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1. 发明授权

US07078389B2 Chemically modified oligonucleotide for site-directed mutagenesis 失效
公开(公告)号：US07078389B2
公开(公告)日：2006-07-18
申请号：US09783338
申请日：2001-02-14
申请人： Peter M. Glazer , Pamela A. Havre
发明人： Peter M. Glazer , Pamela A. Havre
IPC分类号： A01N43/04 , C12Q1/68
CPC分类号： C12N15/113 , C07H21/00 , C12N15/01 , C12N15/102 , C12N2310/15 , C12N2310/3511 , C12Q1/6827
摘要： A mutagenic, triplex-forming oligonucleotide and methods for use thereof wherein the oligonucleotide is chemically modified to incorporate a mutagen and forms a triple-stranded nucleic acid molecule with a specific DNA segment of a target DNA molecule. Upon formation of the triplex, the mutagen is brought into proximity with the target molecule and causes a mutation at a specific site therein. The mutation activates, inactivates or alters the activity and function of the target molecule.

2. 发明申请

US20100172882A1 COMPOSITIONS AND METHODS FOR TARGETED INACTIVATION OF HIV CELL SURFACE RECEPTORS 审中-公开
标题翻译： HIV细胞表面受体靶向灭活的组合物和方法
公开(公告)号：US20100172882A1
公开(公告)日：2010-07-08
申请号：US12522804
申请日：2008-01-11
申请人： Peter M. Glazer , Ranjit Bindra , Erica B. Schleifman
发明人： Peter M. Glazer , Ranjit Bindra , Erica B. Schleifman
IPC分类号： A61K35/12 , C12N15/87 , A61K38/16 , C12N5/00 , A61P31/18
CPC分类号： C12N15/1138 , C12N15/111 , C12N2310/15 , C12N2310/3181 , C12N2310/3519 , C12N2320/30
摘要： Compositions for targeted mutagenesis of cell surface receptors for HIV and methods of their use are provided herein. The compositions include triplex-forming molecules that bind to duplex DNA in a sequence specific manner at target sites to form triple-stranded structures. The triplex-forming molecules can be triplex-forming oligonucleotides (TFOs) or peptide nucleic acids (PNAs). The triplex-forming molecules are useful to induce site-specific homologous recombination in mammalian cells when used in combination with donor oligonucleotides. The triplex-forming molecules target sites within or adjacent to genes that encodes cell surface receptors for human immunodeficiency virus (HIV). This binding stimulates homologous recombination of a donor oligonucleotide to cause mutations in HIV cell surface receptor genes that result in one or more deficiencies in the ability of the encoded receptor to bind to HIV and allow its transport into the cell. Methods for ex vivo and in vivo prophylaxis and therapy of HIV infection using the disclosed compositions are also provided.
摘要翻译：本文提供了用于HIV的细胞表面受体的靶向诱变的组合物及其使用方法。组合物包括在靶位点以序列特异性方式结合双链体DNA的三链体形成分子以形成三链结构。三链体形成分子可以是三重复合形成寡核苷酸（TFO）或肽核酸（PNA）。当与供体寡核苷酸组合使用时，三重形成分子可用于在哺乳动物细胞中诱导位点特异性同源重组。三重形成分子靶向编码人免疫缺陷病毒（HIV）细胞表面受体的基因内或邻近的位点。该结合刺激供体寡核苷酸的同源重组以引起HIV细胞表面受体基因中的突变，其导致编码的受体结合HIV并允许其转运到细胞中的能力的一个或多个缺陷。还提供了使用所公开的组合物进行体外和体内预防和治疗HIV感染的方法。

