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11. 发明申请

US20120251537A1 COMPOSITIONS AND METHODS FOR THE TREATMENT OF INFECTIONS AND TUMORS 审中-公开
标题翻译：用于治疗感染和肿瘤的组合物和方法
公开(公告)号：US20120251537A1
公开(公告)日：2012-10-04
申请号：US13436492
申请日：2012-03-30
申请人： Rafi Ahmed , Rama Amara , Gordon Freeman , Arlene Sharpe
发明人： Rafi Ahmed , Rama Amara , Gordon Freeman , Arlene Sharpe
IPC分类号： A61K39/12 , A61K39/21 , A61K39/245 , A61K39/25 , A61K39/29 , A61K39/235 , A61K39/23 , A61P31/14 , A61P31/22 , A61P31/20 , A61P31/18 , A61P37/04 , A61P35/00 , A61K39/00 , A61P31/00 , A61K39/395
CPC分类号： C07K16/2827 , A61K39/12 , A61K39/395 , A61K2039/505 , A61K2039/507 , A61K2039/5158 , A61K2039/5256 , C07K16/2818 , C07K2317/64 , C12N2710/24143 , C12N2740/16011 , C12N2760/10011 , C12N2760/10034 , C12N2770/24211 , A61K2300/00
摘要： PD-1 antagonists are disclosed that can be used to reduce the expression or activity of PD-1 in a subject. An immune response specific to an infectious agent or to tumor cells can be enhanced using these PD-1 antagonists in conjunction with an antigen from the infectious agent or tumor. Thus, subjects with infections, such as persistent infections can be treated using PD-1 antagonists. In addition, subjects with tumors can be treated using the PD-1 antagonists. In several examples, subjects can be treated by transplanting a therapeutically effective amount of activated T cells that recognize an antigen of interest and by administering a therapeutically effective amount of a PD-1 antagonist.
摘要翻译：公开了可用于降低受试者中PD-1的表达或活性的PD-1拮抗剂。使用这些PD-1拮抗剂与来自感染剂或肿瘤的抗原可以增强特异于感染剂或肿瘤细胞的免疫应答。因此，可以使用PD-1拮抗剂治疗感染的受试者，例如持续感染。此外，可以使用PD-1拮抗剂治疗具有肿瘤的受试者。在几个实例中，可以通过移植治疗有效量的识别感兴趣的抗原的活化T细胞并通过施用治疗有效量的PD-1拮抗剂来治疗受试者。

12. 发明申请

US20110311535A1 NKG2D-FC FOR IMMUNOTHERAPY 审中-公开
标题翻译： NKG2D-FC用于免疫治疗
公开(公告)号：US20110311535A1
公开(公告)日：2011-12-22
申请号：US13140469
申请日：2009-12-18
申请人： Glenn Dranoff , Matthew Vanneman , Gordon Freeman
发明人： Glenn Dranoff , Matthew Vanneman , Gordon Freeman
IPC分类号： A61K39/395 , A61N5/00 , A61P37/04 , A61P35/00 , A61P35/02
CPC分类号： C07K14/70596 , A61K38/177 , A61K45/06 , C07K14/7056 , C07K2319/30
摘要： Methods for cancer immunotherapy are provided. The methods involve the use of a chimeric molecule (e.g., fusion protein) comprising an NKG2D portion and an Fc portion, which binds one or more NKG2D ligands. The methods disclosed herein are useful for the treatment of cancer that is associated with abnormal expression of one or more NKG2D ligands.
摘要翻译：提供了癌症免疫治疗方法。该方法涉及使用包含结合一个或多个NKG2D配体的NKG2D部分和Fc部分的嵌合分子（例如，融合蛋白）。本文公开的方法可用于治疗与一种或多种NKG2D配体的异常表达相关的癌症。

