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1. 发明申请

US20080166338A1 IL-21 AS A REGULATOR OF IMMUNOGLOBIN PRODUCTION 审中-公开
标题翻译： IL-21作为免疫球蛋白生产的调节剂
公开(公告)号：US20080166338A1
公开(公告)日：2008-07-10
申请号：US11958540
申请日：2007-12-18
申请人： Warren J. Leonard , Katsutoshi Ozaki , Rosanne Spolski , Herbert C. Morse , Peter E. Lipsky , Derry Roopenian
发明人： Warren J. Leonard , Katsutoshi Ozaki , Rosanne Spolski , Herbert C. Morse , Peter E. Lipsky , Derry Roopenian
IPC分类号： A61K39/395 , A61P43/00
CPC分类号： C07K14/7155 , A01K67/0276 , A01K2217/05 , A01K2227/105 , A01K2267/0381 , C07K14/5406 , C12N15/8509
摘要： A transgenic mouse is disclosed herein whose somatic and germ cells comprise a disrupted IL-21 receptor gene, the disruption being sufficient to inhibit the binding of IL-21 to an IL-21 receptor, and a disrupted IL-4 gene, the disruption being sufficient to inhibit the production of IL-4 or the binding of IL-4 to the IL-4 receptor. A mouse homozygous for the disrupted IL-21 receptor gene and homozygous for the disrupted IL-4 gene has diminished B cell function. A method is disclosed for altering a B cell activity. The method includes administering a therapeutically effective amount of an agent that interferes with the interaction of IL-21 with an IL-21 receptor, thereby altering the B cell activity. A method is also disclosed for of treating a subject with Job's disorder or atopic disease. A method is also disclosed for treating or preventing an allergic reaction in a subject. A method is also disclosed for treating a subject with an autoimmune or antibody mediated disorder.
摘要翻译：本文公开了一种转基因小鼠，其体细胞和生殖细胞包含破坏的IL-21受体基因，所述破坏足以抑制IL-21与IL-21受体的结合以及破坏的IL-4基因，所述破坏是足以抑制IL-4的产生或IL-4与IL-4受体的结合。对于破坏的IL-21受体基因纯合的小鼠和破坏的IL-4基因是纯合的，具有减少的B细胞功能。公开了用于改变B细胞活性的方法。该方法包括施用治疗有效量的干扰IL-21与IL-21受体相互作用的试剂，由此改变B细胞活性。还公开了用于治疗患有约瑟病或特应性疾病的受试者的方法。还公开了用于治疗或预防受试者的过敏反应的方法。还公开了用自身免疫或抗体介导的病症治疗受试者的方法。

