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1. 发明授权

US5840505A Method for inhibiting adenylosuccinate synthetase activity in methylthioadenosine phosphorylase deficient cells 失效
标题翻译：抑制甲基硫代腺苷磷酸化酶缺陷细胞中腺苷酸琥珀酸合成酶活性的方法
公开(公告)号：US5840505A
公开(公告)日：1998-11-24
申请号：US612542
申请日：1996-03-08
申请人： Carlos J. Carrera , Dennis A. Carson , Howard B. Cottam , Tsutomu Nobori
发明人： Carlos J. Carrera , Dennis A. Carson , Howard B. Cottam , Tsutomu Nobori
IPC分类号： C12N15/09 , A61K31/00 , A61K31/195 , A61K31/198 , A61K45/00 , A61P35/00 , C07H21/04 , C07K7/06 , C07K7/08 , C07K16/40 , C12N1/21 , C12N5/06 , C12N9/10 , C12N9/12 , C12N15/00 , C12N15/02 , C12P19/34 , C12P21/08 , C12Q1/00 , C12Q1/25 , C12Q1/68 , C12R1/19 , C12R1/91 , G01N33/50 , G01N33/566 , G01N33/573 , C12Q1/34 , C12Q1/37 , C12Q1/46 , C12Q1/48
CPC分类号： C07K16/40 , A61K31/00 , A61K31/195 , A61K31/198 , C12N9/1077 , C12Q1/25 , C12Q1/6886 , G01N33/5005 , G01N33/573 , C12Q2600/106 , Y10S435/963 , Y10S435/968 , Y10S435/975
摘要： An in vivo method for depleting mammalian cells of adenosine 5'-monophosphate (AMP) useful in the treatment of certain cancers is provided. According to the method, a population of cells is obtained from a host and assayed for loss of methylthioadenosine phosphorylase (MTAse) activity. MTAse catabolizes methylthioadenosine to adenine for endogenous salvage incorporation into the intracellular AMP pool. The preferred method for assaying loss of MTAse activity is a hybridization technique for detection of a homozygous loss of the gene which encodes MTAse. Hosts having MTAse deficient tumors are treated with a therapeutically effective amount of an agent which inhibits the activity of adenylsuccinate synthetase, which converts inosine 5'-monophosphate to AMP, thus depleting the tumor cells of substrates for de novo AMP production. L-alanosine is the preferred ASS inhibitory agent for use in the method of the invention.
摘要翻译：提供了用于消除用于治疗某些癌症的腺苷5'-单磷酸（AMP）的哺乳动物细胞的体内方法。根据该方法，从宿主获得细胞群并测定甲硫基腺苷磷酸化酶（MTAse）活性的损失。 MTAs将甲基硫代腺苷分解为腺嘌呤，用于内源性补救并入细胞内AMP库。用于测定MTAse活性丧失的优选方法是用于检测编码MTAse的基因的纯合丢失的杂交技术。具有MTAse缺陷肿瘤的宿主用治疗有效量的抑制腺苷酸琥珀酸合成酶的活性的药物进行治疗，所述药物将肌苷5'-单磷酸转化为AMP，从而消耗底物的肿瘤细胞用于从头AMP产生。 L-肌氨酸是用于本发明方法的优选的ASS抑制剂。

2. 发明授权

US5506213A Adminstration of 2'-halo-2'-deoxy adenosine to treat inflammatory bowel disease 失效
标题翻译：管理2'-卤-2'-脱氧腺苷治疗炎症性肠病
公开(公告)号：US5506213A
公开(公告)日：1996-04-09
申请号：US246328
申请日：1994-05-19
申请人： Dennis A. Carson , Carlos J. Carrera
发明人： Dennis A. Carson , Carlos J. Carrera
IPC分类号： C07H19/173 , A61K20060101 , A61K31/52 , A61K31/70 , A61K31/7042 , A61K31/7052 , A61K31/7076 , A61P25/00 , A61P25/28 , A61P37/00 , C07H19/16
CPC分类号： A61K31/70 , C07H19/16
摘要： Novel adenine derivatives whose structures are represented by Formula I, are disclosed, as are methods of using those compounds and others of Formula II to treat monocyte-mediated disorders such as rheumatoid arthritis and multiple sclerosis.
摘要翻译：公开了结构由式I表示的新型腺嘌呤衍生物，以及使用这些化合物和其它式II治疗单核细胞介导的疾病如类风湿性关节炎和多发性硬化的方法。

