公开(公告)号：US08501915B2

公开(公告)日：2013-08-06

申请号：US13546098

申请日：2012-07-11

申请人： Randolph J. Noelle ,  Li Wang

发明人： Randolph J. Noelle ,  Li Wang

IPC分类号： C07K16/00

CPC分类号： C07K16/2827 ,  A61K38/00 ,  A61K2039/505 ,  C07K14/70596 ,  C07K2319/00 ,  C07K2319/30 ,  G01N33/505 ,  Y02A50/412 ,  Y02A50/423

摘要： The present invention relates to novel regulatory T cell proteins. One protein, designated PD-L3, resembles members of the PD-L1 family, and co-stimulates αCD3 proliferation of T cells in vitro. A second, TNF-like, protein has also been identified as being upregulated upon αCD3/αGITR stimulation. This protein has been designated Treg-sTNF. Proteins, antibodies, activated T cells and methods for using the same are disclosed.In particular methods of using these proteins and compounds, preferably antibodies, which bind or modulate (agonize or antagonize) the activity of these proteins, as immune modulators and for the treatment of cancer, autoimmune disease, allergy, infection and inflammatory conditions, e.g. multiple sclerosis is disclosed.

摘要翻译： 本发明涉及新型调节性T细胞蛋白。 称为PD-L3的一种蛋白质类似于PD-L1家族的成员，并且在体外共同刺激T细胞的αCD3增殖。 第二种TNF样蛋白也被鉴定为在αCD3/αGITR刺激下上调。 该蛋白质已被命名为Treg-sTNF。 公开了蛋白质，抗体，活化的T细胞及其使用方法。 特别是使用这些蛋白质和化合物（优选抗体）的方法，其结合或调节（激动或拮抗）这些蛋白质的活性，作为免疫调节剂和用于治疗癌症，自身免疫疾病，变态反应，感染和炎性病症，例如， 公开了多发性硬化。

公开(公告)号：US08231872B2

公开(公告)日：2012-07-31

申请号：US12732371

申请日：2010-03-26

申请人： Randolph J. Noelle ,  Li Wang

发明人： Randolph J. Noelle ,  Li Wang

IPC分类号： A61K39/395

CPC分类号： C07K16/2827 ,  A61K38/00 ,  A61K2039/505 ,  C07K14/70596 ,  C07K2319/00 ,  C07K2319/30 ,  G01N33/505 ,  Y02A50/412 ,  Y02A50/423

摘要： The present invention relates to novel regulatory T cell proteins. One protein, designated PD-L3, resembles members of the PD-L1 family, and co-stimulates αCD3 proliferation of T cells in vitro. A second, TNF-like, protein has also been identified as being upregulated upon αCD3/αGITR stimulation. This protein has been designated Treg-sTNF. Proteins, antibodies, activated T cells and methods for using the same are disclosed.In particular methods of using these proteins and compounds, preferably antibodies, which bind or modulate (agonize or antagonize) the activity of these proteins, as immune modulators and for the treatment of cancer, autoimmune disease, allergy, infection and inflammatory conditions, e.g. multiple sclerosis is disclosed.

摘要翻译： 本发明涉及新型调节性T细胞蛋白。 称为PD-L3的一种蛋白质类似于PD-L1家族的成员，并且在体外共同刺激T细胞的αCD3增殖。 第二种TNF样蛋白也被鉴定为在αCD3/αGITR刺激下上调。 该蛋白质已被命名为Treg-sTNF。 公开了蛋白质，抗体，活化的T细胞和使用它们的方法。 特别是使用这些蛋白质和化合物（优选抗体）的方法，其结合或调节（激动或拮抗）这些蛋白质的活性，作为免疫调节剂和用于治疗癌症，自身免疫疾病，变态反应，感染和炎性病症，例如， 公开了多发性硬化。

公开(公告)号：US20110027278A1

公开(公告)日：2011-02-03

申请号：US12732371

申请日：2010-03-26

申请人： Randolph J. Noelle ,  Li Wang

发明人： Randolph J. Noelle ,  Li Wang

IPC分类号： A61K39/395 ,  A61K38/16 ,  C07K16/00 ,  C12N5/02 ,  C40B30/04

CPC分类号： C07K16/2827 ,  A61K38/00 ,  A61K2039/505 ,  C07K14/70596 ,  C07K2319/00 ,  C07K2319/30 ,  G01N33/505 ,  Y02A50/412 ,  Y02A50/423

