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1. 发明授权

US06576754B2 CD100 antigen and uses therefor 失效
标题翻译： CD100抗原，并用于此
公开(公告)号：US06576754B2
公开(公告)日：2003-06-10
申请号：US08556422
申请日：1995-11-09
申请人： Kathryn T. Hall , Gordon J. Freeman , Joachim L. Schultze , Vassiliki A. Boussiotis , Lee M. Nadler
发明人： Kathryn T. Hall , Gordon J. Freeman , Joachim L. Schultze , Vassiliki A. Boussiotis , Lee M. Nadler
IPC分类号： C07H2104
CPC分类号： C07K14/70503 , A61K38/00 , C07K14/70575 , C07K16/2803 , C07K2319/00
摘要： Isolated nucleic acid molecules encoding novel CD100 molecules which stimulate a leukocyte response, such as a B cell response, including B cell aggregation, B cell differentiation, B cell survival, and/or T cell proliferation are disclosed. These novel molecules have a certain homology to semaphorins, proteins which are growth cone guidance molecules that are critical for guiding growing axons of neurons to their targets. In addition to isolated nucleic acids molecules, antisense nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced are also described. The invention further provides isolated CD100 proteins, fusion proteins and active fragments thereof. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.
摘要翻译：公开了编码新的CD100分子的分离的核酸分子，其刺激白细胞应答，例如B细胞应答，包括B细胞聚集，B细胞分化，B细胞存活和/或T细胞增殖。这些新型分子与semaphorins具有一定的同源性，蛋白质是生长锥形引导分子，对于将神经元的生长轴突引导到其靶点至关重要。还描述了分离的核酸分子，含有本发明的核酸分子的重组表达载体的反义核酸分子，已经引入了表达载体的宿主细胞。本发明还提供了分离的CD100蛋白，融合蛋白及其活性片段。还提供了利用本发明组合物的诊断和治疗方法。

2. 发明授权

US07700102B2 Nucleic acids encoding CD100 molecules 失效
标题翻译：编码CD100分子的核酸
公开(公告)号：US07700102B2
公开(公告)日：2010-04-20
申请号：US10320769
申请日：2002-12-16
申请人： Kathryn T. Hall , Gordon J. Freeman , Joachim L. Schultze , Vassiliki A. Boussiotis , Lee M. Nadler , Laurence Boumsell , Armand Bensussan
发明人： Kathryn T. Hall , Gordon J. Freeman , Joachim L. Schultze , Vassiliki A. Boussiotis , Lee M. Nadler , Laurence Boumsell , Armand Bensussan
IPC分类号： A61K39/395
CPC分类号： C07K14/70503 , A61K38/00 , C07K14/70575 , C07K16/2803 , C07K2319/00
摘要： Isolated nucleic acid molecules encoding novel CD100 molecules which stimulate a leukocyte response, such as a B cell response, including B cell aggregation, B cell differentiation, B cell survival, and/or T cell proliferation are disclosed. These novel molecules have a certain homology to semaphorins, proteins which are growth cone guidance molecules that are critical for guiding growing axons of neurons to their targets. In addition to isolated nucleic acids molecules, antisense nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced are also described. The invention further provides isolated CD100 proteins, fusion proteins and active fragments thereof. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.
摘要翻译：公开了编码新的CD100分子的分离的核酸分子，其刺激白细胞应答，例如B细胞应答，包括B细胞聚集，B细胞分化，B细胞存活和/或T细胞增殖。这些新型分子与semaphorins具有一定的同源性，蛋白质是生长锥形引导分子，对于将神经元的生长轴突引导到其靶点至关重要。还描述了分离的核酸分子，含有本发明的核酸分子的重组表达载体的反义核酸分子，已经引入了表达载体的宿主细胞。本发明还提供了分离的CD100蛋白，融合蛋白及其活性片段。还提供了利用本发明组合物的诊断和治疗方法。

