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1. 发明授权

US5132214A Large scale production of plasminogen activator from normal human colon cells 失效
标题翻译：来自正常人类细胞的大规模生产PLASMINOGEN激活剂
公开(公告)号：US5132214A
公开(公告)日：1992-07-21
申请号：US849933
申请日：1986-04-09
申请人： Joseph Feder , Nicholaos K. Harakas , Jon P. Schaumann , Daniel T. Connolly , Arthur J. Wittwer
发明人： Joseph Feder , Nicholaos K. Harakas , Jon P. Schaumann , Daniel T. Connolly , Arthur J. Wittwer
IPC分类号： C12N9/64 , A61K38/00 , C07K1/14 , C08B37/00 , C12N5/00 , C12N9/72 , C12R1/91
CPC分类号： C12N9/6459 , C08B37/00 , C12Y304/21069 , A61K38/00
摘要： Plasminogen activators (PA) are obtained from cultured normal human colon cells which are adaptable to large scale production. A purified tissue PA (t-PA) is obtained from CCD-18Co normal human colon fibroblast cells which shows chemical differences from Bowes melanoma t-PA.
摘要翻译：纤维蛋白溶酶原激活物（PA）是从适合大规模生产的培养的正常人结肠细胞获得的。从CT-18Co正常人结肠成纤维细胞获得纯化的组织PA（t-PA），其显示与Bowes黑素瘤t-PA的化学差异。

2. 发明授权

US5008196A Stimulation of endothelial cell growth 失效
标题翻译：刺激内皮细胞生长
公开(公告)号：US5008196A
公开(公告)日：1991-04-16
申请号：US87739
申请日：1987-08-21
申请人： Daniel T. Connolly , Joseph Feder
发明人： Daniel T. Connolly , Joseph Feder
IPC分类号： C07K14/52 , C12N5/02
CPC分类号： C07K14/52
摘要： A method of stimulating endothelial cell growth is provided which comprises subjecting said cells to a growth stimulating amount of a highly purified vascular permeability factor having the following characteristics:(a) it has a M.sub.r about 34,000-40,000 as determined by sodium dodecylsulfate polyacrylamide gel electrophoresis;(b) it is a disulfide-linked protein dimer;(c) it has a N-terminal amino acid sequence as follows: ##STR1## (d) it exhibits substantial mitogenic activity to endothelial cells in culture.
摘要翻译：提供刺激内皮细胞生长的方法，其包括使所述细胞经受生长刺激量的具有以下特征的高度纯化的血管通透性因子：（a）通过十二烷基硫酸钠聚丙烯酰胺凝胶电泳测定其具有约34,000-40,000的Mr ; （b）二硫键连接蛋白二聚体; （c）它具有如下的N-末端氨基酸序列：（d）它对培养物中的内皮细胞表现出显着的促有丝分裂活性。

3. 发明授权

US5240848A DNA sequences encoding human vascular permeability factor having 189 amino acids 失效
标题翻译：编码具有189个氨基酸的人血管渗透因子的DNA序列
公开(公告)号：US5240848A
公开(公告)日：1993-08-31
申请号：US377037
申请日：1989-07-10
申请人： Pamela J. Keck , Daniel T. Connolly , Joseph Feder
发明人： Pamela J. Keck , Daniel T. Connolly , Joseph Feder
IPC分类号： C12N15/09 , A61K38/00 , C07K1/16 , C07K1/20 , C07K1/22 , C07K14/47 , C07K14/475 , C07K14/52 , C07K16/24 , C12N5/10 , C12N15/12 , C12P21/02 , C12R1/91
CPC分类号： C07K16/24 , C07K14/52
摘要： A cDNA having a base sequence for human vascular permeability factor has been cloned and characterized and the amino acid sequence of the human vascular permeability factor protein has been determined.

4. 发明授权

US5036003A Antibodies to VPF 失效
标题翻译： VPF抗体
公开(公告)号：US5036003A
公开(公告)日：1991-07-30
申请号：US240780
申请日：1988-09-02
申请人： Jitka V. Olander , Daniel T. Connolly , Steven P. Adams , Joseph Feder
发明人： Jitka V. Olander , Daniel T. Connolly , Steven P. Adams , Joseph Feder
IPC分类号： C07K14/52 , C12P21/08
CPC分类号： C07K14/52
摘要： A method of producing antibodies against vascular permeability factor (VPF) is disclosed which comprises immunizing a host animal with a peptide having an amino acid sequence as follows: ##STR1## or a fragment of said peptide containing an antigenic determinant of VPF.
摘要翻译：公开了一种产生针对血管通透性因子（VPF）的抗体的方法，其包括用具有如下氨基酸序列的肽免疫宿主动物：或者含有抗原决定簇的所述肽的片段的VPF。

