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1. 发明申请

US20050191676A1 Detection of nucleic acids by target-catalyzed product formation 审中-公开
标题翻译：通过靶催化产物形成检测核酸
公开(公告)号：US20050191676A1
公开(公告)日：2005-09-01
申请号：US11054255
申请日：2005-02-09
申请人： Linda Western , Samuel Rose , Edwin Ullman
发明人： Linda Western , Samuel Rose , Edwin Ullman
IPC分类号： C12Q1/68 , C07H21/04 , C12P19/34
CPC分类号： C12Q1/689 , C12Q1/682 , C12Q1/6823 , C12Q2521/319 , C12Q2537/149 , C12Q2521/301 , C12Q2563/101
摘要： A method is disclosed for modifying an oligonucleotide, which method has application to the detection of a polynucleotide analyte. An oligonucleotide is reversibly hybridized with a polynucleotide, for example, a polynucleotide analyte, in the presence of a 5′-nuclease under isothermal conditions. The polynucleotide analyte serves as a recognition element to enable a 5′-nuclease to cleave the oligonucleotide to provide (i) a first fragment-that is substantially non-hybridizable to the polynucleotide analyte and (ii) a second fragment that lies 3′ of the first fragment (in the intact oligonucleotide) and is substantially hybridizable to the polynucleotide analyte. At least a 100-fold molar excess of the first fragment and/or the second fragment are obtained relative to the molar amount of the polynucleotide analyte. The presence of the first fragment and/or the second fragment is detected, the presence thereof indicating the presence of the polynucleotide analyte. The method has particular application to the detection of a polynucleotide analyte such as DNA. Kits for conducting methods in accordance with the present invention are also disclosed.
摘要翻译：公开了一种修饰寡核苷酸的方法，该方法可用于检测多核苷酸分析物。在等温条件下，在5'-核酸酶的存在下，寡核苷酸与多核苷酸例如多核苷酸分析物可逆地杂交。多核苷酸分析物用作识别元件，以使5'-核酸酶切割寡核苷酸以提供（i）与多核苷酸分析物基本上不可杂交的第一片段和（ii）位于3'末端的第3个片段第一片段（在完整寡核苷酸中）并且与多核苷酸分析物基本上可杂交。相对于多核苷酸分析物的摩尔量，获得至少100倍摩尔过量的第一片段和/或第二片段。检测到第一片段和/或第二片段的存在，其存在表明多核苷酸分析物的存在。该方法特别适用于多核苷酸分析物如DNA的检测。还公开了用于根据本发明的方法的套件。

2. 发明授权

US5665357A Antibodies recognizing tumor associated antigen CA 55.1 失效
标题翻译：识别肿瘤相关抗原CA 55.1的抗体
公开(公告)号：US5665357A
公开(公告)日：1997-09-09
申请号：US353400
申请日：1994-12-02
申请人： Michael Samuel Rose , Christopher Boot , Clive Graham Copley , Douglas Stephen Paterson , Susan Margaret Hall , Andrew Firman Wright , David Charles Blakey
发明人： Michael Samuel Rose , Christopher Boot , Clive Graham Copley , Douglas Stephen Paterson , Susan Margaret Hall , Andrew Firman Wright , David Charles Blakey
IPC分类号： A01H5/00 , A01K67/027 , A61K38/00 , A61K39/00 , A61K39/38 , A61K39/395 , A61P35/00 , C07K7/06 , C07K7/08 , C07K14/705 , C07K16/30 , C12N5/10 , C12N7/00 , C12N15/09 , C12N15/13 , C12P21/08 , G01N33/53 , G01N33/577 , C07K19/00 , C12N5/12
CPC分类号： C07K16/3046 , C07K14/705 , A61K38/00
摘要： Antibodies which recognize a tumor related antigen designated CA55.1 such as hybridoma 55.1 deposited as ECACC deposit no. 93081901 in which the complementarity determining regions have the following sequences:a) heavy chainCDR1 G Y W I H (SEQ ID NO: 27)CDR2 E V N P S T G R S D Y N E K F K N (SEQ ID NO: 28)CDR3 E R A Y G Y D D A M D Y (SEQ ID NO: 29)b) light chainCDR1 K S S Q S L L N S R T R K N Y L A (SEQ ID NO: 30)CDR2 W A S T R T S (SEQ ID NO: 31)CDR3 K Q S Y T L R T (SEQ ID NO: 32)or a conservative analogue thereof. The peptide ACEHRGSGWC (SEQ ID NO: 26), as displayed on the surface of bacteriophage NCIMB No. 40638, is a mimic of the tumor related antigen CA55.1.
摘要翻译：识别称为CA55.1的肿瘤相关抗原的抗体，例如作为ECACC保藏号存放的杂交瘤55.1。其中互补决定区具有以下序列：a）重链CDR1 GYWIH（SEQ ID NO：27）CDR2 EVNPSTGRSDYNEKFKN（SEQ ID NO：28）CDR3 ERAYGYDDAMDY（SEQ ID NO：29）b）轻链CDR1 KSSQSLLNSRTRKNYLA SEQ ID NO：30）CDR2 WASTRTS（SEQ ID NO：31）CDR3KQSYTLRT（SEQ ID NO：32）或其保守类似物。如在噬菌体NCIMB号40638的表面上显示的肽ACEHRGSGWC（SEQ ID NO：26）是肿瘤相关抗原CA55.1的模拟物。

