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21.发明授权公开(公告)号：US08426375B2
公开(公告)日：2013-04-23
申请号：US12140334
申请日：2008-06-17
申请人： Ekambar Kandimalla , Daqing Wang , Yukui Li , Dong Yu , FuGang Zhu , Lakshmi Bhagat , Sudhir Agrawal
发明人： Ekambar Kandimalla , Daqing Wang , Yukui Li , Dong Yu , FuGang Zhu , Lakshmi Bhagat , Sudhir Agrawal
CPC分类号： A61K48/00 , A61K31/7088 , A61K39/0008 , A61K2039/55561 , Y02A50/401
摘要： The invention provides novel immune regulatory oligonucleotides (IRO) as antagonist of TLRs and methods of use thereof. These IROs have unique sequences that inhibit or suppress TLR-mediated signaling in response to a TLR ligand or TLR agonist. The methods may have use in the prevention and treatment of cancer, an autoimmune disorder, airway inflammation, inflammatory disorders, infectious disease, skin disorders, allergy, asthma or a disease caused by a pathogen.
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22.发明申请公开(公告)号：US20090087388A1
公开(公告)日：2009-04-02
申请号：US12140334
申请日：2008-06-17
申请人： Ekambar Kandimalla , Daqing Wang , Yukui Li , Dong Yu , FuGang Zhu , Lakshmi Bhagat , Sudhir Agrawal
发明人： Ekambar Kandimalla , Daqing Wang , Yukui Li , Dong Yu , FuGang Zhu , Lakshmi Bhagat , Sudhir Agrawal
IPC分类号： A61K9/12 , A61K31/7088 , A61K39/00 , A61K39/395 , A61K8/49 , A61K38/00 , A61K39/35
CPC分类号： A61K48/00 , A61K31/7088 , A61K39/0008 , A61K2039/55561 , Y02A50/401
摘要： The invention provides novel immune regulatory oligonucleotides (IRO) as antagonist of TLRs and methods of use thereof. These IROs have unique sequences that inhibit or suppress TLR-mediated signaling in response to a TLR ligand or TLR agonist. The methods may have use in the prevention and treatment of cancer, an autoimmune disorder, airway inflammation, inflammatory disorders, infectious disease, skin disorders, allergy, asthma or a disease caused by a pathogen.
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23.发明申请公开(公告)号：US20110009477A1
公开(公告)日：2011-01-13
申请号：US12832439
申请日：2010-07-08
申请人： Dong Yu , Lakshmi Bhagat , Daqing Wang , Ekambar Kandimalla , Sudhir Agrawal
发明人： Dong Yu , Lakshmi Bhagat , Daqing Wang , Ekambar Kandimalla , Sudhir Agrawal
IPC分类号： A61K31/7052 , C07H19/16 , A61P37/06
CPC分类号： A61K31/711 , A61K9/0031 , A61K9/0034 , A61K9/0043 , A61K9/0048 , A61K9/0056 , Y02A50/401 , Y02A50/411 , Y02A50/414
摘要： The invention provides novel oligonucleotide-based TLR antagonists containing a modified immune stimulatory motif and the use of such compounds in the prevention and treatment of TLR-medicated diseases. These oligonucleotide-based TLR antagonists containing a modified immune stimulatory motif have one or more chemical modifications in the immune stimulatory motif, which would be immune stimulatory but for the modification.
摘要翻译： 本发明提供了含有修饰的免疫刺激基序的新型基于寡核苷酸的TLR拮抗剂以及这些化合物在预防和治疗TLR药物疾病中的用途。 含有修饰的免疫刺激基序的这些基于寡核苷酸的TLR拮抗剂在免疫刺激基序中具有一种或多种化学修饰，其将是免疫刺激但是用于修饰。
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公开(公告)号：US08361986B2
公开(公告)日：2013-01-29
申请号：US13156140
申请日：2011-06-08
申请人： Ekambar R. Kandimalla , Mallikarjuna Putta , Daqing Wang , Dong Yu , Lakshmi Bhagat , Sudhir Agrawal
发明人： Ekambar R. Kandimalla , Mallikarjuna Putta , Daqing Wang , Dong Yu , Lakshmi Bhagat , Sudhir Agrawal
CPC分类号： A61K31/711 , A61K39/39
摘要： The invention relates to synthetic chemical compositions that are useful for modulation of Toll-Like Receptor (TLR)-mediated immune responses. In particular, the invention relates to agonists of Toll-Like Receptor 9 (TLR9) that generate unique cytokine and chemokine profiles.
