公开(公告)号：US11672876B2

公开(公告)日：2023-06-13

申请号：US16749370

申请日：2020-01-22

申请人： Biocompatibles UK Limited ,  THE UNITED STATES OF AMERICA, as represented by the Secretary Department of Health and Human Service

发明人： Matthew R. Dreher ,  Bradford J. Wood ,  Ayele H. Negussie ,  Andrew Lennard Lewis ,  Yiqing Tang

IPC分类号： A61K9/00 ,  A61K49/04 ,  C08F116/06 ,  C08L29/04 ,  B82Y5/00

CPC分类号： A61K49/0442 ,  A61K49/0438 ,  A61K49/0476 ,  A61K49/0485 ,  C08F116/06 ,  C08L29/04 ,  B82Y5/00

摘要： This invention concerns imageable, radiopaque embolic beads, which are particularly useful for monitoring embolization procedures. The beads comprise iodine containing compounds which are covalently incorporated into the polymer network of a preformed hydrogel bead. The beads are prepared by activating pre-formed hydrogel beads towards nucleophilic attack and then covalently attaching iodinated compounds into the polymer network. The radiopaque beads may be loaded with chemotherapeutic agents and used in methods of embolizing hyperplastic tissue or solid tumors.

公开(公告)号：US20220074944A1

公开(公告)日：2022-03-10

申请号：US17422972

申请日：2020-01-29

申请人： The United States of America, as Represented by the Secretary,Department of Health and Human Service

发明人： Apurva Kumar Srivastava ,  Dominic Esposito ,  Jeevan Prasaad Govindharajulu ,  Ralph Ewin Parchment ,  James Halpern Doroshow

IPC分类号： G01N33/574 ,  G01N33/543

摘要： Immunoassays to detect the presence of Bcl-2 family heterodimeric complexes are described. The immunoassays are designed to detect one or more of BIM-Bcl-2, BIM-Bcl-xL, BIM-Mcl-1 and BAX-BAK heterodimers. The assays can be used, for example, to select a BH3 mimetic, or other drug targeting the apoptosis pathway, that is effective for treating a specific cancer, or to select a subject who is likely to respond to a particular BH3 mimetic.

公开(公告)号：US20210188921A1

公开(公告)日：2021-06-24

申请号：US16756777

申请日：2018-10-16

申请人： The United States of America, as represented by the Secretary,Department of Health and Human Service

发明人： Peter Kwong ,  John Mascola ,  Gwo-Yu Chuang ,  Hui Geng ,  Yongping Yang ,  Cheng Cheng ,  Jeffrey Boyington ,  Yen-Ting Lai

IPC分类号： C07K14/16 ,  A61K39/12 ,  A61K39/39

摘要： Immunogens comprising a recombinant HIV-1 Env ectodomain trimer stabilized in a prefusion closed conformation and methods of their use and production are disclosed. In several embodiments, the immunogen can be used to elicit an immune response to HIV-1 in a subject.

公开(公告)号：US20200209117A1

公开(公告)日：2020-07-02

申请号：US16328553

申请日：2017-08-29

申请人： The United States of America,as represented by the Secretary, Department of Health and Human Service

发明人： Ronald N. Germain ,  Weizhe Li ,  Michael Y. Gerner

IPC分类号： G01N1/30

摘要： Disclosed are compositions, methods, and kits for clearing tissue that preserve cellular morphology, reporter fluorescence, and epitope labeling which allow for quantitative phenotypic analysis of intact organs. The compositions include, for example, a compound of formula R1—C(X)—NR2R3, wherein R1 is alkyl, haloalkyl, hydroxyalkyl, amino, or alkylamino, X is O or S, and R2 and R3 are independently H, alkyl, or hydroxyalkyl, a salt thereof, or a combination thereof, and at least one non-ionic density gradient medium. Also disclosed are methods for clearing tissue comprising positioning a tissue in a tissue clearing composition and allowing a tissue clearing composition to permeate the tissue. Further disclosed are methods for visualizing tissue characteristics which involve fixing a tissue, staining the tissue, positioning the tissue in the tissue clearing composition and allowing the tissue clearing composition to permeate the tissue, and imaging the tissue utilizing a microscope or tissue scanning device.

公开(公告)号：US20190247407A1

公开(公告)日：2019-08-15

申请号：US16223793

申请日：2018-12-18

申请人： Wayne State University ,  The United States of America as Represented by the Secretary, Department of Health and Human Service

发明人： Kannan Rangaramanujam ,  Sujatha Kannan ,  Roberto Romero ,  Raghavendra S Navath ,  Hui Dai ,  Anupa R. Menjoge

IPC分类号： A61K31/65 ,  A61K47/64 ,  A61K47/59 ,  A61K47/60 ,  A61K38/10 ,  C08G83/00 ,  A61K31/405 ,  A61K31/43 ,  A61K31/57 ,  A61K31/573 ,  A61K31/198

