US20060024670A1 (en) | 2004-05-18 | 2006-02-02 | Luke Catherine J | Influenza virus vaccine composition and methods of use |
KR101158941B1 (ko) | 2004-05-19 | 2012-06-21 | 클라리언트 파이넌스 (비브이아이)리미티드 | 모노아조 염료 |
AU2005252273B2 (en) | 2004-06-07 | 2011-04-28 | Arbutus Biopharma Corporation | Lipid encapsulated interfering RNA |
AU2005251403B2 (en) | 2004-06-07 | 2011-09-01 | Arbutus Biopharma Corporation | Cationic lipids and methods of use |
US7670595B2 (en) | 2004-06-28 | 2010-03-02 | Merck Patent Gmbh | Fc-interferon-beta fusion proteins |
GB0418172D0 (en) | 2004-08-13 | 2004-09-15 | Ic Vec Ltd | Vector |
DE102004042546A1 (de) | 2004-09-02 | 2006-03-09 | Curevac Gmbh | Kombinationstherapie zur Immunstimulation |
DE102004043342A1 (de) | 2004-09-08 | 2006-03-09 | Bayer Materialscience Ag | Blockierte Polyurethan-Prepolymere als Klebstoffe |
CA2586708A1 (en) | 2004-11-05 | 2006-05-11 | Novosom Ag | Improvements in or relating to pharmaceutical compositions comprising an oligonucleotide as an active agent |
WO2006060723A2 (en) | 2004-12-03 | 2006-06-08 | Vical Incorporated | Methods for producing block copolymer/amphiphilic particles |
WO2006074546A1 (en) | 2005-01-13 | 2006-07-20 | Protiva Biotherapeutics, Inc. | Lipid encapsulated interfering rna |
GB0502482D0 (en) | 2005-02-07 | 2005-03-16 | Glaxo Group Ltd | Novel compounds |
CA2597724A1 (en) | 2005-02-14 | 2007-08-02 | Sirna Therapeutics, Inc. | Cationic lipids and formulated molecular compositions containing them |
EP1869106B1 (en) | 2005-03-28 | 2014-06-25 | Dendritic Nanotechnologies, Inc. | Janus dendrimers and dendrons |
EP1912679A4 (en) | 2005-06-15 | 2009-07-29 | Massachusetts Inst Technology | AMINOUS LIPIDS AND ITS USES |
ES2735531T3 (es) | 2005-08-23 | 2019-12-19 | Univ Pennsylvania | ARN que contiene nucleósidos modificados y métodos de uso del mismo |
US9012219B2 (en) | 2005-08-23 | 2015-04-21 | The Trustees Of The University Of Pennsylvania | RNA preparations comprising purified modified RNA for reprogramming cells |
WO2007031091A2 (en) | 2005-09-15 | 2007-03-22 | Santaris Pharma A/S | Rna antagonist compounds for the modulation of p21 ras expression |
WO2007051303A1 (en) | 2005-11-02 | 2007-05-10 | Protiva Biotherapeutics, Inc. | MODIFIED siRNA MOLECULES AND USES THEREOF |
WO2007070705A2 (en) | 2005-12-15 | 2007-06-21 | The Trustees Of The University Of Pennsylvania | Cationic lipid-mediated vectors |
US7238791B1 (en) | 2005-12-16 | 2007-07-03 | Roche Diagnostics Operations, Inc. | 6-monoacetylmorphine derivatives useful in immunoassay |
WO2007073489A2 (en) | 2005-12-22 | 2007-06-28 | Trustees Of Boston University | Molecules for gene delivery and gene therapy, and methods of use thereof |
CN100569877C (zh) | 2005-12-30 | 2009-12-16 | 财团法人工业技术研究院 | 含多uv交联反应基的分枝状结构化合物及其应用 |
CA2649325C (en) | 2006-04-14 | 2019-01-08 | Epicentre Technologies Corporation | Kits and methods for generating 5' capped rna |
US9085778B2 (en) | 2006-05-03 | 2015-07-21 | VL27, Inc. | Exosome transfer of nucleic acids to cells |
US20070275923A1 (en) | 2006-05-25 | 2007-11-29 | Nastech Pharmaceutical Company Inc. | CATIONIC PEPTIDES FOR siRNA INTRACELLULAR DELIVERY |
EP2032652A4 (en) | 2006-06-05 | 2011-08-17 | Massachusetts Inst Technology | NETWORKED DEVELOPABLE POLYMERS AND ITS USE |
US20090186805A1 (en) | 2006-07-06 | 2009-07-23 | Aaron Thomas Tabor | Compositions and Methods for Genetic Modification of Cells Having Cosmetic Function to Enhance Cosmetic Appearance |
FR2904144A1 (fr) | 2006-07-19 | 2008-01-25 | St Microelectronics Rousset | Procede de fabrication d'un wafer de semi-conducteur comprenant un filtre optique integre |
ES2293834B1 (es) | 2006-07-20 | 2009-02-16 | Consejo Superior Investig. Cientificas | Compuesto con actividad inhibidora de las interacciones ubc13-uev, composiciones farmaceuticas que lo comprenden y sus aplicaciones terapeuticas. |
CA2658768C (en) | 2006-07-21 | 2016-05-17 | Massachusetts Institute Of Technology | End-modified poly(beta-amino esters) and uses thereof |
