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1. 发明授权

US09700606B2 HVEM/BTLA, HVEM/CD 160 and HVEM/gD cis complexes and methods of use 有权
公开(公告)号：US09700606B2
公开(公告)日：2017-07-11
申请号：US13003191
申请日：2009-07-08
申请人： Carl F. Ware , Timothy C. Cheung , Marcos W. Steinberg
发明人： Carl F. Ware , Timothy C. Cheung , Marcos W. Steinberg
IPC分类号： A61K47/48 , A61K39/00 , C07K16/28
CPC分类号： A61K39/0005 , C07K16/2803 , C07K16/2818 , C07K16/2878 , C07K2317/73 , C07K2317/74 , C07K2317/75 , C07K2317/76 , C07K2319/30 , G01N2333/70578
摘要： The invention provides HVEM cis complexes which include, for example, HVEM/BTLA, HVEM/CD160 and HVEM/gD cis complexes. The invention provides ligands and agents that bind to HVEM cis complexes, such as antibodies. The invention further provides methods of use of the HVEM cis complexes, and the ligands and agents (e.g., antibodies) that bind to the HVEM cis complexes.

2. 发明申请

US20100021466A1 Antagonistic Human LIGHT-Specific Human Monoclonal Antibodies 有权
标题翻译：拮抗人类LIGHT特异性人类单克隆抗体
公开(公告)号：US20100021466A1
公开(公告)日：2010-01-28
申请号：US12439518
申请日：2007-08-24
申请人： Steven W. Granger , Shinichiro Kato , Carl F. Ware
发明人： Steven W. Granger , Shinichiro Kato , Carl F. Ware
IPC分类号： A61K39/395 , C07K16/18 , C07H21/04 , C12N15/63 , C12N5/00 , C12P21/06 , A61P1/00 , C12N5/02
CPC分类号： C07K16/24 , A61K2039/505 , C07K16/2875 , C07K2317/21 , C07K2317/34 , C07K2317/56 , C07K2317/565 , C07K2317/76
摘要： Provided herein are antibodies, such as fully human antibodies that immunospecifically bind to an hLIGHT polypeptide. Also provided are isolated nucleic acids encoding antibodies, such as fully human antibodies, that immunospecifically bind to a hLIGHT polypeptide. Further provided are vectors and host cells comprising nucleic acids encoding antibodies, such as fully human antibodies, that immunospecifically bind to a hLIGHT polypeptide. Also provided are methods of making antibodies, such as fully human antibodies, that immunospecifically bind to a hLIGHT polypeptide. Also provided herein is a method of treating a hLIGHT-mediated disease in a subject comprising administering to the subject an antibody, such as a fully human antibody, that immunospecifically binds to a hLIGHT polypeptide. In preferred embodiments, that anti-hLIGHT antibodies provided herein will ameliorate, neutralize or otherwise inhibit hLIGHT biological activity in vivo (e.g., the hLIGHT-mediated production or secretion of CCL20, IL-8 or RANTES from a cell expressing a hLIGHT receptor). Also provided herein is a method for the detection of hLIGHT in a sample as well as a method for ameliorating, neutralizing or otherwise inhibiting hLIGHT activity, e.g., in a human subject suffering from a disorder in which hLIGHT activity is detrimental.
摘要翻译：本文提供了抗体，例如免疫特异性结合hLIGHT多肽的完全人抗体。还提供了编码抗体的分离的核酸，例如免疫特异性结合于hLIGHT多肽的完全人抗体。还提供了载体和宿主细胞，其包含免疫特异性结合hLIGHT多肽的编码抗体（例如完全人抗体）的核酸。还提供了制备免疫特异性结合hLIGHT多肽的抗体（例如完全人抗体）的方法。本文还提供了治疗受试者中的hLIGHT介导的疾病的方法，包括向受试者施用免疫特异性结合hLIGHT多肽的抗体，例如完全人抗体。在优选实施方案中，本文提供的抗-HLIGHT抗体将改善，中和或抑制体内的hLIGHT生物活性（例如，hLIGHT介导的来自表达hLIGHT受体的细胞的CCL20，IL-8或RANTES的产生或分泌）。本文还提供了用于检测样品中的hLIGHT的方法以及用于改善，中和或抑制hLIGHT活性的方法，例如在患有hLIGHT活性有害的病症的人类受试者中。