3. 发明授权

US06214571B1 Method for inhibiting adenylosuccinate synthetase activity in malignant methylthioadenosine phosphorylase deficient cells 失效
标题翻译：恶性甲基硫代腺苷磷酸化酶缺陷型细胞中腺苷酸琥珀酸合成酶抑制活性的方法
公开(公告)号：US06214571B1
公开(公告)日：2001-04-10
申请号：US09199137
申请日：1998-11-24
申请人： Carlos J. Carrera , Dennis A. Carson , Howard B. Cottam , Tsutomu Nobori
发明人： Carlos J. Carrera , Dennis A. Carson , Howard B. Cottam , Tsutomu Nobori
IPC分类号： C12Q134
CPC分类号： C12Q1/6886 , A61K31/198 , C12N9/1077
摘要： An in vivo method for depleting mammalian cells of adenosine 5′-monophosphate (AMP) useful in the treatment of certain cancers is provided. According to the method, a population of cells is obtained from a host and assayed for loss of methylthioadenosine phosphorylase (MTAse) activity. MTAse catabolizes methylthioadenosine to adenine for endogenous salvage incorporation into the intracellular AMP pool. The preferred method for assaying loss of MTAse activity is a hybridization technique for detection of a homozygous loss of the gene which encodes MTAse. Hosts having MTAse deficient tumors are treated with a therapeutically effective amount of an agent which inhibits the activity of adenylsuccinate synthetase, which converts inosine 5-monophosphate to AMP, thus depleting the tumor cells of substrates for de novo AMP production. L-alanosine is the preferred ASS inhibitory agent for use in the method of the invention.
摘要翻译：提供了用于消除用于治疗某些癌症的腺苷5'-单磷酸（AMP）的哺乳动物细胞的体内方法。根据该方法，从宿主获得细胞群并测定甲硫基腺苷磷酸化酶（MTAse）活性的损失。 MTAs将甲基硫代腺苷分解为腺嘌呤，用于内源性补救并入细胞内AMP库。用于测定MTAse活性丧失的优选方法是用于检测编码MTAse的基因的纯合丢失的杂交技术。具有MTAse缺陷肿瘤的宿主用治疗有效量的抑制腺苷酸琥珀酸合成酶活性的药物进行治疗，其将5-单磷酸肌苷转化为AMP，从而消耗底物的肿瘤细胞用于从头AMP产生。 L-肌氨酸是用于本发明方法的优选的ASS抑制剂。

4. 发明授权

US5310732A 2-halo-2'-deoxyadenosines in the treatment of rheumatoid arthritis 失效
标题翻译： 2-卤-2'-脱氧腺苷治疗类风湿性关节炎
公开(公告)号：US5310732A
公开(公告)日：1994-05-10
申请号：US838546
申请日：1992-02-19
申请人： Dennis A. Carson , Carlos J. Carrera
发明人： Dennis A. Carson , Carlos J. Carrera
IPC分类号： C07H19/173 , A61K20060101 , A61K31/52 , A61K31/70 , A61K31/7042 , A61K31/7052 , A61K31/7076 , A61P25/00 , A61P25/28 , A61P37/00 , C07H19/16
CPC分类号： A61K31/70 , C07H19/16
摘要： Novel adenine derivatives whose structures are represented by Formula I, are disclosed, as are methods of using those compounds and others of Formula II to treat monocyte-mediated disorders such as rheumatoid arthritis and multiple sclerosis.
摘要翻译：公开了其结构由式I表示的新型腺嘌呤衍生物，以及使用这些化合物和其它式II治疗单核细胞介导的病症如类风湿性关节炎和多发性硬化症的方法。

5. 发明授权

US06210917B1 Method for suppressing multiple drug resistance in cancer cells 失效
标题翻译：抑制癌细胞多重耐药性的方法
公开(公告)号：US06210917B1
公开(公告)日：2001-04-03
申请号：US08956657
申请日：1997-10-23
申请人： Dennis A. Carson , Carlos J. Carrera
发明人： Dennis A. Carson , Carlos J. Carrera
IPC分类号： C12Q134
CPC分类号： C07K16/40 , C12N9/1077 , C12Q1/25 , C12Q1/6886 , C12Q2600/106 , C12Q2600/156 , G01N33/5005 , G01N33/573
摘要： Methods for treating and preventing the onset and maintainance of multiple drug resistance (MDR) in animals undergoing chemotherapy for cancer are provided. According to the methods, target cells are depleted of adenosine 5′-monophosphate (AMP) and adenosine 5′-triphosphate (ATP) such that the cells are unable to support P-glycoprotein activity. According to one method, a population of target cells is obtained from a host and assayed for loss of methylthioadenosine phosphorylase (MTAse) activity. MTAse catabolizes methylthioadenosine to adenine for endogenous salvage incorporation into the intracellular AMP pool. MTAse deficient cells are treated with a purine synthesis inhibitor, such as L-alanosine, which starves the cells of adenine and suppresses P-glycoprotein activity. MTAse competent cells are also treated for MDR with purine synthesis inhibitors. In conjunction with treatment according to the invention, MTAse competent and deficient cells are also treated for malignancy with other anti-cancer drugs. A method for protecting non-malignant cells from adenine starvation during treatment of malignant cells according to the invention is provided.
摘要翻译：提供了治疗和预防接受化疗癌症的动物多发耐药（MDR）发病和维持的方法。根据该方法，靶细胞耗尽腺苷5'-单磷酸（AMP）和腺苷5'-三磷酸（ATP），使得细胞不能支持P-糖蛋白活性。根据一种方法，从宿主获得靶细胞群并测定甲硫基腺苷磷酸化酶（MTAse）活性的损失。 MTAs将甲基硫代腺苷分解为腺嘌呤，用于内源性补救并入细胞内AMP库。 MTAse缺陷细胞用嘌呤合成抑制剂如L-肌氨酸处理，其使腺嘌呤的细胞饥饿并抑制P-糖蛋白活性。 MTAse感受态细胞也用嘌呤合成抑制剂治疗MDR。结合根据本发明的治疗，MTAs感受态细胞和缺陷细胞也用其它抗癌药治疗恶性肿瘤。提供了根据本发明的在恶性细胞治疗期间保护非恶性细胞免于腺嘌呤饥饿的方法。

