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公开(公告)号：US07129267B2
公开(公告)日：2006-10-31
申请号：US10386243
申请日：2003-03-11
IPC分类号： A61K31/381 , A61K31/426 , A61K31/427
CPC分类号： G01N33/573 , A61K31/00 , A61K31/381 , A61K31/426 , A61K31/427 , A61K38/1816 , C12Q1/44 , G01N2500/02 , G01N2500/04 , G01N2500/10 , A61K2300/00
摘要： The effect of EPO on the phosphorylation of the EPO receptor, the activation of the MAP Kinase pathway, and the expression of SHP-1 were analyzed. EPO was observed to cause a decrease in the expression of its negative regulator SHP-1. The decrease observed at both the mRNA and protein level was dose dependent and persisted as long as 24 hr following EPO treatment. EPO can down regulate the expression of its own negative regulator as a means for increased potency in neurons. Assays were generated to identify compounds that are useful in regulating SHP1 activity in neural cells.
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公开(公告)号：US20070009967A1
公开(公告)日：2007-01-11
申请号：US11530222
申请日：2006-09-08
IPC分类号： G01N33/567 , G01N33/53
CPC分类号： G01N33/573 , A61K31/00 , A61K31/381 , A61K31/426 , A61K31/427 , A61K38/1816 , C12Q1/44 , G01N2500/02 , G01N2500/04 , G01N2500/10 , A61K2300/00
摘要： The effect of EPO on the phosphorylation of the EPO receptor, the activation of the MAP Kinase pathway, and the expression of SHP-1 were analyzed. EPO was observed to cause a decrease in the expression of its negative regulator SHP-1. The decrease observed at both the mRNA and protein level was dose dependent and persisted as long as 24 hr following EPO treatment. EPO can down regulate the expression of its own negative regulator as a means for increased potency in neurons. Assays were generated to identify compounds that are useful in regulating SHP1 activity in neural cells.
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公开(公告)号：US20070065885A1
公开(公告)日：2007-03-22
申请号：US11530234
申请日：2006-09-08
IPC分类号： G01N33/567 , G01N33/53
CPC分类号： G01N33/573 , A61K31/00 , A61K31/381 , A61K31/426 , A61K31/427 , A61K38/1816 , C12Q1/44 , G01N2500/02 , G01N2500/04 , G01N2500/10 , A61K2300/00
摘要： The effect of EPO on the phosphorylation of the EPO receptor, the activation of the MAP Kinase pathway, and the expression of SHP-1 were analyzed. EPO was observed to cause a decrease in the expression of its negative regulator SHP-1. The decrease observed at both the mRNA and protein level was dose dependent and persisted as long as 24 hr following EPO treatment. EPO can down regulate the expression of its own negative regulator as a means for increased potency in neurons. Assays were generated to identify compounds that are useful in regulating SHP1 activity in neural cells.
摘要翻译： 分析EPO对EPO受体的磷酸化，MAP激酶途径的激活和SHP-1的表达的影响。 观察到EPO引起其负调节物SHP-1的表达降低。 在mRNA和蛋白质水平上观察到的降低是剂量依赖性的，并且在EPO处理后长达24小时持续。 EPO可以下调其自身负调节因子的表达，作为增加神经元效力的手段。 产生测定以鉴定可用于调节神经细胞中SHP1活性的化合物。
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公开(公告)号：US07259146B2
公开(公告)日：2007-08-21
申请号：US09863600
申请日：2001-05-23
申请人： Virginia Smith-Swintosky , Michael Renzi , Carlos Plata-Salaman , Linda Jolliffe , Francis Farrell , Dana Johnson
发明人： Virginia Smith-Swintosky , Michael Renzi , Carlos Plata-Salaman , Linda Jolliffe , Francis Farrell , Dana Johnson
CPC分类号： C07K14/505 , A61K38/00
摘要： Methods of treating diseases of the nervous system by administration of compositions having the neurological therapeutic activity of human erythropoietin are disclosed. These compositions include therapeutic agents such as peptides, peptide dimers, polypeptides, and proteins that have the full range of biological activity of human erythropoietin or only certain biological activities of erythropoietin. Improved therapeutic regimens where the erythropoietin is administered at concentrations below those required to stimulate hematopoiesis are also provided.
