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1. 发明申请

WO2012012531A2 COMPOSITIONS AND METHODS FEATURING IL-6 AND IL-21 ANTAGONISTS 审中-公开
标题翻译：具有IL-6和IL-21拮抗剂的组合物和方法
公开(公告)号：WO2012012531A2
公开(公告)日：2012-01-26
申请号：PCT/US2011044681
申请日：2011-07-20
申请人： BETH ISRAEL HOSPITAL , STROM TERRY , KOULMANDA MARIA
发明人： STROM TERRY , KOULMANDA MARIA
IPC分类号： C07K16/24 , A61K39/395 , A61P37/00 , C07K14/54 , C07K16/28 , C07K16/46 , C12N15/24
CPC分类号： A61K39/3955 , A61K38/20 , A61K45/06 , C07K14/54 , C07K16/248 , C07K16/468 , C07K2317/76 , C07K2319/30 , A61K2300/00
摘要： The present invention features compositions for inhibiting both the IL-6 and the IL-21 pathways and methods of making and using such compositions. Our work to date indicates the importance of the redundancy of IL-6 and IL-21 to perform certain crucial functions. The pathways can be inhibited by inhibiting the ligands (i.e., IL-6 and IL-21) and/or their respective receptors (i.e., the IL-6 receptor and IL-21 receptor). Alternatively, or in addition, upstream and downstream effectors in the IL-6 and IL-21 pathways can be blocked. The agents used can be antibody or antibody-based proteins or peptides including circulating receptors, optionally coupled to an immunoglobulin or a portion thereof (e.g., the Fc region). Also provided are methods for using the compositions, for example, in organ transplantation, tissue grafting, or autoimmune disorders.
摘要翻译：本发明的特征在于抑制IL-6和IL-21途径的组合物以及制备和使用这种组合物的方法。迄今为止，我们的工作表明了IL-6和IL-21冗余在执行某些关键功能方面的重要性。通过抑制配体（即IL-6和IL-21）和/或它们各自的受体（即IL-6受体和IL-21受体）可以抑制途径。或者或另外，可阻断IL-6和IL-21途径中的上游和下游效应子。所使用的药剂可以是基于抗体或基于抗体的蛋白质或包括循环受体的肽，任选偶联至免疫球蛋白或其部分（例如Fc区）。还提供了使用该组合物的方法，例如在器官移植，组织移植或自身免疫性疾病中。

2. 发明申请

WO2006020849A2 MUTANT INTERLEUKIN-15 POLYPEPTIDES 审中-公开
标题翻译：突变的白细胞介素-15多肽
公开(公告)号：WO2006020849A2
公开(公告)日：2006-02-23
申请号：PCT/US2005/028713
申请日：2005-08-11
申请人： BETH ISRAEL DEACONESS MEDICAL CENTER, INC. , F. HOFFMANN-LA ROCHE AG , ZHENG, Xin, Xiao , STROM, Terry, B. , MOLL, Thomas
发明人： ZHENG, Xin, Xiao , STROM, Terry, B. , MOLL, Thomas
IPC分类号： C07K14/54 , C07H21/04 , C12P21/04
CPC分类号： A61K38/2086 , A61K39/39541 , C07K14/5443 , C07K2319/30 , A61K2300/00
摘要： Mutant IL-15 polyp eptides and compositions including the polypeptides are described herein. In various embodiments, a mutant IL-15 polypeptide is joined to a heterologous polypeptide. Also described herein are uses of the mutant IL-15 polypeptides, e.g., in suppressing immune responses.
摘要翻译：本文描述了突变的IL-15多肽和包含该多肽的组合物。在各种实施方案中，将突变IL-15多肽连接至异源多肽。本文还描述了突变IL-15多肽在例如抑制免疫应答中的用途。

