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41. 发明授权

US06680192B1 Method for producing polymers having a preselected activity 失效
标题翻译：具有预选活性的聚合物的制备方法
公开(公告)号：US06680192B1
公开(公告)日：2004-01-20
申请号：US09726653
申请日：2000-11-28
申请人： Richard A. Lerner , Joseph A. Sorge
发明人： Richard A. Lerner , Joseph A. Sorge
IPC分类号： C12N121
CPC分类号： C07K16/00 , A61K38/00 , C07K16/468 , C07K2317/56
摘要： The present invention relates to a method for isolating from the immunological gene repertoire a gene coding for a receptor having the ability to bind a preselected ligand. Receptors produced by the gene isolated by the method, particularly catalytic receptors, are also contemplated.
摘要翻译：本发明涉及从免疫基因库中分离编码具有结合预选配体的能力的受体的基因的方法。还考虑了通过该方法分离的基因产生的受体，特别是催化受体。

42. 发明授权

US06528254B1 Methods for detection of a target nucleic acid sequence 有权
公开(公告)号：US06528254B1
公开(公告)日：2003-03-04
申请号：US09430692
申请日：1999-10-29
申请人： Joseph A. Sorge
发明人： Joseph A. Sorge
IPC分类号： C12Q168
CPC分类号： C12Q1/686 , C12Q1/6823 , Y10S435/81 , Y10S435/822 , Y10T436/143333 , C12Q2561/109 , C12Q2531/113
摘要： The invention relates to a method of generating a signal indicative of the presence of a target nucleic acid sequence in a sample, where the method includes forming a cleavage structure by incubating a sample containing a target nucleic acid sequence with a nucleic acid polymerase and cleaving the cleavage structure with a FEN nuclease to generate a cleaved nucleic acid fragment. The invention also relates to methods of detecting or measuring a target nucleic acid sequence, where the method includes forming a cleavage structure by incubating a target nucleic acid sequence with a nucleic acid polymerase, cleaving the cleavage structure with a FEN nuclease and detecting or measuring the release of a fragment.

43. 发明授权

US06303313B1 Method for generating libraries of antibody genes comprising amplification of diverse antibody DNAs and methods for using these libraries for the production of diverse antigen combining molecules 失效
标题翻译：产生抗体基因文库的方法，包括扩增多种抗体DNA，以及使用这些文库生产多种抗原结合分子的方法
公开(公告)号：US06303313B1
公开(公告)日：2001-10-16
申请号：US09439732
申请日：1999-11-12
申请人： Michael H. Wigler , Joseph A. Sorge
发明人： Michael H. Wigler , Joseph A. Sorge
IPC分类号： C12Q168
CPC分类号： C12N15/102 , A61K38/00 , C07K16/00 , C07K2319/00 , C12N15/10
摘要： A method of producing libraries of genes encoding antigen-combining molecules or antibodies; a method of producing antigen-combining molecules which does not require an in vivo procedure; a method of obtaining antigen-combining molecules of selected specificity which does not require an in vivo procedure; vectors useful in the present method; and antigen-combining molecules produced by the method. The antigen-combining molecules are useful for the detection, quantitation, purification and neutralization of antigens, as well as for diagnostic, therapeutic and prophylactic purposes.
摘要翻译：一种产生编码抗原结合分子或抗体的基因文库的方法; 生产不需要体内程序的抗原结合分子的方法; 获得不需要体内过程的所选特异性的抗原结合分子的方法; 本方法有用的载体; 和通过该方法产生的抗原结合分子。抗原结合分子可用于抗原的检测，定量，纯化和中和，以及用于诊断，治疗和预防目的。

