公开(公告)号：US4673680A

公开(公告)日：1987-06-16

申请号：US777472

申请日：1985-09-18

申请人： Robert G. Pendleton

发明人： Robert G. Pendleton

IPC分类号： C07D405/04 ,  A61K31/40 ,  A61K31/435 ,  A61K31/44 ,  A61K31/55 ,  A61K45/00 ,  A61P1/00 ,  A61P1/10 ,  A61P25/02 ,  C07D319/00 ,  C07D471/14 ,  C07D491/14 ,  C07D495/14 ,  C07D513/14 ,  A61K31/505

CPC分类号： C07D471/14 ,  A61K31/40 ,  A61K31/44 ,  A61K31/55 ,  C07D491/14 ,  C07D495/14 ,  C07D513/14

摘要： Selective .alpha..sub.2 -adrenergic receptor antagonists are effective in modifying gastrointestinal motility in a manner useful in the treatment of colonic spasm, irritable bowel syndrome and constipation.

摘要翻译： 选择性α2-肾上腺素能受体拮抗剂在治疗结肠痉挛，肠易激综合征和便秘方面有效地改善胃肠蠕动。

公开(公告)号：US20120072123A1

公开(公告)日：2012-03-22

申请号：US13322931

申请日：2010-05-27

申请人： Duncan Brown ,  Julja Burchard ,  Eugen C. Buehler

发明人： Duncan Brown ,  Julja Burchard ,  Eugen C. Buehler

IPC分类号： G06F19/20

CPC分类号： G16B5/00 ,  G16B20/00

摘要： The present invention provides a method for determining the probability that an RNAi compound modulates the expression level of a gene using a linear regression model. The present invention also provides a method for determining the probabilities that an RNAi compound modulates the expression levels of each gene in a set of genes of interest using the linear regression model. The present invention provides a method for determining the seed-sequence-dependent signature size of an RNAi compound using the linear regression model. The invention provides a method for identifying genes having seed-sequence-dependent silencing effect by an siRNA using the linear regression model. The invention further provides a method for selecting from a plurality of siRNAs one or more siRNAs with higher silencing efficacy, specificity and diversity in silencing a target gene in an organism. The invention also provides a method for determining the coefficients of the above linear regression model.

摘要翻译： 本发明提供了使用线性回归模型确定RNAi化合物调节基因表达水平的可能性的方法。 本发明还提供了使用线性回归模型确定RNAi化合物调节一组感兴趣基因中的每个基因的表达水平的概率的方法。 本发明提供了使用线性回归模型确定RNAi化合物的种子序列依赖性特征大小的方法。 本发明提供一种使用线性回归模型鉴定siRNA的具有种子序列依赖性沉默效应的基因的方法。 本发明还提供了从多个siRNA中选择一种或多种沉默效力，特异性和沉默生物体中靶基因多样性的siRNA的方法。 本发明还提供了一种用于确定上述线性回归模型的系数的方法。

公开(公告)号：US08133670B2

公开(公告)日：2012-03-13

申请号：US10860559

申请日：2004-06-02

申请人： Stephen H Friend ,  Michele A Cleary ,  Kristopher A Kilian ,  Ernest M Coffey ,  Gregory J Hannon ,  Patrick Paddison

发明人： Stephen H Friend ,  Michele A Cleary ,  Kristopher A Kilian ,  Ernest M Coffey ,  Gregory J Hannon ,  Patrick Paddison

IPC分类号： C12Q1/68 ,  C12P19/34 ,  C07H21/02 ,  C07H21/04

CPC分类号： C12Q1/6837 ,  Y10S977/792 ,  C12Q2565/513 ,  C12Q2531/113 ,  C12Q2525/161

摘要： The present invention provides methods of making a population of nucleic acid molecules, wherein each nucleic acid molecule comprises a predetermined nucleic acid sequence, each of said methods comprising the steps of: (a) synthesizing, on a substrate, a population of nucleic acid molecules wherein: i) each synthesized nucleic acid molecule comprises a predetermined nucleic acid sequence; and ii) each synthesized nucleic acid molecule is localized to a defined area of said substrate; (b) harvesting said population of synthesized nucleic acid molecules from said substrate to yield harvested nucleic acid molecules; and (c) introducing said harvested nucleic acid molecules into vector molecules.

