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1. 发明申请

US20140187602A1 Anti-Sense Oligonucleotides Targeted Against Exon 9 of IL-23R alpha Gene and Method of Using Same to Induce Exon Skipping and to Treat Inflammatory Bowel Diseases 有权
标题翻译：针对IL-23Rα基因的外显子9的抗感知寡核苷酸及其使用方法诱导外显子跳跃和治疗炎症性肠病
公开(公告)号：US20140187602A1
公开(公告)日：2014-07-03
申请号：US14088553
申请日：2013-11-25
申请人： Grant Gallagher , Raymond Yu , Jonathan Brazaitis
发明人： Grant Gallagher , Raymond Yu , Jonathan Brazaitis
IPC分类号： C12N15/113
CPC分类号： C07K14/7155 , A61K31/7088 , C12N15/113 , C12N15/1138 , C12N2310/11 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2320/33
摘要： The present invention relates to anti-sense oligonucleotides (AONs) used to induce exon 9 skipping in IL-23Rαgene. Exon 9 skipping of the IL23Rα gene ultimately causes specific induction of a novel soluble truncated IL-23Rα (Δ9) protein, characterized by a lack in a transmembrane domain and has a unique eight (8) amino acids (GLKEGSYC) at its C-terminus end as a result of frame-shift. The present invention provides a utility application of the use of AONs to induce production of a Δ9 protein which inhibits IL-23R-mediated cell signaling. More particularly, Δ9 protein blocks STAT3 formation as well as Th17 maturation. There is provided a therapeutic application of AONs in treating a mammal such as a human patient inflicted with Crohn's disease.
摘要翻译：本发明涉及用于诱导IL-23Rα基因中外显子9跳跃的反义寡核苷酸（AON）。 IL23Rα基因的外显子9跳跃最终导致新型可溶性截短的IL-23Rα（＆Dgr; 9）蛋白的特异性诱导，其特征在于缺乏跨膜结构域，并且在其C处具有独特的8（8）个氨基酸（GLKEGSYC）由于帧转移，终端结束。本发明提供了使用AON来诱导抑制IL-23R介导的细胞信号传导的“Dgr”9蛋白的生产应用。更具体地，＆Dgr; 9蛋白质阻断STAT3形成以及Th17成熟。提供了AON治疗哺乳动物如患有克罗恩病的人类患者的治疗应用。

2. 发明申请

US20130172272A1 Novel Polypeptides That Bound to IL-23 Receptor and Inhibit Binding of IL-23 and Cell Signaling Thereof 有权
标题翻译：与IL-23受体结合并抑制IL-23和细胞信号传导的结合的新型多肽
公开(公告)号：US20130172272A1
公开(公告)日：2013-07-04
申请号：US13771305
申请日：2013-02-20
申请人： Grant Gallagher , Raymond Yu , Jonathan Brazaitis
发明人： Grant Gallagher , Raymond Yu , Jonathan Brazaitis
IPC分类号： C07K7/08
CPC分类号： C07K7/08 , A61K38/20 , C07K14/001 , C07K14/54
摘要： The present invention relates to novel polypeptides that bind to IL-23 receptor and inhibit the binding of IL-23 to its corresponding receptor and cell signaling thereof. The novel polypeptides of the present invention has a core structure of WX1X2X3W,where W is tryptophan, and X1, X2 and X3 are amino acids, with the proviso that when one of X1, X2 or X3 is W, the remaining two of X1, X2 or X3 cannot be W. Preferred core structures include WVDYW or WQDYW. The present invention relates a composition containing the novel polypeptides, and use of same in treating IL-23 associated human diseases including, for example, inflammatory bowel diseases, psoriasis and Crohn's disease.
摘要翻译：本发明涉及结合IL-23受体并抑制IL-23与其相应受体和细胞信号传导的结合的新型多肽。本发明的新型多肽具有WX1X2X3W的核心结构，其中W是色氨酸，X 1，X 2和X 3是氨基酸，条件是当X 1，X 2或X 3中的一个为W时，X 1， X2或X3不能为W.优选的核心结构包括WVDYW或WQDYW。本发明涉及含有新多肽的组合物及其在治疗IL-23相关人类疾病中的应用，包括例如炎症性肠病，牛皮癣和克罗恩病。

