公开(公告)号：US09492439B2

公开(公告)日：2016-11-15

申请号：US13634073

申请日：2011-03-11

申请人： Dan Littman ,  Jun R. Huh ,  Wenwei Huang ,  Ruili Huang ,  Erika Elaine Englund

发明人： Dan Littman ,  Jun R. Huh ,  Wenwei Huang ,  Ruili Huang ,  Erika Elaine Englund

IPC分类号： C07D211/06 ,  C07D401/10 ,  C07D403/14 ,  C07D405/06 ,  A61K31/4525 ,  A61K31/12 ,  A61K31/33 ,  A61K31/535 ,  C07C235/34 ,  C07C235/36 ,  C07D211/16 ,  C07D307/52 ,  C07D317/54 ,  C07D317/60 ,  A61K31/4453

CPC分类号： A61K31/55 ,  A61K31/12 ,  A61K31/33 ,  A61K31/4025 ,  A61K31/404 ,  A61K31/4453 ,  A61K31/451 ,  A61K31/4525 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/535 ,  A61K31/5377 ,  C07C235/34 ,  C07C235/36 ,  C07D211/06 ,  C07D211/16 ,  C07D307/52 ,  C07D307/81 ,  C07D317/54 ,  C07D317/60 ,  C07D401/10 ,  C07D403/14 ,  C07D405/06 ,  C07D413/06 ,  C07D413/14

摘要： Amido compounds are disclosed that have a formula represented by the following: and wherein n1, n2, R1a, R1b, R2, R3, R4, R5, and R6 are as described herein. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, inflammatory conditions, autoimmune disorders, cancer, and graft-versus-host disease.

摘要翻译： 公开了具有由以下表示的式的酰氨基化合物：其中n1，n2，R 1a，R 1b，R 2，R 3，R 4，R 5和R 6如本文所述。 化合物可以制备成药物组合物，并且可以用于预防和治疗包括人在内的哺乳动物中的多种病症，包括作为非限制性实例，炎性病症，自身免疫疾病，癌症和移植物抗 - 宿主病。

公开(公告)号：US09101600B2

公开(公告)日：2015-08-11

申请号：US13634102

申请日：2011-03-11

申请人： Dan Littman ,  Jun R. Huh ,  Wenwei Huang ,  Ruili Huang

发明人： Dan Littman ,  Jun R. Huh ,  Wenwei Huang ,  Ruili Huang

IPC分类号： A61K31/4188 ,  A61K31/7048 ,  A61K31/4439 ,  A61K31/519 ,  C07D495/04 ,  C07D471/04 ,  A61P1/04 ,  A61P19/02 ,  A61P29/00 ,  A61K31/33 ,  A61K31/41

CPC分类号： A61K31/33 ,  A61K31/41

摘要： Heterocyclic compounds, and pharmaceutical compositions thereof, are disclosed as RORγt modulators that have a formula represented by the following: and wherein n1, n2, R1, R2, R3, and R4 are as described herein. These compounds may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, inflammatory conditions, autoimmune disorders, cancer, and graft-versus-host disease.

摘要翻译： 公开了杂环化合物及其药物组合物，其具有由下式表示的式RORγt调节剂：其中n1，n2，R1，R2，R3和R4如本文所述。 这些化合物可用于预防和治疗包括人在内的哺乳动物中的多种病症，包括非限制性实例，炎性病症，自身免疫疾病，癌症和移植物抗宿主病。

公开(公告)号：US09765063B2

公开(公告)日：2017-09-19

申请号：US14343410

申请日：2012-09-10

申请人： Dan Littman ,  Jun R. Huh ,  Ruili Huang ,  Wenwei Huang ,  Erika E. Englund

发明人： Dan Littman ,  Jun R. Huh ,  Ruili Huang ,  Wenwei Huang ,  Erika E. Englund

IPC分类号： C07D409/06 ,  C07D209/44 ,  C07D211/14 ,  C07D213/58 ,  C07D333/24 ,  C07D401/06 ,  C07D405/14 ,  A61K31/40 ,  A61K31/4025 ,  A61K31/445 ,  A61K31/4709 ,  A61K31/495 ,  A61K31/496 ,  A61K31/5375 ,  A61K31/5377

CPC分类号： C07D409/06 ,  A61K31/40 ,  A61K31/4025 ,  A61K31/445 ,  A61K31/4709 ,  A61K31/495 ,  A61K31/496 ,  A61K31/5375 ,  A61K31/5377 ,  C07D209/44 ,  C07D211/14 ,  C07D213/58 ,  C07D333/24 ,  C07D401/06 ,  C07D405/14

摘要： Amido compounds are disclosed that have a formula represented by the following: and wherein Cy1, Cy2, n1, n2, R1a, R1b, R2, R3, R4, R5, and R6 are as described herein. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, inflammatory conditions, autoimmune disorders, cancer, and graft-versus-host disease.