2. 发明申请

US20080305076A1 METHOD OF INDUCING MEMORY B CELL DEVELOPMENT AND TERMINAL DIFFERENTIATION 有权
标题翻译：诱导记忆B细胞发育和终末分化的方法
公开(公告)号：US20080305076A1
公开(公告)日：2008-12-11
申请号：US12126166
申请日：2008-05-23
申请人： Catherine Rachel Ettinger , Peter E. Lipsky , Warren J. Leonard , Rosanne Spolski , Herbert C. Morse, III
发明人： Catherine Rachel Ettinger , Peter E. Lipsky , Warren J. Leonard , Rosanne Spolski , Herbert C. Morse, III
IPC分类号： A61K38/20 , C12Q1/02 , C40B30/06 , A61K48/00 , A61K31/711 , G01N33/567 , C12N5/06
CPC分类号： G01N33/5052 , A61K35/17 , A61K38/20 , A61K2035/124 , A61K2039/5158 , C12N5/0635 , C12N2501/052 , C12N2501/23 , C12N2501/50 , C12N2501/52 , G01N2333/54
摘要： A method is disclosed herein for inducing differentiation of a B cell progenitor into a memory B cells and/or a plasma cell. The method includes contacting a population of cells including a mature B cell or a B cell progenitor with an effective amount of IL-21, and isolating memory B cells or plasma cells. In one embodiment, the B cell progenitor is an immature B cell. A method is also disclosed for enhancing an immune response. The method includes contacting a population of cells including a B cell progenitor with an effective amount of IL-21, and isolating memory B cells or plasma cells. The memory B cells and/or the plasma cell are then introduced into the subject to enhance the immune response. A method is also disclosed for treating a subject with a condition comprising a specific deficiency of at least one of memory B cells and plasma cells. A method is disclosed for identifying an agent with a physiological effect on one or more of a memory B cell and a plasma cell differentiation. A method is also disclosed for identifying agents that inhibit an activity of IL-21. Methods are also disclosed for inducing apoptosis of a B cell and for decreasing the number of B cells. A method is also described for producing a B cell hybridoma.
摘要翻译：本文公开了一种用于诱导B细胞祖细胞分化为记忆B细胞和/或浆细胞的方法。该方法包括使包含成熟B细胞或B细胞祖细胞的细胞群与有效量的IL-21接触，并分离记忆B细胞或浆细胞。在一个实施方案中，B细胞祖细胞是未成熟B细胞。还公开了一种用于增强免疫应答的方法。该方法包括使包含B细胞祖细胞的细胞群与有效量的IL-21接触，并分离记忆B细胞或浆细胞。然后将记忆B细胞和/或浆细胞引入受试者以增强免疫应答。还公开了一种用于治疗患有包含存储B细胞和浆细胞中的至少一种的特定缺陷的病症的受试者的方法。公开了用于鉴定对存储B细胞和浆细胞分化中的一种或多种具有生理作用的药剂的方法。还公开了用于鉴定抑制IL-21活性的试剂的方法。还公开了诱导B细胞凋亡和减少B细胞数量的方法。还描述了用于产生B细胞杂交瘤的方法。

3. 发明授权

US07378276B2 Method of inducing memory B cell development and terminal differentiation 有权
标题翻译：诱导记忆B细胞发育和终末分化的方法
公开(公告)号：US07378276B2
公开(公告)日：2008-05-27
申请号：US11197221
申请日：2005-08-03
申请人： Catherine Rachel Ettinger , Peter E. Lipsky , Warren J. Leonard , Rosanne Spolski , Herbert C. Morse, III
发明人： Catherine Rachel Ettinger , Peter E. Lipsky , Warren J. Leonard , Rosanne Spolski , Herbert C. Morse, III
IPC分类号： C12N5/02 , C12N5/08 , A01N37/18 , C07K1/00
CPC分类号： G01N33/5052 , A61K35/17 , A61K38/20 , A61K2035/124 , A61K2039/5158 , C12N5/0635 , C12N2501/052 , C12N2501/23 , C12N2501/50 , C12N2501/52 , G01N2333/54
摘要： A method is disclosed herein for inducing differentiation of a B cell progenitor into a memory B cells and/or a plasma cell. The method includes contacting a population of cells including a mature B cell or a B cell progenitor with an effective amount of IL-21, and isolating memory B cells or plasma cells. In one embodiment, the B cell progenitor is an immature B cell. A method is also disclosed for enhancing an immune response. The method includes contacting a population of cells including a B cell progenitor with an effective amount of IL-21, and isolating memory B cells or plasma cells. The memory B cells and/or the plasma cell are then introduced into the subject to enhance the immune response. A method is also disclosed for treating a subject with a condition comprising a specific deficiency of at least one of memory B cells and plasma cells. A method is disclosed for identifying an agent with a physiological effect on one or more of a memory B cell and a plasma cell differentiation. A method is also disclosed for identifying agents that inhibit an activity of IL-21. Methods are also disclosed for inducing apoptosis of a B cell and for decreasing the number of B cells. A method is also described for producing a B cell hybridoma.
摘要翻译：本文公开了一种用于诱导B细胞祖细胞分化为记忆B细胞和/或浆细胞的方法。该方法包括使包含成熟B细胞或B细胞祖细胞的细胞群与有效量的IL-21接触，并分离记忆B细胞或浆细胞。在一个实施方案中，B细胞祖细胞是未成熟的B细胞。还公开了一种用于增强免疫应答的方法。该方法包括使包含B细胞祖细胞的细胞群与有效量的IL-21接触，并分离记忆B细胞或浆细胞。然后将记忆B细胞和/或浆细胞引入受试者以增强免疫应答。还公开了一种用于治疗患有包含存储B细胞和浆细胞中的至少一种的特定缺陷的病症的受试者的方法。公开了用于鉴定对存储B细胞和浆细胞分化中的一种或多种具有生理作用的药剂的方法。还公开了用于鉴定抑制IL-21活性的试剂的方法。还公开了诱导B细胞凋亡和减少B细胞数量的方法。还描述了用于产生B细胞杂交瘤的方法。

