公开(公告)号：US20240343859A1

公开(公告)日：2024-10-17

申请号：US18628340

申请日：2024-04-05

申请人： University of Rhode Island Board of Trustees ,  Yale University

发明人： Matthew Kiesewetter ,  Kassie Picard ,  Jinal Pothupitiya ,  W. Mark Saltzman

IPC分类号： C08G63/08 ,  A61L27/18 ,  A61L27/54 ,  A61L27/58

CPC分类号： C08G63/08 ,  A61L27/18 ,  A61L27/54 ,  A61L27/58

摘要： Embodiments of the present invention comprises one or more of an article composed of a copolymer, a copolymer made from a process, and a process for the preparation of a copolymer composition by metal free enzyme ring-opening polymerization of a monomer composition comprising i) an ethylene brassylate monomer; ii) a 1-4 dioxan-2-one (DO); iii) lipase B from Candida antarctica (Novozyme® 435) and at an elevated temperature, processing the monomer reactants i) and ii) to a copolymer via ring-opening polymerization under solvent-free conditions and a nitrogen atmosphere in the absence of a metal and the presence of the lipase to produce a random EB-co-DO copolymer.

公开(公告)号：US20230233693A1

公开(公告)日：2023-07-27

申请号：US18002241

申请日：2021-05-27

申请人： Yale University

发明人： W. Mark Saltzman ,  Yuhang Jiang ,  Molly Grun ,  Alexandra Suberi

IPC分类号： A61K47/59 ,  C08G63/685 ,  C08G63/91

CPC分类号： A61K47/593 ,  C08G63/6856 ,  C08G63/916

摘要： Poly(amine-co-ester) polymers, methods of forming active agent-load polyplexes and particles therefrom, and methods of using them for delivery of nucleic acid agents with optimal uptake have been developed. Examples demonstrate critical molecular weights in combination with exposed carboxylic and/or hydroxyl groups, and methods of making. Typically, the compositions are less toxic, more efficient at drug delivery, or a combination thereof compared to a control other transfection reagents. In some embodiments, the compositions are suitable for in vivo delivery, and can be administered systemically to a subject to treat a disease or condition. For poly(amine-co-ester) polymers with specific amine or hydroxyl group containing end-groups in admixture with PEGylated poly(amine-co-ester) polymers, in vivo delivery to the lung by inhalation has been shown.

公开(公告)号：US20220372474A1

公开(公告)日：2022-11-24

申请号：US17620358

申请日：2020-06-22

申请人： Yale University

发明人： Elias Quijano ,  Stanley Oyaghire ,  W. Mark Saltzman ,  Peter Glazer

IPC分类号： C12N15/113 ,  A61K9/14

摘要： Peptide nucleic acid (PNA) oligomers having one or more hydroxymethyl γ-substitutions, also referred to herein as “serγPNA”, are provided. The hydroxymethyl γ-substitution preserves and amplifies the helical preorganization that is valuable for DNA duplex invasion by the oligomer. serγPNA-containing triplex-forming molecules can be used in combination with a donor DNA fragment to facilitate genome modification in vitro and in vivo.

公开(公告)号：US20220339294A1

公开(公告)日：2022-10-27

申请号：US17641516

申请日：2020-09-09

申请人： Yale University

发明人： Hanna Mandl ,  Elias Quijano ,  W. Mark Saltzman ,  Peter Glazer

IPC分类号： A61K47/69 ,  A61K9/00 ,  A61K9/51

摘要： Compositions containing populations of nanoparticles that show selective uptake by tissues and other cell types such as lung cells and/or bone marrow cells are described. The nanoparticles show this uptake by virtue of their size and in the absence of a targeting agent on the surface of the nanoparticles, i.e., passive targeting. The population of nanoparticles contain poly(lactic acid-co-glycolic acid), have a diameter between about 70 nm and about 220 nm, and at least 90% of the nanoparticles have a diameter between about 110 nm and about 129 nm. The nanoparticles are manufactured using a microfluidic system. The compositions can be used to treat lung- and/or blood-related genetic disorders in in vivo gene editing technologies.

公开(公告)号：US20210189431A1

公开(公告)日：2021-06-24

申请号：US17267755

申请日：2019-08-12

申请人： Yale University

发明人： Rachael Putman ,  Adele S. Ricciardi ,  Peter M. Glazer ,  W. Mark Saltzman

IPC分类号： C12N15/873 ,  C12N15/90 ,  C12N15/88

摘要： Methods for gene editing of embryos in vitro are provided. The methods typically include contacting an embryo in vitro with an effective amount of non-enzymatic (e.g., non-nuclease) gene editing active agent(s) optionally encapsulated, entrapped, complexed to or dispersed in polymeric particles to induce at least one alteration in the genome of the embryo. The embryo can be a single cell zygote, however, treatment of male and female gametes prior to fertilization, and embryos having 2, 4, 8, or 16 cells, and including not only zygotes, but also morulas and blastocysts are also provided. Typically, the embryo is contacted with the particles on culture days 0-6 during or following in vitro fertilization.

公开(公告)号：US20200308590A1

公开(公告)日：2020-10-01

申请号：US15998613

申请日：2017-02-16

申请人： Yale University

发明人： Peter M. Glazer ,  W. Mark Saltzman ,  Marie Egan ,  Nicole Ali McNeer

IPC分类号： C12N15/113

摘要： Compositions and methods of genome engineering in vitro and in vivo are provided. In some embodiments, the compositions are triplex forming molecules that bind or hybridize to a target region sequence in the human cystic fibrosis transmembrane conductance regulator (CFTR) gene. Preferably the triplex forming molecules are peptide nucleic acids that include a Hoogsteen binding peptide nucleic acid (PNA) segment and a Watson-Crick binding PNA segment collectively totaling no more than 50 nucleobases in length, wherein the two segments can binid or hybridize to a target region in the CFTR gene having a polypurine sequences and induce strand invasion, displacement, and formation of a triple-stranded molecule among the two PNA segments and the target region's sequence. Methods of using the triplex forming molecules to treat cystic fibrosis are also provided.