3. 发明授权

US06451305B1 Methods for stimulating T cell responses to tumor cells expressing LFA-3 and a CD28 or CTLA4 ligand 失效
标题翻译：刺激表达LFA-3和CD28或CTLA4配体的肿瘤细胞的T细胞应答的方法
公开(公告)号：US06451305B1
公开(公告)日：2002-09-17
申请号：US08457483
申请日：1995-06-01
申请人： Vassiliki A. Boussiotis , Gordon J. Freeman , Lee M. Nadler
发明人： Vassiliki A. Boussiotis , Gordon J. Freeman , Lee M. Nadler
IPC分类号： A61K4800
CPC分类号： C07K16/2818 , A61K38/00 , A61K2039/505 , A61K2039/5158 , C07K14/70528 , C07K14/70532 , C07K16/2806 , C07K16/2824 , C07K16/2827 , C07K16/2845 , C12N5/0636 , C12N2501/23 , C12N2501/51 , C12N2501/599
摘要： Methods for stimulating a T cell response to a tumor cell in a subject with a tumor which involve modifying the tumor cell to express a CD2 ligand and a CD28 or CTLA4 ligand, are disclosed. Methods wherein the tumor cell is obtained from the subject and modified ex vivo to form a modified tumor cell and then the modified tumor cell is administered to the subject, are also disclosed.
摘要翻译：公开了用于刺激受体中肿瘤细胞对涉及修饰肿瘤细胞以表达CD2配体和CD28或CTLA4配体的肿瘤的T细胞应答的方法。还公开了其中从受试者获得肿瘤细胞并离体修饰以形成修饰的肿瘤细胞，然后向受试者施用修饰的肿瘤细胞的方法。

4. 发明授权

US06465251B1 Method of promoting b-cell proliferation and activation with CD40 ligand and cyclosporin 失效
标题翻译：用CD40配体和环孢菌素促进b细胞增殖和活化的方法
公开(公告)号：US06465251B1
公开(公告)日：2002-10-15
申请号：US08748341
申请日：1996-11-13
申请人： Joachim L. Schultze , Gordon J. Freeman , John G. Gribben , Lee M. Nadler
发明人： Joachim L. Schultze , Gordon J. Freeman , John G. Gribben , Lee M. Nadler
IPC分类号： C12N502
CPC分类号： C12N5/0635 , C12N2501/04 , C12N2501/23 , C12N2501/52
摘要： We teach a strategy to obtain large quantities of desired APCs, activated B cells, which are superior in their capacity to present tumor protein antigen in a multiadministration protocol. Human B cells can be obtained from peripheral blood in large numbers. These cells can be activated in vitro by coculture with CD40L (CD40-B cells) and an immunosuppressive agent such as cyclosporin A. They can expanded up to 1×103 to 1×104 fold in 2 weeks or 1×105 to 1×106 fold in 2 months. We demonstrate these cells are most efficient APCs comparable to DCs in stimulating allogeneic CD4+ CD45RA+, CD4+ CD45RO+, and CD8+ T cells. In contrast to DCs, CD40-B cells are fully functional even in the presence of immunosuppressive cytokines such as IL-10 and TGF&bgr;.
摘要翻译：我们教授一种策略，以获得大量所需的APC，活化的B细胞，其在多重给药方案中具有优于其呈递肿瘤蛋白抗原的能力。人B细胞可以从外周血大量获得。这些细胞可以通过与CD40L（CD40-B细胞）和免疫抑制剂如环孢菌素A的共培养在体外进行活化。它们可以在2周内扩增至1×10 3至1×10 4倍，在2个月内可扩增至1×10 5至1×10 6倍。我们证明这些细胞是最有效的APC，与刺激同种异体CD4 + CD45RA +，CD4 + CD45RO +和CD8 + T细胞的DC相当。与DC相反，即使在免疫抑制性细胞因子如IL-10和TGFbeta的存在下，CD40-B细胞也是完全功能的。

