公开(公告)号：US08153608B2

公开(公告)日：2012-04-10

申请号：US12952863

申请日：2010-11-23

申请人： Sudhir Agrawal ,  Lakshmi Bhagat ,  Dong Yu ,  Ekambar R. Kandimalla

发明人： Sudhir Agrawal ,  Lakshmi Bhagat ,  Dong Yu ,  Ekambar R. 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：US07851454B2

公开(公告)日：2010-12-14

申请号：US11877767

申请日：2007-10-24

申请人： Sudhir Agrawal ,  Ekambar R. Kandimalla ,  Dong Yu ,  Lakshmi Bhagat

发明人： Sudhir Agrawal ,  Ekambar R. Kandimalla ,  Dong Yu ,  Lakshmi Bhagat

IPC分类号： A01N43/04 ,  A61K31/70 ,  A61K39/395 ,  A61K39/00 ,  A61K39/38 ,  A61K39/12 ,  A61K39/002 ,  A61K39/02 ,  A61K39/35 ,  A61K39/36 ,  A61K47/00

CPC分类号： C07H21/02 ,  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。

公开(公告)号：US07276489B2

公开(公告)日：2007-10-02

申请号：US10279684

申请日：2002-10-24

申请人： Sudhir Agrawal ,  Ekambar R. Kandimalla ,  Dong Yu ,  Lakshmi Bhagat

发明人： Sudhir Agrawal ,  Ekambar R. Kandimalla ,  Dong Yu ,  Lakshmi Bhagat

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

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.

公开(公告)号：US07749975B2

公开(公告)日：2010-07-06

申请号：US11174450

申请日：2005-07-01

申请人： Sudhir Agrawal ,  Ekambar R. Kandimalla ,  Dong Yu ,  Lakshmi Bhagat

发明人： Sudhir Agrawal ,  Ekambar R. Kandimalla ,  Dong Yu ,  Lakshmi Bhagat

IPC分类号： C07H21/02 ,  C07H21/04 ,  A61K39/38 ,  A61K39/00 ,  A61K39/395 ,  A61K45/00 ,  A61K47/00

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.

公开(公告)号：US08202850B2

公开(公告)日：2012-06-19

申请号：US12957925

申请日：2010-12-01

申请人： Sudhir Agrawal ,  Ekambar R. Kandimalla ,  Dong Yu ,  Lakshmi Bhagat

发明人： Sudhir Agrawal ,  Ekambar R. Kandimalla ,  Dong Yu ,  Lakshmi Bhagat

IPC分类号： C07H21/04 ,  C07H21/02 ,  A01N43/04 ,  A61K39/00 ,  A61K39/38 ,  A61K45/00 ,  A61K47/00 ,  A61K31/70

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：US08008267B2

公开(公告)日：2011-08-30

申请号：US10865245

申请日：2004-06-10

申请人： Ekambar R. Kandimalla ,  Lakshmi Bhagat ,  Rajendra K. Pandey ,  Dong Yu ,  Sudhir Agrawal

发明人： Ekambar R. Kandimalla ,  Lakshmi Bhagat ,  Rajendra K. Pandey ,  Dong Yu ,  Sudhir Agrawal

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

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。

公开(公告)号：US07407944B2

公开(公告)日：2008-08-05

申请号：US10925872

申请日：2004-08-25

申请人： Sudhir Agrawal ,  Ekambar R. Kandimalla ,  Dong Yu ,  Lakshmi Bhagat

发明人： Sudhir Agrawal ,  Ekambar R. Kandimalla ,  Dong Yu ,  Lakshmi Bhagat

IPC分类号： A61K31/70 ,  A61K38/00 ,  A61K38/16 ,  A61K39/00 ,  A61K39/35 ,  A61K39/38 ,  A61K39/12 ,  A61K39/02 ,  A61K39/002 ,  A61K45/00 ,  A61K47/00 ,  A01N43/04 ,  A01N37/18 ,  C07H21/02 ,  C07H21/04

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：US20080152662A1

公开(公告)日：2008-06-26

申请号：US11906781

申请日：2007-10-03

申请人： Sudhir Agrawal ,  Ekambar R. Kandimalla ,  Dong Yu ,  Lakshmi Bhagat

发明人： Sudhir Agrawal ,  Ekambar R. Kandimalla ,  Dong Yu ,  Lakshmi Bhagat

IPC分类号： A61K39/00 ,  C07H21/04

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.

公开(公告)号：US08946175B1

公开(公告)日：2015-02-03

申请号：US13210903

申请日：2011-08-16

申请人： Ekambar R. Kandimalla ,  Lakshmi Bhagat ,  Rajendra K. Pandey ,  Dong Yu ,  Sudhir Agrawal

发明人： Ekambar R. Kandimalla ,  Lakshmi Bhagat ,  Rajendra K. Pandey ,  Dong Yu ,  Sudhir Agrawal

IPC分类号： A61K48/00 ,  A61K45/00 ,  A61K47/00 ,  A61K39/00 ,  A61K39/38

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。

公开(公告)号：US20120201807A1

公开(公告)日：2012-08-09

申请号：US13404309

申请日：2012-02-24

申请人： Sudhir Agrawal ,  Lakshmi Bhagat ,  Dong Yu ,  Ekambar R. Kandimalla

发明人： Sudhir Agrawal ,  Lakshmi Bhagat ,  Dong Yu ,  Ekambar R. Kandimalla

IPC分类号： A61K39/00 ,  A61P37/04 ,  A61K39/35 ,  C07H21/04 ,  A61K39/395

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 immunostimulatory oligonucleotides for use in methods for generating an immune response or for treating a patient in need of immunostimulation. The immunomers and 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和免疫刺激性寡核苷酸。 本发明的免疫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性寡核苷酸并具有可接近的5'末端 。