4. 发明授权

US08247228B2 Method of inducing memory B cell development and terminal differentiation 有权
标题翻译：诱导记忆B细胞发育和终末分化的方法
公开(公告)号：US08247228B2
公开(公告)日：2012-08-21
申请号：US12126166
申请日：2008-05-23
申请人： Catherine Rachel Ettinger , Peter E. Lipsky , Warren J. Leonard , Rosanne Spolski , Herbert C. Morse, III
发明人： Catherine Rachel Ettinger , Peter E. Lipsky , Warren J. Leonard , Rosanne Spolski , Herbert C. Morse, III
IPC分类号： C12N5/00 , C12N5/07
CPC分类号： G01N33/5052 , A61K35/17 , A61K38/20 , A61K2035/124 , A61K2039/5158 , C12N5/0635 , C12N2501/052 , C12N2501/23 , C12N2501/50 , C12N2501/52 , G01N2333/54
摘要： The invention provides a method for promoting differentiation of a mature naïve B cell or a B cell progenitor into a memory B cell or a plasma cell. The method comprises (a) contacting a population of cells comprising a mature naïve B cell or a B cell progenitor with an agent that activates at least one of JAK1, JAK3, STAT3, STAT5A or STAT5B; wherein the population of cells optionally is contacted with an antigen, and (b) isolating the memory B cell or plasma cell.
摘要翻译：本发明提供了促进成熟初始B细胞或B细胞祖细胞分化成记忆B细胞或浆细胞的方法。该方法包括（a）使包含成熟初始B细胞或B细胞祖细胞的细胞群与活化JAK1，JAK3，STAT3，STAT5A或STAT5B中的至少一种的药剂接触; 其中细胞群任选地与抗原接触，和（b）分离记忆B细胞或浆细胞。