13. 发明申请

US20080118511A1 PD-L2 Molecules: Novel PD-1 Ligands and Uses Therefor 有权
标题翻译： PD-L2分子：新型PD-1配体及其用途
公开(公告)号：US20080118511A1
公开(公告)日：2008-05-22
申请号：US11765838
申请日：2007-06-20
申请人： Gordon Freeman , Irene Chernova , Tatyana Chernova , Nelly Malenkovich , Clive R. Wood
发明人： Gordon Freeman , Irene Chernova , Tatyana Chernova , Nelly Malenkovich , Clive R. Wood
IPC分类号： A61K39/395 , C12N5/00 , A61K38/16 , A61P35/00 , A61P37/06 , A61P31/00
CPC分类号： G01N33/6854 , G01N33/5014 , G01N33/505 , G01N33/5052 , G01N33/573 , G01N2800/52
摘要： The invention provides isolated nucleic acids molecules, designated PD-L2 nucleic acid molecules, which encode novel B7-related molecules which are ligands for PD-1. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing PD-L2 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a PD-L2 gene has been introduced or disrupted. The invention further provides isolated PD-L2 polypeptides, fusion proteins, antigenic peptides and anti-PD-L2 antibodies. The invention still further provides methods for promoting or inhibiting the interaction between PD-L2 and PD-1. Diagnostic and treatment methods utilizing compositions of the invention are also provided.
摘要翻译：本发明提供分离的核酸分子，命名为PD-L2核酸分子，其编码作为PD-1配体的新型B7相关分子。本发明还提供了反义核酸分子，含有PD-L2核酸分子的重组表达载体，其中引入了表达载体的宿主细胞，以及已导入或破坏了PD-L2基因的非人类转基因动物。本发明进一步提供分离的PD-L2多肽，融合蛋白，抗原肽和抗-PD-L2抗体。本发明还提供了促进或抑制PD-L2与PD-1之间相互作用的方法。还提供了利用本发明组合物的诊断和治疗方法。

14. 发明申请

US20070065427A1 Agents that modulate immune cell activation and methods of use thereof 有权
标题翻译：调节免疫细胞活化的药剂及其使用方法
公开(公告)号：US20070065427A1
公开(公告)日：2007-03-22
申请号：US11501392
申请日：2006-08-09
申请人： Gordon Freeman , Arlene Sharpe , Janet Buhlman , Didier Mandelbrot
发明人： Gordon Freeman , Arlene Sharpe , Janet Buhlman , Didier Mandelbrot
IPC分类号： A61K39/395
CPC分类号： G01N33/6854 , A61K38/1709 , G01N33/505 , G01N33/6872 , G01N2333/70532 , G01N2500/02
摘要： Disclosed are methods for identifying an agent that modulates an immune response. One such method comprises screening for agents which inhibit the interaction between a PD-1 ligand and a PD-1 polypeptide, and determining whether the agents inhibit the interaction between a PD-1 ligand and a B7 polypeptide, to identify an agent that inhibits PD-1 ligand and PD-1 polypeptide interaction, while not inhibiting the interaction between a PD-1 ligand and a B7 polypeptide, as an agent that modulates an immune response. Another such method comprises screening for agents which inhibit the interaction between a PD-1 ligand and a B7 polypeptide, and determining whether the agents inhibit the interaction between a PD-1 ligand and a PD-1 polypeptide, to identify an agent that inhibits the PD-1 ligand and B7 polypeptide interaction, which does not inhibit the interaction between a PD-1 ligand and a PD-1 polypeptide, as an agent that modulates the immune response. Further disclosed is a method for inhibiting the interaction between a B7 polypeptide and a PD-1 ligand, the method comprising contacting an immune cell bearing a PD-1 ligand, or an immune cell bearing a B7 polypeptide, with an agent that inhibits the interaction between the PD-1 ligand and the B7 polypeptide. Such agents may be an anti-PD-1 ligand antibody or a small molecule. Also disclosed is a method for modulating an immune response. The method comprises contacting an immune cell bearing the PD-1 ligand, or an immune cell bearing the PD-1 polypeptide, with an agent that inhibits interactions between the PD-1 ligand and the PD-1 polypeptide, without inhibiting interactions between the PD-1 ligand and a B7 polypeptide, to thereby modulate an immune response. The agent may be an anti-PD-1 ligand antibody or a small molecule.
摘要翻译：公开了用于鉴定调节免疫应答的药剂的方法。一种这样的方法包括筛选抑制PD-1配体和PD-1多肽之间相互作用的试剂，以及确定试剂是否抑制PD-1配体和B7多肽之间的相互作用，以鉴定抑制PD -1配体和PD-1多肽相互作用，而不抑制PD-1配体和B7多肽之间的相互作用，作为调节免疫应答的试剂。另一种这样的方法包括筛选抑制PD-1配体和B7多肽之间的相互作用的试剂，以及确定试剂是否抑制PD-1配体和PD-1多肽之间的相互作用，以鉴定抑制 PD-1配体和B7多肽相互作用，其不抑制PD-1配体和PD-1多肽之间的相互作用，作为调节免疫应答的试剂。进一步公开的是抑制B7多肽和PD-1配体之间的相互作用的方法，该方法包括将带有PD-1配体的免疫细胞或带有B7多肽的免疫细胞与抑制相互作用的药物接触在PD-1配体和B7多肽之间。这样的试剂可以是抗PD-1配体抗体或小分子。还公开了一种调节免疫应答的方法。该方法包括使携带PD-1配体或携带PD-1多肽的免疫细胞的免疫细胞与抑制PD-1配体和PD-1多肽之间的相互作用的试剂接触，而不抑制PD之间的相互作用 -1配体和B7多肽，从而调节免疫应答。该试剂可以是抗PD-1配体抗体或小分子。

