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1. 发明申请

US20050261228A1 Antisense modulation of interleukin 12 P35 subunit expression 审中-公开
标题翻译：白细胞介素12 P35亚基表达的反义调制
公开(公告)号：US20050261228A1
公开(公告)日：2005-11-24
申请号：US11089191
申请日：2005-03-23
申请人： C. Bennett , Brenda Baker , Susan Freier , Susan Gregory , Ronnie Hanecak , Kevin Anderson , Ming-Yi Chiang , Vickie Brown-Driver , David Ecker , Timothy Vickers , Jacqueline Wyatt , Eric Marcusson , Nicholas Dean , Sanjay Bhanot , Elizabeth Ackermann , Lex Cowsert
发明人： C. Bennett , Brenda Baker , Susan Freier , Susan Gregory , Ronnie Hanecak , Kevin Anderson , Ming-Yi Chiang , Vickie Brown-Driver , David Ecker , Timothy Vickers , Jacqueline Wyatt , Eric Marcusson , Nicholas Dean , Sanjay Bhanot , Elizabeth Ackermann , Lex Cowsert
IPC分类号： A61K38/00 , A61K48/00 , C07H21/04 , C12N15/113 , C12N15/85
CPC分类号： C12N15/1136 , A61K38/00 , C12N2310/315 , C12N2310/321 , C12N2310/3341 , C12N2310/341 , C12N2310/346 , Y02P20/582 , C12N2310/3525
摘要： Compounds, compositions and methods are provided for modulating the expression of Interleukin 12 p35 subunit. The compositions comprise chemically modified antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Interleukin 12 p35 subunit. Methods of using these compounds for modulation of Interleukin 12 p35 subunit expression and for treatment of diseases associated with expression of Interleukin 12 p35 subunit are provided.
摘要翻译：提供化合物，组合物和方法用于调节白细胞介素12p35亚基的表达。组合物包含靶向编码白细胞介素12p35亚基的核酸的化学修饰的反义化合物，特别是反义寡核苷酸。提供了使用这些化合物调节白介素12p35亚基表达和治疗与白细胞介素12p35亚基表达相关的疾病的方法。

2. 发明申请

US20060154885A1 Modulation of SLC26A2 expression 审中-公开
标题翻译：调控SLC26A2表达
公开(公告)号：US20060154885A1
公开(公告)日：2006-07-13
申请号：US11072846
申请日：2005-03-04
申请人： C. Bennett , Brett Monia , Nicholas Dean , Xiaoxing Xu , Sanjay Bhanot , Brenda Baker , Susan Freier , Lex Cowsert , Robert McKay , Muthiah Manoharan , F. Dorr , Jon Holmlund , Alexander Borchers , Vickie Brown-Driver , Jacqueline Wyatt , Shin Flournoy , Elizabeth Ackermann , Hong Zhang , Andrew Watt , Eric Maracusson , Scott Cooper , Erich Koller , Loren Miraglia , William Ricketts , Kenneth Dobie , Tamara Sipes
发明人： C. Bennett , Brett Monia , Nicholas Dean , Xiaoxing Xu , Sanjay Bhanot , Brenda Baker , Susan Freier , Lex Cowsert , Robert McKay , Muthiah Manoharan , F. Dorr , Jon Holmlund , Alexander Borchers , Vickie Brown-Driver , Jacqueline Wyatt , Shin Flournoy , Elizabeth Ackermann , Hong Zhang , Andrew Watt , Eric Maracusson , Scott Cooper , Erich Koller , Loren Miraglia , William Ricketts , Kenneth Dobie , Tamara Sipes
IPC分类号： A61K48/00 , C07H21/02
CPC分类号： C12N15/1138 , A61K48/00 , C12N2310/11 , C12N2310/315 , C12N2310/321 , C12N2310/3341 , C12N2310/341 , C12N2310/346 , C12N2310/3525
摘要： Compounds, compositions and methods are provided for modulating the expression of SLC26A2. The compositions comprise oligonucleotides, targeted to nucleic acid encoding SLC26A2. Methods of using these compounds for modulation of SLC26A2 expression and for diagnosis and treatment of disease associated with expression of SLC26A2 are provided.
摘要翻译：提供化合物，组合物和方法用于调节SLC26A2的表达。组合物包含针对编码SLC26A2的核酸的寡核苷酸。提供了使用这些化合物调节SLC26A2表达和用于诊断和治疗与SLC26A2表达相关的疾病的方法。

