公开(公告)号：US08877722B2

公开(公告)日：2014-11-04

申请号：US13072017

申请日：2011-03-25

申请人： Sudhir Agrawal ,  Ekambar Kandimalla ,  Mallikarjuna Putta ,  Ireneusz Nowak ,  Nicola LaMonica ,  Weiwen Jiang ,  Michael Reardon ,  Tao Lan

发明人： Sudhir Agrawal ,  Ekambar Kandimalla ,  Mallikarjuna Putta ,  Ireneusz Nowak ,  Nicola LaMonica ,  Weiwen Jiang ,  Michael Reardon ,  Tao Lan

IPC分类号： A61K48/00 ,  C07H21/02 ,  C07H21/04

CPC分类号： 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

摘要： 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.

摘要翻译： 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。

公开(公告)号：US08202974B2

公开(公告)日：2012-06-19

申请号：US12703612

申请日：2010-02-10

申请人： Tao Lan ,  Ekambar Kandimalla ,  Daqing Wang ,  Sudhir Agrawal

发明人： Tao Lan ,  Ekambar Kandimalla ,  Daqing Wang ,  Sudhir Agrawal

IPC分类号： C07H21/02 ,  C07H21/04 ,  C12Q1/68 ,  C12N5/00 ,  C12N5/02 ,  A61K49/00 ,  A61K31/70 ,  A01N43/04

CPC分类号： C12N15/117 ,  A61K2039/55561 ,  C12N2310/17 ,  C12N2310/315 ,  C12N2310/317 ,  C12N2310/3183 ,  C12N2310/333 ,  C12N2310/51 ,  C12N2320/31 ,  C12N2320/51

摘要： 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 selectively induce immune modulatory activity through TLR7.

摘要翻译： 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，本发明提供了具有改进的核酸酶和RNA酶稳定性的RNA基寡核糖核苷酸，并且通过TLR7选择性诱导免疫调节活性。

公开(公告)号：US08188261B2

公开(公告)日：2012-05-29

申请号：US12168641

申请日：2008-07-07

申请人： Ekambar Kandimalla ,  Tao Lan ,  Daqing Wang ,  Lakshmi Bhagat ,  Sudhir Agrawal

发明人： Ekambar Kandimalla ,  Tao Lan ,  Daqing Wang ,  Lakshmi Bhagat ,  Sudhir Agrawal

IPC分类号： C07H21/04

CPC分类号： A61K39/39 ,  A61K31/7105 ,  A61K2039/55561 ,  C07H21/02 ,  C12N15/117 ,  C12N2310/17 ,  C12N2310/317 ,  C12N2310/3183 ,  C12N2310/51 ,  C12N2320/51

摘要： The invention relates to the therapeutic use of novel stabilized oligoribonucleotides as immune modulatory agents for immune therapy applications. Specifically, the invention provides novel RNA-based oligoribonucleotides with improved nuclease and RNase stability and that have immune modulatory activity through TLR7 and/or TLR8.

摘要翻译： 本发明涉及新型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，本发明提供了具有改进的核酸酶和核糖核酸酶稳定性并且通过TLR7和/或TLR8具有免疫调节活性的新型的基于RNA的寡核糖核苷酸。

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。

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

IPC分类号： C07H21/02 ,  C07H21/04 ,  A01N43/04 ,  A61K31/70

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 。

公开(公告)号：US20100166805A1

公开(公告)日：2010-07-01

申请号：US12592850

申请日：2009-12-03

申请人： Sudhir Agrawal ,  Fu-Gang Zhu ,  Ekambar Kandimalla

发明人： Sudhir Agrawal ,  Fu-Gang Zhu ,  Ekambar Kandimalla

IPC分类号： A61K39/00 ,  A61K31/7088 ,  A61K38/02 ,  A61K38/16 ,  A61P11/00

CPC分类号： C12N15/117 ,  A61K39/39 ,  A61K2039/55561 ,  C12N2310/17 ,  C12N2310/315 ,  C12N2310/318 ,  C12N2310/3183 ,  C12N2310/32 ,  C12N2310/33 ,  C12N2310/336 ,  C12N2310/52

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.

