公开(公告)号：US06271359B1

公开(公告)日：2001-08-07

申请号：US09291902

申请日：1999-04-14

申请人： James Norris ,  Gary Clawson ,  Caroline Westwater ,  David Schofield ,  Michael Schmidt ,  Brian Hoel ,  Joseph Dolan ,  Wei-Hua Pan

发明人： James Norris ,  Gary Clawson ,  Caroline Westwater ,  David Schofield ,  Michael Schmidt ,  Brian Hoel ,  Joseph Dolan ,  Wei-Hua Pan

IPC分类号： C07H2102

CPC分类号： C12N15/113 ,  A61K38/00 ,  A61K48/00 ,  C12N15/74 ,  C12N2310/111 ,  C12N2310/12 ,  C12N2799/021

摘要： The present invention relates to the discovery, identification and characterization of toxic agents which are lethal to pathogens and methods for targeting such toxic agents to a pathogen or pathogen infected cells in order to treat and/or eradicate the infection. In particular, the present invention relates to toxic agents which target bacteria at different stages of the bacterial life cycle, which are delivered alone or in combination to bacteria or bacteria-infected cells. The invention relates to toxic agents which are lethal to diseased cells and methods for targeting such toxic agents to a diseased cell in order to treat and/or eradicate the disease. The present invention relates to promoter elements which are pathogen-specific or tissue-specific and the use of such promoter elements to achieve pathogen-specific or tissue-specific expression of the toxic agent(s) and/or ribozyme(s) of the present invention. Specifically, the invention relates to the delivery of one or more toxic gene products, antisense RNAs, or ribozymes, or combination thereof. The invention provides a novel system by which multiple pathogenic targets may be simultaneously targeted to cause the death of a pathogen, or cell infected with a pathogen. Further, the invention has important implications in the eradication of drug-resistant bacterium and bacterial pathogens. The invention provides a novel system by which multiple targets may be simultaneously targeted to cause the death of a diseased cell. The invention also has important implications in the eradication of drug-resistant pathogens and drug-resistant diseased cells (such as cancer cells).

摘要翻译： 本发明涉及对病原体致死的毒性试剂的发现，鉴定和表征以及将这些毒性试剂靶向病原体或病原体感染的细胞以便治疗和/或根除感染的方法。 特别地，本发明涉及针对细菌生命周期不同阶段的细菌的毒性试剂，它们单独或组合递送至细菌或细菌感染细胞。 本发明涉及对患病细胞致死的毒物剂和用于将这些毒物剂靶向病变细胞以便治疗和/或根除疾病的方法。 本发明涉及作为病原体特异性或组织特异性的启动子元件以及这些启动子元件用于实现本发明的毒性剂和/或核酶的病原体特异性或组织特异性表达的启动子元件 发明。 具体地，本发明涉及递送一种或多种有毒基因产物，反义RNA或核酶或其组合。 本发明提供了一种新的系统，通过该系统可以同时靶向多种致病性靶标以引起病原体或感染病原体的细胞的死亡。 此外，本发明对消除耐药细菌和细菌病原体具有重要的意义。 本发明提供了一种新颖的系统，通过该系统可以同时靶向多个靶标以引起患病细胞的死亡。 本发明也对消除耐药病原体和耐药性疾病细胞（如癌细胞）具有重要意义。

公开(公告)号：US20050107326A1

公开(公告)日：2005-05-19

申请号：US10935962

申请日：2004-09-08

申请人： James Norris ,  Gary Clawson ,  Caroline Westwater ,  David Schofield ,  Michael Schmidt ,  Brian Hoel ,  Joseph Dolan ,  Wei-Hua Pan

发明人： James Norris ,  Gary Clawson ,  Caroline Westwater ,  David Schofield ,  Michael Schmidt ,  Brian Hoel ,  Joseph Dolan ,  Wei-Hua Pan

IPC分类号： C12N15/09 ,  A61K35/74 ,  A61K35/76 ,  A61K38/00 ,  A61K48/00 ,  A61P31/04 ,  C08K5/20 ,  C08K5/29 ,  C12N7/00 ,  C12N9/00 ,  C12N15/113 ,  C12N15/74 ,  A01K67/00 ,  C07H21/02

CPC分类号： C08K5/20 ,  A61K38/00 ,  A61K48/00 ,  C08K5/29 ,  C12N15/113 ,  C12N15/74 ,  C12N2310/111 ,  C12N2310/12 ,  C12N2310/317 ,  C12N2799/021 ,  C08L69/00