15. 发明申请

US20060233795A1 Methods for selectively modulating a Th2-type response within a population of activated CD4+ T cells 审中-公开
标题翻译：用于选择性调节活化的CD4 + T细胞群体内的Th2型应答的方法
公开(公告)号：US20060233795A1
公开(公告)日：2006-10-19
申请号：US11388754
申请日：2006-03-24
申请人： Gordon Freeman , Vassiliki Boussiotis , Lee Nadler
发明人： Gordon Freeman , Vassiliki Boussiotis , Lee Nadler
IPC分类号： A61K39/395
CPC分类号： C07K14/70532 , A61K2035/124 , A61K2039/57 , C07K2319/30 , C12N5/0636 , C12N2501/51
摘要： Methods for selectively modulating a Th2-type response within a population of activated CD4+ T cells are provided. The methods of the invention involve contacting the CD4+ T cells with an agent which modulates a B7-2-induced signal in the CD4+ T cells, such that the Th2-type response is modulated. Methods for either stimulating or inhibiting Th2 type responses are provided by the invention.
摘要翻译：提供了在活化的CD4 + T细胞群内选择性调节Th2型应答的方法。本发明的方法包括使CD4 + T细胞与调节CD4 + T细胞中B7-2诱导的信号的试剂接触，从而调节Th2型反应。刺激或抑制Th2型反应的方法由本发明提供。

16. 发明申请

US20060099195A1 Tumor cells with increased immunogenicity and uses therfor 有权
标题翻译：肿瘤细胞具有增加的免疫原性，并使用其它药物
公开(公告)号：US20060099195A1
公开(公告)日：2006-05-11
申请号：US11313556
申请日：2005-12-20
申请人： Suzanne Ostrand-Rosenberg , Sivasubramanian Baskar , Laurie Glimcher , Gordon Freeman , Lee Nadler
发明人： Suzanne Ostrand-Rosenberg , Sivasubramanian Baskar , Laurie Glimcher , Gordon Freeman , Lee Nadler
IPC分类号： A61K48/00
CPC分类号： A61K39/0011 , A61K39/00 , A61K48/00 , A61K2039/5152 , A61K2039/5156 , A61K2039/5158 , C07K14/70532 , C07K14/70539
摘要： Tumor cells modified to express a T cell costimulatory molecule are disclosed. In one embodiment, the costimulatory molecule is a CD28/CTLA4 ligand, preferably a B lymphocyte antigen B7. The tumor cells of the invention can be modified by transfection with nucleic acid encoding a T cell costimulatory molecule, by using an agent which induces or increases expression of a T cell costimulatory molecule on the tumor cell surface or by coupling a T cell costimulatory molecule to the tumor cell surface. Tumor cells further modified to express MHC class I and/or class II molecules or in which expression of an MHC associated protein, the invariant chain, is inhibited are also disclosed. The modified tumor cells of the invention can be used in methods for treating-a patient with a tumor, preventing or inhibiting metastatic spread of a tumor or preventing or inhibiting recurrence of a tumor. A method for specifically inducing a CD4+ T cell response against a tumor and a method for treating a tumor by modification of tumor cells in vivo are disclosed.
摘要翻译：公开了修饰以表达T细胞共刺激分子的肿瘤细胞。在一个实施方案中，共刺激分子是CD28 / CTLA4配体，优选B淋巴细胞抗原B7。通过使用诱导或增加T细胞共刺激分子在肿瘤细胞表面上的表达或通过将T细胞共刺激分子与T细胞共刺激分子的偶联的试剂，可以通过用编码T细胞共刺激分子的核酸转染来修饰本发明的肿瘤细胞肿瘤细胞表面。还公开了进一步修饰以表达MHC I类和/或II类分子或其中抑制MHC相关蛋白（不变链）的表达的肿瘤细胞。本发明的修饰的肿瘤细胞可用于治疗患有肿瘤的患者，预防或抑制肿瘤的转移性扩散或预防或抑制肿瘤复发的方法。公开了特异性诱导针对肿瘤的CD4 + T细胞应答的方法和通过体内修饰肿瘤细胞治疗肿瘤的方法。

