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1. 发明授权

US06562819B2 Compounds for inhibition of ceramide-mediated signal transduction 失效
公开(公告)号：US06562819B2
公开(公告)日：2003-05-13
申请号：US09951198
申请日：2001-09-13
申请人： Dennis A. Carson , Howard Cottam
发明人： Dennis A. Carson , Howard Cottam
IPC分类号： C07D21724
CPC分类号： C07D239/545 , C07D213/76 , C07D217/24 , C07D239/96 , C07D473/06 , C07D473/10 , C07D475/02 , C07D513/04
摘要： Novel, heterocyclic compounds having at least one ring nitrogen, disclosed side chains and, in some embodiments, an oxygen ortho to the ring nitrogen inhibit inflammatory responses associated with TNF-&agr; and fibroblast proliferation in vivo and in vitro. The compounds of the invention neither appreciably inhibit the activity of cAMP phosphodiesterase nor the hydrolysis of phosphatidic acid, and are neither cytotoxic nor cytostatic. Preferred compounds of the invention are esters. Methods for the use of the novel compounds to inhibit ceramide-mediated intracellular responses in stimuli in vivo (particularly TN-&agr;) are also described. The methods are expected to be of use in reducing inflammatory responses (for example, after angioplasty), in limiting fibrosis (for example, of the liver in cirrhosis), in inhibiting cell senescence, cell apoptosis and UV induced cutaneous immune suppression. Compounds having enhanced water solubility are also described.

2. 发明授权

US06323201B1 Compounds for inhibition of ceramide-mediated signal transduction 失效
标题翻译：用于抑制神经酰胺介导的信号转导的化合物
公开(公告)号：US06323201B1
公开(公告)日：2001-11-27
申请号：US08858778
申请日：1997-05-19
申请人： Dennis A. Carson , Howard Cottam
发明人： Dennis A. Carson , Howard Cottam
IPC分类号： C07D41306
CPC分类号： C07D239/545 , C07D213/76 , C07D217/24 , C07D239/96 , C07D473/06 , C07D473/10 , C07D475/02 , C07D513/04
摘要： Novel, heterocyclic compounds having at least one ring nitrogen, disclosed side chains and, in some embodiments, an oxygen ortho to the ring nitrogen inhibit inflammatory responses associated with TNF-&agr; and fibroblast proliferation in vivo and in vitro. The compounds of the invention neither appreciably inhibit the activity of cAMP phosphodiesterase nor the hydrolysis of phosphatidic acid, and are neither cytotoxic nor cytostatic. Preferred compounds of the invention are esters. Methods for the use of the novel compounds to inhibit ceramide-mediated intracellular responses in stimuli in vivo (particularly TN-&agr;) are also described. The methods are expected to be of use in reducing inflammatory responses (for example, after angioplasty), in limiting fibrosis (for example, of the liver in cirrhosis), in inhibiting cell senescence, cell apoptosis and UV induced cutaneous immune suppression. Compounds having enhanced water solubility are also described.
摘要翻译：新颖的，具有至少一个环氮的杂环化合物，在一些实施方案中，环氮原子上的氧被抑制与体内和体外TNF-α和成纤维细胞增殖相关的炎性反应。本发明的化合物既不明显地抑制cAMP磷酸二酯酶的活性也不抑制磷脂酸的水解，既不是细胞毒性的也不是细胞抑制的。本发明优选的化合物是酯。还描述了使用新化合物抑制体内刺激中神经酰胺介导的细胞内应答的方法（特别是TN-α）。预期这些方法可用于减少炎症反应（例如血管成形术后），限制纤维化（例如肝硬化），抑制细胞衰老，细胞凋亡和UV诱导的皮肤免疫抑制。还描述了具有增强的水溶性的化合物。