5. 发明授权

US06462091B1 Combinations of cholesteryl ester transfer protein inhibitors and HMG coA reductase inhibitors for cardiovascular indications 失效
标题翻译：胆固醇酯转运蛋白抑制剂和HMG coA还原酶抑制剂用于心血管适应症的组合
公开(公告)号：US06462091B1
公开(公告)日：2002-10-08
申请号：US09466414
申请日：1999-12-17
申请人： Bradley T. Keller , James A. Sikorski , Kevin C. Glenn , Daniel T. Connolly , Mark E. Smith
发明人： Bradley T. Keller , James A. Sikorski , Kevin C. Glenn , Daniel T. Connolly , Mark E. Smith
IPC分类号： A61K31136
CPC分类号： A61K31/585 , A61K31/135 , A61K31/22 , A61K31/36 , A61K31/405 , A61K31/55 , A61K31/575 , A61K31/785 , A61K45/06 , Y10S514/824 , A61K2300/00
摘要： The present invention provides combinations of cardiovascular therapeutic compounds for the prophylaxis or treatment of cardiovascular disease including hypercholesterolemia, atherosclerosis, or hyperlipidemia. Combinations disclosed include an HMG CoA reductase inhibitor combined with a cholesteryl ester transfer protein (CETP) inhibitor.
摘要翻译：本发明提供用于预防或治疗包括高胆固醇血症，动脉粥样硬化或高脂血症的心血管疾病的心血管治疗化合物的组合。所公开的组合包括与胆固醇酯转移蛋白（CETP）抑制剂组合的HMG CoA还原酶抑制剂。

6. 发明授权

US08017313B2 Human G protein-coupled receptor and modulators thereof for the treatment of cardiovascular disorders 有权
标题翻译：人G蛋白偶联受体及其调节剂用于治疗心血管疾病
公开(公告)号：US08017313B2
公开(公告)日：2011-09-13
申请号：US10561132
申请日：2004-06-17
申请人： John W. Adams , Daniel T. Connolly
发明人： John W. Adams , Daniel T. Connolly
IPC分类号： C12Q1/00 , C07K14/705
CPC分类号： G01N33/74 , A01K67/027 , A01K67/0275 , A01K67/0276 , A01K2217/072 , A01K2217/075 , A01K2227/105 , A01K2267/03 , C07K14/705 , C07K14/723 , C07K2319/00 , C12N2799/022 , G01N33/6893 , G01N33/76 , G01N2333/726 , G01N2800/32 , G01N2800/325
摘要： The present invention relates to methods of identifying whether a candidate compound is a modulator of a G protein-coupled receptor (GPCR). In some embodiments, the GPCR is mammalian, preferably human. In some embodiments, the GPCR is expressed endogenously by cardiomyocytes. In some embodiments, the GPCR is coupled to Gq. In some embodiments, the GPCR increases the intracellular level of inositol 1,4,5-triphosphate (IP3). In some embodiments, a modulator of the GPCR is a modulator of cardiomyocyte hypertrophy. The present invention further relates to methods of using a modulator of the GPCR. Preferred modulators are inverse agonists and antagonists. Inverse agonists and antagonists of the invention are useful as therapeutic agents for the prevention or treatment of heart disease, including hypertrophic cardiomyopathy and congestive heart failure, in particular hypertrophic cardiomyopathy resulting from post-myocardial infarction remodeling, cardiac valve disease, sustained cardiac afterload, myocarditis, and familial hypertrophic cardiomyopathy.
摘要翻译：本发明涉及鉴定候选化合物是G蛋白偶联受体（GPCR）的调节剂的方法。在一些实施方案中，GPCR是哺乳动物，优选人。在一些实施方案中，GPCR由心肌细胞内源性表达。在一些实施例中，GPCR耦合到Gq。在一些实施方案中，GPCR增加1,4,5-三磷酸肌醇（IP3）的细胞内水平。在一些实施方案中，GPCR的调节剂是心肌细胞肥大的调节剂。本发明还涉及使用GPCR调制器的方法。优选的调节剂是反向激动剂和拮抗剂。本发明的反向激动剂和拮抗剂可用作预防或治疗心脏病，包括肥厚性心肌病和充血性心力衰竭的治疗剂，特别是由心肌梗死后重建，心脏瓣膜疾病，持续的心脏后负荷，心肌炎引起的肥大性心肌病，和家族性肥厚型心肌病。