摘要翻译： 本发明提供了制备核酸分子群体的方法，其中每个核酸分子包含预定的核酸序列，所述方法中的每一种包括以下步骤：（a）在底物上合成核酸分子群体 其中：i）每个合成的核酸分子包含预定的核酸序列; 和ii）每个合成的核酸分子定位于所述基质的限定区域; （b）从所述底物收获所述合成核酸分子群体以产生收获的核酸分子; 和（c）将所述收获的核酸分子引入载体分子。

公开(公告)号：US20100275625A1

公开(公告)日：2010-11-04

申请号：US12832714

申请日：2010-07-08

申请人： Alan J. Lowenstein

发明人： Alan J. Lowenstein

IPC分类号： F25B49/00

CPC分类号： G06Q50/22 ,  F25D29/00 ,  F25D2400/36 ,  F25D2700/08 ,  F25D2700/12 ,  G06F19/00 ,  G06F19/3462 ,  G06Q10/087 ,  G07F9/026 ,  G07F17/0092

摘要： Intelligent refrigerator system for storing pharmaceutical product containers, such as vials, ampules, syringes, bottles, medication tubes, blister packs and cartons, at the point of dispensing. Embodiments of the invention use product identification technology, such as radio-frequency identification (RFID) tags and readers, to uniquely identify containers as they are added to or removed from the cold storage compartment of the refrigerator, and automatically retrieve from a local or remote database a variety of details associated with the containers and their contents, such as manufacturing data, expiration dates, time out of refrigeration, inventory levels, safety information, usage statistics, known contraindications and warnings, etc. If the details indicate that there is a problem with a particular pharmaceutical (e.g., that it is counterfeit, expired, suspect, spoiled, recalled or almost depleted), then a message or warning is automatically delivered to a human operator via an attached output device, such as a display screen, speaker or printer. Embodiments of the invention may also be configured to monitor and report temperature faults, power failures and other anomalies associated with the refrigerator or cold storage compartment.

摘要翻译： 用于储存医药产品容器的智能冰箱系统，例如小瓶，安瓿，注射器，瓶，药物管，泡罩包装和纸箱。 本发明的实施例使用诸如射频识别（RFID）标签和读取器的产品识别技术来唯一地识别容器，因为它们被添加到冰箱的冷藏室或从冰箱的冷藏室中移除，并且从本地或远程 数据库与容器及其内容相关的各种细节，例如制造数据，有效期限，制冷时间，库存水平，安全信息，使用统计，已知的禁忌症和警告等。如果细节表明存在 特定药物的问题（例如，假冒，过期，怀疑，损坏，召回或几乎耗尽），则通过附加的输出设备（例如显示屏幕，扬声器）自动地向人类操作者传送消息或警告 或打印机。 本发明的实施例还可以被配置为监视和报告与冰箱或冷藏室相关联的温度故障，电源故障和其它异常。

公开(公告)号：US20100222322A1

公开(公告)日：2010-09-02

申请号：US11922682

申请日：2006-06-23

申请人： Scott E. Wolkenberg ,  Zhijian Zhao ,  Craig W. Lindsley

发明人： Scott E. Wolkenberg ,  Zhijian Zhao ,  Craig W. Lindsley

IPC分类号： A61K31/404 ,  A61P31/18 ,  C07D403/12 ,  C07D401/12 ,  A61K31/454 ,  A61K31/496

CPC分类号： A61K31/551 ,  C07D209/42 ,  C07D401/04 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04

摘要： Indole compounds of Formula (I) are HIV reverse transcriptase inhibitors, wherein R1, R2, R3, R4 and R5 are defined herein. The compounds of Formula (I) and their pharmaceutically acceptable salts are useful in the inhibition of HIV reverse transcriptase, the prophylaxis and treatment of infection by HIV and in the prophylaxis, delay in the onset, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

摘要翻译： 式（I）的吲哚化合物是HIV逆转录酶抑制剂，其中R 1，R 2，R 3，R 4和R 5在本文中定义。 式（I）化合物及其药学上可接受的盐可用于抑制HIV逆转录酶，预防和治疗艾滋病毒感染以及预防，延迟发作和治疗艾滋病。 化合物及其盐可以用作药物组合物中的成分，任选与其它抗病毒剂，免疫调节剂，抗生素或疫苗组合使用。

公开(公告)号：US20100197763A1

公开(公告)日：2010-08-05

申请号：US12598570

申请日：2008-05-02

申请人： Vasant Jadhav ,  Ivan Richards ,  Walter Strapps ,  Chandra Vargeese

发明人： Vasant Jadhav ,  Ivan Richards ,  Walter Strapps ,  Chandra Vargeese

IPC分类号： A61K31/713 ,  C07H21/02 ,  A61P11/00

CPC分类号： C12N15/1137 ,  A01K2207/05 ,  A01K2227/105 ,  A01K2267/0368 ,  C12N2310/14 ,  C12N2310/317 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/332 ,  C12N2310/3521