17. 发明授权

US07038013B2 B7-4 polypeptides and uses therefor 有权
标题翻译： B7-4多肽及其用途
公开(公告)号：US07038013B2
公开(公告)日：2006-05-02
申请号：US10002775
申请日：2001-11-02
申请人： Gordon Freeman , Vassiliki Boussiotis , Tatyana Chernova , Nelly Malenkovich
发明人： Gordon Freeman , Vassiliki Boussiotis , Tatyana Chernova , Nelly Malenkovich
IPC分类号： C07K14/47 , C07K14/725 , C07K16/46 , A61K38/17 , A61K39/395
CPC分类号： A61K45/06 , A61K39/00 , A61K2039/55516 , C07K14/70503 , C07K14/70532 , C07K16/2803 , C07K16/2827 , C07K2317/21 , C07K2317/24 , C07K2317/622 , C07K2319/30
摘要： The invention provides isolated nucleic acids molecules, designated B7-4 nucleic acid molecules, which encode novel B7-4 polypeptides. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing B7-4 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a B7-4 gene has been introduced or disrupted. The invention still further provides isolated B7-4 proteins, fusion proteins, antigenic peptides and anti-B7-4 antibodies. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.
摘要翻译：本发明提供编码新的B7-4多肽的分离的核酸分子，命名为B7-4核酸分子。本发明还提供反义核酸分子，含有B7-4核酸分子的重组表达载体，其中引入了表达载体的宿主细胞，以及引入或破坏了B7-4基因的非人转基因动物。本发明还进一步提供分离的B7-4蛋白，融合蛋白，抗原肽和抗B7-4抗体。还提供了利用本发明组合物的诊断，筛选和治疗方法。

18. 发明授权

US06936704B1 Nucleic acids encoding costimulatory molecule B7-4 有权
标题翻译：编码共刺激分子B7-4的核酸
公开(公告)号：US06936704B1
公开(公告)日：2005-08-30
申请号：US09644934
申请日：2000-08-23
申请人： Gordon Freeman , Vassiliki Boussiotis , Tatyana Chernova , Nelly Malenkovich
发明人： Gordon Freeman , Vassiliki Boussiotis , Tatyana Chernova , Nelly Malenkovich
IPC分类号： G01N33/50 , A61K38/00 , A61K39/00 , A61K39/395 , A61K45/06 , A61P35/00 , A61P37/02 , C07K14/705 , C07K16/28 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/09 , C12N15/12 , C12P21/02 , G01N33/15 , G01N33/53 , C07H21/04 , C12N15/63 , C12N15/87
CPC分类号： A61K45/06 , A61K39/00 , A61K2039/55516 , C07K14/70503 , C07K14/70532 , C07K16/2803 , C07K16/2827 , C07K2317/21 , C07K2317/24 , C07K2317/622 , C07K2319/30
摘要： The invention provides isolated nucleic acids molecules, designated B7-4 nucleic acid molecules, which encode novel B7-4 polypeptides. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing B7-4 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a B7-4 gene has been introduced or disrupted. The invention still further provides isolated B7-4 proteins, fusion proteins, antigenic peptides and anti-B7-4 antibodies. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.
摘要翻译：本发明提供编码新的B7-4多肽的分离的核酸分子，命名为B7-4核酸分子。本发明还提供反义核酸分子，含有B7-4核酸分子的重组表达载体，其中引入了表达载体的宿主细胞，以及引入或破坏了B7-4基因的非人转基因动物。本发明还进一步提供分离的B7-4蛋白，融合蛋白，抗原肽和抗B7-4抗体。还提供了利用本发明组合物的诊断，筛选和治疗方法。

