公开(公告)号：US10682374B2

公开(公告)日：2020-06-16

申请号：US16126897

申请日：2018-09-10

申请人： Massachusetts Institute of Technology

发明人： Yizhou Dong ,  Kevin Thomas Love ,  Robert S. Langer ,  Daniel Griffith Anderson ,  Delai Chen ,  Yi Chen ,  Arturo Jose Vegas ,  Akinleye C. Alabi ,  Yunlong Zhang

IPC分类号： A61K31/7105 ,  C07D233/64 ,  C07D403/06 ,  C07D241/08 ,  C07C229/12 ,  C07C229/22 ,  C07C229/26 ,  C07D487/06 ,  C07D207/16 ,  C07D209/20 ,  C07C271/22 ,  C07C229/36 ,  C07C237/08 ,  C07C237/12 ,  C12N15/88 ,  C12N15/87 ,  C07C229/24 ,  C07C279/14 ,  C07C323/58 ,  C07D209/24 ,  C07D265/32 ,  C07D413/06 ,  C07D487/04 ,  C12Q1/02 ,  G01N33/15 ,  A61K31/711 ,  A61K47/22

摘要： Described herein are compounds and compositions characterized, in certain embodiments, by conjugation of various groups, such as lipophilic groups, to an amino or amide group of an amino acid, a linear or cyclic peptide, a linear or cyclic polypeptide, or structural isomer thereof, to provide compounds of the present invention, collectively referred to herein as “APPLs”. Such APPLs are deemed useful for a variety of applications, such as, for example, improved nucleotide delivery. Exemplary APPLs include, but are not limited to, compounds of Formula (I), (II), (III), (IV), (V), and (VI), and salts thereof, as described herein: wherein m, n, p, R′, R1, R2, R3, R4, R5, R8, Z, W, Y, and Z are as defined herein.

公开(公告)号：US20150203439A1

公开(公告)日：2015-07-23

申请号：US14599004

申请日：2015-01-16

申请人： Massachusetts Institute of Technology

发明人： Kerry Peter Mahon ,  Kevin Thomas Love ,  Christopher G. Levins ,  Kathryn Ann Whitehead ,  Robert S. Langer ,  Daniel Griffith Anderson

IPC分类号： C07C217/08 ,  A61K38/02 ,  A61K31/7088 ,  A61K47/16 ,  C07C215/14

CPC分类号： C07D295/13 ,  A61K9/107 ,  A61K9/1271 ,  A61K9/5123 ,  A61K31/7088 ,  A61K38/02 ,  A61K47/16 ,  A61K47/54 ,  A61K47/545 ,  A61K48/0025 ,  B01J2531/0252 ,  B01J2531/845 ,  C07C215/14 ,  C07C217/08 ,  C12N15/111 ,  C12N15/1137 ,  C12N15/88 ,  C12N2310/14 ,  C12N2310/3515 ,  C12N2320/32

摘要： Aminoalcohol lipidoids are prepared by reacting an amine with an epoxide-terminated compound are described. Methods of preparing aminoalcohol lipidoids from commercially available starting materials are also provided. Aminoalcohol lipidoids may be prepared from racemic or stereochemically pure epoxides. Aminoalcohol lipidoids or salts forms thereof are preferably biodegradable and biocompatible and may be used in a variety of drug delivery systems. Given the amino moiety of these aminoalcohol lipidoid compounds, they are particularly suited for the delivery of polynucleotides. Complexes, micelles, liposomes or particles containing the inventive lipidoids and polynucleotide have been prepared. The inventive lipidoids may also be used in preparing microparticles for drug delivery. They are particularly useful in delivering labile agents given their ability to buffer the pH of their surroundings.

摘要翻译： 氨基醇类固醇通过使胺与环氧化物封端的化合物反应来制备。 还提供了从市售的原料制备氨基醇类固醇的方法。 氨基醇类固醇可以由外消旋或立体化学纯环氧化物制备。 氨基醇类固醇或其盐形式优选是可生物降解的和生物相容的并且可以用于各种药物递送系统中。 鉴于这些氨基醇类脂质化合物的氨基部分，它们特别适用于递送多核苷酸。 已经制备了含有本发明的类脂和多核苷酸的复合物，胶束，脂质体或颗粒。 本发明的类脂质也可用于制备用于药物递送的微粒。 考虑到缓冲其周围环境的pH值，它们特别适用于提供不稳定剂。

公开(公告)号：US20230124955A1

公开(公告)日：2023-04-20

申请号：US17893918

申请日：2022-08-23

申请人： Massachusetts Institute of Technology

发明人： Yizhou Dong ,  Kevin Thomas Love ,  Robert S. Langer ,  Daniel Griffith Anderson ,  Delai Chen ,  Yi Chen ,  Arturo Jose Vegas ,  Akinleye C. Alabi ,  Yunlong Zhang