3. 发明授权

US2595545A Film reeling apparatus 失效
标题翻译：薄膜卷取机
公开(公告)号：US2595545A
公开(公告)日：1952-05-06
申请号：US79269447
申请日：1947-12-19
申请人： BENJAMIN ROSE , SAMUEL ROSE
发明人： BENJAMIN ROSE , SAMUEL ROSE
IPC分类号： G03D13/04
CPC分类号： G03D13/043

4. 发明申请

US20100062006A9 Method and composition for the treatment of cancer by the enzymatic conversion of soluble radioactive toxic precipitates in the cancer 有权
公开(公告)号：US20100062006A9
公开(公告)日：2010-03-11
申请号：US10898585
申请日：2004-07-23
申请人： George Mayers , Samuel Rose , Lottie Rose
发明人： George Mayers , Samuel Rose , Lottie Rose
IPC分类号： G01N33/53 , G01N33/567 , A61K49/00 , A61K39/395
CPC分类号： C07K16/30 , A61K2039/505 , C07K2317/31 , C07K2317/77
摘要： The invention features compositions and methods for treating or alleviating a symptom of cancer. The compositions and methods of the invention direct supra-lethal doses of radiation, called Hot-Spots, to virtually all cancer cell types.

5. 发明授权

US6080383A Method and composition for the treatment of cancer by the enzymatic conversion of soluble radioactive toxic agents into radioactive toxic precipitates in the cancer 失效
公开(公告)号：US6080383A
公开(公告)日：2000-06-27
申请号：US782219
申请日：1997-01-13
申请人： Samuel Rose
发明人： Samuel Rose
IPC分类号： A61K45/00 , A61K31/717 , A61K31/722 , A61K31/74 , A61K38/00 , A61K49/00 , A61K51/04 , A61P35/00 , C07K16/00 , A61K51/00 , A61M36/14
CPC分类号： A61K51/0497 , A61K2039/505 , C07K2317/31 , Y02P20/582
摘要： A method for the treatment of cancer is disclosed which is capable of directing supra-lethal doses of radiation, called Hot-Spots, virtually exclusively to the cancer. The present invention involves a multi-step therapy process and includes a class of novel chemical agents. In accordance with the present invention, it was discovered that soluble precipitable materials can be made to accumulate as non-digestible precipitates in targeted cells as a result of enzyme action within the targeted cells. Accumulation is achieved by administering to the living host a soluble binary reagent made by attaching a targeting agent to a novel chemical agent which is a soluble precipitable material. The binary reagent binds to antigenic receptors on targeted cells which endocytose the binary reagent and transport it into the lysosomes where enzymes detach the soluble precipitable material from the targeting agent, causing it to precipitate, accumulate, and be retained in the cells. Increasing amounts of precipitate can be made to accumulate in cells by continuing the administration of the binary reagent. The accumulated precipitate is relocated to the extra-cellular fluid by selectively killing a fraction of cancer cells. Now relocated in the extra-cellular fluid of the cancer, the precipitate is used as a "platform" from which to generate Hot-Spots. A bispecific reagent with a non-mammalian enzyme moiety is made to bind to the precipitate. A soluble radioactive material is administered which is converted by the enzyme moiety of the bound bispecific reagent into a new form which is retained adjacent to the precipitate for an extended period of time, thereby generating Hot-Spots which non-selectively kill all cells adjacent to the precipitate in the extra-cellular fluid of the cancer.

