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    Use of etodolac to treat hyperplasia
    3.
    发明授权
    Use of etodolac to treat hyperplasia 失效

    公开(公告)号：US07211599B2

    公开(公告)日：2007-05-01

    申请号：US10667208

    申请日：2003-09-19

    申请人： Dennis A. Carson ,  Lorenzo M. Leoni ,  Mary Patricia Corr

    发明人： Dennis A. Carson ,  Lorenzo M. Leoni ,  Mary Patricia Corr

    IPC分类号： A61K31/40 ,  A61K31/56 ,  A61K31/50 ,  A61K31/18 ,  A61K31/12

    CPC分类号： A61K31/12 ,  A61K31/18 ,  A61K31/40 ,  A61K31/407 ,  A61K31/4745 ,  A61K31/496 ,  A61K31/50 ,  A61K31/56 ,  A61K31/675 ,  A61K31/7052

    摘要： The present invention provides a therapeutic method to treat non-malignant diseases characterized by the excessive tissue growth, e.g., hyperplastic diseases, comprising administering to a mammal (e.g., human) afflicted with excessive tissue growth, an effective amount of a derivative of an indole compound of formula (I):formula (I): wherein R1 is lower alkyl, (hydroxy)lower alkyl, lower alkenyl, lower alkynyl, lower cycloalkyl, phenyl, benzyl or 2-thienyl; R2, R3, R4 and R5 are the same or different and are each hydrogen or lower alkyl; each R6 is individually hydrogen, lower alkyl, hydroxy, (hydroxy)lower alkyl, lower alkoxy, benzyloxy, lower alkanoyloxy, nitro or halo, R7 is hydrogen, lower alkyl or lower alkenyl, X is oxy and thio, Y is carbonyl, —(CH2)1-3—, —(C1-C3)alkyl(CO)—, or —(CH2)1-3SO2—; Z is hydroxy, lower alkoxy, (C2-C4)acyloxy, —N(R8)(R9), phenylamino, (ω-(4-pyridyl)(C2-C4 alkoxy), (ω-((R8)(R9)amino)(C2-C4 alkoxy), an amino acid ester of (ω-(HO)(C2-C4))alkoxy, —N(R8)CH(R8)CO2H, 1′-D-glucuronyloxy, —SO3H, —PO4H2, —N(NO)(OH), —SO2NH2, —PO(OH)(NH2), —OCH2CH2N(CH3)3+, or tetrazolyl; wherein R8 and R9 are each H, (C1-C3)alkyl or together with N are a 5- or 6-membered heterocyclic ring comprising 1-3 N(R8), S or nonperoxide O; n is 0, 1, 2, or 3; wherein R8 and R9 are each H, (C1-C3)alkyl or together with N are a 5- or 6-membered heterocyclic ring comprising 1-3 N(R8), S or nonperoxide O; each alkyl or phenyl group of R1, R2, R3, R4, R5, R6, R7 and Z is optionally substituted with 1, 2, or 3 (C1-C4)alkyl groups; or a pharmaceutically acceptable salt thereof.

    Cyclin dependent kinase 4 inhibitor
    5.
    发明授权
    Cyclin dependent kinase 4 inhibitor 失效
    细胞周期蛋白依赖性激酶4抑制剂

    公开(公告)号：US06689864B1

    公开(公告)日：2004-02-10

    申请号：US08921954

    申请日：1997-08-26

    申请人： Dennis A. Carson ,  Tsutomu Nobori

    发明人： Dennis A. Carson ,  Tsutomu Nobori

    IPC分类号： C07K100

    CPC分类号： C07K16/18 ,  A61K38/00 ,  C07K14/4703

    摘要： A gene that encodes an inhibitor of CDK4 has been discovered and its genomic nucleotide sequence has been identified. Susceptibility to certain cancers has been shown to be causatively related to the deletion of, or polymorphisms in, the CDK4I gene. The invention is therefore directed to the gene (CDK4I), the inhibitor protein, as well as therapeutic and diagnostic methods which utilize both the CDK4I gene and the CDK4I protein.

