JP2020531418A - 脂質ナノ粒子製剤における使用のための脂質 - Google Patents
脂質ナノ粒子製剤における使用のための脂質 Download PDFInfo
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Classifications
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- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C229/06—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton
- C07C229/10—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings
- C07C229/16—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of hydrocarbon radicals substituted by amino or carboxyl groups, e.g. ethylenediamine-tetra-acetic acid, iminodiacetic acids
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- C07C219/02—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C219/04—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C219/06—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having the hydroxy groups esterified by carboxylic acids having the esterifying carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms of an acyclic saturated carbon skeleton
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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Abstract
Description
を有する化合物またはその薬学的に許容される塩、互変異性体、プロドラッグもしくは立体異性体が提供される。
(i)哺乳動物において、特に、このような哺乳動物がその状態に対する素因を有するが、それを有するとまだ診断されていない場合、その疾患もしくは状態が生じるのを防止すること、
(ii)疾患もしくは状態を阻害する、すなわち、その発症を抑止すること、
(iii)疾患もしくは状態を緩和する、すなわち、その疾患もしくは状態の退行を引き起こすこと、または
(iv)疾患もしくは状態に起因する症状を緩和する、すなわち、根底にある疾患もしくは状態に対処することなく疼痛を緩和すること
を含む。本明細書で使用される場合、「疾患」および「状態」という用語は、交換可能に使用してもよいし、または特定の疾病もしくは状態が公知の原因物質を有さないこともあり(そのため、病因がまだ解決されておらず)、したがって疾患としてまだ認識されていないが、望ましくない状態もしくは症候群としてのみ認識され、程度の差はあるが特定の一連の症状が臨床医により確認されているという点で異なる場合もある。
ある態様では、本発明は、オリゴヌクレオチドと共に脂質ナノ粒子を形成するために、他の脂質成分、例えば、中性脂質、荷電脂質、ステロイドおよび/またはポリマーコンジュゲート脂質などと組み合わせることが可能である新規脂質化合物を提供する。理論に制約されることを望むことなく、これらの脂質ナノ粒子は、血清中でオリゴヌクレオチドを分解から遮蔽し、in vitroおよびin vivoでのオリゴヌクレオチドの細胞への有効な送達を提供すると考えられている。
L1は、−O(C=O)R1、−(C=O)OR1、−C(=O)R1、−OR1、−S(O)xR1、−S−SR1、−C(=O)SR1、−SC(=O)R1、−NRaC(=O)R1、−C(=O)NRbRc、−NRaC(=O)NRbRc、−OC(=O)NRbRcまたは−NRaC(=O)OR1であり、
L2は、−O(C=O)R2、−(C=O)OR2、−C(=O)R2、−OR2、−S(O)xR2、−S−SR2、−C(=O)SR2、−SC(=O)R2、−NRdC(=O)R2、−C(=O)NReRf、−NRdC(=O)NReRf、−OC(=O)NReRf;−NRdC(=O)OR2またはR2への直接結合であり、
G1およびG2は、それぞれ独立して、C2〜C12アルキレンまたはC2〜C12アルケニレンであり、
G3は、C1〜C24アルキレン、C2〜C24アルケニレン、C3〜C8シクロアルキレンまたはC3〜C8シクロアルケニレンであり、
Ra、Rb、RdおよびReは、それぞれ独立して、HまたはC1〜C12アルキルまたはC1〜C12アルケニルであり、
RcおよびRfは、それぞれ独立して、C1〜C12アルキルまたはC2〜C12アルケニルであり、
R1およびR2は、それぞれ独立して、分岐状C6〜C24アルキルまたは分岐状C6〜C24アルケニルであり、
R3は−N(R4)R5であり、
R4はC1〜C12アルキルであり、
R5は置換C1〜C12アルキルであり、
xは、0、1または2であり、
アルキル、アルケニル、アルキレン、アルケニレン、シクロアルキレン、シクロアルケニレン、アリールおよびアラルキルは各々、他に特定されていない限り、独立して置換されているまたは置換されていない。
R7aおよびR7bは、出現ごとに独立して、HまたはC1〜C12アルキルであり、
aは2〜12の整数であり、
R7a、R7bおよびaは各々、R1およびR2がそれぞれ独立して6〜20個の炭素原子を含むように選択される。例えば、一部の実施形態では、aは、5〜9または8〜12の範囲の整数である。
Rgは、出現ごとに独立して、HまたはC1〜C6アルキルであり、
Rhは、出現ごとに独立して、C1〜C6アルキルであり、
Riは、出現ごとに独立して、C1〜C6アルキレンである)
からなる群より選択される1つまたはそれより多くの置換基で置換されている。
Rgは、出現ごとに独立して、HまたはC1〜C6アルキルであり、
Rhは、出現ごとに独立して、C1〜C6アルキルであり、
Riは、出現ごとに独立して、C1〜C6アルキレンである)
からなる群より選択される1つまたはそれより多くの置換基で置換されている。
R8およびR9は、それぞれ独立して、10〜30個の炭素原子を含有する直鎖状または分岐状のアルキル、アルケニル、またはアルキニルであり、アルキル、アルケニルまたはアルキニルは、1つまたは複数のエステル結合により、必要に応じて分断されており、
wは30〜60の範囲の平均値を有する)
を有するペグ化脂質またはその薬学的に許容される塩、互変異性体もしくは立体異性体を含む。
R8およびR9は、それぞれ独立して、10〜30個の炭素原子を含有する直鎖状または分岐状のアルキル、アルケニルまたはアルキニルであり、アルキル、アルケニルまたはアルキニルは、1つまたは複数のエステル結合により、必要に応じて分断されており、
wは、30〜60の範囲の平均値を有する)
を有するペグ化脂質またはその薬学的に許容される塩、互変異性体もしくは立体異性体を含む。
またはその薬学的に許容される塩、互変異性体もしくは立体異性体を作製する例示的方法を例示している。当業者は、同様の方法で、または当業者に公知の他の方法を組み合わせることによりこれらの化合物を作製可能であり得ることが理解されている。当業者であれば、適当な開始構成成分を使用し、必要に応じて合成のパラメーターを改変することによって、以下に具体的に示されていない、構造(I)の他の化合物を、以下に記載されているものと同様の方式で作製可能であることもまた理解されている。一般的に、開始構成成分は、Sigma Aldrich、Lancaster Synthesis,Inc.、Maybridge、Matrix Scientific、TCIおよびFluorochem USAなどの供給元から得てもよく、当業者に公知の情報元に従い合成してもよく(例えば、Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 5th edition (Wiley, December 2000)を参照されたい)、または本発明に記載の通り調製してもよい。
脂質ナノ粒子組成物を使用したルシフェラーゼmRNAのin vivo評価
構造(I)の脂質、DSPC、コレステロールおよびPEG−脂質を、50:10:38.5:1.5または47.5:10:40.8:1.7のモル比で、エタノール中で可溶化した。脂質ナノ粒子(LNP)を、全脂質のmRNAに対する重量比約10:1〜30:1で調製した。簡単に説明すると、10〜50mMのクエン酸緩衝液、pH4で、mRNAを0.2mg/mLに希釈した。シリンジポンプを使用して、15mL/分を超える全流量で、エタノール性脂質溶液とmRNA水溶液を約1:5〜1:3(vol/vol)の比で混合した。次いで、エタノールを除去し、外部の緩衝液を透析によりPBSに置き換えた。最後に、脂質ナノ粒子を、0.2μm細孔の無菌フィルターを介して濾過した。
製剤化した脂質のpKaの決定