公开(公告)号：US20150057278A1

公开(公告)日：2015-02-26

申请号：US14343410

申请日：2012-09-10

申请人： Dan Littman ,  Jun R. Huh ,  Ruili Huang ,  Wenwei Huang ,  Erika E. Englund

发明人： Dan Littman ,  Jun R. Huh ,  Ruili Huang ,  Wenwei Huang ,  Erika E. Englund

IPC分类号： C07D409/06 ,  C07D209/44 ,  C07D211/14 ,  C07D401/06 ,  C07D405/14 ,  C07D213/58 ,  C07D333/24

CPC分类号： C07D409/06 ,  A61K31/40 ,  A61K31/4025 ,  A61K31/445 ,  A61K31/4709 ,  A61K31/495 ,  A61K31/496 ,  A61K31/5375 ,  A61K31/5377 ,  C07D209/44 ,  C07D211/14 ,  C07D213/58 ,  C07D333/24 ,  C07D401/06 ,  C07D405/14

摘要： Amido compounds are disclosed that have a formula represented by the following: and wherein Cy1, Cy2, n1, n2, R1a, R1b, R2, R3, R4, R5, and R6 are as described herein. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, inflammatory conditions, autoimmune disorders, cancer, and graft-versus-host disease.

摘要翻译： 公开了具有下列表示的式的酰氨基化合物：其中Cy1，Cy2，n1，n2，R1a，R1b，R2，R3，R4，R5和R6如本文所述。 化合物可以制备成药物组合物，并且可以用于预防和治疗包括人在内的哺乳动物中的多种病症，包括作为非限制性实例，炎性病症，自身免疫疾病，癌症和移植物抗 - 宿主病。

公开(公告)号：US20130085162A1

公开(公告)日：2013-04-04

申请号：US13634073

申请日：2011-03-11

申请人： Dan Littman ,  Jun R. Huh ,  Wenwei Huang ,  Ruili Huang ,  Erika Elaine Englund

发明人： Dan Littman ,  Jun R. Huh ,  Wenwei Huang ,  Ruili Huang ,  Erika Elaine Englund

IPC分类号： A61K31/4525 ,  A61K31/4453 ,  C07D211/06 ,  C07D401/10

CPC分类号： A61K31/55 ,  A61K31/12 ,  A61K31/33 ,  A61K31/4025 ,  A61K31/404 ,  A61K31/4453 ,  A61K31/451 ,  A61K31/4525 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/535 ,  A61K31/5377 ,  C07C235/34 ,  C07C235/36 ,  C07D211/06 ,  C07D211/16 ,  C07D307/52 ,  C07D307/81 ,  C07D317/54 ,  C07D317/60 ,  C07D401/10 ,  C07D403/14 ,  C07D405/06 ,  C07D413/06 ,  C07D413/14

摘要： Amido compounds are disclosed that have a formula represented by the following: and wherein n1, n2, R1a, R1b, R2, R3, R4, R5, and R6 are as described herein. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, inflammatory conditions, autoimmune disorders, cancer, and graft-versus-host disease.

摘要翻译： 公开了具有由以下表示的式的酰氨基化合物：其中n1，n2，R1a，R1b，R2，R3，R4，R5和R6如本文所述。 化合物可以制备成药物组合物，并且可以用于预防和治疗包括人在内的哺乳动物中的多种病症，包括作为非限制性实例，炎性病症，自身免疫疾病，癌症和移植物抗 - 宿主病。