MX2009003548A (es) | 2006-10-03 | 2009-04-15 | Alnylam Pharmaceuticals Inc | Formulaciones que contienen lipidos. |
CA2665620A1 (en) | 2006-10-12 | 2008-04-17 | Copernicus Therapeutics Inc. | Codon optimized cftr |
DE102006051516A1 (de) | 2006-10-31 | 2008-05-08 | Curevac Gmbh | (Basen-)modifizierte RNA zur Expressionssteigerung eines Proteins |
EP1920765A1 (en) | 2006-11-07 | 2008-05-14 | Medigene AG | Liposome preparation by single-pass process |
US8268586B2 (en) | 2006-12-21 | 2012-09-18 | Novozymes, Inc. | Modified messenger RNA stabilizing sequences for expressing genes in bacterial cells |
US7700734B2 (en) * | 2007-01-09 | 2010-04-20 | Shu-Wha Lin | Recombinant human factor IX and use thereof |
DE102007001370A1 (de) | 2007-01-09 | 2008-07-10 | Curevac Gmbh | RNA-kodierte Antikörper |
US8859229B2 (en) | 2007-02-02 | 2014-10-14 | Yale University | Transient transfection with RNA |
EP2139461A2 (en) | 2007-03-20 | 2010-01-06 | Recepticon Aps | Amino derivatives to prevent nephrotoxicity and cancer |
JP5186126B2 (ja) | 2007-03-29 | 2013-04-17 | 公益財団法人地球環境産業技術研究機構 | 新規トリアジン誘導体ならびにその製法およびそのガス分離膜としての用途 |
EP2144609B1 (en) | 2007-04-18 | 2014-10-29 | Cornerstone Pharmaceuticals, Inc. | Pharmaceutical formulations containing lipoic acid derivatives |
US8678686B2 (en) | 2007-05-01 | 2014-03-25 | Pgr-Solutions | Multi-chain lipophilic polyamines |
US20090163705A1 (en) | 2007-05-21 | 2009-06-25 | Alnylam Pharmaceuticals, Inc. | Cationic lipids |
WO2009024599A1 (en) | 2007-08-23 | 2009-02-26 | Novartis Ag | Methods for detecting oligonucleotides |
WO2009030254A1 (en) | 2007-09-04 | 2009-03-12 | Curevac Gmbh | Complexes of rna and cationic peptides for transfection and for immunostimulation |
NZ584048A (en) | 2007-10-02 | 2012-08-31 | Marina Biotech Inc | Lipopeptides for delivery of nucleic acids |
WO2009046739A1 (en) | 2007-10-09 | 2009-04-16 | Curevac Gmbh | Composition for treating prostate cancer (pca) |
EP2221371B1 (en) | 2007-11-22 | 2013-11-13 | Japan Science and Technology Agency | Translation regulation system in cell or artificial cell model by using low-molecular-weight rna |
CA2910760C (en) | 2007-12-04 | 2019-07-09 | Muthiah Manoharan | Targeting lipids |
AU2008342535B2 (en) | 2007-12-27 | 2015-02-05 | Arbutus Biopharma Corporation | Silencing of polo-like kinase expression using interfering RNA |
WO2009120247A2 (en) | 2007-12-27 | 2009-10-01 | The Ohio State University Research Foundation | Lipid nanoparticle compositions and methods of making and using the same |
WO2009088891A1 (en) | 2008-01-02 | 2009-07-16 | Alnylam Pharmaceuticals, Inc. | Screening method for selected amino lipid-containing compositions |
CA3044134A1 (en) | 2008-01-02 | 2009-07-09 | Arbutus Biopharma Corporation | Improved compositions and methods for the delivery of nucleic acids |
EP2240509A1 (en) | 2008-02-08 | 2010-10-20 | Intercell AG | Flaviviridae mutants comprising a deletion in the capsid protein for use as vaccines |
WO2009126933A2 (en) | 2008-04-11 | 2009-10-15 | Alnylam Pharmaceuticals, Inc. | Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components |
CN102119217B (zh) | 2008-04-15 | 2015-06-03 | 普洛体维生物治疗公司 | 用于核酸递送的新型制剂 |
WO2009127230A1 (en) | 2008-04-16 | 2009-10-22 | Curevac Gmbh | MODIFIED (m)RNA FOR SUPPRESSING OR AVOIDING AN IMMUNOSTIMULATORY RESPONSE AND IMMUNOSUPPRESSIVE COMPOSITION |
US20090263407A1 (en) | 2008-04-16 | 2009-10-22 | Abbott Laboratories | Cationic Lipids and Uses Thereof |
US8222221B2 (en) | 2008-06-04 | 2012-07-17 | The Board Of Regents Of The University Of Texas System | Modulation of gene expression through endogenous small RNA targeting of gene promoters |
WO2010009277A2 (en) | 2008-07-15 | 2010-01-21 | Novartis Ag | Immunogenic amphipathic peptide compositions |
WO2010009065A2 (en) | 2008-07-15 | 2010-01-21 | Novartis Ag | Amphipathic peptide compositions |