他の箇所で記載されているように、製剤化した脂質のpKaは、核酸の送達のためのLNPの有効性と相関する(Jayaraman et al, Angewandte Chemie, International Edition (2012), 51(34), 8529-8533;Semple et al, Nature Biotechnology 28, 172-176 (2010)を参照されたい)。一部の実施形態では、pKaの好ましい範囲は約5〜約7である。2−(p−トルイジノ)−6−ナフタレンスルホン酸(TNS)の蛍光に基づくアッセイを使用して、構造(I)の代表的化合物のpKaを脂質ナノ粒子において決定した。PBS中に、構造(I)の化合物/DSPC/コレステロール/PEG−脂質(50/10/38.5/1.5または47.5:10:40.8:1.7mol%)を総脂質濃度0.4mMで含む脂質ナノ粒子を、実施例1に記載されているようなインラインプロセスを使用して調製した。TNSは、蒸留水中100μMストック溶液として調製した。10mM HEPES、10mM MES、10mM酢酸アンモニウム、および130mM NaCl(このpHは2.5〜11の範囲である)を含有する2mLの緩衝化溶液中で、ベシクルを24μMの脂質に希釈した。一定分量のTNS溶液を加えて、最終濃度を1μMにし、ボルテックス混合した後、321nmおよび445nmの励起および発光波長を使用する、SLM Aminco Series 2 Luminescence Spectrophotometerで、室温で蛍光強度を測定した。シグモイドの適合度分析(best fit analysis)を蛍光データに適用し、最大半量の蛍光強度を引き起こすpHとしてpKaを測定した。
in vivoルシフェラーゼmRNA発現げっ歯類モデルを使用する様々なカチオン性脂質を含有する脂質ナノ粒子製剤の有効性の決定
表2に示されているカチオン性脂質は、核酸で以前に試験されたものである。比較する目的で、これらの脂質を、実施例1においておよびPCT/US10/22614(これによって、その全体が参照により本明細書に組み込まれる)において記載されているように、株混合法を使用して、FLuc mRNA(L−6107)を含有する脂質ナノ粒子を製剤化するためにも使用した。脂質ナノ粒子は、以下のモル比:50%カチオン性脂質/10%ジステアロイルホスファチジルコリン(DSPC)/38.5%コレステロール/1.5%PEG脂質(「PEG−DMG」、すなわち、1−(モノメトキシ−ポリエチレングリコール)−2,3−ジミリストイルグリセロール、2000の平均PEG分子量を持つ)を使用して製剤化され得る。代替実施形態では、カチオン性脂質、DSPC、コレステロールおよびPEG−脂質は、約47.5:10:40.8:1.7のモル比で製剤化される。実施例1に記載の通り尾静脈注射を介した投与の4時間後、肝臓内のルシフェラーゼ発現を測定することによって、相対的な活性を決定した。0.3および1.0mgのmRNA/kgの用量での活性を比較し、実施例1に記載の通り、投与の4時間後に測定したルシフェラーゼ(ng)/肝臓(g)として表現した。
6−ブロモヘキサン酸(16mmol、3.12g)、2−ヘキシル−1−デカノール(22.4mmol、5.43g)およびDMAP(8mmol、976mg)のDCM(50mL)溶液に、DCC(17.6mmol、3.62g)を加えた。生成した混合物を室温で16時間撹拌した。沈殿物(DCU)を濾過によって除去した。濾液を濃縮し、生成した残留油状物質/固体をシリカゲル上でのカラムクロマトグラフィー(ヘキサン中0〜5%酢酸エチル)により精製した。これにより、所望の生成物を無色の油状物質として得た(5.79g、無色の油状物質、13.8mmol、86%)。
2−アミノエタノール(333mg、5.46mmol)の35mlの無水THF溶液に、4−1(4.37g、10.4mmol)、炭酸カリウム(1.44g、10.4mmol)、炭酸セシウム(534mg、1.64mmol)およびヨウ化ナトリウム(30mg)を加えた。生成した混合物を密閉圧力フラスコ内で、70Cで6日間加熱した。溶媒を減圧下で蒸発させ、残渣をヘキサンおよび酢酸エチル(94:4)の混合物中に入れ、水およびブラインで洗浄した。有機層を分離し、無水硫酸ナトリウムで乾燥させた。乾燥抽出物(320mL)をシリカゲルのカラムに充填した。カラムを、ヘキサン、EtOAcおよびトリエチルアミン(95:5:0〜80:20:1)の混合物で溶出した。これにより、所望の生成物を無色の油状物質として得た(2.68g、3.63mmol、70%)。1HNMR (400 MHz, CDCl3) δ: 3.97 (d, 5.8 Hz, 4H), 3.53 (t, 5.3 Hz, 2H), 3.08-2.79 (br. 1H), 2.57 (t, 5.3 Hz, 2H), 2.45 (t様, 7.4 Hz, 4H), 2.31 (t, 7.5 Hz, 4H), 1.67-1.59 (m, 6H), 1.51-1.41 (m, 4H), 1.38-1.10 (52H), 0.89 (t様, 6.8 Hz, 12H).
1mLのCHC13中の4−2(300mg、0.41mmol)の氷冷溶液に、5mLのクロロホルム中の塩化チオニル(1.23mmol、146mg)を、Ar雰囲気下、滴下添加した。SOCl2の添加(1〜2分)が完了した後、氷浴を取り除き、反応混合物を室温(20C)で16時間撹拌した。クロロホルムおよびSOCl2の減圧下での除去により、濃厚な暗赤色の油状物質を得た。粗生成物をシリカゲル上でのフラッシュカラムクロマトグラフィー(微量のEt3Nを含むクロロホルム中0〜1%MeOH)により精製した。所望の生成物を褐色油状物質として得た(190mg、0.25mmol、61%)。
4−3(190mg、0.25mmol)をTHF(5mL)に溶解させた。溶液に、N,N−ジイソプロピルエチルアミン(0.217mL)および4−4(0.75mmol、140mg;1−ブロモノナンおよびアミノエタノールから調製)を加えた。密閉混合物を69Cで一晩加熱した。翌日、ヨウ化ナトリウム(10mg)を混合物に加え、加熱(65Cで)を再開した。3日後、混合物を冷却し、濃縮した。粗生成物をシリカゲル上でのカラムクロマトグラフィーにより精製し、ヘキサン、EtOAcおよびトリエチルアミン(95:5:0〜80:20:1)の混合物で溶出した。これにより、所望の生成物を無色の油状物質として得た(150mg、0.17mmol、66%)。1HNMR (400 MHz, CDCl3) δ: 4.90-4.20 (br. 1H), 3.97 (d, 5.8 Hz, 4H), 3.52 (t, 5.0 Hz, 2H), 2.61-2.53 (m, 4H), 2.52-2.45 (m, 4H), 2.45-2.40 (m, 4H), 2.31 (t, 7.5 Hz, 4H), 1.69-1.60 (m, 6H), 1.52-1.40 (m, 6H), 1.36-1.18 (64H), 0.89 (t様, 6.8 Hz, 15H).
2−ブチルオクタン酸(26.9mmol、5.388g)、9−ブロモ−1−ノナノール(4g、18mmol)およびDMAP(9mmol、1.10g)のDCM(40mL)溶液に、DCC(19.8mmol、4.08g)を加えた。生成した混合物を室温で16時間撹拌した。沈殿物(DCU)を濾過によって除去した。濾液を濃縮し、粗生成物をシリカゲル上でのフラッシュドライカラムクロマトグラフィー(ヘキサン中0〜3%酢酸エチル)により精製した。所望の化合物を無色の油状物質として得た(6.42g、15.8mmol、88%)。
圧力フラスコ内の11−1(2.41g、5.94mmol)、2−アミノエタノール(185mg、3.03mmol)、N,N−ジイソプロピルエチルアミン(1.32mL)および無水アセトニトリル(20mL)の混合物を、80℃で16時間加熱した。溶媒を減圧下で蒸発させ、粗生成物をシリカゲル上でのフラッシュドライカラムクロマトグラフィー(ヘキサン−EtOAc−Et3N、99:1:0〜80:20:1)により精製した。所望の化合物を無色の油状物質として得た(1.441g、無色の油状物質、2.03mmol、68%)。
8mLのCHC13中の11−2(1.441g、2.03mmol)の氷冷溶液に、塩化チオニル(6.09mmol、725mg)のクロロホルム(25mL)溶液を、Ar雰囲気下、滴下添加した。SOCl2の添加の完了後、氷浴を取り除き、反応混合物を室温(20C)で16時間撹拌した。CHC13およびSOCl2の減圧下での除去により、濃厚な褐色油状物質、1.730gを得た。粗生成物(1.730g)をシリカゲル上でのフラッシュドライカラムクロマトグラフィー(シリカゲル230〜400メッシュグレード、微量のEt3Nを含むクロロホルム中1%MeOH)により精製した。所望の化合物を褐色油状物質として得た(1.35g、1.8mmol、91%)。
THF(6mL)中の11−3(268mg、0.37mmol)、8−1(0.75mmol、130mg)、N,N−ジイソプロピルエチルアミン(0.22mL)およびヨウ化ナトリウム(10mg)の混合物を密閉し、70℃で3日間加熱した。混合物を冷却し、濃縮した。粗生成物をシリカゲル上でのフラッシュドライカラムクロマトグラフィー(微量のEt3Nを含むクロロホルム中0〜5%MeOH)により精製した。所望の化合物を無色の油状物質として得た(135mg、0.16mmol、43%)。1HNMR (400 MHz, CDCl3) δ:4.06 (t, 6.6 Hz, 4H), 3.64 (t, 6.6 Hz, 2H), 2.57-2.51 (m, 2H), 2.45-2.38 (m, 6H), 2.35-2.27 (m, 4H), 2.22 (s, 3H), 1.66-1.52 (m, 推定11H), 1.50-1.38 (m, 10H), 1.38-1.10 (54H), 0.90-0.85 (m, 12H).
