公开(公告)号：US20110243880A1

公开(公告)日：2011-10-06

申请号：US13073815

申请日：2011-03-28

申请人： Aleksandr Yurkovetskiy ,  Mao Yin ,  Timothy B. Lowinger ,  Carolina B. Cabral ,  Charles E. Hammond ,  Cheri A. Stevenson

发明人： Aleksandr Yurkovetskiy ,  Mao Yin ,  Timothy B. Lowinger ,  Carolina B. Cabral ,  Charles E. Hammond ,  Cheri A. Stevenson

IPC分类号： A61K47/48 ,  C08G65/48 ,  C12N5/071 ,  C12N5/078 ,  C12N5/09 ,  C12N5/079

CPC分类号： C08L59/00 ,  A61K47/59 ,  A61K48/0041 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/12 ,  C12N2310/14 ,  C12N2320/32

摘要： A polynucleotide delivery vehicle comprising a modified polymer is provided herein, the modified polymer having the following formula: in which W1, W2, W3, W4, W5, W6, Z1, Z2, Z3, Z4, Z5, Z9, R1, R2, R3, R4, R5, n1, n2, n3, n4, n5, and n6 are defined herein. Also disclosed are methods of delivering a polynucleotide to the cytoplasm of a selected tissue type or cell type and methods of reducing expression of a gene in a cell or a subject in need thereof with the modified polymer.

摘要翻译： 本文提供了包含改性聚合物的多核苷酸递送载体，所述改性聚合物具有下式：其中W1，W2，W3，W4，W5，W6，Z1，Z2，Z3，Z4，Z5，Z9，R1，R2， R3，R4，R5，n1，n2，n3，n4，n5和n6在本文中定义。 还公开了将多核苷酸递送至所选组织类型或细胞类型的细胞质的方法以及在有需要的细胞或受试者中用改性聚合物降低基因表达的方法。

公开(公告)号：US08349308B2

公开(公告)日：2013-01-08

申请号：US13073815

申请日：2011-03-28

申请人： Aleksandr Yurkovetskiy ,  Mao Yin ,  Timothy B. Lowinger ,  Carolina B. Cabral ,  Charles E. Hammond ,  Cheri A. Stevenson

发明人： Aleksandr Yurkovetskiy ,  Mao Yin ,  Timothy B. Lowinger ,  Carolina B. Cabral ,  Charles E. Hammond ,  Cheri A. Stevenson

IPC分类号： A61K31/74 ,  A61K47/48 ,  C07H21/04 ,  C12N15/11

CPC分类号： C08L59/00 ,  A61K47/59 ,  A61K48/0041 ,  C12N15/111 ,  C12N2310/11 ,  C12N2310/12 ,  C12N2310/14 ,  C12N2320/32

摘要： A polynucleotide delivery vehicle comprising a modified polymer is provided herein, the modified polymer having the following formula: in which W1, W2, W3, W4, W5, W6, Z1, Z2, Z3, Z4, Z5, Z9, R1, R2, R3, R4, R5, n1, n2, n3, n4, n5, and n6 are defined herein. Also disclosed are methods of delivering a polynucleotide to the cytoplasm of a selected tissue type or cell type and methods of reducing expression of a gene in a cell or a subject in need thereof with the modified polymer.

摘要翻译： 本文提供了包含改性聚合物的多核苷酸递送载体，所述改性聚合物具有下式：其中W1，W2，W3，W4，W5，W6，Z1，Z2，Z3，Z4，Z5，Z9，R1，R2， R3，R4，R5，n1，n2，n3，n4，n5和n6在本文中定义。 还公开了将多核苷酸递送至所选组织类型或细胞类型的细胞质的方法以及在有需要的细胞或受试者中用改性聚合物降低基因表达的方法。

公开(公告)号：US08524214B2

公开(公告)日：2013-09-03

申请号：US12789047

申请日：2010-05-27

申请人： Aleksandr Yurkovetskiy ,  Mao Yin ,  Gui Liu ,  Laura C. Akullian ,  John J. Kane ,  Cheri A. Stevenson ,  Charles E. Hammond ,  Russell C. Petter ,  John H. Van Duzer ,  Timothy B. Lowinger