3. 发明申请

WO2005033144A2 TIM-3 LIGANDS AND METHODS THEREOF 审中-公开
标题翻译： TIM-3配体及其方法
公开(公告)号：WO2005033144A2
公开(公告)日：2005-04-14
申请号：PCT/US2004/032749
申请日：2004-10-04
申请人： BRIGHAM AND WOMEN'S HOSPITAL , BETH ISRAEL DEACONESS MEDICAL CENTER , KUCHROO, Vijay, K. , STROM, Terry , CHA, Eugene, K. , CHAKRAVARTI, Sumone , SABATOS, Catherine , ZHU, Chen , ZHENG, Xin, Xiao , SANCHEZ-FUEGO, Alberto
发明人： KUCHROO, Vijay, K. , STROM, Terry , CHA, Eugene, K. , CHAKRAVARTI, Sumone , SABATOS, Catherine , ZHU, Chen , ZHENG, Xin, Xiao , SANCHEZ-FUEGO, Alberto
IPC分类号： C07K16/00
CPC分类号： C07K16/18 , C07K14/4713 , C07K14/70503 , C07K16/28 , C07K2319/30 , G01N33/505
摘要： The invention relates to isolated polypeptides and acids encoding polypeptides which comprise a tim-3 IgV domain and a tim-3 intracellular domain, wherein the polypeptides do not comprise a tim-3 mucin domain or a tim-3 transmembrane domain. In addition, the invention relates to methods of modulating immune responses in a subject, comprising administering to the subject a therapeutically effective amount of an agent that modulates tim-3 activity. Immune responses include, but are not limited to, immune tolerance, transplantation tolerance, Th1 responses and Th2 responses.
摘要翻译：本发明涉及分离的多肽和编码多肽的酸，其包含tim-3 IgV结构域和tim-3细胞内结构域，其中所述多肽不包含tim-3粘蛋白结构域或tim-3跨膜结构域。此外，本发明涉及调节受试者中的免疫应答的方法，包括向受试者施用治疗有效量的调节tim-3活性的药剂。免疫反应包括但不限于免疫耐受性，移植耐受性，Th1应答和Th2应答。

4. 发明申请

WO2003087320A3 ANTAGONISTS OF IL-21 AND MODULATION OF IL-21-MEDIATED T CELL RESPONSES 审中-公开
公开(公告)号：WO2003087320A3
公开(公告)日：2003-10-23
申请号：PCT/US2003/010736
申请日：2003-04-08
申请人： BETH ISRAEL DEACONESS MEDICAL CENTER, INC. , MOLL, Thomas , STROM, Terry, B. , ZHENG, Xin, Xiao
发明人： MOLL, Thomas , STROM, Terry, B. , ZHENG, Xin, Xiao
IPC分类号： C12N5/10
摘要： The present invention is based, in part, on the creation of molecules that antagonize the receptor for interleukin-21 (IL-21). The antagonist can be, for example, a mutant of IL-21 (mIL-21). Moreover, the mIL-21 polypeptide can be joined to ( e.g ., joined by way of a peptide bond to) a heterologous polypeptide ( i.e ., a non-IL-21 polypeptide), such as an Fc region of an immunoglobulin molecule ("mIL-21/Fc"). Such antagonists have been shown to inhibit cellular proliferation in response to either anti-CD3 monoclonal antibodies or anti-CD3 antibodies applied together with IL-2, IL-15, or either cytokine (IL-2 or IL-15) together with IL-21 (these studies and their significance are described further below). Accordingly, the present invention features polypeptides that include a mutant IL-21 sequence, nucleic acids encoding those mutants, compositions containing them, and methods of using them in a variety of diagnostic, prognostic, and treatment regimes.

5. 发明申请

WO2003087320A2 ANTAGONISTS OF IL-21 AND MODULATION OF IL-21-MEDIATED T CELL RESPONSES 审中-公开
标题翻译： IL-21的拮抗剂和IL-21介导的T细胞应答的调节
公开(公告)号：WO2003087320A2
公开(公告)日：2003-10-23
申请号：PCT/US2003/010736
申请日：2003-04-08
申请人： BETH ISRAEL DEACONESS MEDICAL CENTER, INC. , MOLL, Thomas , STROM, Terry, B. , ZHENG, Xin, Xiao
发明人： MOLL, Thomas , STROM, Terry, B. , ZHENG, Xin, Xiao
IPC分类号： C12N
CPC分类号： C07K14/54 , A61K38/00 , A61K48/00 , A61K2039/505 , C07K14/5443 , C07K14/55 , C07K14/7155 , C07K2319/00
摘要： The present invention is based, in part, on the creation of molecules that antagonize the receptor for interleukin-21 (IL-21). The antagonist can be, for example, a mutant of IL-21 (mIL-21). Moreover, the mIL-21 polypeptide can be joined to ( e.g ., joined by way of a peptide bond to) a heterologous polypeptide ( i.e ., a non-IL-21 polypeptide), such as an Fc region of an immunoglobulin molecule ("mIL-21/Fc"). Such antagonists have been shown to inhibit cellular proliferation in response to either anti-CD3 monoclonal antibodies or anti-CD3 antibodies applied together with IL-2, IL-15, or either cytokine (IL-2 or IL-15) together with IL-21 (these studies and their significance are described further below). Accordingly, the present invention features polypeptides that include a mutant IL-21 sequence, nucleic acids encoding those mutants, compositions containing them, and methods of using them in a variety of diagnostic, prognostic, and treatment regimes.
摘要翻译：本发明部分地基于产生拮抗白细胞介素-21（IL-21）受体的分子。拮抗剂可以是例如IL-21（mIL-21）的突变体。此外，mIL-21多肽可以连接到（例如，通过肽键连接）异源多肽（即非IL-21多肽），例如免疫球蛋白分子的Fc区（“mIL -21 / FC“）。已经显示这样的拮抗剂响应于与IL-2，IL-15或细胞因子（IL-2或IL-15）一起应用的抗CD3单克隆抗体或抗CD3抗体与IL- 21（这些研究及其意义在下面进一步描述）。因此，本发明的特征在于包括突变型IL-21序列的多肽，编码这些突变体的核酸，含有它们的组合物，以及在各种诊断，预后和治疗方案中使用它们的方法。