摘要： The present invention relates to the discovery, identification and characterization of toxic agents which are lethal to pathogens and methods for targeting such toxic agents to a pathogen or pathogen infected cells in order to treat and/or eradicate the infection. In particular, the present invention relates to toxic agents which target bacteria at different stages of the bacterial life cycle, which are delivered alone or in combination to bacteria or bacteria-infected cells. The invention relates to toxic agents which are lethal to diseased cells and methods for targeting such toxic agents to a diseased cell in order to treat and/or eradicate the disease. The present invention relates to promoter elements which are pathogen-specific or tissue-specific and the use of such promoter elements to achieve pathogen-specific or tissue-specific expression of the toxic agent(s) and/or ribozyme(s) of the present invention. Specifically, the invention relates to the delivery of one or more toxic gene products, antisense RNAs, or ribozymes, or combination thereof. The invention provides a novel system by which multiple pathogenic targets may be simultaneously targeted to cause the death of a pathogen, or cell infected with a pathogen. Further, the invention has important implications in the eradication of drug-resistant bacterium and bacterial pathogens. The invention provides a novel system by which multiple targets may be simultaneously targeted to cause the death of a diseased cell. The invention has important implications in the eradication of drug-resistant pathogens (such as antibiotic resistant bacteria) and drug-resistant diseased cells (such as drug-resistant cancer cells).

摘要翻译： 本发明涉及对病原体致死的毒性试剂的发现，鉴定和表征以及将这些毒性试剂靶向病原体或病原体感染的细胞以便治疗和/或根除感染的方法。 特别地，本发明涉及针对细菌生命周期不同阶段的细菌的毒性试剂，它们单独或组合递送至细菌或细菌感染细胞。 本发明涉及对患病细胞致死的毒物剂和用于将这些毒物剂靶向病变细胞以便治疗和/或根除疾病的方法。 本发明涉及作为病原体特异性或组织特异性的启动子元件以及这些启动子元件用于实现本发明的毒性剂和/或核酶的病原体特异性或组织特异性表达的启动子元件 发明。 具体地，本发明涉及递送一种或多种有毒基因产物，反义RNA或核酶或其组合。 本发明提供了一种新的系统，通过该系统可以同时靶向多种致病性靶标以引起病原体或感染病原体的细胞的死亡。 此外，本发明对消除耐药细菌和细菌病原体具有重要的意义。 本发明提供了一种新颖的系统，通过该系统可以同时靶向多个靶标以引起患病细胞的死亡。 本发明对消除耐药性病原体（如抗生素抗性细菌）和耐药性疾病细胞（如耐药性癌细胞）具有重要意义。

公开(公告)号：US20060223774A1

公开(公告)日：2006-10-05

申请号：US11375690

申请日：2006-03-13

申请人： James Norris ,  Caroline Westwater ,  David Schofield ,  Michael Schmidt ,  Brian Hoel ,  Joseph Dolan ,  Gary Clawson ,  Wei-Hua Pan

发明人： James Norris ,  Caroline Westwater ,  David Schofield ,  Michael Schmidt ,  Brian Hoel ,  Joseph Dolan ,  Gary Clawson ,  Wei-Hua Pan

IPC分类号： A61K48/00 ,  C07H21/02

CPC分类号： C12N15/1131 ,  A61K38/00 ,  C12N15/113 ,  C12N15/74 ,  C12N2310/111 ,  C12N2310/12 ,  C12N2310/317 ,  C12Q1/6811 ,  C12Q2521/337

摘要： The present invention relates to the discovery, identification and characterization of toxic agents which are lethal to pathogens and methods for targeting such toxic agents to a pathogen or pathogen infected cells in order to treat and/or eradicate the infection. In particular, the present invention relates to toxic agents which target bacteria at different stages of the bacterial life cycle, which are delivered alone or in combination to bacteria or bacteria-infected cells. The invention relates to toxic agents which are lethal to diseased cells and methods for targeting such toxic agents to a diseased cell in order to treat and/or eradicate the disease. The present invention relates to promoter elements which are pathogen-specific or tissue-specific and the use of such promoter elements to achieve pathogen-specific or tissue-specific expression of the toxic agent(s) and/or ribozyme(s) of the present invention. Specifically, the invention relates to the delivery of one or more toxic gene products, antisense RNAs, or ribozymes, or combination thereof. The invention provides a novel system by which multiple pathogenic targets may be simultaneously targeted to cause the death of a pathogen, or cell infected with a pathogen. Further, the invention has important implications in the eradication of drug-resistant bacterium and bacterial pathogens. The invention provides a novel system by which multiple targets may be simultaneously targeted to cause the death of a diseased cell. The invention has important implications in the eradication of drug-resistant pathogens (such as antibiotic resistant bacteria) and drug-resistant diseased cells (such as drug-resistant cancer cells).

