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1. 发明申请

US20100136061A1 LIGHT-MEDIATED ANTI-CELL PROLIFERATIVE COMPOSITIONS AND METHODS 有权
标题翻译：光介导的抗细胞增殖组合物和方法
公开(公告)号：US20100136061A1
公开(公告)日：2010-06-03
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： C12N5/09 , A61K39/00 , A61K35/12 , A61P35/04
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.
摘要翻译：肿瘤坏死因子超家族成员LIGHT（p30; TNFSF-14）是诱导针对肿瘤的免疫应答的细胞因子。使用一种新颖的生物化学方法用LIGHT装饰肿瘤细胞的表面。 LIGHT装饰细胞可用于对表达新病原体或病原体相关抗原的细胞进行疫苗接种和诱导有效的持续免疫。描述了LIGHT的变体，其增强与细胞受体（例如LTβ受体）的结合，并减少抑制剂（例如，诱饵受体3）增加刺激免疫能力的调节。

2. 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.

3. 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。

4. 发明申请

US20100104559A1 US CIP-COMPOSITIONS AND METHODS FOR MODULATING RESPONSES MEDIATED OR ASSOCIATED WITH BTLA ACTIVITY 有权
标题翻译：美国CIP组合物和调节与BTLA活性相关的反应的方法
公开(公告)号：US20100104559A1
公开(公告)日：2010-04-29
申请号：US12482426
申请日：2009-06-10
申请人： Carl F. Ware , Carl De Trez , Michael Croft , Timothy C. Cheung , Ian R. Humphreys , Karen G. Porter , Christopher A. Benedict , Mitchell Kronenberg , Marcos W. Steinberg
发明人： Carl F. Ware , Carl De Trez , Michael Croft , Timothy C. Cheung , Ian R. Humphreys , Karen G. Porter , Christopher A. Benedict , Mitchell Kronenberg , Marcos W. Steinberg
IPC分类号： A61K39/395 , C12N5/00 , A61K38/00 , A61P35/00 , A61P29/00
CPC分类号： A61K38/177 , A61K2039/505 , C07K16/2818 , C07K2317/73
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。

5. 发明授权

US08349320B2 Compositions and methods for modulating responses mediated or associated with BTLA activity 有权
标题翻译：用于调节介导或与BTLA活性相关的反应的组合物和方法
公开(公告)号：US08349320B2
公开(公告)日：2013-01-08
申请号：US12482426
申请日：2009-06-10
申请人： Carl F. Ware , Carl De Trez , Michael Croft , Timothy C. Cheung , Ian R. Humphreys , Karen G. Potter , Christopher A. Benedict , Mitchell Kronenberg , Marcos W. Steinberg
发明人： Carl F. Ware , Carl De Trez , Michael Croft , Timothy C. Cheung , Ian R. Humphreys , Karen G. Potter , Christopher A. Benedict , Mitchell Kronenberg , Marcos W. Steinberg
IPC分类号： A61K39/395
CPC分类号： A61K38/177 , A61K2039/505 , C07K16/2818 , C07K2317/73
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。

6. 发明申请

US20110123551A1 HVEM/BTLA, HVEM/CD 160 AND HVEM/GD CIS COMPLEXES AND METHODS OF USE 有权
标题翻译： HVEM / BTLA，HVEM / CD 160和HVEM / GD CIS复合物及其使用方法
公开(公告)号：US20110123551A1
公开(公告)日：2011-05-26
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： A61K39/395 , C07K14/47 , A61K38/17 , C07K16/28 , C12N5/071 , C12N5/078 , C12N5/0781 , C12N5/0783 , G01N33/68 , A61P35/00 , A61P29/00 , A61P37/06 , A61P37/02 , A61P25/28
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.
摘要翻译：本发明提供HVEM顺式复合物，其包括例如HVEM / BTLA，HVEM / CD160和HVEM / gD顺式复合物。本发明提供了与HVEM顺式复合物如抗体结合的配体和试剂。本发明还提供使用HVEM顺式复合物的方法，以及结合HVEM顺式复合物的配体和试剂（例如抗体）。

7. 发明授权

US10106619B2 Virus vaccination and treatment methods with OX40 agonist compositions 有权
公开(公告)号：US10106619B2
公开(公告)日：2018-10-23
申请号：US11867621
申请日：2007-10-04
申请人： Michael Croft , Shahram Salek-Ardakani , Magdalini Moutaftsi , Alessandro Sette , Carl F. Ware
发明人： Michael Croft , Shahram Salek-Ardakani , Magdalini Moutaftsi , Alessandro Sette , Carl F. Ware
IPC分类号： C07K16/28 , A61K39/00 , A61K39/12
摘要： The invention relates to compositions and methods that employ OX40 (CD134), a TNFR superfamily protein, agonists. The invention includes among other things administering an OX40 agonist alone or in combination with a viral antigen, or live or attenuated virus, to treat a viral infection, or for vaccination or immunization.

8. 发明申请

US20120076798A1 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：US20120076798A1
公开(公告)日：2012-03-29
申请号：US13240356
申请日：2011-09-22
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 , C12N15/13 , C12N1/21 , C12P21/00 , C12N5/16 , C07K16/24 , C12N5/10
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 that immunospecifically bind to an hLIGHT polypeptide; isolated nucleic acids encoding the antibodies; vectors and host cells comprising nucleic acids encoding the antibodies; methods of making the antibodies; and a method of treating a hLIGHT-mediated disease in a subject comprising administering to the subject the antibodies. In preferred embodiments, the 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：本文提供了免疫特异性结合于hLIGHT多肽的抗体; 编码抗体的分离的核酸; 载体和宿主细胞，其包含编码抗体的核酸; 制备抗体的方法; 以及治疗受试者中的hLIGHT介导的疾病的方法，包括向受试者施用抗体。在优选的实施方案中，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。

9. 发明授权

US07575745B2 Ligand for herpes simplex virus entry mediator and methods of use 有权
标题翻译：单纯疱疹病毒进入介体的配体和使用方法
公开(公告)号：US07575745B2
公开(公告)日：2009-08-18
申请号：US11513290
申请日：2006-08-29
申请人： Carl F. Ware
发明人： Carl F. Ware
IPC分类号： A61K39/395 , C07K14/47 , C07K16/18
CPC分类号： G01N33/6863 , A61K38/00 , A61K2039/505 , C07K14/005 , C07K14/47 , C07K14/5255 , C07K14/705 , C07K14/70578 , C07K16/2878 , C07K2317/74 , C07K2319/00 , C07K2319/30 , C12N2710/16622 , G01N33/56983 , G01N2500/00
摘要： A novel polypeptide ligand, p30, or LIGHT, for herpes virus entry mediator, HVEM, is provided. LIGHT is useful for modulating immune responses and in inhibiting infection and/or subsequent proliferation by herpesvirus. HVEM fusion proteins are also provided. Methods for treating subjects with lymphoid cell disorders, tumors, autoimmune diseases, inflammatory disorders or those having or suspected of having a herpesvirus infection, utilizing p30 and the fusion proteins of the invention, are also provided.
摘要翻译：提供了一种用于疱疹病毒进入介质HVEM的新型多肽配体p30或LIGHT。光可用于调节免疫应答和抑制疱疹病毒感染和/或随后的增殖。还提供HVEM融合蛋白。还提供了利用p30和本发明的融合蛋白来治疗患有淋巴细胞疾病，肿瘤，自身免疫疾病，炎症性疾病或具有或怀疑患有疱疹病毒感染的受试者的方法。

10. 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。

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