公开(公告)号：US09555413B2

公开(公告)日：2017-01-31

申请号：US14667615

申请日：2015-03-24

Applicant: Massachusetts Institute of Technology

Inventor： Rohit Nandkumar Karnik ,  Seungpyo Hong ,  Ying Mei ,  Daniel Griffith Anderson ,  Jeffrey Michael Karp ,  Robert S. Langer ,  Suman Bose

IPC: B01L3/00 ,  C12N5/00 ,  C12M3/06 ,  C12M1/00

CPC classification number: C12N5/0068 ,  B01L3/502715 ,  B01L3/502761 ,  B01L2200/0647 ,  B01L2300/0877 ,  B01L2300/16 ,  C12M23/16 ,  C12M47/02 ,  C12N5/0062 ,  C12N2501/58 ,  C12N2501/585 ,  C12N2533/50 ,  C12N2533/52 ,  C12N2535/10

Abstract: The present invention provides systems for cell separation based on cell rolling on surfaces along edges of regions coated with cell adhesion molecules. A variety of designs of coated regions and edges are disclosed.

Abstract translation: 本发明提供了基于在细胞粘附分子包被的区域的边缘上的表面上的细胞滚动的细胞分离系统。 公开了涂覆区域和边缘的各种设计。

公开(公告)号：US20160137785A1

公开(公告)日：2016-05-19

申请号：US14941384

申请日：2015-11-13

Applicant: Massachusetts Institute of Technology

Inventor： Minglin Ma ,  Wendy F. Liu ,  Robert S. Langer ,  Daniel Griffith Anderson

IPC: C08G73/02 ,  A61K47/48 ,  A61L31/10 ,  A61K31/7088 ,  A61K47/34 ,  A61K9/127

CPC classification number: C08G73/0206 ,  A61K9/1273 ,  A61K31/7088 ,  A61K47/34 ,  A61K47/59 ,  A61L31/10 ,  C08G59/22 ,  C08G59/306 ,  C08G59/50 ,  C08G73/02 ,  C09D5/1637 ,  C09D179/02 ,  Y10T428/31725

Abstract: A new class of poly(beta-amino alcohols) (PBAAs) has been prepared using combinatorial polymerization. The inventive PBAAs may be used in biotechnology and biomedical applications as coatings (such as coatings of films or multilayer films for medical devices or implants), additives, materials, excipients, non-biofouling agents, micropatterning agents, and cellular encapsulation agents. When used as surface coatings, these PBAAs elicited different levels of inflammation, both in vitro and in vivo, depending on their chemical structures. The large chemical diversity of this class of materials allowed us to identify polymer coatings that inhibit macrophage activation in vitro. Furthermore, these coatings reduce the recruitment of inflammatory cells, and reduce fibrosis, following the subcutaneous implantation of carboxylated polystyrene microparticles. These polymers may be used to form polyelectrolyte complex capsules for cell encapsulation. The invention may also have many other biological applications such as antimicrobial coatings, DNA or siRNA delivery, and stem cell tissue engineering.

公开(公告)号：US20160009657A1

公开(公告)日：2016-01-14

申请号：US14643845

申请日：2015-03-10

Applicant: Massachusetts Institute of Technology

Inventor： Daniel Griffith Anderson ,  Andreas Zumbuehl ,  Elizaveta S. Leshchiner ,  Robert S. Langer ,  Michael Solomon Goldberg

IPC: C07D233/61 ,  C07C229/12 ,  A61K47/22 ,  C07C231/12 ,  C07C227/10 ,  A61K47/18 ,  C07C229/16 ,  C07C237/06

CPC classification number: C07D233/61 ,  A61K9/1617 ,  A61K47/18 ,  A61K47/22 ,  A61K48/00 ,  A61K48/0033 ,  C07C227/10 ,  C07C229/12 ,  C07C229/14 ,  C07C229/16 ,  C07C229/18 ,  C07C231/12 ,  C07C237/06 ,  C07D211/26 ,  C07D243/08 ,  C07D295/12 ,  C07D307/14 ,  C07D317/28 ,  C12N15/88