摘要翻译： 本发明涉及对病原体致死的毒性试剂的发现，鉴定和表征以及将这些毒性试剂靶向病原体或病原体感染的细胞以便治疗和/或根除感染的方法。 特别地，本发明涉及针对细菌生命周期不同阶段的细菌的毒性试剂，它们单独或组合递送至细菌或细菌感染细胞。 本发明涉及对患病细胞致死的毒物剂和用于将这些毒物剂靶向病变细胞以便治疗和/或根除疾病的方法。 本发明涉及作为病原体特异性或组织特异性的启动子元件以及这些启动子元件用于实现本发明的毒性剂和/或核酶的病原体特异性或组织特异性表达的启动子元件 发明。 具体地，本发明涉及递送一种或多种有毒基因产物，反义RNA或核酶或其组合。 本发明提供了一种新的系统，通过该系统可以同时靶向多种致病性靶标以引起病原体或感染病原体的细胞的死亡。 此外，本发明对消除耐药细菌和细菌病原体具有重要的意义。 本发明提供了一种新颖的系统，通过该系统可以同时靶向多个靶标以引起患病细胞的死亡。 本发明对消除耐药性病原体（如抗生素抗性细菌）和耐药性疾病细胞（如耐药性癌细胞）具有重要意义。

公开(公告)号：US07575918B2

公开(公告)日：2009-08-18

申请号：US10935962

申请日：2004-09-08

申请人： James Norris ,  Gary Clawson ,  Caroline Westwater ,  David Schofield ,  Michael G. Schmidt ,  Brian Hoel ,  Joseph Dolan ,  Wei-Hua Pan

发明人： James Norris ,  Gary Clawson ,  Caroline Westwater ,  David Schofield ,  Michael G. Schmidt ,  Brian Hoel ,  Joseph Dolan ,  Wei-Hua Pan

IPC分类号： C07H21/04 ,  C07H21/02 ,  C12Q1/68 ,  A61K31/70

CPC分类号： C08K5/20 ,  A61K38/00 ,  A61K48/00 ,  C08K5/29 ,  C12N15/113 ,  C12N15/74 ,  C12N2310/111 ,  C12N2310/12 ,  C12N2310/317 ,  C12N2799/021 ,  C08L69/00

摘要： The present invention relates to the discovery, identification and characterization of toxic agents which are lethal to pathogens and methods for targeting such toxic agents to a pathogen or pathogen infected cells in order to treat and/or eradicate the infection. In particular, the present invention relates to toxic agents which target bacteria at different stages of the bacterial life cycle, which are delivered alone or in combination to bacteria or bacteria-infected cells. The invention relates to toxic agents which are lethal to diseased cells and methods for targeting such toxic agents to a diseased cell in order to treat and/or eradicate the disease. The present invention relates to promoter elements which are pathogen-specific or tissue-specific and the use of such promoter elements to achieve pathogen-specific or tissue-specific expression of the toxic agent(s) and/or ribozyme(s) of the present invention. Specifically, the invention relates to the delivery of one or more toxic gene products, antisense RNAs, or ribozymes, or combination thereof. The invention provides a novel system by which multiple pathogenic targets may be simultaneously targeted to cause the death of a pathogen, or cell infected with a pathogen. Further, the invention has important implications in the eradication of drug-resistant bacterium and bacterial pathogens. The invention provides a novel system by which multiple targets may be simultaneously targeted to cause the death of a diseased cell. The invention has important implications in the eradication of drug-resistant pathogens (such as antibiotic resistant bacteria) and drug-resistant diseased cells (such as drug-resistant cancer cells).