3. 发明申请

US20070015723A1 Antiviral oligonucleotides having a conserved G4 core sequence 审中-公开
标题翻译：具有保守G4核心序列的抗病毒寡核苷酸
公开(公告)号：US20070015723A1
公开(公告)日：2007-01-18
申请号：US11436901
申请日：2006-05-17
申请人： Ronnie Hanecak , Kevin Anderson , C. Bennett , Ming-Yi Chiang , Vickie Brown-Driver , David Ecker , Timothy Vickers , Jacqueline Wyatt
发明人： Ronnie Hanecak , Kevin Anderson , C. Bennett , Ming-Yi Chiang , Vickie Brown-Driver , David Ecker , Timothy Vickers , Jacqueline Wyatt
IPC分类号： A61K48/00
CPC分类号： A61K31/70 , A61K38/00 , C07H21/00 , C12N15/1133 , C12N15/1137 , C12N15/115 , C12N15/117 , C12N2310/151 , C12N2310/18 , C12N2310/315 , C12N2310/321 , C12N2310/341 , C12N2310/346 , C12Q1/701 , C12Y207/07049 , C12Y301/01004 , C12N2310/3521
摘要： Modified oligonucleotides having a conserved G4 sequence and a sufficient number of flanking nucleotides to significantly inhibit the activity of a virus or phospholipase A2 or to modulate the telomere length of a chromosome are provided. G4 quartet oligonucleotide structures are also provided. Methods of prophylaxis, diagnostics and therapeutics for viral-associated diseases and diseases associated with elevated levels of phospholipase A2 are also provided. Methods of modulating telomere length of a chromosome are also provided; modulation of telomere length is believed to play a role in the aging process of a cell and in control of malignant cell growth.
摘要翻译：修饰的寡核苷酸具有保守的GAT4序列和足够数量的侧翼核苷酸以显着抑制病毒或磷脂酶A 2的活性或调节染色体的端粒长度被提供。还提供了G 4四重寡核苷酸结构。还提供了与升高的磷脂酶A 2 2水平相关的病毒相关疾病和疾病的预防，诊断和治疗方法。还提供了调节染色体端粒长度的方法; 相信端粒长度的调节在细胞的衰老过程中和恶性细胞生长的控制中起作用。

4. 发明授权

US5698391A Methods for synthetic unrandomization of oligomer fragments 失效
标题翻译：寡聚体片段的合成无规化方法
公开(公告)号：US5698391A
公开(公告)日：1997-12-16
申请号：US357396
申请日：1994-12-16
申请人： Phillip Dan Cook , David J. Ecker , Jacqueline Wyatt , Thomas W. Bruice , Kevin Anderson , Ronnie Hanecak , Timothy Vickers , Peter Davis , Susan M. Freier , Yogesh S. Sanghvi , Vickie Brown-Driver
发明人： Phillip Dan Cook , David J. Ecker , Jacqueline Wyatt , Thomas W. Bruice , Kevin Anderson , Ronnie Hanecak , Timothy Vickers , Peter Davis , Susan M. Freier , Yogesh S. Sanghvi , Vickie Brown-Driver
IPC分类号： C12Q1/68 , G01N33/53 , C12Q1/70
CPC分类号： C12Q1/6811 , G01N33/5308
摘要： Methods useful for the determination of oligomers which have specific activity for a target molecule from a pool of primarily randomly assembled oligomers are provided. The disclosed methods involve repeated syntheses of increasingly simplified sets of oligomers coupled with selection procedures for determining oligomers having the highest activity. Freedom from the use of enzymes allows the application of these methods to any molecules which can be oligomerized in a controlled fashion.
摘要翻译：提供了用于测定从主要随机组装的低聚物库中的靶分子具有比活性的低聚物的方法。所公开的方法涉及重复合成越来越简单的低聚体组合，以及用于确定具有最高活性的寡聚体的选择程序。不使用酶允许将这些方法应用于可以以受控方式低聚的任何分子。