摘要翻译： 公开了通过施用具有人促红细胞生成素神经学治疗活性的组合物治疗神经系统疾病的方法。 这些组合物包括治疗剂，例如肽，肽二聚体，多肽和蛋白质，其具有人类促红细胞生成素的全部生物学活性或只有促红细胞生成素的某些生物学活性。 还提供了改善的促红细胞生成素以低于刺激造血所需浓度的浓度给药的治疗方案。
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公开(公告)号：US20090170759A1
公开(公告)日：2009-07-02
申请号：US11776003
申请日：2007-07-11
申请人： Virginia Smith-Swintosky , Michael Renzi , Carlos Plata-Salaman , Linda Jolliffe , Francis Farrell , Dana Johnson
发明人： Virginia Smith-Swintosky , Michael Renzi , Carlos Plata-Salaman , Linda Jolliffe , Francis Farrell , Dana Johnson
CPC分类号： A61K38/1816 , A61K47/60 , C07K14/505
摘要： Methods of treating diseases of the nervous system by administration of compositions having the neurological therapeutic activity of human erythropoietin are disclosed. These compositions include therapeutic agents such as peptides, peptide dimers, polypeptides, and proteins that have the full range of biological activity of human erythropoietin or only certain biological activities of erythropoietin. Improved therapeutic regimens where the erythropoietin is administered at concentrations below those required to stimulate hematopoiesis are also provided.
摘要翻译： 公开了通过施用具有人促红细胞生成素神经学治疗活性的组合物治疗神经系统疾病的方法。 这些组合物包括治疗剂，例如肽，肽二聚体，多肽和蛋白质，其具有人类促红细胞生成素的全部生物学活性或只有促红细胞生成素的某些生物学活性。 还提供了改善的促红细胞生成素以低于刺激造血所需浓度的浓度给药的治疗方案。
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公开(公告)号：US06303594B1
公开(公告)日：2001-10-16
申请号：US09526224
申请日：2000-03-15
申请人： Linda Jolliffe , William Murray , Virginia Pulito , Allan Reitz , Xiaobing Li , Linda Mulcahy , Cynthia Maryanoff , Frank Villani
发明人： Linda Jolliffe , William Murray , Virginia Pulito , Allan Reitz , Xiaobing Li , Linda Mulcahy , Cynthia Maryanoff , Frank Villani
IPC分类号： A61K3155
摘要： This invention relates to a series of arylsubstituted piperazines, of Formula I pharmaceutical compositions containing them and intermediates used in their manufacture. The compounds of the invention selectively inhibit binding to the &agr;-1a adrenergic receptor, a receptor which has been implicated in benign prostatic hyperplasia. As such the compounds are potentially useful in the treatment of this and other disease.
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7.发明申请公开(公告)号：US20060002933A1
公开(公告)日：2006-01-05
申请号：US11221900
申请日：2005-09-09
申请人： Jeffrey Bluestone , Robert Zivin , Linda Jolliffe
发明人： Jeffrey Bluestone , Robert Zivin , Linda Jolliffe
IPC分类号： A61K39/395 , C07K16/28
CPC分类号： C07K16/2809 , A61K38/00 , A61K2039/505 , C07K2317/24 , C07K2317/52 , C07K2317/56 , C07K2317/74 , C07K2317/75 , C07K2317/76 , C07K2317/92 , C07K2319/00
摘要： The binding specificity of the murine OKT3 has been transferred into a human antibody framework in order to reduce its immunogenicity. “Humanized” anti-CD3 mAbs, such as gOKT3-5 and gOKT3-7, have been shown to retain, in vitro, all the properties of native OKT3, including T cell activation which has been correlated, in vivo, with the severe side-effects observed in transplant recipients after the first administration of the mAb. Disclosed are modified versions of humanized anti-CD3 mAbs that do not have the property of T cell activation. Further dislosed are methods of using such mAbs.