Claims (49)
- 以下の構造(I):
L1は、−O(C=O)R1、−(C=O)OR1、−C(=O)R1、−OR1、−S(O)xR1、−S−SR1、−C(=O)SR1、−SC(=O)R1、−NRaC(=O)R1、−C(=O)NRbRc、−NRaC(=O)NRbRc、−OC(=O)NRbRcまたは−NRaC(=O)OR1であり、
L2は、−O(C=O)R2、−(C=O)OR2、−C(=O)R2、−OR2、−S(O)xR2、−S−SR2、−C(=O)SR2、−SC(=O)R2、−NRdC(=O)R2、−C(=O)NReRf、−NRdC(=O)NReRf、−OC(=O)NReRf;−NRdC(=O)OR2またはR2への直接結合であり、
G1およびG2は、それぞれ独立して、C2〜C12アルキレンまたはC2〜C12アルケニレンであり、
G3は、C1〜C24アルキレン、C2〜C24アルケニレン、C3〜C8シクロアルキレンまたはC3〜C8シクロアルケニレンであり、
Ra、Rb、RdおよびReは、それぞれ独立して、HまたはC1〜C12アルキルまたはC1〜C12アルケニルであり、
RcおよびRfは、それぞれ独立して、C1〜C12アルキルまたはC2〜C12アルケニルであり、
R1およびR2は、それぞれ独立して、分岐状C6〜C24アルキルまたは分岐状C6〜C24アルケニルであり、
R3は−N(R4)R5であり、
R4はC1〜C12アルキルであり、
R5は置換されているC1〜C12アルキルであり、
xは、0、1または2であり、
アルキル、アルケニル、アルキレン、アルケニレン、シクロアルキレン、シクロアルケニレン、アリールおよびアラルキルは各々、他に特定されていない限り、独立して置換されているかまたは置換されていない、
化合物またはその薬学的に許容される塩、プロドラッグもしくは立体異性体。 - G3が置換されていない、請求項1に記載の化合物。
- G3がC1〜C12アルキレンである、請求項1または2のいずれか一項に記載の化合物。
- G3がC2またはC3アルキレンである、請求項1から3のいずれか一項に記載の化合物。
- L1が、−O(C=O)R1、−(C=O)OR1または−C(=O)NRbRcであり、L2が、−O(C=O)R2、−(C=O)OR2または−C(=O)NReRfである、請求項1から5のいずれか一項に記載の化合物。
- yおよびzが、それぞれ独立して、2〜12の範囲の整数である、請求項5、6または8のいずれか一項に記載の化合物。
- yおよびzが、それぞれ独立して、4〜10の範囲の整数である、請求項5、6または8のいずれか一項に記載の化合物。
- R1およびR2が、それぞれ独立して、分岐状C6〜C24アルキルである、請求項1から10のいずれか一項に記載の化合物。
- aが8〜12の整数である、請求項12に記載の化合物。
- R7aの少なくとも1つの出現がHである、請求項12または13のいずれか一項に記載の化合物。
- R7aが出現ごとにHである、請求項12または13のいずれか一項に記載の化合物。
- R7bの少なくとも1つの出現がC1〜C8アルキルである、請求項12または15のいずれか一項に記載の化合物。
- C1〜C8アルキルが、メチル、エチル、n−プロピル、イソ−プロピル、n−ブチル、イソ−ブチル、tert−ブチル、n−ヘキシルまたはn−オクチルである、請求項16に記載の化合物。
- Rb、Rc、ReおよびRfが、それぞれ独立して、C3〜C12アルキルである、請求項6から10のいずれか一項に記載の化合物。
- Rb、Rc、ReおよびRfがn−ヘキシルである、請求項6から11のいずれか一項に記載の化合物。
- Rb、Rc、ReおよびRfがn−オクチルである、請求項6から11のいずれか一項に記載の化合物。
- R4が、置換されているかまたは置換されていない、メチル、エチル、プロピル、n−ブチル、n−ヘキシル、n−オクチルまたはn−ノニルである、請求項1から21のいずれか一項に記載の化合物。
- R4が置換されていない、請求項22に記載の化合物。
- R4が、−ORg、−NRgC(=O)Rh、−C(−O)NRgRh、−C(=O)Rh、−OC(=O)Rh、−C(=O)ORhおよび−ORiOHからなる群より選択される1つまたはそれより多くの置換基で置換されており、
Rgが、出現ごとに独立して、HまたはC1〜C6アルキルであり、
Rhが、出現ごとに独立して、C1〜C6アルキルであり、
Riが、出現ごとに独立して、C1〜C6アルキレンである、請求項22のいずれか一項に記載の化合物。 - R5が、置換されている、メチル、エチル、プロピル、n−ブチル、n−ヘキシル、n−オクチルまたはn−ノニルである、請求項1から24のいずれか一項に記載の化合物。
- R5が置換されているエチルまたは置換されているプロピルである、請求項25に記載の化合物。
- R4が置換されていないメチルである、請求項25または26のいずれか一項に記載の化合物。
- R5がヒドロキシルで置換されている、請求項25から27のいずれか一項に記載の化合物。
- R5が、−ORg、−NRgC(=O)Rh、−C(=O)NRgRh、−C(=O)Rh、−OC(=O)Rh、−C(=O)ORhおよび−ORiOHからなる群より選択される1つまたはそれより多くの置換基で置換されており、
Rgが、出現ごとに独立して、HまたはC1〜C6アルキルであり、
Rhが、出現ごとに独立して、C1〜C6アルキルであり、
Riが、出現ごとに独立して、C1〜C6アルキレンである、請求項25から27のいずれか一項に記載の化合物。 - 表1中の化合物から選択される化合物。
- 請求項1から31のいずれか一項に記載の化合物と治療剤とを含む、組成物。
- 中性脂質、ステロイドおよびポリマーコンジュゲート脂質から選択される1つまたはそれより多くの賦形剤をさらに含む、請求項32に記載の組成物。
- 前記組成物が、DSPC、DPPC、DMPC、DOPC、POPC、DOPEおよびSMから選択される1つまたはそれより多くの中性脂質を含む、請求項33に記載の組成物。
- 前記中性脂質がDSPCである、請求項34に記載の組成物。
- 前記化合物対前記中性脂質のモル比が、約2:1〜約8:1の範囲である、請求項32から35のいずれか一項に記載の組成物。
- 前記ステロイドがコレステロールである、請求項33から36のいずれか一項に記載の組成物。
- 前記化合物対コレステロールのモル比が、5:1〜1:1の範囲である、請求項37に記載の組成物。
- 前記ポリマーコンジュゲート脂質がペグ化脂質である、請求項33から38のいずれか一項に記載の組成物。
- 前記化合物対ペグ化脂質のモル比が、約100:1〜約20:1の範囲である、請求項39に記載の組成物。
- 前記ペグ化脂質が、PEG−DAG、PEG−PE、PEG−S−DAG、PEG−cerまたはPEGジアルコキシプロピルカルバメートである、請求項39または40のいずれか一項に記載の組成物。
- R8およびR9が、それぞれ独立して、12〜16個の炭素原子を含有する直鎖状のアルキル鎖である、請求項42に記載の組成物。
- 前記wの平均が約49である、請求項42または43のいずれか一項に記載の組成物。
- 前記治療剤が核酸を含む、請求項31から44のいずれか一項に記載の組成物。
- 前記核酸が、アンチセンスおよびメッセンジャーRNAから選択される、請求項45に記載の組成物。
- 治療剤を、それを必要とする患者に投与するための方法であって、前記方法は、請求項32から46のいずれか一項に記載の組成物を調製または提供するステップと、前記組成物を前記患者に投与するステップとを含む、方法。
- 請求項1から31のいずれか一項に記載の化合物を含む、脂質ナノ粒子。
- 請求項48に記載の脂質ナノ粒子と、薬学的に許容される希釈剤または賦形剤とを含む、医薬組成物。
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Families Citing this family (58)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA3003055C (en) | 2015-10-28 | 2023-08-01 | Acuitas Therapeutics, Inc. | Lipids and lipid nanoparticle formulations for delivery of nucleic acids |
US11969506B2 (en) | 2017-03-15 | 2024-04-30 | Modernatx, Inc. | Lipid nanoparticle formulation |
US11357856B2 (en) | 2017-04-13 | 2022-06-14 | Acuitas Therapeutics, Inc. | Lipids for delivery of active agents |
JP7297676B2 (ja) | 2017-04-28 | 2023-06-26 | アクイタス セラピューティクス インコーポレイテッド | 新規なカルボニル脂質、および核酸を送達するための脂質ナノ粒子製剤 |
US11524932B2 (en) | 2017-08-17 | 2022-12-13 | Acuitas Therapeutics, Inc. | Lipids for use in lipid nanoparticle formulations |
US11542225B2 (en) | 2017-08-17 | 2023-01-03 | Acuitas Therapeutics, Inc. | Lipids for use in lipid nanoparticle formulations |
CA3073018A1 (en) | 2017-08-17 | 2019-02-21 | Acuitas Therapeutics, Inc. | Lipids for use in lipid nanoparticle formulations |
EP3852911A2 (en) | 2018-09-21 | 2021-07-28 | Acuitas Therapeutics, Inc. | Systems and methods for manufacturing lipid nanoparticles and liposomes |
CA3114699A1 (en) | 2018-10-09 | 2020-04-16 | The University Of British Columbia | Compositions and systems comprising transfection-competent vesicles free of organic-solvents and detergents and methods related thereto |
JP7523449B2 (ja) | 2019-01-11 | 2024-07-26 | アクイタス セラピューティクス インコーポレイテッド | 活性剤の脂質ナノ粒子送達のための脂質 |
WO2020255010A1 (en) | 2019-06-18 | 2020-12-24 | Janssen Sciences Ireland Unlimited Company | Combination of recombinant interleukin 12 construct and hepatitis b virus (hbv) vaccines |
JP2022537324A (ja) | 2019-06-18 | 2022-08-25 | ヤンセン・サイエンシズ・アイルランド・アンリミテッド・カンパニー | B型肝炎ウイルス(hbv)ワクチンおよび抗pd-1抗体の組合せ |
CN114340664A (zh) | 2019-06-18 | 2022-04-12 | 爱尔兰詹森科学公司 | 乙型肝炎病毒(HBV)疫苗和靶向HBV的RNAi的组合 |
KR20220041080A (ko) | 2019-06-18 | 2022-03-31 | 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 | B형 간염 바이러스(hbv) 백신 및 항-pd-1 또는 항-pc-l1 항체의 조합 |
CA3141323A1 (en) | 2019-06-18 | 2020-12-24 | Helen Horton | Recombinant interleukin 12 construct and uses thereof |
WO2020255062A1 (en) | 2019-06-20 | 2020-12-24 | Janssen Sciences Ireland Unlimited Company | Lipid nanoparticle or liposome delivery of hepatitis b virus (hbv) vaccines |
AU2020350759A1 (en) | 2019-09-19 | 2022-03-31 | Modernatx, Inc. | Branched tail lipid compounds and compositions for intracellular delivery of therapeutic agents |
JP2022548320A (ja) | 2019-09-23 | 2022-11-17 | オメガ セラピューティクス, インコーポレイテッド | アポリポタンパク質b(apob)遺伝子発現をモジュレートするための組成物および方法 |
CA3147643A1 (en) | 2019-09-23 | 2021-04-01 | Omega Therapeutics, Inc. | Compositions and methods for modulating hepatocyte nuclear factor 4-alpha (hnf4.alpha.) gene expression |
EP4118207A1 (en) | 2020-03-11 | 2023-01-18 | Omega Therapeutics, Inc. | Compositions and methods for modulating forkhead box p3 (foxp3) gene expression |
WO2021204179A1 (en) | 2020-04-09 | 2021-10-14 | Suzhou Abogen Biosciences Co., Ltd. | Nucleic acid vaccines for coronavirus |
TW202204309A (zh) | 2020-04-09 | 2022-02-01 | 大陸商蘇州艾博生物科技有限公司 | 脂質奈米粒子組成物 |
WO2022008613A1 (en) | 2020-07-08 | 2022-01-13 | Janssen Sciences Ireland Unlimited Company | Rna replicon vaccines against hbv |