3. 发明授权

US09523073B2 Elisa for a naturally-occurring soluble truncated form of IL-23 receptor 有权
标题翻译： Elisa用于天然存在的可溶性截短形式的IL-23受体
公开(公告)号：US09523073B2
公开(公告)日：2016-12-20
申请号：US13065867
申请日：2011-03-31
申请人： Grant Gallagher , Raymond Yu , Joyce Eskdale , Jonathan Brazaitis
发明人： Grant Gallagher , Raymond Yu , Joyce Eskdale , Jonathan Brazaitis
IPC分类号： G01N33/53 , C12N5/071 , C07K14/715 , A61K38/00
CPC分类号： G01N33/6893 , A61K38/00 , C07K14/7155 , C12N5/0602 , G01N33/6863 , G01N2333/705 , G01N2800/065 , G01N2800/368
摘要： A naturally-occurring soluble truncated IL-23Rα protein (i.e., Δ9 IL-23Rα) is shown to be present in a biological sample and can serve as a diagnostic tool for autoimmune diseases. There is provided an enzyme-linked immunosorbent assay (ELISA) and test kit for the serological detection of the soluble truncated form of IL-23Rα protein. More particularly, antibody-sandwich ELISA method and kits for Δ9 IL-23Rα as an antigen were developed to detect Δ9 IL-23Rα levels in biological samples from a mammal and a human patient and are used as a diagnostic index. The present disclosed ELISA has utility as a diagnostic tool to detect Crohn's disease in patients using EDTA-plasma.
摘要翻译：天然存在的可溶性截短的IL-23Rα蛋白（即Δ9IL-23Rα）显示存在于生物学样品中，并且可以作为自身免疫性疾病的诊断工具。提供了用于血清学检测IL-23Rα蛋白的可溶性截短形式的酶联免疫吸附测定（ELISA）和测试试剂盒。更具体地，开发了用于Δ9IL-23Rα作为抗原的抗体夹心ELISA方法和试剂盒，以检测来自哺乳动物和人类患者的生物样品中的Δ9IL-23Rα水平，并用作诊断指标。本公开的ELISA可用作诊断工具，用于检测使用EDTA-血浆的患者的克罗恩病。

4. 发明申请

US20120071422A1 Therapeutic application of isolated naturally-occuring soluble truncated forms of IL-23 receptor 审中-公开
标题翻译：分离的天然存在的可溶性截短形式的IL-23受体的治疗应用
公开(公告)号：US20120071422A1
公开(公告)日：2012-03-22
申请号：US13065878
申请日：2011-03-31
申请人： Grant Gallagher , Raymond Yu , Jonathan Brazaitis
发明人： Grant Gallagher , Raymond Yu , Jonathan Brazaitis
IPC分类号： A61K38/17 , C12P21/02 , C12N5/071 , C07K14/715
CPC分类号： G01N33/6893 , A61K38/00 , C07K14/7155 , C12N5/0602 , G01N33/6863 , G01N2333/705 , G01N2800/065 , G01N2800/368
摘要： The present invention relates to an isolated naturally-occurring soluble truncated IL-23Rα protein, which is a translated protein resulting from a mRNA splice variant of IL-23Rα. The soluble IL-23Rα proteins (e.g., Δ9 and Δ8,9) represents a novel soluble IL-23Rα protein, which is lacking a transmembrane domain and has a unique eight (8) amino acids (GLKEGSYC) at its C-terminus end (due to frame-shift). ELISA reveals that Δ9 is present in blood and can serve as a diagnostic tool for auto-immune diseases including Crohn's disease. There is also provided a method of recombinant production for this soluble truncated form of IL-23Rα protein. More importantly, the present invention provides an utility application of the Δ9 and Δ8,9 protein in inhibit IL-23R-mediated cell signaling. More particularly, Δ9 and Δ8,9 blocks STAT3 formation as well as Th17 maturation. There is provided a therapeutic application of Δ9 and Δ8,9 in treating a human patient inflicted with Crohn's disease.
摘要翻译：本发明涉及分离的天然存在的可溶性截短的IL-23Rα蛋白，其是由IL-23Rα的mRNA剪接变体产生的翻译蛋白。可溶性IL-23Rα蛋白（例如，＆Dgr; 9和＆Dgr; 8,9）代表一种新的可溶性IL-23Rα蛋白，其缺乏跨膜结构域，并且在其C处具有独特的8（8）个氨基酸（GLKEGSYC） - 终结（由于帧移）。 ELISA显示，Dgr。9存在于血液中，可用作包括克罗恩病在内的自身免疫疾病的诊断工具。还提供了这种可溶性截短形式的IL-23Rα蛋白的重组生产方法。更重要的是，本发明提供了抑制IL-23R介导的细胞信号传导的“D”和“D”和“D”。更具体地，＆Dgr; 9和＆Dgr; 8,9阻断STAT3形成以及Th17成熟。在治疗患有克罗恩病的人类患者中提供了＆Dgr。9和＆Dgr; 8,9的治疗应用。