JP5024216B2 (ja) | 2008-07-23 | 2012-09-12 | トヨタ自動車株式会社 | 内燃機関の点火時期制御装置及び点火時期制御方法 |
US20100035249A1 (en) | 2008-08-05 | 2010-02-11 | Kabushiki Kaisha Dnaform | Rna sequencing and analysis using solid support |
US8404198B2 (en) | 2008-08-27 | 2013-03-26 | Life Technologies Corporation | Apparatus for and method of processing biological samples |
WO2010037408A1 (en) | 2008-09-30 | 2010-04-08 | Curevac Gmbh | Composition comprising a complexed (m)rna and a naked mrna for providing or enhancing an immunostimulatory response in a mammal and uses thereof |
CA2740000C (en) | 2008-10-09 | 2017-12-12 | Tekmira Pharmaceuticals Corporation | Improved amino lipids and methods for the delivery of nucleic acids |
WO2010045512A2 (en) | 2008-10-16 | 2010-04-22 | Mdrna , Inc. | Processes and compositions for liposomal and efficient delivery of gene silencing therapeutics |
US9080211B2 (en) | 2008-10-24 | 2015-07-14 | Epicentre Technologies Corporation | Transposon end compositions and methods for modifying nucleic acids |
US20120009222A1 (en) | 2008-10-27 | 2012-01-12 | Massachusetts Institute Of Technology | Modulation of the immune response |
JP6087504B2 (ja) | 2008-11-07 | 2017-03-01 | 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 |
KR102344392B1 (ko) | 2008-11-10 | 2021-12-28 | 알닐람 파마슈티칼스 인코포레이티드 | 치료제 운반용 신규 지질 및 조성물 |
CN102216462A (zh) | 2008-11-17 | 2011-10-12 | 安龙制药公司 | 用于核酸递送系统的支化阳离子脂质 |
US9023820B2 (en) | 2009-01-26 | 2015-05-05 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing apolipoprotein C-III expression |
AU2010208035B2 (en) | 2009-01-29 | 2016-06-23 | Arbutus Biopharma Corporation | Improved lipid formulation for the delivery of nucleic acids |
US20100222489A1 (en) | 2009-02-27 | 2010-09-02 | Jiang Dayue D | Copolymer composition, membrane article, and methods thereof |
NZ594995A (en) | 2009-03-12 | 2013-06-28 | Alnylam Pharmaceuticals Inc | LIPID FORMULATED COMPOSITIONS AND METHODS FOR INHIBITING EXPRESSION OF HUMAN KINESIN FAMILY MEMBER 11 (Eg5) AND VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) GENES |
CN102334237B (zh) | 2009-04-02 | 2015-05-13 | 西蒙公司 | 电信接线板 |
PT2419144T (pt) | 2009-04-17 | 2019-09-16 | Univ Oxford Innovation Ltd | Composição para a administração de material genético |
US9220682B2 (en) | 2009-04-22 | 2015-12-29 | Emory University | Nanocarrier therapy for treating invasive tumors |
NZ621981A (en) | 2009-05-05 | 2015-09-25 | Tekmira Pharmaceuticals Corp | Lipid compositions |
EA201791744A3 (ru) | 2009-06-10 | 2018-07-31 | Арбутус Биофарма Корпорэйшн | Улучшенная липидная композиция |
US8273869B2 (en) * | 2009-06-15 | 2012-09-25 | Alnylam Pharmaceuticals, Inc. | Lipid formulated dsRNA targeting the PCSK9 gene |
US9051567B2 (en) | 2009-06-15 | 2015-06-09 | Tekmira Pharmaceuticals Corporation | Methods for increasing efficacy of lipid formulated siRNA |
WO2011000106A1 (en) | 2009-07-01 | 2011-01-06 | Protiva Biotherapeutics, Inc. | Improved cationic lipids and methods for the delivery of therapeutic agents |
CA2767129C (en) | 2009-07-01 | 2015-01-06 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing apolipoprotein b |
US9018187B2 (en) | 2009-07-01 | 2015-04-28 | Protiva Biotherapeutics, Inc. | Cationic lipids and methods for the delivery of therapeutic agents |
EP2450031B1 (en) | 2009-07-02 | 2018-08-29 | Konica Minolta Holdings, Inc. | Method for producing liposomes by two-stage emulsification method using outer aqueous phase containing specific dispersing agent, method for producing liposome dispersion or dry powder thereof using the method for producing liposomes, and liposome dispersion or dry powder thereof produced thereby |
CA2766907A1 (en) | 2009-07-06 | 2011-01-13 | Novartis Ag | Self replicating rna molecules and uses thereof |
US8716464B2 (en) | 2009-07-20 | 2014-05-06 | Thomas W. Geisbert | Compositions and methods for silencing Ebola virus gene expression |
CN102574818B (zh) | 2009-07-30 | 2015-02-25 | 萨尔瓦特实验室股份有限公司 | Apaf-1抑制剂化合物 |