6. 发明授权

US5508178A Nucleic acid amplification using single primer 失效
公开(公告)号：US5508178A
公开(公告)日：1996-04-16
申请号：US194140
申请日：1994-02-09
申请人： Samuel Rose , Thomas C. Goodman , Linda M. Western , Martin Becker , Edwin F. Ullman
发明人： Samuel Rose , Thomas C. Goodman , Linda M. Western , Martin Becker , Edwin F. Ullman
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/6858 , Y10S435/81
摘要： A method is disclosed for determining the presence of a polynucleotide analyte in a sample suspected of containing the analyte. The method comprises (a) forming as a result of the presence of an analyte a single stranded polynucleotide comprising a target polynucleotide binding sequence flanked by first and second polynucleotide sequences that differ from the sequence of the analyte or a sequence complementary to the analyte sequence, (b) forming multiple copies of the single stranded polynucleotide, and (c) detecting the single stranded polynucleotide. Also disclosed is a method of producing at least one copy of a single stranded polynucleotide. The method comprises (a) forming in the presence of nucleoside triphosphates and template dependent polynucleotide polymerase an extension of a polynucleotide primer at least the 3'-end of which has at least a 10 base sequence hybridizable with a second sequence flanking the 3'-end of the single stranded polynucleotide, the second sequence being partially or fully complementary with at least a 10 base first sequence flanking the 5' end of the single stranded polynucleotide, (b) dissociating the extended polynucleotide primer and the single stranded polynucleotide, (c) repeating step a and (d) dissociating the extended polynucleotide primer and the copy of the single stranded polynucleotide.

7. 发明授权

US07807136B2 Method and composition for the treatment of cancer by the enzymatic conversion of soluble radioactive toxic precipitates in the cancer 有权
标题翻译：通过癌症中可溶性放射性毒性沉淀物的酶转化治疗癌症的方法和组合物
公开(公告)号：US07807136B2
公开(公告)日：2010-10-05
申请号：US10898585
申请日：2004-07-23
申请人： George L. Mayers , Samuel Rose , Lottie Rose, legal representative
发明人： George L. Mayers , Samuel Rose
IPC分类号： A61K49/00
CPC分类号： C07K16/30 , A61K2039/505 , C07K2317/31 , C07K2317/77
摘要： The invention features compositions and methods for treating or alleviating a symptom of cancer. The compositions and methods of the invention direct supra-lethal doses of radiation, called Hot-Spots, to virtually all cancer cell types.
摘要翻译：本发明的特征在于治疗或缓解癌症症状的组合物和方法。本发明的组合物和方法直接将超致命剂量的辐射称为热点，几乎所有的癌细胞类型。

8. 发明申请

US20050113290A1 Method and composition for treating cancer by converting soluble radioactive toxic agents into insoluble radioactive toxic precipitates via the action of non-mammalian enzymes bound to the non-endocytosing receptors of target cells 审中-公开
标题翻译：通过结合靶细胞的非内吞受体的非哺乳动物酶的作用将可溶性放射性毒素转化为不溶性放射性毒性沉淀物来治疗癌症的方法和组合物
公开(公告)号：US20050113290A1
公开(公告)日：2005-05-26
申请号：US10949671
申请日：2004-09-25
申请人： Samuel Rose
发明人： Samuel Rose
IPC分类号： A61K38/47 , A61K38/48 , A61K38/50 , A61K45/06 , A61K48/00 , A61K31/737
CPC分类号： A61K38/47 , A61K38/50 , A61K38/51 , A61K45/06
摘要： A method for the treatment of cancer is disclosed which is capable of directing supra-lethal doses of radiation, called Hot-Spots, virtually exclusively to the cancer. The present invention involves a multi-step therapy process and includes a class of novel chemical agent. In accordance with the present invention, it was discovered that soluble precipitable materials can be made to accumulate as non-digestible precipitates in the extra-cellular fluid in the cancer region as a result of non-mammalian enzyme action. Precipitate accumulation is achieved by prior administration of a bispecific reagent with a non-mammalian enzyme moiety and a agent capable of binding to non-endocytosing receptors of target cancer cells. A soluble radioactive toxic therapeutic agent is then administered, the soluble toxic therapeutic agent being adapted to be converted by the non-mammalian enzyme moiety of the bound bispecific reagent into a new form which is retained adjacent to the target cancer cells for an extended period of time, thereby generating Hot-Spots which non-selectively kill all cells in the cancer region adjacent to the bispecific reagent.
摘要翻译：公开了一种治疗癌症的方法，其能够实际上专门针对癌症引导称为热点的超致命剂量的辐射。本发明涉及一种多步骤治疗方法，包括一类新型化学试剂。根据本发明，发现由于非哺乳动物酶作用，可溶性可沉淀物质可以作为不可消化的沉淀物积聚在癌症区域中的细胞外流体中。通过先前给予非哺乳动物酶部分的双特异性试剂和能够结合靶癌细胞的非内吞受体的试剂来实现沉淀物积累。然后施用可溶性放射性毒性治疗剂，所述可溶性毒性治疗剂适于由结合的双特异性试剂的非哺乳动物酶部分转化为与靶癌细胞相邻的新形式延长的时间从而产生不选择性地杀死邻近双特异性试剂的癌症区域中的所有细胞的热点。

