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1. 发明申请

WO2014194293A1 IMPROVED METHODS FOR THE SELECTION OF PATIENTS FOR PD-1 OR B7-H4 TARGETED THERAPIES, AND COMBINATION THERAPIES THEREOF 审中-公开
标题翻译：用于选择PD-1或B7-H4靶向治疗患者的改进方法及其组合治疗
公开(公告)号：WO2014194293A1
公开(公告)日：2014-12-04
申请号：PCT/US2014/040388
申请日：2014-05-30
申请人： AMPLIMMUNE, INC.
发明人： LANGERMANN, Solomon , MAY, Rena , MARSHALL, Shannon
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886
摘要： The present disclosure relates to improved methods for selecting patients who would be amenable for PD-1 and B7-H4 pathway targeted therapies and combination therapies, and for treating such patients. In particular, the disclosure pertains to improved PD-1 targeted therapies and combination therapies for treating patients who have failed treatment with BRAF/MEK inhibitors or other inhibitors of the RAS-RAF-MEK-ERK pathway. The disclosure further pertains to improved PD-1 targeted therapies and combination therapies to overcome resistance caused by "tumor dormancy" and to prevent the selection/outgrowth of rapidly, progressing, resistant tumors in the presence of various small molecule inhibitors. The present disclosure additionally provides a PD-1 targeted therapy which involves the administration of an immunomodulatory molecule such as a PD-1-binding fusion protein/antibody (e.g., an anti-PD-1 antibody, a B7-DC-Ig, a B7-H1-Ig, etc.) with a BRAF inhibitor ("BRAFi") or other small molecule as an initial treatment regimen in such selected patients.
摘要翻译：本公开涉及用于选择适合于PD-1和B7-H4途径靶向治疗和联合疗法的患者以及用于治疗这些患者的改进方法。特别地，本公开涉及用于治疗患有BRAF / MEK抑制剂或RAS-RAF-MEK-ERK途径的其它抑制剂治疗失败的患者的改善的PD-1靶向治疗和组合疗法。本发明还涉及改进的PD-1靶向疗法和组合疗法以克服由“肿瘤休眠”引起的抗性，并且在各种小分子抑制剂的存在下防止快速，进展中的抗性肿瘤的选择/生长。本公开另外提供了PD-1靶向治疗，其涉及免疫调节分子例如PD-1结合融合蛋白/抗体（例如，抗PD-1抗体，B7-DC-Ig， B7-H1-Ig等）与BRAF抑制剂（“BRAFi”）或其他小分子作为初始治疗方案。

2. 发明申请

WO2010027828A2 PD-1 ANTAGONISTS AND METHODS OF USE THEREOF 审中-公开
标题翻译： PD-1拮抗剂及其使用方法
公开(公告)号：WO2010027828A2
公开(公告)日：2010-03-11
申请号：PCT/US2009/054971
申请日：2009-08-25
申请人： AMPLIMMUNE, INC. , LANGERMANN, Solomon , LIU, Linda
发明人： LANGERMANN, Solomon , LIU, Linda
IPC分类号： A61K38/18
CPC分类号： A61K39/39 , A61K31/664 , A61K38/00 , A61K38/177 , A61K39/3955 , A61K39/39558 , C07K14/4748 , C07K14/521 , C07K14/70532 , C07K14/7158 , C07K2319/33 , C12N15/62 , Y02A50/385 , Y02A50/409 , Y02A50/411
摘要： Compositions and methods for enhancing and/or prolonging the activation of 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) or overcoming T cell exhaustion and/or anergy are provided. Suitable compositions include PD-I receptor antagonists that bind to and block the endogenous PD-I receptor without triggering inhibitory signals from PD-I, or bind to and block PD-I receptor ligands and preventing them from interacting with PD-I receptors. Methods for using the PD-I receptor antagonists to enhance immune responses in subjects in need thereof are provided.
摘要翻译：用于增强和/或延长T细胞活化的组合物和方法（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细胞的分化和效应功能和/或促进T细胞存活）或提供克服T细胞耗尽和/或无反应性。合适的组合物包括结合并阻断内源性PD-1受体的PD-1受体拮抗剂，而不触发PD-1的抑制信号，或结合并阻断PD-1受体配体并阻止它们与PD-1受体相互作用。提供了在有需要的受试者中使用PD-1受体拮抗剂增强免疫应答的方法。