摘要： A nanodevice composition including N-acetyl cysteine linked to a dendrimer, such as a PAMAM dendrimer or a multiarm PEG polymer, is provided. Also provided is a nanodevice for targeted delivery of a compound to a location in need of treatment. The nanodevice includes a PAMAM dendrimer or multiarm PEG polymer, linked to the compound via a disulfide bond. There is provided a nanodevice composition for localizing and delivering therapeutically active agents, the nanodevice includes a PAMAM dendrimer or multiarm PEG polymer and at least one therapeutically active agent attached to the PAMAM dendrimer or multiarm PEG polymer. A method of site-specific delivery of a therapeutically active agent, by attaching a therapeutically active agent to a PAMAM dendrimer or multiarm PEG polymer using a disulfide bond, administering the PAMAM dendrimer or multiarm PEG polymer to a patient in need of treatment, localizing the dendrimer or multiarm PEG polymer to a site in need of treatment, and releasing the therapeutically active agent at the site in need of treatment.

公开(公告)号：US20190077849A1

公开(公告)日：2019-03-14

申请号：US15772443

申请日：2016-11-03

申请人： The United States of America,as represented by the Secretary, Department of Health and Human Service ,  The Trustees of Columbia University in the City of New York

发明人： Peter Kwong ,  Young Do Kwon ,  Ivelin Georgiev ,  Gilad Ofek ,  Baoshan Zhang ,  Krisha McKee ,  John Mascola ,  Mark Connors ,  Gwo-Yu Chuang ,  Sijy O'Dell ,  Robert Bailer ,  Mark Louder ,  Mangaiarkarasi Asokan ,  Richard Schwartz ,  Jonathan Cooper ,  Kevin Carlton ,  Michael Bender ,  Amarendra Pegu ,  Lawrence Shapiro ,  Tatyana Gindin ,  Lisa Kueltzo

IPC分类号： C07K16/10 ,  A61P31/18

摘要： Neutralizing antibodies that specifically bind to HIV-1 Env and antigen binding fragments of these antibodies are disclosed. Nucleic acids encoding these antibodies, vectors and host cells are also provided. Methods for detecting HIV-1 using these antibodies are disclosed. In addition, the use of these antibodies, antigen binding fragment, nucleic acids and vectors to prevent and/or treat an HIV-1 infection is disclosed.

公开(公告)号：US20180259759A1

公开(公告)日：2018-09-13

申请号：US15904916

申请日：2018-02-26

申请人： The United States of America,as represented by the Secretary, Department of Health and Human Service

发明人： Do-Hyun Kim ,  Ilko Kolev Ilev ,  Robert Harold James ,  Don Calogero

IPC分类号： G02B21/00 ,  G02B21/06 ,  G02B21/18 ,  G02B21/02 ,  A61F2/16

CPC分类号： G02B21/0032 ,  A61F2/16 ,  A61F2240/008 ,  G01B11/06 ,  G01N21/41 ,  G01N2021/4126 ,  G02B21/02 ,  G02B21/06 ,  G02B21/18

摘要： Systems and methods for conducting contact-free thickness and refractive-index measurements of transparent objects, such as intraocular lenses using a dual confocal microscopy system are disclosed.

公开(公告)号：US09492564B2

公开(公告)日：2016-11-15

申请号：US14270836

申请日：2014-05-06

申请人： Duke University ,  The United States of America as represented by the Secretary, Department of Health and Human Service

发明人： Darell Bigner ,  Chien-Tsun Kuan ,  Ira H. Pastan ,  Charles Peagram

IPC分类号： A61K39/395 ,  A61K47/48 ,  C07K16/28 ,  A61K39/00

CPC分类号： C07K16/2863 ,  A61K38/00 ,  A61K39/39558 ,  A61K47/6829 ,  A61K47/6849 ,  A61K2039/505 ,  A61K2039/545 ,  C07K14/21 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/622 ,  C07K2317/624 ,  C07K2317/92 ,  C07K2319/04 ,  C07K2319/55

摘要： We tested the in vitro and in vivo efficacy of a recombinant bispecific immunotoxin that recognizes both EGFRwt and tumor-specific EGFRvIII receptors. A single chain antibody was cloned from a hybridoma and fused to toxin, carrying a C-terminal peptide which increases retention within cells. The binding affinity and specificity of the recombinant bispecific immunotoxin for the EGFRwt and the EGFRvIII proteins was measured. In vitro cytotoxicity was measured. In vivo activity of the recombinant bispecific immunotoxin was evaluated in subcutaneous models and compared to that of an established monospecific immunotoxin. In our preclinical studies, the bispecific recombinant immunotoxin, exhibited significant potential for treating brain tumors.