BR112023000327A2 (pt) | 2020-07-16 | 2023-01-31 | Acuitas Therapeutics Inc | Lipídeos catiônicos para o uso em nanopartículas lipídicas |
TW202245809A (zh) | 2020-12-18 | 2022-12-01 | 美商詹森藥物公司 | 用於治療b型肝炎病毒感染之組合療法 |
CA3203442A1 (en) | 2020-12-28 | 2022-07-07 | Arcturus Therapeutics, Inc. | Transcription activator-like effector nucleases (talens) targeting hbv |
US11524023B2 (en) | 2021-02-19 | 2022-12-13 | Modernatx, Inc. | Lipid nanoparticle compositions and methods of formulating the same |
AR125204A1 (es) * | 2021-03-24 | 2023-06-21 | Modernatx Inc | Compuestos de lípidos de cola ramificada y composiciones para la administración intracelular de agentes terapéuticos |
EP4351651A1 (en) * | 2021-05-28 | 2024-04-17 | Renagade Therapeutics Management Inc. | Lipid nanoparticles and methods of use thereof |
EP4367242A2 (en) | 2021-07-07 | 2024-05-15 | Omega Therapeutics, Inc. | Compositions and methods for modulating secreted frizzled receptor protein 1 (sfrp1) gene expression |
WO2023023055A1 (en) | 2021-08-16 | 2023-02-23 | Renagade Therapeutics Management Inc. | Compositions and methods for optimizing tropism of delivery systems for rna |
KR20240049810A (ko) | 2021-09-03 | 2024-04-17 | 큐어백 에스이 | 핵산 전달용 신규 지질 나노입자 |
EP4396355A1 (en) | 2021-09-03 | 2024-07-10 | GlaxoSmithKline Biologicals S.A. | Substitution of nucleotide bases in self-amplifying messenger ribonucleic acids |
EP4402123A1 (en) | 2021-09-14 | 2024-07-24 | Renagade Therapeutics Management Inc. | Cyclic lipids and methods of use thereof |
WO2023044343A1 (en) | 2021-09-14 | 2023-03-23 | Renagade Therapeutics Management Inc. | Acyclic lipids and methods of use thereof |
AR127312A1 (es) | 2021-10-08 | 2024-01-10 | Suzhou Abogen Biosciences Co Ltd | Compuestos lipídicos ycomposiciones de nanopartículas lipídicas |
EP4422698A1 (en) | 2021-10-29 | 2024-09-04 | CureVac SE | Improved circular rna for expressing therapeutic proteins |
WO2023081756A1 (en) | 2021-11-03 | 2023-05-11 | The J. David Gladstone Institutes, A Testamentary Trust Established Under The Will Of J. David Gladstone | Precise genome editing using retrons |
WO2023122752A1 (en) * | 2021-12-23 | 2023-06-29 | Renagade Therapeutics Management Inc. | Constrained lipids and methods of use thereof |
WO2023141602A2 (en) | 2022-01-21 | 2023-07-27 | Renagade Therapeutics Management Inc. | Engineered retrons and methods of use |
WO2023144330A1 (en) | 2022-01-28 | 2023-08-03 | CureVac SE | Nucleic acid encoded transcription factor inhibitors |
AU2023214198A1 (en) * | 2022-01-31 | 2024-08-15 | Genevant Sciences Gmbh | Ionizable cationic lipids for lipid nanoparticles |
WO2023154451A1 (en) | 2022-02-10 | 2023-08-17 | Christiana Care Gene Editing Institute, Inc. | Methods for lipid nanoparticle delivery of crispr/cas system |
WO2023173203A1 (en) * | 2022-03-14 | 2023-09-21 | Nanovation Therapeutics Inc. | Synthetic method for producing ionizable amino lipids |
WO2023177904A1 (en) | 2022-03-18 | 2023-09-21 | Modernatx, Inc. | Sterile filtration of lipid nanoparticles and filtration analysis thereof for biological applications |
WO2023196931A1 (en) | 2022-04-07 | 2023-10-12 | Renagade Therapeutics Management Inc. | Cyclic lipids and lipid nanoparticles (lnp) for the delivery of nucleic acids or peptides for use in vaccinating against infectious agents |
WO2023218420A1 (en) | 2022-05-13 | 2023-11-16 | Janssen Pharmaceuticals, Inc. | Mrna compositions for inducing latent hiv-1 reversal |
WO2023227608A1 (en) | 2022-05-25 | 2023-11-30 | Glaxosmithkline Biologicals Sa | Nucleic acid based vaccine encoding an escherichia coli fimh antigenic polypeptide |
WO2023233290A1 (en) | 2022-05-31 | 2023-12-07 | Janssen Sciences Ireland Unlimited Company | Rnai agents targeting pd-l1 |
WO2023235589A1 (en) * | 2022-06-03 | 2023-12-07 | University Of Cincinnati | Ionizable lipids, lipid nanoparticles for mrna delivery and methods of making the same |
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 |
WO2024020346A2 (en) | 2022-07-18 | 2024-01-25 | Renagade Therapeutics Management Inc. | Gene editing components, systems, and methods of use |
WO2024044147A1 (en) | 2022-08-23 | 2024-02-29 | Modernatx, Inc. | Methods for purification of ionizable lipids |
WO2024044723A1 (en) | 2022-08-25 | 2024-02-29 | Renagade Therapeutics Management Inc. | Engineered retrons and methods of use |
DE202023106198U1 (de) | 2022-10-28 | 2024-03-21 | CureVac SE | Impfstoff auf Nukleinsäurebasis |
WO2024133160A1 (en) | 2022-12-19 | 2024-06-27 | Glaxosmithkline Biologicals Sa | Hepatitis b compositions |
CN115677518B (zh) * | 2023-01-05 | 2023-04-14 | 北京悦康科创医药科技股份有限公司 | 用于递送核酸的可电离阳离子脂质化合物和组合物及用途 |
CN116375592A (zh) * | 2023-01-05 | 2023-07-04 | 北京悦康科创医药科技股份有限公司 | 长效低毒的新型阳离子脂质化合物及其组合物 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013086373A1 (en) * | 2011-12-07 | 2013-06-13 | Alnylam Pharmaceuticals, Inc. | Lipids for the delivery of active agents |
WO2016176330A1 (en) * | 2015-04-27 | 2016-11-03 | The Trustees Of The University Of Pennsylvania | Nucleoside-modified rna for inducing an adaptive immune response |
WO2017075531A1 (en) * | 2015-10-28 | 2017-05-04 | Acuitas Therapeutics, Inc. | Novel lipids and lipid nanoparticle formulations for delivery of nucleic acids |
JP2017522376A (ja) * | 2014-06-25 | 2017-08-10 | アクイタス セラピューティクス インコーポレイテッド | 核酸の送達のための新規脂質および脂質ナノ粒子製剤 |
WO2018200943A1 (en) * | 2017-04-28 | 2018-11-01 | Acuitas Therapeutics, Inc. | Novel carbonyl lipids and lipid nanoparticle formulations for delivery of nucleic acids |
JP2020500539A (ja) * | 2016-12-09 | 2020-01-16 | サンガモ セラピューティクス, インコーポレイテッド | 標的特異的ヌクレアーゼの送達 |
Family Cites Families (211)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2856420A (en) | 1955-12-15 | 1958-10-14 | Minnesota Mining & Mfg | Perfluoro- and perfluorochlorocarboxylic acid esters of amino alcohols |
US3340299A (en) | 1964-03-27 | 1967-09-05 | Air Reduction | Tetrasubstituted ethylene diamines |
GB1277947A (en) | 1968-08-22 | 1972-06-14 | Armour Ind Chem Co | Compositions and method for controlling insect pests |
US4491583A (en) | 1970-08-07 | 1985-01-01 | Pfizer Inc. | Interferon induction in animals by amines |
US3729564A (en) | 1970-12-16 | 1973-04-24 | Pfizer | N-secondary alkyl alkanediamines and derivatives thereof as anti-inflammatory agents |
JPS5122416B2 (ja) | 1972-11-11 | 1976-07-09 | ||
JPS5718088B2 (ja) | 1972-06-22 | 1982-04-14 | ||
DE2633615C3 (de) | 1976-07-27 | 1981-08-13 | Bayer Ag, 5090 Leverkusen | Verfahren zum Färben von synthetischen Polyamid-Fasermaterialien |
DE3010599A1 (de) | 1979-03-22 | 1980-10-09 | Continental Pharma | Derivate von glycinamid, deren herstellung und verwendung |
