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1. 发明申请

WO1990012024A1 METHOD OF SYNTHESIZING OLIGONUCLEOTIDES ADAPTABLE TO LARGE SCALE SYNTHESES 审中-公开
标题翻译：合成适合大规模合成的寡核苷酸的方法
公开(公告)号：WO1990012024A1
公开(公告)日：1990-10-18
申请号：PCT/US1990001865
申请日：1990-04-05
申请人： WORCESTER FOUNDATION FOR EXPERIMENTAL BIOLOGY
发明人： WORCESTER FOUNDATION FOR EXPERIMENTAL BIOLOGY , AGRAWAL, Sudhir , ZAMECNIK, Paul, C.
IPC分类号： C07H21/00
CPC分类号： C07H21/00 , B01J19/0046 , B01J2219/00286 , B01J2219/00391 , B01J2219/005 , B01J2219/0059 , B01J2219/00596 , B01J2219/0068 , B01J2219/00722 , C40B40/06 , C40B60/14
摘要： A method of producing synthetic oligonucleotides on a small or large scale using H-phosphonate nucleoside monomers is described. The method can be used to synthesize oligonucleotides of any length, including oligodeoxyribonucleotides and oligoribonucleotides. The method results in a coupling efficiency of greater than 97 % and consumes only two to three equivalents of monomer to activator per coupling reaction. In addition, the method does not require a separate capping step and capping reagent because the activating reagent serves a self-capping function thereby preventing elongation of failed sequences. The H-phosphonate linkages of the fully synthesized oligonucleotide can be oxidized with a variety of reagents to obtain either phosphate diester or other types of modified oligonucleotides.
摘要翻译：描述了使用H-膦酸酯核苷单体小规模生产合成寡核苷酸的方法。该方法可用于合成任何长度的寡核苷酸，包括寡脱氧核糖核苷酸和寡核糖核苷酸。该方法导致大于97％的偶联效率，并且每偶联反应仅消耗2至3当量的活化剂单体。此外，该方法不需要单独的封盖步骤和封盖试剂，因为活化试剂起到自封顶功能，从而防止失效序列的伸长。完全合成的寡核苷酸的H-膦酸酯键可以用各种试剂进行氧化以获得磷酸二酯或其它类型的修饰的寡核苷酸。

2. 发明申请

WO1987007300A2 INHIBITION OF HTLV-III BY EXOGENOUS OLIGONUCLEOTIDES 审中-公开
标题翻译：通过异源寡核苷酸抑制HTLV-III
公开(公告)号：WO1987007300A2
公开(公告)日：1987-12-03
申请号：PCT/US1987001211
申请日：1987-05-22
申请人： WORCESTER FOUNDATION FOR EXPERIMENTAL BIOLOGY
发明人： WORCESTER FOUNDATION FOR EXPERIMENTAL BIOLOGY , GOODCHILD, John , ZAMECNIK, Paul, C.
IPC分类号： C12N15/00
CPC分类号： A61K31/70 , C07H21/00 , C12N15/1131 , C12N15/1132 , C12N2310/315 , C12Q1/701 , C12Q1/703 , G01N33/56988
摘要： Inhibition of HTLV-III by administration of an oligonucleotide complementary to highly conserved regions of the HTLV-III genome necessary for HTLV-III replication and/or gene expression is described, as are oligodeoxynucleotide sequences which are complementary to those regions, methods of inhibiting HTLV-III replication and gene expression and methods of determining the presence or absence of HTLV-III virus in samples such as blood, saliva, urine and tears.