44. 发明授权

US5556772A Polymerase compositions and uses thereof 失效
标题翻译：聚合酶组合物及其用途
公开(公告)号：US5556772A
公开(公告)日：1996-09-17
申请号：US197791
申请日：1994-02-16
申请人： Joseph A. Sorge , Rebecca L. Mullinax
发明人： Joseph A. Sorge , Rebecca L. Mullinax
IPC分类号： C12N9/12 , C12Q1/68 , C12P19/34
CPC分类号： C12N9/1252 , C12Q1/686
摘要： The subject invention provides novel compositions containing a mixture of (a) an enzyme that possesses substantial 3'-5' exonuclease activity (b) a DNA polymerase with less 3'-5' exonuclease activity than the enzyme with substantial 3'-5' exonuclease activity. Preferably, the DNA polymerase for inclusion in the compositions are DNA polymerases that substantially lack 3'-5' exonuclease activity. A preferred embodiment of the invention is a composition comprising the Taq DNA polymerase (isolated from Thermus aquaticus) and the Pfu DNA polymerase (isolated from Pyrococcus furiosus). Another aspect of the invention is to provide methods for synthesizing polynucleotides, typically DNA, using compositions comprising an enzyme that possesses substantial 3'-5' exonuclease activity and a DNA polymerase with less 3'-5' exonuclease activity than the enzymes possessing substantial 3'-5' exonuclease activity, preferably a DNA polymerase that substantially lacks 3'-5' exonuclease activity. Another aspect of the invention involves the use the subject method of polynucleotide synthesis to carry out the synthesis step in a polymerase chain reaction experiment. Yet another aspect of the invention is to provide kits for the synthesis of polynucleotides, wherein the kits comprise an enzyme that possesses substantial 3'-5' exonuclease activity and a DNA polymerase with less 3'-5' exonuclease activity than the enzyme possessing substantial 3'-5' exonuclease activity.
摘要翻译：本发明提供了包含（a）具有大量3'-5'核酸外切酶活性的酶的混合物的新型组合物（b）具有比实际3'-5'核酸外切酶活性大的3'-5'核酸外切酶活性的3' 核酸外切酶活性。优选地，包含在组合物中的DNA聚合酶是基本上缺乏3'-5'核酸外切酶活性的DNA聚合酶。本发明的优选实施方案是包含Taq DNA聚合酶（从Thermus aquaticus分离）和Pfu DNA聚合酶（从激烈热球菌分离的）的组合物。本发明的另一方面是提供使用包含具有大量3'-5'核酸外切酶活性的酶的组合物和具有比具有实质3的酶的3'-5'外切核酸酶活性少的DNA聚合酶合成多核苷酸（通常为DNA）的方法 '-5'核酸外切酶活性，优选基本上缺乏3'-5'核酸外切酶活性的DNA聚合酶。本发明的另一方面涉及使用聚合酶链反应实验中的多核苷酸合成的主题方法进行合成步骤。本发明的另一方面是提供用于合成多核苷酸的试剂盒，其中所述试剂盒包含具有显着3'-5'核酸外切酶活性的酶和具有比具有实质性的酶的酶更少3'-5'外切核酸酶活性的DNA聚合酶 3'-5'核酸外切酶活性。

45. 发明授权

US5487985A Arbitrarily primed polymerase chain reaction method for fingerprinting genomes 失效
标题翻译：用于指纹基因组的任意引物聚合酶链反应方法
公开(公告)号：US5487985A
公开(公告)日：1996-01-30
申请号：US959119
申请日：1992-10-09
申请人： Michael McClelland , John T. Welsh , Joseph A. Sorge
发明人： Michael McClelland , John T. Welsh , Joseph A. Sorge
IPC分类号： C12Q1/68 , C12P19/34
CPC分类号： C12Q1/689 , C12Q2600/156
摘要： A rapid method for generating a set of discrete DNA amplification products characteristic of a genome as a "fingerprint" comprises the steps of: priming target nucleic acid of a genome or from a cellular RNA preparation with an single-stranded primer to form primed nucleic acid such that a substantial degree of internal-mismatching occurs between the primer end the target nucleic acid; amplifying the primed nucleic acid by performing at least one cycle of polymerase chain reaction amplification; and amplifying the product of step (2) by performing at least about 10 cycles of polymerase chain reaction amplification. The method is known as the arbitrarily primed polymerase chain reaction (AP-PCR) method and is suitable for the identification of bacterial species and strains, including Staphylococcus and Streptococcus species, mammals and plants. The method of the present invention can identify species, cell types or tissues rapidly, using only a small amount of biological material, and does not require knowledge of the nucleotide sequence or other molecular biology of the nucleic acids of the organisms to be identified. The method can also be used to generate detectable polymorphisms for use in genetic mapping of animals and humans, and be used to detect differential gene expression within tissues
摘要翻译：用于产生一组基因组特征的离散DNA扩增产物作为“指纹”的快速方法包括以下步骤：用单链引物引发基因组或来自细胞RNA制备物的靶核酸以形成引发的核酸使得目标核酸的引物末端之间发生相当程度的内部错配; 通过进行聚合酶链反应扩增的至少一个循环来扩增引发的核酸; 并通过进行至少约10个循环的聚合酶链反应扩增来扩增步骤（2）的产物。该方法被称为任意引物的聚合酶链反应（AP-PCR）方法，适用于鉴定细菌和菌株，包括葡萄球菌和链球菌属，哺乳动物和植物。本发明的方法可以使用仅少量生物材料快速鉴定物种，细胞类型或组织，并且不需要知道要鉴定的生物体的核酸的核苷酸序列或其他分子生物学。该方法还可用于产生用于动物和人类遗传图谱的可检测多态性，并用于检测组织内差异基因表达