3. 发明授权

US07279463B2 Triple-helix forming oligonucleotides for targeted mutagenesis 失效
标题翻译：三螺旋形成用于靶向诱变的寡核苷酸
公开(公告)号：US07279463B2
公开(公告)日：2007-10-09
申请号：US09978333
申请日：2001-10-15
申请人： Peter M. Glazer
发明人： Peter M. Glazer
IPC分类号： A61K31/7088 , A61K31/713 , C07H21/02 , C07H21/04
CPC分类号： C12N15/113 , C12N15/01 , C12N15/102 , C12N2310/15
摘要： A high affinity, triplex-forming oligonucleotide and methods for use thereof wherein an oligonucleotide is used to form a triple-stranded nucleic acid molecule with a specific DNA segment of a target DNA molecule. Upon formation of the triplex, the binding of the oligonucleotide stimulates mutagenesis within or adjacent to the target sequence using cellular DNA synthesis or repair mechanisms thereby producing heritable changes in a human or animal. The mutation activates, inactivates or alters the activity and function of the target molecule. This mutation may be the result of a recombinagenic mechanism induced by the oligonucleotide.
摘要翻译：高亲和力，三重复合形成寡核苷酸及其使用方法，其中寡核苷酸用于形成具有靶DNA分子的特异性DNA区段的三链核酸分子。在形成三链体时，寡核苷酸的结合使用细胞DNA合成或修复机制刺激靶序列内或与靶序列相邻的突变，从而在人或动物中产生可遗传的变化。该突变激活，失活或改变靶分子的活性和功能。该突变可能是由寡核苷酸诱导的重组机制的结果。

4. 发明申请

US20140050723A1 Cell-Penetrating Anti-DNA Antibodies and Uses Thereof Inhibit DNA Repair 有权
标题翻译：细胞穿透抗DNA抗体及其用途抑制DNA修复
公开(公告)号：US20140050723A1
公开(公告)日：2014-02-20
申请号：US14009327
申请日：2012-04-02
申请人： James E. Hansen , Peter M. Glazer , Richard H. Weisbart , Robert N. Nishimura , Grace Chan
发明人： James E. Hansen , Peter M. Glazer , Richard H. Weisbart , Robert N. Nishimura , Grace Chan
IPC分类号： C07K16/18
CPC分类号： C07K16/18 , A61K31/337 , A61K31/475 , A61K31/513 , A61K31/704 , A61K31/7068 , A61K33/24 , A61K39/39558 , A61K45/06 , A61K2039/505 , C07K16/44 , C07K2317/622 , C07K2317/73 , C07K2317/77 , A61K2300/00
摘要： Antibodies that penetrate cell nuclei and inhibit DNA repair or interfere with DNA metabolism are provided for treatment of cancer (both directly and by sensitizing cancer cells to DNA-damaging treatments) or inhibiting or preventing viral infection, proliferation or metabolism. The method involves treating cells with a composition containing cell-penetrating anti-DNA antibodies or derivatives thereof, alone or in combination with treatment that induces DNA damage such as DNA-damaging chemotherapy or radiation. The impact of the cell-penetrating anti-DNA antibodies or derivatives thereof is potentiated in cancer cells that are deficient in DNA repair, and the cell-penetrating anti-DNA antibodies or derivatives thereof are synthetically lethal to cancer cells with DNA repair deficiencies.
摘要翻译：提供穿透细胞核并抑制DNA修复或干扰DNA代谢的抗体用于治疗癌症（直接和通过致敏癌细胞对DNA损伤性治疗）或抑制或预防病毒感染，增殖或代谢。该方法包括用包含细胞穿透性抗DNA抗体或其衍生物的组合物单独或与诱导DNA损伤如DNA损伤性化学疗法或辐射的治疗组合处理细胞。细胞穿透性抗DNA抗体或其衍生物的影响在DNA修复缺陷的癌细胞中被增强，并且细胞穿透抗DNA抗体或其衍生物对具有DNA修复缺陷的癌细胞是合成致死的。

