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1. 发明授权

US06306583B1 Human brain phosphodiesterase 失效
标题翻译：人脑磷酸二酯酶
公开(公告)号：US06306583B1
公开(公告)日：2001-10-23
申请号：US08445474
申请日：1995-05-22
申请人： George P. Livi , Megan M. McLaughlin , Theodore J. Torphy
发明人： George P. Livi , Megan M. McLaughlin , Theodore J. Torphy
IPC分类号： C12Q168
CPC分类号： C12N9/16
摘要： Isolated cDNA clones from human brain (frontal cortex) cDNA libraries that encode a unique subtype of the low Km, cAMP-specific phosphodiesterases (PDE IVs) are disclosed. Analysis of the distribution of hPDE IVB mRNA expression in various human tissues using a nonconserved fragment of the cDNA as a probe revealed a restricted pattern of expression, with an ˜4-kb mRNA detected in brain, heart, lung and skeletal muscle and not in placenta, liver, kidney or pancreas. Furthermore, an additional ˜5-kb hPDE IVB-related mRNA species was detected in brain tissue. Expression of hPDE IVB in a genetically-engineered PDE-deficient strain of the yeast Saccharomym cerevisiae resulted in the overproduction of cAMP PDE activity which displayed the expected kinetic characteristics for a PDE IV: 1) low Km (4.3 &mgr;M) for cAMP, 2) high Km (>3 mM) for cGMP, and 3) sensitivity to rolipram (Ki=0.085 &mgr;M), a selective inhibitor of PDE IV. Recombinant hPDE IVB also bound [3H] R-rolipram saturably and with a high affinity. Analysis of [3H] R-rolipram binding data revealed curvilinear Scatchard plots, suggesting the presence of two non-interacting high affinity rolipram binding sites (Kd=0.4 and 6 nM) or a negatively cooperative interaction among multiple binding sites. This novel enzyme is particularly useful for screening candidate compounds for their ability to serve as potential anti-depressant, antiasthmatic or anti-inflammatory agents.
摘要翻译：公开了编码低Km，cAMP特异性磷酸二酯酶（PDE IV）的独特亚型的来自人脑（额叶皮质）cDNA文库的分离的cDNA克隆。使用cDNA的非保守片段作为探针分析各种人体组织中hPDE IVB mRNA表达的分布，显示出限制性表达模式，在脑，心脏，肺和骨骼肌中检测到〜4-kb mRNA，而不是在胎盘，肝，肾或胰腺。此外，在脑组织中检测到另外约5kb的hPDE IVB相关mRNA种类。在酵母酿酒酵母的遗传工程化PDE缺陷菌株中表达hPDE IVB导致过量产生cAMP PDE活性，其显示PDE IV的预期动力学特征：1）cAMP低Km（4.3μM），2）对于cGMP，高Km（> 3mM），以及3）灵敏度为咯利普兰（Ki =0.085μM），PDE IV的选择性抑制剂。重组hPDE IVB也以饱和和高亲和力结合[3H] R-咯利普兰。 [3H] R-咯利普兰结合数据的分析显示曲线Scatchard图，表明存在两个非相互作用的高亲和力咯利普兰结合位点（Kd = 0.4和6nM）或多个结合位点之间的负配位相互作用。该新型酶特别用于筛选候选化合物作为潜在的抗抑郁剂，抗哮喘或抗炎剂的能力。