DK2459231T3 (en) | 2009-07-31 | 2016-09-05 | Ethris Gmbh | RNA with a combination of unmodified and modified nucleotides for protein expression |
DE102009043342A1 (de) | 2009-09-29 | 2011-03-31 | Bayer Technology Services Gmbh | Stoffe für selbstorganisierte Träger zur kontrollierten Freisetzung eines Wirkstoffs |
WO2011062132A1 (ja) | 2009-11-20 | 2011-05-26 | コニカミノルタホールディングス株式会社 | W/o/wエマルションの製造方法およびこれを用いたリポソームの製造方法、並びにこれらの方法に用いられる孔膜 |
NZ700688A (en) | 2009-12-01 | 2016-02-26 | Shire Human Genetic Therapies | Delivery of mrna for the augmentation of proteins and enzymes in human genetic diseases |
EP3623474A1 (en) | 2009-12-07 | 2020-03-18 | The Trustees of The University of Pennsylvania | Rna preparations comprising purified modified rna for reprogramming cells |
WO2011069529A1 (en) | 2009-12-09 | 2011-06-16 | Curevac Gmbh | Mannose-containing solution for lyophilization, transfection and/or injection of nucleic acids |
ES2749426T3 (es) | 2009-12-18 | 2020-03-20 | Univ British Columbia | Métodos y composiciones para administración de ácidos nucleicos |
EP2338520A1 (de) | 2009-12-21 | 2011-06-29 | Ludwig Maximilians Universität | Konjugat mit Zielfindungsligand und dessen Verwendung |
AU2014259532B2 (en) | 2009-12-23 | 2016-09-08 | Novartis Ag | Lipids, lipid compositions, and methods of using them |
AU2010334911A1 (en) | 2009-12-23 | 2012-07-12 | Novartis Ag | Lipids, lipid compositions, and methods of using them |
US20130123338A1 (en) | 2010-05-12 | 2013-05-16 | Protiva Biotherapeutics, Inc. | Novel cationic lipids and methods of use thereof |
KR101198715B1 (ko) * | 2010-05-14 | 2012-11-13 | 한국생명공학연구원 | 핵산 및 친수성 음이온 화합물의 고효율 포획을 위한 비대칭 리포솜 및 이의 제조방법 |
DK2575764T3 (en) | 2010-06-03 | 2017-08-07 | Alnylam Pharmaceuticals Inc | BIODEGRADABLE LIPIDS FOR THE ACTIVATION OF ACTIVE AGENTS |
CN101863544B (zh) | 2010-06-29 | 2011-09-28 | 湖南科技大学 | 一种氰尿酸基重金属螯合絮凝剂及其制备方法 |
US9006417B2 (en) | 2010-06-30 | 2015-04-14 | Protiva Biotherapeutics, Inc. | Non-liposomal systems for nucleic acid delivery |
DK3243526T3 (da) | 2010-07-06 | 2020-02-17 | Glaxosmithkline Biologicals Sa | Levering af rna til at udløse flere immunsignalveje |
WO2012006369A2 (en) | 2010-07-06 | 2012-01-12 | Novartis Ag | Immunisation of large mammals with low doses of rna |
US9770463B2 (en) | 2010-07-06 | 2017-09-26 | Glaxosmithkline Biologicals Sa | Delivery of RNA to different cell types |
EP2590626B1 (en) | 2010-07-06 | 2015-10-28 | GlaxoSmithKline Biologicals SA | Liposomes with lipids having an advantageous pka-value for rna delivery |
JP6025721B2 (ja) | 2010-07-06 | 2016-11-16 | ノバルティス アーゲー | カチオン性水中油型エマルジョン |
RS63817B1 (sr) | 2010-07-06 | 2023-01-31 | Glaxosmithkline Biologicals Sa | Čestice za isporuku slične virionu za molekule samoreplicirajuće rnk |
WO2012016184A2 (en) | 2010-07-30 | 2012-02-02 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for delivery of active agents |
US8822663B2 (en) | 2010-08-06 | 2014-09-02 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
WO2012019630A1 (en) | 2010-08-13 | 2012-02-16 | Curevac Gmbh | Nucleic acid comprising or coding for a histone stem-loop and a poly(a) sequence or a polyadenylation signal for increasing the expression of an encoded protein |
WO2012027675A2 (en) | 2010-08-26 | 2012-03-01 | Massachusetts Institute Of Technology | Poly(beta-amino alcohols), their preparation, and uses thereof |
PL2611467T3 (pl) | 2010-08-31 | 2022-08-16 | Glaxosmithkline Biologicals Sa | Małe liposomy do dostarczania rna kodującego immunogen |
BR112013004865A2 (pt) | 2010-08-31 | 2016-06-07 | Novartis Ag | lípidos adequados para entrega lipossomal de codificadores de proteínas rna |
EP4119155A1 (en) | 2010-08-31 | 2023-01-18 | GlaxoSmithKline Biologicals S.A. | Pegylated liposomes for delivery of immunogen-encoding rna |
HUE058896T2 (hu) | 2010-10-01 | 2022-09-28 | Modernatx Inc | N1-metil-pszeudo-uracilt tartalmazó ribonukleinsavak és azok felhasználásai |
