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41.发明授权Method of site-specific alteration of RNA and production of encoded polypeptides 失效RNA的位点特异性改变方法和编码多肽的产生
公开(公告)号：US5366878A
公开(公告)日：1994-11-22
申请号：US36503
申请日：1993-03-24
Applicant: Thoru Pederson , Sudhir Agrawal , Sandra Mayrand , Paul C. Zamecnik
Inventor： Thoru Pederson , Sudhir Agrawal , Sandra Mayrand , Paul C. Zamecnik
CPC classification number: C12N15/113 , C12N15/102 , C12N15/8233 , C12N15/8235 , C12N2310/3125 , C12N2310/314 , C12N2310/315
Abstract: 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.
Abstract translation: 在RNA分子中选择的核苷酸的定点改变（去除或去除，随后替换）的方法以及在该方法中有用的混合的磷酸酯骨架寡核苷酸。 本发明还涉及生产由本发明方法改变的RNA分子编码的多肽或蛋白质的方法。 通过使用本方法，实现RNA分子的定点切割，然后切除RNA分子的所选择的或靶区段。
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42.发明授权Method of site-specific alteration of RNA and production of encoded polypeptides 失效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：US5149797A
公开(公告)日：1992-09-22
申请号：US480269
申请日：1990-02-15
Applicant: Thoru Pederson , Sudhir Agrawal , Sandra Mayrand , Paul C. Zamecnik
Inventor： Thoru Pederson , Sudhir Agrawal , Sandra Mayrand , Paul C. Zamecnik
IPC: C12N15/09 , C12N15/10 , C12N15/113 , C12N15/82
CPC classification number: C12N15/113 , C12N15/102 , C12N15/8233 , C12N15/8235 , C12N2310/3125 , C12N2310/314 , C12N2310/315
Abstract: 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.
Abstract translation: 在RNA分子中选择的核苷酸的定点改变（去除或去除，随后替换）的方法以及在该方法中有用的混合的磷酸酯骨架寡核苷酸。 本发明还涉及生产由本发明方法改变的RNA分子编码的多肽或蛋白质的方法。 通过使用本方法，实现RNA分子的定点切割，然后切除RNA分子的所选择的或靶区段。
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公开(公告)号：US08853375B2
公开(公告)日：2014-10-07
申请号：US12192432
申请日：2008-08-15
Applicant: Ekambar Kandimalla , Lakshmi Bhagat , Mallikarjuna Putta , Daqing Wang , Sudhir Agrawal
Inventor： Ekambar Kandimalla , Lakshmi Bhagat , Mallikarjuna Putta , Daqing Wang , Sudhir Agrawal
CPC classification number: A61K31/711 , A61K9/0014 , A61K9/0019 , A61K9/0031 , A61K9/0034 , A61K9/0043 , A61K9/0048 , A61K9/0056 , A61K9/0073 , A61K2039/55561 , Y02A50/401 , Y02A50/412 , Y02A50/414
Abstract: The invention relates to TLR9 antagonist compounds and their therapeutic or prophylactic use. The invention provides novel immune regulatory oligonucleotides and immunomers as antagonist of TLRs and methods of use thereof. These immune regulatory oligonucleotides have unique sequences that suppress, without completely ablating, TLR-mediated signaling in response to a TLR ligand or TLR signaling agonist. The methods may have use in the prevention and treatment of autoimmunity, inflammation, inflammatory bowel disease, lupus, allergy, asthma, infection, sepsis, cancer and immunodeficiency.
Abstract translation: 本发明涉及TLR9拮抗剂化合物及其治疗或预防用途。 本发明提供新的免疫调节寡核苷酸和作为TLR拮抗剂的免疫体及其使用方法。 这些免疫调节寡核苷酸具有独特的序列，其能够在不完全消除TLR介导的TLR配体或TLR信号激动剂的信号传导的情况下抑制。 该方法可用于预防和治疗自身免疫，炎症，炎性肠病，狼疮，过敏，哮喘，感染，败血症，癌症和免疫缺陷。
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44.发明授权Modulation of immunostimulatory activity of immunostimulatory oligonucleotide analogs by positional chemical changes 有权通过位置化学变化调节免疫刺激性寡核苷酸类似物的免疫刺激活性公开(公告)号：US08716253B2
公开(公告)日：2014-05-06
申请号：US10694075
申请日：2003-10-27
Applicant: Ekambar R. Kandimalla , Qiuyan Zhao , Dong Yu , Sudhir Agrawal
Inventor： Ekambar R. Kandimalla , Qiuyan Zhao , Dong Yu , Sudhir Agrawal
CPC classification number: C12N15/117 , A61K31/7088 , A61K31/7115 , A61K2039/55561 , C07H21/00 , C12N2310/18 , C12N2310/3125 , C12N2310/317 , C12N2310/318 , C12N2310/32 , C12N2310/321 , C12N2310/33 , C12N2310/334 , C12N2310/336 , C12N2310/3521
Abstract: The invention relates to the therapeutic use of oligonucleotides or oligonucleotide analogs as immunostimulatory agents in immunotherapy applications. The invention provides methods for enhancing the immune response caused by immunostimulatory oligonucleotide compounds.