公开(公告)号：US20100111935A1

公开(公告)日：2010-05-06

申请号：US12612370

申请日：2009-11-04

申请人： Lakshmi Bhagat ,  Ekambar Kandimalla ,  Mallikarjuna Putta ,  Daqing Wang ,  Dong Yu ,  Sudhir Agrawal

发明人： Lakshmi Bhagat ,  Ekambar Kandimalla ,  Mallikarjuna Putta ,  Daqing Wang ,  Dong Yu ,  Sudhir Agrawal

IPC分类号： A61K48/00 ,  C07H21/02 ,  A61P29/00 ,  A61P11/00 ,  A61P17/00 ,  A61K39/395

CPC分类号： C12N15/1138 ,  C07H21/00 ,  C12N2310/11

摘要： Antisense oligonucleotide compounds, compositions and methods are provided for down regulating the expression of TLR2. The compositions comprise antisense oligonucleotides targeted to nucleic acids encoding TLR2. The compositions may also comprise antisense oligonucleotides targeted to nucleic acids encoding TLR2 in combination with other therapeutic and/or prophylactic compounds and/or compositions. Methods of using these compounds and compositions for down-regulating TLR2 expression and for prevention or treatment of diseases wherein modulation of TLR2 expression would be beneficial are provided.

摘要翻译： 提供反义寡核苷酸化合物，组合物和方法用于下调TLR2的表达。 组合物包含靶向编码TLR2的核酸的反义寡核苷酸。 组合物还可以包含靶向编码TLR2的核酸与其它治疗和/或预防化合物和/或组合物组合的反义寡核苷酸。 提供这些化合物和组合物用于下调TLR2表达和预防或治疗其中调节TLR2表达将是有益的疾病的方法。

公开(公告)号：US07566702B2

公开(公告)日：2009-07-28

申请号：US11234075

申请日：2005-09-22

申请人： Sudhir Agrawal ,  Ekambar Kandimalla ,  Dong Yu

发明人： Sudhir Agrawal ,  Ekambar Kandimalla ,  Dong Yu

IPC分类号： C07H21/02 ,  C07H21/04 ,  A01N43/04 ,  A61K31/70

CPC分类号： A61K39/39 ,  A61K2039/55561

摘要： The invention provides an immunostimulatory nucleic acid. In certain embodiments according to this aspect of the invention, the sequence of the immunostimulatory oligonucleotide and/or immunomer is at least partially self-complementary.

摘要翻译： 本发明提供免疫刺激性核酸。 在根据本发明的该方面的某些实施方案中，免疫刺激性寡核苷酸和/或免疫反应物的序列至少部分自身互补。

公开(公告)号：US20070219153A1

公开(公告)日：2007-09-20

申请号：US11641551

申请日：2006-12-19

申请人： Ekambar Kandimalla ,  Mallikarjuna Putta ,  Sudhir Agrawal

发明人： Ekambar Kandimalla ,  Mallikarjuna Putta ,  Sudhir Agrawal

IPC分类号： A61K48/00 ,  A61K8/96 ,  C07H21/04

CPC分类号： C12N15/117 ,  A61K39/39 ,  A61K48/00 ,  A61K2039/55561 ,  C07H21/00 ,  C07H21/04 ,  C12N2310/17 ,  C12N2310/315 ,  C12N2310/318 ,  C12N2310/336

摘要： The invention provides a palindromic immune modulatory nucleic acid. The invention also provides methods for generating, enhancing and modifying the immune response caused by palindromic immune modulatory compounds used for immunotherapy applications

摘要翻译： 本发明提供了回文免疫调节核酸。 本发明还提供用于产生，增强和修饰由用于免疫治疗应用的回文免疫调节化合物引起的免疫应答的方法

公开(公告)号：US20070179103A1

公开(公告)日：2007-08-02

申请号：US11234396

申请日：2005-09-22

申请人： Sudhir Agrawal ,  Ekambar Kandimalla ,  Dong Yu

发明人： Sudhir Agrawal ,  Ekambar Kandimalla ,  Dong Yu

IPC分类号： A61K48/00 ,  A61K8/96 ,  A61K39/395 ,  A61K39/00 ,  C07H21/04

CPC分类号： A61K31/711 ,  A61K38/2013 ,  A61K39/39 ,  A61K2039/55561 ,  A61N2005/1098 ,  C12N15/117 ,  C12N2310/17 ,  C12N2310/315 ,  C12N2310/318 ,  C12N2310/334 ,  C12N2310/336 ,  C12N2310/3519 ,  A61K2300/00

摘要： The invention provides an immunostimulatory nucleic acid. In certain embodiments according to this aspect of the invention, the sequence of the immunostimulatory oligonucleotide and/or immunomer is at least partially self-complementary.

摘要翻译： 本发明提供免疫刺激性核酸。 在根据本发明的该方面的某些实施方案中，免疫刺激性寡核苷酸和/或免疫反应物的序列至少部分自身互补。