US8853377B2 (en) | 2010-11-30 | 2014-10-07 | Shire Human Genetic Therapies, Inc. | mRNA for use in treatment of human genetic diseases |
WO2012116715A1 (en) | 2011-03-02 | 2012-09-07 | Curevac Gmbh | Vaccination in newborns and infants |
WO2012113413A1 (en) | 2011-02-21 | 2012-08-30 | Curevac Gmbh | Vaccine composition comprising complexed immunostimulatory nucleic acids and antigens packaged with disulfide-linked polyethyleneglycol/peptide conjugates |
WO2012116714A1 (en) | 2011-03-02 | 2012-09-07 | Curevac Gmbh | Vaccination in elderly patients |
EP2691443B1 (en) | 2011-03-28 | 2021-02-17 | Massachusetts Institute of Technology | Conjugated lipomers and uses thereof |
WO2012133737A1 (ja) | 2011-03-31 | 2012-10-04 | 公益財団法人地球環境産業技術研究機構 | 架橋性アミン化合物、該化合物を用いた高分子膜及びその製造方法 |
US8710200B2 (en) | 2011-03-31 | 2014-04-29 | Moderna Therapeutics, Inc. | Engineered nucleic acids encoding a modified erythropoietin and their expression |
CN103687957A (zh) | 2011-05-17 | 2014-03-26 | 现代治疗公司 | 工程化核酸及其用于非人类脊椎动物的方法 |
EP2532649B1 (en) | 2011-06-07 | 2015-04-08 | Incella GmbH | Amino lipids, their synthesis and uses thereof |
JP6184945B2 (ja) * | 2011-06-08 | 2017-08-23 | 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 | mRNA送達のための脂質ナノ粒子組成物および方法 |
AU2012267578B2 (en) | 2011-06-08 | 2017-04-20 | Translate Bio, Inc. | Cleavable lipids |
WO2013003475A1 (en) | 2011-06-27 | 2013-01-03 | Cellscript, Inc. | Inhibition of innate immune response |
RU2606846C2 (ru) | 2011-07-06 | 2017-01-10 | Новартис Аг | Эмульсии типа "масло в воде", которые содержат нуклеиновые кислоты |
JP2014520806A (ja) | 2011-07-06 | 2014-08-25 | ノバルティス アーゲー | Rna分子の送達のための有用なn:p比を有するリポソーム |
ES2702318T3 (es) | 2011-07-06 | 2019-02-28 | Glaxosmithkline Biologicals Sa | Emulsiones catiónicas de aceite en agua |
CA2840989A1 (en) | 2011-07-06 | 2013-01-10 | Novartis Ag | Immunogenic combination compositions and uses thereof |
CA2841047A1 (en) | 2011-07-06 | 2013-01-10 | Novartis Ag | Immunogenic compositions and uses thereof |
MX366055B (es) | 2011-08-31 | 2019-06-26 | Novartis Ag | Liposomas pegilados para admistracion de acido ribonucleico (arn) que codifica para inmunogeno. |
US9464124B2 (en) | 2011-09-12 | 2016-10-11 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
EP3384938A1 (en) | 2011-09-12 | 2018-10-10 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
WO2013039857A1 (en) | 2011-09-12 | 2013-03-21 | modeRNA Therapeutics | Engineered nucleic acids and methods of use thereof |
RS62993B1 (sr) | 2011-10-03 | 2022-03-31 | Modernatx Inc | Modifikovani nukleozidi, nukleotidi, i nukleinske kiseline, i njihove upotrebe |
CA2850792A1 (en) | 2011-10-05 | 2013-04-11 | Protiva Biotherapeutics Inc. | Compositions and methods for silencing aldehyde dehydrogenase |
AU2012328570B2 (en) | 2011-10-27 | 2017-08-31 | Massachusetts Institute Of Technology | Amino acid derivatives functionalized on the n-terminus capable of forming drug encapsulating microspheres and uses thereof |
WO2013090186A1 (en) | 2011-12-14 | 2013-06-20 | modeRNA Therapeutics | Modified nucleic acids, and acute care uses thereof |
EP2791364A4 (en) | 2011-12-14 | 2015-11-11 | Moderna Therapeutics Inc | METHODS OF RESPONSE TO A BIOLOGICAL THREAT |
CN104114572A (zh) | 2011-12-16 | 2014-10-22 | 现代治疗公司 | 经修饰的核苷、核苷酸和核酸组合物 |
CA2859691A1 (en) | 2011-12-21 | 2013-06-27 | Moderna Therapeutics, Inc. | Methods of increasing the viability or longevity of an organ or organ explant |
US20140371302A1 (en) | 2011-12-29 | 2014-12-18 | Modema Therapeutics, Inc. | Modified mrnas encoding cell-penetrating polypeptides |
EP4372081A2 (en) | 2011-12-30 | 2024-05-22 | Cellscript, Llc | Making and using in vitro-synthesized ssrna for introducing into mammalian cells to induce a biological or biochemical effect |
US20150030576A1 (en) | 2012-01-10 | 2015-01-29 | Moderna Therapeutics, Inc. | Methods and compositions for targeting agents into and across the blood-brain barrier |