5. 发明授权

US07195758B2 Methods of inducing a T cell mediated immune response by administering antigen presenting B cells 有权
标题翻译：通过施用抗原呈递B细胞诱导T细胞介导的免疫应答的方法
公开(公告)号：US07195758B2
公开(公告)日：2007-03-27
申请号：US10186416
申请日：2002-07-01
申请人： Joachim L. Schultze , Gordon J. Freeman , John G. Gribben , Lee M. Nadler
发明人： Joachim L. Schultze , Gordon J. Freeman , John G. Gribben , Lee M. Nadler
IPC分类号： A01N1/00 , A61K35/14 , A61K35/26
CPC分类号： C12N5/0635 , C12N2501/04 , C12N2501/23 , C12N2501/52
摘要： We teach a strategy to obtain large quantities of desired APCs, activated B cells, which are superior in their capacity to present tumor protein antigen in a multiadministration protocol. Human B cells can be obtained from peripheral blood in large numbers. These cells can be activated in vitro by coculture with CD40L (CD40-B cells) and an immunosuppressive agent such as cyclosporin A. They can expanded up to 1×103 to 1×104 fold in 2 weeks or 1×105 to 1×106 fold in 2 months. We demonstrate these cells are most efficient APCs comparable to DCs in stimulating allogeneic CD4+ CD45RA+, CD4+ CD45RO+, and CD8+ T cells. In contrast to DCs, CD40-B cells are fully functional even in the presence of immunosuppressive cytokines such as IL-10 and TGFβ.
摘要翻译：我们教授一种策略，以获得大量所需的APC，活化的B细胞，其在多重给药方案中具有优于其呈递肿瘤蛋白抗原的能力。人B细胞可以从外周血大量获得。这些细胞可以通过与CD40L（CD40-B细胞）和免疫抑制剂如环孢菌素A共培养在体外进行活化。它们可以扩增至1×10 3至1×10 4个/ 在2个月内为1倍或1×10 5至1×10 6倍。我们证明这些细胞是最有效的APC，与刺激同种异体CD4 + CD45RA + +，+ CD4 + CD45RO + >和CD8 + T细胞。与DC相反，即使在免疫抑制性细胞因子如IL-10和TGFbeta的存在下，CD40-B细胞也是完全功能的。

6. 发明授权

US5942607A B7-2: a CTLA4/CD28 ligand 失效
标题翻译： B7-2：CTLA4 / CD28配体
公开(公告)号：US5942607A
公开(公告)日：1999-08-24
申请号：US101624
申请日：1993-07-26
申请人： Gordon J. Freeman , Lee M. Nadler , Gary S. Gray
发明人： Gordon J. Freeman , Lee M. Nadler , Gary S. Gray
IPC分类号： A61K38/00 , C07K14/705 , C07K16/28 , C12N15/12 , C12N15/85 , C07H21/00
CPC分类号： C12N15/8509 , C07K14/70532 , C07K16/2827 , A01K2217/05 , A01K2217/075 , A01K2267/03 , A01K2267/0381 , A61K38/00 , C07K2317/73 , C07K2319/30
摘要： Isolated nucleic acids encoding novel CTLA4/CD28 ligands which costimulate T cell activation are disclosed. In one embodiment, the isolated nucleic acid has a sequence which encodes a B lymphocyte activation antigen, B7-2. Preferably, the nucleic acid is a DNA molecule comprising at least a portion of a nucleotide sequence shown in FIG. 8, SEQ ID NO: 1. The nucleic acid sequences of the invention can be integrated into various expression vectors, which in turn can direct the synthesis of the corresponding proteins or peptides in a variety of hosts, particularly eukaryotic cells, such as mammalian and insect cell culture. Also disclosed are host cells transformed to produce proteins or peptides encoded by the nucleic acid sequences of the invention and isolated proteins and peptides which comprise at least a portion of a novel B lymphocyte antigen.
摘要翻译：公开了分泌的编码新型CTLA4 / CD28配体的核酸，其共同刺激T细胞活化。在一个实施方案中，分离的核酸具有编码B淋巴细胞活化抗原B7-2的序列。优选地，核酸是包含图1所示的核苷酸序列的至少一部分的DNA分子。 8，SEQ ID NO：1。本发明的核酸序列可以整合到各种表达载体中，其又可以指导各种宿主，特别是真核细胞（例如哺乳动物和哺乳动物）中相应的蛋白质或肽的合成昆虫细胞培养。还公开了转化以产生由本发明的核酸序列编码的蛋白质或肽的宿主细胞和包含至少一部分新型B淋巴细胞抗原的分离的蛋白质和肽。

