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1. 发明申请

US20100040614A1 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：US20100040614A1
公开(公告)日：2010-02-18
申请号：US12521302
申请日：2007-12-26
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： A61K39/395 , A61K39/00 , A61P31/12
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。

2. 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。

3. 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.

4. 发明申请

US20100151492A1 METHODS FOR THE TREATMENT OF INFECTIONS AND TUMORS 有权
标题翻译：治疗感染和肿瘤的方法
公开(公告)号：US20100151492A1
公开(公告)日：2010-06-17
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： G01N33/53 , C12Q1/02
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.
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。还公开了用于测定施用PD-1拮抗剂的受试者中PD-1拮抗剂的功效的方法。在一些实施方案中，这些方法包括测量来自施用PD-1拮抗剂的受试者的样品中记忆B细胞的增殖。

5. 发明授权

US08652465B2 Methods and compositions for the treatment of persistent infections 有权
标题翻译：用于治疗持续感染的方法和组合物
公开(公告)号：US08652465B2
公开(公告)日：2014-02-18
申请号：US11449919
申请日：2006-06-08
申请人： Gordon Freeman , Arlene Sharpe , David M. Dorfman , Rafi Ahmed , Daniel Barber , E. John Wherry
发明人： Gordon Freeman , Arlene Sharpe , David M. Dorfman , Rafi Ahmed , Daniel Barber , E. John Wherry
IPC分类号： A61K39/395 , C07K16/00
CPC分类号： C07K16/2803 , A61K31/713 , A61K38/1709 , A61K39/39 , A61K39/3955 , A61K39/39558 , A61K45/06 , A61K2039/505 , A61K2039/507 , A61K2039/55516 , A61K2039/55566 , A61K2039/572 , C07K16/2818 , C07K16/2827 , C07K2317/70 , C07K2317/73 , C07K2317/74 , C07K2317/76 , C12N15/1138 , C12N2310/14 , G01N33/5011 , G01N33/505 , G01N33/57484 , G01N33/57492 , G01N2800/26 , Y02A50/412 , Y02A50/467 , Y02A50/58
摘要： The present invention provides methods and compositions for the treatment, prevention, or reduction of persistent infections, such as chronic infections, latent infections, and slow infections and cancer. The methods and compositions of the invention are also useful for the alleviation of one or more symptoms associated with such infections and cancer.
摘要翻译：本发明提供用于治疗，预防或减少持续感染例如慢性感染，潜伏感染，慢感染和癌症的方法和组合物。本发明的方法和组合物还可用于缓解与这种感染和癌症相关的一种或多种症状。

6. 发明申请

US20070122378A1 Methods and compositions for the treatment of persistent infections 有权
标题翻译：用于治疗持续感染的方法和组合物
公开(公告)号：US20070122378A1
公开(公告)日：2007-05-31
申请号：US11449919
申请日：2006-06-08
申请人： Gordon Freeman , Arlene Sharpe , David Dorfman , Rafi Ahmed , Daniel Barber , E. Wherry
发明人： Gordon Freeman , Arlene Sharpe , David Dorfman , Rafi Ahmed , Daniel Barber , E. Wherry
IPC分类号： A61K39/395 , A61K38/21 , A61K38/20 , A61K38/19 , A61K48/00 , C12Q1/70 , G01N33/569 , G01N33/574 , G01N33/554
CPC分类号： C07K16/2803 , A61K31/713 , A61K38/1709 , A61K39/39 , A61K39/3955 , A61K39/39558 , A61K45/06 , A61K2039/505 , A61K2039/507 , A61K2039/55516 , A61K2039/55566 , A61K2039/572 , C07K16/2818 , C07K16/2827 , C07K2317/70 , C07K2317/73 , C07K2317/74 , C07K2317/76 , C12N15/1138 , C12N2310/14 , G01N33/5011 , G01N33/505 , G01N33/57484 , G01N33/57492 , G01N2800/26 , Y02A50/412 , Y02A50/467 , Y02A50/58
摘要： The present invention provides methods and compositions for the treatment, prevention, or reduction of persistent infections, such as chronic infections, latent infections, and slow infections and cancer. The methods and compositions of the invention are also useful for the alleviation of one or more symptoms associated with such infections and cancer.
摘要翻译：本发明提供用于治疗，预防或减少持续感染例如慢性感染，潜伏感染，慢感染和癌症的方法和组合物。本发明的方法和组合物还可用于缓解与这种感染和癌症相关的一种或多种症状。