WO2013120499A1 (en) | 2012-02-15 | 2013-08-22 | Curevac Gmbh | Nucleic acid comprising or coding for a histone stem-loop and a poly (a) sequence or a polyadenylation signal for increasing the expression of an encoded pathogenic antigen |
WO2013120497A1 (en) | 2012-02-15 | 2013-08-22 | Curevac Gmbh | Nucleic acid comprising or coding for a histone stem-loop and a poly(a) sequence or a polyadenylation signal for increasing the expression of an encoded therapeutic protein |
HUE041494T2 (hu) | 2012-02-24 | 2019-05-28 | Arbutus Biopharma Corp | Trialkil-kationos lipidek és alkalmazási módszereik |
DK3578659T3 (da) | 2012-03-27 | 2024-02-05 | CureVac SE | Kunstige nukelinsyremolekyler til forbedret protein- eller peptidekspression |
BR112014024131A2 (pt) | 2012-03-29 | 2017-07-25 | Shire Human Genetic Therapies | lipídios catiônicos ionizáveis |
US9877919B2 (en) | 2012-03-29 | 2018-01-30 | Translate Bio, Inc. | Lipid-derived neutral nanoparticles |
US9572897B2 (en) | 2012-04-02 | 2017-02-21 | Modernatx, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
US9303079B2 (en) | 2012-04-02 | 2016-04-05 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins |
US20140275229A1 (en) | 2012-04-02 | 2014-09-18 | Moderna Therapeutics, Inc. | Modified polynucleotides encoding udp glucuronosyltransferase 1 family, polypeptide a1 |
DE18200782T1 (de) | 2012-04-02 | 2021-10-21 | Modernatx, Inc. | Modifizierte polynukleotide zur herstellung von proteinen im zusammenhang mit erkrankungen beim menschen |
US20150050354A1 (en) | 2012-04-02 | 2015-02-19 | Moderna Therapeutics, Inc. | Modified polynucleotides for the treatment of otic diseases and conditions |
US9283287B2 (en) | 2012-04-02 | 2016-03-15 | Moderna Therapeutics, Inc. | Modified polynucleotides for the production of nuclear proteins |
JP2015518705A (ja) | 2012-04-02 | 2015-07-06 | モデルナ セラピューティクス インコーポレイテッドModerna Therapeutics,Inc. | ヒト疾患に関連する生物製剤およびタンパク質の産生のための修飾ポリヌクレオチド |
BR112014029807A2 (pt) | 2012-06-08 | 2017-06-27 | Ethris Gmbh | administração pulmonar de rna mensageiro |
EP3536787A1 (en) | 2012-06-08 | 2019-09-11 | Translate Bio, 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 |
RU2488732C1 (ru) | 2012-07-26 | 2013-07-27 | Общество с ограниченной ответственностью "Новые композитные технологии" | Способ изготовления напорной комбинированной трубы |
CA2884870C (en) | 2012-08-13 | 2022-03-29 | Massachusetts Institute Of Technology | Amine-containing lipidoids and uses thereof |
EP4074834A1 (en) | 2012-11-26 | 2022-10-19 | ModernaTX, Inc. | Terminally modified rna |
WO2014089216A1 (en) | 2012-12-04 | 2014-06-12 | Tekmira Pharmaceuticals Corporation | In vitro release assay for liposome encapsulated vincristine |
EP2929035A1 (en) | 2012-12-07 | 2015-10-14 | Shire Human Genetic Therapies, Inc. | Lipidic nanoparticles for mrna delivering |
US20150315541A1 (en) | 2012-12-13 | 2015-11-05 | Moderna Therapeutics, Inc. | Modified polynucleotides for altering cell phenotype |
EP2931319B1 (en) | 2012-12-13 | 2019-08-21 | ModernaTX, Inc. | Modified nucleic acid molecules and uses thereof |
JP2016504050A (ja) | 2013-01-17 | 2016-02-12 | モデルナ セラピューティクス インコーポレイテッドModerna Therapeutics,Inc. | 細胞表現型の改変のためのシグナルセンサーポリヌクレオチド |
WO2014158795A1 (en) | 2013-03-12 | 2014-10-02 | Moderna Therapeutics, Inc. | Diagnosis and treatment of fibrosis |
EP2968391A1 (en) | 2013-03-13 | 2016-01-20 | Moderna Therapeutics, Inc. | Long-lived polynucleotide molecules |
EP2971010B1 (en) | 2013-03-14 | 2020-06-10 | ModernaTX, Inc. | Formulation and delivery of modified nucleoside, nucleotide, and nucleic acid compositions |
CN105209633A (zh) | 2013-03-14 | 2015-12-30 | 夏尔人类遗传性治疗公司 | 信使rna加帽效率的定量评估 |
ES2680595T3 (es) | 2013-03-14 | 2018-09-10 | Translate Bio, Inc. | Evaluación cuantitativa para eficacia de ARN mensajero para tapar |
EP2970955B1 (en) | 2013-03-14 | 2018-11-14 | Translate Bio, Inc. | Methods for purification of messenger rna |
ES2647832T3 (es) | 2013-03-14 | 2017-12-26 | Translate Bio, Inc. | Ácidos ribonucleicos con nucleótidos modificados con 4-tio y procedimientos relacionados |