5. 发明授权

US07993919B2 Method of inducing memory B cell development and terminal differentiation 有权
标题翻译：诱导记忆B细胞发育和终末分化的方法
公开(公告)号：US07993919B2
公开(公告)日：2011-08-09
申请号：US10579988
申请日：2004-11-18
申请人： Warren J. Leonard , Peter Lipsky , Herbert C. Morse, III , Catherine Rachel Ettinger , Rosanne Spolski
发明人： Warren J. Leonard , Peter Lipsky , Herbert C. Morse, III , Catherine Rachel Ettinger , Rosanne Spolski
IPC分类号： C12N5/00 , C12N5/071
CPC分类号： G01N33/5052 , A61K35/17 , A61K38/20 , A61K2035/124 , A61K2039/5158 , C12N5/0635 , C12N2501/052 , C12N2501/23 , C12N2501/50 , C12N2501/52 , G01N2333/54
摘要： A method is disclosed herein for inducing differentiation of a B cell progenitor into a memory B cells and/or a plasma cell. The method includes contacting a population of cells including a mature B cell or a B cell progenitor with an effective amount of IL-21, and isolating memory B cells or plasma cells. In one embodiment, the B cell progenitor is an immature B cell. A method is also disclosed for enhancing an immune response. The method includes contacting a population of cells including a B cell progenitor with an effective amount of IL-21, and isolating memory B cells or plasma cells. The memory B cells arid/or the plasma cell are then introduced into the subject to enhance the immune response. A method is also disclosed for treating a subject with a condition comprising a specific deficiency of at least one of memory B cells and plasma cells. A method is disclosed for identifying an agent with a physiological effect on one or more of a memory B cell and a plasma cell differentiation. A method is also disclosed for identifying agents that inhibit an activity of IL-21.
摘要翻译：本文公开了一种用于诱导B细胞祖细胞分化为记忆B细胞和/或浆细胞的方法。该方法包括使包含成熟B细胞或B细胞祖细胞的细胞群与有效量的IL-21接触，并分离记忆B细胞或浆细胞。在一个实施方案中，B细胞祖细胞是未成熟B细胞。还公开了一种用于增强免疫应答的方法。该方法包括使包含B细胞祖细胞的细胞群与有效量的IL-21接触，并分离记忆B细胞或浆细胞。然后将记忆B细胞和/或浆细胞引入受试者以增强免疫应答。还公开了一种用于治疗患有包含存储B细胞和浆细胞中的至少一种的特定缺陷的病症的受试者的方法。公开了用于鉴定对存储B细胞和浆细胞分化中的一种或多种具有生理作用的药剂的方法。还公开了用于鉴定抑制IL-21活性的试剂的方法。

6. 发明授权

US07332645B2 IL-21 as a regulator of immunoglobin production 有权
标题翻译： IL-21作为免疫球蛋白生产的调节剂
公开(公告)号：US07332645B2
公开(公告)日：2008-02-19
申请号：US11027868
申请日：2004-12-30
申请人： Warren J. Leonard , Katsutoshi Ozaki , Rosanne Spolski
发明人： Warren J. Leonard , Katsutoshi Ozaki , Rosanne Spolski
IPC分类号： A01K67/00 , A01K67/033 , A01K67/027 , C07H21/02 , C07H21/04 , C12N15/00
CPC分类号： C07K14/7155 , A01K67/0276 , A01K2217/05 , A01K2227/105 , A01K2267/0381 , C07K14/5406 , C12N15/8509
摘要： A transgenic mouse is disclosed herein whose somatic and germ cells comprise a disrupted IL-21 receptor gene, the disruption being sufficient to inhibit the binding of IL-21 to an IL-21 receptor, and a disrupted IL-4 gene, the disruption being sufficient to inhibit the production of IL-4 or the binding of IL-4 to the IL-4 receptor. A mouse homozygous for the disrupted IL-21 receptor gene and homozygous for the disrupted IL-4 gene has diminished B cell function. A method is disclosed for altering a B cell activity. The method includes administering a therapeutically effective amount of an agent that interferes with the interaction of IL-21 with an IL-21 receptor, thereby altering the B cell activity. A method is also disclosed for of treating a subject with Job's disorder or atopic disease. A method is also disclosed for treating or preventing an allergic reaction in a subject. A method is also disclosed for treating a subject with an autoimmune or antibody mediated disorder.
摘要翻译：本文公开了一种转基因小鼠，其体细胞和生殖细胞包含破坏的IL-21受体基因，所述破坏足以抑制IL-21与IL-21受体的结合以及破坏的IL-4基因，所述破坏是足以抑制IL-4的产生或IL-4与IL-4受体的结合。对于破坏的IL-21受体基因纯合的小鼠和破坏的IL-4基因是纯合的，具有减少的B细胞功能。公开了用于改变B细胞活性的方法。该方法包括施用治疗有效量的干扰IL-21与IL-21受体相互作用的试剂，由此改变B细胞活性。还公开了用于治疗患有约瑟病或特应性疾病的受试者的方法。还公开了用于治疗或预防受试者的过敏反应的方法。还公开了用自身免疫或抗体介导的病症治疗受试者的方法。