    摘要翻译： 已经发现了编码CDK4抑制剂的基因，并且已经鉴定了其基因组核苷酸序列。 已经显示某些癌症的易感性与CDK4I基因的缺失或多态性有关。 因此，本发明涉及基因（CDK4I），抑制剂蛋白质，以及利用CDK4I基因和CDK4I蛋白质的治疗和诊断方法。

    Tumor suppressor gene and methods for detection of cancer, monitoring of tumor progression and cancer treatment
    6.
    发明授权
    Tumor suppressor gene and methods for detection of cancer, monitoring of tumor progression and cancer treatment 失效
    肿瘤抑制基因和癌症检测方法，肿瘤进展监测和癌症治疗

    公开(公告)号：US06689561B1

    公开(公告)日：2004-02-10

    申请号：US08227800

    申请日：1994-04-14

    申请人： Dennis A. Carson ,  Tsutomu Nobori

    发明人： Dennis A. Carson ,  Tsutomu Nobori

    IPC分类号： C12Q168

    CPC分类号： C07K14/4703 ,  A61K38/00 ,  C07K16/18

    摘要： A gene that encodes an inhibitor of CDK4 has been discovered and its genomic nucleotide sequence has been identified. Susceptibility to certain cancers has been shown to be causatively related to the deletion of, or polymorphisms in, the CDK4I gene. The invention is therefore directed to the gene (CDK4I), the inhibitor protein, as well as therapeutic and diagnostic methods which utilize both the CDK4I gene and the CDK4I protein.

    摘要翻译： 已经发现了编码CDK4抑制剂的基因，并且已经鉴定了其基因组核苷酸序列。 已经显示某些癌症的易感性与CDK4I基因的缺失或多态性有关。 因此，本发明涉及基因（CDK4I），抑制剂蛋白质，以及利用CDK4I基因和CDK4I蛋白质的治疗和诊断方法。

    Method for early diagnosis of, and determination of prognosis in, cancer
    7.
    发明授权
    Method for early diagnosis of, and determination of prognosis in, cancer 失效
    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。

    Method for treating allergic lung disease
    8.
    发明授权
    Method for treating allergic lung disease 失效
    治疗过敏性肺病的方法

    公开(公告)号：US06426336B1

    公开(公告)日：2002-07-30

    申请号：US09689445

    申请日：2000-10-12

    申请人： Dennis A. Carson ,  Eval Raz

    发明人： Dennis A. Carson ,  Eval Raz

    IPC分类号： A01N4304

    CPC分类号： C07K14/005 ,  A61B17/20 ,  A61B17/205 ,  A61K38/00 ,  A61K39/00 ,  A61K39/12 ,  A61K39/145 ,  A61K39/35 ,  A61K48/00 ,  A61K2039/51 ,  A61K2039/5154 ,  A61K2039/53 ,  A61K2039/541 ,  A61K2039/55561 ,  A61K2039/57 ,  C07K14/245 ,  C07K14/495 ,  C07K14/5406 ,  C07K14/55 ,  C07K14/77 ,  C07K16/00 ,  C07K2317/77 ,  C12N15/87 ,  C12N2760/16022 ,  C12N2760/16034 ,  G01N33/5091 ,  Y10S514/958

    摘要： The invention is directed to a method for treating both the early and late phases of allergic asthma by introducing naked polynucleotides which operatively encode for the asthma-initiating antigen into the host. The antigen-encoding polynucleotides are administered to host tissues which contain a high concentration of antigen presenting cells (e.g., skin and mucosa) relative to other host tissues. Expression of the asthma-initiating antigen encoding polynucleotides of the invention inside of antigen presenting cells (without substantial secretion therefrom) induces antigen tolerance while suppressing IgE antibody formation in the early phase of the disease, and also suppresses cytokine-mediated eosinophil accumulation in the late phase of the disease. Devices and compositions for use in the methods of the invention are also described.