Abstract translation: 本发明涉及在免疫治疗应用中寡核苷酸或寡核苷酸类似物作为免疫刺激剂的治疗用途。 本发明提供了增强由免疫刺激性寡核苷酸化合物引起的免疫应答的方法。
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公开(公告)号：US20130142778A1
公开(公告)日：2013-06-06
申请号：US13072017
申请日：2011-03-25
Applicant: SUDHIR AGRAWAL , EKAMBAR KANDIMALLA , MALLIKARJUNA PUTTA , Ireneusz Nowak , Nicola LaMonica , Weiwen Jiang , Michael Reardon , Tao Lan
Inventor： SUDHIR AGRAWAL , EKAMBAR KANDIMALLA , MALLIKARJUNA PUTTA , Ireneusz Nowak , Nicola LaMonica , Weiwen Jiang , Michael Reardon , Tao Lan
IPC: C12N15/113 , A61K39/35 , A61K39/395 , A61K38/02 , A61K31/7088 , A61K39/00
CPC classification number: C12N15/113 , A61K31/7088 , A61K31/7105 , A61K31/712 , A61K31/713 , A61K38/02 , A61K39/00 , A61K39/35 , A61K39/395 , A61K45/06 , C12N15/111 , C12N15/1138 , C12N2310/113 , C12N2310/14 , C12N2310/317 , C12N2310/318 , C12N2310/344 , C12N2310/50 , C12N2310/51 , C12N2310/52 , C12N2320/30
Abstract: The inventors have examined the means for providing more efficacious miRNA blocking compounds. The inventors have discovered new structural features that surprisingly improve the efficacy of miRNA blocking molecules. These features include the presence of multiple 3′ ends and a linker at the 5′ ends. Surprisingly, these features improve the efficacy of the gene expression blocking compounds in a manner that decreases the compound's biologic instability. Even more surprisingly, this effect has been found to be applicable to both DNA and RNA oligonucleotide-based compounds and to have application in traditional antisense and RNAi technology.
Abstract translation: 本发明人已经研究了提供更有效的miRNA阻断化合物的方法。 本发明人已经发现了惊人地改善miRNA阻断分子的功效的新结构特征。 这些特征包括多个3'末端的存在和在5'端的接头。 令人惊讶的是，这些特征以降低化合物生物学不稳定性的方式提高了基因表达阻断化合物的功效。 更令人惊奇的是，这种效应已被发现适用于基于DNA和RNA的寡核苷酸类化合物，并且应用于传统的反义和RNAi技术。
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Patent Agency Ranking
46.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
Applicant: Ekambar Kandimalla , Daqing Wang , Yukui Li , Dong Yu , FuGang Zhu , Lakshmi Bhagat , Sudhir Agrawal
Inventor： Ekambar Kandimalla , Daqing Wang , Yukui Li , Dong Yu , FuGang Zhu , Lakshmi Bhagat , Sudhir Agrawal
CPC classification number: A61K48/00 , A61K31/7088 , A61K39/0008 , A61K2039/55561 , Y02A50/401
Abstract: 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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公开(公告)号：US08361986B2
公开(公告)日：2013-01-29
申请号：US13156140
申请日：2011-06-08
Applicant: Ekambar R. Kandimalla , Mallikarjuna Putta , Daqing Wang , Dong Yu , Lakshmi Bhagat , Sudhir Agrawal
Inventor： Ekambar R. Kandimalla , Mallikarjuna Putta , Daqing Wang , Dong Yu , Lakshmi Bhagat , Sudhir Agrawal
CPC classification number: A61K31/711 , A61K39/39
Abstract: 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.