7. 发明授权

US07731953B2 Methods for use of TSLP and agonists and antagonists thereof 有权
标题翻译：使用TSLP及其激动剂及其拮抗剂的方法
公开(公告)号：US07731953B2
公开(公告)日：2010-06-08
申请号：US11762357
申请日：2007-06-13
申请人： Warren J. Leonard , Akhilesh Pandey , Amin Al-Shami , Rosanne Spolski
发明人： Warren J. Leonard , Akhilesh Pandey , Amin Al-Shami , Rosanne Spolski
IPC分类号： A01N63/00 , C12N5/071
CPC分类号： A61K35/17 , A01K67/0276 , A01K2217/075 , A01K2217/15 , A01K2227/105 , A01K2267/0387 , A61K9/0078 , A61K31/7088 , A61K38/00 , A61K41/00 , A61K45/06 , A61K48/00 , A61K2039/505 , C07K14/5418 , C07K16/244 , A61K2300/00
摘要： Methods are disclosed herein for specifically inducing proliferation of CD4+ T cells. The methods are of use in treating immunodeficiencies, such as an immunodeficiency produced by infection with an immunodeficiency virus, such as infection with a human immunodeficiency virus (HIV). The methods include contacting isolated mammalian CD4+ T cells with an effective amount of a thymic stromal derived lymphopoietin (TSLP) polypeptide or a therapeutically effective amount of nucleic acid encoding the TSLP polypeptide, thereby inducing proliferation of the T cells. Methods are also disclosed for treating an IgE mediated disorder, such as asthma. The methods include administering to a subject a therapeutically effective amount of a TSLP antagonist. Transgenic mice are also disclosed herein. The somatic and germ cells of these mice include a disrupted thymic stromal lymphopoietin receptor (TSLP) gene, the disruption being sufficient to inhibit the interaction of TSLP with its receptor, and a disrupted γc gene, the disruption being sufficient to reduce signaling through the γc. The mice exhibit diminished thymic cellularity. Methods of using these mice for drug screening are also disclosed.
摘要翻译：本文公开了特异性诱导CD4 + T细胞增殖的方法。该方法可用于治疗免疫缺陷，例如由免疫缺陷病毒感染产生的免疫缺陷，例如人免疫缺陷病毒（HIV）的感染。所述方法包括使分离的哺乳动物CD4 + T细胞与有效量的胸腺基质衍生的淋巴细胞生成素（TSLP）多肽或治疗有效量的编码TSLP多肽的核酸接触，从而诱导T细胞的增殖。还公开了用于治疗IgE介导的病症如哮喘的方法。所述方法包括向受试者施用治疗有效量的TSLP拮抗剂。本文还公开了转基因小鼠。这些小鼠的体细胞和生殖细胞包括破坏的胸腺基质淋巴细胞生成素受体（TSLP）基因，破坏足以抑制TSLP与其受体的相互作用，以及破坏的γc基因，破坏足以减少通过γc的信号转导。小鼠表现出胸腺细胞减少。还公开了将这些小鼠用于药物筛选的方法。

