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1. 发明申请

WO2011020024A2 METHODS OF MODULATING IMMUNE FUNCTION 审中-公开
标题翻译：调节免疫功能的方法
公开(公告)号：WO2011020024A2
公开(公告)日：2011-02-17
申请号：PCT/US2010/045479
申请日：2010-08-13
申请人： THE JOHNS HOPKINS UNIVERSITY , CHEN, Lieping
发明人： CHEN, Lieping
IPC分类号： C07K14/705
CPC分类号： C07K16/2827 , A61K39/3955 , A61K45/06 , A61K2039/505 , A61N5/10 , C07K14/70521 , C07K14/70532 , C07K16/2818 , C07K2317/21 , C07K2317/24 , C07K2317/31 , C07K2317/73 , C07K2317/74 , C07K2317/76 , C07K2319/30
摘要： Presented herein are therapeutic agents that modulate one or more immune functions and uses of such therapeutic agents in the prevention, treatment and management of diseases. In one aspect, the therapeutic agents modulate one or more signal transduction pathways induced by the binding of B7-H7 to B7-H7CR, or the binding of B7-H2 to either ICOS, CD28, or CTLA-4. In another aspect, the therapeutic agents modulate the binding of B7-H7 to B7-H7CR, or the binding of B7-H2 to either ICOS, CD28, or CTLA-4. The therapeutic agents can be used in the prevention, treatment and/or management of diseases in which it might be useful to modulate one or more immune functions (e.g.,cancer, infectious disease, autoimmune disease, and transplantation rejection). In another aspect, presented herein are methods for identifying receptor-ligand interactions.
摘要翻译：本文提供的是调节一种或多种这些治疗剂的免疫功能和用途的治疗剂，用于预防，治疗和控制疾病。在一个方面，治疗剂调节由B7-H7与B7-H7CR的结合诱导的一种或多种信号转导途径，或B7-H2与ICOS，CD28或CTLA-4的结合。另一方面，治疗剂调节B7-H7与B7-H7CR的结合，或B7-H2与ICOS，CD28或CTLA-4的结合。治疗剂可以用于预防，治疗和/或治疗其中可能有用的调节一种或多种免疫功能（例如癌症，感染性疾病，自身免疫疾病和移植排斥）的疾病。在另一方面，本文提出了鉴定受体 - 配体相互作用的方法。

2. 发明申请

WO2007065014A2 METHODS AND COMPOSITIONS TO INCREASE IMMUNE FUNCTION 审中-公开
标题翻译：增加免疫功能的方法和组合
公开(公告)号：WO2007065014A2
公开(公告)日：2007-06-07
申请号：PCT/US2006/046279
申请日：2006-12-04
申请人： THE JOHNS HOPKINS UNIVERSITY , CHEN, Lieping
发明人： CHEN, Lieping
IPC分类号： A61K39/395
CPC分类号： C07K16/2878 , A61K2039/505 , C07K2317/74 , Y02A50/403
摘要： The invention generally features compositions and methods that are useful for increasing immune function. Such methods can be employed to enhance innate immunity for the prevention or treatment of pathogen infections (e.g., bacterial, viral, or fungal infections), lymphopenia, or cancer by stimulating a CDl 37 polypeptide expressed on an immune cell, such as a memory T cell. The invention further comprises a mouse lacking detectable levels of CD 137, cells derived from the mouse, and methods of producing additional knockouts animals.
摘要翻译：本发明通常具有可用于增加免疫功能的组合物和方法。这种方法可用于通过刺激在免疫细胞上表达的CD117多肽（例如记忆T）来增强预防或治疗病原体感染（例如细菌，病毒或真菌感染），淋巴细胞减少或癌症的先天免疫细胞。本发明还包括缺少可检测水平的CD137，来自小鼠的细胞的小鼠，以及产生额外敲除动物的方法。