6. 发明授权

US06576420B1 Method for early diagnosis of, and determination of prognosis in, cancer 失效
标题翻译：癌症早期诊断和预后评估方法
公开(公告)号：US06576420B1
公开(公告)日：2003-06-10
申请号：US09335231
申请日：1999-06-17
申请人： Dennis A. Carson , Mathias Schmid , Carlos J. Carrera
发明人： Dennis A. Carson , Mathias Schmid , Carlos J. Carrera
IPC分类号： C12Q168
CPC分类号： C12Q1/6886 , C12Q2600/112
摘要： The invention provides a method for diagnosis of, and determining a prognosis for, cancer causatively associated with derangements of chromosome 9p21. Underlying the invention is the discovery that such derangements have their genesis in deletions occurring centromeric to STS 3.21, most often including breakpoints in exon 8 and/or between exons 4 and 5 of the gene which codes for methylthioadenosine phosphorylase. As the cancer and tumor development advance, deletions in 9p21 progress centromerically from the genesis point toward the gene encoding p16. Thus, the method of the invention is performed by determining whether (a) portions of the 9p21 region including and telomeric to STS 3.21 are deleted; and (b) portions of the 9p21 region centromeric to STS 3.21 are deleted; wherein a positive finding in step (a) and a negative finding in step(b) are indicative of a cancer in an early stage of tumor development and a positive finding in step (b) is indicative of a cancer in an advanced stage of tumor development.
摘要翻译：本发明提供了用于诊断和确定与9p21染色体紊乱有关的癌症的预后的方法。本发明的基础是这样的发现，即这种紊乱在其发生着丝粒到STS 3.21的缺失中起源，其中通常包括编码甲硫基腺苷磷酸化酶的基因的外显子8和/或外显子4和5之间的断点。随着癌症和肿瘤发展的进展，9p21的缺失从成因指向编码p16的基因。因此，本发明的方法是通过确定（a）是否删除了（a）包括和端粒的9p21区域到STS 3.21的部分; 和（b）9p21区域着丝粒到STS 3.21的部分被删除; 其中步骤（a）中的阳性发现和步骤（b）中的阴性结果指示肿瘤发展早期的癌症，并且步骤（b）中的阳性发现指示肿瘤晚期的癌症发展。

7. 发明授权

US5541164A 2-halo-2'-deoxyadenosines in the treatment of monocyte-mediated inflammatory disease conditions 失效
标题翻译： 2-卤代-2'-脱氧腺苷治疗单核细胞介导的炎性疾病状况
公开(公告)号：US5541164A
公开(公告)日：1996-07-30
申请号：US233056
申请日：1994-04-26
申请人： Dennis A. Carson , Carlos J. Carrera
发明人： Dennis A. Carson , Carlos J. Carrera
IPC分类号： C07H19/173 , A61K20060101 , A61K31/52 , A61K31/70 , A61K31/7042 , A61K31/7052 , A61K31/7076 , A61P25/00 , A61P25/28 , A61P37/00 , C07H19/16
CPC分类号： A61K31/70 , C07H19/16
摘要： Novel adenine derivatives whose structures are represented by Formula I, are disclosed, as are methods of using those compounds and others of Formula II to treat monocyte-mediated disorders such as rheumatoid arthritis and multiple sclerosis.
摘要翻译：公开了结构由式I表示的新型腺嘌呤衍生物，以及使用这些化合物和其它式II治疗单核细胞介导的疾病如类风湿性关节炎和多发性硬化的方法。

8. 发明授权

US5106837A Adenosine derivatives with therapeutic activity 失效
标题翻译：具有治疗活性的腺苷衍生物
公开(公告)号：US5106837A
公开(公告)日：1992-04-21
申请号：US460351
申请日：1990-01-03
申请人： Dennis A. Carson , Carlos J. Carrera
发明人： Dennis A. Carson , Carlos J. Carrera
IPC分类号： C07H19/16
CPC分类号： C07H19/16
摘要： Novel adenine derivatives whose structures are represented by Formula I, are disclosed, as are methods of using those compounds and others of Formula II to treat monocyte-mediated disorders and autoimmune diseases.
摘要翻译：公开了其结构由式I表示的新型腺嘌呤衍生物，以及使用那些化合物和其它式II治疗单核细胞介导的病症和自身免疫性疾病的方法。

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