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公开(公告)号：US07410975B2
公开(公告)日：2008-08-12
申请号：US10872196
申请日：2004-06-18
IPC分类号： A61K31/517 , C07D239/72 , C07D239/93 , C07D239/94
CPC分类号： A61K31/437 , A61K31/122 , A61K31/382 , A61K31/4462 , A61K31/4709 , A61K31/496 , A61K31/517 , A61K31/5415 , A61K31/55 , A61K31/553 , C07D221/10 , C07D239/94 , C07D239/95 , C07D405/12
摘要： The invention provides methods and compositions useful for modulating signaling through Toll-like receptors. The methods involve contacting a TLR-expressing cell with a small molecule having a core structure including at least two rings. Certain of the compounds are 4-primary amino quinolines. Many of the compounds and methods are useful specifically for inhibiting immune stimulation involving at least one of TLR9, TLR8, TLR7, and TLR3. The methods may have use in the treatment of autoimmunity, inflammation, allergy, asthma, graft rejection, graft versus host disease, infection, sepsis, cancer, and immunodeficiency.
摘要翻译： 本发明提供了用于通过Toll样受体调节信号传导的方法和组合物。 所述方法包括使TLR表达细胞与具有包含至少两个环的核心结构的小分子接触。 某些化合物是4-伯氨基喹啉。 许多化合物和方法专门用于抑制涉及TLR9，TLR8，TLR7和TLR3中的至少一种的免疫刺激。 该方法可用于治疗自身免疫，炎症，过敏，哮喘，移植物排斥，移植物抗宿主病，感染，败血症，癌症和免疫缺陷。
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公开(公告)号：US20050119273A1
公开(公告)日：2005-06-02
申请号：US10872196
申请日：2004-06-18
IPC分类号： A01N43/54 , A61K31/517 , C07D239/72 , C07D471/00 , C07K20060101
CPC分类号： A61K31/437 , A61K31/122 , A61K31/382 , A61K31/4462 , A61K31/4709 , A61K31/496 , A61K31/517 , A61K31/5415 , A61K31/55 , A61K31/553 , C07D221/10 , C07D239/94 , C07D239/95 , C07D405/12
摘要： The invention provides methods and compositions useful for modulating signaling through Toll-like receptors. The methods involve contacting a TLR-expressing cell with a small molecule having a core structure including at least two rings. Certain of the compounds are 4-primary amino quinolines. Many of the compounds and methods are useful specifically for inhibiting immune stimulation involving at least one of TLR9, TLR8, TLR7, and TLR3. The methods may have use in the treatment of autoimmunity, inflammation, allergy, asthma, graft rejection, graft versus host disease, infection, sepsis, cancer, and immunodeficiency.
摘要翻译： 本发明提供了用于通过Toll样受体调节信号传导的方法和组合物。 所述方法包括使TLR表达细胞与具有包含至少两个环的核心结构的小分子接触。 某些化合物是4-伯氨基喹啉。 许多化合物和方法专门用于抑制涉及TLR9，TLR8，TLR7和TLR3中的至少一种的免疫刺激。 该方法可用于治疗自身免疫，炎症，过敏，哮喘，移植物排斥，移植物抗宿主病，感染，败血症，癌症和免疫缺陷。
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公开(公告)号：US08354522B2
公开(公告)日：2013-01-15
申请号：US13046871
申请日：2011-03-14
CPC分类号： A61K39/39 , A61K31/7105 , A61K2039/55561 , C12N15/117 , C12N2310/17 , C12N2310/315
摘要： The invention provides immunostimulatory compositions and use of those compounds in the preparation of medicaments for the treatment of disease as well as in vitro uses. In particular, the compositions of the invention include immunostimulatory oligoribonucleotides that incorporate a sequence-dependent immunostimulatory sequence motif. Specific modifications involving phosphate linkages, nucleotide analogs, adducts, and combinations thereof are provided. Compositions of the invention, which optionally can include an antigen, can be used alone or together with other treatments to stimulate or enhance an immune response. Also provided are compositions and methods useful for treating a subject having an infection, a cancer, an allergic condition, asthma, airway remodeling, or immunodeficiency. Immunostimulatory oligoribonucleotides of the invention are believed to stimulate Toll-like receptor 8 (TLR8).
