公开(公告)号：US20230124955A1

公开(公告)日：2023-04-20

申请号：US17893918

申请日：2022-08-23

Applicant: Massachusetts Institute of Technology

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

IPC: 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

Abstract: 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

Applicant: Massachusetts Institute of Technology

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

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

CPC classification number: 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

Abstract: 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：US20190076462A1

公开(公告)日：2019-03-14

申请号：US16126897

申请日：2018-09-10

Applicant: Massachusetts Institute of Technology

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

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

Abstract: 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：US20140329884A1

公开(公告)日：2014-11-06

申请号：US14267530

申请日：2014-05-01

Applicant: Massachusetts Institute of Technology

Inventor： Yizhou Dong ,  Akinleye C. Alabi ,  Hao Yin ,  Joseph R. Dorkin ,  Delai Chen ,  Robert S. Langer ,  Daniel Griffith Anderson ,  Ahmed A. Eltoukhy

IPC: C07D251/30 ,  A61K31/713 ,  A61K31/53

CPC classification number: C07D251/30 ,  A61K31/53 ,  A61K31/713

Abstract: The present invention provides novel 1,3,5-triazinane-2,4,6-trione derivatives, such as compounds of any one of Formulae (I) and (II), and salts 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, or plasmid DNA). 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, liver diseases, and lung diseases.

Abstract translation: 本发明提供新的1,3,5-三氮杂环丁烷-2,4,6-三酮衍生物，如式（I）和（II）中任一项的化合物及其盐，以及制备该化合物的方法。 还提供了包含本发明化合物和试剂（例如siRNA，mRNA或质粒DNA）的组合物。 本发明还提供了使用组合物将试剂递送至受试者（例如，受试者的肝脏，脾脏或肺）或细胞的方法和试剂盒，并用于治疗和/或预防一系列疾病，例如遗传 疾病，增殖性疾病，血液疾病，神经系统疾病，肝脏疾病和肺部疾病。

公开(公告)号：US09895443B2

公开(公告)日：2018-02-20

申请号：US14900869

申请日：2014-06-26

Applicant: Massachusetts Institute of Technology

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

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

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

Abstract: 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

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

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

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

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

Abstract: 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.

Abstract translation: 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：US09315472B2

公开(公告)日：2016-04-19

申请号：US14267530

申请日：2014-05-01

Applicant: Massachusetts Institute of Technology

Inventor： Yizhou Dong ,  Akinleye C. Alabi ,  Hao Yin ,  Joseph R. Dorkin ,  Delai Chen ,  Robert S. Langer ,  Daniel Griffith Anderson ,  Ahmed A. Eltoukhy

IPC: C07D251/30 ,  A61K31/53 ,  A61K31/713

CPC classification number: C07D251/30 ,  A61K31/53 ,  A61K31/713

Abstract: The present invention provides novel 1,3,5-triazinane-2,4,6-trione derivatives, such as compounds of any one of Formulae (I) and (II), and salts 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, or plasmid DNA). 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, liver diseases, and lung diseases.

Abstract translation: 本发明提供新的1,3,5-三氮杂环丁烷-2,4,6-三酮衍生物，如式（I）和（II）中任一项的化合物及其盐，以及制备该化合物的方法。 还提供了包含本发明化合物和试剂（例如siRNA，mRNA或质粒DNA）的组合物。 本发明还提供了使用组合物将试剂递送至受试者（例如，受试者的肝脏，脾脏或肺）或细胞的方法和试剂盒，并用于治疗和/或预防一系列疾病，例如遗传 疾病，增殖性疾病，血液疾病，神经系统疾病，肝脏疾病和肺部疾病。

公开(公告)号：US11458158B2

公开(公告)日：2022-10-04

申请号：US16867291

申请日：2020-05-05

Applicant: Massachusetts Institute of Technology

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

IPC: 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

Abstract: 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：US10086013B2

公开(公告)日：2018-10-02

申请号：US15340082

申请日：2016-11-01

Applicant: Massachusetts Institute of Technology

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

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

Abstract: 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：US20180036333A9

公开(公告)日：2018-02-08

申请号：US15340082

申请日：2016-11-01

Applicant: Massachusetts Institute of Technology

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

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

CPC classification number: 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

Abstract: 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.