8. 发明授权

US07402659B2 Thymic stromal lymphopoietin receptor molecules and uses thereof 有权
标题翻译：胸腺基质淋巴细胞生成素受体分子及其用途
公开(公告)号：US07402659B2
公开(公告)日：2008-07-22
申请号：US11052527
申请日：2005-02-07
申请人： Akhilesh Pandey , Katsutoshi Ozaki , Heinz Baumann , Steven D. Levin , Andrew G. Farr , Warren J. Leonard , Harvey F. Lodish
发明人： Akhilesh Pandey , Katsutoshi Ozaki , Heinz Baumann , Steven D. Levin , Andrew G. Farr , Warren J. Leonard , Harvey F. Lodish
IPC分类号： C07K14/475 , C12N15/02 , C12P21/02
CPC分类号： C07K14/7155 , A61K38/00 , C07K2319/30
摘要： The present invention provides Thymic Stromal Lymphopoietin Receptor (TSLPR) polypeptides and nucleic acid molecules encoding the same. The invention also provides selective binding agents, vectors, host cells, and methods for producing TSLPR polypeptides. The invention further provides pharmaceutical compositions and methods for the diagnosis, treatment, amelioration, and/or prevention of diseases, disorders, and conditions associated with TSLPR polypeptides.
摘要翻译：本发明提供了胸腺基质淋巴细胞生成素受体（TSLPR）多肽和编码其的核酸分子。本发明还提供选择性结合剂，载体，宿主细胞和用于产生TSLPR多肽的方法。本发明还提供了用于诊断，治疗，改善和/或预防与TSLPR多肽相关的疾病，病症和病症的药物组合物和方法。

9. 发明授权

US06955895B2 Thymic stromal lymphopoietin receptor molecules and uses thereof 有权
公开(公告)号：US06955895B2
公开(公告)日：2005-10-18
申请号：US09895593
申请日：2001-06-28
申请人： Akhilesh Pandey , Katsutoshi Ozaki , Heinz Baumann , Steven D. Levin , Andrew G. Farr , Warren J. Leonard , Harvey F. Lodish
发明人： Akhilesh Pandey , Katsutoshi Ozaki , Heinz Baumann , Steven D. Levin , Andrew G. Farr , Warren J. Leonard , Harvey F. Lodish
IPC分类号： A61K38/00 , C07K14/715 , C12N15/12 , C07K14/47 , C07K14/705 , C12N5/10 , C12P21/02
CPC分类号： C07K14/7155 , A61K38/00 , C07K2319/30
摘要： The present invention provides Thymic Stromal Lymphopoietin Receptor (TSLPR) polypeptides and nucleic acid molecules encoding the same. The invention also provides selective binding agents, vectors, host cells, and methods for producing TSLPR polypeptides. The invention further provides pharmaceutical compositions and methods for the diagnosis, treatment, amelioration, and/or prevention of diseases, disorders, and conditions associated with TSLPR polypeptides.

10. 发明授权

US07902348B2 Janus family kinases and identification of immune modulators 有权
标题翻译： Janus家族激酶和免疫调节剂的鉴定
公开(公告)号：US07902348B2
公开(公告)日：2011-03-08
申请号：US12354668
申请日：2009-01-15
申请人： John J. O'Shea , Warren J. Leonard , James A. Johnston , Sarah M. Russell , Daniel W. McVicar , Masaru Kawamura
发明人： John J. O'Shea , Warren J. Leonard , James A. Johnston , Sarah M. Russell , Daniel W. McVicar , Masaru Kawamura
IPC分类号： C12N15/52 , C12N15/12
CPC分类号： C12N9/1205 , A61K48/00 , C07K16/40
摘要： An isolated polynucleotide encodes JAK-3 protein. JAK-3 protein is a protein tyrosine kinase having a molecular weight of approximately 125 kDa which has tandem non-identical catalytic domains, lacks SH2 or SH3 domains, and is expressed in NK cells and stimulated or transformed T cells, but not in resting T cells. The protein itself and antibodies to this protein are also presented. Further, methods of identifying therapeutic agents for modulating the immune system make use of the foregoing.
摘要翻译：分离的多核苷酸编码JAK-3蛋白。 JAK-3蛋白是具有约125kDa分子量的蛋白酪氨酸激酶，其具有串联的不相同的催化结构域，缺少SH2或SH3结构域，并且在NK细胞和刺激或转化的T细胞中表达，但不在休息T 细胞。蛋白质本身和对该蛋白质的抗体也被提出。此外，鉴定用于调节免疫系统的治疗剂的方法利用上述。

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