US4883751A (en) | 1986-05-28 | 1989-11-28 | New York University | Specific immunoassay for heparin |
US6077509A (en) | 1990-03-30 | 2000-06-20 | Autoimmune, Inc. | Peptide fragments of myelin basic protein |
JP2588339B2 (ja) | 1992-06-02 | 1997-03-05 | 花王株式会社 | 新規ジアミノジエステル及びその製造法 |
US6197553B1 (en) | 1994-07-15 | 2001-03-06 | Merck & Co., Inc. | Method for large scale plasmid purification |
FR2727679B1 (fr) | 1994-12-05 | 1997-01-03 | Rhone Poulenc Rorer Sa | Nouveaux agents de transfection et leurs applications pharmaceutiques |
US5981501A (en) | 1995-06-07 | 1999-11-09 | Inex Pharmaceuticals Corp. | Methods for encapsulating plasmids in lipid bilayers |
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 |
AU723163B2 (en) | 1995-06-07 | 2000-08-17 | Tekmira Pharmaceuticals Corporation | Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer |
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 |
WO1997003939A1 (en) | 1995-07-21 | 1997-02-06 | Genta Incorporated | Novel amide-based cationic lipids |
DE19605175A1 (de) | 1996-02-13 | 1997-08-14 | Sourovoi Andrej Dr | Lipidverbindungen und deren Verwendung |
JPH103643A (ja) | 1996-06-12 | 1998-01-06 | Fuji Photo Film Co Ltd | ディスク状磁気記録媒体 |
EP0948587B1 (en) | 1996-10-11 | 2003-05-07 | Infineum Holdings BV | Fuel compositions |
CA2217550A1 (en) | 1996-10-22 | 1998-04-22 | F. Hoffmann-La Roche Ag | Cationic lipids for gene therapy |
US6884430B1 (en) | 1997-02-10 | 2005-04-26 | Aventis Pharma S.A. | Formulation of stabilized cationic transfection agent(s) /nucleic acid particles |
US5965542A (en) | 1997-03-18 | 1999-10-12 | Inex Pharmaceuticals Corp. | Use of temperature to control the size of cationic liposome/plasmid DNA complexes |
US5756785A (en) | 1997-03-21 | 1998-05-26 | Lambent Technologies, Inc. | Guerbet betaines |
FR2763943B1 (fr) | 1997-05-28 | 1999-07-09 | Rhone Poulenc Rorer Sa | Composes, leur preparation et leur utilisation pour le transfert d'acides nucleiques dans les cellules |
US6395713B1 (en) | 1997-07-23 | 2002-05-28 | Ribozyme Pharmaceuticals, Inc. | Compositions for the delivery of negatively charged molecules |
DE69834133D1 (de) | 1997-12-23 | 2006-05-18 | Inex Pharmaceuticals Corp | Polyamid-oligomere |
US6410328B1 (en) | 1998-02-03 | 2002-06-25 | Protiva Biotherapeutics Inc. | Sensitizing cells to compounds using lipid-mediated gene and compound delivery |
US6986902B1 (en) | 1998-04-28 | 2006-01-17 | Inex Pharmaceuticals Corporation | Polyanionic polymers which enhance fusogenicity |
US6013813A (en) | 1998-06-17 | 2000-01-11 | Hansotech Inc | Guerbet based sorbitan esters |
US6333433B1 (en) | 1998-11-09 | 2001-12-25 | Council Of Scientific Industrial Research | Process for synthesis of novel cationic amphiphiles containing N-hydroxyalkl group for intracellular delivery of biologically active molecules |
US6656498B1 (en) | 1998-11-25 | 2003-12-02 | Vanderbilt University | Cationic liposomes for gene transfer |
US5919743A (en) | 1998-12-28 | 1999-07-06 | Petroferm Inc. | Guerbet branched quaternary compounds in personal care applications |
US7112337B2 (en) | 1999-04-23 | 2006-09-26 | Alza Corporation | Liposome composition for delivery of nucleic acid |
US6211140B1 (en) | 1999-07-26 | 2001-04-03 | The Procter & Gamble Company | Cationic charge boosting systems |
EP1619254B1 (en) | 1999-09-09 | 2010-12-22 | CureVac GmbH | Transfer of mRNA using polycationic compounds |
GB9930533D0 (en) | 1999-12-23 | 2000-02-16 | Mitsubishi Tokyo Pharm Inc | Nucleic acid delivery |
JP2001338416A (ja) | 2000-05-25 | 2001-12-07 | Sony Corp | ディスク状磁気記録媒体 |
US20040142474A1 (en) | 2000-09-14 | 2004-07-22 | Expression Genetics, Inc. | Novel cationic lipopolymer as a biocompatible gene delivery agent |
AU2003205048B2 (en) | 2002-01-09 | 2009-02-26 | Transave, Inc. | Efficient liposomal encapsulation |
JP4111856B2 (ja) | 2002-04-12 | 2008-07-02 | 昭和電工株式会社 | 安定化されたアスコルビン酸誘導体 |
DK1519714T3 (da) | 2002-06-28 | 2011-01-31 | Protiva Biotherapeutics Inc | Fremgangsmåde og apparat til fremstilling af liposomer |
DE10229872A1 (de) | 2002-07-03 | 2004-01-29 | Curevac Gmbh | Immunstimulation durch chemisch modifizierte RNA |
US6620794B1 (en) | 2002-07-08 | 2003-09-16 | Colonial Chemical Inc. | Guerbet functionalized phospholipids |
AU2003266301A1 (en) | 2002-08-22 | 2004-03-11 | Cytos Biotechnology Ag | Inducible alphaviral/orip based gene expression system |
AU2004257373B2 (en) | 2003-07-16 | 2011-03-24 | Arbutus Biopharma Corporation | Lipid encapsulated interfering RNA |
DE10335833A1 (de) | 2003-08-05 | 2005-03-03 | Curevac Gmbh | Transfektion von Blutzellen mit mRNA zur Immunstimulation und Gentherapie |
NZ592917A (en) | 2003-09-15 | 2012-12-21 | Protiva Biotherapeutics Inc | Stable polyethyleneglycol (PEG) dialkyloxypropyl (DAA) lipid conjugates |
EP1750673B1 (en) | 2004-05-17 | 2009-12-02 | Tekmira Pharmaceuticals Corporation | Liposomal formulations comprising dihydrosphingomyelin and methods of use thereof |
EP1766035B1 (en) | 2004-06-07 | 2011-12-07 | Protiva Biotherapeutics Inc. | Lipid encapsulated interfering rna |
ATE537263T1 (de) | 2004-06-07 | 2011-12-15 | Protiva Biotherapeutics Inc | Kationische lipide und verwendungsverfahren |
DE102004042546A1 (de) | 2004-09-02 | 2006-03-09 | Curevac Gmbh | Kombinationstherapie zur Immunstimulation |
CN101346468B (zh) * | 2005-06-15 | 2016-03-30 | 麻省理工学院 | 含胺脂质和其用途 |
WO2007012191A1 (en) | 2005-07-27 | 2007-02-01 | Protiva Biotherapeutics, Inc. | Systems and methods for manufacturing liposomes |
EP4332227A1 (en) | 2005-08-23 | 2024-03-06 | The Trustees of the University of Pennsylvania | Rna containing modified nucleosides and methods of use thereof |
JP4681425B2 (ja) | 2005-11-15 | 2011-05-11 | 花王株式会社 | 毛髪弾性改善剤 |
DE102006035618A1 (de) | 2006-07-31 | 2008-02-07 | Curevac Gmbh | Nukleinsäure der Formel (I): GlXmGn, insbesondere als immunstimulierendes Adjuvanz |
EP2695608B1 (en) | 2006-10-03 | 2016-11-23 | Arbutus Biopharma Corporation | Lipid containing formulations |
DE102007001370A1 (de) | 2007-01-09 | 2008-07-10 | Curevac Gmbh | RNA-kodierte Antikörper |
WO2008109806A2 (en) | 2007-03-08 | 2008-09-12 | Massachusetts Institute Of Technology | Electrostatic coating of particles for drug delivery |
WO2009030254A1 (en) | 2007-09-04 | 2009-03-12 | Curevac Gmbh | Complexes of rna and cationic peptides for transfection and for immunostimulation |
WO2009046739A1 (en) | 2007-10-09 | 2009-04-16 | Curevac Gmbh | Composition for treating prostate cancer (pca) |
EP3141265A1 (en) | 2007-12-04 | 2017-03-15 | Alnylam Pharmaceuticals, Inc. | Carbohydrate conjugates as delivery agents for oligonucleotides |