5. 发明申请

US20050244869A1 Modulation of transthyretin expression 审中-公开
标题翻译：转甲状腺素蛋白表达的调节
公开(公告)号：US20050244869A1
公开(公告)日：2005-11-03
申请号：US11097928
申请日：2005-04-01
申请人： Vickie Brown-Driver , Ravi Jain
发明人： Vickie Brown-Driver , Ravi Jain
IPC分类号： A61K48/00 , C07H21/02 , C12N15/113 , C12Q1/68
CPC分类号： C12N15/113 , C12N15/1136 , C12N2310/11 , C12N2310/315 , C12N2310/321 , C12N2310/3341 , C12N2310/341 , C12N2310/346 , C12N2310/3525 , C12Q1/6883 , C12Q2600/136 , C12Q2600/158 , Y10T436/143333
摘要： Compounds, compositions and methods are provided for modulating the expression of transthyretin. The compositions comprise oligonucleotides, targeted to nucleic acid encoding transthyretin. Methods of using these compounds for modulation of transthyretin expression and for diagnosis and treatment of diseases and conditions associated with expression of transthyretin are provided.
摘要翻译：提供化合物，组合物和方法用于调节转甲状腺激素的表达。组合物包含针对核酸编码转甲状腺素蛋白的寡核苷酸。提供了使用这些化合物调节转甲状腺素蛋白表达和用于诊断和治疗与转甲状腺素蛋白表达相关的疾病和病症的方法。

6. 发明申请

US20070178111A1 Identification and application of antibiotic synergy 有权
标题翻译：鉴定和应用抗生素协同作用
公开(公告)号：US20070178111A1
公开(公告)日：2007-08-02
申请号：US11636379
申请日：2006-12-08
申请人： Vickie Brown-Driver , Kedar GC , John Finn , Robert Haselbeck , Mark Hilgers , Karen Shaw , Mark Stidham
发明人： Vickie Brown-Driver , Kedar GC , John Finn , Robert Haselbeck , Mark Hilgers , Karen Shaw , Mark Stidham
IPC分类号： A61K48/00 , A61K39/40 , A61K31/43 , A61K31/545
CPC分类号： A61K31/43 , A61K31/545 , A61K39/40 , A61K45/06 , Y02A50/469 , Y02A50/47 , Y02A50/482 , Y02A50/484 , A61K2300/00
摘要： The present invention provides a pharmaceutical composition useful for treating bacterial infections in humans and animals which comprises administering to a human or animal in need thereof, an antibacterially effective combination of a β-lactam antibiotic and an inhibitor of any bacterial peptidoglycan biosynthesis enzyme, especially GlmU, GlmU, MurA, MurB, MurC, MurD, MurE, MurF, MurG, MraY, and UppS. Further provided is a method of discovering synergists for antibiotics including: a) expressing in a cell an antisense nucleic acid against a nucleic acid encoding a gene product so as to reduce the activity or amount of the gene product in the cell, thereby producing a cell sensitized to an antibiotic; b) characterizing the sensitization of the cell to the antibiotic and selecting pairs of antibiotics and genes that result in antibiotic efficacy at one-fifth or less the concentration required in the absence of the antisense gene; c) screening for chemical compounds that inhibit the gene product corresponding to the selected synergistic gene; and d) selecting or creating chemical analogs that inhibit the gene product corresponding to the selected synergistic gene such that the inhibition occurs in the bacteria.
摘要翻译：本发明提供了用于治疗人和动物细菌感染的药物组合物，其包括对有需要的人或动物施用β-内酰胺抗生素和任何细菌肽聚糖生物合成酶的抑制剂的抗菌有效组合，特别是GlmU ，GlmU，MurA，MurB，MurC，MurD，MurE，MurF，MurG，MraY和UppS。进一步提供了发现抗生素增效剂的方法，包括：a）在细胞中表达反义核酸对抗编码基因产物的核酸，以降低细胞中基因产物的活性或数量，从而产生细胞对抗生素敏感; b）表征细胞对抗生素的致敏性，并选择一组抗生素和基因，其抗生素效力为不存在反义基因所需浓度的五分之一或更低。 c）筛选抑制与所选协同基因相对应的基因产物的化合物; 和d）选择或产生抑制与所选择的协同基因相对应的基因产物的化学类似物，使得在细菌中发生抑制。