7. 发明授权

US07459544B2 Nucleic acids encoding B7-2 fusion proteins 失效
标题翻译：编码B7-2融合蛋白的核酸
公开(公告)号：US07459544B2
公开(公告)日：2008-12-02
申请号：US10429079
申请日：2003-05-02
申请人： Gordon J. Freeman , Lee M. Nadler , Gary S. Gray
发明人： Gordon J. Freeman , Lee M. Nadler , Gary S. Gray
IPC分类号： C07H21/04
CPC分类号： C07K16/2827 , A01K67/0276 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2217/075 , A01K2217/30 , A01K2227/105 , A01K2267/01 , A01K2267/03 , A01K2267/0325 , A01K2267/0331 , A01K2267/0381 , A61K38/00 , C07K14/70503 , C07K14/70532 , C07K2317/73 , C07K2319/00 , C07K2319/02 , C07K2319/30 , C12N15/8509
摘要： Nucleic acids encoding novel CTLA4/CD28 ligands which costimulate T cell activation are disclosed. In one embodiment, the nucleic acid has a sequence which encodes a B lymphocyte antigen, B7-2. Preferably, the nucleic acid is a DNA molecule comprising at least a portion of a nucleotide sequence shown in FIG. 8, SEQ ID NO:1 or FIG. 14, SEQ ID NO:23. The nucleic acid sequences of the invention can be integrated into various expression vectors, which in turn direct the synthesis of the corresponding proteins or peptides in a variety of hosts, particularly eukaryotic cells, such as mammalian and insect cell culture. Also disclosed are host cells transformed to produce proteins or peptides encoded by the nucleic acid sequences of the invention and isolated proteins and peptides which comprise at least a portion of a novel B lymphocyte antigen. Proteins and peptides described herein can be administered to subjects to enhance or suppress T cell-mediated immune responses.
摘要翻译：公开了编码协同T细胞活化的新型CTLA4 / CD28配体的核酸。在一个实施方案中，核酸具有编码B淋巴细胞抗原B7-2的序列。优选地，核酸是包含图1所示的核苷酸序列的至少一部分的DNA分子。 8，SEQ ID NO：1或图3。 14，SEQ ID NO：23。本发明的核酸序列可以整合到各种表达载体中，这又指导了多种宿主，特别是真核细胞如哺乳动物和昆虫细胞培养物中的相应蛋白质或肽的合成。还公开了转化以产生由本发明的核酸序列编码的蛋白质或肽的宿主细胞和包含至少一部分新型B淋巴细胞抗原的分离的蛋白质和肽。本文所述的蛋白质和肽可以施用于受试者以增强或抑制T细胞介导的免疫应答。

8. 发明授权

US07153934B2 T cell costimulatory polypeptides containing alternative domains 失效
标题翻译：含有替代结构域的T细胞共刺激多肽
公开(公告)号：US07153934B2
公开(公告)日：2006-12-26
申请号：US09962969
申请日：2001-09-24
申请人： Arlene H. Sharpe , Francescopaolo Borriello , Gordon J. Freeman , Lee M. Nadler
发明人： Arlene H. Sharpe , Francescopaolo Borriello , Gordon J. Freeman , Lee M. Nadler
IPC分类号： C07K14/435 , C07K14/705
CPC分类号： C07K14/70532 , A01K2217/05
摘要： Structural forms of T cell costimulatory polypeptides are described. These forms comprise an alternative structural domain (i.e., a structural domain having an amino acid sequence which differs from a known amino acid sequence) or have a structural domain deleted or added. The structural forms correspond to naturally-occurring alternatively spliced forms of T cell costimulatory polypeptides or variants thereof which can be produced by standard recombinant DNA techniques. In one embodiment, the T cell costimulatory polypeptide of the invention contains an alternative cytoplasmic domain. In another embodiment, the T cell costimulatory polypeptide of the invention contains an alternative signal peptide domain or has an immunoglobulin variable region-like domain deleted. The alternative structural forms of T cell costimulatory polypeptides can be used to identify agents which stimulate the expression of alternative forms of costimulatory polypeptides and to identify components of the signal transduction pathway which results in costimulation of T cells.
摘要翻译：描述了T细胞共刺激多肽的结构形式。这些形式包括可选择的结构域（即，具有不同于已知氨基酸序列的氨基酸序列的结构域）或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细胞共刺激多肽或其变体。在一个实施方案中，本发明的T细胞共刺激多肽含有替代细胞质结构域。在另一个实施方案中，本发明的T细胞共刺激多肽含有替代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细胞共刺激多肽的替代结构形式可用于鉴定刺激替代形式的共刺激多肽的表达并鉴定导致T细胞共刺激的信号转导途径的组分的试剂。