IPC分类号： A61K31/7105 ,  C07D233/64 ,  C07D403/06 ,  C07D241/08 ,  C07C229/12 ,  C07C229/22 ,  C07C229/26 ,  C07D487/06 ,  C07D207/16 ,  C07D209/20 ,  C07C271/22 ,  C07C229/36 ,  C07C237/08 ,  C07C237/12 ,  C12N15/88 ,  C12N15/87 ,  C07C229/24 ,  C07C279/14 ,  C07C323/58 ,  C07D209/24 ,  C07D265/32 ,  C07D413/06 ,  C07D487/04 ,  C12Q1/02 ,  G01N33/15 ,  A61K31/711 ,  A61K47/22

摘要： Described herein are compounds and compositions characterized, in certain embodiments, by conjugation of various groups, such as lipophilic groups, to an amino or amide group of an amino acid, a linear or cyclic peptide, a linear or cyclic polypeptide, or structural isomer thereof, to provide compounds of the present invention, collectively referred to herein as “APPLs”. Such APPLs are deemed useful for a variety of applications, such as, for example, improved nucleotide delivery. Exemplary APPLs include, but are not limited to, compounds of Formula (I), (II), (III), (IV), (V), and (VI), and salts thereof, as described herein: wherein m, n, p, R′, R1, R2, R3, R4, R5, R8, Z, W, Y, and Z are as defined herein.

公开(公告)号：US20170165290A1

公开(公告)日：2017-06-15

申请号：US15340082

申请日：2016-11-01

申请人： Massachusetts Institute of Technology

发明人： Yizhou Dong ,  Kevin Thomas Love ,  Robert S. Langer ,  Daniel Griffith Anderson ,  Delai Chen ,  Yi Chen ,  Arturo Jose Vegas ,  Akinleye C. Alabi ,  Yunlong Zhang

IPC分类号： A61K31/7105 ,  A61K47/22 ,  C07D241/08 ,  A61K31/711

CPC分类号： A61K31/7105 ,  A61K31/711 ,  A61K47/22 ,  A61K2121/00 ,  C07C229/12 ,  C07C229/22 ,  C07C229/24 ,  C07C229/26 ,  C07C229/36 ,  C07C237/08 ,  C07C237/12 ,  C07C271/22 ,  C07C279/14 ,  C07C323/58 ,  C07D207/16 ,  C07D209/20 ,  C07D209/24 ,  C07D233/64 ,  C07D241/08 ,  C07D265/32 ,  C07D403/06 ,  C07D413/06 ,  C07D487/04 ,  C07D487/06 ,  C12N15/87 ,  C12N15/88 ,  C12Q1/025 ,  G01N33/15

摘要： Described herein are compounds and compositions characterized, in certain embodiments, by conjugation of various groups, such as lipophilic groups, to an amino or amide group of an amino acid, a linear or cyclic peptide, a linear or cyclic polypeptide, or structural isomer thereof, to provide compounds of the present invention, collectively referred to herein as “APPLs”. Such APPLs are deemed useful for a variety of applications, such as, for example, improved nucleotide delivery. Exemplary APPLs include, but are not limited to, compounds of Formula (I), (II), (III), (IV), (V), and (VI), and salts thereof, as described herein: wherein m, n, p, R′, R1, R2, R3, R4, R5, R8, Z, W, Y, and Z are as defined herein.

公开(公告)号：US20130158021A1

公开(公告)日：2013-06-20

申请号：US13662002

申请日：2012-10-26

申请人： Massachusetts Institute of Technology

发明人： Yizhou Dong ,  Kevin Thomas Love ,  Robert S. Langer ,  Daniel Griffith Anderson ,  Delai Chen ,  Yi Chen ,  Arturo Jose Vagas ,  Akinleye Alabi ,  Yunlong Zhang

IPC分类号： C07C323/58 ,  C12Q1/02 ,  C07D241/08 ,  C12N15/87 ,  C07D487/04 ,  C07D413/06 ,  C07C279/14 ,  C07C229/12 ,  C07C229/24 ,  C07D209/24 ,  C07D233/64 ,  C07D265/32 ,  G01N33/15 ,  C07D403/06

CPC分类号： A61K31/7105 ,  A61K31/711 ,  A61K47/22 ,  A61K2121/00 ,  C07C229/12 ,  C07C229/22 ,  C07C229/24 ,  C07C229/26 ,  C07C229/36 ,  C07C237/08 ,  C07C237/12 ,  C07C271/22 ,  C07C279/14 ,  C07C323/58 ,  C07D207/16 ,  C07D209/20 ,  C07D209/24 ,  C07D233/64 ,  C07D241/08 ,  C07D265/32 ,  C07D403/06 ,  C07D413/06 ,  C07D487/04 ,  C07D487/06 ,  C12N15/87 ,  C12N15/88 ,  C12Q1/025 ,  G01N33/15