EP3431592A1 (en) | 2013-03-14 | 2019-01-23 | Translate Bio, Inc. | Mrna therapeutic compositions and use to treat diseases and disorders |
HUE055044T2 (hu) | 2013-03-14 | 2021-10-28 | Translate Bio Inc | MRNS-kódolt ellenanyagok bejuttatására szolgáló eljárások és készítmények |
EA037922B1 (ru) | 2013-03-14 | 2021-06-07 | Шир Хьюман Дженетик Терапис, Инк. | мРНК CFTR И КОМПОЗИЦИИ ДЛЯ ЛЕЧЕНИЯ МУКОВИСЦИДОЗА У МЛЕКОПИТАЮЩЕГО |
EP2971165A4 (en) | 2013-03-15 | 2016-11-23 | Moderna Therapeutics Inc | DISSOLUTION OF DNA FRAGMENTS IN MRNA MANUFACTURING METHODS |
US11377470B2 (en) | 2013-03-15 | 2022-07-05 | Modernatx, Inc. | Ribonucleic acid purification |
WO2014152027A1 (en) | 2013-03-15 | 2014-09-25 | Moderna Therapeutics, Inc. | Manufacturing methods for production of rna transcripts |
US20160032273A1 (en) | 2013-03-15 | 2016-02-04 | Moderna Therapeutics, Inc. | Characterization of mrna molecules |
ES2795249T3 (es) | 2013-03-15 | 2020-11-23 | Translate Bio Inc | Mejora sinérgica de la administración de ácidos nucleicos a través de formulaciones mezcladas |
WO2014144711A1 (en) | 2013-03-15 | 2014-09-18 | Moderna Therapeutics, Inc. | Analysis of mrna heterogeneity and stability |
US8980864B2 (en) | 2013-03-15 | 2015-03-17 | Moderna Therapeutics, Inc. | Compositions and methods of altering cholesterol levels |
WO2014144767A1 (en) | 2013-03-15 | 2014-09-18 | Moderna Therapeutics, Inc. | Ion exchange purification of mrna |
US9315472B2 (en) | 2013-05-01 | 2016-04-19 | 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 |
JP6620093B2 (ja) | 2013-07-23 | 2019-12-11 | アービュートゥス バイオファーマ コーポレイションArbutus Biopharma Corporation | メッセンジャーrnaを送達するための組成物及び方法 |
MX369469B (es) | 2013-08-21 | 2019-11-08 | Curevac Ag | Vacuna contra el virus respiratorio sincitial. |
AU2014315287A1 (en) | 2013-09-03 | 2015-03-12 | Moderna Therapeutics, Inc. | Chimeric polynucleotides |
EP3041938A1 (en) | 2013-09-03 | 2016-07-13 | Moderna Therapeutics, Inc. | Circular polynucleotides |
EP3052106A4 (en) | 2013-09-30 | 2017-07-19 | ModernaTX, Inc. | Polynucleotides encoding immune modulating polypeptides |
WO2015051173A2 (en) | 2013-10-02 | 2015-04-09 | Moderna Therapeutics, Inc | Polynucleotide molecules and uses thereof |
US10385088B2 (en) | 2013-10-02 | 2019-08-20 | Modernatx, Inc. | Polynucleotide molecules and uses thereof |
WO2015058069A1 (en) | 2013-10-18 | 2015-04-23 | Moderna Therapeutics, Inc. | Compositions and methods for tolerizing cellular systems |
EP4036241A1 (en) | 2013-10-22 | 2022-08-03 | Translate Bio, Inc. | Cns delivery of mrna and uses thereof |
EP3060257B1 (en) * | 2013-10-22 | 2021-02-24 | Translate Bio, Inc. | Lipid formulations for delivery of messenger rna |
ES2954366T3 (es) | 2013-10-22 | 2023-11-21 | Translate Bio Inc | Terapia de ácido ribonucleico mensajero para la deficiencia de argininosuccinato sintetasa |
CA2928186A1 (en) | 2013-10-22 | 2015-04-30 | Shire Human Genetic Therapies, Inc. | Mrna therapy for phenylketonuria |
WO2015085318A2 (en) | 2013-12-06 | 2015-06-11 | Moderna Therapeutics, Inc. | Targeted adaptive vaccines |
EP3053585A1 (en) | 2013-12-13 | 2016-08-10 | Moderna Therapeutics, Inc. | Alternative nucleic acid molecules and uses thereof |
KR102399799B1 (ko) | 2013-12-30 | 2022-05-18 | 큐어백 아게 | 인공 핵산 분자 |
US20170002060A1 (en) | 2014-01-08 | 2017-01-05 | Moderna Therapeutics, Inc. | Polynucleotides for the in vivo production of antibodies |
CA2935878C (en) | 2014-03-12 | 2023-05-02 | Curevac Ag | Combination of vaccination and ox40 agonists |
US10405937B2 (en) | 2014-04-09 | 2019-09-10 | Arbutus Medical Inc. | Drill cover and chuck mechanism |
PT3134131T (pt) | 2014-04-23 | 2022-03-24 | Modernatx Inc | Vacinas de ácidos nucleicos |
BR112016026980B1 (pt) | 2014-06-10 | 2022-05-03 | Curevac Real Estate Gmbh | Método para sintetizar uma molécula de rna de uma dada sequência |
