发明名称 Polymeric micelles for polynucleotide encapsulation
摘要 The present invention provides micelles having a polynucleotide encapsulated therein, the micelle comprising copolymers comprising hydrophobic moieties in a cationic complexing block. The invention further provides methods of preparing and using said micelles, and compositions thereof.
申请公布号 US8747904(B2) 申请公布日期 2014.06.10
申请号 US201213591122 申请日期 2012.08.21
申请人 Intezyne Technologies, Inc. 发明人 Mirosevich Janni;Cardoen Gregoire;Sill Kevin N.;Skaff Habib
分类号 A61K31/7088;A61K9/14;A61K9/127;A61K48/00 主分类号 A61K31/7088
代理机构 代理人
主权项 1. A micelle having a polynucleotide encapsulated therein, comprising a diblock copolymer of formula I-b: wherein: n is 50-2500;x1 is 0 to 250;x2 is 0 to 250;z1 is 0 to 250, provided that x1 and z1 are not simultaneously zero;z2 is 0 to 250, provided that z1 and z2 are not simultaneously zero; Rx is a natural or unnatural amino acid side-chain group that is hydrophobic; Rz is -L-R4 wherein: L is a bivalent, straight or branched, C4-20 alkylene chain wherein at least one methylene unit of -L- is replaced by —C(O)NR— and 1-10 additional methylene units are independently replaced by —N(R)— or -Het-;Het is a bivalent 5-6 membered saturated, partially unsaturated, or aromatic ring having at least one nitrogen and 0-3 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur; R4 is R or N(R)2;each R is hydrogen or C1-6 aliphatic, or two R on the same nitrogen are taken together with the nitrogen to form a 5-6 membered heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R1 is —Z(CH2CH2Y)p(CH2)tR3, wherein: Z is a valence bond, a bivalent triazolyl moiety, —O—, —S—, —C≡C—, or —CH2—;each Y is independently —O— or —S—;p is 0-10;t is 0-10; and R3 is hydrogen, —N3, —CN, a mono-protected amine, a di-protected amine, a protected aldehyde, a protected hydroxyl, a protected carboxylic acid, a protected thiol, a 9-30 membered crown ether, or an optionally substituted group selected from aliphatic, a 5-8 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, an 8-10 membered saturated, partially unsaturated, or aryl bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a detectable moiety or a targeting group; Q is a valence bond or a bivalent, saturated or unsaturated, straight or branched C1-12 alkylene chain, wherein 0-6 methylene units of Q are independently replaced by -Cy-, —O—, —NH—, —S—, —OC(O)—, —C(O)O—, —C(O)—, —SO—, —SO2—, —NHSO2—, —SO2NH—, —NHC(O)—, —C(O)NH—, —OC(O)NH—, or —NHC(O)O—, wherein: -Cy- is an optionally substituted 5-8 membered bivalent, saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an optionally substituted 8-10 membered bivalent saturated, partially unsaturated, or aryl bicyclic ring having 0-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R2 is selected from an optionally substituted aliphatic group or a fusogenic peptide.
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