摘要： Described herein are compounds and compositions characterized, in certain embodiments, by conjugation of various groups, such as lipophilic groups, to an amino or amide group of an amino acid, a linear or cyclic peptide, a linear or cyclic polypeptide, or structural isomer thereof, to provide compounds of the present invention, collectively referred to herein as “APPLs”. Such APPLs are deemed useful for a variety of applications, such as, for example, improved nucleotide delivery. Exemplary APPLs include, but are not limited to, compounds of Formula (I), (II), (III), (IV), (V), and (VI), and salts thereof, as described herein: wherein m, n, p, R′, R1, R2, R3, R4, R5, R8, Z, W, Y, and Z are as defined herein.

摘要翻译： 本文描述的是化合物和组合物，在某些实施方案中，通过将各种基团如亲脂基团与氨基酸，线性或环状肽，线性或环状多肽或其结构异构体的氨基或酰胺基团缀合， ，以提供本文共同称为“应用”的本发明化合物。 这样的APPL被认为对于各种应用是有用的，例如改进的核苷酸递送。 示例性应用包括但不限于本文所述的式（I），（II），（III），（IV），（V）和（VI）及其盐的化合物：其中m，n ，p，R'，R 1，R 2，R 3，R 4，R 5，R 8，Z，W，Y和Z如本文所定义。

公开(公告)号：US09895443B2

公开(公告)日：2018-02-20

申请号：US14900869

申请日：2014-06-26

申请人： Massachusetts Institute of Technology

发明人： Akinleye C. Alabi ,  Kevin Thomas Love ,  Daniel Griffith Anderson ,  Robert S. Langer

IPC分类号： A61K47/22 ,  C07C323/12 ,  C07D207/09 ,  C07D295/15 ,  C12N15/113 ,  A61K9/127

CPC分类号： A61K47/22 ,  A61K9/127 ,  C07C323/12 ,  C07D207/09 ,  C07D295/15 ,  C12N15/113 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2320/32

摘要： The present invention provides multi-tailed lipid compounds, and salts and stereoisomers thereof, and methods of preparing the compounds. Also provided are compositions including a compound of the invention and an agent (e.g., an siRNA, mRNA, plasmid DNA, small molecule, protein, peptide). The present invention also provides methods, and kits using the compositions for delivering an agent to a subject (e.g., to the liver, spleen, or lung of the subject) or cell and for treating and/or preventing a range of diseases, such as genetic diseases, proliferative diseases, hematological diseases, neurological diseases, immunological diseases, gastrointestinal diseases (e.g., liver diseases), respiratory diseases (e.g., lung diseases), painful conditions, psychiatric disorders, metabolic disorders, and spleen diseases.

公开(公告)号：US20160158363A1

公开(公告)日：2016-06-09

申请号：US14900869

申请日：2014-06-26

申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY

发明人： Akinleye C. Alabi ,  Kevin Thomas Love ,  Daniel Griffith Anderson ,  Robert S. Langer

IPC分类号： A61K47/22 ,  C07D207/09 ,  C12N15/113 ,  C07D295/15

CPC分类号： A61K47/22 ,  A61K9/127 ,  C07C323/12 ,  C07D207/09 ,  C07D295/15 ,  C12N15/113 ,  C12N15/1137 ,  C12N2310/14 ,  C12N2320/32

摘要： The present invention provides multi-tailed lipid compounds, and salts and stereoisomers thereof, and methods of preparing the compounds. Also provided are compositions including a compound of the invention and an agent (e.g., an siRNA, mRNA, plasmid DNA, small molecule, protein, peptide). The present invention also provides methods, and kits using the compositions for delivering an agent to a subject (e.g., to the liver, spleen, or lung of the subject) or cell and for treating and/or preventing a range of diseases, such as genetic diseases, proliferative diseases, hematological diseases, neurological diseases, immunological diseases, gastrointestinal diseases (e.g., liver diseases), respiratory diseases (e.g., lung diseases), painful conditions, psychiatric disorders, metabolic disorders, and spleen diseases.

