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1. 发明授权

US07531175B2 Methods for modulation of immune responses using humanized immunoglobulins reactive with B7-1 molecules 失效
标题翻译：使用与B7-1分子反应的人源化免疫球蛋白调节免疫应答的方法
公开(公告)号：US07531175B2
公开(公告)日：2009-05-12
申请号：US10986089
申请日：2004-11-12
申请人： Man Sung Co , Maximiliano Vasquez , Beatriz Carreno , Abbie Cheryl Celniker , Mary Collins , Samuel Goldman , Gary S. Gray , Andrea Knight , Denise O'Hara , Bonita Rup , Geertruida M. Veldman
发明人： Man Sung Co , Maximiliano Vasquez , Beatriz Carreno , Abbie Cheryl Celniker , Mary Collins , Samuel Goldman , Gary S. Gray , Andrea Knight , Denise O'Hara , Bonita Rup , Geertruida M. Veldman
IPC分类号： A61K39/395 , C07K16/28
CPC分类号： C07K16/2827 , A61K39/395 , A61K2039/505 , C07K2317/24 , C07K2317/52 , C07K2319/00 , C07K2319/30 , A61K2300/00
摘要： The invention relates to humanized anti-B7-2 and anti-B7-1 antibodies, wherein each comprise a variable region of non-human origin and at least a portion of an immunoglobulin of human origin. The invention also pertains to methods of treatment for various autoimmune diseases, transplant rejection, inflammatory disorders and infectious diseases by administering humanized anti-B7-2 and/or anti-B7-1 antibodies.
摘要翻译：本发明涉及人源化抗B7-2和抗B7-1抗体，其中每个包含非人源可变区和至少一部分人源免疫球蛋白。本发明还涉及通过施用人源化抗B7-2和/或抗B7-1抗体治疗各种自身免疫疾病，移植排斥，炎症性疾病和感染性疾病的方法。

2. 发明授权

US06984383B1 Method of transplanting cells by contacting donor cells with B7-1-and B7-2-specific immunoglobulins 失效
标题翻译：通过使供体细胞与B7-1和B7-2特异性免疫球蛋白接触来移植细胞的方法
公开(公告)号：US06984383B1
公开(公告)日：2006-01-10
申请号：US09626731
申请日：2000-07-27
申请人： Man Sung Co , Maximiliano Vasquez , Beatriz Carreno , Abbie Cheryl Celniker , Mary Collins , Samuel Goldman , Gary S. Gray , Andrea Knight , Denise O'Hara , Bonita Rup , Geertruida M. Veldman
发明人： Man Sung Co , Maximiliano Vasquez , Beatriz Carreno , Abbie Cheryl Celniker , Mary Collins , Samuel Goldman , Gary S. Gray , Andrea Knight , Denise O'Hara , Bonita Rup , Geertruida M. Veldman
IPC分类号： A61K39/395 , A61K35/26 , A61K35/28 , C07K16/28
CPC分类号： C07K16/2827 , A61K39/395 , A61K2039/505 , C07K2317/24 , C07K2317/52 , C07K2317/73 , C07K2319/00 , C07K2319/30 , A61K2300/00
摘要： The invention relates to a humanized anti-B7-2 antibody that comprises a variable region of nonhuman origin and at least a portion of an immunoglobulin of human origin. The invention also pertains to methods of treatment for various autoimmune diseases, transplant rejection, inflammatory disorders and infectious diseases by administering humanized anti-B7-2 and/or anti-B7-1 antibodies.
摘要翻译：本发明涉及包含非人源可变区和人源免疫球蛋白的至少一部分的人源化抗B7-2抗体。本发明还涉及通过施用人源化抗B7-2和/或抗B7-1抗体治疗各种自身免疫疾病，移植排斥，炎症性疾病和感染性疾病的方法。