摘要翻译： 本发明提供免疫刺激组合物和这些化合物在制备用于治疗疾病和体外用途的药物中的用途。 特别地，本发明的组合物包括掺入序列依赖性免疫刺激序列基序的免疫刺激性寡核糖核苷酸。 提供涉及磷酸键，核苷酸类似物，加合物及其组合的具体修饰。 任选地可以包括抗原的本发明的组合物可以单独使用或与其它治疗一起使用以刺激或增强免疫应答。 还提供了可用于治疗患有感染，癌症，过敏性疾病，哮喘，气道重塑或免疫缺陷的受试者的组合物和方法。 认为本发明的免疫刺激性寡核糖核苷酸可刺激Toll样受体8（TLR8）。
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公开(公告)号：US20070232622A1
公开(公告)日：2007-10-04
申请号：US11543314
申请日：2006-10-04
IPC分类号： A61K31/519 , A61P37/00 , C07D239/70 , C12N5/00
CPC分类号： A61K31/437 , A61K31/122 , A61K31/382 , A61K31/4462 , A61K31/4709 , A61K31/496 , A61K31/517 , A61K31/5415 , A61K31/55 , A61K31/553 , C07D221/10 , C07D239/94 , C07D239/95 , C07D405/12
摘要： The invention provides methods and compositions useful for modulating signaling through Toll-like receptors. The methods involve contacting a TLR-expressing cell with a small molecule having a core structure including at least two rings. Certain of the compounds are 4-primary amino quinolines. Many of the compounds and methods are useful specifically for inhibiting immune stimulation involving at least one of TLR9, TLR8, TLR7, and TLR3. The methods may have use in the treatment of autoimmunity, inflammation, allergy, asthma, graft rejection, graft versus host disease, infection, sepsis, cancer, and immunodeficiency.
摘要翻译： 本发明提供了用于通过Toll样受体调节信号传导的方法和组合物。 所述方法包括使TLR表达细胞与具有包含至少两个环的核心结构的小分子接触。 某些化合物是4-伯氨基喹啉。 许多化合物和方法专门用于抑制涉及TLR9，TLR8，TLR7和TLR3中的至少一种的免疫刺激。 该方法可用于治疗自身免疫，炎症，过敏，哮喘，移植物排斥，移植物抗宿主病，感染，败血症，癌症和免疫缺陷。
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公开(公告)号：US20070142315A1
公开(公告)日：2007-06-21
申请号：US11603978
申请日：2006-11-22
CPC分类号： A61K39/39 , A61K31/7105 , A61K2039/55561 , C12N15/117 , C12N2310/17 , C12N2310/315
摘要： The invention provides immunostimulatory compositions and use of those compounds in the preparation of medicaments for the treatment of disease as well as in vitro uses. In particular, the compositions of the invention include immunostimulatory oligoribonucleotides that incorporate a sequence-dependent immunostimulatory sequence motif. Specific modifications involving phosphate linkages, nucleotide analogs, adducts, and combinations thereof are provided. Compositions of the invention, which optionally can include an antigen, can be used alone or together with other treatments to stimulate or enhance an immune response. Also provided are compositions and methods useful for treating a subject having an infection, a cancer, an allergic condition, asthma, airway remodeling, or immunodeficiency. Immunostimulatory oligoribonucleotides of the invention are believed to stimulate Toll-like receptor 8 (TLR8).
摘要翻译： 本发明提供免疫刺激组合物和这些化合物在制备用于治疗疾病和体外用途的药物中的用途。 特别地，本发明的组合物包括掺入序列依赖性免疫刺激序列基序的免疫刺激性寡核糖核苷酸。 提供涉及磷酸键，核苷酸类似物，加合物及其组合的具体修饰。 任选地可以包括抗原的本发明的组合物可以单独使用或与其它治疗一起使用以刺激或增强免疫应答。 还提供了可用于治疗患有感染，癌症，过敏性疾病，哮喘，气道重塑或免疫缺陷的受试者的组合物和方法。 认为本发明的免疫刺激性寡核糖核苷酸可刺激Toll样受体8（TLR8）。
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公开(公告)号：US20050256073A1
公开(公告)日：2005-11-17
申请号：US11061140
申请日：2005-02-18
IPC分类号： A61K31/7088 , A61K31/7105 , A61K31/7125 , A61K39/39 , A61K48/00 , C12N15/11 , C12Q1/68
CPC分类号： A61K39/39 , A61K2039/55561
摘要： Immunostimulatory sequence-specific RNA oligonucleotides corresponding to 3′ terminal sequences of single-stranded minus-sense RNA genomic RNAs are provided. Also provided are compositions and methods relating to an immunostimulatory 4-mer RNA motif provided as 5′-C/U-U-G/U-U-3′. Incorporation of this short RNA motif is sufficient to confer new and altered immunostimulatory properties in new and existing oligonucleotides, including CpG oligodeoxynucleotides. Also provided are methods for use of the immunostimulatory RNA oligonucleotides and DNA:RNA chimeric oligonucleotides of the invention to induce an immune response in vitro and in vivo, as well as to treat allergy, asthma, infection, and cancer in a subject. Single-stranded oligoribonucleotides of the invention are believed to signal through a Toll-like receptor (TLR) chosen from TLR9, TLR8, TLR7, and TLR3. The oligoribonucleotides can also be used in a method to screen for TLR antagonists.