5. 发明申请

US20160115218A1 Anti-Sense Oligonucleotides Targeted Against Exon 9 of IL-23R-alpha Gene and Method of Using Same to Induce Exon Skipping and to Treat Inflammatory Bowel Diseases 审中-公开
标题翻译：针对IL-23R-α基因外显子9的抗感知寡核苷酸及其使用方法诱导外显子跳跃和治疗炎症性肠病
公开(公告)号：US20160115218A1
公开(公告)日：2016-04-28
申请号：US14918657
申请日：2015-10-21
申请人： Grant Gallagher , Raymond Yu , Jonathan Brazaitis
发明人： Grant Gallagher , Raymond Yu , Jonathan Brazaitis
IPC分类号： C07K14/715 , C12N15/113
CPC分类号： C07K14/7155 , A61K31/7088 , C12N15/113 , C12N15/1138 , C12N2310/11 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2320/33
摘要： The present invention relates to anti-sense oligonucleotides (AONs) used to induce exon 9 skipping in IL-23Rα gene. Exon 9 skipping of the IL23Rα gene ultimately causes specific induction of a novel soluble truncated IL-23Rα (Δ9) protein, characterized by a lack in a transmembrane domain and has a unique eight (8) amino acids (GLKEGSYC) at its C-terminus end as a result of frame-shift. The present invention provides a utility application of the use of AONs to induce production of a Δ9 protein which inhibits IL-23R-mediated cell signaling. More particularly, Δ9 protein blocks STAT3 formation as well as Th17 maturation. There is provided a therapeutic application of AONs in treating a mammal such as a human patient inflicted with Crohn's disease.
摘要翻译：本发明涉及用于诱导IL-23Rα基因中外显子9跳跃的反义寡核苷酸（AON）。 IL23Rα基因的外显子9跳跃最终导致新型可溶性截短的IL-23Rα（＆Dgr; 9）蛋白的特异性诱导，其特征在于缺乏跨膜结构域，并且在其C处具有独特的8（8）个氨基酸（GLKEGSYC）由于帧转移，终端结束。本发明提供了使用AON来诱导抑制IL-23R介导的细胞信号传导的“Dgr”9蛋白的生产应用。更具体地，＆Dgr; 9蛋白质阻断STAT3形成以及Th17成熟。提供了AON治疗哺乳动物如患有克罗恩病的人类患者的治疗应用。

6. 发明申请

US20130183755A1 THERAPEUTIC APPLICATION OF ISOLATED NATURALLY-OCCURRING SOLUBLE TRUNCATED FORMS OF IL-23 RECEPTOR 审中-公开
标题翻译： IL-23受体分离自然可解交联形式的治疗应用
公开(公告)号：US20130183755A1
公开(公告)日：2013-07-18
申请号：US13748066
申请日：2013-01-23
申请人： Grant Gallagher , Raymond Yu , Jonathan Brazaitis
发明人： Grant Gallagher , Raymond Yu , Jonathan Brazaitis
IPC分类号： C12N5/071
CPC分类号： G01N33/6893 , A61K38/00 , C07K14/7155 , C12N5/0602 , G01N33/6863 , G01N2333/705 , G01N2800/065 , G01N2800/368
摘要： The present invention relates to an isolated naturally-occurring soluble truncated IL-23Rα protein, which is a translated protein resulting from a mRNA splice variant of IL-23Rα. The soluble IL-23Rα proteins (e.g., Δ9 and Δ8,9) represents a novel soluble IL-23Rα protein, which is lacking a transmembrane domain and has a unique eight (8) amino acids (GLKEGSYC) at its C-terminus end (due to frame-shift). ELISA reveals that Δ9 is present in blood and can serve as a diagnostic tool for auto-immune diseases including Crohn's disease. There is also provided a method of recombinant production for this soluble truncated form of IL-23Rα protein. More importantly, the present invention provides an utility application of the Δ9 and Δ8,9 protein in inhibit IL-23R-mediated cell signaling. More particularly, Δ9 and Δ8,9 blocks STAT3 formation as well as Th17 maturation. There is provided a therapeutic application of Δ9 and Δ8,9 in treating a human patient inflicted with Crohn's disease.
摘要翻译：本发明涉及分离的天然存在的可溶性截短的IL-23Rα蛋白，其是由IL-23Rα的mRNA剪接变体产生的翻译蛋白。可溶性IL-23Rα蛋白（例如，Delta9和Delta8,9）代表一种新的可溶性IL-23Rα蛋白，其缺乏跨膜结构域，并且在其C末端具有独特的八（8）个氨基酸（GLKEGSYC）由于帧移）。 ELISA显示，Delta9存在于血液中，可用作包括克罗恩病在内的自身免疫疾病的诊断工具。还提供了这种可溶性截短形式的IL-23Rα蛋白的重组生产方法。更重要的是，本发明提供了Delta9和Delta8,9蛋白在抑制IL-23R介导的细胞信号传导中的应用。更具体地，Delta9和Delta8,9阻断STAT3形成以及Th17成熟。提供了Delta9和Delta8,9在治疗患有克罗恩病的人类患者中的治疗应用。