摘要： The present invention relates to novel regulatory T cell proteins. One protein, designated PD-L3, resembles members of the PD-L1 family, and co-stimulates αCD3 proliferation of T cells in vitro. A second, TNF-like, protein has also been identified as being upregulated upon αCD3/αGITR stimulation. This protein has been designated Treg-sTNF. Proteins, antibodies, activated T cells and methods for using the same are disclosed.In particular methods of using these proteins and compounds, preferably antibodies, which bind or modulate (agonize or antagonize) the activity of these proteins, as immune modulators and for the treatment of cancer, autoimmune disease, allergy, infection and inflammatory conditions, e.g. multiple sclerosis is disclosed

摘要翻译： 本发明涉及新型调节性T细胞蛋白。 称为PD-L3的一种蛋白质类似于PD-L1家族的成员，并且在体外共同刺激T细胞的αCD3增殖。 第二种TNF样蛋白也被鉴定为在αCD3/αGITR刺激下上调。 该蛋白质已被命名为Treg-sTNF。 公开了蛋白质，抗体，活化的T细胞和使用它们的方法。 特别是使用这些蛋白质和化合物（优选抗体）的方法，其结合或调节（激动或拮抗）这些蛋白质的活性，作为免疫调节剂和用于治疗癌症，自身免疫疾病，变态反应，感染和炎性病症，例如， 公开了多发性硬化

公开(公告)号：US20180237525A9

公开(公告)日：2018-08-23

申请号：US14686422

申请日：2015-04-14

申请人： Randolph J. Noelle ,  Li Wang ,  Thomas Broughton ,  Lorenzo F. Sempere ,  Janet Louise Lines

发明人： Randolph J. Noelle ,  Li Wang ,  Thomas Broughton ,  Lorenzo F. Sempere ,  Janet Louise Lines

IPC分类号： C07K16/28 ,  C07K16/30 ,  A61K45/06 ,  A61K39/00 ,  A61K39/395

CPC分类号： C07K16/2827 ,  A61K38/00 ,  A61K39/00 ,  A61K39/0005 ,  A61K39/3955 ,  A61K45/06 ,  A61K2039/505 ,  A61K2039/507 ,  A61K2039/57 ,  A61P35/00 ,  A61P37/00 ,  C07K7/08 ,  C07K16/30 ,  C07K16/3015 ,  C07K16/3023 ,  C07K2317/75 ,  C07K2317/76

摘要： The present invention is directed to synergic or additive therapies comprising the administration of a VISTA antagonist and a PD-1, PD-L1 or POD-L3 antagonist; or the combination of a VISTA agonist and a -1, PD-L1 or POD-L3 agonist which combinations respectively elicit an additive or synergistic effect at promoting T cell immunity or inhibiting T cell immunity, i.e., CD4, CD8 or Th1 immunity. The agonists and antagonists may be in the same or separate compositions and may be administered together or separately administered in either order.

公开(公告)号：US11123426B2

公开(公告)日：2021-09-21

申请号：US15317552

申请日：2015-06-11

申请人： Kathy A. Green ,  Li Wang ,  Randolph J. Noelle ,  William R. Green

发明人： Kathy A. Green ,  Li Wang ,  Randolph J. Noelle ,  William R. Green

IPC分类号： A61K31/198 ,  A61K39/395 ,  C07K16/28 ,  A61K45/06

摘要： Methods for alleviating the suppression of humoral immunity by myeloid-dependent suppressor cells (MDSCs) are provided which include the administration of a VISTA antagonist and an iNOS/NO inhibitor in a subject in need thereof, e.g., subjects with cancer or infectious disease wherein VISTA is aberrantly expressed. This combination has been discovered to elicit a synergistic or additive effect on alleviating suppression of humoral immunity by VISTA which is elicited by MDSCs.