5. 发明申请

US20110293585A1 COMPOSITIONS AND METHODS FOR TREATMENT OF LYSOSOMAL STORAGE DISORDERS 审中-公开
标题翻译：用于治疗LYSOSOMAL存储障碍的组合物和方法
公开(公告)号：US20110293585A1
公开(公告)日：2011-12-01
申请号：US13091921
申请日：2011-04-21
申请人： Jacob del Campo , Ranjit S. Bindra , Peter M. Glazer
发明人： Jacob del Campo , Ranjit S. Bindra , Peter M. Glazer
IPC分类号： A61K48/00 , A61P3/00 , C12Q1/68 , A61P43/00 , C07H21/00 , A61K38/08
CPC分类号： A61K48/005 , C12N15/113 , C12N2310/152 , C12N2310/3181 , C12N2310/3519
摘要： Compositions and methods for treating lysosomal storage diseases are disclosed. Lysosomal dysfunction is usually the result of deficiency of a single enzyme necessary for the metabolism of lipids, glycoproteins (sugar containing proteins) or mucopolysaccharides which are fated for breakdown or recycling. The compositions contain triplex-forming molecules which can be used to induce site-specific homologous recombination in mammalian cells when combined with donor DNA molecules, by stimulating cellular DNA synthesis, recombination, and repair mechanisms. The methods are particular useful for correcting point mutations in genes associated with lysosomal storage diseases such as Gaucher's disease, Fabry disease, and Hurler syndrome. Methods for determining the frequency of target gene repair and assessing the restoration of the enzymatic activity of corrected polypeptides are also disclosed. Ex vivo and in vivo methods of gene correction in patients are also provided.
摘要翻译：公开了用于治疗溶酶体贮积病的组合物和方法。溶酶体功能障碍通常是脂肪，糖蛋白（含糖蛋白）或粘多糖的代谢所必需的单一酶的缺乏的结果，这些蛋白质被命运用于分解或再循环。组合物含有三重形成分子，其可以通过刺激细胞DNA合成，重组和修复机制与哺乳动物细胞中的供体DNA分子结合来诱导位点特异性同源重组。该方法特别可用于校正与溶酶体储存疾病如戈谢氏病，法布里病和赫勒综合征相关的基因中的点突变。还公开了确定靶基因修复频率和评估校正多肽的酶活性恢复的方法。还提供了患者基因修复的离体和体内方法。

6. 发明授权

US09701740B2 Cell-penetrating anti-DNA antibodies and uses thereof inhibit DNA repair 有权
公开(公告)号：US09701740B2
公开(公告)日：2017-07-11
申请号：US14009327
申请日：2012-04-02
申请人： James E. Hansen , Peter M. Glazer , Richard H. Weisbart , Robert N. Nishimura , Grace Chan
发明人： James E. Hansen , Peter M. Glazer , Richard H. Weisbart , Robert N. Nishimura , Grace Chan
IPC分类号： C07K16/18 , A61K39/00 , A61K39/395 , C07K16/44 , A61K31/704 , A61K45/06 , A61K31/337 , A61K31/475 , A61K31/513 , A61K31/7068 , A61K33/24
CPC分类号： C07K16/18 , A61K31/337 , A61K31/475 , A61K31/513 , A61K31/704 , A61K31/7068 , A61K33/24 , A61K39/39558 , A61K45/06 , A61K2039/505 , C07K16/44 , C07K2317/622 , C07K2317/73 , C07K2317/77 , A61K2300/00
摘要： Antibodies that penetrate cell nuclei and inhibit DNA repair or interfere with DNA metabolism are provided for treatment of cancer (both directly and by sensitizing cancer cells to DNA-damaging treatments) or inhibiting or preventing viral infection, proliferation or metabolism. The method involves treating cells with a composition containing cell-penetrating anti-DNA antibodies or derivatives thereof, alone or in combination with treatment that induces DNA damage such as DNA-damaging chemotherapy or radiation. The impact of the cell-penetrating anti-DNA antibodies or derivatives thereof is potentiated in cancer cells that are deficient in DNA repair, and the cell-penetrating anti-DNA antibodies or derivatives thereof are synthetically lethal to cancer cells with DNA repair deficiencies.