9. 发明授权

US06824779B1 Methods for inhibiting the interaction of B7-2 with its natural ligand 失效
标题翻译：抑制B7-2与天然配体相互作用的方法
公开(公告)号：US06824779B1
公开(公告)日：2004-11-30
申请号：US09425516
申请日：1999-10-22
申请人： Gordon J. Freeman , Lee M. Nadler , Gary S. Gray
发明人： Gordon J. Freeman , Lee M. Nadler , Gary S. Gray
IPC分类号： A61K39395
CPC分类号： A01K67/0276 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2217/075 , A01K2217/30 , A01K2227/105 , A01K2267/0325 , A01K2267/0331 , A61K38/00 , C07K14/70503 , C07K14/70532 , C07K16/2827 , C07K2317/73 , C07K2319/00 , C07K2319/02 , C07K2319/30 , C12N15/8509
摘要： The present invention relates to, inter alia, methods for inhibiting the interaction of the B-lymphocyte antigen, B7-2, with its natural ligand on the surface of an immune cell are disclosed. The methods comprise contacting the immune cell with an agent which inhibits B7-2 binding with its natural ligand, to thereby inhibit the interaction. Examples of such agents are provided, and include a soluble form of B7-2, an antibody that recognized B7-2. The method may also include contacting the immune cell with an agent that blocks the interaction of B7-1 with its natural ligand. Further, the method may include contacting the immune cell with an immunomodulating agent, for example, an antibody reactive with CD28, an antibody reactive with CTLA4, an antibody reactive with a cytokine, a CTLA4Ig fusion protein, a CD28Ig fusion protein, and an immunosuppressive drug. Both in vivo and in vitro applications of the method are disclosed.
摘要翻译：本发明尤其涉及用于抑制B淋巴细胞抗原B7-2与其天然配体在免疫细胞表面上的相互作用的方法。所述方法包括使免疫细胞与抑制B7-2与其天然配体结合的试剂接触，从而抑制相互作用。提供这些试剂的实例，并且包括可溶形式的B7-2，其是识别B7-2的抗体。该方法还可以包括使免疫细胞与阻断B7-1与其天然配体的相互作用的试剂接触。此外，该方法可以包括使免疫细胞与免疫调节剂接触，例如与CD28反应的抗体，与CTLA4反应的抗体，与细胞因子反应的抗体，CTLA4Ig融合蛋白，CD28Ig融合蛋白和免疫抑制药物。公开了该方法的体内和体外应用。

10. 发明授权

US06653444B1 Polypeptides comprising a B7 extracellular domain 失效
标题翻译：包含B7细胞外结构域的多肽
公开(公告)号：US06653444B1
公开(公告)日：2003-11-25
申请号：US08453386
申请日：1995-05-30
申请人： Gordon J. Freeman , Arnold S. Freedman , Lee M. Nadler
发明人： Gordon J. Freeman , Arnold S. Freedman , Lee M. Nadler
IPC分类号： C07K14705
CPC分类号： C07K14/70532 , A01K2217/075
摘要： Isolated nucleic acid molecules encoding a B cell activation antigen, B7, are provided. In one embodiment, the nucleic acid molecules are DNA sequences. The DNA sequences of the invention can be integrated into various expression vectors, which in turn can direct the synthesis of the corresponding proteins or peptides in a variety of hosts, particularly eukaryotic cells, such as mammalian and insect cell culture. Also provided are host cells transformed to produce proteins or peptides encoded by the DNA molecules of the present invention and purified proteins and peptides which comprise at least a portion of the B cell activation antigen. The proteins and peptides comprise at least a portion of the mature form of the B7 activation antigen and preferably comprise a soluble form of the B7 protein.
摘要翻译：提供编码B细胞活化抗原B7的分离的核酸分子。在一个实施方案中，核酸分子是DNA序列。本发明的DNA序列可以整合到各种表达载体中，这又可以引导各种宿主，特别是真核细胞如哺乳动物和昆虫细胞培养物中相应的蛋白质或肽的合成。还提供了转化以产生由本发明的DNA分子编码的蛋白质或肽的宿主细胞和包含至少一部分B细胞活化抗原的纯化的蛋白质和肽。蛋白质和肽包含至少一部分成熟形式的B7活化抗原，并且优选包含可溶形式的B7蛋白。

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