摘要翻译： 本发明涉及对病原体致死的毒性试剂的发现，鉴定和表征以及将这些毒性试剂靶向病原体或病原体感染的细胞以便治疗和/或根除感染的方法。 特别地，本发明涉及针对细菌生命周期不同阶段的细菌的毒性试剂，它们单独或组合递送至细菌或细菌感染细胞。 本发明涉及对患病细胞致死的毒物剂和用于将这些毒物剂靶向病变细胞以便治疗和/或根除疾病的方法。 本发明涉及作为病原体特异性或组织特异性的启动子元件以及这些启动子元件用于实现本发明的毒性剂和/或核酶的病原体特异性或组织特异性表达的启动子元件 发明。 具体地，本发明涉及递送一种或多种有毒基因产物，反义RNA或核酶或其组合。 本发明提供了一种新的系统，通过该系统可以同时靶向多种致病性靶标以引起病原体或感染病原体的细胞的死亡。 此外，本发明对消除耐药细菌和细菌病原体具有重要的意义。 本发明提供了一种新颖的系统，通过该系统可以同时靶向多个靶标以引起患病细胞的死亡。 本发明对消除耐药性病原体（如抗生素抗性细菌）和耐药性疾病细胞（如耐药性癌细胞）具有重要意义。

公开(公告)号：US20050118719A1

公开(公告)日：2005-06-02

申请号：US10494880

申请日：2002-11-07

申请人： Michael Schmidt ,  David Schofield ,  Caroline Westwater ,  Joseph Dolan ,  Brian Hoel ,  Philip Werner ,  James Norris ,  Laura Kasman

发明人： Michael Schmidt ,  David Schofield ,  Caroline Westwater ,  Joseph Dolan ,  Brian Hoel ,  Philip Werner ,  James Norris ,  Laura Kasman

IPC分类号： C07K14/01 ,  C12N1/21 ,  C12N15/63 ,  C12N15/73 ,  C12N15/74 ,  C07H21/04

CPC分类号： C12N15/74 ,  C07K14/005 ,  C12N15/63 ,  C12N15/635 ,  C12N15/73 ,  C12N2795/10122

摘要： The invention provides methods and materials involved in delivering nucleic acid to cells and regulating expression of nucleic acid in cells.

摘要翻译： 本发明提供了将核酸递送至细胞并调节核酸在细胞中的表达所涉及的方法和材料。

公开(公告)号：US20060272546A1

公开(公告)日：2006-12-07

申请号：US10558072

申请日：2004-04-07

申请人： Clive Foster ,  David Schofield ,  Helen O'Shaughnessy

发明人： Clive Foster ,  David Schofield ,  Helen O'Shaughnessy

IPC分类号： C09D11/00 ,  C09D11/02 ,  C07D221/22

CPC分类号： C09K19/3483 ,  C09B5/62 ,  C09D11/328 ,  C09K19/60 ,  C09K19/606

摘要： An ink comprising a liquid medium and a colorant, wherein the liquid medium comprises water and a water-miscible organic solvent and the colorant is of Formula (1), wherein the colorant is dissolved in the liquid medium: Formula (1) wherein: each independently is a water-solubilising group selected from sulfo, carboxy, phosphato and poly(ethylene oxide); each Z independently is optionally substituted alkyl, optionally substituted aryl or optionally substituted aralkyl; each Q independently is a direct bond or —NR— wherein R is H, optionally substituted aryl or optionally substituted alkyl; rings A,B,C and D are each independently unsubstituted or carry a substituent selected from optionally substituted alkyl, optionally substituted aryl and optionally substituted aralkyl; each n independently is from 1 to 3; and each m independently is 0, 1 or 2; provided that when either or both of the groups represented by Q is a direct bond then at least one n has a value of at least 2. Also colourants and ink-jet printing processes, cartridges and prints.

摘要翻译： 一种包含液体介质和着色剂的油墨，其中所述液体介质包括水和水混溶性有机溶剂，并且所述着色剂具有式（1），其中所述着色剂溶解在液体介质中：式（1）其中： 独立地是选自磺基，羧基，磷酸酯和聚（环氧乙烷）的水溶性基团; 每个Z独立地是任选取代的烷基，任选取代的芳基或任选取代的芳烷基; 每个Q独立地是直接键或-NR-，其中R是H，任选取代的芳基或任选取代的烷基; 环A，B，C和D各自独立地是未取代的或携带选自任选取代的烷基，任选取代的芳基和任选取代的芳烷基的取代基; 每个n独立地为1至3; 并且每个m独立地为0,1或2; 条件是当由Q表示的基团中的任一个或两个是直接键合时，至少一个n的值至少为2.还有着色剂和喷墨印刷方法，墨盒和印刷品。

公开(公告)号：US4663343A

公开(公告)日：1987-05-05

申请号：US756634

申请日：1985-07-19

申请人： David C. Horwell ,  David Schofield

发明人： David C. Horwell ,  David Schofield

IPC分类号： C07D295/135 ,  C07D207/06 ,  A61K31/40

CPC分类号： C07D295/135

摘要： Substituted naphthalenyloxy- or naphthalenylthiooxyamides of trans-1,2-diaminocyclohexanes possess selective kappa opioid receptor site binding activity and are thus useful as analgesic or diuretic agents. Methods of preparing the compounds, pharmaceutical compositions, and a method for their use as analgesic agents are also disclosed.