摘要： The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression and/or activity, including PDE4B1, PDE4B2, and PDE4B3 gene expression and/or activity. The present invention is also directed to compounds, compositions, and methods relating to traits, diseases and conditions that respond to the modulation of expression and/or activity of genes involved in cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression pathways or other cellular processes that mediate the maintenance or development of such traits, diseases and conditions, including but not limited to IL-6, IL-7, IL-8, IL-15, TNF-alpha and matrix metalloproteinases (MMPs), such as MMP-I, MMP-2, MMP-3, MMP-9 and MMP-12. Specifically, the invention relates to double stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA), and multifunctional siNA molecules capable of mediating RNA interference (RNAi) against cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression, including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. The present invention also relates to small nucleic acid molecules, such as siNA, siRNA, antisense and others that can inhibit the function of endogenous RNA molecules or RNAi pathway components (RNAi inhibitors), such as endogenous micro-RNA (miRNA) (e.g, miRNA inhibitors) or endogenous short interfering RNA (siRNA), (e.g., siRNA inhibitors) or that can inhibit the function of RISC (e.g., RISC inhibitors), to modulate PDE4B gene expression by interfering with the regulatory function of such endogenous RNAs or proteins associated with such endogenous RNAs (e.g., RISC) including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. Such small nucleic acid molecules are useful, for example, in providing compositions to prevent, inhibit, or reduce inflammatory, respiratory, and autoimmune diseases, traits, and conditions, and/or other disease states associated with PDE4B gene expression or activity in a subject or organism.

公开(公告)号：US20100197630A1

公开(公告)日：2010-08-05

申请号：US12664715

申请日：2008-06-16

申请人： Julianne A. Hunt ,  Rogelio L. Martinez ,  Peter J. Sinclair ,  Ramzi F. Sweis

发明人： Julianne A. Hunt ,  Rogelio L. Martinez ,  Peter J. Sinclair ,  Ramzi F. Sweis

IPC分类号： A61K31/714 ,  C07D263/57 ,  A61K31/423 ,  C07F5/02 ,  A61K31/69 ,  C07D413/12 ,  A61K31/4439 ,  C07D417/12 ,  A61K31/427 ,  A61K31/5377 ,  A61K31/496 ,  A61P9/10 ,  A61K31/455 ,  A61K31/519

CPC分类号： C07D263/57 ,  C07D413/12 ,  C07D417/12 ,  C07F5/025

摘要： Compounds having the structure of Formula I, including pharmaceutically acceptable salts of the compounds, are potent CETP inhibitors, and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis. In formula I, A-B is an arylamide moiety.

摘要翻译： 具有式I结构的化合物，包括化合物的药学上可接受的盐，是有效的CETP抑制剂，可用于升高HDL-胆固醇，降低LDL-胆固醇，以及用于治疗或预防动脉粥样硬化。 在式I中，A-B是芳基酰胺部分。

公开(公告)号：US07756644B2

公开(公告)日：2010-07-13

申请号：US11430214

申请日：2006-05-08

申请人： Arthur Fridman ,  Ansuman Bagchi ,  Wendy Bailey

发明人： Arthur Fridman ,  Ansuman Bagchi ,  Wendy Bailey

IPC分类号： G01N33/53 ,  G06F19/00 ,  C12Q1/70

CPC分类号： G06F19/18 ,  G06F19/22 ,  G06F19/24

摘要： Methodology for the automated selection and/or optimization of T-cell epitopes is disclosed. The invention provides a data processing system which utilizes sequence-based statistical pattern recognition to compute an epitope selection matrix based on the informational content of epitopes known to bind to a particular major histocompatibility class I allele. The resulting Bayes-corrected scoring matrix is used to predict the relative binding affinities of candidate T-cell epitopes derived from immunologically relevant antigens of self or foreign origin. One aspect of the invention describes an analytical method for identification of modifications in known or predicted T-cell epitopes that confer upon the epitopes the ability to elicit stronger cellular immune response due to more efficient processing and/or presentation to T-cells. The disclosed epitope identification algorithm is applicable to the design of vaccines for infectious diseases, cancer and autoimmune diseases as well as for developing methods for the in vitro evaluation of cellular immunity.