7. 发明授权

US08298543B2 Identification and application of antibiotic synergy 有权
标题翻译：鉴定和应用抗生素协同作用
公开(公告)号：US08298543B2
公开(公告)日：2012-10-30
申请号：US13102856
申请日：2011-05-06
申请人： Vickie Brown-Driver , Kedar GC , John M. Finn , Robert Haselbeck , Mark Hilgers , Karen Shaw , Mark Stidham
发明人： Vickie Brown-Driver , Kedar GC , John M. Finn , Robert Haselbeck , Mark Hilgers , Karen Shaw , Mark Stidham
IPC分类号： A61K31/00 , A61K31/43 , A61K39/00
CPC分类号： A61K31/43 , A61K31/545 , A61K39/40 , A61K45/06 , Y02A50/469 , Y02A50/47 , Y02A50/482 , Y02A50/484 , A61K2300/00
摘要： The present invention provides a pharmaceutical composition useful for treating bacterial infections in humans and animals which comprises administering to a human or animal in need thereof, an antibacterially effective combination of a β-lactam antibiotic and an inhibitor of any bacterial peptidoglycan biosynthesis enzyme, especially GlmU, GlmU, MurA, MurB, MurC, MurD, MurE, MurF, MurG, MraY, and UppS. Further provided is a method of discovering synergists for antibiotics including: a) expressing in a cell an antisense nucleic acid against a nucleic acid encoding a gene product so as to reduce the activity or amount of the gene product in the cell, thereby producing a cell sensitized to an antibiotic; b) characterizing the sensitization of the cell to the antibiotic and selecting pairs of antibiotics and genes that result in antibiotic efficacy at one-fifth or less the concentration required in the absence of the antisense gene; c) screening for chemical compounds that inhibit the gene product corresponding to the selected synergistic gene; and d) selecting or creating chemical analogs that inhibit the gene product corresponding to the selected synergistic gene such that the inhibition occurs in the bacteria.
摘要翻译：本发明提供了一种可用于治疗人和动物细菌感染的药物组合物，其包括对有需要的人或动物施用抗生素有效组合的β-内酰胺抗生素和任何细菌肽聚糖生物合成酶的抑制剂，特别是 GlmU，GlmU，MurA，MurB，MurC，MurD，MurE，MurF，MurG，MraY，和UppS。进一步提供了发现抗生素增效剂的方法，包括：a）在细胞中表达反义核酸对编码基因产物的核酸，以降低细胞中基因产物的活性或数量，从而产生细胞对抗生素敏感; b）表征细胞对抗生素的致敏性，并选择一组抗生素和基因，其抗生素效力为不存在反义基因所需浓度的五分之一或更低。 c）筛选抑制与所选协同基因相对应的基因产物的化合物; 和d）选择或产生抑制与所选择的协同基因相对应的基因产物的化学类似物，使得在细菌中发生抑制。