摘要翻译： 我们测试了识别EGFR重组和肿瘤特异性EGFRvIII受体的重组双特异性免疫毒素的体外和体内功效。 从杂交瘤中克隆单链抗体并与毒素融合，携带增加细胞内保留的C-末端肽。 测量了重组双特异性免疫毒素对EGFRwt和EGFRvIII蛋白的结合亲和力和特异性。 测量体外细胞毒性。 在皮下模型中评估重组双特异性免疫毒素的体内活性，并与已建立的单特异性免疫毒素的体内活性进行比较。 在我们的临床前研究中，双特异性重组免疫毒素显示出显着的治疗脑肿瘤的潜力。

公开(公告)号：US09452973B2

公开(公告)日：2016-09-27

申请号：US14398830

申请日：2013-03-15

申请人： The United States of America, as Represented by the Secretary, Department of Health and Human Service ,  The Florida International University Board of Trustees

发明人： Juan Jose Marugan ,  Jingbo Xiao ,  Marc Ferrer-Alegre ,  Catherine Chen ,  Noel Southall ,  Wei Zheng ,  Alexander Agoulnik ,  Irina Agoulnik

IPC分类号： A61K31/166 ,  C07C233/64 ,  C07C237/42 ,  C07C255/57 ,  C07D213/75 ,  C07C255/60 ,  C07C257/18 ,  C07D213/79 ,  C07D213/80 ,  C07D213/81 ,  C07D213/82 ,  C07C271/28 ,  C07D317/68 ,  C07D333/20 ,  C07D333/38 ,  C07D333/40 ,  C07C311/29 ,  C07D235/18 ,  C07C323/62 ,  C07C257/04 ,  C07C233/63 ,  C07D261/18 ,  C07C235/64 ,  C07C237/30 ,  C07C237/40 ,  C07D209/08 ,  C07D209/46 ,  C07D295/088 ,  C07D295/205 ,  C07D307/52 ,  C07D307/68 ,  C07D317/66 ,  C07D235/06 ,  C07D403/10 ,  C07D487/04 ,  C07D295/135 ,  C07C317/36 ,  C07C317/40 ,  C07C317/44 ,  C07C323/42

CPC分类号： C07D333/38 ,  C07C233/63 ,  C07C235/64 ,  C07C237/30 ,  C07C237/40 ,  C07C237/42 ,  C07C251/24 ,  C07C255/57 ,  C07C255/60 ,  C07C257/04 ,  C07C257/18 ,  C07C271/28 ,  C07C311/29 ,  C07C317/36 ,  C07C317/40 ,  C07C317/44 ,  C07C323/42 ,  C07C323/62 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/10 ,  C07C2601/14 ,  C07C2601/16 ,  C07C2601/18 ,  C07C2602/08 ,  C07C2603/74 ,  C07D209/08 ,  C07D209/46 ,  C07D211/26 ,  C07D213/75 ,  C07D213/79 ,  C07D213/80 ,  C07D213/81 ,  C07D213/82 ,  C07D235/06 ,  C07D235/08 ,  C07D235/14 ,  C07D235/18 ,  C07D257/04 ,  C07D261/18 ,  C07D295/088 ,  C07D295/135 ,  C07D295/205 ,  C07D307/52 ,  C07D307/68 ,  C07D317/66 ,  C07D317/68 ,  C07D333/20 ,  C07D333/40 ,  C07D403/10 ,  C07D487/04

摘要： Disclosed are modulators of the human relaxin receptor 1, for example, of formula (I), wherein A, R1, and R2 are as defined herein, that are useful in treating mammalian relaxin receptor 1 mediated facets of human health, e.g., cardiovascular disease. Also disclosed is a composition comprising a pharmaceutically suitable carrier and at least one compound of the disclosure, and a method for therapeutic intervention in a facet of mammalian health that is mediated by a human relaxin receptor 1.

摘要翻译： 公开了人类松弛素受体1的调节剂，例如式（I）的化合物，其中A，R 1和R 2如本文所定义，其可用于治疗哺乳动物松弛素受体1介导的人体健康方面，例如心血管疾病 。 还公开了包含药学上合适的载体和本公开的至少一种化合物的组合物，以及由人松弛素受体1介导的哺乳动物健康的方面的治疗性干预的方法。

公开(公告)号：US20150283111A1

公开(公告)日：2015-10-08

申请号：US14442865

申请日：2013-11-13

申请人： THE UNITED STATES OF AMERICA,AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICE

发明人： Leonard M. Neckers ,  Carole Sourbier ,  Jane B. Neckers ,  Min-Jung Lee ,  John A. Beutler ,  W. Marston Linehan ,  Bradley T. Scroggins ,  Sunmin Lee

IPC分类号： A61K31/35 ,  A61K45/06

CPC分类号： A61K31/35 ,  A61K31/352 ,  A61K45/06 ,  A61K2300/00

摘要： Disclosed is a method of activating protein kinase C theta (PKCθ) in an HIV or HTLV infected animal comprising administering to the animal an effective amount of a compound of formula (I): Formula (I), or an epimer thereof; wherein Ar and R1-R6 are described herein. Examples of diseases or conditions associated with PKCθ include HIV1 infection, AIDS, HTLV infection, and adult T cell leukemia/lymphoma.

摘要翻译： 公开了一种在HIV或HTLV感染的动物中激活蛋白激酶Cθ（PKC）的方法，包括向动物施用有效量的式（I）化合物：式（I）或其差向异构体; 其中Ar和R 1 -R 6在本文中描述。 与PKC相关的疾病或病症的例子; 包括HIV1感染，艾滋病，HTLV感染和成人T细胞白血病/淋巴瘤。