发明人： Aleksandr Yurkovetskiy ,  Mao Yin ,  Gui Liu ,  Laura C. Akullian ,  John J. Kane ,  Cheri A. Stevenson ,  Charles E. Hammond ,  Russell C. Petter ,  John H. Van Duzer ,  Timothy B. Lowinger

IPC分类号： A61K31/045 ,  A61K31/04 ,  A61K31/13 ,  A61K31/21 ,  A61K31/33 ,  A61K31/695 ,  A61K31/765

CPC分类号： C07D519/04 ,  A61K47/59 ,  C07D491/22 ,  G01N2500/00 ,  Y10T436/145555

摘要： Polyal-Drug conjugates comprising a variable rate-releasing linker are described along with methods of making such conjugates. Uses for such Polyal-Drug conjugates is also described.

摘要翻译： 描述包含可变速率释放连接体的多价 - 药物共轭物以及制备这种缀合物的方法。 也描述了这种多种药物共轭物的用途。

公开(公告)号：US08685383B2

公开(公告)日：2014-04-01

申请号：US13493899

申请日：2012-06-11

申请人： Aleksandr Yurkovetskiy ,  Mao Yin ,  Timothy B. Lowinger ,  Joshua D. Thomas ,  Charles E. Hammond ,  Cheri A. Stevenson ,  Natalya D. Bodyak ,  Patrick R. Conlon ,  Dmitry R. Gumerov

发明人： Aleksandr Yurkovetskiy ,  Mao Yin ,  Timothy B. Lowinger ,  Joshua D. Thomas ,  Charles E. Hammond ,  Cheri A. Stevenson ,  Natalya D. Bodyak ,  Patrick R. Conlon ,  Dmitry R. Gumerov

IPC分类号： A61K31/74 ,  A61K47/48 ,  A61K38/04 ,  C08G63/48 ,  C08G63/91 ,  C08G65/32 ,  C08L67/00 ,  C08G65/333 ,  C08G65/334

CPC分类号： A61K47/59 ,  A61K31/4745 ,  A61K47/64 ,  A61K47/6803 ,  A61K47/6849 ,  A61K47/6883 ,  C07K7/02 ,  C07K16/32 ,  C08G65/33396 ,  C08G65/334

摘要： A drug conjugate is provided herein. The conjugate comprises a protein based recognition-molecule (PBRM) and a polymeric carrier substituted with one or more -LD-D, the protein based recognition-molecule being connected to the polymeric carrier by LP. Each occurrence of D is independently a therapeutic agent having a molecular weight ≦5 kDa. LD and LP are linkers connecting the therapeutic agent and PBRM to the polymeric carrier respectively. Also disclosed are polymeric scaffolds useful for conjugating with a PBRM to form a polymer-drug-PBRM conjugate described herein, compositions comprising the conjugates, methods of their preparation, and methods of treating various disorders with the conjugates or their compositions.

公开(公告)号：US20100305149A1

公开(公告)日：2010-12-02

申请号：US12789047

申请日：2010-05-27

申请人： Aleksandr Yurkovetskiy ,  Mao Yin ,  Gui Liu ,  Laura C. Akullian ,  John J. Kane ,  Cheri A. Stevenson ,  Charles E. Hammond ,  Russell C. Petter ,  John H. Van Duzer ,  Timothy B. Lowinger

发明人： Aleksandr Yurkovetskiy ,  Mao Yin ,  Gui Liu ,  Laura C. Akullian ,  John J. Kane ,  Cheri A. Stevenson ,  Charles E. Hammond ,  Russell C. Petter ,  John H. Van Duzer ,  Timothy B. Lowinger

IPC分类号： A61K31/439 ,  A61P35/00 ,  A61P35/04 ,  C07D487/18 ,  C07D491/22 ,  G01N33/50

CPC分类号： C07D519/04 ,  A61K47/59 ,  C07D491/22 ,  G01N2500/00 ,  Y10T436/145555

摘要： Polyal-Drug conjugates comprising a variable rate-releasing linker are described along with methods of making such conjugates. Uses for such Polyal-Drug conjugates is also described.