摘要翻译： 公开了用于T细胞表位的自动选择和/或优化的方法。 本发明提供一种数据处理系统，其利用基于序列的统计模式识别来计算基于已知结合特定主要组织相容性I等位基因的表位的信息含量的表位选择矩阵。 所得贝叶斯校正后的评分矩阵用于预测衍生自自身或外来来源免疫相关抗原的候选T细胞表位的相对结合亲和力。 本发明的一个方面描述了用于鉴定已知或预测的T细胞表位的修饰的分析方法，其赋予表位由于更有效的处理和/或呈递给T细胞引起更强的细胞免疫应答的能力。 所公开的表位识别算法适用于感染性疾病，癌症和自身免疫性疾病的疫苗的设计以及用于开发体外评价细胞免疫的方法。

公开(公告)号：US07745639B2

公开(公告)日：2010-06-29

申请号：US10506702

申请日：2003-03-04

申请人： Michael J. Breslin ,  Paul J. Coleman ,  Christopher D. Cox ,  J. Christopher Culberson ,  George D. Hartman ,  Brenda J. Mariano ,  Maricel Torrent

发明人： Michael J. Breslin ,  Paul J. Coleman ,  Christopher D. Cox ,  J. Christopher Culberson ,  George D. Hartman ,  Brenda J. Mariano ,  Maricel Torrent

IPC分类号： C07D231/06 ,  A01N43/56

CPC分类号： C07D401/04 ,  C04B35/632 ,  C07D231/06 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D403/06 ,  C07D403/12 ,  C07D405/04 ,  C07D405/12 ,  C07D413/04 ,  C07D417/04

摘要： The present invention relates to dihydropyrazole compounds that are useful for treating cellular proliferative diseases, for treating disorders associated with KSP kinesin activity, and for inhibiting KSP kinesin. The invention also related to compositions which comprise these compounds, and methods of using them to treat cancer in mammals.

摘要翻译： 本发明涉及可用于治疗细胞增殖性疾病，治疗与KSP驱动蛋白活性相关的疾病和用于抑制KSP驱动蛋白的二氢吡唑化合物。 本发明还涉及包含这些化合物的组合物，以及使用它们治疗哺乳动物癌症的方法。

公开(公告)号：US20100137405A1

公开(公告)日：2010-06-03

申请号：US12598565

申请日：2008-05-02

申请人： Vasant Jadhav ,  Ivan Richards ,  Walter Strapps ,  Chandra Vargeese

发明人： Vasant Jadhav ,  Ivan Richards ,  Walter Strapps ,  Chandra Vargeese

IPC分类号： A61K31/7105 ,  C07H21/02 ,  A61P11/06 ,  A61P11/08

CPC分类号： C12N15/1137 ,  A01K2207/05 ,  A01K2227/105 ,  A01K2267/0368 ,  C12N2310/14 ,  C12N2310/317 ,  C12N2310/321 ,  C12N2310/322 ,  C12N2310/332 ,  C12N2310/3521

摘要： The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression and/or activity, including PDE4B1, PDE4B2, and PDE4B3 gene expression and/or activity. The present invention is also directed to compounds, compositions, and methods relating to traits, diseases and conditions that respond to the modulation of expression and/or activity of genes involved in cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression pathways or other cellular processes that mediate the maintenance or development of such traits, diseases and conditions, including but not limited to IL-6, IL-I, IL-8, IL-15, TNF-alpha and matrix metalloproteinases (MMPs), such as MMP-I, MMP-2, MMP-3, MMP-9 and MMP-12. Specifically, the invention relates to double stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA), and multifunctional siNA molecules capable of mediating RNA interference (RNAi) against cyclic nucleotide type 4 phosphodiesterase (PDE4B) gene expression, including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. The present invention also relates to small nucleic acid molecules, such as siNA, siRNA, antisense and others that can inhibit the function of endogenous RNA molecules or RNAi pathway components (RNAi inhibitors), such as endogenous micro-RNA (miRNA) (e.g, miRNA inhibitors) or endogenous short interfering RNA (siRNA), (e.g., siRNA inhibitors) or that can inhibit the function of RISC (e.g., RISC inhibitors), to modulate PDE4B gene expression by interfering with the regulatory function of such endogenous RNAs or proteins associated with such endogenous RNAs (e.g., RISC) including cocktails of such small nucleic acid molecules and lipid nanoparticle (LNP) formulations of such small nucleic acid molecules. Such small nucleic acid molecules are useful, for example, in providing compositions to prevent, inhibit, or reduce inflammatory, respiratory, and autoimmune diseases, traits, and conditions, and/or other disease states associated with PDE4B gene expression or activity in a subject or organism.