摘要翻译： 提供了对应于单链负义RNA基因组RNA的3'末端序列的免疫刺激序列特异性RNA寡核苷酸。 还提供了与作为5'-C / U-U-G-U-U-3'提供的免疫刺激性4聚体RNA基序相关的组合物和方法。 引入这种短RNA基序足以在新的和现有的寡核苷酸（包括CpG寡脱氧核苷酸）中赋予新的和改变的免疫刺激性质。 还提供了使用本发明的免疫刺激性RNA寡核苷酸和DNA：RNA嵌合寡核苷酸在体外和体内诱导免疫应答以及治疗受试者中的过敏，哮喘，感染和癌症的方法。 据信本发明的单链寡核糖核苷酸通过选自TLR9，TLR8，TLR7和TLR3的Toll样受体（TLR）发出信号。 寡核糖核苷酸也可用于筛选TLR拮抗剂的方法中。
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公开(公告)号：US20110300164A1
公开(公告)日：2011-12-08
申请号：US13053818
申请日：2011-03-22
CPC分类号： A61K39/39 , A61K2039/55561
摘要： Immunostimulatory sequence-specific RNA oligonucleotides corresponding to 3′ terminal sequences of single-stranded minus-sense RNA genomic RNAs are provided. Also provided are compositions and methods relating to an immunostimulatory 4-mer RNA motif provided as 5′-C/U-U-G/U-U-3′. Incorporation of this short RNA motif is sufficient to confer new and altered immunostimulatory properties in new and existing oligonucleotides, including CpG oligodeoxynucleotides. Also provided are methods for use of the immunostimulatory RNA oligonucleotides and DNA:RNA chimeric oligonucleotides of the invention to induce an immune response in vitro and in vivo, as well as to treat allergy, asthma, infection, and cancer in a subject. Single-stranded oligoribonucleotides of the invention are believed to signal through a Toll-like receptor (TLR) chosen from TLR9, TLR8, TLR7, and TLR3. The oligoribonucleotides can also be used in a method to screen for TLR antagonists.
摘要翻译： 提供了对应于单链负义RNA基因组RNA的3'末端序列的免疫刺激序列特异性RNA寡核苷酸。 还提供了与作为5'-C / U-U-G-U-U-3'提供的免疫刺激性4聚体RNA基序相关的组合物和方法。 引入这种短RNA基序足以在新的和现有的寡核苷酸（包括CpG寡脱氧核苷酸）中赋予新的和改变的免疫刺激性质。 还提供了使用本发明的免疫刺激性RNA寡核苷酸和DNA：RNA嵌合寡核苷酸在体外和体内诱导免疫应答以及治疗受试者中的过敏，哮喘，感染和癌症的方法。 据信本发明的单链寡核糖核苷酸通过选自TLR9，TLR8，TLR7和TLR3的Toll样受体（TLR）发出信号。 寡核糖核苷酸也可用于筛选TLR拮抗剂的方法中。
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公开(公告)号：US20110206719A1
公开(公告)日：2011-08-25
申请号：US13046871
申请日：2011-03-14
IPC分类号： A61K39/385 , C07H21/02 , A61K31/7088 , A61K39/00 , A61P31/00 , A61P37/04
CPC分类号： A61K39/39 , A61K31/7105 , A61K2039/55561 , C12N15/117 , C12N2310/17 , C12N2310/315
摘要： The invention provides immunostimulatory compositions and use of those compounds in the preparation of medicaments for the treatment of disease as well as in vitro uses. In particular, the compositions of the invention include immunostimulatory oligoribonucleotides that incorporate a sequence-dependent immunostimulatory sequence motif. Specific modifications involving phosphate linkages, nucleotide analogs, adducts, and combinations thereof are provided. Compositions of the invention, which optionally can include an antigen, can be used alone or together with other treatments to stimulate or enhance an immune response. Also provided are compositions and methods useful for treating a subject having an infection, a cancer, an allergic condition, asthma, airway remodeling, or immunodeficiency. Immunostimulatory oligoribonucleotides of the invention are believed to stimulate Toll-like receptor 8 (TLR8).
