公开(公告)号：US20150203439A1

公开(公告)日：2015-07-23

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 ,  A61K38/02 ,  A61K31/7088 ,  A61K47/16 ,  C07C215/14

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：US09080014B2

公开(公告)日：2015-07-14

申请号：US13673354

申请日：2012-11-09

Applicant: Massachusetts Institute of Technology ,  The Brigham and Women's Hospital, Inc.

Inventor： Frank X. Gu ,  Omid C. Farokhzad ,  Robert S. Langer ,  Benjamin A. Teply

IPC: A61K9/51 ,  C08G63/91 ,  A61K47/48 ,  A61K51/12 ,  B82Y5/00

CPC classification number: C08G63/912 ,  A61K9/5153 ,  A61K47/549 ,  A61K47/593 ,  A61K47/60 ,  A61K47/6935 ,  A61K47/6937 ,  A61K49/00 ,  A61K51/1244 ,  B82Y5/00 ,  Y10S977/773 ,  Y10S977/906 ,  Y10S977/915 ,  Y10T428/2982

Abstract: A method includes producing libraries of nanoparticles having highly controlled properties, which can be formed by mixing together two or more macromolecules in different ratios. One or more of the macromolecules may be a polymeric conjugate of a moiety to a biocompatible polymer. The nanoparticle may contain a drug. The moiety may include a polypeptide or a polynucleotide, such as an aptamer. The moiety may be a targeting moiety, an imaging moiety, a chelating moiety, a charged moiety, or a therapeutic moiety. Another aspect is directed to systems and methods of producing such polymeric conjugates. In some embodiments, a solution containing a polymer is contacted with a liquid, such as an immiscible liquid, to form nanoparticles containing the polymeric conjugate. Other methods use such libraries, use or administer such polymeric conjugates, or promote the use of such polymeric conjugates. Kits involving such polymeric conjugates are also described.

Abstract translation: 一种方法包括制备具有高度控制性质的纳米颗粒的文库，其可通过将两种或多种不同比例的大分子混合在一起形成。 一个或多个大分子可以是部分与生物相容性聚合物的聚合物缀合物。 纳米颗粒可以含有药物。 该部分可以包括多肽或多核苷酸，例如适体。 该部分可以是靶向部分，成像部分，螯合部分，带电部分或治疗部分。 另一方面涉及制备这种聚合物共轭物的体系和方法。 在一些实施方案中，将含有聚合物的溶液与诸如不混溶液体的液体接触以形成含有聚合物缀合物的纳米颗粒。 其他方法使用这种文库，使用或施用这种聚合物缀合物，或促进使用这种聚合物缀合物。 还描述了涉及这种聚合物共轭物的试剂盒。

公开(公告)号：US20140314864A1

公开(公告)日：2014-10-23

申请号：US14322738

申请日：2014-07-02

Applicant: Massachusetts Institute of Technology ,  The Brigham and Women's Hospital, Inc.

Inventor： Jianjun Cheng ,  Omid C. Farokhzad ,  Robert S. Langer ,  Benjamin A. Teply ,  Stephen E. Zale

IPC: A61K9/50 ,  C12N15/115 ,  C07K16/00 ,  A61K31/337

CPC classification number: A61K9/5031 ,  A61K9/5153 ,  A61K9/5192 ,  A61K31/337 ,  A61K47/549 ,  A61K47/6869 ,  A61K47/6935 ,  A61K47/6937 ,  C07K16/00 ,  C12N15/115

Abstract: The present invention provides a drug delivery system for targeted delivery of therapeutic agent-containing particles to tissues, cells, and intracellular compartments. The invention provides targeted particles comprising a particle, one or more targeting moieties, and one or more therapeutic agents to be delivered and pharmaceutical compositions comprising inventive targeted particles. The present invention provides methods of designing, manufacturing, and using inventive targeted particles and pharmaceutical compositions thereof.