7. 发明申请

US20120171704A1 Elisa for a naturally-occurring soluble truncated form of IL-23 receptor 有权
标题翻译： Elisa用于天然存在的可溶性截短形式的IL-23受体
公开(公告)号：US20120171704A1
公开(公告)日：2012-07-05
申请号：US13065867
申请日：2011-03-31
申请人： Grant Gallagher , Raymond Yu , Joyce Eskdale , Jonathan Brazaitis
发明人： Grant Gallagher , Raymond Yu , Joyce Eskdale , Jonathan Brazaitis
IPC分类号： G01N33/577 , G01N33/566
CPC分类号： G01N33/6893 , A61K38/00 , C07K14/7155 , C12N5/0602 , G01N33/6863 , G01N2333/705 , G01N2800/065 , G01N2800/368
摘要： A naturally-occurring soluble truncated IL-23Rα protein (i.e., Δ9 IL-23Rα) is shown to be present in a biological sample and can serve as a diagnostic tool for autoimmune diseases. There is provided an enzyme-linked immunosorbent assay (ELISA) and test kit for the serological detection of the soluble truncated form of IL-23Rα protein. More particularly, antibody-sandwich ELISA method and kits for Δ9 IL-23Rα as an antigen were developed to detect Δ9 IL-23Rα levels in biological samples from a mammal and a human patient and are used as a diagnostic index. The present disclosed ELISA has utility as a diagnostic tool to detect Crohn's disease in patients using EDTA-plasma.
摘要翻译：天然存在的可溶性截短的IL-23Rα蛋白（即，＆Dgr; 9 IL-23Rα）显示存在于生物学样品中，并可用作自身免疫性疾病的诊断工具。提供了用于血清学检测IL-23Rα蛋白的可溶性截短形式的酶联免疫吸附测定（ELISA）和测试试剂盒。更具体地，开发了抗体夹心ELISA方法和用于Dgr。9 IL-23Rα作为抗原的试剂盒，以检测来自哺乳动物和人类患者的生物样品中的Dgr。9 IL-23Rα水平，并用作诊断指标。本公开的ELISA可用作诊断工具，用于检测使用EDTA-血浆的患者的克罗恩病。

8. 发明授权

US09605027B2 Polypeptides that bound to IL-23 receptor and inhibit binding of IL-23 and cell signaling thereof 有权
公开(公告)号：US09605027B2
公开(公告)日：2017-03-28
申请号：US14922630
申请日：2015-10-26
申请人： Grant Gallagher , Raymond Yu , Jonathan Brazaitis
发明人： Grant Gallagher , Raymond Yu , Jonathan Brazaitis
IPC分类号： C07K7/64 , C07K7/06 , H04N1/10 , C07K14/435 , A61K38/12 , A61K38/00 , H04N1/193
CPC分类号： C07K7/64 , A61K38/00 , A61K38/12 , C07K7/06 , C07K14/435 , H04N1/1013 , H04N1/193 , H04N2201/0081 , H04N2201/0446
摘要： The present invention relates to novel linear and cyclic polypeptides that bind to IL-23 receptor and inhibit the binding of IL-23 to its corresponding receptor and cell signaling thereof. The novel polypeptides of the present invention has a core structure of WX1X2X3W, where W is tryptophan, and X1, X2 and X3 are amino acids, with the proviso that when one of X1, X2 or X3 is W, the remaining two of X1, X2 or X3 cannot be W. Preferred core structures include WVDYW or WQDYW. The present invention relates a composition containing the novel polypeptides (linear or cyclic), and use of same in inhibiting cell functions including production of IL-22 and IL-17F from immune cells as well as in treating IL-23 associated human diseases including, for example, inflammatory bowel diseases, psoriasis and Crohn's disease, ulcerative colitis and multiple sclerosis.