Abstract translation: 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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48.发明授权Stabilized immune modulatory RNA (SIMRA) compounds for TLR7 and TLR8 有权用于TLR7和TLR8的稳定免疫调节RNA（SIMRA）化合物公开(公告)号：US08106173B2
公开(公告)日：2012-01-31
申请号：US11697422
申请日：2007-04-06
Applicant: Ekambar R. Kandimalla , Tao Lan , Yukui Li , Dong Yu , Daqing Wang , Mallikarjuna Reddy Putta , Sudhir Agrawal
Inventor： Ekambar R. Kandimalla , Tao Lan , Yukui Li , Dong Yu , Daqing Wang , Mallikarjuna Reddy Putta , Sudhir Agrawal
CPC classification number: C07K14/665 , A61K31/713 , A61K39/0005 , A61K39/395 , A61K39/3955 , C12N15/117 , C12N2310/17 , C12N2310/315 , C12N2310/318 , C12N2310/3183 , C12N2310/321 , C12N2310/33 , C12N2310/331 , C12N2310/336 , C12N2310/3521
Abstract: The invention relates to the therapeutic use of stabilized oligoribonucleotides as immune modulatory agents for immune therapy applications. Specifically, the invention provides RNA based oligoribonucleotides with improved nuclease and RNase stability and that have immune modulatory activity through TLR7 and/or TLR8.
Abstract translation: 本发明涉及稳定的寡核糖核苷酸作为免疫治疗应用的免疫调节剂的治疗用途。 具体地，本发明提供具有改进的核酸酶和核糖核酸酶稳定性的基于RNA的寡核糖核苷酸，并且通过TLR7和/或TLR8具有免疫调节活性。
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公开(公告)号：US20120016004A1
公开(公告)日：2012-01-19
申请号：US13038924
申请日：2011-03-02
Applicant: SUDHIR AGRAWAL , EKAMBAR KANDIMALLA , MALLIKARJUNA PUTTA , TAO LAN , LAKSHMI BHAGAT , DAQING WANG , DONG YU
Inventor： SUDHIR AGRAWAL , EKAMBAR KANDIMALLA , MALLIKARJUNA PUTTA , TAO LAN , LAKSHMI BHAGAT , DAQING WANG , DONG YU
IPC: A61K31/7088 , C07H21/02 , C07H21/00
CPC classification number: C12N15/1138 , C12N2310/11 , C12N2310/152 , C12N2310/321 , C12N2310/3519 , C12N2310/51
Abstract: The inventors have examined the means for providing more efficacious gene expression blocking compounds. The inventors have discovered new structural features that surprisingly improve the efficacy of gene expression blocking molecules. These features include the presence of multiple 3′ ends and a linker at the 5′ ends. Surprisingly, these features improve the efficacy of the gene expression blocking compounds in a manner that decreases the compound's biologic instability. Even more surprisingly, this effect has been found to be applicable to both DNA and RNA oligonucleotide-based compounds and to have application in traditional antisense and RNAi technologies.
Abstract translation: 本发明人已经研究了提供更有效的基因表达阻断化合物的方法。 发明人已经发现了惊人地改善基因表达阻断分子的功效的新结构特征。 这些特征包括多个3'末端的存在和在5'端的接头。 令人惊讶的是，这些特征以降低化合物生物学不稳定性的方式提高了基因表达阻断化合物的功效。 更令人惊奇的是，这种效应已经被发现适用于基于DNA和RNA的寡核苷酸类化合物，并且应用于传统的反义和RNAi技术。
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50.发明申请MODULATION OF IMMUNOSTIMULATORY PROPERTIES OF OLIGONUCLEOTIDE-BASED COMPOUNDS BY OPTIMAL PRESENTATION OF 5' ENDS 有权通过5'末端的最佳显示调节寡核苷酸类化合物的免疫学性质公开(公告)号：US20110229456A1
公开(公告)日：2011-09-22
申请号：US12957925
申请日：2010-12-01
Applicant: SUDHIR AGRAWAL , EKAMBAR R. KANDIMALLA , DONG YU , LAKSHMI BHAGAT
Inventor： SUDHIR AGRAWAL , EKAMBAR R. KANDIMALLA , DONG YU , LAKSHMI BHAGAT
IPC: A61K31/712 , A61K39/00 , A61K39/395 , C07H21/04 , C07H21/00 , A61K31/7125 , A61K38/02 , A61P37/04 , A61P35/00
CPC classification number: C07H21/04 , A61K39/39 , A61K2039/55561
Abstract: 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.
Abstract translation: 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。
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