US20110045473A1 (en) | 2008-01-02 | 2011-02-24 | De Fougerolles Antonin | Liver screening method |
WO2009088891A1 (en) | 2008-01-02 | 2009-07-16 | Alnylam Pharmaceuticals, Inc. | Screening method for selected amino lipid-containing compositions |
EP2176408B9 (en) | 2008-01-31 | 2015-11-11 | Curevac GmbH | NUCLEIC ACIDS COMPRISING FORMULA (NuGiXmGnNv)a AND DERIVATIVES THEREOF AS AN IMMUNOSTIMULATING AGENTS /ADJUVANTS |
CA2721183C (en) | 2008-04-11 | 2019-07-16 | Alnylam Pharmaceuticals, Inc. | Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components |
JP5475753B2 (ja) | 2008-04-15 | 2014-04-16 | プロチバ バイオセラピューティクス インコーポレイティッド | 核酸送達用の脂質製剤 |
WO2009132131A1 (en) | 2008-04-22 | 2009-10-29 | Alnylam Pharmaceuticals, Inc. | Amino lipid based improved lipid formulation |
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 |
PL2350043T3 (pl) | 2008-10-09 | 2014-09-30 | Tekmira Pharmaceuticals Corp | Ulepszone aminolipidy i sposoby dostarczania kwasów nukleinowych |
WO2010048536A2 (en) | 2008-10-23 | 2010-04-29 | Alnylam Pharmaceuticals, Inc. | Processes for preparing lipids |
US20120009222A1 (en) * | 2008-10-27 | 2012-01-12 | Massachusetts Institute Of Technology | Modulation of the immune response |
WO2010054384A1 (en) | 2008-11-10 | 2010-05-14 | Alnylam Pharmaceuticals, Inc. | Lipids and compositions for the delivery of therapeutics |
CA3039251C (en) | 2008-11-10 | 2024-01-09 | Arbutus Biopharma Corporation | Novel lipids and compositions for the delivery of therapeutics |
EP2362728A1 (en) | 2008-11-17 | 2011-09-07 | Enzon Pharmaceuticals, Inc. | Releasable polymeric lipids for nucleic acids delivery system |
CA3036963A1 (en) | 2009-01-29 | 2010-08-05 | Arbutus Biopharma Corporation | Lipid formulations comprising cationic lipid and a targeting lipid comprising n-acetyl galactosamine for delivery of nucleic acid |
EP3097908A1 (en) | 2009-05-05 | 2016-11-30 | Arbutus Biopharma Corporation | Lipid compositions |
AU2010245933B2 (en) | 2009-05-05 | 2016-06-16 | Arbutus Biopharma Corporation | Methods of delivering oligonucleotides to immune cells |
SG10201403054SA (en) | 2009-06-10 | 2014-10-30 | Tekmira Pharmaceuticals Corp | Improved lipid formulation |
US9051567B2 (en) | 2009-06-15 | 2015-06-09 | Tekmira Pharmaceuticals Corporation | Methods for increasing efficacy of lipid formulated siRNA |
US9018187B2 (en) | 2009-07-01 | 2015-04-28 | Protiva Biotherapeutics, Inc. | Cationic lipids and methods for the delivery of therapeutic agents |
US8569256B2 (en) | 2009-07-01 | 2013-10-29 | Protiva Biotherapeutics, Inc. | Cationic lipids and methods for the delivery of therapeutic agents |
JP5766188B2 (ja) | 2009-07-01 | 2015-08-19 | プロチバ バイオセラピューティクス インコーポレイティッド | 固形腫瘍に治療剤を送達するための脂質製剤 |
RU2585227C2 (ru) | 2009-07-15 | 2016-05-27 | Новартис Аг | Композиции белка f rsv и способы их получения |
WO2011036557A1 (en) | 2009-09-22 | 2011-03-31 | The University Of British Columbia | Compositions and methods for enhancing cellular uptake and intracellular delivery of lipid particles |
CN102712935B (zh) | 2009-11-04 | 2017-04-26 | 不列颠哥伦比亚大学 | 含有核酸的脂质粒子及相关的方法 |
US20130022649A1 (en) | 2009-12-01 | 2013-01-24 | Protiva Biotherapeutics, Inc. | Snalp formulations containing antioxidants |
AU2010328336B2 (en) | 2009-12-07 | 2017-03-02 | Arbutus Biopharma Corporation | Compositions for nucleic acid delivery |
NZ600725A (en) | 2009-12-18 | 2015-08-28 | Univ British Colombia | Methods and compositions for delivery of nucleic acids |
EP2567951B1 (en) | 2010-04-28 | 2018-09-19 | Kyowa Hakko Kirin Co., Ltd. | Cationic lipid |
JP5902617B2 (ja) | 2010-04-28 | 2016-04-13 | 協和発酵キリン株式会社 | カチオン性脂質 |
US9254327B2 (en) | 2010-05-10 | 2016-02-09 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for delivery of active agents |
US8865675B2 (en) | 2010-05-12 | 2014-10-21 | Protiva Biotherapeutics, Inc. | Compositions and methods for silencing apolipoprotein B |
JP2013527856A (ja) | 2010-05-12 | 2013-07-04 | プロチバ バイオセラピューティクス インコーポレイティッド | 陽イオン性脂質およびその使用方法 |
EP2575895A2 (en) | 2010-05-24 | 2013-04-10 | Merck Sharp & Dohme Corp. | Novel amino alcohol cationic lipids for oligonucleotide delivery |
NZ605079A (en) | 2010-06-03 | 2015-08-28 | Alnylam Pharmaceuticals Inc | Biodegradable lipids for the delivery of active agents |
WO2012000104A1 (en) | 2010-06-30 | 2012-01-05 | Protiva Biotherapeutics, Inc. | Non-liposomal systems for nucleic acid delivery |
US9770463B2 (en) | 2010-07-06 | 2017-09-26 | Glaxosmithkline Biologicals Sa | Delivery of RNA to different cell types |
LT2590676T (lt) | 2010-07-06 | 2016-10-25 | Glaxosmithkline Biologicals Sa | Viriono tipo išnešiojančios dalelės, skirtos besireplikuojančioms rnr molekulėms |
HUE047796T2 (hu) | 2010-07-06 | 2020-05-28 | Glaxosmithkline Biologicals Sa | RNS bevitele több immunútvonal bekapcsolására |
SI2591114T1 (sl) | 2010-07-06 | 2016-10-28 | Glaxosmithkline Biologicals S.A. | Imunizacija velikih sesalcev z majhnimi odmerki RNA |
WO2012016184A2 (en) | 2010-07-30 | 2012-02-02 | Alnylam Pharmaceuticals, Inc. | Methods and compositions for delivery of active agents |
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 |
ES2918192T3 (es) | 2010-08-31 | 2022-07-14 | Glaxosmithkline Biologicals Sa | Liposomas pegilados para la administración de ARN que codifica para inmunógeno |
ES2923634T3 (es) | 2010-08-31 | 2022-09-29 | Glaxosmithkline Biologicals Sa | Liposomas pequeños para la administración de ARN que codifica para inmunógeno |
EP3542789A3 (en) | 2010-08-31 | 2020-01-01 | GlaxoSmithKline Biologicals SA | Lipids suitable for liposomal delivery of protein-coding rna |
US8466122B2 (en) | 2010-09-17 | 2013-06-18 | Protiva Biotherapeutics, Inc. | Trialkyl cationic lipids and methods of use thereof |
EP3520813B1 (en) | 2010-10-11 | 2023-04-19 | GlaxoSmithKline Biologicals S.A. | Antigen delivery platforms |
US20120136073A1 (en) * | 2010-11-15 | 2012-05-31 | Life Technologies Corporation | Amine-Containing Transfection Reagents and methods for making and using same |
WO2012089225A1 (en) | 2010-12-29 | 2012-07-05 | Curevac Gmbh | Combination of vaccination and inhibition of mhc class i restricted antigen presentation |
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 |
EP2691101A2 (en) | 2011-03-31 | 2014-02-05 | Moderna Therapeutics, Inc. | Delivery and formulation of engineered nucleic acids |
US8691750B2 (en) | 2011-05-17 | 2014-04-08 | Axolabs Gmbh | Lipids and compositions for intracellular delivery of biologically active compounds |
JP2014522842A (ja) | 2011-07-06 | 2014-09-08 | ノバルティス アーゲー | 免疫原性組み合わせ組成物およびその使用 |