摘要翻译： 描述包含可变速率释放连接体的多价 - 药物共轭物以及制备这种缀合物的方法。 也描述了这种多种药物共轭物的用途。

公开(公告)号：US20120321583A1

公开(公告)日：2012-12-20

申请号：US13493899

申请日：2012-06-11

申请人： Aleksandr Yurkovetskiy ,  Mao Yin ,  Timothy B. Lowinger ,  Joshua D. Thomas ,  Charles E. Hammond ,  Cheri A. Stevenson ,  Natalya D. Bodyak ,  Patrick R. Conlon ,  Dmitry R. Gumerov

发明人： Aleksandr Yurkovetskiy ,  Mao Yin ,  Timothy B. Lowinger ,  Joshua D. Thomas ,  Charles E. Hammond ,  Cheri A. Stevenson ,  Natalya D. Bodyak ,  Patrick R. Conlon ,  Dmitry R. Gumerov

IPC分类号： C08G65/333 ,  C08G65/332 ,  A61P35/00 ,  A61P35/02 ,  A61K47/48 ,  C07K5/103

CPC分类号： A61K47/59 ,  A61K31/4745 ,  A61K47/64 ,  A61K47/6803 ,  A61K47/6849 ,  A61K47/6883 ,  C07K7/02 ,  C07K16/32 ,  C08G65/33396 ,  C08G65/334

摘要： A drug conjugate is provided herein. The conjugate comprises a protein based recognition-molecule (PBRM) and a polymeric carrier substituted with one or more -LD-D, the protein based recognition-molecule being connected to the polymeric carrier by LP. Each occurrence of D is independently a therapeutic agent having a molecular weight ≦5 kDa. LD and LP are linkers connecting the therapeutic agent and PBRM to the polymeric carrier respectively. Also disclosed are polymeric scaffolds useful for conjugating with a PBRM to form a polymer-drug-PBRM conjugate described herein, compositions comprising the conjugates, methods of their preparation, and methods of treating various disorders with the conjugates or their compositions.

摘要翻译： 本文提供药物缀合物。 缀合物包含基于蛋白质的识别分子（PBRM）和被一个或多个-LD-D取代的聚合物载体，基于蛋白质的识别分子通过LP连接到聚合物载体上。 每次出现的D独立地是具有分子量＆nlE; 5kDa的治疗剂。 LD和LP分别是将治疗剂和PBRM分别连接到聚合物载体的接头。 还公开了可用于与PBRM缀合以形成本文所述的聚合物 - 药物-PBRM缀合物的聚合物支架，包含缀合物的组合物，其制备方法，以及用缀合物或其组合物治疗各种病症的方法。

公开(公告)号：US20130158046A1

公开(公告)日：2013-06-20

申请号：US13769024

申请日：2013-02-15

申请人： Laura C. Akullian ,  Russell C. Petter ,  John J. Kane ,  Charles E. Hammond ,  Mao Yin ,  Aleksandr Yurkovetskiy ,  Cheri A. Stevenson

发明人： Laura C. Akullian ,  Russell C. Petter ,  John J. Kane ,  Charles E. Hammond ,  Mao Yin ,  Aleksandr Yurkovetskiy ,  Cheri A. Stevenson

IPC分类号： C07D303/40 ,  C07D303/18

CPC分类号： C07D303/40 ,  A61K47/59 ,  C07D303/18 ,  C07D303/22 ,  C07D303/36 ,  C07D405/14 ,  C07D487/08

摘要： Fumagillin analog polymer conjugates, methods of making fumagillin analog polymer conjugates, compositions comprising a polymer conjugate of a fumagillin analog, and methods for treating cancer, or treating angiogenic diseases comprising administering to a subject in need thereof an effective amount of a polymer conjugate of a fumagillin analog, are described. Also described are novel fumagillin analogs, methods of making fumagillin analogs, compositions comprising at least one fumagillin analog, and methods for treating cancer, or treating angiogenic diseases comprising administering to a subject in need thereof an effective amount of a fumagillin analog.