6. 发明申请

WO0181916A3 METHODS OF EVALUATING TRANSPLANT REJECTION 审中-公开
标题翻译：评估运输拒收的方法
公开(公告)号：WO0181916A3
公开(公告)日：2003-08-21
申请号：PCT/US0113014
申请日：2001-04-23
申请人： BETH ISRAEL HOSPITAL , CORNELL RES FOUNDATION INC , MA NALLI , STROM TERRY , SOARES MIGUEL C , FERRAN CHRISTINE , SUTHANTHIRAN MANIKKAM , VASCONCELLOS LAURO , AVIHINGSANON YINGYOS
发明人： MA NALLI , STROM TERRY , SOARES MIGUEL C , FERRAN CHRISTINE , SUTHANTHIRAN MANIKKAM , VASCONCELLOS LAURO , AVIHINGSANON YINGYOS
IPC分类号： C12Q1/68 , G01N33/68
CPC分类号： C12Q1/6809 , C12Q1/6876 , C12Q1/6883 , C12Q1/6895 , C12Q2600/118 , C12Q2600/158 , G01N33/6893 , G01N2800/245
摘要： The invention relates to methods of evaluating transplant rejection in a host comprising determining a heightened magnitude of gene expression of genes in rejection-associated gene clusters. The disclosed gene clusters include genes that are substantially co-expressed with cytotoxic lymphocyte pro-apoptotic genes, cytoprotective genes and several other cytokine and immune cell genes.
摘要翻译：本发明涉及评估宿主中移植排斥反应的方法，其包括确定排斥相关基因簇中基因的基因表达的增加的程度。所公开的基因簇包括与细胞毒性淋巴细胞促凋亡基因，细胞保护基因和若干其它细胞因子和免疫细胞基因基本共表达的基因。

7. 发明申请

WO1997044058A1 COMPOUNDS THAT INHIBIT THE BINDING OF RAF-1 OR 14-3-3 PROTEINS TO THE BETA CHAIN OF IL-2 RECEPTOR, AND PHARMACEUTICAL COMPOSITIONS CONTAINING SAME 审中-公开
标题翻译：抑制RAF-1或14-3-3蛋白与IL-2受体的β链和含有其的药物组合物的结合的化合物
公开(公告)号：WO1997044058A1
公开(公告)日：1997-11-27
申请号：PCT/US1997008542
申请日：1997-05-22
申请人： APPLIED RESEARCH SYSTEMS ARS HOLDING N.V. , STROM, Terry , MASLINSKI, Wlodzimierz
发明人： APPLIED RESEARCH SYSTEMS ARS HOLDING N.V.
IPC分类号： A61K38/20
CPC分类号： C12N9/1205 , A61K38/00 , C07K14/4705 , C07K14/7155 , C12Q1/485 , G01N33/6869 , G01N2500/04 , Y10S424/81
摘要： The invention relates to compounds, such as proteins, peptides and organic compounds, capable of blocking or inhibiting the binding interaction of Raf-1 or 14-3-3 proteins to the beta chain of IL-2, and pharmaceutical compositions containing such compounds. In vitro assays for isolating, identifying and characterizing such compound capable of inhibiting interaction of Raf-1 or 14-3-3 proteins to IL-2 beta are also provided.
摘要翻译：本发明涉及能够阻断或抑制Raf-1或14-3-3蛋白与IL-2的β链的结合相互作用的化合物，例如蛋白质，肽和有机化合物，以及含有这些化合物的药物组合物。还提供了用于分离，鉴定和表征能够抑制Raf-1或14-3-3蛋白与IL-2β的相互作用的化合物的体外测定。