Abstract: Nitrogen-containing lipids prepared from the conjugate addition of amines to acrylates, acrylamides, or other carbon-carbon double bonds conjugated to electron-withdrawing groups are described. Methods of preparing these lipids from commercially available starting materials are also provided. These amine-containing lipids or salts forms of these lipids are preferably biodegradable and biocompatible and may be used in a variety of drug delivery systems. Given the amino moiety of these lipids, they are particularly suited for the delivery of polynucleotides. Complexes or nanoparticles containing the inventive lipid and polynucleotide have been prepared. The inventive lipids may also be used to in preparing microparticle for drug delivery. They are particularly useful in delivering labile agents given their ability to buffer the pH of their surroundings.

Abstract translation: 描述了从共轭加成胺到丙烯酸酯，丙烯酰胺或与吸电子基团共轭的其它碳 - 碳双键制备的含氮脂质。 还提供了从市售的起始原料制备这些脂质的方法。 这些含脂质的脂质或这些脂质的盐形式优选是可生物降解的和生物相容的，并可用于各种药物递送系统。 鉴于这些脂质的氨基部分，它们特别适用于递送多核苷酸。 已经制备了含有本发明的脂质和多核苷酸的复合物或纳米颗粒。 本发明的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：US20130158021A1

公开(公告)日：2013-06-20

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 Vagas ,  Akinleye Alabi ,  Yunlong Zhang

IPC: 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 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.

Abstract translation: 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：US11679165B2

公开(公告)日：2023-06-20

申请号：US16879065

申请日：2020-05-20

Applicant: Massachusetts Institute of Technology

Inventor： Daniel Griffith Anderson ,  Joseph R. Dorkin ,  Owen Shea Fenton ,  Kevin John Kauffman ,  Rebecca L. McClellan

IPC: A61K48/00 ,  C07D241/08 ,  A61K47/54 ,  A61K38/18

CPC classification number: A61K48/0033 ,  A61K38/1816 ,  A61K47/545 ,  C07D241/08

Abstract: Provided herein are compounds of Formula (I), and salts thereof, wherein each instance of RL is independently optionally substituted C6-C40 alkenyl. Further provided are compositions comprising a compound of Formula (I) and an agent. Further provided are methods and kits using the compositions for delivering an agent to a subject or cell and for treating and/or preventing a range of diseases. Further provided are methods of preparing compounds of Formula (I) and precursors thereof.

公开(公告)号：US11414393B2

公开(公告)日：2022-08-16

申请号：US17070486

申请日：2020-10-14

Applicant: Massachusetts Institute of Technology

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

IPC: 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

Abstract: 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：US20210260195A1

公开(公告)日：2021-08-26

申请号：US17122068

申请日：2020-12-15

Applicant: Massachusetts Institute of Technology

Inventor： James E. Dahlman ,  Avraham D. Schroeder ,  Daniel Griffith Anderson ,  Robert S. Langer ,  Christopher G. Levins

IPC: A61K47/22 ,  A61K47/54 ,  A61K47/59 ,  A61K47/69 ,  C07D257/02 ,  C07D273/08 ,  A61K9/00 ,  A61K47/34 ,  C08G73/10 ,  A61K9/127 ,  C07D273/00 ,  C07D295/084 ,  C12N15/113

Abstract: The present invention provides inventive conjugated polyethyleneimine (PEI) polymers and conjugated aza-macrocycles (collectively referred to herein as “conjugated lipomers” or “lipomers”) containing one or more groups of the formula (iii): wherein R3 and R4 are as defined herein. Also provided are compositions comprising the inventive conjugated lipomers, and methods of preparation and use.

公开(公告)号：US20190177289A1

公开(公告)日：2019-06-13

申请号：US16208295

申请日：2018-12-03

Applicant: Massachusetts Institute of Technology

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

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

Abstract: 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：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：US10189802B2

公开(公告)日：2019-01-29

申请号：US15417530

申请日：2017-01-27

Applicant: Massachusetts Institute of Technology

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

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

Abstract: 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.