7. 发明申请

US20070106070A1 Novel forms of T cell costimulatory molecules and uses therefor 失效
标题翻译：新型形式的T细胞共刺激分子及其用途
公开(公告)号：US20070106070A1
公开(公告)日：2007-05-10
申请号：US11589275
申请日：2006-10-26
申请人： Arlene Sharpe , Francescopaolo Borriello , Gordon Freeman , Lee Nadler
发明人： Arlene Sharpe , Francescopaolo Borriello , Gordon Freeman , Lee Nadler
IPC分类号： C07H21/04
CPC分类号： C07K14/70532 , A01K2217/05
摘要： Novel structural forms of T cell costimulatory molecules are described. These structural forms comprise a novel structural domain or have a structural domain deleted or added. The structural forms correspond to naturally-occurring alternatively spliced forms of T cell costimulatory molecules or variants thereof which can be produced by standard recombinant DNA techniques. In one embodiment, the T cell costimulatory molecule of the invention contains a novel cytoplasmic domain. In another embodiment, the T cell costimulatory molecule of the invention contains a novel signal peptide domain or has an immunoglobulin variable region-like domain deleted. The novel structural forms of T cell costimulatory molecules can be used to identify agents which stimulate the expression of alternative forms of costimulatory molecules and to identify components of the signal transduction pathway which results in costimulation of T cells.
摘要翻译：描述了T细胞共刺激分子的新型结构形式。这些结构形式包括一个新的结构域或者具有缺失或添加的结构域。结构形式对应于可以通过标准重组DNA技术产生的天然存在的可变剪接形式的T细胞共刺激分子或其变体。在一个实施方案中，本发明的T细胞共刺激分子含有新的细胞质结构域。在另一个实施方案中，本发明的T细胞共刺激分子含有新的信号肽结构域或具有免疫球蛋白可变区域结构域缺失。 T细胞共刺激分子的新型结构形式可用于鉴定刺激替代形式的共刺激分子表达的试剂，并鉴定导致T细胞共刺激的信号转导通路的成分。

8. 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。

9. 发明申请

US20050129670A1 Tumor cells modified to express B7-2 with increased immunogenicity and uses therefor 审中-公开
标题翻译：肿瘤细胞修饰以表达B7-2，增加免疫原性，并用于此
公开(公告)号：US20050129670A1
公开(公告)日：2005-06-16
申请号：US10767561
申请日：2004-01-28
申请人： Gordon Freeman , Lee Nadler , Gary Gray
发明人： Gordon Freeman , Lee Nadler , Gary Gray
IPC分类号： A01K67/027 , A61K38/00 , C07K14/705 , C07K16/28 , C12N15/85 , A61K48/00
CPC分类号： C12N15/8509 , A01K67/0271 , A01K2217/05 , A01K2227/105 , A01K2267/03 , A61K38/00 , C07K14/70532 , C07K16/2827 , C07K2319/00 , C07K2319/30
摘要： Tumor cells modified to express one or more T cell costimulatory molecules are disclosed. Preferred costimulatory molecules are B7-2 and B7-3. The tumor cells of the invention can be modified by transfection with nucleic acid encoding B7-2 and/or B7-3, by using an agent which induces or increases expression of B7-2 and/or B7-3 on the tumor cell or by coupling B7-2 and/or B7-3 to the tumor cell. Tumor cells modified to express B7-2 and/or B7-3 can be further modified to express B7. 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：公开了修饰以表达一种或多种T细胞共刺激分子的肿瘤细胞。优选的共刺激分子是B7-2和B7-3。本发明的肿瘤细胞可以通过用编码B7-2和/或B7-3的核酸转染，通过使用诱导或增加肿瘤细胞上B7-2和/或B7-3表达的试剂或通过将B7-2和/或B7-3偶联到肿瘤细胞。修饰以表达B7-2和/或B7-3的肿瘤细胞可进一步修饰以表达B7。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。

10. 发明授权

US5238839A Nucleic Acids Encoding proteins which induce immunological effector cell activation and chemattraction, vectors, and recombinant cells 失效
标题翻译：核酸编码诱导免疫效应细胞活化和化学吸收，载体和重组细胞的蛋白质
公开(公告)号：US5238839A
公开(公告)日：1993-08-24
申请号：US732185
申请日：1991-07-18
申请人： Harvey I. Cantor , Roberto Patarca , Joel L. Schwartz , Gordon Freeman
发明人： Harvey I. Cantor , Roberto Patarca , Joel L. Schwartz , Gordon Freeman
IPC分类号： A61K38/00 , C07K14/52 , C07K16/24
CPC分类号： C07K16/24 , C07K14/52 , A61K38/00 , C07K2317/77
摘要： The present invention relates to genes and their encoded proteins which induce immunological effector cell activation and chemattraction. The proteins of the invention attract subsets of immunological effector cells and stimulate them to express their specialized effector cell functions. Such proteins, termed Ap-1 proteins, are expressed by lymphoid cells, and bind to effector cells such as macrophages and mast cells. In particular, the ApPursuant to the provisions of 35 U.S.C. .sctn.202(c), it is hereby acknoledged that the Governament has certain rights in this invention, which was made in part with funds from the National Institutes of Health.
摘要翻译：本发明涉及诱导免疫效应细胞活化和化学诱导的基因及其编码的蛋白质。本发明的蛋白质吸引免疫效应细胞的子集并刺激它们表达其特异的效应细胞功能。称为Ap-1蛋白的蛋白质由淋巴细胞表达，并结合效应细胞如巨噬细胞和肥大细胞。特别地，Ap-1蛋白诱导巨噬细胞吞噬作用，II类主要组织相容性分子的表达，细胞毒性和迁移，并诱导造血祖细胞分化。 Ap-1分子在炎症或免疫疾病或肿瘤的治疗或诊断中可能是有价值的。

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