7. 发明授权

US07611832B2 Human G protein-coupled receptor and modulators thereof for the treatment of ischemic heart disease and congestive heart failure 有权
标题翻译：人G蛋白偶联受体及其调节剂用于治疗缺血性心脏病和充血性心力衰竭
公开(公告)号：US07611832B2
公开(公告)日：2009-11-03
申请号：US10523100
申请日：2003-07-25
申请人： John W. Adams , Daniel T. Connolly
发明人： John W. Adams , Daniel T. Connolly
IPC分类号： C12Q1/00 , C07K14/705
CPC分类号： G01N33/74 , A01K2217/05 , A01K2217/075 , A01K2267/03 , C07K14/705 , G01N2333/726 , G01N2500/04
摘要： The present invention relates to methods of identifying whether a candidate compound is a modulator of an orphan G protein-coupled receptor (GPCR). Preferably the GPCR is human. In some embodiments, the GPCR is expressed endogenously by cardiomyocytes. In some embodiments, the GPCR is coupled to Gi and lowers the level of intracellular cAMP. In some embodiments, overexpression of the GPCR promotes survival of cardiomyocytes. In some embodiments, overexpression of the GPCR rescues cardiomyoctes from hypoxia/reoxygenation induced apoptosis. In some embodiments, the GPCR is down-regulated in individuals with congestive heart failure. Agonists of the invention are envisioned to be useful as therapeutic agents for the treatment of ischemic heart disease, including myocardial infarction, post-myocardial infarction remodeling, and congestive heart failure.
摘要翻译：本发明涉及鉴定候选化合物是否为孤儿G蛋白偶联受体（GPCR）的调节剂的方法。优选GPCR是人。在一些实施方案中，GPCR由心肌细胞内源性表达。在一些实施方案中，GPCR与Gi偶联并降低细胞内cAMP的水平。在一些实施方案中，GPCR的过表达促进心肌细胞的存活。在一些实施方案中，GPCR的过表达从心肌缺血/再氧化诱导的细胞凋亡中拯救心肌细胞。在一些实施方案中，GPCR在具有充血性心力衰竭的个体中下调。预期本发明的激动剂可用作治疗缺血性心脏病，包括心肌梗死，心肌梗死后重建和充血性心力衰竭的治疗剂。

8. 发明授权

US06794396B2 Substituted pyridines useful for inhibiting cholesteryl ester transfer protein activity 失效
标题翻译：用于抑制胆固醇酯转移蛋白活性的取代的吡啶
公开(公告)号：US06794396B2
公开(公告)日：2004-09-21
申请号：US10403903
申请日：2003-03-31
申请人： Len F. Lee , Kevin C. Glenn , Daniel T. Connolly , David G. Corley , Daniel L. Flynn , Ashton T. Hamme , Shridhar G. Hegde , Michele A. Melton , Roger J. Schilling , James A. Sikorski , Nancy N. Wall , Jeffery A. Zablocki
发明人： Len F. Lee , Kevin C. Glenn , Daniel T. Connolly , David G. Corley , Daniel L. Flynn , Ashton T. Hamme , Shridhar G. Hegde , Michele A. Melton , Roger J. Schilling , James A. Sikorski , Nancy N. Wall , Jeffery A. Zablocki
IPC分类号： C07D21302
CPC分类号： A61K31/44
摘要： A class of substituted pyridines that are useful for inhibiting the activity of cholesteryl ester transfer protein, and have the structural formula (IA), wherein R2, R3, R4, R5, and R6 are defined in the claims.
摘要翻译：一类可用于抑制胆固醇酯转移蛋白活性的取代吡啶，并具有结构式（IA），其中R 2，R 3，R 4，R 5和R 6在权利要求书中定义。