EP2729168A2 (en) | 2011-07-06 | 2014-05-14 | Novartis AG | Immunogenic compositions and uses thereof |
WO2013016058A1 (en) | 2011-07-22 | 2013-01-31 | Merck Sharp & Dohme Corp. | Novel bis-nitrogen containing cationic lipids for oligonucleotide delivery |
EP2734531A1 (en) | 2011-07-22 | 2014-05-28 | Université de Strasbourg | Phospholipid-detergent conjugates and uses thereof |
US9126966B2 (en) | 2011-08-31 | 2015-09-08 | Protiva Biotherapeutics, Inc. | Cationic lipids and methods of use thereof |
EP3508220A1 (en) | 2011-08-31 | 2019-07-10 | GlaxoSmithKline Biologicals S.A. | Pegylated liposomes for delivery of immunogen-encoding rna |
CA3186126A1 (en) | 2011-09-21 | 2013-03-28 | Sangamo Biosciences, Inc. | Methods and compositions for regulation of transgene expression |
AU2012315965A1 (en) | 2011-09-27 | 2014-04-03 | Alnylam Pharmaceuticals, Inc. | Di-aliphatic substituted PEGylated lipids |
EP2768958B1 (en) | 2011-10-18 | 2019-08-14 | Dicerna Pharmaceuticals, Inc. | Amine cationic lipids and uses thereof |
ES2912739T3 (es) | 2011-10-27 | 2022-05-27 | Massachusetts Inst Technology | Derivados de aminoácidos funcionalizados en el extremo N-terminal capaces de formar microesferas de encapsulación de fármacos |
JP2013095755A (ja) | 2011-11-02 | 2013-05-20 | Kyowa Hakko Kirin Co Ltd | カチオン性脂質 |
WO2013086322A1 (en) | 2011-12-07 | 2013-06-13 | Alnylam Pharmaceuticals, Inc. | Branched alkyl and cycloalkyl terminated biodegradable lipids for the delivery of active agents |
ES2921724T1 (es) | 2011-12-07 | 2022-08-31 | Alnylam Pharmaceuticals Inc | Lípidos biodegradables para la administración de agentes activos |
WO2013090648A1 (en) | 2011-12-16 | 2013-06-20 | modeRNA Therapeutics | Modified nucleoside, nucleotide, and nucleic acid compositions |
EP2623121A1 (en) | 2012-01-31 | 2013-08-07 | Bayer Innovation GmbH | Pharmaceutical composition comprising a polymeric carrier cargo complex and an antigen |
WO2013113326A1 (en) | 2012-01-31 | 2013-08-08 | Curevac Gmbh | Pharmaceutical composition comprising a polymeric carrier cargo complex and at least one protein or peptide antigen |
WO2013113325A1 (en) | 2012-01-31 | 2013-08-08 | Curevac Gmbh | Negatively charged nucleic acid comprising complexes for immunostimulation |
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 |
WO2013120498A1 (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 allergenic antigen or an autoimmune self-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 |
CN102604115B (zh) | 2012-02-22 | 2013-07-10 | 天津大学 | 羧甲基壳聚糖季铵盐/pamam核壳纳米粒及制备方法 |
SG11201405157PA (en) | 2012-02-24 | 2014-10-30 | Protiva Biotherapeutics Inc | Trialkyl cationic lipids and methods of use thereof |
WO2013143555A1 (en) | 2012-03-26 | 2013-10-03 | Biontech Ag | Rna formulation for immunotherapy |
SG10201607968WA (en) | 2012-03-27 | 2016-12-29 | Curevac Ag | Artificial nucleic acid molecules for improved protein or peptide expression |
CN104220599A (zh) | 2012-03-27 | 2014-12-17 | 库瑞瓦格有限责任公司 | 人工核酸分子 |
AU2013240051B2 (en) | 2012-03-27 | 2017-11-30 | Sirna Therapeutics, Inc. | Diether based biodegradable cationic lipids for siRNA delivery |
MX358706B (es) | 2012-03-27 | 2018-08-31 | Curevac Ag | Moleculas de acido nucleico artificiales que comprenden un top 5´utr. |
WO2013174409A1 (en) | 2012-05-25 | 2013-11-28 | Curevac Gmbh | Reversible immobilization and/or controlled release of nucleic acid containing nanoparticles by (biodegradable) polymer coatings |
US20150140068A1 (en) | 2012-07-06 | 2015-05-21 | Novartis Ag | Immunogenic compositions and uses thereof |
US9415109B2 (en) | 2012-07-06 | 2016-08-16 | Alnylam Pharmaceuticals, Inc. | Stable non-aggregating nucleic acid lipid particle formulations |
WO2014028487A1 (en) | 2012-08-13 | 2014-02-20 | Massachusetts Institute Of Technology | Amine-containing lipidoids and uses thereof |
US9687448B2 (en) | 2012-12-07 | 2017-06-27 | Alnylam Pharmaceuticals, Inc. | Nucleic acid lipid particle formulations |
MX2015008847A (es) | 2013-01-10 | 2015-10-30 | Novartis Ag | Composiciones inmunogenicas de virus de influenza y usos de las mismas. |
CN105073135A (zh) | 2013-02-22 | 2015-11-18 | 库瑞瓦格有限责任公司 | 疫苗接种和抑制pd-1途径的组合 |
KR102310921B1 (ko) | 2013-03-14 | 2021-10-13 | 다이서나 파마수이티컬, 인크. | 음이온성 약제를 제형화하는 방법 |
US20160032316A1 (en) | 2013-03-14 | 2016-02-04 | The Trustees Of The University Of Pennsylvania | Purification and Purity Assessment of RNA Molecules Synthesized with Modified Nucleosides |
WO2014160284A1 (en) | 2013-03-14 | 2014-10-02 | The Trustees Of The University Of Pennsylvania | Compositions and methods for treatment of stroke |
AU2014310931B2 (en) | 2013-08-21 | 2019-12-19 | CureVac SE | Rabies vaccine |
CA2915904A1 (en) | 2013-08-21 | 2015-02-26 | Curevac Ag | Composition and vaccine for treating prostate cancer |
MX369469B (es) | 2013-08-21 | 2019-11-08 | Curevac Ag | Vacuna contra el virus respiratorio sincitial. |
CN105473157A (zh) | 2013-08-21 | 2016-04-06 | 库瑞瓦格股份公司 | 组合疫苗 |
WO2015024667A1 (en) | 2013-08-21 | 2015-02-26 | Curevac Gmbh | Method for increasing expression of rna-encoded proteins |
ES2806575T3 (es) | 2013-11-01 | 2021-02-18 | Curevac Ag | ARN modificado con propiedades inmunoestimuladoras disminuidas |
EP3071547B1 (en) | 2013-11-18 | 2024-07-10 | Arcturus Therapeutics, Inc. | Ionizable cationic lipid for rna delivery |
SG10201903381TA (en) | 2013-12-30 | 2019-05-30 | Curevac Ag | Artificial nucleic acid molecules |
CA2927254C (en) | 2013-12-30 | 2023-10-24 | Curevac Ag | Artificial nucleic acid molecules |
US20170042870A1 (en) | 2014-02-17 | 2017-02-16 | The Brigham And Women's Hospital, Inc. | Targeted nanoparticle compositions and methods of their use to treat obesity |
EP3556353A3 (en) | 2014-02-25 | 2020-03-18 | Merck Sharp & Dohme Corp. | Lipid nanoparticle vaccine adjuvants and antigen delivery systems |
EP3129050A2 (en) | 2014-04-01 | 2017-02-15 | CureVac AG | Polymeric carrier cargo complex for use as an immunostimulating agent or as an adjuvant |
JP6881813B2 (ja) | 2014-04-23 | 2021-06-02 | モデルナティーエックス, インコーポレイテッド | 核酸ワクチン |
US10309541B2 (en) | 2014-05-22 | 2019-06-04 | Flowserve S.R.L. | Guide element for a valve actuator and actuator provided with said guide element |
JP6778175B2 (ja) | 2014-07-16 | 2020-10-28 | ノバルティス アーゲー | 脂質ナノ粒子ホスト中に核酸を封入する方法 |
JP6339884B2 (ja) | 2014-07-17 | 2018-06-06 | 富士フイルム株式会社 | イミダゾール化合物およびそれを含有するリポソーム |
US9816074B2 (en) | 2014-07-25 | 2017-11-14 | Sangamo Therapeutics, Inc. | Methods and compositions for modulating nuclease-mediated genome engineering in hematopoietic stem cells |