摘要翻译： 反式-1,2-二氨基环己烷的取代萘氧基或萘基硫代氧酰胺具有选择性κ阿片受体位点结合活性，因此可用作止痛剂或利尿剂。 还公开了制备化合物的方法，药物组合物及其用作止痛剂的方法。

公开(公告)号：US20070276132A1

公开(公告)日：2007-11-29

申请号：US10583272

申请日：2004-12-06

申请人： Clive Foster ,  David Schofield ,  Julie Downey ,  Neil Burnham ,  Philip Double ,  Roy Bradbury

发明人： Clive Foster ,  David Schofield ,  Julie Downey ,  Neil Burnham ,  Philip Double ,  Roy Bradbury

IPC分类号： C07C245/08

CPC分类号： C07D251/20 ,  C09B31/072

摘要： A compound of Formula (1) and salts thereof: wherein: Q is an optionally substituted aryl ring; Y is CO2H, SO3H or PO3H2; R and X are substituents; m is 0 to 3; n is 0 to 6; and q is 0 to 6. Also compositions comprising these compounds, ink-jet inks, an ink jet process and an ink-jet cartridge.

摘要翻译： 式（1）的化合物及其盐：其中：Q是任选取代的芳基环; Y是CO 2 H，SO 3 H或PO 3 H 2 H; R和X是取代基; m为0〜3; n为0〜6; 和q为0至6.还包含这些化合物的组合物，喷墨油墨，喷墨工艺和喷墨墨盒。

公开(公告)号：US06479714B1

公开(公告)日：2002-11-12

申请号：US09242899

申请日：1999-02-26

申请人： David Schofield ,  Mark Bailey ,  Michael John Monteith

发明人： David Schofield ,  Mark Bailey ,  Michael John Monteith

IPC分类号： C07C2700

CPC分类号： C07C29/147 ,  C07C31/22

摘要： A process for the preparation of butane triols is provided. In the process, a malic acid diester is reduced with sodium borohydride in the presence of an ether and an alcohol. Preferably, the malic acid diester is an ethyl or methyl ester, the ether is tetrahydrofuran or bis(2-methoxyethyl) ether (diglyme), and the alcohol comprises ethanol. Advantageously, the reaction is carried out at ambient temperature.

摘要翻译： 提供了制备丁三醇的方法。 在此过程中，在醚和醇的存在下，用硼氢化钠还原苹果酸二酯。 优选地，苹果酸二酯是乙基或甲酯，醚是四氢呋喃或双（2-甲氧基乙基）醚（二甘醇二甲醚），醇包括乙醇。 有利地，反应在环境温度下进行。

公开(公告)号：US4786747A

公开(公告)日：1988-11-22

申请号：US48505

申请日：1987-05-11

申请人： John D. Jones ,  David Schofield

发明人： John D. Jones ,  David Schofield

IPC分类号： C07C255/29 ,  C07C67/00 ,  C07C253/00 ,  C07C255/24 ,  C07C255/30 ,  C07C255/32 ,  C07C255/58 ,  C07C323/24 ,  C07D319/18 ,  C07C121/66

CPC分类号： C07C255/00

摘要： Benzamides of the formula (I): ##STR1## in which Ar is optionally substituted aryl; X is O, S or NH and R is optionally substituted alkyl or alkenyl when X is O or S, or is optionally substituted alkanoyl when X is NH, are prepared by(a) reacting a compound of the formula (II):ArCONHCH.sub.2 CN (II) with a brominating agent in a solvent which is substantially chemically inert to the reactants and in which compound (II) is soluble, to form a compound of the formula (III): ##STR2## and (b) reacting the compound (III) with a compound RXH.Preferably, bromination is carried out rapidly in dried ethyl acetate.The process avoids hydration of the CN group of the compound (III) to a carbamoyl group obviating a subsequent dehydration step later.The intermediate compound (III) is novel.The substituted benzamides are useful as herbicides and fungicides.