公开(公告)号：US09200058B2

公开(公告)日：2015-12-01

申请号：US13635874

申请日：2011-03-18

申请人： Young Woo Park ,  Ki Won Jo ,  Srok Ho Yoo ,  Jung Yu ,  Sun-Ha Yoon ,  Ji Hyun Park ,  Eun Jung Song ,  Jong-Ho Lee ,  Min Ji Seo ,  Sun Jung Cho ,  Mi La Cho ,  Ho Youn Kim ,  Mi Kyung Park ,  Hye Jwa Oh ,  Jin Sil Park ,  Yun Ju Woo ,  Jae Kyeong Byun ,  Jun Geol Ryu

发明人： Young Woo Park ,  Ki Won Jo ,  Srok Ho Yoo ,  Jung Yu ,  Sun-Ha Yoon ,  Ji Hyun Park ,  Eun Jung Song ,  Jong-Ho Lee ,  Min Ji Seo ,  Sun Jung Cho ,  Mi La Cho ,  Ho Youn Kim ,  Mi Kyung Park ,  Hye Jwa Oh ,  Jin Sil Park ,  Yun Ju Woo ,  Jae Kyeong Byun ,  Jun Geol Ryu

IPC分类号： C07K14/715

CPC分类号： C07K14/7151 ,  C07K14/7155 ,  C07K2319/00

摘要： The present invention relates to TNFR2-IL21R fusion protein acting as a double-antagonist to TNF-alpha (α) and IL-21. The composition containing the double antagonist to TNF-α and Il-21 (TNFR2-IL21R fusion protein), known as major causes of autoimmune rheumatoid arthritis, one of autoimmune diseases, can reduce the secretion of inflammatory cytokine, increase the secretion of anti-inflammatory cytokine, and suppress the differentiation of osteoclasts better than single proteins such as TNFR2-Fc and IL21R-Fc. The TNFR2-IL21R fusion protein of the present invention has not only excellent treatment effect on arthritis in CIA mouse model not also excellent treatment effect on autoimmune rheumatoid arthritis by increasing the expression of Treg, the immune suppressive cells. Therefore, the TNFR2-IL21R fusion protein of the present invention can be effectively used as an active ingredient for the composition for the prevention and treatment of autoimmune disease.

摘要翻译： 本发明涉及作为TNF-α（α）和IL-21的双重拮抗剂的TNFR2-IL21R融合蛋白。 含有TNF-α和II-21（TNFR2-IL21R融合蛋白）的双重拮抗剂的组合物，被称为自身免疫性类风湿性关节炎的主要原因（自身免疫性疾病之一）可以减少炎性细胞因子的分泌， 炎性细胞因子，并且比单一蛋白如TNFR2-Fc和IL21R-Fc更好地抑制破骨细胞的分化。 本发明的TNFR2-IL21R融合蛋白不仅对CIA小鼠模型的关节炎具有优异的治疗作用，而且通过增加免疫抑制细胞Treg的表达，对自身免疫性类风湿性关节炎也不是很好的治疗效果。 因此，本发明的TNFR2-IL21R融合蛋白可以有效地用作预防和治疗自身免疫性疾病的组合物的活性成分。

公开(公告)号：US20130022642A1

公开(公告)日：2013-01-24

申请号：US13635874

申请日：2011-03-18

申请人： Young Woo Park ,  Ki Won Jo ,  Srok Ho Yoo ,  Jung Yu ,  Sun-Ha Yoon ,  Ji Hyun Park ,  Eun Jung Song ,  Jong-Ho Lee ,  Min Ji Seo ,  Sun Jung Cho ,  Mi La Cho ,  Ho Youn Kim ,  Mi Kyung Park ,  Hye Jwa Oh ,  Jin Sil Park ,  Yun Ju Woo ,  Jae Kyeong Byun ,  Jun Geol Ryu

发明人： Young Woo Park ,  Ki Won Jo ,  Srok Ho Yoo ,  Jung Yu ,  Sun-Ha Yoon ,  Ji Hyun Park ,  Eun Jung Song ,  Jong-Ho Lee ,  Min Ji Seo ,  Sun Jung Cho ,  Mi La Cho ,  Ho Youn Kim ,  Mi Kyung Park ,  Hye Jwa Oh ,  Jin Sil Park ,  Yun Ju Woo ,  Jae Kyeong Byun ,  Jun Geol Ryu

IPC分类号： C07K19/00 ,  C12N15/63 ,  C12N1/21 ,  C12N5/10 ,  A61K38/17 ,  A61P21/00 ,  A61P3/10 ,  A61P19/02 ,  A61P37/06 ,  A61P25/00 ,  A61P17/00 ,  C12N15/62 ,  A61P7/06