3. 发明授权

US06905681B1 Methods for selectively stimulating proliferation of T cells 失效
标题翻译：选择性刺激T细胞增殖的方法
公开(公告)号：US06905681B1
公开(公告)日：2005-06-14
申请号：US09349915
申请日：1999-07-08
申请人： Carl H. June , Craig B. Thompson , Gary J. Nabel , Gary S. Gray , Paul D. Rennert
发明人： Carl H. June , Craig B. Thompson , Gary J. Nabel , Gary S. Gray , Paul D. Rennert
IPC分类号： A61K35/14 , A61K35/17 , A61K35/28 , A61K38/00 , A61K38/17 , A61K38/46 , A61K39/00 , A61K39/02 , A61K39/12 , A61K48/00 , C07K14/705 , C07K16/00 , C07K16/28 , C12N5/0783 , A61K35/26
CPC分类号： C12N5/0636 , A61K35/17 , A61K38/00 , A61K48/00 , A61K2039/505 , A61K2039/5158 , C07K14/705 , C07K14/70521 , C07K14/70532 , C07K16/00 , C07K16/2806 , C07K16/2809 , C07K16/2812 , C07K16/2815 , C07K16/2818 , C07K16/2833 , C07K16/2866 , C07K16/289 , C07K16/2896 , C07K2317/24 , C07K2317/34 , C07K2317/54 , C07K2317/55 , C07K2317/73 , C07K2317/74 , C07K2319/00 , C07K2319/30 , C12N2501/51 , C12N2501/515 , C12N2501/599 , C12N2740/16011 , C12N2795/00011
摘要： Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR)/CD3 complex or the CD2 surface protein. To induce proliferation of an activated population T cells, an accessory molecule on the surface of the T cells, such as CD28, is stimulated with a ligand which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.
摘要翻译：描述了通过激活T细胞群并用结合辅助分子的配体刺激T细胞表面上的辅助分子来诱导T细胞群体增殖的方法。 T细胞增殖发生在没有外源生长因子或附属细胞的情况下。通过刺激T细胞受体（TCR）/ CD3复合物或CD2表面蛋白来完成T细胞活化。为了诱导活化的群体T细胞的增殖，T细胞表面上的辅助分子如CD28被与配合分子结合的配体刺激。通过本发明的方法扩增的T细胞群体可以被遗传转导并用于免疫治疗，或可用于诊断方法。

4. 发明授权

US06723705B1 Tumor cells modified to express B7-2 with increased immunogenicity and uses therefor 失效
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：US06723705B1
公开(公告)日：2004-04-20
申请号：US09206132
申请日：1998-12-07
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： A61K3170
CPC分类号： A01K67/0271 , A01K2217/05 , A01K2217/075 , A01K2267/0331 , A61K38/00 , C07K14/70532 , C07K16/2827 , C07K2319/00 , C07K2319/30 , C12N15/8509
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。

5. 发明授权

US06130316A Fusion proteins of novel CTLA4/CD28 ligands and uses therefore 失效
标题翻译：新型CTLA4 / CD28配体的融合蛋白及其用途
公开(公告)号：US06130316A
公开(公告)日：2000-10-10
申请号：US280757
申请日：1994-07-26
申请人： Gordon J. Freeman , Lee M. Nadler , Gary S. Gray , Edward Greenfield
发明人： Gordon J. Freeman , Lee M. Nadler , Gary S. Gray , Edward Greenfield
IPC分类号： A61K38/00 , C07K14/705 , C07K16/28 , C12N15/85 , C07K19/00 , C07H21/00
CPC分类号： C07K16/2827 , C07K14/70532 , C12N15/8509 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2217/075 , A01K2267/01 , A01K2267/03 , A01K2267/0381 , A61K38/00 , C07K2317/73 , C07K2319/00 , C07K2319/30
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。

6. 发明授权

US07592007B2 Methods of inhibiting T cell proliferation or IL-2 accumulation with CTLA-4 specific antibodies 失效
标题翻译：用CTLA-4特异性抗体抑制T细胞增殖或IL-2积累的方法
公开(公告)号：US07592007B2
公开(公告)日：2009-09-22
申请号：US10732847
申请日：2003-12-09
申请人： John G. Gribben , Gordon J. Freeman , Lee M. Nadler , Paul Rennert , Cindy L. Jellis , Edward Greenfield , Gary S. Gray
发明人： John G. Gribben , Gordon J. Freeman , Lee M. Nadler , Paul Rennert , Cindy L. Jellis , Edward Greenfield , Gary S. Gray
IPC分类号： A61K39/395 , C07K16/28
CPC分类号： C07K14/70521 , A61K38/00 , C07K14/70532 , C07K16/2818 , C07K2317/34
摘要： Isolated ligands which bind a molecule expressed on the surface of T cells and induce antigen specific apoptosis in activated T cells are disclosed. Preferably, the T cell surface molecule is CTLA4 and the ligand is a monoclonal anti-CTLA4 antibody that binds to an epitope of CTLA4 distinct from the binding sites of B7-1 and B7-2. Upon binding of the antibody to CTLA4 on an activated T cell, in the presence of an antigenic signal, antigen specific apoptosis is induced. The invention also describes a novel natural CTLA4 ligand, distinct from B7-1 and B7-2, which mediates induction of apoptosis. Pharmaceutical compositions of anti-CTLA4 antibodies or other isolated CTLA4 ligands which can be administered to subjects to induce T cell apoptosis, thereby clonally deleting antigen specific T cells, such as alloreactive T cells in transplantation situations or autoreactive T cells in autoimmune disorders, are also disclosed. Methods for inducing T cell apoptosis in vitro with an anti-CTLA4 antibody or other ligand of the invention together with an antigen specific signal are also disclosed, e.g., for use in purging alloreactive T cells from donor bone marrow prior to bone marrow transplantation to inhibit graft versus host disease.
摘要翻译：公开了结合在T细胞表面上表达并在活化的T细胞中诱导抗原特异性凋亡的分子的分离的配体。优选地，T细胞表面分子是CTLA4，并且配体是结合与B7-1和B7-2的结合位点不同的CTLA4的表位的单克隆抗CTLA4抗体。当抗体与CTLA4在活化的T细胞上结合时，在抗原信号存在下，诱导抗原特异性凋亡。本发明还描述了一种与介导细胞凋亡诱导的B7-1和B7-2不同的新型天然CTLA4配体。抗CTLA4抗体或其他分离的CTLA4配体的药物组合物也可以被给予受试者诱导T细胞凋亡，从而克隆地删除抗原特异性T细胞，例如移植情况下的同种异体反应性T细胞或自身免疫性疾病中的自身反应性T细胞，披露还公开了用本发明的抗CTLA4抗体或其他配体与抗原特异性信号一起体外诱导T细胞凋亡的方法，例如用于在骨髓移植之前从供体骨髓中清除同种异体反应性T细胞以抑制移植物抗宿主病。