2. 发明授权

US6150150A Human brain phosphodiesterase 有权
标题翻译：人脑磷酸二酯酶
公开(公告)号：US6150150A
公开(公告)日：2000-11-21
申请号：US192702
申请日：1998-11-16
申请人： George P. Livi , Megan M. McLaughlin , Theodore J. Torphy
发明人： George P. Livi , Megan M. McLaughlin , Theodore J. Torphy
IPC分类号： G01N33/53 , C07H21/04 , C07K14/47 , C07K16/40 , C07K19/00 , C08L101/16 , C12N1/19 , C12N1/21 , C12N9/16 , C12N15/09 , C12N15/55 , C12P21/08 , C12Q1/02 , C12Q1/44 , C12R1/865 , G01N33/573 , C12N9/22
CPC分类号： C12N9/16
摘要： Isolated cDNA clones from human brain (frontal cortex) cDNA libraries that encode a unique subtype of the low K.sub.m, cAMP-specific phosphodiesterases (PDE IVs) are disclosed. Analysis of the distribution of hPDE IV.sub.B mRNA expression in various human tissues using a nonconserved fragment of the cDNA as a probe revealed a restricted pattern of expression, with an .about.4-kb mRNA detected in brain, heart, lung and skeletal muscle and not in placenta, liver, kidney or pancreas. Furthermore, an additional .about.5-kb hPDE IV.sub.B.sup.- related mRNA species was detected in brain tissue. Expression of hPDE IV.sub.B in a genetically-engineered PDE-deficient strain of the yeast Saccharomyces cerevisiae resulted in the overproduction of cAMP PDE activity which displayed the expected kinetic characteristics for a PDE IV: 1) low K.sub.m (4.3 .mu.M) for cAMP, 2) high K.sub.m (>3 mM) for cGMP, and 3) sensitivity to rolipram (K.sub.i =0.085 .mu.M), a selective inhibitor of PDE IV. Recombinant hPDE IV.sub.B also bound [.sup.3 H] R-rolipram saturably and with a high affinity. Analysis of [.sup.3 H] R-rolipram binding data revealed curvilinear Scatchard plots, suggesting the presence of two non-interacting high affinity rolipram binding sites (K.sub.d =0.4 and 6 nM) or a negatively cooperative interaction among multiple binding sites.This novel enzyme is particularly useful for screening candidate compounds for their ability to serve as potential anti-depressant, antiasthmatic or anti-inflammatory agents.
摘要翻译：公开了编码低Km，cAMP特异性磷酸二酯酶（PDE IV）的独特亚型的来自人脑（额叶皮质）cDNA文库的分离的cDNA克隆。使用cDNA的非保守片段作为探针分析各种人体组织中hPDE IVB mRNA表达的分布，显示出限制性表达模式，在脑，心脏，肺和骨骼肌中检测到差异4-kb mRNA，而不是在胎盘，肝，肾或胰腺。此外，在脑组织中检测到另外的DIFFERENCE 5-kb hPDE IVB相关mRNA种类。在酵母酿酒酵母的遗传工程化PDE缺陷菌株中表达hPDE IVB导致cAMP PDE活性过度产生，其显示PDE IV的预期动力学特征：1）cAMP低的Km（4.3μM），2 ）对于cGMP高Km（> 3mM），和3）灵敏度对咯利普兰（Ki =0.085μM），PDE IV的选择性抑制剂。重组hPDE IVB也以饱和和高亲和力结合[3H] R-咯利普兰。 [3H] R-咯利普兰结合数据的分析显示曲线Scatchard图，表明存在两个非相互作用的高亲和力咯利普兰结合位点（Kd = 0.4和6nM）或多个结合位点之间的负配位相互作用。这种新型酶特别可用于筛选候选化合物作为潜在的抗抑郁剂，抗哮喘或抗炎药的能力。