Abstract translation: 本发明提供了用于将组合物，细胞和细胞内区室靶向递送含治疗剂的颗粒的药物递送系统。 本发明提供了包含颗粒，一种或多种靶向部分和一种或多种待递送治疗剂和包含本发明靶向颗粒的药物组合物的靶向颗粒。 本发明提供了设计，制造和使用本发明的靶向颗粒及其药物组合物的方法。

公开(公告)号：US20140308336A1

公开(公告)日：2014-10-16

申请号：US14250025

申请日：2014-04-10

Applicant: Massachusetts Institute of Technology ,  The General Hospital Corporation

Inventor： Laura Indolfi ,  Elazer R. Edelman ,  Robert S. Langer ,  Jeffrey W. Clark ,  David T. Ting ,  Cristina Rosa Annamaria Ferrone ,  Matteo Ligorio

IPC: A61K9/70 ,  A61F2/04 ,  A61K31/337

CPC classification number: A61L31/10 ,  A61F2/915 ,  A61F2002/041 ,  A61F2230/0021 ,  A61K9/0024 ,  A61K9/0034 ,  A61K9/7007 ,  A61K31/337 ,  A61K47/34 ,  A61L31/148 ,  A61L31/16 ,  A61L2300/416 ,  A61L2300/604 ,  A61L2300/606 ,  A61L2420/06 ,  C08L67/04

Abstract: Drug-eluting devices and methods for the treatment of tumors of the pancreas, biliary system, gallbladder, liver, small bowel, or colon, are provided. Methods include deploying a drug-eluting device having a film which includes a mixture of a degradable polymer and a chemotherapeutic drug, wherein the film has a thickness from about 2 μm to about 1000 μm, into a tissue site and releasing a therapeutically effective amount of the chemotherapeutic drug from the film to treat the tumor, wherein the release of the therapeutically effective amount of the drug from the film is controlled by in vivo degradation of the polymer at the tissue site.

Abstract translation: 提供了用于治疗胰腺，胆汁系统，胆囊，肝脏，小肠或结肠肿瘤的药物洗脱装置和方法。 方法包括部署具有膜的药物洗脱装置，该膜包括可降解聚合物和化学治疗药物的混合物，其中所述膜具有约2μm至约1000μm的厚度，进入组织部位并释放治疗有效量的 来自膜的化学治疗药物以治疗肿瘤，其中通过在组织部位的聚合物的体内降解来控制来自膜的治疗有效量的药物的释放。

公开(公告)号：US20140094399A1

公开(公告)日：2014-04-03

申请号：US14029552

申请日：2013-09-17

Applicant: Massachusetts Institute of Technology

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

IPC: A61K47/34

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.

Abstract translation: 描述了从双（仲胺）或伯胺向双（丙烯酸酯）共轭加成制备的聚（＆（bgr。 - 氨基酯））。 还提供了从市售的原料制备这些聚合物的方法。 这些含叔胺的聚合物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。 鉴于这些聚合物的聚（胺）性质，它们特别适用于递送多核苷酸。 已经制备了含有聚合物/多核苷酸复合物的纳米颗粒。 本发明的聚合物也可以用于包封待递送的其它试剂。 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：US20140037736A1

公开(公告)日：2014-02-06

申请号：US14046827

申请日：2013-10-04

Applicant: Massachusetts Institute of Technology ,  President and Fellows of Harvard College ,  The Brigham and Women's Hospital, Inc.

Inventor： Jinjun Shi ,  Frank Alexis ,  Matteo Iannacone ,  Elliott Ashley Moseman ,  Pamela Basto ,  Robert S. Langer ,  Omid C. Farokhzad ,  Ulrich H. von Andrian ,  Elena Tonti

IPC: A61K47/48

CPC classification number: A61K47/48869 ,  A61K39/00 ,  A61K47/6925 ,  A61K47/6935

Abstract: The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides nanocarriers capable of stimulating an immune response in T cells and/or in B cells. The invention provides nanocarriers that comprise an immunofeature surface. The nanocarriers are capable of targeting antigen presenting cells when administered to a subject. The invention provides pharmaceutical compositions comprising inventive nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive nanocarriers and pharmaceutical compositions thereof.