3. 发明申请

WO1994005315A1 TREATMENT OF TUMORS WITH NEUROTROPHIC FACTORS AND CELL PROLIFERATION INHIBITORS 审中-公开
标题翻译：神经营养因子和细胞增殖抑制剂治疗肿瘤
公开(公告)号：WO1994005315A1
公开(公告)日：1994-03-17
申请号：PCT/US1993008088
申请日：1993-08-26
申请人： WORCESTER FOUNDATION FOR EXPERIMENTAL BIOLOGY
发明人： WORCESTER FOUNDATION FOR EXPERIMENTAL BIOLOGY , LoPRESTI, Patrizia , POLUHA, Wojciech , POLUHA, Dorota, K. , ROSS, Alonzo, H.
IPC分类号： A61K37/02
CPC分类号： C07K14/71 , A61K31/045 , A61K31/17 , A61K31/7072 , A61K38/185 , A61K45/06 , A61K48/00 , A61K2300/00
摘要： Disclosed are methods and compositions for treating a neuroblastoma. The methods include contacting the neuroblastoma with a neurotrophic factor and less than a lethal dose of an inhibitor of cell proliferation for about 1 to 15 days, and then maintaining the neuroblastoma in contact with the neurotrophic factor for an additional 1 to 15 days. The composition includes a neurotrophic factor such as the neurotropin, nerve growth factor, and an inhibitor of cell proliferation such as aphidicolin, thymidine, or hydroxyurea. Also disclosed are methods for inducing the remission or differentiation of, or eliminating, a neuroblastoma.
摘要翻译：公开了治疗神经母细胞瘤的方法和组合物。所述方法包括将神经母细胞瘤与神经营养因子和小于致死剂量的细胞增殖抑制剂接触约1至15天，然后将神经母细胞瘤与神经营养因子接触另外1至15天。组合物包括神经营养因子，例如神经营养蛋白，神经生长因子和细胞增殖抑制剂，例如阿奇霉素，胸苷或羟基脲。还公开了诱导神经母细胞瘤的缓解或分化或消除神经母细胞瘤的方法。

4. 发明申请

WO1993015194A1 ENHANCEMENT OF RIBOZYME CATALYTIC ACTIVITY BY A NEIGHBORING FACILITATOR OLIGONUCLEOTIDE 审中-公开
标题翻译：邻苯二甲酸二乙酯加成蓖麻油催化活性的研究
公开(公告)号：WO1993015194A1
公开(公告)日：1993-08-05
申请号：PCT/US1993000783
申请日：1993-02-04
申请人： WORCESTER FOUNDATION FOR EXPERIMENTAL BIOLOGY , GOODCHILD, John
发明人： WORCESTER FOUNDATION FOR EXPERIMENTAL BIOLOGY
IPC分类号： C12N15/11
CPC分类号： C12N15/1132 , A61K38/00 , C07K14/005 , C12N2310/111 , C12N2310/121 , C12N2740/16022
摘要： Methods are disclosed for increasing ribozyme catalytic activity without reducing specificity, which methods comprise contacting an RNA molecule with a ribozyme and a facilitator oligonucleotide. The present invention further provides compositions comprising a ribozyme and an effective amount of a facilitator oligonucleotide. Methods are also disclosed for reducing the concentration of Mg and Mn required by a ribozyme to catalytically cleave target RNA.
摘要翻译：公开了用于增加核酶催化活性而不降低特异性的方法，该方法包括使RNA分子与核酶和促进剂寡核苷酸接触。本发明还提供了包含核酶和有效量的辅助性寡核苷酸的组合物。还公开了降低核酶催化裂解靶RNA所需的Mg 2+和Mn 2+浓度的方法。

5. 发明申请

WO1991012323A1 METHOD OF SITE-SPECIFIC ALTERATION OF RNA AND PRODUCTION OF ENCODED POLYPEPTIDES 审中-公开
标题翻译： RNA的特异性修饰方法和编码的多聚体的生产方法
公开(公告)号：WO1991012323A1
公开(公告)日：1991-08-22
申请号：PCT/US1991000968
申请日：1991-02-13
申请人： WORCESTER FOUNDATION FOR EXPERIMENTAL BIOLOGY
发明人： WORCESTER FOUNDATION FOR EXPERIMENTAL BIOLOGY , PEDERSON, Thoru , AGRAWAL, Sudhir , MAYRAND, Sandra , ZAMECNIK, Paul, C.
IPC分类号： C12N15/10
CPC分类号： C12N15/113 , C12N15/102 , C12N15/8233 , C12N15/8235 , C12N2310/3125 , C12N2310/314 , C12N2310/315
摘要： A method of site-directed alteration (removal or removal followed by replacement) of selected nucleotides in an RNA molecule, as well as to mixed phosphate backbone oligonucleotides useful in the method. It further relates to a method of producing polypeptides or proteins encoded by the RNA molecule altered by the present method. Through use of the present method, site-directed cleavage of an RNA molecule is effected, followed by excision of the selected or target segment of the RNA molecule.