公开(公告)号：US08399512B2

公开(公告)日：2013-03-19

申请号：US12276856

申请日：2008-11-24

申请人： Laura C. Akullian ,  Russell C. Petter ,  John J. Kane ,  Charles E. Hammond ,  Mao Yin ,  Aleksandr Yurkovetskiy ,  Cheri A. Stevenson

发明人： Laura C. Akullian ,  Russell C. Petter ,  John J. Kane ,  Charles E. Hammond ,  Mao Yin ,  Aleksandr Yurkovetskiy ,  Cheri A. Stevenson

IPC分类号： A61K31/335 ,  C07D303/00

CPC分类号： C07D303/40 ,  A61K47/59 ,  C07D303/18 ,  C07D303/22 ,  C07D303/36 ,  C07D405/14 ,  C07D487/08

摘要： Fumagillin analog polymer conjugates, methods of making fumagillin analog polymer conjugates, compositions comprising a polymer conjugate of a fumagillin analog, and methods for treating cancer, or treating angiogenic diseases comprising administering to a subject in need thereof an effective amount of a polymer conjugate of a fumagillin analog, are described. Also described are novel fumagillin analogs, methods of making fumagillin analogs, compositions comprising at least one fumagillin analog, and methods for treating cancer, or treating angiogenic diseases comprising administering to a subject in need thereof an effective amount of a fumagillin analog.

摘要翻译： 烟曲霉素类似物聚合物缀合物，制备烟曲霉素类似物聚合物共轭物的方法，包含烟曲霉素类似物的聚合物缀合物的组合物，以及用于治疗癌症的方法或治疗血管发生疾病的方法，包括向有需要的受试者施用有效量的 烟曲霉素类似物。 还描述了新的烟曲霉素类似物，制备烟曲霉素类似物的方法，包含至少一种烟曲霉素类似物的组合物，以及用于治疗癌症的方法或治疗血管发生疾病，包括向有需要的受试者施用有效量的烟曲霉素类似物。

公开(公告)号：US08088762B2

公开(公告)日：2012-01-03

申请号：US12636316

申请日：2009-12-11

申请人： Richard A. Earl ,  Maiko Ezawa ,  Xinqin Fang ,  David S. Garvey ,  Ricky D. Gaston ,  Subhash P. Khanapure ,  L. Gordon Letts ,  Chia-En Lin ,  Ramani R. Ranatunge ,  Stewart K. Richardson ,  Joseph D. Schroeder ,  Cheri A. Stevenson ,  Shiow-Jyi Wey

发明人： Richard A. Earl ,  Maiko Ezawa ,  Xinqin Fang ,  David S. Garvey ,  Ricky D. Gaston ,  Subhash P. Khanapure ,  L. Gordon Letts ,  Chia-En Lin ,  Ramani R. Ranatunge ,  Stewart K. Richardson ,  Joseph D. Schroeder ,  Cheri A. Stevenson ,  Shiow-Jyi Wey

IPC分类号： A61K31/54 ,  A61K31/44 ,  A61K31/425 ,  C07D498/02 ,  C07D295/02 ,  C07D333/22

CPC分类号： C07D493/04 ,  C07C291/02 ,  C07C311/17 ,  C07C317/18 ,  C07C323/12 ,  C07C327/28 ,  C07D209/18 ,  C07D211/22 ,  C07D211/56

摘要： The invention describes novel nitrosated nonsteroidal anti-inflammatory drugs (NSAIDs) and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated NSAID, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated NSAID, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating inflammation, pain and fever; for treating gastrointestinal disorders; for facilitating wound healing; for treating and/or preventing gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; for treating inflammatory disease states and/or disorders; and for treating and/or preventing ophthalmic diseases and/or disorders.