3. 发明授权

US5795964A Lymphotoxin-beta and lymphotoxin-beta complexes 失效
标题翻译：淋巴毒素-β和淋巴毒素-β复合物
公开(公告)号：US5795964A
公开(公告)日：1998-08-18
申请号：US467070
申请日：1995-06-06
申请人： Jeffrey Browning , Carl F. Ware
发明人： Jeffrey Browning , Carl F. Ware
IPC分类号： A61K38/00 , C07K14/525 , C07K14/46 , C07K14/435 , C07K14/52
CPC分类号： C07K14/5255 , C07K14/525 , A61K38/00
摘要： This invention relates to lymphotoxin-.beta., a lymphocyte membrane type protein. This protein is found on the surface of a number of cells, including phorbol ester (PMA) stimulated T cell hybridoma II-23.D7 cells. This invention also relates to complexes formed between lymphotoxin-.beta. and other peptides such as lymphotoxin-.alpha. and to complexes comprising multiple subunits of lymphotoxin-.beta.. These proteins and complexes are useful in holding LT-.alpha. formed within the cell on the cell surface where the LT-.alpha./LT-.beta. complex may act as an inflammation regulating agent, a tumor growth inhibiting agent, a T cell inhibiting agent, a T cell activating agent, an autoimmune disease regulating agent, or an HIV inhibiting agent. Furthermore, the antitumor activity of the LT-.alpha./LT-.beta. complex may be delivered to tumor cells by tumor infiltrating lymphocytes (TILs) transfected with the gene for LT-.beta..
摘要翻译：本发明涉及淋巴细胞膜型蛋白质淋巴细胞毒素-β。这种蛋白质在许多细胞的表面发现，包括佛波酯（PMA）刺激的T细胞杂交瘤II-23.D7细胞。本发明还涉及在淋巴毒素-β和其它肽如淋巴毒素-α之间形成的复合物以及包含淋巴毒素-β的多个亚基的复合物。这些蛋白质和复合物可用于保持在细胞表面上形成的LT-α，其中LT-α/ LT-β复合物可以作为炎症调节剂，肿瘤生长抑制剂，T细胞抑制剂， T细胞活化剂，自身免疫疾病调节剂或HIV抑制剂。此外，LT-α/ LT-β复合物的抗肿瘤活性可通过用LT-β基因转染的肿瘤浸润淋巴细胞（TIL）递送至肿瘤细胞。

4. 发明授权

US09694058B2 Light-mediated anti-cell proliferative compositions and methods 有权
公开(公告)号：US09694058B2
公开(公告)日：2017-07-04
申请号：US12446729
申请日：2007-10-25
申请人： Carl F Ware , Timothy C. Cheung , Theresia A. Banks
发明人： Carl F Ware , Timothy C. Cheung , Theresia A. Banks
IPC分类号： A61K39/00 , C12N5/071 , C07K14/52 , C07K14/705
CPC分类号： A61K39/0011 , A61K2039/5152 , A61K2039/6006 , C07K14/70575 , C12N5/067 , C12N5/0672 , C12N2501/105 , C12N2501/11 , C12N2501/33 , C12N2503/02
摘要： The tumor-necrosis factor superfamily member LIGHT (p30; TNFSF-14) is a cytokine for inducing immune responses against tumors. A novel biochemical approach is used to decorate the surface of tumor cells with LIGHT. LIGHT decorated cells can be used to vaccinate and induce effective, sustained immunity against cells expressing neo or pathogen associated antigens. Variants of LIGHT are described that enhance binding to cellular receptors (e.g., LT beta receptor) and decrease regulation by inhibitors (e.g., Decoy Receptor 3) increasing ability to stimulate immunity.