7. 发明授权

US5962426A Triple-helix forming oligonucleotides for targeted mutagenesis 失效
标题翻译：三螺旋形成用于靶向诱变的寡核苷酸
公开(公告)号：US5962426A
公开(公告)日：1999-10-05
申请号：US476712
申请日：1995-06-07
申请人： Peter M. Glazer
发明人： Peter M. Glazer
IPC分类号： C12N15/09 , A61K31/70 , A61K48/00 , A61P31/12 , A61P35/00 , C07H21/00 , C07H21/04 , C12N15/01 , C12N15/05 , C12N15/10 , C12N15/113 , C12Q1/68
CPC分类号： C12N15/113 , C07H21/00 , C12N15/01 , C12N15/102 , C12Q1/6827 , C12N2310/15 , C12N2310/3511
摘要： A high affinity, triplex-forming oligonucleotide and methods for use thereof wherein an oligonucleotide is used to form a triple-stranded nucleic acid molecule with a specific DNA segment of a target DNA molecule. Upon formation of the triplex, the binding of the oligonucleotide stimulates mutagenesis within or adjacent to the target sequence using cellular DNA synthesis or repair mechanisms. The mutation activates, inactivates or alters the activity and function of the target molecule.
摘要翻译：高亲和力，三重复合形成寡核苷酸及其使用方法，其中寡核苷酸用于形成具有靶DNA分子的特异性DNA区段的三链核酸分子。在形成三链体时，寡核苷酸的结合使用细胞DNA合成或修复机制刺激靶序列内或与靶序列相邻的突变。该突变激活，失活或改变靶分子的活性和功能。

8. 发明申请

US20110262406A1 COMPOSITIONS AND METHODS FOR TARGETED INACTIVATION OF HIV CELL SURFACE RECEPTORS 审中-公开
标题翻译： HIV细胞表面受体靶向灭活的组合物和方法
公开(公告)号：US20110262406A1
公开(公告)日：2011-10-27
申请号：US13091918
申请日：2011-04-21
申请人： Jacob del Campo , Erica Beth Schleifman , Ranjit S. Bindra , Peter M. Glazer
发明人： Jacob del Campo , Erica Beth Schleifman , Ranjit S. Bindra , Peter M. Glazer
IPC分类号： A61K35/12 , A61P31/18 , A61K31/7088 , C12N15/01 , C12N5/071
CPC分类号： C12N15/1138 , C12N15/111 , C12N2310/15 , C12N2310/3181 , C12N2320/33
摘要： Compositions for targeted mutagenesis of cell surface receptors for HIV and methods of their use are provided herein. The compositions include triplex-forming molecules that displace the polypyrimidine strand of target duplex and form a triple-stranded structure and hybrid duplex in a sequence specific manner with the polypurine strand of the target duplex. The triplex-forming molecules include a mixed-sequence “tail” which increases the stringency of binding to the target duplex, improves the frequency of modification at the target site, and reduces the requirement for a polypurine:polypyrimidine stretch. Methods for using the triplex-forming molecules in combination with one or more donor oligonucleotides for targeted modification of sites within or adjacent to genes that encodes cell surface receptors for human immunodeficiency virus (HIV) are also disclosed. Methods for ex vivo and in vivo prophylaxis and therapy of HIV infection using the disclosed compositions are also provided.
摘要翻译：本文提供了用于HIV的细胞表面受体的靶向诱变的组合物及其使用方法。组合物包括取代目标双链体的聚嘧啶链的三链体形成分子，并以序列特异性方式与目标双链体的多肽链形成三链结构和杂合双链体。三重形成分子包括混合序列“尾”，其增加了与目标双链体的结合的严格性，改善了靶位点修饰的频率，并且降低了对于聚亚胺的聚对亚胺的拉伸。还公开了将三链体形成分子与一种或多种供体寡核苷酸组合用于靶向修饰编码人免疫缺陷病毒（HIV）的细胞表面受体的基因内或邻近的基因的方法。还提供了使用所公开的组合物进行体外和体内预防和治疗HIV感染的方法。