摘要翻译： 本发明描述了新的亚硝化非甾体抗炎药（NSAID）及其药学上可接受的盐，以及包含至少一种亚硝化NSAID的新组合物，和任选的至少一种捐赠，转移或释放一氧化氮的化合物，刺激内源性合成 一氧化氮，提高内源性内源水平的内源性松弛因子，或者是一氧化氮合成酶的底物和/或至少一种治疗剂。 本发明还提供了包含至少一种亚硝化NSAID和至少一种捐赠，转移或释放一氧化氮的化合物的新型组合物，提高内源性内皮衍生的舒张因子水平，刺激一氧化氮的内源性合成，或是一氧化氮的底物 合酶和/或至少一种治疗剂。 本发明还提供了包含至少一种亚硝化NSAID和任选的至少一种一氧化氮供体和/或至少一种治疗剂的新型试剂盒。 本发明还提供了治疗炎症，疼痛和发烧的方法; 用于治疗胃肠道疾病; 促进伤口愈合; 用于治疗和/或预防由使用非甾体抗炎化合物引起的胃肠道，肾脏和/或呼吸道毒性物质; 用于治疗炎性疾病状态和/或病症; 并用于治疗和/或预防眼科疾病和/或病症。

公开(公告)号：US20110098253A1

公开(公告)日：2011-04-28

申请号：US12980077

申请日：2010-12-28

申请人： Richard Earl ,  Maiko Ezawa ,  Xinquin Fang ,  David S. Garvey ,  Ricky D. Gaston ,  Subhash P. Khanapure ,  L. Gordon Letts ,  Chia-En Lin ,  Ramani R. Ranatunge ,  Stewart K. Richardson ,  Joseph D. Schroeder ,  Cheri A. Stevenson ,  Shiow-Jyi Wey

发明人： Richard Earl ,  Maiko Ezawa ,  Xinquin Fang ,  David S. Garvey ,  Ricky D. Gaston ,  Subhash P. Khanapure ,  L. Gordon Letts ,  Chia-En Lin ,  Ramani R. Ranatunge ,  Stewart K. Richardson ,  Joseph D. Schroeder ,  Cheri A. Stevenson ,  Shiow-Jyi Wey

IPC分类号： A61K31/216 ,  A61K31/34 ,  A61K31/662 ,  A61K31/357 ,  A61K31/445 ,  A61K31/27 ,  A61K31/495 ,  A61K31/405 ,  A61K31/56 ,  A61K31/401 ,  A61P1/00 ,  A61P1/04 ,  A61P35/02 ,  A61P31/04 ,  A61P9/00 ,  A61P29/00 ,  A61P19/02 ,  A61P11/06 ,  A61P35/00 ,  A61P25/28

CPC分类号： C07D493/04 ,  C07C291/02 ,  C07C311/17 ,  C07C317/18 ,  C07C323/12 ,  C07C327/28 ,  C07D209/18 ,  C07D211/22 ,  C07D211/56

摘要： The invention also provides methods for treating inflammation, pain and fever; for treating gastrointestinal disorders; for facilitating wound healing; for treating and/or preventing gastrointestinal, renal and/or respiratory toxicities resulting from the use of nonsteroidal antiinflammatory compounds; for treating inflammatory disease states and/or disorders; and for treating and/or preventing ophthalmic diseases and/or disorders comprising administration of novel compositions comprising at least one nitrosated NSAID, and, optionally, at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent.

摘要翻译： 本发明还提供了治疗炎症，疼痛和发烧的方法; 用于治疗胃肠道疾病; 促进伤口愈合; 用于治疗和/或预防由使用非甾体抗炎化合物引起的胃肠道，肾脏和/或呼吸道毒性物质; 用于治疗炎性疾病状态和/或病症; 以及用于治疗和/或预防眼科疾病和/或病症，包括施用包含至少一种亚硝化NSAID的新组合物，和任选地至少一种捐赠，转移或释放一氧化氮的化合物，提高内源性内皮水平的内源性放松 因子，刺激一氧化氮的内源性合成或者是一氧化氮合酶和/或至少一种治疗剂的底物。