3. 发明申请

WO2010027827A3 TARGETED COSTIMULATORY POLYPEPTIDES AND METHODS OF USE TO TREAT CANCER 审中-公开
公开(公告)号：WO2010027827A3
公开(公告)日：2010-03-11
申请号：PCT/US2009/054969
申请日：2009-08-25
申请人： AMPLIMMUNE, INC. , LANGERMANN, Solomon
发明人： LANGERMANN, Solomon
IPC分类号： C07K14/47 , C07K14/705 , C07K14/52 , C07K14/715
摘要： Compositions are provided that are targeted to tumors or tumor- associated neovasculature and enhance the function of tumor-infiltrating T cells. The compositions include fusion proteins that contain a T cell binding domain and a tumor/tumor-associated neovasculature targeting domain. The fusion proteins optionally contain a peptide/polypeptide linker domain and a domain that mediates dimerization or multimerization. The T cell binding domain can be a costimulatory molecule. Methods for using the fusion proteins to enhance an immune response are provided. Therapeutic uses for the disclosed compositions include the induction of tumor immunity.

4. 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.

5. 发明申请

WO2014186798A1 RECEPTORS FOR B7-H4 审中-公开
标题翻译： B7-H4受体
公开(公告)号：WO2014186798A1
公开(公告)日：2014-11-20
申请号：PCT/US2014/038623
申请日：2014-05-19
申请人： AMPLIMMUNE, INC.
发明人： LANGERMANN, Solomon , PODOJIL, Joseph R. , MILLER, Stephen D.
IPC分类号： G01N33/564 , A61K38/00 , A61K39/00 , G01N33/68
CPC分类号： G01N33/564 , A61K38/00 , A61K38/1709 , A61K38/177 , A61K38/1774 , C07K14/70532 , C07K14/71 , C07K16/2827 , C07K2317/76 , C07K2319/30 , C12N15/1138 , G01N33/6893 , G01N2333/70532 , G01N2800/24 , G01N2800/245 , G01N2800/52
摘要： Isolated cell surface receptors for B7-H4 have been identified based on function. B7-H4 receptor activation by B7-H4 on the dendritic cell, T follicular helper cell and germinal center B cell membrane stimulates inhibitory signaling in those leukocytes. B7-H4 receptor activation decreases production and/or secretion of proinflammatory cytokines, and promotes anti-inflammatory cytokine by mature DC and T cells. Modulators of B7-H4 receptor polypeptides and methods for their therapeutic use are also provided.
摘要翻译：已经基于功能鉴定了B7-H4的分离的细胞表面受体。通过B7-H4在树突状细胞，T滤泡辅助细胞和生发中心B细胞膜上的B7-H4受体激活刺激那些白细胞中的抑制性信号传导。 B7-H4受体活化降低促炎细胞因子的产生和/或分泌，并通过成熟的DC和T细胞促进抗炎细胞因子。还提供了B7-H4受体多肽的调节剂及其治疗用途的方法。