公开(公告)号：US09217035B2

公开(公告)日：2015-12-22

申请号：US13901704

申请日：2013-05-24

申请人： Randolph J. Noelle ,  Li Wang

发明人： Randolph J. Noelle ,  Li Wang

IPC分类号： A61K38/00 ,  C07K14/705 ,  C07K16/28 ,  G01N33/50 ,  A61K39/00

CPC分类号： C07K16/2827 ,  A61K38/00 ,  A61K2039/505 ,  C07K14/70596 ,  C07K2319/00 ,  C07K2319/30 ,  G01N33/505 ,  Y02A50/412 ,  Y02A50/423

摘要： The present invention relates to novel regulatory T cell proteins. One protein, designated PD-L3, resembles members of the PD-L1 family, and co-stimulates αCD3 proliferation of T cells in vitro. A second, TNF-like, protein has also been identified as being upregulated upon αCD3/αGITR stimulation. This protein has been designated Treg-sTNF. Proteins, antibodies, activated T cells and methods for using the same are disclosed.In particular methods of using these proteins and compounds, preferably antibodies, which bind or modulate (agonize or antagonize) the activity of these proteins, as immune modulators and for the treatment of cancer, autoimmune disease, allergy, infection and inflammatory conditions, e.g. multiple sclerosis is disclosed.

摘要翻译： 本发明涉及新型调节性T细胞蛋白。 称为PD-L3的一种蛋白质类似于PD-L1家族的成员，并且在体外共同刺激T细胞的αCD3增殖。 第二种TNF样蛋白也被鉴定为在αCD3/αGITR刺激下上调。 该蛋白质已被命名为Treg-sTNF。 公开了蛋白质，抗体，活化的T细胞及其使用方法。 特别是使用这些蛋白质和化合物（优选抗体）的方法，其结合或调节（激动或拮抗）这些蛋白质的活性，作为免疫调节剂和用于治疗癌症，自身免疫疾病，变态反应，感染和炎性病症，例如， 公开了多发性硬化。

公开(公告)号：US20120301484A1

公开(公告)日：2012-11-29

申请号：US13546098

申请日：2012-07-11

申请人： Randolph J. Noelle ,  Li Wang

发明人： Randolph J. Noelle ,  Li Wang

IPC分类号： C07K16/28 ,  A61K39/395

CPC分类号： C07K16/2827 ,  A61K38/00 ,  A61K2039/505 ,  C07K14/70596 ,  C07K2319/00 ,  C07K2319/30 ,  G01N33/505 ,  Y02A50/412 ,  Y02A50/423

摘要： The present invention relates to novel regulatory T cell proteins. One protein, designated PD-L3, resembles members of the PD-L1 family, and co-stimulates αCD3 proliferation of T cells in vitro. A second, TNF-like, protein has also been identified as being upregulated upon αCD3/αGITR stimulation. This protein has been designated Treg-sTNF. Proteins, antibodies, activated T cells and methods for using the same are disclosed.In particular methods of using these proteins and compounds, preferably antibodies, which bind or modulate (agonize or antagonize) the activity of these proteins, as immune modulators and for the treatment of cancer, autoimmune disease, allergy, infection and inflammatory conditions, e.g. multiple sclerosis is disclosed

摘要翻译： 本发明涉及新型调节性T细胞蛋白。 称为PD-L3的一种蛋白质类似于PD-L1家族的成员，并且在体外共同刺激T细胞的αCD3增殖。 第二种TNF样蛋白也被鉴定为在αCD3/αGITR刺激下上调。 该蛋白质已被命名为Treg-sTNF。 公开了蛋白质，抗体，活化的T细胞和使用它们的方法。 特别是使用这些蛋白质和化合物（优选抗体）的方法，其结合或调节（激动或拮抗）这些蛋白质的活性，作为免疫调节剂和用于治疗癌症，自身免疫疾病，变态反应，感染和炎性病症，例如， 公开了多发性硬化

公开(公告)号：US20160083472A1

公开(公告)日：2016-03-24

申请号：US14686422

申请日：2015-04-14

申请人： Randolph J. Noelle ,  Li Wang ,  Thomas Broughton ,  Lorenzo F. Sempere ,  Janet Louise Lines

发明人： Randolph J. Noelle ,  Li Wang ,  Thomas Broughton ,  Lorenzo F. Sempere ,  Janet Louise Lines