7. 发明授权

US06905680B2 Methods of treating HIV infected subjects 失效
标题翻译：治疗艾滋病毒感染者的方法
公开(公告)号：US06905680B2
公开(公告)日：2005-06-14
申请号：US08592711
申请日：1996-01-26
申请人： Carl H. June , Craig B. Thompson , Gary J. Nabel , Gary S. Gray , Paul D. Rennert
发明人： Carl H. June , Craig B. Thompson , Gary J. Nabel , Gary S. Gray , Paul D. Rennert
IPC分类号： A61K35/14 , A61K35/17 , A61K35/28 , A61K38/00 , A61K38/17 , A61K38/46 , A61K39/00 , A61K39/02 , A61K39/12 , A61K48/00 , C07K14/705 , C07K16/00 , C07K16/28 , C12N5/0783 , A61K35/26
CPC分类号： C12N5/0636 , A61K35/17 , A61K38/00 , A61K39/02 , A61K39/12 , A61K48/00 , A61K2039/505 , A61K2039/507 , A61K2039/5158 , C07K14/705 , C07K14/70521 , C07K14/70532 , C07K16/00 , C07K16/2806 , C07K16/2809 , C07K16/2812 , C07K16/2815 , C07K16/2818 , C07K16/2833 , C07K16/2866 , C07K16/289 , C07K16/2896 , C07K2317/24 , C07K2317/34 , C07K2317/54 , C07K2317/55 , C07K2317/73 , C07K2317/74 , C07K2319/00 , C07K2319/30 , C12N2501/51 , C12N2501/515 , C12N2501/599 , C12N2710/00088 , C12N2740/16011
摘要： Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR)/CD3 complex or the CD2 surface protein. To induce proliferation of an activated population T cells, an accessory molecule on the surface of the T cells, such as CD28, is stimulated with a ligand which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.
摘要翻译：描述了通过激活T细胞群并用结合附属分子的配体刺激T细胞表面上的辅助分子来诱导T细胞群体增殖的方法。 T细胞增殖发生在没有外源生长因子或附属细胞的情况下。通过刺激T细胞受体（TCR）/ CD3复合物或CD2表面蛋白来完成T细胞活化。为了诱导活化的群体T细胞的增殖，T细胞表面上的辅助分子如CD28被与配合分子结合的配体刺激。通过本发明的方法扩增的T细胞群体可以被遗传转导并用于免疫治疗，或可用于诊断方法。