8. 发明申请

WO2008033890A3 COMPOSITIONS CONTAINING ALPHA-1-ANTITRYPSIN AND METHODS FOR USE 审中-公开
公开(公告)号：WO2008033890A3
公开(公告)日：2008-03-20
申请号：PCT/US2007/078231
申请日：2007-09-12
申请人： BETH ISRAEL DEACONESS MEDICAL CENTER, INC. , THE GENERAL HOSPITAL CORPORATION , FLIER, Jeffrey , KOULMANDA, Maria , STROM, Terry B.
发明人： FLIER, Jeffrey , KOULMANDA, Maria , STROM, Terry B.
IPC分类号： A01N37/18 , A61K38/00
摘要： Methods and compositions for treating patients (e.g., patients who are insulin resistant, patients who have diabetes, or are at risk for developing diabetes) are disclosed herein. The methods can include administration of an a1 antitrypsin (AAT) polypeptide or an agent, such as a nucleic acid molecule or organic compound, that promotes the expression or activity of a1-antitrypsin.

9. 发明申请

WO2005033144A3 TIM-3 POLYPEPTIDES 审中-公开
标题翻译： TIM-3多糖
公开(公告)号：WO2005033144A3
公开(公告)日：2005-06-16
申请号：PCT/US2004032749
申请日：2004-10-04
申请人： BRIGHAM & WOMENS HOSPITAL , BETH ISRAEL HOSPITAL , KUCHROO VIJAY K , STROM TERRY , CHA EUGENE K , CHAKRAVARTI SUMONE , SABATOS CATHERINE , ZHU CHEN , ZHENG XIN XIAO , SANCHEZ-FUEGO ALBERTO
发明人： KUCHROO VIJAY K , STROM TERRY , CHA EUGENE K , CHAKRAVARTI SUMONE , SABATOS CATHERINE , ZHU CHEN , ZHENG XIN XIAO , SANCHEZ-FUEGO ALBERTO
IPC分类号： C07H21/04 , C07K14/47 , C07K14/705 , C07K16/18 , C07K16/28 , C12N5/06 , A61K38/17 , A61P37/02 , C12N15/12
CPC分类号： C07K16/18 , C07K14/4713 , C07K14/70503 , C07K16/28 , C07K2319/30 , G01N33/505
摘要： The invention relates to isolated polypeptides and acids encoding polypeptides which comprise a tim-3 IgV domain and a tim-3 intracellular domain, wherein the polypeptides do not comprise a tim-3 mucin domain or a tim-3 transmembrane domain. In addition, the invention relates to methods of modulating immune responses in a subject, comprising administering to the subject a therapeutically effective amount of an agent that modulates tim-3 activity. Immune responses include, but are not limited to, immune tolerance, transplantation tolerance, Th1 responses and Th2 responses.
摘要翻译：本发明涉及分离的多肽和编码多肽的酸，其包含tim-3 IgV结构域和tim-3细胞内结构域，其中所述多肽不包含tim-3粘蛋白结构域或tim-3跨膜结构域。此外，本发明涉及调节受试者中的免疫应答的方法，包括向受试者施用治疗有效量的调节tim-3活性的药剂。免疫反应包括但不限于免疫耐受性，移植耐受性，Th1应答和Th2应答。

10. 发明申请

WO9922766A3 USE OF ANTI-IL-12 ANTIBODIES IN TRANSPLANTATION REJECTION 审中-公开
标题翻译：抗-IL-12抗体在移植排斥反应中的应用
公开(公告)号：WO9922766A3
公开(公告)日：1999-08-05
申请号：PCT/US9823264
申请日：1998-10-30
申请人： STROM TERRY , LI XIAN CHANG , ZAND MARTIN , ZHENG XIN XIAO
发明人： STROM TERRY , LI XIAN CHANG , ZAND MARTIN , ZHENG XIN XIAO
IPC分类号： A61K39/395 , A61P37/06 , C07K16/24 , A61K31/71 , A61K38/13
CPC分类号： C07K16/244 , A61K39/395 , A61K2039/505 , A61K38/13 , A61K31/17 , A61K2300/00
摘要： Methods are disclosed for reducing or ameliorating chronic rejection of a transplanted tissue by administration of an anti-IL-12 antibody, alone or in combination with other beneficial therapeutic agents.
摘要翻译：公开了通过单独或与其他有益治疗剂联合施用抗-IL-12抗体来减少或缓解移植组织的慢性排斥的方法。

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