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公开(公告)号：US06710048B2
公开(公告)日：2004-03-23
申请号：US09955780
申请日：2001-09-19
申请人： Gee-Hong Kuo , Peter J. Connolly , Catherine Prouty , Alan DeAngelis , Aihua Wang , Linda Jolliffe , Steve Middleton , Stuart Emanuel
发明人： Gee-Hong Kuo , Peter J. Connolly , Catherine Prouty , Alan DeAngelis , Aihua Wang , Linda Jolliffe , Steve Middleton , Stuart Emanuel
IPC分类号： A61K31505
CPC分类号： C07D401/04 , C07D401/14 , C07D405/14
摘要： The present invention provides pyrazine derivatives that inhibit tyrosine kinase activity. Certain pyrazine derivatives are selective inhibitors of vascular endothelial growth factor (VEGF) receptor tyrosine kinase. The present invention also provides pharmaceutical formulations containing the pyrazine derivatives and methods of use of these formulations as anti-tumor agents and to treat solid-tumor cancers, angiogenesis, diabetic retinopathy, rheumatoid arthritis, endometriosis and psoriasis.
摘要翻译： 本发明提供抑制酪氨酸激酶活性的吡嗪衍生物。 某些吡嗪衍生物是血管内皮生长因子（VEGF）受体酪氨酸激酶的选择性抑制剂。 本发明还提供含有吡嗪衍生物的药物制剂以及这些制剂用作抗肿瘤剂并用于治疗实体瘤，血管生成，糖尿病性视网膜病，类风湿性关节炎，子宫内膜异位和银屑病的方法。
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9.发明授权Arylsubstituted piperazines useful in the treatment of benign prostatic hyperplasia 有权用于治疗良性前列腺增生的芳基取代哌嗪公开(公告)号：US06890921B1
公开(公告)日：2005-05-10
申请号：US09526224
申请日：2000-03-15
申请人： Linda Jolliffe , William Murray , Virginia Pulito , Allen Reitz , Xiaobing Li , Linda Mulcahy , Cynthia Maryanoff , Frank Villani
发明人： Linda Jolliffe , William Murray , Virginia Pulito , Allen Reitz , Xiaobing Li , Linda Mulcahy , Cynthia Maryanoff , Frank Villani
IPC分类号： C07D295/12 , A61K31/397 , A61K31/40 , A61K31/4015 , A61K31/402 , A61K31/4025 , A61K31/445 , A61K31/496 , A61K31/55 , A61P13/08 , C07D205/08 , C07D207/12 , C07D207/26 , C07D207/27 , C07D207/28 , C07D209/44 , C07D209/48 , C07D211/40 , C07D211/76 , C07D221/20 , C07D223/10 , C07D225/02 , C07D225/08 , C07D241/04 , C07D295/08 , C07D295/13 , C07D401/12 , C07D403/12
CPC分类号： C07D207/27 , C07D207/28 , C07D209/48 , C07D211/76 , C07D223/10 , C07D295/13
摘要： This invention relates to a series of arylsubstituted piperazines, of Formula I pharmaceutical compositions containing them and intermediates used in their manufacture. The compounds of the invention selectively inhibit binding to the α-1a adrenergic receptor, a receptor which has been implicated in benign prostatic hyperplasia. As such the compounds are potentially useful in the treatment of this and other disease.
摘要翻译： 本发明涉及一系列含有它们的式I药物组合物和其制备中使用的中间体的芳基取代哌嗪。 本发明的化合物选择性地抑制与α-1a肾上腺素能受体的结合，α受体是与良性前列腺增生有关的受体。 因此，这些化合物在治疗这种疾病和其他疾病中潜在有用。
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10.发明申请公开(公告)号：US20060292142A1
公开(公告)日：2006-12-28
申请号：US11509974
申请日：2006-08-25
申请人： Jeffrey Bluestone , Robert Zivin , Linda Jolliffe
发明人： Jeffrey Bluestone , Robert Zivin , Linda Jolliffe
IPC分类号： A61K39/395 , C07K16/28
CPC分类号： C07K16/2809 , A61K38/00 , A61K2039/505 , C07K2317/24 , C07K2317/52 , C07K2317/56 , C07K2317/74 , C07K2317/75 , C07K2317/76 , C07K2317/92 , C07K2319/00
摘要： The binding specificity of the murine OKT3 has been transferred into a human antibody framework in order to reduce its immunogenicity. “Humanized” anti-CD3 mAbs, such as gOKT3-5 and gOKT3-7, have been shown to retain, in vitro, all the properties of native OKT3, including T cell activation which has been correlated, in vivo, with the severe side-effects observed in transplant recipients after the first administration of the mAb. Disclosed are modified versions of humanized anti-CD3 mAbs that do not have the property of T cell activation. Further dislosed are methods of using such mAbs.
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