公开(公告)号：US09895451B2

公开(公告)日：2018-02-20

申请号：US14547051

申请日：2014-11-18

申请人： Yale University

发明人： W. Mark Saltzman ,  Junwei Zhang ,  Jiangbing Zhou ,  Zhaozhong Jiang

IPC分类号： A61K47/48 ,  A61K47/59 ,  A61K31/7088 ,  A61K9/51 ,  C08G63/685 ,  A61K47/34 ,  A61K9/107 ,  C12N15/87

CPC分类号： A61K47/593 ,  A61K9/1075 ,  A61K9/5146 ,  A61K31/7088 ,  A61K47/34 ,  C08G63/685 ,  C12N15/87

摘要： Polyamine-co-ester-co-ortho ester) polymers, methods of forming active agent-load nanoparticles therefrom, and methods of using the nanoparticles for drug delivery are disclosed. The nanoparticles can be coated with an agent that reduces surface charge, an agent that increases cell-specific targeting, or a combination thereof. Typically, the loaded nanoparticles are less toxic, more efficient at drug delivery, or a combination thereof compared to a control or other transfection reagents.

公开(公告)号：US20140342003A1

公开(公告)日：2014-11-20

申请号：US14293733

申请日：2014-06-02

申请人： Yale University

发明人： W. Mark Saltzman ,  Zhaozhong Jiang ,  Jiangbing Zhou

IPC分类号： A61K47/34 ,  A61K9/14 ,  C08G63/685 ,  C12N15/87 ,  A61K31/7088 ,  A61K9/50 ,  C12N15/113

CPC分类号： C08G63/6852 ,  A61K9/1075 ,  A61K31/337 ,  A61K31/7088 ,  A61K31/711 ,  A61K38/1774 ,  A61K38/1793 ,  A61K38/44 ,  A61K47/34 ,  A61K48/0041 ,  C08G63/88 ,  C12N15/87 ,  C12N15/88 ,  C12P13/001 ,  C12Y113/12007

摘要： Poly(amine-co-ester) polymers, methods of forming active agent-load nanoparticles therefrom, and methods of using the nanoparticles for drug delivery are disclosed. The nanoparticles can be coated with an agent that reduces surface charge, an agent that increases cell-specific targeting, or a combination thereof. Typically, the loaded nanoparticles are less toxic, more efficient at drug delivery, or a combination thereof compared to a control other transfection reagents. In some embodiments, the nanoparticles are suitable for in vivo delivery, and can be administered systemically to a subject to treat a disease or condition.

摘要翻译： 公开了聚（胺 - 共酯）聚合物，其中形成活性剂负载纳米颗粒的方法，以及使用该纳米颗粒用于药物递送的方法。 纳米颗粒可以用减少表面电荷的试剂，增加细胞特异性靶向的试剂或其组合来涂覆。 通常，加载的纳米颗粒在药物递送下毒性较小，效率更高，或与其它转染试剂相比较，其组合。 在一些实施方案中，纳米颗粒适合于体内递送，并且可以全身施用于受试者以治疗疾病或病症。

公开(公告)号：US20240092968A1

公开(公告)日：2024-03-21

申请号：US18361630

申请日：2023-07-28

申请人： Yale University

发明人： W. Mark Saltzman ,  Yuhang Jiang

IPC分类号： C08G63/685 ,  A61K47/59

CPC分类号： C08G63/685 ,  A61K47/595

摘要： Poly(amine-co-ester) polymers, methods of forming active agent-load polyplexes and particles therefrom, and methods of using them for delivery of nucleic acid agents with optimal uptake have been developed. Examples demonstrate critical molecular weights in combination with exposed carboxylic and/or hydroxyl groups, and methods of making. Typically, the compositions are less toxic, more efficient at drug delivery, or a combination thereof compared to a control other transfection reagents. In some embodiments, the compositions are suitable for in vivo delivery, and can be administered systemically to a subject to treat a disease or condition.

公开(公告)号：US20230172870A1

公开(公告)日：2023-06-08

申请号：US18063613

申请日：2022-12-08

申请人： Yale University

发明人： Alexandra Piotrowski-Daspit ,  Claire Albert ,  W. Mark Saltzman

IPC分类号： A61K9/51 ,  A61K47/60 ,  A61K47/34

CPC分类号： A61K9/5153 ,  A61K47/60 ,  A61K47/34 ,  B82Y5/00

摘要： Nanoparticles useful for drug delivery are described. In one aspect, the nanoparticles contain poly(amine-co-ester)s or poly(amine-co-amide)s (PACE) modified with poly(ethylene glycol) (PACE-PEG), and can be optionally blended with a second PACE polymer optionally containing endgroup modifications. In another aspect, the nanoparticles contain a core containing a PACE polymer optionally containing endgroup modifications, and a polymeric surfactant non-covalently conjugated to the surface of the nanoparticles. The nanoparticles contain a peptide or protein targeting moiety that is covalently conjugated to the PACE-PEG polymer or to the surfactant on the surface of the nanoparticles via a linkage that contains a succinimide or substituted sulfone moiety, respectively. The nanoparticles provide as a versatile platform for the delivery of nucleic acids, such as mRNA.