摘要翻译： 本发明涉及可用于调节Toll样受体（TLR）介导的免疫应答的合成化学组合物。 特别地，本发明涉及产生独特细胞因子和趋化因子分布的Toll样受体9（TLR9）的激动剂。
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公开(公告)号：US20060019918A1
公开(公告)日：2006-01-26
申请号：US11173938
申请日：2005-07-01
申请人： Sudhir Agrawal , Lakshmi Bhagat , Dong Yu , Ekambar Kandimalla
发明人： Sudhir Agrawal , Lakshmi Bhagat , Dong Yu , Ekambar Kandimalla
CPC分类号： C12N15/117 , C07H21/00 , C07H21/02 , C07H21/04 , C12N15/111 , C12N2310/17 , C12N2310/33 , C12N2310/3519 , C12N2310/51
摘要： The invention relates to the therapeutic use of oligonucleotides as immunostimulatory agents in immunotherapy applications. More particularly, the invention provides immunomers and an immunostimulatory oligonucleotides for use in methods for generating an immune response or for treating a patient in need of immunostimulation. The immunomers and an immunostimulatory oligonucleotides of the invention preferably comprise novel purines. The immunomers according to the invention further comprise at least two oligonucleotides linked at their 3′ ends, internucleoside linkages or functionalized nucleobase or sugar to a non-nucleotidic linker, at least one of the oligonucleotides being an immunomodulatory oligonucleotide and having an accessible 5′ end.
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26.发明申请Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5' ends 有权通过最优化5'末端调节基于寡核苷酸的化合物的免疫刺激性质公开(公告)号：US20070173469A1
公开(公告)日：2007-07-26
申请号：US10925873
申请日：2004-08-25
申请人： Sudhir Agrawal , Ekambar Kandimalla , Dong Yu , Lakshmi Bhagat
发明人： Sudhir Agrawal , Ekambar Kandimalla , Dong Yu , Lakshmi Bhagat
CPC分类号： C07H21/04 , A61K39/39 , A61K2039/55561
摘要： The invention relates to the therapeutic use of oligonucleotides as immunostimulatory agents in immunotherapy applications. More particularly, the invention provides immunomers for use in methods for generating an immune response or for treating a patient in need of immunostimulation. The immunomers of the invention comprise at least two oligonucleotides linked at their 3′ ends, internucleoside linkages or functionalized nucleobase or sugar to a non-nucleotidic linker, at least one of the oligonucleotides being an immunostimulatory oligonucleotide and having an accessible 5′ end.
摘要翻译： 本发明涉及在免疫治疗应用中寡核苷酸作为免疫刺激剂的治疗用途。 更具体地，本发明提供了用于产生免疫应答的方法或用于治疗需要免疫刺激的患者的免疫
性。 本发明的免疫体包含至少两个在其3'末端连接的寡核苷酸，核苷间键或官能化核碱基或糖与非核苷酸连接体，至少一个寡核苷酸是免疫刺激性寡核苷酸并具有可接近的5'端。-
公开(公告)号：US20070093439A1
公开(公告)日：2007-04-26
申请号：US11257769
申请日：2005-10-25
申请人： Sudhir Agrawal , Ekambar Kandimalla , Dong Yu , Lakshmi Bhagat
发明人： Sudhir Agrawal , Ekambar Kandimalla , Dong Yu , Lakshmi Bhagat
CPC分类号： A61K39/39 , A61K2039/55561
摘要： The invention relates to modulation of the immune system. More particularly, the invention relates to modulating the immune system through the use of oligonucleotide-derived compounds. The invention provides immunostimulatory agents that are less expensive to make than existing immunostimulatory oligonucleotides. The immunostimulatory agents according to the invention can, in preferred embodiments, cause immune stimulation across species lines.