3. 发明授权

US5932477A Polynucleotides encoding human brain phosphodiesterase 失效
标题翻译：编码人脑磷酸二酯酶的多核苷酸
公开(公告)号：US5932477A
公开(公告)日：1999-08-03
申请号：US942521
申请日：1997-10-02
申请人： George P. Livi , Megan M. McLaughlin , Theodore J. Torphy
发明人： George P. Livi , Megan M. McLaughlin , Theodore J. Torphy
IPC分类号： G01N33/53 , C07H21/04 , C07K14/47 , C07K16/40 , C07K19/00 , C08L101/16 , C12N1/19 , C12N1/21 , C12N9/16 , C12N15/09 , C12N15/55 , C12P21/08 , C12Q1/02 , C12Q1/44 , C12R1/865 , G01N33/573 , C12N5/10 , C12N1/15 , C12N15/12
CPC分类号： C12N9/16
摘要： Isolated cDNA clones from human brain (frontal cortex) cDNA libraries that encode a unique subtype of the low K.sub.m, cAMP-specific phosphodiesterases (PDE IVs) are disclosed. Analysis of the distribution of hPDE IV.sub.B mRNA expression in various human tissues using a nonconserved fragment of the cDNA as a probe revealed a restricted pattern of expression, with an .about.4-kb MRNA detected in brain, heart, lung and skeletal muscle and not in placenta, liver, kidney or pancreas. Furthermore, an additional .about.5-kb hPDE IV.sub.B.sup.- related mRNA species was detected in brain tissue. Expression of hPDE IV.sub.B in a genetically-engineered PDE-deficient strain of the yeast Saccharomyces cerevisiae resulted in the overproduction of cAMP PDE activity which displayed the expected kinetic characteristics for a PDE IV: 1) low K.sub.m (4.3 .mu.M) for cAMP, 2) high K.sub.m (>3 mM) for cGMP, and 3) sensitivity to rolipram (K.sub.i =0.085 .mu.M), a selective inhibitor of PDE IV. Recombinant HPDE IV.sub.B also bound �.sup.3 H!R-rolipram saturably and with a high affinity. Analysis of �.sup.3 H!R-rolipram binding data revealed curvilinear Scatchard plots, suggesting the presence of two non-interacting high affinity rolipram binding sites (K.sub.d =0.4 and 6 nM) or a negatively cooperative interaction among multiple binding sites. This novel enzyme is particularly useful for screening candidate compounds for their ability to serve as potential anti-depressant, antiasthmatic or anti-inflammatory agents.
摘要翻译：公开了编码低Km，cAMP特异性磷酸二酯酶（PDE IV）的独特亚型的来自人脑（额叶皮质）cDNA文库的分离的cDNA克隆。使用cDNA的非保守片段作为探针分析各种人体组织中hPDE IVB mRNA表达的分布，显示了在脑，心脏，肺和骨骼肌中检测到差异4-kb MRNA的限制性表达模式，而不是在胎盘，肝，肾或胰腺。此外，在脑组织中检测到另外的DIFFERENCE 5-kb hPDE IVB相关mRNA种类。在酵母酿酒酵母的遗传工程化PDE缺陷菌株中表达hPDE IVB导致cAMP PDE活性过度产生，其显示PDE IV的预期动力学特征：1）cAMP低的Km（4.3μM），2 ）对于cGMP高Km（> 3mM），和3）灵敏度对咯利普兰（Ki =0.085μM），PDE IV的选择性抑制剂。重组HPDE IVB还以饱和的和高亲和力结合[3H] R-咯利普兰。 [3H] R-咯利普兰结合数据的分析显示曲线Scatchard图，表明存在两个非相互作用的高亲和力咯利普兰结合位点（Kd = 0.4和6nM）或多个结合位点之间的负配位相互作用。这种新型酶特别可用于筛选候选化合物作为潜在的抗抑郁剂，抗哮喘或抗炎药的能力。

4. 发明授权

US6159716A Human protein kinase HOACF72 失效
标题翻译：人类蛋白激酶HOACF72
公开(公告)号：US6159716A
公开(公告)日：2000-12-12
申请号：US350484
申请日：1999-07-09
申请人： Caretha L. Creasy , George P. Livi , Damien J. Dunnington , Usman Shabon
发明人： Caretha L. Creasy , George P. Livi , Damien J. Dunnington , Usman Shabon
IPC分类号： G01N33/15 , A61K31/70 , A61K38/55 , A61K39/395 , A61K48/00 , A61P9/00 , A61P11/00 , A61P13/02 , A61P15/00 , A61P17/00 , A61P25/00 , A61P25/28 , A61P29/00 , A61P31/00 , A61P43/00 , C07K16/40 , C12N1/21 , C12N5/10 , C12N9/12 , C12N15/09 , C12N15/54 , C12P21/08 , C12Q1/02 , C12Q1/68 , C12N9/00 , C12N21/06
CPC分类号： C12N9/1205 , A61K48/00
摘要： hYAK1 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing hYAK1 polypeptides and polynucleotides in the design of protocols for the treatment of bone loss including osteoporosis; inflammatory diseases such as Adult Respiratory Disease Syndrome (ARDS), Rheumatoid arthris, Osteoarthritis, Inflammatory Bowel Disease (IBD), psoriasis, dermatitis, asthma, allergies; infections such as bacterial, fungal, protozoan and viral infections, particularly infections caused by HIV-1 or HIV-2; HIV-associated cachexia and other immunodeficiency disorders; septic shock; pain; injury; cancers; anorexia; bulimia; Parkinson's disease; cardiovascular disease including restenosis, atherosclerosis, acute heart failure, myocardial infarction; hypotension; hypertension; urinary retention; angina pectoris; ulcers; benign prostatic hypertrophy; and psychotic and neurological disorders, including anxiety, schizophrenia, manic depression, delirium, dementia, severe mental retardation and dyskinesias, such as Huntington's disease or Gilles dela Tourett's syndrome, among others, and diagnostic assays for such conditions.
摘要翻译：公开了通过重组技术生产这种多肽的hYAK1多肽和多核苷酸和方法。还公开了在设计用于治疗包括骨质疏松症的骨丢失的方案中使用hYAK1多肽和多核苷酸的方法; 炎性疾病如成人呼吸系统综合症（ARDS），类风湿性关节炎，骨关节炎，炎性肠病（IBD），牛皮癣，皮炎，哮喘，过敏; 感染如细菌，真菌，原生动物和病毒感染，特别是HIV-1或HIV-2引起的感染; HIV相关性恶病质和其他免疫缺陷病症; 败血性休克疼痛; 伤害癌症; 厌食症贪食帕金森病心血管疾病包括再狭窄，动脉粥样硬化，急性心力衰竭，心肌梗塞; 低血压高血压; 尿潴留心绞痛; 溃疡良性前列腺肥大; 以及精神病和神经障碍，包括焦虑，精神分裂症，躁狂抑郁症，del妄，痴呆，严重的精神发育迟滞和运动障碍，如亨廷顿病或Gilles dela Tourett综合征，以及此类病症的诊断测定。