5. 发明授权

US08058402B2 Antagonistic human LIGHT-specific human monoclonal antibodies 有权
标题翻译：拮抗人类LIGHT特异性人单克隆抗体
公开(公告)号：US08058402B2
公开(公告)日：2011-11-15
申请号：US12439518
申请日：2007-08-24
申请人： Steven W. Granger , Shinichiro Kato , Carl F. Ware
发明人： Steven W. Granger , Shinichiro Kato , Carl F. Ware
IPC分类号： C12P21/08
CPC分类号： C07K16/24 , A61K2039/505 , C07K16/2875 , C07K2317/21 , C07K2317/34 , C07K2317/56 , C07K2317/565 , C07K2317/76
摘要： Provided herein are antibodies, such as fully human antibodies that immunospecifically bind to an hLIGHT polypeptide. Also provided are isolated nucleic acids encoding antibodies, such as fully human antibodies, that immunospecifically bind to a hLIGHT polypeptide. Further provided are vectors and host cells comprising nucleic acids encoding antibodies, such as fully human antibodies, that immunospecifically bind to a hLIGHT polypeptide. Also provided are methods of making antibodies, such as fully human antibodies, that immunospecifically bind to a hLIGHT polypeptide. Also provided herein is a method of treating a hLIGHT-mediated disease in a subject comprising administering to the subject an antibody, such as a fully human antibody, that immunospecifically binds to a hLIGHT polypeptide. In preferred embodiments, that anti-hLIGHT antibodies provided herein will ameliorate, neutralize or otherwise inhibit hLIGHT biological activity in vivo (e.g., the hLIGHT-mediated production or secretion of CCL20, IL-8 or RANTES from a cell expressing a hLIGHT receptor). Also provided herein is a method for the detection of hLIGHT in a sample as well as a method for ameliorating, neutralizing or otherwise inhibiting hLIGHT activity, e.g., in a human subject suffering from a disorder in which hLIGHT activity is detrimental.
摘要翻译：本文提供了抗体，例如免疫特异性结合hLIGHT多肽的完全人抗体。还提供了编码抗体的分离的核酸，例如免疫特异性结合于hLIGHT多肽的完全人抗体。还提供了载体和宿主细胞，其包含免疫特异性结合hLIGHT多肽的编码抗体（例如完全人抗体）的核酸。还提供了制备免疫特异性结合hLIGHT多肽的抗体（例如完全人抗体）的方法。本文还提供了治疗受试者中的hLIGHT介导的疾病的方法，包括向受试者施用免疫特异性结合hLIGHT多肽的抗体，例如完全人抗体。在优选实施方案中，本文提供的抗-HLIGHT抗体将改善，中和或抑制体内的hLIGHT生物活性（例如，hLIGHT介导的来自表达hLIGHT受体的细胞的CCL20，IL-8或RANTES的产生或分泌）。本文还提供了用于检测样品中的hLIGHT的方法以及用于改善，中和或抑制hLIGHT活性的方法，例如在患有hLIGHT活性有害的病症的人类受试者中。

6. 发明申请

US20100034815A1 METHOD FOR RESTORING DENDRITIC CELL POPULATIONS 有权
标题翻译：恢复细胞群体的方法
公开(公告)号：US20100034815A1
公开(公告)日：2010-02-11
申请号：US12483159
申请日：2009-06-11
申请人： Carl F. Ware , Carl De Trez
发明人： Carl F. Ware , Carl De Trez
IPC分类号： A61K39/395 , C12Q1/68 , C12N5/02
CPC分类号： G01N33/5088 , A61K2039/505 , C07K16/242 , G01N33/5047 , G01N2333/70517 , G01N2333/70575 , G01N2800/24
摘要： The present invention provides methods for restoring and increasing dendritic cell populations in a subject by modulation of the lymphotoxin-β receptor (LTβR) via LTβR agonists. The invention also provides methods for screening for agents capable of restoring or increasing dendritic cell populations. The invention further provides a method for the treatment of immunodeficiency by administration of an LTβR agonist.
摘要翻译：本发明提供通过LTbetaR激动剂调节淋巴毒素-β受体（LTbetaR）来恢复和增加受试者的树突状细胞群体的方法。本发明还提供了筛选能够恢复或增加树突细胞群体的试剂的方法。本发明还提供了通过施用LTbetaR激动剂治疗免疫缺陷的方法。