摘要翻译： 本发明提供免疫刺激组合物和这些化合物在制备用于治疗疾病和体外用途的药物中的用途。 特别地，本发明的组合物包括掺入序列依赖性免疫刺激序列基序的免疫刺激性寡核糖核苷酸。 提供涉及磷酸键，核苷酸类似物，加合物及其组合的具体修饰。 任选地可以包括抗原的本发明的组合物可以单独使用或与其它治疗一起使用以刺激或增强免疫应答。 还提供了可用于治疗患有感染，癌症，过敏性疾病，哮喘，气道重塑或免疫缺陷的受试者的组合物和方法。 认为本发明的免疫刺激性寡核糖核苷酸可刺激Toll样受体8（TLR8）。
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公开(公告)号：US20100316659A1
公开(公告)日：2010-12-16
申请号：US12633963
申请日：2009-12-09
IPC分类号： A61K39/00 , C07H21/02 , A61K31/7105 , A61P37/02
CPC分类号： A61K39/39 , A61K31/7105 , A61K2039/55561 , C12N15/117 , C12N2310/17 , C12N2310/315
摘要： The invention provides immunostimulatory compositions and use of those compounds in the preparation of medicaments for the treatment of disease as well as in vitro uses. In particular, the compositions of the invention include immunostimulatory oligoribonucleotides that incorporate a sequence-dependent immunostimulatory sequence motif. Specific modifications involving phosphate linkages, nucleotide analogs, adducts, and combinations thereof are provided. Compositions of the invention, which optionally can include an antigen, can be used alone or together with other treatments to stimulate or enhance an immune response. Also provided are compositions and methods useful for treating a subject having an infection, a cancer, an allergic condition, asthma, airway remodeling, or immunodeficiency. Immunostimulatory oligoribonucleotides of the invention are believed to stimulate Toll-like receptor 8 (TLR8).
摘要翻译： 本发明提供免疫刺激组合物和这些化合物在制备用于治疗疾病和体外用途的药物中的用途。 特别地，本发明的组合物包括掺入序列依赖性免疫刺激序列基序的免疫刺激性寡核糖核苷酸。 提供涉及磷酸键，核苷酸类似物，加合物及其组合的具体修饰。 任选地可以包括抗原的本发明的组合物可以单独使用或与其它治疗一起使用以刺激或增强免疫应答。 还提供了可用于治疗患有感染，癌症，过敏性疾病，哮喘，气道重塑或免疫缺陷的受试者的组合物和方法。 认为本发明的免疫刺激性寡核糖核苷酸可刺激Toll样受体8（TLR8）。
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公开(公告)号：US07662949B2
公开(公告)日：2010-02-16
申请号：US11603978
申请日：2006-11-22
CPC分类号： A61K39/39 , A61K31/7105 , A61K2039/55561 , C12N15/117 , C12N2310/17 , C12N2310/315
摘要： The invention provides immunostimulatory compositions and use of those compounds in the preparation of medicaments for the treatment of disease as well as in vitro uses. In particular, the compositions of the invention include immunostimulatory oligoribonucleotides that incorporate a sequence-dependent immunostimulatory sequence motif. Specific modifications involving phosphate linkages, nucleotide analogs, adducts, and combinations thereof are provided. Compositions of the invention, which optionally can include an antigen, can be used alone or together with other treatments to stimulate or enhance an immune response. Also provided are compositions and methods useful for treating a subject having an infection, a cancer, an allergic condition, asthma, airway remodeling, or immunodeficiency. Immunostimulatory oligoribonucleotides of the invention are believed to stimulate Toll-like receptor 8 (TLR8).
摘要翻译： 本发明提供免疫刺激组合物和这些化合物在制备用于治疗疾病和体外用途的药物中的用途。 特别地，本发明的组合物包括掺入序列依赖性免疫刺激序列基序的免疫刺激性寡核糖核苷酸。 提供涉及磷酸键，核苷酸类似物，加合物及其组合的具体修饰。 任选地可以包括抗原的本发明的组合物可以单独使用或与其它治疗一起使用以刺激或增强免疫应答。 还提供了可用于治疗患有感染，癌症，过敏性疾病，哮喘，气道重塑或免疫缺陷的受试者的组合物和方法。 认为本发明的免疫刺激性寡核糖核苷酸可刺激Toll样受体8（TLR8）。
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