6. 发明申请

WO2013025779A1 ANTI-B7-H4 ANTIBODIES AND THEIR USES 审中-公开
标题翻译：抗B7-H4抗体及其用途
公开(公告)号：WO2013025779A1
公开(公告)日：2013-02-21
申请号：PCT/US2012/050903
申请日：2012-08-15
申请人： AMPLIMMUNE, INC. , LIU, Linda , MARSHALL, Shannon , LANGERMANN, Solomon
发明人： LIU, Linda , MARSHALL, Shannon , LANGERMANN, Solomon
IPC分类号： C12P21/08 , C07K16/00 , C07K16/28
CPC分类号： C07K16/2827 , C07K16/30 , C07K2317/565 , C07K2317/76 , C07K2317/77
摘要： The present invention relates to antibodies (including anti-B7-H4 antibodies) and their antigen-binding fragments and to other molecules (including fusion proteins that bind to the cognate antigen/receptor, etc.) 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. The invention particularly concerns the use of such molecules 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 T AM -mediated immune suppression.
摘要翻译：本发明涉及抗体（包括抗B7-H4抗体）及其抗原结合片段以及能够免疫特异性结合B7-抗体的其它分子（包括与同源抗原/受体结合的融合蛋白等） H4和这些分子在诊断和治疗癌症等疾病中的应用。本发明特别涉及使用这种分子来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/或降低TAM介导的免疫抑制。

7. 发明申请

WO2012145493A1 ANTIBODIES AND OTHER MOLECULES THAT BIND B7-H1 AND PD-1 审中-公开
标题翻译： B7-H1和PD-1的抗体和其他分子
公开(公告)号：WO2012145493A1
公开(公告)日：2012-10-26
申请号：PCT/US2012/034223
申请日：2012-04-19
申请人： AMPLIMMUNE, INC. , LANGERMANN, Solomon , LIU, Linda , MARSHALL, Shannon , YAO, Sheng
发明人： LANGERMANN, Solomon , LIU, Linda , MARSHALL, Shannon , YAO, Sheng
IPC分类号： A61K39/395 , C07K16/28 , C07K16/30
CPC分类号： C07K16/2827 , A61K39/3955 , C07K16/28 , C07K16/2803 , C07K16/2818 , C07K2317/21 , C07K2317/24 , C07K2317/31 , C07K2317/55 , C07K2317/565 , C07K2317/75 , C07K2317/76 , G01N33/6854
摘要： The present invention relates to antibodies and their antigen-binding fragments and to other molecules that are capable of immunospecifically binding to B7-H1 or PD-1. In some embodiments such molecules are additionally capable of modulating the ability of B7-H1 or B7-DC to bind to PD-1 or are capable of affecting the signaling activity of the B7-H1 or PD-1. The invention additionally concerns the uses of such molecules in the diagnosis and treatment of cancer and other diseases.
摘要翻译：本发明涉及抗体及其抗原结合片段和能够免疫特异性结合B7-H1或PD-1的其它分子。在一些实施方案中，此类分子另外能够调节B7-H1或B7-DC结合PD-1或能够影响B7-H1或PD-1的信号传导活性的能力。本发明还涉及这些分子在诊断和治疗癌症和其它疾病中的用途。

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

WO2011066342A2 SIMULTANEOUS INHIBITION OF PD-L1/PD-L2 审中-公开
标题翻译：同时抑制PD-L1 / PD-L2
公开(公告)号：WO2011066342A2
公开(公告)日：2011-06-03
申请号：PCT/US2010/057940
申请日：2010-11-24
申请人： AMPLIMMUNE, INC. , LANGERMANN, Solomon
发明人： LANGERMANN, Solomon
IPC分类号： A61K39/395
CPC分类号： A61K38/17 , C07K2319/30
摘要： Methods and compositions for treating an infection or disease that results from (1) failure to elicit rapid T cell mediated responses, (2) induction of T cell exhaustion, T cell anergy or both, or (3) failure to activate monocytes, macrophages, dendritic cells and/or other APCs, for example, as required to kill intracellular pathogens. The method and compositions solve the problem of undesired T cell inhibition by simultaneously inhibiting the PD-1 ligands, PD-L1 and PD-L2. The immune response can be modulated by providing antagonists which bind with different affinity, by varying the dosage of agent which is administered, by intermittent dosing over a regime, and combinations thereof, that provides for dissociation of agent from the molecule to which it is bound prior to being administered again. In some cases it may be particularly desirable to stimulate the immune system, then remove the stimulation.
摘要翻译：用于治疗由于（1）不能引发快速T细胞介导的反应导致的感染或疾病的方法和组合物，（2）诱导T细胞衰竭，T细胞无反应或两者，或（3）未激活单核细胞，巨噬细胞，树突状细胞和/或其他APC，例如根据需要杀死细胞内病原体。该方法和组合物通过同时抑制PD-1配体PD-L1和PD-L2来解决不想要的T细胞抑制的问题。可以通过提供以不同亲和力结合的拮抗剂来调节免疫应答，通过改变施用的药剂的剂量，通过间歇给药在其制剂上及其组合来提供试剂与其结合的分子的解离在再次施用之前。在某些情况下，特别希望刺激免疫系统，然后去除刺激。