3. 发明申请

WO2007041694A2 COMPOSITIONS AND METHODS FOR TREATING INFLAMMATION 审中-公开
标题翻译：用于治疗炎症的组合物和方法
公开(公告)号：WO2007041694A2
公开(公告)日：2007-04-12
申请号：PCT/US2006/039072
申请日：2006-10-04
申请人： THE JOHNS HOPKINS UNIVERSITY , CHEN, Lieping , TAMADA, Koji
发明人： CHEN, Lieping , TAMADA, Koji
IPC分类号： A61K39/395 , A01K67/027 , A61P29/00
CPC分类号： C07K14/70575 , A61K38/00 , A61K2039/505 , C07K16/2878 , C07K2317/76 , Y02A50/463
摘要： The present invention relates to compositions to treat inflammation (LIGHT pathway) related disorders, and specifically liver inflammation or hepatitis. The invention also relates to methods treating LIGHT pathway related disorders. The invention further relates to kits for treating LIGHT pathway related disorders in a subject. The invention further relates to methods of identifying novel treatments for treating LIGHT pathway related disorders in a subject.
摘要翻译：本发明涉及治疗炎症（LIGHT途径）相关疾病，特别是肝脏炎症或肝炎的组合物。本发明还涉及治疗LIGHT途径相关疾病的方法。本发明还涉及用于治疗受试者中LIGHT通路相关疾病的试剂盒。本发明还涉及鉴定用于治疗受试者中LIGHT通路相关疾病的新疗法的方法。

4. 发明申请

WO2009046313A2 NOVEL COMPOSITIONS AND METHODS FOR STIMULATING ERYTHROPOIESIS IN A MAMMAL 审中-公开
标题翻译：新的组合物和方法用于在哺乳动物中刺激红细胞生成素
公开(公告)号：WO2009046313A2
公开(公告)日：2009-04-09
申请号：PCT/US2008/078769
申请日：2008-10-03
申请人： UNIVERSITY OF MARYLAND, BALTIMORE , THE JOHNS HOPKINS UNIVERSITY , TAMADA, Koji , CHEN, Lieping
发明人： TAMADA, Koji , CHEN, Lieping
IPC分类号： C07K16/18 , C07K16/28
CPC分类号： C07K16/2878 , A61K2039/505 , C07K2317/74
摘要： The present invention relates to compositions comprising an agent which activates herpes virus entry mediator (HVEM). The present invention also relates to compositions comprising an agonist of HVEM. The present invention also relates to methods of stimulating erythropoiesis in a mammal, comprising administering to a mammal a composition comprising an agent which activates HVEM, or is an agonist of HVEM. The present invention also relates to methods for treating an anemic disorder, comprising administering to a mammal suffering therefrom an agent which activates HVEM.
摘要翻译：本发明涉及包含活化疱疹病毒进入介质（HVEM）的试剂的组合物。本发明还涉及包含HVEM激动剂的组合物。本发明还涉及在哺乳动物中刺激红细胞生成的方法，包括向哺乳动物施用包含活化HVEM的药剂或HVEM激动剂的组合物。本发明还涉及治疗贫血性疾病的方法，其包括向患有其的哺乳动物施用激活HVEM的药剂。

5. 发明申请

WO2009029342A2 B7-DC VARIANTS 审中-公开
标题翻译： B7-DC变量
公开(公告)号：WO2009029342A2
公开(公告)日：2009-03-05
申请号：PCT/US2008/069819
申请日：2008-07-11
申请人： THE JOHNS HOPKINS UNIVERSITY , CHEN, Lieping
发明人： CHEN, Lieping
IPC分类号： C07K14/705 , A61K38/17
CPC分类号： C07K14/70532 , A61K38/00
摘要： Compositions and methods for costimulating T cells (i.e., increasing antigen-specific proliferation of T cells, enhancing cytokine production by T cells, stimulating differentiation ad effector functions of T cells and/or promoting T cell survival) are provided. Suitable compositions include variant B7-DC polypeptides, fragments and fusion proteins thereof. Variant B7-DC polypeptides have reduced binding affinity for the inhibitory PD-I ligand and substantially retain the ability to costiniulate T cells. Methods for using variant B7-DC polypeptides to stimulate immune responses in subjects in need thereof are provided.
摘要翻译：提供了共刺激T细胞的组合物和方法（即，增加T细胞的抗原特异性增殖，增强T细胞的细胞因子产生，刺激T细胞的分化和效应子功能和/或促进T细胞存活）。合适的组合物包括变体B7-DC多肽，其片段和融合蛋白。变体B7-DC多肽具有降低的对抑制性PD-1配体的结合亲和力，并且基本上保留了T细胞成本的能力。提供了使用变体B7-DC多肽刺激有需要的受试者的免疫应答的方法。