46. 发明授权

US5395591A Apparatus of irradiating biological specimens 失效
标题翻译：照射生物标本的装置
公开(公告)号：US5395591A
公开(公告)日：1995-03-07
申请号：US999434
申请日：1992-12-30
申请人： William C. Zimlich, Jr. , Joseph A. Sorge
发明人： William C. Zimlich, Jr. , Joseph A. Sorge
IPC分类号： C07K17/00 , C12Q1/68 , G05D25/02
CPC分类号： C07K17/00 , C12Q1/68 , Y10T436/25
摘要： A method of irradiating a biological specimen with ultraviolet, in particular a polynucleotide specimen selected from DNA or RNA, or optionally a protein. In the case where the specimen is DNA or RNA, or potentially proteins, the specimen is irradiated to cross-link the specimen to a substrate. In the case where the specimen is DNA, the specimen can also be irradiated to form thymine dimers. The method uses an apparatus which permits relatively precise control of the total ultraviolet dose received by the specimen, despite any changes of ultraviolet flux from the lamps which may occur from during any one experiment, or between a number of experiments. Thus, the method allows relatively highly reproducible results to be obtained.
摘要翻译：用紫外线照射生物样本的方法，特别是选自DNA或RNA的多核苷酸标本，或任选的蛋白质。在标本是DNA或RNA或潜在的蛋白质的情况下，照射样品以将样品交联到基底上。在标本为DNA的情况下，也可以照射样品以形成胸腺嘧啶二聚体。该方法使用允许相对精确地控制由样品接收的总紫外线剂量的装置，尽管在任何一个实验期间或在多个实验之间可能发生来自灯的紫外线通量的任何变化。因此，该方法允许获得相对高度可重复的结果。

47. 发明申请

US20130183345A1 Treatment of Bladder Cancer Following Detection of Expression Levels of Certain Progression Markers 审中-公开
标题翻译：检测某些进展标记的表达水平后膀胱癌的治疗
公开(公告)号：US20130183345A1
公开(公告)日：2013-07-18
申请号：US13791370
申请日：2013-03-08
申请人： Lars Dyrskjøt Andersen , Torben Falck Orntoft , Joseph A. Sorge , Alexey Novoradovsky
发明人： Lars Dyrskjøt Andersen , Torben Falck Orntoft , Joseph A. Sorge , Alexey Novoradovsky
IPC分类号： A61K35/74
CPC分类号： A61K35/74 , C12Q1/6886 , C12Q2600/118 , C12Q2600/158
摘要： Disclosed is determining expression levels of protective or harmful markers for bladder cancer prognosis and treatment; particularly, determining the expression levels of protective markers (COL4A3BP, MBNL2, FABP4, NEK1 and SKAP2) and harmful markers (COL4A1, UBE2C, BIRC5, COL18A1, KPNA2, MSN, ACTA2, and CDC25B) and making treatment decisions in consideration of increased or decreased risk of progression based on the marker expression levels.
摘要翻译：公开了确定膀胱癌预后和治疗的保护性或有害标志物的表达水平; 特别是确定保护性标记（COL4A3BP，MBNL2，FABP4，NEK1和SKAP2）和有害标记（COL4A1，UBE2C，BIRC5，COL18A1，KPNA2，MSN，ACTA2和CDC25B）的表达水平，并考虑到增加或基于标记物表达水平降低进展的风险。