摘要翻译： 本发明涉及免疫系统的调节。 更具体地，本发明涉及通过使用寡核苷酸衍生的化合物调节免疫系统。 本发明提供免疫刺激剂，其比现有免疫刺激性寡核苷酸便宜。 在优选实施方案中，根据本发明的免疫刺激剂可以跨物种系引起免疫刺激。
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公开(公告)号：US20060287261A1
公开(公告)日：2006-12-21
申请号：US11173794
申请日：2005-07-01
申请人： Sudhir Agrawal , Lakshmi Bhagat , Dong Yu , Ekambar Kandimalla
发明人： Sudhir Agrawal , Lakshmi Bhagat , Dong Yu , Ekambar Kandimalla
CPC分类号： C12N15/117 , C07H21/00 , C07H21/02 , C07H21/04 , C12N15/111 , C12N2310/17 , C12N2310/33 , C12N2310/3519 , C12N2310/51
摘要： The invention relates to the therapeutic use of oligonucleotides as immunostimulatory agents in immunotherapy applications. More particularly, the invention provides immunomers and an immunostimulatory oligonucleotides for use in methods for generating an immune response or for treating a patient in need of immunostimulation. The immunomers and an immunostimulatory oligonucleotides of the invention preferably comprise novel purines. The immunomers according to the invention further comprise at least two oligonucleotides linked at their 3′ ends, internucleoside linkages or functionalized nucleobase or sugar to a non-nucleotidic linker, at least one of the oligonucleotides being an immunomodulatory oligonucleotide and having an accessible 5′ end.
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公开(公告)号：US20050026861A1
公开(公告)日：2005-02-03
申请号：US10865245
申请日：2004-06-10
申请人： Ekambar Kandimalla , Lakshmi Bhagat , Rajendra Pandey , Dong Yu , Sudhir Agrawal
发明人： Ekambar Kandimalla , Lakshmi Bhagat , Rajendra Pandey , Dong Yu , Sudhir Agrawal
CPC分类号： C12N15/117 , C12N2310/17 , C12N2310/315 , C12N2310/3183 , C12N2310/321 , C12N2310/336 , C12N2310/53 , C12N2320/51 , C12N2310/3521
摘要： The invention provides immunostimulatory oligonucleotides having at least one CpG dinucleotide and a secondary structure at the 5′- or 3′-end. These oligonucleotides have either reduced or improved immunostimulatory properties. The invention establishes that 5′-terminal secondary structures affect immunostimulatory activity significantly more than those at the 3′-end. The invention also provides methods for increasing or decreasing the immunostimulatory activity of a CpG-containing nucleic acid.
摘要翻译： 本发明提供了在5'-或3'-末端具有至少一个CpG二核苷酸和二级结构的免疫刺激性寡核苷酸。 这些寡核苷酸具有降低的或改善的免疫刺激性质。 本发明确定5'-末端二级结构比3'-末端显着地影响免疫刺激活性。 本发明还提供了增加或降低含CpG的核酸的免疫刺激活性的方法。
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30.发明授权Modulation of immunostimulatory properties of oligonucleotide-based compounds by utilizing modified immunostimulatory dinucleotides 失效通过利用修饰的免疫刺激二核苷酸调节基于寡核苷酸的化合物的免疫刺激性质公开(公告)号：US07863250B2
公开(公告)日：2011-01-04
申请号：US11174002
申请日：2005-07-01
申请人： Sudhir Agrawal , Lakshmi Bhagat , Dong Yu , Ekambar Kandimalla
发明人： Sudhir Agrawal , Lakshmi Bhagat , Dong Yu , Ekambar Kandimalla
CPC分类号： C12N15/117 , C07H21/00 , C07H21/02 , C07H21/04 , C12N15/111 , C12N2310/17 , C12N2310/33 , C12N2310/3519 , C12N2310/51
摘要： The invention relates to the therapeutic use of oligonucleotides as immunostimulatory agents in immunotherapy applications. More particularly, the invention provides immunomers and an immunostimulatory oligonucleotides for use in methods for generating an immune response or for treating a patient in need of immunostimulation. The immunomers and an immunostimulatory oligonucleotides of the invention preferably comprise novel purines. The immunomers according to the invention further comprise at least two oligonucleotides linked at their 3′ ends, internucleoside linkages or functionalized nucleobase or sugar to a non-nucleotidic linker, at least one of the oligonucleotides being an immunomodulatory oligonucleotide and having an accessible 5′ end.
摘要翻译： 本发明涉及在免疫治疗应用中寡核苷酸作为免疫刺激剂的治疗用途。 更具体地，本发明提供用于产生免疫应答的方法或用于治疗需要免疫刺激的患者的免疫学和免疫刺激性寡核苷酸。 本发明的免疫原和免疫刺激寡核苷酸优选包含新的嘌呤。 根据本发明的免疫反应物还包含至少两个在其3'末端连接的寡核苷酸，核苷间键或官能化核碱基或糖与非核酸连接体，至少一个寡核苷酸是免疫调节寡核苷酸并具有可接近的5'末端 。
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