6. 发明申请

WO1995013298A1 AGRIN RECEPTOR 审中-公开
公开(公告)号：WO1995013298A1
公开(公告)日：1995-05-18
申请号：PCT/US1994005387
申请日：1994-05-16
申请人： WORCESTER FOUNDATION FOR EXPERIMENTAL BIOLOGY , FALLON, Justin , BOWE, Mark, A. , McKECHNIE, Beth, A. , NASTUK, Mary, A. , LESZYK, John, D.
发明人： WORCESTER FOUNDATION FOR EXPERIMENTAL BIOLOGY
IPC分类号： C07K14/705
CPC分类号： C07K14/70571
摘要： The present invention relates to agrin receptors, peptides associated with agrin receptors. The invention also relates to the production of antibodies to the agrin receptor. The instant invention provides for the use of agrin receptor in diagnostic assays, testing assays and labelling assays. The instant invention discloses specific amino acid sequences for agrin receptor subunits.
摘要翻译：本发明涉及集聚蛋白受体，与集聚蛋白受体相关的肽。本发明还涉及产生集聚蛋白受体的抗体。本发明提供了在诊断测定，测试测定和标记测定中使用集聚蛋白受体。本发明公开了集聚蛋白受体亚基的特异性氨基酸序列。

7. 发明申请

WO1994002498A1 HYBRID OLIGONUCLEOTIDE PHOSPHOROTHIOATES 审中-公开
标题翻译：混合寡核苷酸磷酸酯
公开(公告)号：WO1994002498A1
公开(公告)日：1994-02-03
申请号：PCT/US1993006884
申请日：1993-07-22
申请人： WORCESTER FOUNDATION FOR EXPERIMENTAL BIOLOGY , METELEV, Valeri , AGRAWAL, Sudhir
发明人： WORCESTER FOUNDATION FOR EXPERIMENTAL BIOLOGY
IPC分类号： C07H21/00
CPC分类号： C12N15/113 , C07H21/00 , C12N15/1132 , C12N2310/313 , C12N2310/315 , C12N2310/321 , C12N2310/341 , C12N2310/346 , C12N2310/3521
摘要： The invention provides hybrid oligonucleotides having phosphorothioate or phosphorodithioate internucleotide linkages, and both deoxyribonucleosides and ribonucleosides or 2'-substituted ribonucleosides. Such hybrid oligonucleotides have superior properties of duplex formation with RNA, nuclease resistance, and RNase H activation.
摘要翻译：本发明提供了具有硫代磷酸酯或二硫代磷酸酯核苷酸间键的杂交寡核苷酸，以及脱氧核糖核苷和核糖核苷或2'-取代的核糖核苷。这样的杂交寡核苷酸具有优异的双链体形成与RNA，核酸酶抗性和RNA酶H活化的性质。

8. 发明申请

WO1992014845A1 DIAGNOSING CYSTIC FIBROSIS AND OTHER GENETIC DISEASES USING FLUORESCENCE RESONANCE ENERGY TRANSFER (FRET) 审中-公开
标题翻译：使用荧光共振能量转移（FRET）诊断CYSTIC FIBROSIS和其他遗传病
公开(公告)号：WO1992014845A1
公开(公告)日：1992-09-03
申请号：PCT/US1992001591
申请日：1992-02-26
申请人： WORCESTER FOUNDATION FOR EXPERIMENTAL BIOLOGY , ZAMECNIK, Paul, C. , AGRAWAL, Sudhir
发明人： WORCESTER FOUNDATION FOR EXPERIMENTAL BIOLOGY
IPC分类号： C12Q01/68
CPC分类号： C12Q1/6818
摘要： The present invention relates to a method of detecting in DNA obtained from an individual an abnormality in DNA which is associated with a genetic desease, with particular reference to cystic fibrosis, using oligonucleotide probes. The probes are labeled with two different fluorophores and hybridize to the regions of normal DNA which correspond to a region of DNA where an abnormal nucleotide sequence exists in a gene, such as that associated with that of cystic fibrosis. Hybridization is detected by fluorescence resonance energy transfer (FRET).
摘要翻译：本发明涉及使用寡核苷酸探针从个体获得的DNA中检测与DNA遗传病相关的异常的方法，特别是涉及囊性纤维化。探针用两种不同的荧光团标记，并与正常DNA区域相对应，该区域对应于基因中存在异常核苷酸序列的DNA区域，例如与囊性纤维化相关的核酸序列。通过荧光共振能量转移（FRET）检测杂交。