8. 发明申请

US20110294774A1 IDENTIFICATION AND APPLICATION OF ANTIBIOTIC SYNERGY 有权
标题翻译：抗生素合成的鉴定与应用
公开(公告)号：US20110294774A1
公开(公告)日：2011-12-01
申请号：US13102856
申请日：2011-05-06
申请人： Vickie Brown-Driver , Kedar GC , John M. Finn , Robert Haselbeck , Mark Hilgers , Karen Shaw , Mark Stidham
发明人： Vickie Brown-Driver , Kedar GC , John M. Finn , Robert Haselbeck , Mark Hilgers , Karen Shaw , Mark Stidham
IPC分类号： A61K31/545 , A61P31/04 , A61K31/43 , A61K31/431 , A61K31/546 , A61K31/5365
CPC分类号： A61K31/43 , A61K31/545 , A61K39/40 , A61K45/06 , Y02A50/469 , Y02A50/47 , Y02A50/482 , Y02A50/484 , A61K2300/00
摘要： The present invention provides a pharmaceutical composition useful for treating bacterial infections in humans and animals which comprises administering to a human or animal in need thereof, an antibacterially effective combination of a β-lactam antibiotic and an inhibitor of any bacterial peptidoglycan biosynthesis enzyme, especially GlmU, GlmU, MurA, MurB, MurC, MurD, MurE, MurF, MurG, MraY, and UppS. Further provided is a method of discovering synergists for antibiotics including: a) expressing in a cell an antisense nucleic acid against a nucleic acid encoding a gene product so as to reduce the activity or amount of the gene product in the cell, thereby producing a cell sensitized to an antibiotic; b) characterizing the sensitization of the cell to the antibiotic and selecting pairs of antibiotics and genes that result in antibiotic efficacy at one-fifth or less the concentration required in the absence of the antisense gene; c) screening for chemical compounds that inhibit the gene product corresponding to the selected synergistic gene; and d) selecting or creating chemical analogs that inhibit the gene product corresponding to the selected synergistic gene such that the inhibition occurs in the bacteria.
摘要翻译：本发明提供了一种可用于治疗人和动物细菌感染的药物组合物，其包括对有需要的人或动物施用抗生素有效组合的β-内酰胺抗生素和任何细菌肽聚糖生物合成酶的抑制剂，特别是 GlmU，GlmU，MurA，MurB，MurC，MurD，MurE，MurF，MurG，MraY和UppS。进一步提供了发现抗生素增效剂的方法，包括：a）在细胞中表达反义核酸对抗编码基因产物的核酸，以降低细胞中基因产物的活性或数量，从而产生细胞对抗生素敏感; b）表征细胞对抗生素的致敏性，并选择一组抗生素和基因，其抗生素效力为不存在反义基因所需浓度的五分之一或更低。 c）筛选抑制与所选协同基因相对应的基因产物的化合物; 和d）选择或产生抑制与所选择的协同基因相对应的基因产物的化学类似物，使得在细菌中发生抑制。