EP3708668B1 (en) | 2014-12-12 | 2022-07-27 | CureVac AG | Artificial nucleic acid molecules for improved protein expression |
EP3233113A1 (en) | 2014-12-16 | 2017-10-25 | CureVac AG | Ebolavirus and marburgvirus vaccines |
EP3494982A1 (en) | 2014-12-30 | 2019-06-12 | CureVac AG | Artificial nucleic acid molecules |
CN104876831B (zh) | 2015-04-03 | 2017-05-17 | 苏州圣诺生物医药技术有限公司 | 脂质修饰精胺衍生物及利用该衍生物制备的脂质体 |
WO2016165825A1 (en) | 2015-04-13 | 2016-10-20 | Curevac Ag | Method for producing rna compositions |
WO2016184822A1 (en) | 2015-05-15 | 2016-11-24 | Curevac Ag | Prime-boost regimens involving administration of at least one mrna construct |
US20180296663A1 (en) | 2015-06-17 | 2018-10-18 | Curevac Ag | Vaccine composition |
IL283545B2 (en) | 2015-06-29 | 2023-09-01 | Acuitas Therapeutics Inc | Lipids and nanoparticulate lipid formulations for delivery of nucleic acids |
US20200085852A1 (en) | 2015-08-05 | 2020-03-19 | Curevac Ag | Epidermal mrna vaccine |
DK3332019T3 (da) | 2015-08-07 | 2020-02-17 | Curevac Ag | Fremgangsmåde til in vivo-produktionen af rna i en værtscelle |
US20180237786A1 (en) | 2015-08-28 | 2018-08-23 | Curevac Ag | Artificial nucleic acid molecules |
WO2017048770A1 (en) | 2015-09-15 | 2017-03-23 | Regulus Therapeutics, Inc. | Systems, compositions, and methods for formulating nucleic acid compositions |
EP4286012A3 (en) | 2015-09-17 | 2024-05-29 | ModernaTX, Inc. | Compounds and compositions for intracellular delivery of therapeutic agents |
WO2017070616A2 (en) | 2015-10-22 | 2017-04-27 | Modernatx, Inc. | Sexually transmitted disease vaccines |
DE20164728T1 (de) | 2015-10-22 | 2021-09-30 | Modernatx, Inc. | Impfstoffe gegen atemwegsvirus |
US11413346B2 (en) | 2015-11-09 | 2022-08-16 | Curevac Ag | Rotavirus vaccines |
US20180312545A1 (en) | 2015-11-09 | 2018-11-01 | Curevac Ag | Optimized nucleic acid molecules |
WO2017112865A1 (en) | 2015-12-22 | 2017-06-29 | Modernatx, Inc. | Compounds and compositions for intracellular delivery of agents |
US20190022247A1 (en) | 2015-12-30 | 2019-01-24 | Acuitas Therapeutics, Inc. | Lipids and lipid nanoparticle formulations for delivery of nucleic acids |
SG10201913630YA (en) | 2016-02-17 | 2020-03-30 | Curevac Ag | Zika virus vaccine |
US20170266292A1 (en) | 2016-03-21 | 2017-09-21 | The Research Foundation For The State University Of New York | Lipidic compound-telodendrimer hybrid nanoparticles and methods of making and uses thereof |
BR112018069795A2 (pt) | 2016-03-30 | 2019-01-29 | Intellia Therapeutics Inc | formulações de nanopartículas lipídicas para componentes de crispr/cas |
US20190343942A1 (en) | 2016-04-22 | 2019-11-14 | Curevac Ag | Rna encoding a tumor antigen |
US20180126003A1 (en) | 2016-05-04 | 2018-05-10 | Curevac Ag | New targets for rna therapeutics |
EP3454835B1 (en) | 2016-05-09 | 2021-03-31 | Astrazeneca AB | Lipid nanoparticles comprising lipophilic anti-inflammatory agents and methods of use thereof |
US20190298657A1 (en) | 2016-05-18 | 2019-10-03 | Modernatx, Inc. | Polynucleotides Encoding Acyl-CoA Dehydrogenase, Very Long-Chain for the Treatment of Very Long-Chain Acyl-CoA Dehydrogenase Deficiency |
AU2017350488B2 (en) | 2016-10-26 | 2022-06-23 | Acuitas Therapeutics Inc. | Lipid nanoparticle mRNA vaccines |
US20190274968A1 (en) | 2016-10-27 | 2019-09-12 | The Trustees Of The University Of Pennsylvania | Nucleoside-modified rna for inducing an adaptive immune response |
US11357856B2 (en) | 2017-04-13 | 2022-06-14 | Acuitas Therapeutics, Inc. | Lipids for delivery of active agents |
WO2018191719A1 (en) | 2017-04-13 | 2018-10-18 | Acuitas Therapeutics, Inc. | Lipid delivery of therapeutic agents to adipose tissue |
US12029790B2 (en) | 2017-07-31 | 2024-07-09 | Ohio State Innovation Foundation | Biomimetic nanomaterials and uses thereof |
CA3073018A1 (en) | 2017-08-17 | 2019-02-21 | Acuitas Therapeutics, Inc. | Lipids for use in lipid nanoparticle formulations |
US11524932B2 (en) | 2017-08-17 | 2022-12-13 | Acuitas Therapeutics, Inc. | Lipids for use in lipid nanoparticle formulations |
US11542225B2 (en) | 2017-08-17 | 2023-01-03 | Acuitas Therapeutics, Inc. | Lipids for use in lipid nanoparticle formulations |
WO2019089828A1 (en) | 2017-10-31 | 2019-05-09 | Acuitas Therapeutics, Inc. | Lamellar lipid nanoparticles |
EP3867225A1 (en) | 2018-10-18 | 2021-08-25 | Acuitas Therapeutics, Inc. | Lipids for lipid nanoparticle delivery of active agents |
JP7523449B2 (ja) | 2019-01-11 | 2024-07-26 | アクイタス セラピューティクス インコーポレイテッド | 活性剤の脂質ナノ粒子送達のための脂質 |
CN114901253A (zh) | 2019-08-14 | 2022-08-12 | 爱康泰生治疗公司 | 用于递送核酸的改进的脂质纳米颗粒 |
BR112023000327A2 (pt) | 2020-07-16 | 2023-01-31 | Acuitas Therapeutics Inc | Lipídeos catiônicos para o uso em nanopartículas lipídicas |
-
2018
- 2018-08-16 CA CA3073020A patent/CA3073020A1/en active Pending
- 2018-08-16 US US16/638,733 patent/US11639329B2/en active Active
- 2018-08-16 EP EP18782814.0A patent/EP3668833A1/en active Pending
- 2018-08-16 WO PCT/US2018/000293 patent/WO2019036008A1/en unknown
- 2018-08-16 JP JP2020508372A patent/JP7355731B2/ja active Active
-
2023
- 2023-06-29 JP JP2023107156A patent/JP2023138986A/ja active Pending
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013086373A1 (en) * | 2011-12-07 | 2013-06-13 | Alnylam Pharmaceuticals, Inc. | Lipids for the delivery of active agents |
JP2017522376A (ja) * | 2014-06-25 | 2017-08-10 | アクイタス セラピューティクス インコーポレイテッド | 核酸の送達のための新規脂質および脂質ナノ粒子製剤 |
WO2016176330A1 (en) * | 2015-04-27 | 2016-11-03 | The Trustees Of The University Of Pennsylvania | Nucleoside-modified rna for inducing an adaptive immune response |
WO2017075531A1 (en) * | 2015-10-28 | 2017-05-04 | Acuitas Therapeutics, Inc. | Novel lipids and lipid nanoparticle formulations for delivery of nucleic acids |
JP2020500539A (ja) * | 2016-12-09 | 2020-01-16 | サンガモ セラピューティクス, インコーポレイテッド | 標的特異的ヌクレアーゼの送達 |
WO2018200943A1 (en) * | 2017-04-28 | 2018-11-01 | Acuitas Therapeutics, Inc. | Novel carbonyl lipids and lipid nanoparticle formulations for delivery of nucleic acids |
Non-Patent Citations (2)
Title |
---|
CHEN, DELAI ET AL.: "Rapid Discovery of Potent siRNA-Containing Lipid Nanoparticles Enabled by Controlled Microfluidic Fo", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 134, no. 16, JPN6022023691, 2012, pages 6948 - 6951, XP002715254, ISSN: 0004798835, DOI: 10.1021/ja301621z * |
ZHANG, XINFU ET AL.: "Biodegradable Amino-Ester Nanomaterials for Cas9 mRNA Delivery in Vitro and in Vivo", ACS APPLIED MATERIALS & INTERFACES, vol. 9, no. 30, JPN6022023690, 7 July 2017 (2017-07-07), pages 25481 - 25487, XP055526064, ISSN: 0005006209, DOI: 10.1021/acsami.7b08163 * |
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