19. 发明申请

US20050095593A1 T cell regulatory genes associated with immune disease 有权
标题翻译：与免疫疾病相关的T细胞调节基因
公开(公告)号：US20050095593A1
公开(公告)日：2005-05-05
申请号：US10663497
申请日：2003-09-15
申请人： Jennifer McIntire , Rosemarie Dekruyff , Dale Umetsu , Gordon Freeman
发明人： Jennifer McIntire , Rosemarie Dekruyff , Dale Umetsu , Gordon Freeman
IPC分类号： A61K20060101 , C07K14/705 , C12Q1/68
CPC分类号： C12Q1/6883 , C07K14/70503 , C12Q2600/136 , C12Q2600/156 , C12Q2600/158 , C12Q2600/172
摘要： A genetic locus and corresponding family of proteins associated with regulation of immune development, function, and cell survival are provided. The locus comprising the TIM family is genetically associated with immune dysfunction, including atopy, autoimmunity, inflammatory bowel disease, dysplasia, and susceptibility to blood-bourne infectious diseases. Polymorphisms in the human TIM-1 gene and exposure to Hepatitis A Virus (HAV) are shown to be associated with protection from the development of atopy.
摘要翻译：提供了与调节免疫发育，功能和细胞存活相关的遗传基因座和相应的蛋白质家族。包括TIM家族的基因座在遗传上与免疫功能障碍有关，包括特应性，自身免疫，炎性肠病，发育异常和对血液传染性疾病的易感性。人TIM-1基因的多态性和甲型肝炎病毒（HAV）的暴露显示与保护免受特应性的发展有关。

20. 发明授权

US09598491B2 Methods for the treatment of infections and tumors 有权
公开(公告)号：US09598491B2
公开(公告)日：2017-03-21
申请号：US12626848
申请日：2009-11-27
申请人： Rafi Ahmed , Rama Amara , Vijayakumar Velu , Kehmia Titanji , Gordon Freeman
发明人： Rafi Ahmed , Rama Amara , Vijayakumar Velu , Kehmia Titanji , Gordon Freeman
IPC分类号： C12Q1/02 , C07K16/28 , A61K31/7105 , A61K39/39 , A61K39/395 , G01N33/50 , G01N33/569 , A61K39/00
CPC分类号： G01N33/5052 , A61K31/7105 , A61K39/0011 , A61K39/12 , A61K39/39 , A61K39/39541 , A61K2039/505 , A61K2039/507 , A61K2039/55516 , C07K16/2803 , C07K16/2818 , C07K16/2827 , C07K2317/24 , C07K2317/74 , C07K2317/76 , C12N15/1138 , C12N2310/14 , C12N2760/10034 , G01N33/5088 , G01N33/56966 , G01N2333/52 , G01N2800/26 , Y02A50/41 , A61K2300/00
摘要： PD-1 antagonists are disclosed that can be used to reduce the expression or activity of PD-1 in a subject. An immune response specific to an infectious agent or to tumor cells can be enhanced using these PD-1 antagonists in conjunction with an antigen from the infectious agent or tumor. Thus, subjects with infections, such as persistent infections can be treated using PD-1 antagonists. In addition, subjects with tumors can be treated using the PD-1 antagonists. In several examples, subjects can be treated by transplanting a therapeutically effective amount of activated T cells that recognize an antigen of interest and by administering a therapeutically effective amount of a PD-1 antagonist. Methods are also disclosed for determining the efficacy of a PD-1 antagonist in a subject administered the PD-1 antagonist. In some embodiments, these methods include measuring proliferation of memory B cells in a sample from a subject administered the PD-1 antagonist.

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