    摘要翻译： 本发明涉及一种通过引入裸露的多核苷酸来治疗过敏性哮喘的早期和晚期的方法，该多核苷酸可操作地编码哮喘起始抗原进入宿主。 将抗原编码多核苷酸相对于其他宿主组织施用于含有高浓度抗原呈递细胞（例如皮肤和粘膜）的宿主组织。 本发明的抗原呈递细胞内的哮喘起始抗原编码多核苷酸（无大量分泌）在疾病早期抑制IgE抗体形成的同时诱导抗原耐受，并且还抑制晚期的细胞因子介导的嗜酸性粒细胞积累 疾病阶段。 还描述了用于本发明方法的装置和组合物。

    Polymerase chain reaction assays to determine the presence and concentration of a target nucleic acid in a sample
    10.
    发明授权
    Polymerase chain reaction assays to determine the presence and concentration of a target nucleic acid in a sample 失效
    聚合酶链反应测定法以确定样品中靶核酸的存在和浓度

    公开(公告)号：US5747251A

    公开(公告)日：1998-05-05

    申请号：US442141

    申请日：1995-05-16

    申请人： Dennis A. Carson ,  Hitoshi Kohsaka

    发明人： Dennis A. Carson ,  Hitoshi Kohsaka

    IPC分类号： C12Q1/68 ,  C07H21/04 ,  C12P19/34 ,  C12Q1/70

    CPC分类号： C12Q1/6851

    摘要： Combinations of polymerization, non-competitive hybridization and assay techniques is disclosed. In one aspect of the method, one member of a regular or anchored primer pair is modified to include a coupling agent capable of forming a tight bond (resistant to uncoupling in an alkaline denaturing environment) with a reactant. Competitive PCR is performed and the PCR products are coupled via the coupling agent to a reactant on the surface of a solid phase support. The bond between the reactant and the solid phase support in this and all embodiments is also resistant to uncoupling in an alkaline denaturing environment. In another aspect of the method, a primer is tightly coupled to the bound reactant and a polymerization of the competitor and target nucleic acids is performed on the solid phase. A third embodiment uses at least three primers, one of which is internal to the PCR templates and is bound to the solid phase support on which the entire PCR takes place. In the first two embodiments, sense strands are completely removed from solution with the bound antisense strands of the PCR products. Hybridization with sequence-specific probes is then performed in the absence of competition for binding by the sense strands. Sense strand removal and hybridization is optional in the third embodiment, where the bound three-primer PCR products can be detected by a detectible signal. Quantification of the target template may preferably be achieved in all embodiments by an enzyme-linked immunosorbent assay (ELISA), using ELISA data analysis software and standard curves.

    摘要翻译： 公开了聚合，非竞争性杂交和测定技术的组合。 在该方法的一个方面，将规则或锚定引物对的一个成员修饰为包含能够与反应物形成紧密键合（对碱性变性环境中的解偶联的抗性）的偶联剂。 进行竞争性PCR，PCR产物通过偶联剂偶联到固相载体表面的反应物上。 在这个和所有实施方案中，反应物和固相载体之间的键在碱性变性环境中也抵抗解偶联。 在该方法的另一方面，引物与结合的反应物紧密耦合，并且在固相上进行竞争剂和靶核酸的聚合。 第三个实施方案使用至少三个引物，其中一个引物位于PCR模板的内部，并结合到其上进行整个PCR的固相载体上。 在前两个实施方案中，有义链通过PCR产物的结合反义链从溶液中完全除去。 然后在不存在通过有义链结合的竞争的情况下进行与序列特异性探针的杂交。 在第三实施方案中，有义链去除和杂交是任选的，其中结合的三引物PCR产物可以通过可检测信号检测。 可以使用ELISA数据分析软件和标准曲线，优选通过酶联免疫吸附测定（ELISA）在所有实施方案中实现靶模板的定​​量。