9. 发明授权

US08618070B2 Anti-sense oligonucleotides targeted against exon 9 of IL-23Rα gene and method of using same to induce exon skipping and to treat inflammatory bowel diseases 有权
标题翻译：针对IL-23Rα基因外显子9的反义寡核苷酸及其使用方法诱导外显子跳跃和治疗炎症性肠病
公开(公告)号：US08618070B2
公开(公告)日：2013-12-31
申请号：US13068064
申请日：2011-05-02
申请人： Grant Gallagher , Raymond Yu , Jonathan Brazaitis
发明人： Grant Gallagher , Raymond Yu , Jonathan Brazaitis
IPC分类号： C12N15/11
CPC分类号： C07K14/7155 , A61K31/7088 , C12N15/113 , C12N15/1138 , C12N2310/11 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2320/33
摘要： The present invention relates to anti-sense oligonucleotides (AONs) used to induce exon 9 skipping in IL-23Rα gene. Exon 9 skipping of the IL23Rα gene ultimately causes specific induction of a novel soluble truncated IL-23Rα (Δ9) protein, characterized by a lack in a transmembrane domain and has a unique eight (8) amino acids (GLKEGSYC) at its C-terminus end as a result of frame-shift. The present invention provides a utility application of the use of AONs to induce production of a Δ9 protein which inhibits IL-23R-mediated cell signaling. More particularly, Δ9 protein blocks STAT3 formation as well as Th17 maturation. There is provided a therapeutic application of AONs in treating a mammal such as a human patient inflicted with Crohn's disease.
摘要翻译：本发明涉及用于诱导IL-23Rα基因突变的外显子9的反义寡核苷酸（AON）。 IL23Ralpha基因的外显子9跳跃最终导致新型可溶性截短的IL-23Rα（Delta9）蛋白的特异性诱导，其特征在于缺少跨膜结构域，并且在其C末端具有独特的8（8）个氨基酸（GLKEGSYC）作为帧移的结果。本发明提供了使用AON诱导抑制IL-23R介导的细胞信号传导的Delta9蛋白的生产的实用应用。更具体地，Delta9蛋白质阻断STAT3形成以及Th17成熟。提供了AON治疗哺乳动物如患有克罗恩病的人类患者的治疗应用。

10. 发明申请

US20130035365A1 Anti-sense oligonucleotides targeted against exon 9 of IL-23R alpha gene and method of using same to induce exon skipping and to treat inflammatory bowel diseases 有权
标题翻译：针对IL-23Rα基因外显子9的反义寡核苷酸及其使用方法诱导外显子跳跃和治疗炎症性肠病
公开(公告)号：US20130035365A1
公开(公告)日：2013-02-07
申请号：US13068064
申请日：2011-05-02
申请人： Grant Gallagher , Raymond Yu , Jonathan Brazaitis
发明人： Grant Gallagher , Raymond Yu , Jonathan Brazaitis
IPC分类号： C07H21/04 , A61P1/00 , A61K31/7088
CPC分类号： C07K14/7155 , A61K31/7088 , C12N15/113 , C12N15/1138 , C12N2310/11 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2320/33
摘要： The present invention relates to anti-sense oligonucleotides (AONs) used to induce exon 9 skipping in IL-23Rα gene. Exon 9 skipping of the IL23Rα gene ultimately causes specific induction of a novel soluble truncated IL-23Rα (Δ9) protein, characterized by a lack in a transmembrane domain and has a unique eight (8) amino acids (GLKEGSYC) at its C-terminus end as a result of frame-shift. The present invention provides a utility application of the use of AONs to induce production of a Δ9 protein which inhibits IL-23R-mediated cell signaling. More particularly, Δ9 protein blocks STAT3 formation as well as Th17 maturation. There is provided a therapeutic application of AONs in treating a mammal such as a human patient inflicted with Crohn's disease.
摘要翻译：本发明涉及用于诱导IL-23Rα基因中外显子9跳跃的反义寡核苷酸（AON）。 IL23Rα基因的外显子9跳跃最终导致新型可溶性截短的IL-23Rα（＆Dgr; 9）蛋白的特异性诱导，其特征在于缺乏跨膜结构域，并且在其C处具有独特的8（8）个氨基酸（GLKEGSYC）由于帧转移，终端结束。本发明提供了使用AON来诱导抑制IL-23R介导的细胞信号传导的“Dgr”9蛋白的生产应用。更具体地，＆Dgr; 9蛋白质阻断STAT3形成以及Th17成熟。提供了AON治疗哺乳动物如患有克罗恩病的人类患者的治疗应用。

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