US20170175129A1 (en) | 2014-06-19 | 2017-06-22 | Moderna Therapeutics, Inc. | Alternative nucleic acid molecules and uses thereof |
WO2015196128A2 (en) | 2014-06-19 | 2015-12-23 | Moderna Therapeutics, Inc. | Alternative nucleic acid molecules and uses thereof |
CA2953341C (en) | 2014-06-25 | 2023-01-24 | Acuitas Therapeutics Inc. | Lipids and lipid nanoparticle formulations for delivery of nucleic acids |
WO2016005004A1 (en) | 2014-07-11 | 2016-01-14 | Biontech Rna Pharmaceuticals Gmbh | Stabilization of poly(a) sequence encoding dna sequences |
US10272161B2 (en) | 2014-07-16 | 2019-04-30 | Ethris Gmbh | RNA for use in the treatment of ligament or tendon lesions |
US10415037B2 (en) | 2014-10-02 | 2019-09-17 | Arbutus Biopharma Corporation | Compositions and methods for silencing hepatitis B virus gene expression |
WO2016071857A1 (en) | 2014-11-07 | 2016-05-12 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing ebola virus expression |
EP3218508A4 (en) | 2014-11-10 | 2018-04-18 | Modernatx, Inc. | Multiparametric nucleic acid optimization |
WO2016077125A1 (en) | 2014-11-10 | 2016-05-19 | Moderna Therapeutics, Inc. | Alternative nucleic acid molecules containing reduced uracil content and uses thereof |
EP3247363A4 (en) | 2015-01-21 | 2018-10-03 | Moderna Therapeutics, Inc. | Lipid nanoparticle compositions |
WO2016118725A1 (en) | 2015-01-23 | 2016-07-28 | Moderna Therapeutics, Inc. | Lipid nanoparticle compositions |
WO2016154127A2 (en) | 2015-03-20 | 2016-09-29 | Protiva Biotherapeutics, Inc. | Compositions and methods for treating hypertriglyceridemia |
WO2016164762A1 (en) | 2015-04-08 | 2016-10-13 | Moderna Therapeutics, Inc. | Polynucleotides encoding low density lipoprotein receptor egf-a and intracellular domain mutants and methods of using the same |
WO2016183366A2 (en) | 2015-05-12 | 2016-11-17 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing expression of hepatitis d virus rna |
WO2016197133A1 (en) | 2015-06-04 | 2016-12-08 | Protiva Biotherapeutics, Inc. | Delivering crispr therapeutics with lipid nanoparticles |
US20180245074A1 (en) | 2015-06-04 | 2018-08-30 | Protiva Biotherapeutics, Inc. | Treating hepatitis b virus infection using crispr |
EP3307305A4 (en) | 2015-06-10 | 2019-05-22 | Modernatx, Inc. | TARGETED ADAPTIVE VACCINES |
US20180208932A1 (en) | 2015-07-29 | 2018-07-26 | Arbutus Biopharma Corporation | Compositions and methods for silencing hepatitis b virus gene expression |
PL3350333T3 (pl) | 2015-09-17 | 2022-03-07 | Modernatx, Inc. | Polinukleotydy zawierające region stabilizujący ogon |
WO2017049286A1 (en) | 2015-09-17 | 2017-03-23 | Moderna Therapeutics, Inc. | Polynucleotides containing a morpholino linker |
US20190054112A1 (en) | 2015-09-18 | 2019-02-21 | Moderna Therapeutics, Inc. | Polynucleotide formulations for use in the treatment of renal diseases |
WO2017102010A1 (en) | 2015-12-17 | 2017-06-22 | Biontech Rna Pharmaceuticals Gmbh | Novel cytokine fusion proteins |
EP3394237A1 (en) | 2015-12-21 | 2018-10-31 | CureVac AG | Inlay for a culture plate and corresponding method for preparing a culture plate system with such inlay |
EP3701963A1 (en) | 2015-12-22 | 2020-09-02 | CureVac AG | Method for producing rna molecule compositions |
WO2017109161A1 (en) | 2015-12-23 | 2017-06-29 | Curevac Ag | Method of rna in vitro transcription using a buffer containing a dicarboxylic acid or tricarboxylic acid or a salt thereof |
US9834510B2 (en) | 2015-12-30 | 2017-12-05 | Arcturus Therapeutics, Inc. | Aromatic ionizable cationic lipid |
WO2017117528A1 (en) | 2015-12-30 | 2017-07-06 | Acuitas Therapeutics, Inc. | Lipids and lipid nanoparticle formulations for delivery of nucleic acids |
AU2019258679A1 (en) | 2018-04-25 | 2020-10-15 | Ethris Gmbh | Cryoprotective agents for particulate formulations |
-
2012
- 2012-06-08 JP JP2014514907A patent/JP6184945B2/ja active Active
- 2012-06-08 DK DK12728007.1T patent/DK2717893T3/da active
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