10. 发明申请

WO2011026122A2 B7-H4 FUSION PROTEINS AND METHODS OF USE THEREOF 审中-公开
标题翻译： B7-H4融合蛋白及其使用方法
公开(公告)号：WO2011026122A2
公开(公告)日：2011-03-03
申请号：PCT/US2010/047366
申请日：2010-08-31
申请人： AMPLIMMUNE, INC. , LANGERMANN, Solomon , LIU, Linda , PODOJIL, Joseph, R. , MILLER, Stephen, D. , MARSHALL, Shannon
发明人： LANGERMANN, Solomon , LIU, Linda , PODOJIL, Joseph, R. , MILLER, Stephen, D. , MARSHALL, Shannon
IPC分类号： C07K14/705 , C07K16/28 , G01N33/68 , G01N33/564 , G01N33/50 , A61K38/17 , A61K47/48
CPC分类号： C07K14/70532 , A61K9/0019 , A61K38/00 , A61K38/1709 , A61K39/44 , C07K16/2827 , C07K2317/50 , C07K2317/56 , C07K2317/72 , C07K2319/30 , C07K2319/32 , G01N33/6863 , G01N33/6866 , G01N33/6869 , G01N2800/52
摘要： Fusion proteins containing B7-H4 polypeptides are disclosed. The B7-H4 fusion proteins can include full-length B7-H4 polypeptides, or can contain a fragment of a full-length B7-H4 polypeptide, including some or all of the extracellular domain of the B7-H4 polypeptide. Methods for using the fusion proteins to downregulate T cell activation and for the treatment of inflammatory and autoimmune diseases and disorders are also disclosed. The B7-H4 fusion proteins are useful for treating inflammation by inhibiting or reducing differentiation, proliferation, activity, and/or cytokine production and/or secretion by ThI, ThI 7, Th22, and/or other cells that secrete, or cause other cells to secrete, inflammatory molecules, including, but not limited to, IL-lβ, TNF-α, TGF-beta, IFN-γ, IL-17, IL-6, IL-23, IL-22, IL-21, and MMPs; or enhancing IL-IO secretion by Tregs, increasing the differentiation of Tregs, increasing the number of Tregs, or combinations thereof.
摘要翻译：公开了含有B7-H4多肽的融合蛋白。 B7-H4融合蛋白可以包括全长B7-H4多肽，或者可以包含全长B7-H4多肽的片段，包括B7-H4多肽的一些或全部细胞外结构域。还公开了使用融合蛋白下调T细胞活化和治疗炎症和自身免疫性疾病和病症的方法。 B7-H4融合蛋白可用于通过抑制或降低Th1，Th17，Th22和/或分泌或引起其他细胞的分化，增殖，活性和/或细胞因子产生和/或分泌来治疗炎症以分泌炎性分子，包括但不限于IL-1β，TNF-α，TGF-β，IFN-γ，IL-17，IL-6，IL-23，IL-22，IL-21和基质金属蛋白酶; 或增强Treg分泌IL-10，增加Treg分化，增加Treg数量或其组合。

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