7. 发明申请

US20090311280A1 NOVEL TNF RECEPTOR REGULATORY DOMAIN 审中-公开
标题翻译：新型TNF受体调节区
公开(公告)号：US20090311280A1
公开(公告)日：2009-12-17
申请号：US11721308
申请日：2005-12-09
申请人： Timothy C. Cheung , Ian R. Humphreys , Karen G. Potter , Christopher A. Benedict , Carl F. Ware , Carl De Trez , Michael Croft , Mitchell Kronenberg
发明人： Timothy C. Cheung , Ian R. Humphreys , Karen G. Potter , Christopher A. Benedict , Carl F. Ware , Carl De Trez , Michael Croft , Mitchell Kronenberg
IPC分类号： A61K39/00 , C07K7/00 , C07K7/06 , C07K7/08 , C07K14/045 , C07K14/435 , C12N15/11 , C07K16/28 , C07K16/08 , C07K1/00 , C12N5/06 , A61K38/16
CPC分类号： C07K14/70578 , A61K38/00 , C07K2317/00 , C07K2317/74 , Y02A50/463
摘要： Herpesvirus entry mediator (HVEM) is a member of the tumor necrosis factor receptor superfamily (TNFRSF) and acts as a molecular switch that modulates T cell activation by propagating positive signals from the TNF related ligand, LIGHT (p30, TNFSF14), or inhibitory signals through the immunoglobulin superfamily member, B and T lymphocyte attenuator (BTLA). A novel binding site for BTLA is disclosed, located in cysteine-rich domain-1 of HVEM. BTLA binding site on HVEM overlaps with the binding site for the Herpes Simplex virus-1 envelope glycoprotein D (gD), but is distinct from where LIGHT binds, yet gD inhibits the binding of both ligands. A BTLA activating protein present in human cytomegalovirus is identified as UL144. UL144 binds BTLA, but not LIGHT, and inhibits T cell proliferation.
摘要翻译：疱疹病毒进入介质（HVEM）是肿瘤坏死因子受体超家族（TNFRSF）的成员，并且作为通过从TNF相关配体LIGHT（p30，TNFSF14）或抑制性信号传播阳性信号调节T细胞活化的分子开关通过免疫球蛋白超家族成员B和T淋巴细胞衰减（BTLA）。公开了位于HVEM的富含半胱氨酸的结构域1中的BTLA的新结合位点。 HVEM上的BTLA结合位点与单纯疱疹病毒-1包膜糖蛋白D（gD）的结合位点重叠，但不同于LIGHT结合的位置，而gD抑制两个配体的结合。存在于人巨细胞病毒中的BTLA激活蛋白被鉴定为UL144。 UL144结合BTLA，但不结合LIGHT，并抑制T细胞增殖。

8. 发明授权

US5670149A Lymphotoxin-.beta., Lymphotoxin-.beta. complexes, pharmaceutical preparations and therapeutic uses thereof 失效
标题翻译：淋巴毒素-β，淋巴毒素-β复合物，药物制剂及其治疗用途
公开(公告)号：US5670149A
公开(公告)日：1997-09-23
申请号：US476489
申请日：1995-06-06
申请人： Jeffrey Browning , Carl F. Ware
发明人： Jeffrey Browning , Carl F. Ware
IPC分类号： A61K38/00 , C07K14/525 , A61K39/395
CPC分类号： C07K14/5255 , C07K14/525 , A61K38/00
摘要： This invention relates to lymphotoxin-.beta., a lymphocyte membrane type protein. This protein is found on the surface of a number of cells, including phorbol ester (PNA) stimulated T cell hybridoma II-23.D7 cells. This invention also relates to complexes formed between lymphotoxin-.beta. and other peptides such as lymphotoxin-.alpha. and to complexes comprising multiple subunits of lymphotoxin-.beta.. These proteins and complexes are useful in holding LT-.alpha. formed within the cell on the cell surface where the LT-.alpha./LT-.beta. complex may act as an inflammation regulating agent, a tumor growth inhibiting agent, a T cell inhibiting agent, a T cell activating agent, an autoimmune disease regulating agent, or an HIV inhibiting agent. Furthermore, the antitumor activity of the LT-.alpha./LT-.beta. complex may be delivered to tumor cells by tumor infiltrating lymphocytes (TILs) transfected with the gene for LT-.beta..
摘要翻译：本发明涉及淋巴细胞膜型蛋白质淋巴细胞毒素-β。这种蛋白质在许多细胞的表面发现，包括佛波酯（PNA）刺激的T细胞杂交瘤II-23.D7细胞。本发明还涉及在淋巴毒素-β和其它肽如淋巴毒素-α之间形成的复合物以及包含淋巴毒素-β的多个亚基的复合物。这些蛋白质和复合物可用于保持在细胞表面上形成的LT-α，其中LT-α/ LT-β复合物可以作为炎症调节剂，肿瘤生长抑制剂，T细胞抑制剂， T细胞活化剂，自身免疫疾病调节剂或HIV抑制剂。此外，LT-α/ LT-β复合物的抗肿瘤活性可通过用LT-β基因转染的肿瘤浸润淋巴细胞（TIL）递送至肿瘤细胞。