6. 发明申请

WO2009089149A1 B7-H1 (CD274) ANTAGONISTS INDUCE APOPTOSIS OF TUMOR CELLS 审中-公开
标题翻译： B7-H1（CD274）拮抗剂诱导肿瘤细胞凋亡
公开(公告)号：WO2009089149A1
公开(公告)日：2009-07-16
申请号：PCT/US2009/030104
申请日：2009-01-05
申请人： THE JOHNS HOPKINS UNIVERSITY , CHEN, Lieping
发明人： CHEN, Lieping
IPC分类号： A61K39/395 , A61P35/00 , A61P37/04
CPC分类号： C07K16/2827 , A61K2039/505
摘要： Compositions and methods for restoring killing of cancer cells are provided. Preferably, the compositions are administered to a subject in an effective amount to antagonize, inhibit, reduce, or block B7-H1 mediated signal transduction in cancer cells expressing B7-H1. It has been discovered that B7-H1 transmits an anti-apoptotic signal in cancer cells that increases the resistance of the cancer cells to CTL mediated cytolysis and to Fas induced cell death. It is believed that blocking the transmission of the anti- apoptotic signal by B7-H1 increases the susceptibility of the cancer cells to apoptosis and CTL cytolysis thereby enhancing the death of cancer cells. Preferred compounds or B7-H1 antagonists include antibodies that bind to B7-H1, B7-H1 receptors, or ligands of B7-H1 such as PD-I or B7-1. Additional B7-H1 antagonists include small molecules, for example small molecules that bind the cytoplasmic portion of B7-H1 or the extracellular portion of B7-H1 and inhibit, reduce, block or interfere with B7-H1 signal transduction. Methods for treating one or more symptoms associated with cancer or hyperproliferation are also provided.
摘要翻译：提供了恢复杀死癌细胞的组合物和方法。优选地，组合物以有效量施用于受试者以拮抗，抑制，降低或阻断表达B7-H1的癌细胞中的B7-H1介导的信号转导。已经发现B7-H1在癌细胞中传递抗细胞凋亡信号，其增加了癌细胞对CTL介导的细胞溶解和Fas诱导的细胞死亡的抗性。相信通过B7-H1阻断抗凋亡信号的传递增加了癌细胞对凋亡和CTL细胞溶解的敏感性，从而增强了癌细胞的死亡。优选的化合物或B7-H1拮抗剂包括结合B7-H1，B7-H1受体或B7-H1的配体如PD-1或B7-1的抗体。另外的B7-H1拮抗剂包括小分子，例如结合B7-H1的细胞质部分或B7-H1细胞外部分并抑制，减少，阻断或干扰B7-H1信号转导的小分子。还提供了治疗与癌症或过度增生相关的一种或多种症状的方法。

7. 发明申请

WO2014190356A3 ANTI-B7-H5 ANTIBODIES AND THEIR USES 审中-公开
公开(公告)号：WO2014190356A3
公开(公告)日：2014-11-27
申请号：PCT/US2014/039621
申请日：2014-05-27
申请人： AMPLIMMUNE, INC. , THE JOHNS HOPKINS UNIVERSITY
发明人： CHEN, Lieping , YAO, Sheng , LIU, Linda , LANGERMANN, Solomon
IPC分类号： C07K14/705 , C07K16/28 , A61K39/00
摘要： The present invention relates to antibodies and their antigen-binding fragments and to other molecules that are capable of immunospecifically binding to the B7-H5 ligand of the B7-H5:CD28H pathway, and to the uses of such molecules in the treatment and diagnosis of autoimmune disease, transplant rejection and other inflammatory diseases.

8. 发明申请

WO2014100823A1 ANTI-H7CR ANTIBODIES 审中-公开
标题翻译： ANTI-H7CR抗体
公开(公告)号：WO2014100823A1
公开(公告)日：2014-06-26
申请号：PCT/US2013/077586
申请日：2013-12-23
申请人： AMPLIMMUNE, INC. , THE JOHNS HOPKINS UNIVERSITY
发明人： LANGERMANN, Solomon , LIU, Linda , YAO, Sheng , CHEN, Lieping
IPC分类号： C07K16/28
CPC分类号： C07K16/2818 , C07K16/2827 , C07K2317/24 , C07K2317/31 , C07K2317/33 , C07K2317/56 , C07K2317/565 , C07K2317/74 , C07K2317/75 , C07K2317/76 , C07K2317/92 , C07K2319/30 , C12N15/1037 , G01N33/57492 , G01N2333/70521
摘要： Antibodies and humanized variants thereof and their antigen-binding fragments and to other molecules that are capable of immunospecifically binding to the B7-H7 counter-receptor, H7CR, and their uses in enhancing immune responses and the treatment and diagnosis of cancer and other diseases are provided.
摘要翻译：抗体及其人源化变体及其抗原结合片段以及能够免疫特异性结合B7-H7反受体H7CR的其他分子及其在增强免疫应答和癌症和其他疾病的治疗和诊断中的用途是提供。