5. 发明授权

US5817466A Conserved yeast nucleic acid sequences 失效
标题翻译：保守的酵母核酸序列
公开(公告)号：US5817466A
公开(公告)日：1998-10-06
申请号：US878106
申请日：1997-06-18
申请人： Lois L. Hoyer , George P. Livi , Allan R. Shatzman
发明人： Lois L. Hoyer , George P. Livi , Allan R. Shatzman
IPC分类号： C12N15/09 , C07K14/40 , C12Q1/68 , C07H1/02 , C07H1/04
CPC分类号： C12Q1/6895 , C07K14/40
摘要： This invention relates to nucleic acid sequences conserved in strains of yeasts. More particularly, this invention relates to segments of the ALS1 gene of Candida albicans useful as probes and primers for the identification of yeast, particularly Candida, infections.
摘要翻译：本发明涉及在酵母菌株中保守的核酸序列。更具体地，本发明涉及可用作鉴定酵母特别是假丝酵母属感染的探针和引物的白色念珠菌ALS1基因片段。

6. 发明授权

US06909029B2 Caenorhabditis elegans chemosensory bioassay for seven transmembrane receptor ligands 失效
标题翻译：秀丽隐杆线虫化学感应生物测定用于七个跨膜受体配体
公开(公告)号：US06909029B2
公开(公告)日：2005-06-21
申请号：US09963990
申请日：2001-09-26
申请人： George P. Livi , Christopher Shelton
发明人： George P. Livi , Christopher Shelton
IPC分类号： A01K67/033 , G01N33/50 , G01N33/00 , A01K67/00
CPC分类号： A01K67/0336 , G01N33/5085 , G01N2333/705
摘要： This invention relates to methods for producing a transgenic C. elegans that expresses a human 7TMR pan-neuronally, such that said transgenic C. elegans exhibits a known phenotype. These transgenic C. elegans can be used in a variety of ways, including, but not limited to: (1) screening and identifying substances that bind to and activate particular human 7TMRs; (2) screening for substances that antagonize human 7TMR activation; (3) identifying human 7TMRs that may respond to particular substances; and (4) evaluating the specificity and efficacy of substances on human 7TMR activation.
摘要翻译：本发明涉及用于产生表达人7TMR泛神经元的转基因秀丽隐杆线虫的方法，使得所述转基因秀丽隐杆线虫表现出已知的表型。这些转基因秀丽隐杆线虫可以以各种方式使用，包括但不限于：（1）筛选和鉴定结合并激活特定人类7TMR的物质; （2）筛选拮抗人7TMR活化的物质; （3）识别可能对特定物质作出反应的人类7TMRs; 和（4）评估物质对人7TMR活化的特异性和功效。