公开(公告)号：US20130065842A1

公开(公告)日：2013-03-14

申请号：US13634102

申请日：2011-03-11

申请人： Dan Littman ,  Jun R. Huh ,  Wenwei Huang ,  Ruili Huang

发明人： Dan Littman ,  Jun R. Huh ,  Wenwei Huang ,  Ruili Huang

IPC分类号： A61K31/4188 ,  A61K31/7048 ,  A61K31/57 ,  A61K31/496 ,  A61K31/4439 ,  A61K31/4709 ,  A61K31/519 ,  A61K31/5377 ,  C07J17/00 ,  C07D495/04 ,  C07D471/04 ,  C07D413/12 ,  C07D401/12 ,  C07D417/14 ,  C07D403/06 ,  A61P29/00 ,  A61P37/00 ,  A61P19/02 ,  A61P3/10 ,  A61P25/00 ,  A61P17/06 ,  A61P11/00 ,  A61P9/10 ,  A61P11/06 ,  A61P11/02 ,  A61P37/08 ,  A61P1/04 ,  C07D491/147

CPC分类号： A61K31/33 ,  A61K31/41

摘要： Heterocyclic compounds, and pharmaceutical compositions thereof, are disclosed as RORγt modulators that have a formula represented by the following: and wherein n1, n2, R1, R2, R3, and R4 are as described herein. These compounds may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, inflammatory conditions, autoimmune disorders, cancer, and graft-versus-host disease.

摘要翻译： 公开了杂环化合物及其药物组合物，其具有由下式表示的式RORγt调节剂：其中n1，n2，R1，R2，R3和R4如本文所述。 这些化合物可用于预防和治疗包括人在内的哺乳动物中的多种病症，包括非限制性实例，炎性病症，自身免疫疾病，癌症和移植物抗宿主病。

公开(公告)号：US09358281B2

公开(公告)日：2016-06-07

申请号：US12925068

申请日：2010-10-12

申请人： Dan Littman ,  Nicolas Manel

发明人： Dan Littman ,  Nicolas Manel

IPC分类号： A61K39/21 ,  A61P37/00 ,  C12Q1/70 ,  G01N33/569 ,  C07K14/005 ,  A61K39/12 ,  A61K39/00

CPC分类号： A61K39/21 ,  A61K39/12 ,  A61K2039/5258 ,  A61K2039/53 ,  A61K2039/57 ,  A61K2039/6031 ,  C07K14/005 ,  C12N2740/16011 ,  C12N2740/16034 ,  C12N2740/16222 ,  C12Q1/70 ,  G01N33/56988 ,  G01N2333/16 ,  G01N2500/10

摘要： The present invention relates to enhancing, modulating or stimulating the innate immune response to HIV-1 and other viral pathogens and to the modulation and application of immune modulators and peptides for HIV-1 or other pathogen vaccines. The invention provides methods and means to activate an innate response to HIV-1 utilizing or via the HIV capsid protein or peptide, including modulating the binding of cyclophilin A to HIV capsid protein and modulating the ability of HIV to activate the major innate transcription factor IRF3 and interferon. Methods and assays are provided for screening for compounds, agents, or peptides capable of enhancing or activating innate immune response, particularly to HIV-1.

摘要翻译： 本发明涉及增强，调节或刺激HIV-1和其他病毒病原体的先天免疫应答，以及用于HIV-1或其它病原体疫苗的免疫调节剂和肽的调节和应用。 本发明提供了利用或经由HIV衣壳蛋白或肽激活对HIV-1的先天应答的方法和手段，包括调节亲环蛋白A与HIV衣壳蛋白的结合并调节HIV激活主要先天转录因子IRF3的能力 和干扰素。 提供了用于筛选能够增强或激活先天免疫应答，特别是HIV-1的化合物，试剂或肽的方法和测定。

公开(公告)号：US20150224152A1

公开(公告)日：2015-08-13

申请号：US14526911

申请日：2014-10-29

申请人： Dan Littman ,  Ivaylo Ivanov ,  Eoin Brodie ,  Yoshinori Umesaki ,  Kenya Honda

发明人： Dan Littman ,  Ivaylo Ivanov ,  Eoin Brodie ,  Yoshinori Umesaki ,  Kenya Honda

IPC分类号： A61K35/74 ,  C12Q1/68

CPC分类号： A61K35/74 ,  A61K39/39 ,  A61K2035/122 ,  A61K2039/55594 ,  C12Q1/6881 ,  C12Q2600/158 ,  C12Q2600/16 ,  Y02A50/484

摘要： The present invention relates to methods for treating or reducing the risk of or preventing diseases caused by or associated with pathogenic bacteria. More particularly, the present invention relates to methods for treating or reducing the risk of or preventing diseases caused by or associated with pathogenic bacteria of the gastrointestinal (GI) tract. The present invention further relates to methods for promoting pathways induced by commensal bacteria of the GI tract that lead to Th17 differentiation, which in turn leads to localized and systemic accumulation of Th17 cells. Compositions and medicaments are also described herein that are used alleviate and/or prevent symptoms associated with diseases caused by or associated with pathogenic bacteria. Accordingly, the compositions, medicaments and methods described herein may be used to address the needs of patients or subjects that would benefit from increased Th17 cell differentiation.

