公开(公告)号：US20200330501A1

公开(公告)日：2020-10-22

申请号：US16867291

申请日：2020-05-05

Applicant: Massachusetts Institute of Technology

Inventor： Yizhou Dong ,  Kevin 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：US10682374B2

公开(公告)日：2020-06-16

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 ,  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：US20160114042A1

公开(公告)日：2016-04-28

申请号：US14987717

申请日：2016-01-04

Applicant: Massachusetts Institute of Technology

Inventor： Daniel Griffith Anderson ,  Kathryn Ann Whitehead ,  Joseph R. Dorkin ,  Arturo Jose Vegas ,  Yunlong Zhang ,  Robert S. Langer

IPC: A61K47/22 ,  C07D241/04 ,  C12N15/113 ,  C07D295/13

CPC classification number: A61K47/22 ,  A61K9/1272 ,  A61K9/5123 ,  A61K31/225 ,  A61K31/357 ,  A61K31/40 ,  A61K31/445 ,  A61K31/495 ,  A61K31/4985 ,  A61K31/573 ,  A61K31/704 ,  A61K31/713 ,  A61K45/06 ,  A61K47/18 ,  A61K47/542 ,  A61K47/543 ,  A61K47/6925 ,  C07C225/06 ,  C07C229/12 ,  C07C229/14 ,  C07C229/24 ,  C07C229/26 ,  C07C229/28 ,  C07C229/34 ,  C07C2601/14 ,  C07D207/09 ,  C07D211/14 ,  C07D211/26 ,  C07D211/34 ,  C07D241/04 ,  C07D295/13 ,  C07D295/15 ,  C07D295/16 ,  C07D319/16 ,  C07D319/18 ,  C07D487/04 ,  C12N15/111 ,  C12N15/1137 ,  C12N15/88 ,  C12N2310/14 ,  C12N2320/32 ,  A61K2300/00

Abstract: Provided herein are lipidoids that may be prepared from the conjugate addition of alkylamines to acrylates. In some embodiments, provided lipidoids are biodegradable and may be used in a variety of drug delivery systems. Given the amino moiety of the lipidoids, they are well-suited for the delivery of polynucleotides, in addition to other agents. Nanoparticles containing the inventive lipidoids and polynucleotides have been prepared and have been shown to be effective in delivering siRNA.

Abstract translation: 本文提供的是可以通过将烷基胺偶联加成丙烯酸酯制备的类脂。 在一些实施方案中，提供的类脂质是可生物降解的并且可以用于多种药物递送系统中。 考虑到类固醇的氨基部分，除了其它药剂之外，它们非常适合于递送多核苷酸。 已经制备了含有本发明的类脂和多核苷酸的纳米颗粒，并且已显示其在递送siRNA方面是有效的。

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.

公开(公告)号：US09867869B2

公开(公告)日：2018-01-16

申请号：US14652011

申请日：2013-12-12

Applicant: Massachusetts Institute of Technology ,  The Children's Medical Center Corporation

Inventor： Daniel G. Anderson ,  Hung-Chieh Chou ,  Michael J. Webber ,  Benjamin C. Tang ,  Yair Levi ,  Yunlong Zhang ,  Rosemary Lynn Kanasty ,  Arturo Jose Vegas ,  Robert S. Langer

IPC: A61K38/28 ,  A61K47/48 ,  G01N33/66 ,  G01N33/74

CPC classification number: A61K38/28 ,  A61K47/54 ,  A61K47/542 ,  A61K47/543 ,  A61K47/549 ,  A61K47/554 ,  G01N33/66 ,  G01N33/74 ,  G01N2333/62

Abstract: Compounds, compositions, and methods for “smart” delivery of a therapeutic, prophylactic or diagnostic agent, such as glucose-mediated delivery of insulin through glucose-sensing insulin derivatives, are provided. The insulin derivatives bind serum albumin or agglomerate in vivo. The insulin derivatives effectively dissociate to release insulin in a hyperglycemic condition, where the complexation of glucose to a glucose-sensing element alters properties of the insulin derivative leading to the dissociation. The compounds, compositions, and methods provide a delivery strategy for both self-regulated and long-term diabetes management.

公开(公告)号：US09512073B2

公开(公告)日：2016-12-06

申请号：US13662002

申请日：2012-10-26

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 ,  C07C229/00 ,  C07C323/58 ,  C07D233/64 ,  C07D403/06 ,  C07D241/08 ,  C07C229/12 ,  C07C229/22 ,  C07C229/26 ,  C07D487/06 ,  C07D207/16 ,  C07D209/20 ,  C12N15/87 ,  C07C229/24 ,  C07C279/14 ,  C07D209/24 ,  C07D265/32 ,  C07D413/06 ,  C07D487/04 ,  C12Q1/02 ,  G01N33/15 ,  C07C271/22 ,  C07C229/36 ,  C07C237/08 ,  C07C237/12 ,  C12N15/88

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：US20140161830A1

公开(公告)日：2014-06-12

申请号：US14089603

申请日：2013-11-25

Applicant: Massachusetts Institute of Technology

Inventor： Daniel Griffith Anderson ,  Kathryn Ann Whitehead ,  Joseph R. Dorkin ,  Arturo Jose Vegas ,  Yunlong Zhang

IPC: C07C229/26 ,  A61K31/4965 ,  A61K31/445 ,  A61K31/40 ,  A61K31/357 ,  A61K31/24 ,  A61K31/225 ,  C07D487/04 ,  C07D295/15 ,  C07D211/34 ,  C07D207/09 ,  C07D319/16 ,  C07C229/34 ,  C07C229/28 ,  C07C229/24 ,  A61K45/06 ,  C07D241/04 ,  A61K31/4985

CPC classification number: A61K47/22 ,  A61K9/1272 ,  A61K9/5123 ,  A61K31/225 ,  A61K31/357 ,  A61K31/40 ,  A61K31/445 ,  A61K31/495 ,  A61K31/4985 ,  A61K31/573 ,  A61K31/704 ,  A61K31/713 ,  A61K45/06 ,  A61K47/18 ,  A61K47/542 ,  A61K47/543 ,  A61K47/6925 ,  C07C225/06 ,  C07C229/12 ,  C07C229/14 ,  C07C229/24 ,  C07C229/26 ,  C07C229/28 ,  C07C229/34 ,  C07C2601/14 ,  C07D207/09 ,  C07D211/14 ,  C07D211/26 ,  C07D211/34 ,  C07D241/04 ,  C07D295/13 ,  C07D295/15 ,  C07D295/16 ,  C07D319/16 ,  C07D319/18 ,  C07D487/04 ,  C12N15/111 ,  C12N15/1137 ,  C12N15/88 ,  C12N2310/14 ,  C12N2320/32 ,  A61K2300/00

Abstract: Provided herein are lipidoids that may be prepared from the conjugate addition of alkylamines to acrylates. In some embodiments, provided lipidoids are biodegradable and may be used in a variety of drug delivery systems. Given the amino moiety of the lipidoids, they are well-suited for the delivery of polynucleotides, in addition to other agents. Nanoparticles containing the inventive lipidoids and polynucleotides have been prepared and have been shown to be effective in delivering siRNA.

Abstract translation: 本文提供的是可以通过将烷基胺偶联加成丙烯酸酯制备的类脂。 在一些实施方案中，提供的类脂质是可生物降解的并且可以用于多种药物递送系统中。 考虑到类固醇的氨基部分，除了其它药剂之外，它们非常适合于递送多核苷酸。 已经制备了含有本发明的类脂和多核苷酸的纳米颗粒，并且已显示其在递送siRNA方面是有效的。

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.