Abstract translation: 本发明提供用于将纳米载体递送至免疫系统细胞的组合物和系统。 本发明提供能够刺激T细胞和/或B细胞中的免疫应答的纳米载体。 本发明提供了包含免疫电泳表面的纳米载体。 当给予受试者时，纳米载体能够靶向抗原呈递细胞。 本发明提供包含本发明纳米载体的药物组合物。 本发明提供了设计，制造和使用本发明的纳米载体及其药物组合物的方法。

公开(公告)号：US12138034B2

公开(公告)日：2024-11-12

申请号：US18541818

申请日：2023-12-15

Applicant: Massachusetts Institute of Technology ,  The Brigham and Women's Hospital, Inc. ,  The General Hospital Corporation

Inventor： Robert S. Langer ,  Carlo Giovanni Traverso ,  Malvika Verma ,  Feyisope Eweje ,  Christoph Winfried Johannes Steiger ,  Junwei Li ,  Nhi Phan ,  Hen-Wei Huang ,  Jacqueline Chu ,  John Ashraf Fou Salama

IPC: A61B5/07 ,  A61B5/00

Abstract: Drug delivery articles, resident articles, and retrieval systems e.g., for gram-level dosing, are generally provided. In some embodiments, the residence articles are configured for transesophageal administration, transesophageal retrieval, and/or gastric retention to/in a subject. In certain embodiments, the residence article includes dimensions configured for transesophageal administration with a gastric resident system. In some cases, the residence article may be configured to control drug release e.g., with zero-order drug kinetics with no potential for burst release for weeks to months. In some embodiments, the residence articles described herein comprise biocompatible materials and/or are safe for gastric retention. In certain embodiments, the residence article includes dimensions configured for transesophageal retrieval. In some cases, the residence articles described herein may comprise relatively large doses of drug (e.g., greater than or equal to 1 gram).

公开(公告)号：US20240366719A1

公开(公告)日：2024-11-07

申请号：US18660924

申请日：2024-05-10

Applicant: Massachusetts Institute of Technology ,  The Brigham and Women's Hospital, Inc.

Inventor： Robert S. Langer ,  Carlo Giovanni Traverso ,  Junwei Li ,  Thomas Wang ,  Ameya R. Kirtane ,  Yunhua Shi

IPC: A61K38/17 ,  A61K31/495 ,  A61K45/06 ,  A61L24/04 ,  A61L24/06 ,  A61L24/08 ,  A61L27/16 ,  A61L27/18 ,  A61L27/20 ,  C12N9/08

Abstract: The present disclosure provides compositions, methods, and kits that enable the in situ growth of polymers on or within a subject. In some aspects, the monomer, dopamine, polymerizes in vivo to form a polymer on a tissue. In additional aspects, the compositions, methods, and kits are useful for treating or preventing a disease or disorder.

公开(公告)号：US20240316216A1

公开(公告)日：2024-09-26

申请号：US18698888

申请日：2022-10-06

Applicant: Massachusetts Institute of Technology

Inventor： Robert S. Langer ,  Li-Huei Tsai ,  Owen Shea Fenton ,  Joel Blanchard ,  Jason Andresen ,  Julia Bonner ,  William Ralvenius

IPC: A61K48/00 ,  A61K47/14 ,  A61K47/28

CPC classification number: A61K48/0033 ,  A61K47/14 ,  A61K47/28 ,  A61K48/0058

Abstract: Provided herein are methods of selectively delivering an agent to a cell, comprising contacting the cell with a composition comprising an agent and lipids selected from: (a) an ionizable amino lipid, (b) a sterol, (c) a phospholipid, and (d) a PEG-lipid. The methods are selective for delivery to microglia over other neuroglia, such as astrocytes.

公开(公告)号：US12097307B2

公开(公告)日：2024-09-24

申请号：US17377124

申请日：2021-07-15

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

Inventor： Arturo Vegas ,  Joshua C. Doloff ,  Omid Veiseh ,  Minglin Ma ,  Robert S. Langer ,  Daniel G. Anderson

IPC: A61K9/50 ,  A61K9/00 ,  A61K9/48 ,  A61K35/39 ,  A61K47/36 ,  A61L29/08 ,  A61L31/10 ,  A61L33/08 ,  C07D487/04 ,  C08B37/00 ,  C12N5/00 ,  C12N5/071

CPC classification number: A61L29/085 ,  A61K9/0024 ,  A61K9/4816 ,  A61K9/5036 ,  A61K35/39 ,  A61K47/36 ,  A61L31/10 ,  A61L33/08 ,  C07D487/04 ,  C08B37/0084 ,  C12N5/0012 ,  C12N5/0677

Abstract: Covalently modified alginate polymers, possessing enhanced biocompatibility and tailored physiochemical properties, as well as methods of making and use thereof, are disclosed herein. The covalently modified alginates are useful as a matrix for coating of any material where reduced fibrosis is desired, such as encapsulated cells for transplantation and medical devices implanted or used in the body.