公开(公告)号：US10117934B2

公开(公告)日：2018-11-06

申请号：US14995842

申请日：2016-01-14

Applicant: Massachusetts Institute of Technology

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

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

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：US10011817B2

公开(公告)日：2018-07-03

申请号：US15394557

申请日：2016-12-29

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.

公开(公告)号：US20170204075A1

公开(公告)日：2017-07-20

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 ,  C07C215/14 ,  C12N15/113 ,  A61K9/107 ,  A61K31/7088

CPC classification number: 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

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：US09700627B2

公开(公告)日：2017-07-11

申请号：US14811613

申请日：2015-07-28

Applicant: Massachusetts Institute of Technology

Inventor： Robert S. Langer ,  David M. Lynn ,  David A. Putnam ,  Mansoor M. Amiji ,  Daniel Griffith Anderson

IPC: A61K47/34 ,  A61K9/51 ,  C08G73/02 ,  C08G73/06 ,  A61K31/711 ,  A61K31/713 ,  C08G63/685 ,  C12N15/88 ,  B82Y5/00 ,  A61K47/48

CPC classification number: A61K47/34 ,  A61K9/5146 ,  A61K31/711 ,  A61K31/713 ,  A61K47/59 ,  A61K47/593 ,  A61K47/6929 ,  B82Y5/00 ,  C08G63/685 ,  C08G73/02 ,  C08G73/0273 ,  C08G73/06 ,  C08G73/0611 ,  C08G73/0616 ,  C12N15/88

Abstract: Poly(β-amino esters) prepared from the conjugate addition of bis(secondary amines) or primary amines to a bis(acrylate ester) are described. Methods of preparing these polymers from commercially available starting materials are also provided. These tertiary amine-containing polymers are preferably biodegradable and biocompatible and may be used in a variety of drug delivery systems. Given the poly(amine) nature of these polymers, they are particularly suited for the delivery of polynucleotides. Nanoparticles containing polymer/polynucleotide complexes have been prepared. The inventive polymers may also be used to encapsulate other agents to be delivered. They are particularly useful in delivering labile agents given their ability to buffer the pH of their surroundings.

公开(公告)号：US09556110B2

公开(公告)日：2017-01-31

申请号：US14599004

申请日：2015-01-16

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

CPC classification number: 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

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.

Abstract translation: 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：US20160367686A1

公开(公告)日：2016-12-22

申请号：US15186361

申请日：2016-06-17

Applicant: Massachusetts Institute of Technology

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

IPC: A61K47/48 ,  A61K38/18 ,  A61K48/00 ,  C07D241/08

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.

Abstract translation: 本文提供了式（I）的化合物及其盐，其中每个RL的实例独立地为任选取代的C 6 -C 40烯基。 还提供了包含式（I）的化合物和试剂的组合物。 还提供了使用组合物将试剂递送至受试者或细胞并用于治疗和/或预防一系列疾病的方法和试剂盒。 还提供了制备式（I）化合物及其前体的方法。

公开(公告)号：US09439968B2

公开(公告)日：2016-09-13

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 ,  C07D295/13 ,  C07D241/04 ,  C12N15/113

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.

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：US20140105960A1

公开(公告)日：2014-04-17

申请号：US14050320

申请日：2013-10-09

Applicant: Massachusetts Institute of Technology

Inventor： JANETA ZOLDAN ,  Robert S. Langer ,  Daniel S. Kohane ,  Daniel Griffith Anderson ,  Akihiko Kusanagi ,  Hila Epstein-Barash ,  Beata Chertok

IPC: A61K38/18 ,  A61K47/36 ,  A61K47/38 ,  A61K35/44

CPC classification number: A61K38/1866 ,  A61K9/0024 ,  A61K9/127 ,  A61K35/44 ,  A61K35/545 ,  A61K38/1858 ,  A61K47/36 ,  A61K47/38 ,  A61L27/20 ,  A61L27/3834 ,  A61L27/52 ,  A61L27/54 ,  A61L2300/414 ,  A61L2300/602 ,  A61L2300/626

Abstract: Provided herein are hydrogels and hydrogel-forming compositions that are useful for, among others, tissue regeneration in vivo. Methods for generating such hydrogels, for example, from such hydrogel-forming compositions are also provided herein. Therapeutic methods employing hydrogels and hydrogel-forming composition, for example, for restoration of tissue perfusion in the context of acute ischemia, are also provided. The disclosure also describes kits comprising components useful for generating hydrogels as described herein.

Abstract translation: 本文提供水凝胶和形成水凝胶的组合物，其可用于组织再生体内。 本文还提供了从这种水凝胶形成组合物产生这种水凝胶的方法。 还提供了使用水凝胶和水凝胶形成组合物的治疗方法，例如用于在急性缺血的情况下恢复组织灌注。 本公开还描述了包含可用于产生如本文所述的水凝胶的组分的试剂盒。