3. 发明申请

US20090324551A1 TLR AGONISTS 审中-公开
公开(公告)号：US20090324551A1
公开(公告)日：2009-12-31
申请号：US12064529
申请日：2006-08-21
申请人： Dennis A. Carson , Kenji Takabayshi , Suzanne Grimshaw , Howard B. Cottam , Michael Chan , Christina C.N. Wu
发明人： Dennis A. Carson , Kenji Takabayshi , Suzanne Grimshaw , Howard B. Cottam , Michael Chan , Christina C.N. Wu
IPC分类号： A61K45/00 , C07D473/00 , A61K31/522 , C12N1/20 , C12N7/00 , A61P35/00
CPC分类号： C07D473/16 , C07D473/18 , C07D473/24 , C07D473/34
摘要： The present invention provides for TLR agonist conjugates (compounds) and compositions, as well as methods of using them. The compounds of the invention are broad-spectrum, long-lasting, and non-toxic combination of synthetic immunostimulatory agents, which are useful for activating the immune system of a mammal, preferably a human and can help direct the pharmacophore to the receptor within the endosomes of target cells and enhance the signal transduction induced by the pharmacophore.
摘要翻译：本发明提供了TLR激动剂缀合物（化合物）和组合物，以及使用它们的方法。本发明的化合物是合成免疫刺激剂的广谱，持久和无毒组合，其可用于激活哺乳动物，优选人的免疫系统，并且可以帮助将药效团引导至受体内的受体靶细胞的内体，并增强由药效团诱导的信号转导。

4. 发明授权

US07250404B2 Lipid-mediated polynucleotide administration to deliver a biologically active peptide and to induce a cellular immune response 失效
标题翻译：脂质介导的多核苷酸施用以递送生物活性肽并诱导细胞免疫应答
公开(公告)号：US07250404B2
公开(公告)日：2007-07-31
申请号：US10202858
申请日：2002-07-26
申请人： Philip L Felgner , Jon A Wolff , Gary H Rhodes , Robert Wallace Malone , Dennis A. Carson
发明人： Philip L Felgner , Jon A Wolff , Gary H Rhodes , Robert Wallace Malone , Dennis A. Carson
IPC分类号： A61K48/00 , A61K9/127 , C12N15/88
CPC分类号： C07K14/005 , A61K9/1272 , A61K48/00 , C07K14/61 , C12N9/0069 , C12N9/1033 , C12N9/1247 , C12N9/78 , C12N15/87 , C12N2740/16122 , C12Y113/12007
摘要： A method for delivering an isolated polynucleotide to the interior of a cell in a vertebrate, comprising the interstitial introduction of an isolated polynucleotide into a tissue of the vertebrate where the polynucleotide is taken up by the cells of the tissue and exerts a therapeutic effect on the vertebrate. The method can be used to deliver a therapeutic polypeptide to the cells of the vertebrate, to provide an immune response upon in vivo translation of the polynucleotide, to deliver antisense polynucleotides, to deliver receptors to the cells of the vertebrate, or to provide transitory gene therapy.
摘要翻译：一种用于将分离的多核苷酸递送至脊椎动物细胞内部的方法，包括将分离的多核苷酸间插入脊椎动物的组织中，其中所述多核苷酸被组织的细胞吸收并对其施用治疗效果脊椎动物。该方法可用于将治疗性多肽递送至脊椎动物的细胞，以在多核苷酸的体内翻译中提供免疫应答，递送反义多核苷酸，将受体递送至脊椎动物的细胞，或提供短暂基因治疗。

5. 发明授权

US07211599B2 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.

6. 发明授权

US06696441B1 Inhibition of p53-induced stress response 失效
标题翻译：抑制p53诱导的应激反应
公开(公告)号：US06696441B1
公开(公告)日：2004-02-24
申请号：US09637531
申请日：2000-08-11
申请人： Howard B. Cottam , Lorenzo M. Leoni , Dennis A. Carson
发明人： Howard B. Cottam , Lorenzo M. Leoni , Dennis A. Carson
IPC分类号： A61K31425
CPC分类号： C07D513/04 , A61K31/519 , C07D487/04
摘要： The present invention provides compounds that act to suppress p53 activity in mammalian cells, and a method to effectively suppress p53 activity in the cells of a mammal subject to a stress or pathology that is ameliorated by such suppression.
摘要翻译：本发明提供了用于抑制哺乳动物细胞中p53活性的化合物，以及有效抑制经受这种抑制而改善的应激或病理学的哺乳动物细胞中p53活性的方法。

7. 发明授权

US06689864B1 Cyclin dependent kinase 4 inhibitor 失效
标题翻译：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。

8. 发明授权

US06689561B1 Tumor suppressor gene and methods for detection of cancer, monitoring of tumor progression and cancer treatment 失效
标题翻译：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。

9. 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。

10. 发明授权

US06426336B1 Method for treating allergic lung disease 失效
标题翻译：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。

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