9. 发明申请

US20050058652A1 Method and composition for the treatment of cancer by the enzymatic conversion of soluble radioactive toxic precipitates in the cancer 有权
标题翻译：通过癌症中可溶性放射性毒性沉淀物的酶转化治疗癌症的方法和组合物
公开(公告)号：US20050058652A1
公开(公告)日：2005-03-17
申请号：US10898585
申请日：2004-07-23
申请人： George Mayers , Samuel Rose , Lottie Rose
发明人： George Mayers , Samuel Rose , Lottie Rose
IPC分类号： C07K16/30 , G01N33/53 , A61K39/395 , A61K49/00 , G01N33/567
CPC分类号： C07K16/30 , A61K2039/505 , C07K2317/31 , C07K2317/77
摘要： The invention features compositions and methods for treating or alleviating a symptom of cancer. The compositions and methods of the invention direct supra-lethal doses of radiation, called Hot-Spots, to virtually all cancer cell types.
摘要翻译：本发明的特征在于治疗或缓解癌症症状的组合物和方法。本发明的组合物和方法直接将超致命剂量的辐射称为热点，几乎所有的癌细胞类型。

10. 发明授权

US5816259A Method for the diagnosis and treatment of cancer by the accumulation of radioactive precipitates in targeted cells 失效
标题翻译：通过靶向细胞中放射性沉淀物的积累来诊断和治疗癌症的方法
公开(公告)号：US5816259A
公开(公告)日：1998-10-06
申请号：US782380
申请日：1997-01-13
申请人： Samuel Rose
发明人： Samuel Rose
IPC分类号： A61K51/12 , A61B19/00
CPC分类号： A61K51/12
摘要： A method for the accumulation of trace-labeled or therapeutic insoluble molecules in targeted cells of a living host for purposes including diagnosis, therapy, and research in cell biology. The method enables soluble precipitable materials, which can be trace-labeled or therapeutic, to be made to accumulate as non-digestible precipitates in targeted cells as a result of enzyme action within the targeted cells. Accumulation is achieved by administering to the living host a soluble binary reagent having a targeting agent attached to a chemical agent which is a soluble precipitable material. The binary reagent binds to antigenic receptors on targeted cells which endocytosed the binary reagent and transport it into the lysosomes where enzymes detach the soluble precipitable material from the targeting agent, causing it to precipitate, accumulate, and be retained in the cells. Continuing the administration of the binary reagent forms an accumulation of precipitate which becomes a stable insoluble tracer agent or a stable insoluble therapeutic agent in the targeted cells. The method can be applied to the diagnosis and scanning of certain diseased states, and to the therapy of certain diseased states, such as cancer, by generating supra-lethal micro-regions of radiation around targeted cells called Hot-Spots which are capable of killing, non-specifically, all cells in the immediate micro-region.
摘要翻译：用于在活体宿主的靶细胞中积累痕量标记或治疗不溶性分子的方法，包括细胞生物学中的诊断，治疗和研究。该方法使可溶性可沉淀材料（其可以是痕量标记的或治疗性的）作为靶细胞中的酶作用的结果在靶细胞中积累为不可消化的沉淀物。通过向活体宿主施用可溶性二元试剂来实现累积，所述可溶性二元试剂具有连接到作为可溶性可沉淀材料的化学试剂的靶向剂。二元试剂结合靶向细胞上的抗原受体，其内吞胞外二元试剂并将其转运到溶酶体中，其中酶将可溶性可沉淀物质从靶向剂分离，导致其沉淀，积聚并保留在细胞中。继续施用二元试剂形成沉淀物的沉积物，其成为靶细胞中稳定的不溶性示踪剂或稳定的不溶性治疗剂。该方法可以应用于某些疾病状态的诊断和扫描，以及对某些疾病状态如癌症的治疗，通过在能够杀死的称为热点的靶细胞周围产生辐射周围的超致命微区，非特异性地，即时微区域中的所有细胞。

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