9. 发明授权

US08021665B2 Identification and application of antibiotic synergy 有权
标题翻译：鉴定和应用抗生素协同作用
公开(公告)号：US08021665B2
公开(公告)日：2011-09-20
申请号：US11636379
申请日：2006-12-08
申请人： Vickie Brown-Driver , Kedar GC , John M. Finn , Robert Haselbeck , Mark Hilgers , Karen Shaw , Mark Stidham
发明人： Vickie Brown-Driver , Kedar GC , John M. Finn , Robert Haselbeck , Mark Hilgers , Karen Shaw , Mark Stidham
IPC分类号： A61K31/00 , A61K31/43 , A61K39/00
CPC分类号： A61K31/43 , A61K31/545 , A61K39/40 , A61K45/06 , Y02A50/469 , Y02A50/47 , Y02A50/482 , Y02A50/484 , A61K2300/00
摘要： The present invention provides a pharmaceutical composition useful for treating bacterial infections in humans and animals which comprises administering to a human or animal in need thereof, an antibacterially effective combination of a β-lactam antibiotic and an inhibitor of any bacterial peptidoglycan biosynthesis enzyme, especially GlmU, GlmU, MurA, MurB, MurC, MurD, MurE, MurF, MurG, MraY, and UppS. Further provided is a method of discovering synergists for antibiotics including: a) expressing in a cell an antisense nucleic acid against a nucleic acid encoding a gene product so as to reduce the activity or amount of the gene product in the cell, thereby producing a cell sensitized to an antibiotic; b) characterizing the sensitization of the cell to the antibiotic and selecting pairs of antibiotics and genes that result in antibiotic efficacy at one-fifth or less the concentration required in the absence of the antisense gene; c) screening for chemical compounds that inhibit the gene product corresponding to the selected synergistic gene; and d) selecting or creating chemical analogs that inhibit the gene product corresponding to the selected synergistic gene such that the inhibition occurs in the bacteria.
摘要翻译：本发明提供了一种可用于治疗人和动物细菌感染的药物组合物，其包括对有需要的人或动物施用抗生素有效组合的β-内酰胺抗生素和任何细菌肽聚糖生物合成酶的抑制剂，特别是 GlmU，GlmU，MurA，MurB，MurC，MurD，MurE，MurF，MurG，MraY和UppS。进一步提供了发现抗生素增效剂的方法，包括：a）在细胞中表达反义核酸对抗编码基因产物的核酸，以降低细胞中基因产物的活性或数量，从而产生细胞对抗生素敏感; b）表征细胞对抗生素的致敏性，并选择一组抗生素和基因，其抗生素效力为不存在反义基因所需浓度的五分之一或更低。 c）筛选抑制与所选协同基因相对应的基因产物的化合物; 和d）选择或产生抑制与所选择的协同基因相对应的基因产物的化学类似物，使得在细菌中发生抑制。

10. 发明申请

US20110143359A1 Method for Identifying Drug-Sensitizing Antisense DNA Fragments and Use Thereof 审中-公开
标题翻译：鉴定药物敏感反义DNA片段及其用途的方法
公开(公告)号：US20110143359A1
公开(公告)日：2011-06-16
申请号：US13033128
申请日：2011-02-23
申请人： Robert Haselbeck , Mark Hilgers , Karen Shaw , Vickie Brown-Driver , Kedar GC , John M. Finn , Mark Stidham
发明人： Robert Haselbeck , Mark Hilgers , Karen Shaw , Vickie Brown-Driver , Kedar GC , John M. Finn , Mark Stidham
IPC分类号： C12Q1/68
CPC分类号： C12N15/111 , C12N15/1137 , C12N2310/11 , C12N2320/11 , C12N2330/30 , C12Y101/01158 , C12Y105/01003 , C12Y205/01031 , C12Y601/0101
摘要： The invention provides a method for generating and selecting drug-sensitizing antisense DNA fragments. In one embodiment, the method includes identifying a gene of interest using knowledge of bacterial physiology, biochemistry, genetics, genomics, and other means. The method includes PCR amplification of a gene of interest using genomic DNA as a template; fragmentation of the DNA by sonication or other means; selecting DNA fragments no longer than 400 base pairs; ligating the DNA fragments into a suitable expression plasmid with a selectable marker; transforming the plasmids containing the DNA fragments into the organism from which the gene of interest originated; and selecting clones from transformed cells that show a phenotypic difference of the clone grown in the presence of the inducer relative to the phenotype in the absence of inducer.
摘要翻译：本发明提供了生产和选择药物敏化反义DNA片段的方法。在一个实施方案中，该方法包括使用细菌生理学，生物化学，遗传学，基因组学和其他方法的知识来鉴定感兴趣的基因。该方法包括使用基因组DNA作为模板对感兴趣的基因进行PCR扩增; 通过超声处理或其他方法破碎DNA; 选择不超过400个碱基对的DNA片段; 将DNA片段连接到具有选择性标记的合适的表达质粒中; 将含有DNA片段的质粒转化为目标基因来源的生物体; 并选择来自转化细胞的克隆，其在不存在诱导物的情况下显示在诱导物存在下生长的克隆相对于表型的表型差异。

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