摘要翻译： 本发明提供多尾脂质化合物及其盐和立体异构体，以及制备化合物的方法。 还提供了包含本发明化合物和试剂（例如siRNA，mRNA，质粒DNA，小分子，蛋白质，肽）的组合物。 本发明还提供了使用组合物将试剂递送到受试者（例如，受试者的肝脏，脾脏或肺部）或细胞并用于治疗和/或预防一系列疾病的方法和试剂盒，例如 遗传疾病，增殖性疾病，血液病，神经系统疾病，免疫疾病，胃肠道疾病（如肝脏疾病），呼吸系统疾病（如肺部疾病），疼痛病症，精神疾病，代谢疾病和脾脏疾病等。

公开(公告)号：US11458158B2

公开(公告)日：2022-10-04

申请号：US16867291

申请日：2020-05-05

申请人： Massachusetts Institute of Technology

发明人： Yizhou Dong ,  Kevin Thomas Love ,  Robert S. Langer ,  Daniel Griffith Anderson ,  Delai Chen ,  Yi Chen ,  Arturo Jose Vegas ,  Akinleye C. Alabi ,  Yunlong Zhang

IPC分类号： A61K31/7105 ,  C07D233/64 ,  C07D403/06 ,  C07D241/08 ,  C07C229/12 ,  C07C229/22 ,  C07C229/26 ,  C07D487/06 ,  C07D207/16 ,  C07D209/20 ,  C07C271/22 ,  C07C229/36 ,  C07C237/08 ,  C07C237/12 ,  C12N15/88 ,  C12N15/87 ,  C07C229/24 ,  C07C279/14 ,  C07C323/58 ,  C07D209/24 ,  C07D265/32 ,  C07D413/06 ,  C07D487/04 ,  C12Q1/02 ,  G01N33/15 ,  A61K31/711 ,  A61K47/22

摘要： Described herein are compounds and compositions characterized, in certain embodiments, by conjugation of various groups, such as lipophilic groups, to an amino or amide group of an amino acid, a linear or cyclic peptide, a linear or cyclic polypeptide, or structural isomer thereof, to provide compounds of the present invention, collectively referred to herein as “APPLs”. Such APPLs are deemed useful for a variety of applications, such as, for example, improved nucleotide delivery. Exemplary APPLs include, but are not limited to, compounds of Formula (I), (II), (III), (IV), (V), and (VI), and salts thereof, as described herein: wherein m, n, p, R′, R1, R2, R3, R4, R5, R8, Z, W, Y, and Z are as defined herein.

公开(公告)号：US20210101875A1

公开(公告)日：2021-04-08

申请号：US17070486

申请日：2020-10-14

申请人： Massachusetts Institute of Technology

发明人： Kerry Peter Mahon ,  Kevin Thomas Love ,  Christopher G. Levins ,  Kathryn Ann Whitehead ,  Robert S. Langer ,  Daniel Griffith Anderson

IPC分类号： C07D295/13 ,  A61K9/127 ,  A61K9/51 ,  A61K47/16 ,  A61K48/00 ,  C07C215/14 ,  C12N15/11 ,  C12N15/88 ,  A61K47/54 ,  C07C217/08 ,  A61K31/7088 ,  A61K38/02 ,  A61K9/107 ,  C12N15/113

摘要： Aminoalcohol lipidoids are prepared by reacting an amine with an epoxide-terminated compound are described. Methods of preparing aminoalcohol lipidoids from commercially available starting materials are also provided. Aminoalcohol lipidoids may be prepared from racemic or stereochemically pure epoxides. Aminoalcohol lipidoids or salts forms thereof are preferably biodegradable and biocompatible and may be used in a variety of drug delivery systems. Given the amino moiety of these aminoalcohol lipidoid compounds, they are particularly suited for the delivery of polynucleotides. Complexes, micelles, liposomes or particles containing the inventive lipidoids and polynucleotide have been prepared. The inventive lipidoids may also be used in preparing microparticles for drug delivery. They are particularly useful in delivering labile agents given their ability to buffer the pH of their surroundings.

公开(公告)号：US10086013B2

公开(公告)日：2018-10-02

申请号：US15340082

申请日：2016-11-01

申请人： Massachusetts Institute of Technology

发明人： Yizhou Dong ,  Kevin Thomas Love ,  Robert S. Langer ,  Daniel Griffith Anderson ,  Delai Chen ,  Yi Chen ,  Arturo Jose Vegas ,  Akinleye C. Alabi ,  Yunlong Zhang

IPC分类号： A61K31/535 ,  A61K31/7105 ,  A61K31/711 ,  C07D241/08 ,  A61K47/22

摘要： Described herein are compounds and compositions characterized, in certain embodiments, by conjugation of various groups, such as lipophilic groups, to an amino or amide group of an amino acid, a linear or cyclic peptide, a linear or cyclic polypeptide, or structural isomer thereof, to provide compounds of the present invention, collectively referred to herein as “APPLs”. Such APPLs are deemed useful for a variety of applications, such as, for example, improved nucleotide delivery. Exemplary APPLs include, but are not limited to, compounds of Formula (I), (II), (III), (IV), (V), and (VI), and salts thereof, as described herein: wherein m, n, p, R′, R1, R2, R3, R4, R5, R8, Z, W, Y, and Z are as defined herein.