CPC分类号： C07K14/7151 ,  C07K14/7155 ,  C07K2319/00

摘要： The present invention relates to TNFR2-IL21R fusion protein acting as a double-antagonist to TNF-alpha (α) and IL-21. The composition containing the double antagonist to TNF-α and Il-21 (TNFR2-IL21R fusion protein), known as major causes of autoimmune rheumatoid arthritis, one of autoimmune diseases, can reduce the secretion of inflammatory cytokine, increase the secretion of anti-inflammatory cytokine, and suppress the differentiation of osteoclasts better than single proteins such as TNFR2-Fc and IL21R-Fc. The TNFR2-IL21R fusion protein of the present invention has not only excellent treatment effect on arthritis in CIA mouse model not also excellent treatment effect on autoimmune rheumatoid arthritis by increasing the expression of Treg, the immune suppressive cells. Therefore, the TNFR2-IL21R fusion protein of the present invention can be effectively used as an active ingredient for the composition for the prevention and treatment of autoimmune disease.

摘要翻译： 本发明涉及作为TNF-α（α）和IL-21的双重拮抗剂的TNFR2-IL21R融合蛋白。 含有TNF-α和II-21（TNFR2-IL21R融合蛋白）的双重拮抗剂的组合物，被称为自身免疫性类风湿性关节炎的主要原因（自身免疫性疾病之一）可以减少炎性细胞因子的分泌， 炎性细胞因子，并且比单一蛋白如TNFR2-Fc和IL21R-Fc更好地抑制破骨细胞的分化。 本发明的TNFR2-IL21R融合蛋白不仅对CIA小鼠模型的关节炎具有优异的治疗作用，而且通过增加免疫抑制细胞Treg的表达，对自身免疫性类风湿性关节炎也不是很好的治疗效果。 因此，本发明的TNFR2-IL21R融合蛋白可以有效地用作预防和治疗自身免疫性疾病的组合物的活性成分。

公开(公告)号：US20130017226A1

公开(公告)日：2013-01-17

申请号：US13635868

申请日：2011-03-18

申请人： Young Woo Park ,  Ki Won Jo ,  Srok Ho Yoo ,  Jung Yu ,  Dong Ji Kim ,  Sun-Ha Yoon ,  Eun Jung Song ,  Eun Kyung Lee ,  Jin Mi Oh ,  Kyu Won Cho ,  Mi La Cho ,  Ho Youn Kim ,  Mi Kyung Park ,  Hye Jwa Oh ,  Jin Sil Park ,  Yun Ju Woo ,  Jae Kyeong Byun ,  Jun Geol Ryu

发明人： Young Woo Park ,  Ki Won Jo ,  Srok Ho Yoo ,  Jung Yu ,  Dong Ji Kim ,  Sun-Ha Yoon ,  Eun Jung Song ,  Eun Kyung Lee ,  Jin Mi Oh ,  Kyu Won Cho ,  Mi La Cho ,  Ho Youn Kim ,  Mi Kyung Park ,  Hye Jwa Oh ,  Jin Sil Park ,  Yun Ju Woo ,  Jae Kyeong Byun ,  Jun Geol Ryu

IPC分类号： C07K19/00 ,  C12N15/63 ,  C12N1/21 ,  C12N5/10 ,  A61K38/17 ,  A61P19/04 ,  A61P7/06 ,  A61P3/10 ,  A61P19/02 ,  A61P25/00 ,  A61P17/00 ,  A61P21/00 ,  C12N15/62 ,  A61P37/06

CPC分类号： C07K14/525 ,  C07K14/70575 ,  C07K2319/32 ,  Y10S514/814 ,  Y10S514/885 ,  Y10S514/886 ,  Y10S514/903

摘要： The present invention relates to TNFR2-TWEAKR fusion protein, more precisely to TNFR2-TWEAKR fusion protein acting as a double-antagonist to TNF-α and TWEAK, known as major causes of autoimmune arthritis which is one of autoimmune diseases. When the composition comprising TNFR2-TWEAKR fusion protein was treated to Th17 cells, the secretion of the inflammatory cytokine IL-17 was reduced but the secretion of the anti-inflammatory cytokine IL-10 generated in Treg cells was increased. Such effect of TNFR2-TWEAKR fusion protein was far greater than that of a single protein such as TNFR2-Fc or TWEAK-Fc. The TNFR2-TWEAKR fusion protein of the present invention has not only excellent treatment effect on arthritis in CIA mouse model not also excellent treatment effect on autoimmune rheumatoid arthritis by increasing the expression of Treg, the immune suppressive cells. Therefore, the TNFR2-TWEAKR fusion protein of the present invention can be effectively used as an active ingredient for the composition for the prevention and treatment of autoimmune disease.