IPC分类号： C07K16/28 ,  A61K39/395 ,  A61K39/00 ,  C07K16/30 ,  A61K45/06

CPC分类号： C07K16/2827 ,  A61K38/00 ,  A61K39/00 ,  A61K39/0005 ,  A61K39/3955 ,  A61K45/06 ,  A61K2039/505 ,  A61K2039/507 ,  A61K2039/57 ,  A61P35/00 ,  A61P37/00 ,  C07K7/08 ,  C07K16/30 ,  C07K16/3015 ,  C07K16/3023 ,  C07K2317/75 ,  C07K2317/76

摘要： The present invention is directed to synergic or additive therapies comprising the administration of a VISTA antagonist and a PD-1, PD-L1 or POD-L3 antagonist; or the combination of a VISTA agonist and a -1, PD-L1 or POD-L3 agonist which combinations respectively elicit an additive or synergistic effect at promoting T cell immunity or inhibiting T cell immunity, i.e., CD4, CD8 or Th1 immunity. The agonists and antagonists may be in the same or separate compositions and may be administered together or separately administered in either order.

摘要翻译： 本发明涉及包括施用VISTA拮抗剂和PD-1，PD-L1或POD-L3拮抗剂的协同或添加剂疗法; 或VISTA激动剂和-1，PD-L1或POD-L3激动剂的组合，其组合分别在促进T细胞免疫或抑制T细胞免疫（即CD4，CD8或Th1免疫）方面引起添加剂或协同效应。 激动剂和拮抗剂可以在相同或分开的组合物中，并且可以一起施用或以任何顺序分开施用。

公开(公告)号：US20140037634A1

公开(公告)日：2014-02-06

申请号：US13901704

申请日：2013-05-24

申请人： Randolph J. Noelle ,  Li Wang

发明人： Randolph J. Noelle ,  Li Wang

IPC分类号： C07K16/28 ,  G01N33/50 ,  C07K14/705

CPC分类号： C07K16/2827 ,  A61K38/00 ,  A61K2039/505 ,  C07K14/70596 ,  C07K2319/00 ,  C07K2319/30 ,  G01N33/505 ,  Y02A50/412 ,  Y02A50/423

摘要： The present invention relates to novel regulatory T cell proteins. One protein, designated PD-L3, resembles members of the PD-L1 family, and co-stimulates αCD3 proliferation of T cells in vitro. A second, TNF-like, protein has also been identified as being upregulated upon αCD3/αGITR stimulation. This protein has been designated Treg-sTNF. Proteins, antibodies, activated T cells and methods for using the same are disclosed.In particular methods of using these proteins and compounds, preferably antibodies, which bind or modulate (agonize or antagonize) the activity of these proteins, as immune modulators and for the treatment of cancer, autoimmune disease, allergy, infection and inflammatory conditions, e.g. multiple sclerosis is disclosed

摘要翻译： 本发明涉及新型调节性T细胞蛋白。 称为PD-L3的一种蛋白质类似于PD-L1家族的成员，并且在体外共同刺激T细胞的αCD3增殖。 第二种TNF样蛋白也被鉴定为在αCD3/αGITR刺激下上调。 该蛋白质已被命名为Treg-sTNF。 公开了蛋白质，抗体，活化的T细胞和使用它们的方法。 特别是使用这些蛋白质和化合物（优选抗体）的方法，其结合或调节（激动或拮抗）这些蛋白质的活性，作为免疫调节剂和用于治疗癌症，自身免疫疾病，变态反应，感染和炎性病症，例如， 公开了多发性硬化

公开(公告)号：US20130136734A1

公开(公告)日：2013-05-30

申请号：US13648808

申请日：2012-10-10

申请人： Randolph J. Noelle

发明人： Randolph J. Noelle

IPC分类号： C07K16/18

CPC分类号： C07K16/2875 ,  A61K2039/505 ,  C07K16/18 ,  C07K2317/24 ,  C07K2317/41 ,  C07K2317/52 ,  C07K2317/565 ,  C07K2317/71 ,  C07K2317/732

摘要： Improved anti-CD154 antibodies are provided herein which have ablated FcR binding and/or complement binding/activation. The use of these antibodies for inducing tolerance and treating immune diseases including autoimmunity, inflammation and allergic disorders is disclosed herein.

摘要翻译： 本文提供了已经消除了FcR结合和/或补体结合/活化的抗CD154抗体。 本文公开了这些抗体用于诱导耐受性和治疗包括自身免疫，炎症和过敏性疾病的免疫疾病的用途。