摘要翻译： 本发明涉及用于治疗或降低由病原菌引起或与其相关的疾病的风险或预防疾病的方法。 更具体地，本发明涉及用于治疗或降低由胃肠道（GI）道的病原菌引起或与之相关的疾病的风险或预防疾病的方法。 本发明还涉及促进导致Th17分化的胃肠道共生细菌诱导的途径的方法，其又导致Th17细胞的局部和全身积累。 本文还描述了组合物和药物，其用于缓解和/或预防与由致病细菌引起或与病原体细菌相关的疾病相关的症状。 因此，本文所述的组合物，药物和方法可用于满足将从Th17细胞分化增加中受益的患者或受试者的需要。

公开(公告)号：US20170159057A1

公开(公告)日：2017-06-08

申请号：US15358668

申请日：2016-11-22

申请人： Dan Littman ,  Gerard Eberl ,  Liang Zhou ,  Ivaylo Ivanov

发明人： Dan Littman ,  Gerard Eberl ,  Liang Zhou ,  Ivaylo Ivanov

IPC分类号： C12N15/113

CPC分类号： C12N15/1138 ,  A61K39/0011 ,  A61K39/39 ,  A61K2039/55522 ,  C07K16/2803 ,  C12N2310/14 ,  C12N2310/531

摘要： The present invention relates to expression of RORγt in cells and tissues and the effect of expression of this gene on proliferation of specific immune cells and in promotion of immune cell aggregates and in induction of IL17 producing cells. Furthermore, the invention relates to methods and agents that may decrease function of the gene product (the protein) or expression of this gene in individuals experiencing an inflammatory condition, an autoimmune disease or a food allergy, or any other condition whereby it is desirable to inhibit an immune response. In addition, methods and agents useful for enhancing the function of RORγt with agonists or expression of this gene are also considered for use whereby it is desirable to increase immunity to a pathogen or tumor cell, for example, for use in conjunction with a vaccine. Screening methods for identifying novel modulators (antagonists and agonists) of RORγt are also disclosed.

公开(公告)号：US20150218563A1

公开(公告)日：2015-08-06

申请号：US14589336

申请日：2015-01-05

申请人： Dan Littman ,  Gerard Eberl ,  Liang Zhou ,  Ivaylo Ivanov

发明人： Dan Littman ,  Gerard Eberl ,  Liang Zhou ,  Ivaylo Ivanov

IPC分类号： C12N15/113

CPC分类号： C12N15/1138 ,  A61K39/0011 ,  A61K39/39 ,  A61K2039/55522 ,  C07K16/2803 ,  C12N2310/14 ,  C12N2310/531

摘要： The present invention relates to expression of RORγt in cells and tissues and the effect of expression of this gene on proliferation of specific immune cells and in promotion of immune cell aggregates and in induction of IL17 producing cells. Furthermore, the invention relates to methods and agents that may decrease function of the gene product (the protein) or expression of this gene in individuals experiencing an inflammatory condition, an autoimmune disease or a food allergy, or any other condition whereby it is desirable to inhibit an immune response. In addition, methods and agents useful for enhancing the function of RORγt with agonists or expression of this gene are also considered for use whereby it is desirable to increase immunity to a pathogen or tumor cell, for example, for use in conjunction with a vaccine. Screening methods for identifying novel modulators (antagonists and agonists) of RORγt are also disclosed.

摘要翻译： 本发明涉及细胞和组织中RORγt的表达以及该基因表达对特异性免疫细胞增殖和促进免疫细胞聚集和诱导IL17产生细胞的作用。 此外，本发明涉及可以减少经历炎症状况，自身免疫疾病或食物过敏的个体的基因产物（蛋白质）或该基因的表达或其他任何其它条件的功能的方法和试剂， 抑制免疫反应。 此外，还考虑用于增强RORγt与激动剂或该基因表达的功能的方法和试剂，因此期望提高对病原体或肿瘤细胞的免疫力，例如与疫苗结合使用。 还公开了用于鉴定RORγt的新型调节剂（拮抗剂和激动剂）的筛选方法。