摘要翻译： 本发明涉及TNFR2-TWEAKR融合蛋白，更确切地说，作为TNF-α和TWEAK的双拮抗剂的TNFR2-TWEAKR融合蛋白，被称为自身免疫性疾病之一的自身免疫性关节炎的主要原因。 当将包含TNFR2-TWEAKR融合蛋白的组合物治疗至Th17细胞时，炎性细胞因子IL-17的分泌减少，但在Treg细胞中产生的抗炎细胞因子IL-10的分泌增加。 TNFR2-TWEAKR融合蛋白的这种作用远远大于单一蛋白如TNFR2-Fc或TWEAK-Fc的这种作用。 本发明的TNFR2-TWEAKR融合蛋白不仅对CIA小鼠模型的关节炎具有优异的治疗作用，而且通过增加免疫抑制细胞Treg的表达，对自身免疫性类风湿性关节炎也不是很好的治疗效果。 因此，本发明的TNFR2-TWEAKR融合蛋白可以有效地用作预防和治疗自身免疫性疾病的组合物的活性成分。

公开(公告)号：US08916525B2

公开(公告)日：2014-12-23

申请号：US13635868

申请日：2011-03-18

申请人： Young Woo Park ,  Ki Won Jo ,  Srok Ho Yoo ,  Jung Yu ,  Dong Jin Kim ,  Sun-Ha Yoon ,  Eun Jung Song ,  Eun Kyung Lee ,  Jin Mi Oh ,  Kyu Won Cho ,  Mi La Cho ,  Ho Youn Kim ,  Mi Kyung Park ,  Hye Jwa Oh ,  Jin Sil Park ,  Yun Ju Woo ,  Jae Kyeong Byun ,  Jun Geol Ryu

发明人： Young Woo Park ,  Ki Won Jo ,  Srok Ho Yoo ,  Jung Yu ,  Dong Jin Kim ,  Sun-Ha Yoon ,  Eun Jung Song ,  Eun Kyung Lee ,  Jin Mi Oh ,  Kyu Won Cho ,  Mi La Cho ,  Ho Youn Kim ,  Mi Kyung Park ,  Hye Jwa Oh ,  Jin Sil Park ,  Yun Ju Woo ,  Jae Kyeong Byun ,  Jun Geol Ryu

IPC分类号： A61K38/17 ,  A61P17/00 ,  A61P19/02 ,  A61P19/04 ,  A61P21/00 ,  A61P25/00 ,  A61P3/10 ,  A61P7/06 ,  C07K14/525 ,  C07K14/705

CPC分类号： C07K14/525 ,  C07K14/70575 ,  C07K2319/32 ,  Y10S514/814 ,  Y10S514/885 ,  Y10S514/886 ,  Y10S514/903

摘要： The present invention relates to TNFR2-TWEAKR fusion protein, more precisely to TNFR2-TWEAKR fusion protein acting as a double-antagonist to TNF-α and TWEAK, known as major causes of autoimmune arthritis which is one of autoimmune diseases. When the composition comprising TNFR2-TWEAKR fusion protein was treated to Th17 cells, the secretion of the inflammatory cytokine IL-17 was reduced but the secretion of the anti-inflammatory cytokine IL-10 generated in Treg cells was increased. Such effect of TNFR2-TWEAKR fusion protein was far greater than that of a single protein such as TNFR2-Fc or TWEAK-Fc. The TNFR2-TWEAKR fusion protein of the present invention has not only excellent treatment effect on arthritis in CIA mouse model not also excellent treatment effect on autoimmune rheumatoid arthritis by increasing the expression of Treg, the immune suppressive cells. Therefore, the TNFR2-TWEAKR fusion protein of the present invention can be effectively used as an active ingredient for the composition for the prevention and treatment of autoimmune disease.

摘要翻译： 本发明涉及TNFR2-TWEAKR融合蛋白，更确切地说，作为TNF-α和TWEAK的双拮抗剂的TNFR2-TWEAKR融合蛋白，被称为自身免疫性疾病之一的自身免疫性关节炎的主要原因。 当将包含TNFR2-TWEAKR融合蛋白的组合物治疗至Th17细胞时，炎性细胞因子IL-17的分泌减少，但在Treg细胞中产生的抗炎细胞因子IL-10的分泌增加。 TNFR2-TWEAKR融合蛋白的这种作用远远大于单一蛋白如TNFR2-Fc或TWEAK-Fc的这种作用。 本发明的TNFR2-TWEAKR融合蛋白不仅对CIA小鼠模型的关节炎具有优异的治疗作用，而且通过增加免疫抑制细胞Treg的表达，对自身免疫性类风湿性关节炎也不是很好的治疗效果。 因此，本发明的TNFR2-TWEAKR融合蛋白可以有效地用作预防和治疗自身免疫性疾病的组合物的活性成分。