7. 发明授权

US5972606A Human protein kinase HOACF72 失效
标题翻译：人类蛋白激酶HOACF72
公开(公告)号：US5972606A
公开(公告)日：1999-10-26
申请号：US802466
申请日：1997-02-19
申请人： Caretha L. Creasy , George P. Livi , Damien J. Dunnington , Usman Shabon
发明人： Caretha L. Creasy , George P. Livi , Damien J. Dunnington , Usman Shabon
IPC分类号： G01N33/15 , A61K31/70 , A61K38/55 , A61K39/395 , A61K48/00 , A61P9/00 , A61P11/00 , A61P13/02 , A61P15/00 , A61P17/00 , A61P25/00 , A61P25/28 , A61P29/00 , A61P31/00 , A61P43/00 , C07K16/40 , C12N1/21 , C12N5/10 , C12N9/12 , C12N15/09 , C12N15/54 , C12P21/08 , C12Q1/02 , C12Q1/68 , C07H21/04 , C12N5/00 , C12P21/06
CPC分类号： C12N9/1205 , A61K48/00
摘要： hYAK1 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing hYAK1 polypeptides and polynucleotides in the design of protocols for the treatment of bone loss including osteoporosis; inflammatory diseases such as Adult Respiratory Disease Syndromne (ARDS), Rheumatoid arthritis, Osteoarthritis, Inflammatory Bowel Disease (IBD), psoriasis, dermatitis, asthma, allergies; infections such as bacterial, fungal, protozoan and viral infections, particularly infections caused by HIV-1 or HIV-2; HIV-associated cachexia and other immunodeficiency disorders; septic shock; pain; injury; cancers; anorexia; bulimia; Parkinson's disease; cardiovascular disease including restenosis, atherosclerosis, acute heart failure, myocardial infarction; hypotension; hypertension; urinary retention; angina pectoris; ulcers; benign prostatic hypertrophy; and psychotic and neurological disorders, including anxiety, schizophrenia, manic depression, delirium, dementia, severe mental retardation and dyskinesias, such as Huntington's disease or Gilles dela Tourett's syndrome, among others, and diagnostic assays for such conditions.
摘要翻译：公开了通过重组技术生产这种多肽的hYAK1多肽和多核苷酸和方法。还公开了在设计用于治疗骨丢失（包括骨质疏松症）的方案中使用hYAK1多肽和多核苷酸的方法; 炎性疾病如成人呼吸系统疾病综合征（ARDS），类风湿性关节炎，骨关节炎，炎性肠病（IBD），牛皮癣，皮炎，哮喘，过敏; 感染如细菌，真菌，原生动物和病毒感染，特别是HIV-1或HIV-2引起的感染; HIV相关性恶病质和其他免疫缺陷病症; 败血性休克疼痛; 伤害癌症; 厌食症贪食帕金森病心血管疾病包括再狭窄，动脉粥样硬化，急性心力衰竭，心肌梗塞; 低血压高血压; 尿潴留心绞痛; 溃疡良性前列腺肥大; 以及精神病和神经障碍，包括焦虑，精神分裂症，躁狂抑郁症，del妄，痴呆，严重的精神发育迟滞和运动障碍，如亨廷顿病或Gilles dela Tourett综合征，以及此类病症的诊断测定。

8. 发明授权

US5668263A Conserved yeast nucleic acid sequences 失效
标题翻译：保守的酵母核酸序列
公开(公告)号：US5668263A
公开(公告)日：1997-09-16
申请号：US357962
申请日：1994-12-16
申请人： Lois L. Hoyer , George P. Livi , Allan R. Shatzman
发明人： Lois L. Hoyer , George P. Livi , Allan R. Shatzman
IPC分类号： C12N15/09 , C07K14/40 , C12Q1/68 , C07H21/02
CPC分类号： C12Q1/6895 , C07K14/40
摘要： This invention relates to nucleic acid sequences conserved in strains of yeasts. More particularly, this invention relates to segments of the ALSl gene of Candida albicans useful as probes and primers for the identification of yeast, particularly Candida, infections.
摘要翻译：本发明涉及在酵母菌株中保守的核酸序列。更具体地，本发明涉及可用作鉴定酵母特别是假丝酵母属感染的探针和引物的白色念珠菌ALS1基因片段。

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