9. 发明授权

US5661004A Lymphotoxin-.beta., lymphotoxin-.beta. complexes, pharmaceutical preparations and therapeutic uses thereof 失效
标题翻译：淋巴毒素-β，淋巴毒素-β复合物，药物制剂及其治疗用途
公开(公告)号：US5661004A
公开(公告)日：1997-08-26
申请号：US484272
申请日：1995-06-07
申请人： Jeffrey Browning , Carl F. Ware
发明人： Jeffrey Browning , Carl F. Ware
IPC分类号： A61K35/14 , A61K38/00 , A61K39/395 , A61K45/00 , A61P29/00 , A61P31/18 , A61P35/00 , A61P37/00 , A61P37/02 , A61P43/00 , C07K1/22 , C07K14/00 , C07K14/52 , C07K14/525 , C07K14/705 , C07K14/725 , C07K16/00 , C07K16/24 , C07K16/28 , C07K19/00 , C12N5/10 , C12N15/09 , C12N15/12 , C12P21/02 , C12N15/00 , C12N15/11 , C12N15/85
CPC分类号： C07K14/5255 , C07K14/525 , A61K38/00
摘要： This invention relates to lymphotoxin-.beta., a lymphocyte membrane type protein. This protein is found on the surface of a number of cells, including phorbol ester (PMA) stimulated T cell hybridoma II-23.D7 cells. This invention also relates to complexes formed between lymphotoxin-.beta. and other peptides such as lymphotoxin-.alpha. and to complexes comprising multiple subunits of lymphotoxin-.beta.. These proteins and complexes are useful in holding LT-.alpha. formed within the cell on the cell surface where the LT-.alpha./LT.beta. complex may act as an inflammation regulating agent, a tumor growth inhibiting agent, a T cell inhibiting agent, a T cell activating agent, an autoimmune disease regulating agent, or an HIV inhibiting agent. Furthermore, the antitumor activity of the LT-.alpha./LT-.beta. complex may be delivered to tumor cells by tumor infiltrating lymphocytes (TILs) transfected with the gene for LT-.beta..
摘要翻译：本发明涉及淋巴细胞膜型蛋白质淋巴细胞毒素-β。这种蛋白质在许多细胞的表面发现，包括佛波酯（PMA）刺激的T细胞杂交瘤II-23.D7细胞。本发明还涉及在淋巴毒素-β和其它肽如淋巴毒素-α之间形成的复合物以及包含淋巴毒素-β的多个亚基的复合物。这些蛋白质和复合物可用于保持在细胞表面上形成的LT-α，其中LT-α/LTβ复合物可以作为炎症调节剂，肿瘤生长抑制剂，T细胞抑制剂，T 细胞活化剂，自身免疫疾病调节剂或HIV抑制剂。此外，LT-α/ LT-β复合物的抗肿瘤活性可通过用LT-β基因转染的肿瘤浸润淋巴细胞（TIL）递送至肿瘤细胞。

10. 发明申请

US20120251505A1 HUMAN LYMPHOID TISSUE INDUCER (LTi) CELL COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：人淋巴组织诱导因子（LTi）细胞组成及使用方法
公开(公告)号：US20120251505A1
公开(公告)日：2012-10-04
申请号：US13394010
申请日：2010-09-03
申请人： Carl F. Ware , Vasileios Bekiaris
发明人： Carl F. Ware , Vasileios Bekiaris
IPC分类号： A61K35/26 , C12Q1/04 , G01N33/569 , A61P31/18 , C12Q1/02 , C40B30/06 , A61P31/22 , C12N5/0789 , C12Q1/68
CPC分类号： G01N33/5047 , A61K35/00 , C12N5/0651 , C12N2501/2307 , C12N2502/256
摘要： The invention provides human lymphoid tissue inducer (LTi) cells, methods of producing human lymphoid tissue inducer (LTi) cells, and methods of using human lymphoid tissue inducer (LTi) cells. Such methods include treatment of a subject that would benefit from human lymphoid tissue inducer (LTi) cells, for example, an immunocompromised or immunosuppressed subject.
摘要翻译：本发明提供人类淋巴组织诱导物（LTi）细胞，产生人淋巴组织诱导物（LTi）细胞的方法，以及使用人类淋巴组织诱导物（LTi）细胞的方法。这样的方法包括治疗受益于人类淋巴组织诱导物（LTi）细胞的受试者，例如免疫受损或免疫抑制受试者。

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