9. 发明申请

US20110086905A1 Pseudocomplementary Oligonucleotides for Targeted Gene Therapy 有权
标题翻译：用于靶向基因治疗的伪互补寡核苷酸
公开(公告)号：US20110086905A1
公开(公告)日：2011-04-14
申请号：US12753016
申请日：2010-04-01
申请人： Peter M. Glazer
发明人： Peter M. Glazer
IPC分类号： A61K48/00 , C12N15/09 , A61P43/00
CPC分类号： C12N15/907 , A61K48/005
摘要： Compositions and methods for targeted gene therapy are disclosed. Compositions containing double duplex-forming pseudocomplementary oligonucleotides are administered in combination with a donor oligonucleotide that is homologous to a target sequence on a double-stranded DNA molecule in need of repair or replacement. By activating cellular mechanisms involved in DNA synthesis, repair and recombination, the double duplex-forming pseudocomplementary oligonucleotides can introduce one or more mutations at a site of interest by increasing the efficiency of targeted recombination of the donor oligonucleotide. The pseudocomplementary oligonucleotides/donor oligonucleotide compositions may be administered in combination with a second therapeutic agent that enhances access of the pseudocomplementary oligonucleotides and/or the donor oligonucleotide to the target site, an agent that enhances or increases DNA repair or recombination, or an agent that enhances uptake or delivery of the oligonucleotides.
摘要翻译：公开了靶向基因治疗的组合物和方法。含有双重双链形成假互补寡核苷酸的组合物与需要修复或替换的双链DNA分子上的靶序列同源的供体寡核苷酸组合施用。通过激活涉及DNA合成，修复和重组的细胞机制，双重双链体形成假互补寡核苷酸可以通过增加供体寡核苷酸靶向重组的效率，在目标位点引入一个或多个突变。假互补寡核苷酸/供体寡核苷酸组合物可以与增强伪补体寡核苷酸和/或供体寡核苷酸对靶位点的接触的第二治疗剂，增强或增加DNA修复或重组的试剂，或者增强寡核苷酸的摄取或递送。

10. 发明授权

US07407752B2 Oligonucleotide complexes for use as anti-viral therapeutics 失效
标题翻译：用作抗病毒治疗剂的寡核苷酸复合物
公开(公告)号：US07407752B2
公开(公告)日：2008-08-05
申请号：US10830287
申请日：2004-04-21
申请人： John D. Kriesel , Brandt B. Jones , Charles B. Grissom , Geoff Herpin , Peter M. Glazer
发明人： John D. Kriesel , Brandt B. Jones , Charles B. Grissom , Geoff Herpin , Peter M. Glazer
IPC分类号： C12Q1/68 , A61K39/245
CPC分类号： C12N15/1131 , C12N15/1132 , C12N15/1133 , C12N2310/152 , C12N2310/3511
摘要： The methods disclosed herein are of use for the treatment of a wide variety of diseases. In particular, the methods provide for the targeting of a transcription altering agent to a specific target site of a viral genome in order to inactivate the virus. In addition, the methods provide for a triplex-forming oligonucleotide capable of interacting with a target site in a viral genome in order to alter transcription. The methods of the present invention may be used against viral pathogens or agents of bioterrorism.
摘要翻译：本文公开的方法可用于治疗各种各样的疾病。特别地，所述方法提供将转录改变剂靶向病毒基因组的特异性靶位点以灭活病毒。此外，所述方法提供能够与病毒基因组中的靶位点相互作用的三重复合形成寡核苷酸，以便改变转录。本发明的方法可以用于抗病毒病原体或生物恐怖症的试剂。

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