48. 发明授权

US08268605B2 Compositions and methods utilizing DNA polymerases 有权
标题翻译：使用DNA聚合酶的组合物和方法
公开(公告)号：US08268605B2
公开(公告)日：2012-09-18
申请号：US09896923
申请日：2001-06-29
申请人： Joseph A. Sorge , Connie Jo Hansen , Holly Hogrefe
发明人： Joseph A. Sorge , Connie Jo Hansen , Holly Hogrefe
IPC分类号： C12N9/12
CPC分类号： B82Y5/00 , B82Y10/00 , C12N9/1252 , C12N9/1276
摘要： The invention features a novel isolated Family B DNA polymerase, a Thermococcus polymerase JDF-3, and mutant recombinant forms thereof. Mutant polymerases of the invention are deficient in 3′ to 5′ exonuclease activity and/or exhibit reduced discrimination against non-conventional nucleotides relative to the wild-type form of the polymerase.
摘要翻译：本发明的特征在于新的分离的家族B DNA聚合酶，热球菌聚合酶JDF-3及其突变体重组形式。本发明的突变型聚合酶相对于野生型形式的聚合酶，缺乏3'至5'核酸外切酶活性和/或表现出对非常规核苷酸的降低的鉴别。

49. 发明授权

US07846661B2 Methods of detecting an amplified nucleic acid 有权
标题翻译：检测扩增核酸的方法
公开(公告)号：US07846661B2
公开(公告)日：2010-12-07
申请号：US11606651
申请日：2006-11-29
申请人： Joseph A. Sorge
发明人： Joseph A. Sorge
IPC分类号： C12Q1/68 , C12P19/34 , C07H21/00 , C07H21/02 , C07H21/04
CPC分类号： C12Q1/6823 , C12Q1/6816 , C12Q2521/301 , C12Q2531/113 , C12Q2521/307 , C12Q2525/161 , C12Q2525/301 , C12Q2561/109 , C12Q2565/519 , C12Q2561/101 , C12Q2521/107
摘要： The present invention is directed to methods of generating a signal indicative of the presence of said target nucleic acid sequence in a sample, comprising, incubating a sample comprising a an amplified target nucleic acid and a nucleic acid polymerase which substantially lacks 5′ to 3′ exonuclease activity, adding a thermostable fen nuclease consisting of 5′ to 3′ exonuclease and/or endonuclease activity so as to cleave a cleavage structure and generate a signal.
摘要翻译：本发明涉及产生指示样品中所述靶核酸序列存在的信号的方法，包括：将包含扩增的目标核酸和基本上不含5'至3'的核酸聚合酶的样品外切核酸酶活性，加入由5'至3'外切核酸酶和/或核酸内切酶活性组成的热稳定核酸酶切割裂解结构并产生信号。

50. 发明授权

US07659069B2 Binary signaling assay using a split-polymerase 有权
标题翻译：使用裂解聚合酶的二元信号测定
公开(公告)号：US07659069B2
公开(公告)日：2010-02-09
申请号：US11897892
申请日：2007-08-31
申请人： Alexander Belyaev , Craig Robert Monell , Joseph A. Sorge
发明人： Alexander Belyaev , Craig Robert Monell , Joseph A. Sorge
IPC分类号： C12Q1/68
CPC分类号： C12N15/62 , C07K2319/30 , C12N9/1252 , C12Q1/686 , G01N33/542 , G01N33/58 , G01N2458/10 , C12Q2521/101
摘要： The present invention provides methods, kits and compositions for the detection of an analyte. In the methods of the invention, a complex is formed between two or more analyte specific probes (ASP) and an analyte. The analyte specific probes each have a portion of a polymerase which interact to form a functional polymerase complex upon binding of the ASP to the analyte. The functional polymerase complex then generates a detectable signal which is indicative of the presence and/or amount of the analyte in the sample.
摘要翻译：本发明提供了用于检测分析物的方法，试剂盒和组合物。在本发明的方法中，在两种或更多种分析物特异性探针（ASP）和分析物之间形成复合物。分析物特异性探针各自具有聚合酶的一部分，其在ASP与分析物结合时相互作用以形成功能性聚合酶复合物。然后，功能性聚合酶复合物产生可检测的信号，其指示样品中分析物的存在和/或量。

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