9. 发明申请

WO1990009393A1 METHOD OF SEPARATING OLIGONUCLEOTIDES FROM A MIXTURE 审中-公开
标题翻译：从混合物中分离寡核苷酸的方法
公开(公告)号：WO1990009393A1
公开(公告)日：1990-08-23
申请号：PCT/US1990000850
申请日：1990-02-15
申请人： WORCESTER FOUNDATION FOR EXPERIMENTAL BIOLOGY
发明人： WORCESTER FOUNDATION FOR EXPERIMENTAL BIOLOGY , AGRAWAL, Sudhir , ZAMECNIK, Paul, C.
IPC分类号： C07H21/00
CPC分类号： C07H21/00 , C07H1/06
摘要： A method of purifying full length synthetic target oligonucleotides from a mixture of oligonucleotides, particularly from a mixture containing truncated or failed sequences. The method involves attaching a short nucleotide sequence complementary to the 5' end of a target oligonucleotide to a solid support. The complementarity between the most 5' nucleotides of the target oligonucleotide and the bound oligonucleotide results in hybridization which serves to retain the target oligonucleotide. Truncated or failed sequences lacking 5' sequences complementary to the attached oligonucleotide, fail to hybridize and therefore are not retained. The method makes it possible to purify gram quantities of synthetic deoxyribonucleic acids or ribonucleic acids and sequences which have modifications, such as on the phosphate backbone. The support-bound nucleotide sequences are stable under conditions of purification and therefore can be reused.
摘要翻译：从寡核苷酸的混合物，特别是含有截短或失败序列的混合物中纯化全长合成靶寡核苷酸的方法。该方法包括将与靶寡核苷酸的5'末端互补的短核苷酸序列连接到固体支持物上。靶寡核苷酸的最多5'核苷酸与结合的寡核苷酸之间的互补性导致用于保留靶寡核苷酸的杂交。缺少与所连接的寡核苷酸互补的5'序列的截短或失败序列不能杂交，因此不保留。该方法使得可以纯化克数量的合成脱氧核糖核酸或核糖核酸和具有修饰的序列，例如在磷酸酯骨架上。支持结合的核苷酸序列在纯化条件下是稳定的，因此可以重复使用。

10. 发明申请

WO1986000930A1 RETROVIRAL VACCINES AND VECTORS AND METHODS FOR THEIR CONSTRUCTION 审中-公开
标题翻译：退化疫苗及其构建方法及方法
公开(公告)号：WO1986000930A1
公开(公告)日：1986-02-13
申请号：PCT/US1985001352
申请日：1985-07-18
申请人： WORCESTER FOUNDATION FOR EXPERIMENTAL BIOLOGY
发明人： WORCESTER FOUNDATION FOR EXPERIMENTAL BIOLOGY , ROBINSON, Harriet
IPC分类号： C12N15/00
CPC分类号： C12N15/86 , A61K38/00 , A61K39/00 , C07K14/005 , C12N2740/13022 , C12N2740/13043
摘要： Retroviruses and retrovirus vectors that either are or are not shed into eggs and therefore either do or do not undergo congenital transmission, and methods for making them. This invention is based on the discovery that the ability of exogenous avian leukosis viruses to undergo congenital transmission is determined by gag sequences of the viral genome.
摘要翻译：反转录病毒和逆转录病毒载体，不论是或不会排卵，因此要么做或不经历先天性传播，要么制造它们的方法。本发明基于外源性禽白血病病毒进行先天性传播的能力由病毒基因组的gag序列确定的发现。

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