9. 发明授权

US07829298B2 Human G protein-coupled receptors for metabolic-related disorders 有权
标题翻译：人G蛋白偶联受体代谢相关疾病
公开(公告)号：US07829298B2
公开(公告)日：2010-11-09
申请号：US10930662
申请日：2004-08-31
申请人： David J. Unett , Ruoping Chen , Jeremy G. Richman , Daniel T. Connolly , Huong T. Dang , Bryan J. Choi , James N. Leonard , Yaron Hakak , Chen W. Liaw , Dominic P. Behan , Derek T. Chalmers , Michael R. Lerner , Kevin P. Lowitz
发明人： David J. Unett , Ruoping Chen , Jeremy G. Richman , Daniel T. Connolly , Huong T. Dang , Bryan J. Choi , James N. Leonard , Yaron Hakak , Chen W. Liaw , Dominic P. Behan , Derek T. Chalmers , Michael R. Lerner , Kevin P. Lowitz
IPC分类号： G01N33/53
CPC分类号： C07D403/02 , A01K2217/00 , A01K2227/105 , A01K2267/03 , A61K31/4439 , C07K14/705 , G01N33/566 , G01N2333/726 , G01N2500/00
摘要： The present invention relates to methods of identifying whether a candidate compound is a modulator of a G protein-coupled receptor (GPCR). In preferred embodiments, the GPCR is human. In other preferred embodiments, the GPCR is coupled to Gi and lowers the level of intracellular cAMP. In other preferred embodiments, the GPCR is expressed endogenously by adipocytes. In further preferred embodiments, the GPCR inhibits intracellular lipolysis. In other further preferred embodiments, the GPCR is a nicotinic acid receptor. The present invention also relates to methods of using a modulator of said GPCR. Preferred modulator is agonist. Agonists of the invention are useful as therapeutic agents for the prevention or treatment of metabolic-related disorders, including dyslipidemia, atherosclerosis, coronary heart disease, stroke, insulin resistance, and type 2 diabetes.
摘要翻译：本发明涉及鉴定候选化合物是G蛋白偶联受体（GPCR）的调节剂的方法。在优选的实施方案中，GPCR是人。在其它优选实施方案中，GPCR与Gi偶联并降低细胞内cAMP的水平。在其它优选实施方案中，GPCR由脂肪细胞内源性表达。在进一步优选的实施方案中，GPCR抑制细胞内脂肪分解。在其它进一步优选的实施方案中，GPCR是烟酸受体。本发明还涉及使用所述GPCR的调节剂的方法。优选的调节剂是激动剂。本发明的激动剂可用作预防或治疗代谢相关疾病，包括血脂异常，动脉粥样硬化，冠心病，中风，胰岛素抵抗和2型糖尿病的治疗剂。

10. 发明申请

US20080139628A1 Compositions For Treating Flushing And Lipid-Associated Disorders Comprising Niacin Receptor Partial Agonists 审中-公开
标题翻译：用于治疗包含烟酸受体部分激动剂的潮红和脂质相关疾病的组合物
公开(公告)号：US20080139628A1
公开(公告)日：2008-06-12
申请号：US11718539
申请日：2005-11-01
申请人： Dominic P. Behan , Daniel T. Connolly , Jeremy G. Richman
发明人： Dominic P. Behan , Daniel T. Connolly , Jeremy G. Richman
IPC分类号： A61K31/4406 , C07D403/04 , A61K31/41 , A61P3/00 , C07D231/14 , A61K31/415
CPC分类号： A61K45/06 , A61K31/00 , A61K31/415 , A61K31/416 , A61K31/4162 , A61K31/455 , A61K2300/00
摘要： The invention provides a method of reducing flushing induced by niacin or a niacin analog in a subject, comprising administering to said subject an effective flush reducing amount of a niacin receptor partial agonist. In addition, the invention provides a method of reducing flushing induced by niacin or a niacin analog in a subject, comprising administering to said subject an effective flush reducing amount of a niacin receptor partial agonist and an effective lipid altering amount of niacin or a niacin analog. The invention further provides a method of reducing flushing induced by niacin or a niacin analog in a subject, comprising administering to said subject an effective flush reducing amount of a niacin receptor partial agonist and subsequently administering to said subject an effective lipid altering amount of niacin or a niacin analog.
摘要翻译：本发明提供了一种减少受试者中烟酸或烟酸类似物引起的潮红的方法，包括向所述受试者施用有效冲洗减少量的烟酸受体部分激动剂。此外，本发明提供了一种减少受试者中烟酸或烟酸类似物引起的潮红的方法，包括向所述受试者施用有效冲洗减少量的烟酸受体部分激动剂和有效的脂质改变量的烟酸或烟酸类似物。本发明进一步提供了一种减少受试者中烟酸或烟酸类似物引起的潮红的方法，包括向所述受试者施用有效冲洗减少量的烟酸受体部分激动剂，随后向所述受试者施用有效的脂质改变量的烟酸或烟酸类似物。

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