8. 发明授权

US06887466B2 Methods for selectively stimulating proliferation of T cells 失效
公开(公告)号：US06887466B2
公开(公告)日：2005-05-03
申请号：US09350202
申请日：1999-07-08
申请人： Carl H. June , Craig B. Thompson , Gary J. Nabel , Gary S. Gray , Paul D. Rennert
发明人： Carl H. June , Craig B. Thompson , Gary J. Nabel , Gary S. Gray , Paul D. Rennert
IPC分类号： A61K35/14 , A61K35/17 , A61K35/28 , A61K38/00 , A61K38/17 , A61K38/46 , A61K39/00 , A61K39/02 , A61K39/12 , A61K48/00 , C07K14/705 , C07K16/00 , C07K16/28 , C12N5/0783 , A61K35/26
CPC分类号： C12N5/0636 , A61K35/17 , A61K38/00 , A61K48/00 , A61K2039/505 , A61K2039/5158 , C07K14/705 , C07K14/70521 , C07K14/70532 , C07K16/00 , C07K16/2806 , C07K16/2809 , C07K16/2812 , C07K16/2815 , C07K16/2818 , C07K16/2833 , C07K16/2866 , C07K16/289 , C07K16/2896 , C07K2317/24 , C07K2317/34 , C07K2317/54 , C07K2317/55 , C07K2317/73 , C07K2317/74 , C07K2319/00 , C07K2319/30 , C12N2501/51 , C12N2501/515 , C12N2501/599 , C12N2740/16011 , C12N2795/00011
摘要： Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR)/CD3 complex or the CD2 surface protein. To induce proliferation of an activated population T cells, an accessory molecule on the surface of the T cells, such as CD28, is stimulated with a ligand which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.

9. 发明授权

US06534055B1 Methods for selectively stimulating proliferation of T cells 失效
标题翻译：选择性刺激T细胞增殖的方法
公开(公告)号：US06534055B1
公开(公告)日：2003-03-18
申请号：US08435816
申请日：1995-05-04
申请人： Carl H. June , Craig B. Thompson , Gary J. Nabel , Gary S. Gray , Paul D. Rennert
发明人： Carl H. June , Craig B. Thompson , Gary J. Nabel , Gary S. Gray , Paul D. Rennert
IPC分类号： A61K3514
CPC分类号： C12N5/0636 , A61K48/00 , A61K2039/505 , A61K2039/5158 , C07K14/705 , C07K14/70521 , C07K14/70532 , C07K2319/00 , C07K2319/30 , C12N2501/51 , C12N2501/515 , C12N2501/599 , C12N2740/16011 , C12N2795/14111
摘要： Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR)/CD3 complex or the CD2 surface protein. To induce proliferation of an activated population T cells, an accessory molecule on the surface of the T cells, such as CD28, is stimulated with a ligand which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.
摘要翻译：描述了通过激活T细胞群并用结合附属分子的配体刺激T细胞表面上的辅助分子来诱导T细胞群体增殖的方法。 T细胞增殖发生在没有外源生长因子或附属细胞的情况下。通过刺激T细胞受体（TCR）/ CD3复合物或CD2表面蛋白来完成T细胞活化。为了诱导活化的群体T细胞的增殖，T细胞表面上的辅助分子如CD28被与配合分子结合的配体刺激。通过本发明的方法扩增的T细胞群体可以被遗传转导并用于免疫治疗，或可用于诊断方法。

10. 发明授权

US5858358A Methods for selectively stimulating proliferation of T cells 失效
标题翻译：选择性刺激T细胞增殖的方法
公开(公告)号：US5858358A
公开(公告)日：1999-01-12
申请号：US253751
申请日：1994-06-03
申请人： Carl H. June , Craig B. Thompson , Gary J. Nabel , Gary S. Gray , Paul D. Rennert , Gordon J. Freeman
发明人： Carl H. June , Craig B. Thompson , Gary J. Nabel , Gary S. Gray , Paul D. Rennert , Gordon J. Freeman
IPC分类号： C07K14/705 , C07K16/28 , A61K39/395 , C07K16/00
CPC分类号： C07K14/705 , C07K14/70521 , C07K16/2806 , C07K16/2809 , C07K16/2812 , C07K16/2815 , C07K16/2818 , C07K16/2833 , C07K16/2866 , C07K16/289 , C07K16/2896 , A61K2039/505 , A61K2039/5158 , C07K2317/24 , C07K2317/34 , C07K2317/54 , C07K2317/74 , C07K2319/30 , C12N2501/51 , C12N2501/515 , C12N2501/599
摘要： Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR)/CD3 complex or the CD2 surface protein. To induce proliferation of an activated population T cells, an accessory molecule on the surface of the T cells, such as CD28 or CD9, is stimulated with a ligand which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.
摘要翻译：描述了通过激活T细胞群并用结合附属分子的配体刺激T细胞表面上的辅助分子来诱导T细胞群体增殖的方法。 T细胞增殖发生在没有外源生长因子或附属细胞的情况下。通过刺激T细胞受体（TCR）/ CD3复合物或CD2表面蛋白来完成T细胞活化。为了诱导活化的群体T细胞的增殖，T细胞表面上的辅助分子例如CD28或CD9被与辅助分子结合的配体刺激。通过本发明的方法扩增的T细胞群体可以被遗传转导并用于免疫治疗，或可用于诊断方法。

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