9. 发明申请

WO2014100483A1 ANTI-HUMAN B7-H4 ANTIBODIES AND THEIR USES 审中-公开
标题翻译：抗人B7-H4抗体及其用途
公开(公告)号：WO2014100483A1
公开(公告)日：2014-06-26
申请号：PCT/US2013/076701
申请日：2013-12-19
申请人： AMPLIMMUNE, INC. , THE JOHNS HOPKINS UNIVERSITY
发明人： LANGERMAN, Solomon , LIU, Linda , YAO, Sheng , CHEN, Lieping , OVERSTREET, Michael, Glen
IPC分类号： A61K39/00 , G01N33/68
CPC分类号： C07K16/2827 , A61K2039/505 , C07K16/30 , C07K16/3069 , C07K2317/24 , C07K2317/30 , C07K2317/31 , C07K2317/34 , C07K2317/56 , C07K2317/73 , C07K2317/732 , C07K2317/76 , C07K2317/77 , C07K2317/92 , G01N33/574
摘要： Anti-human B7-H4 antibody "6H3", antigen-binding fragments, derivatives, and humanized variants thereof that are capable of immunospecifically binding to B7-H4, and the uses of such molecules in the diagnosis and the treatment of cancer and other diseases are disclosed. In preferred embodiments, the molecules are used to retard or prevent tumor growth, inhibit tumor- mediated suppression, eliminate tumors and/or deplete or block the activity of tumor-associated macrophages ("TAMs") so as to alter their activity and/or decrease TAM-mediated immune suppression.
摘要翻译：能够免疫特异性结合B7-H4的抗人B7-H4抗体“6H3”，其抗原结合片段，衍生物和人源化变体，以及这些分子在诊断和治疗癌症和其它疾病中的用途被披露。在优选的实施方案中，分子用于延缓或预防肿瘤生长，抑制肿瘤介导的抑制，消除肿瘤和/或消耗或阻断肿瘤相关巨噬细胞（“TAM”）的活性，从而改变其活性和/或减少TAM介导的免疫抑制。

10. 发明申请

WO2006088464A2 A METHOD OF USING AN ANTI-CD137 ANTIBODY AS AN AGENT FOR RADIOIMMUNOTHERAPY OR RADIOIMMUNODETECTION 审中-公开
标题翻译：使用抗CD137抗体作为放射免疫学或放射免疫测定法的方法
公开(公告)号：WO2006088464A2
公开(公告)日：2006-08-24
申请号：PCT/US2005/005405
申请日：2005-02-18
申请人： GTC BIOTHERAPEUTICS, INC. , STROME, Scott, E. , SCHINDLER, Daniel , CHEN, Lieping , MEADE, Harry , ECHELARD, Yann
发明人： STROME, Scott, E. , SCHINDLER, Daniel , CHEN, Lieping , MEADE, Harry , ECHELARD, Yann
IPC分类号： A61K39/395 , C07K16/30
CPC分类号： C07K16/2878 , A61K47/6817 , A61K47/6829 , A61K47/6849 , A61K51/1027 , A61K2039/507 , C07K2317/12 , C07K2317/74 , C07K2317/75
摘要： The current invention relates to the development and methods of use of a recombinant agonistic antibody anti-human CD137, and glycosylation variants thereof. These antibodies act as anti-cancer agents and/or immune modulators that are effective in shrinking solid tumors or other cancerous indications and preventing their recurrence. The types of cancer for which the contemplated antibody is effective in treating also include leukemia and lymphoma. In a preferred imbodiment the recombinant antibodies of the current invention were produced in and purified from the milk of transgenic animals. In another preferred embodiment of the current invention the agonistic anti-CD137 antibodies of the invention can be conjugated to radionuclides for radioimmunodetection or radioimmunotherapeutic purposes, or conjugated to a toxin for enhanced therapeutic treatment of various cancers.
摘要翻译：本发明涉及重组激动抗体抗人CD137及其糖基化变体的开发和使用方法。这些抗体作为有效减少实体瘤或其他癌症适应症并防止其复发的抗癌剂和/或免疫调节剂。预期抗体对其治疗有效的癌症类型还包括白血病和淋巴瘤。在优选的实施方案中，本发明的重组抗体在转基因动物的牛奶中制备并纯化。在本发明的另一优选实施方案中，本发明的激动性抗CD137抗体可以与放射性核素缀合以用于放射免疫检测或放射免疫治疗目的，或与毒素结合以增强各种癌症的治疗性治疗。

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