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1. 发明申请

WO2015120138A3 AGENTS THAT MODULATE RGMb-NEOGENIN-BMP SIGNALING AND METHODS OF USE THEREOF 审中-公开
标题翻译：调节RGMb-NEOGENIN-BMP信号传导的药剂及其使用方法
公开(公告)号：WO2015120138A3
公开(公告)日：2015-11-12
申请号：PCT/US2015014595
申请日：2015-02-05
申请人： DANA FARBER CANCER INST INC , BOSTON CHILDREN S HOSPITAL
发明人： DEKRUYFF ROSEMARIE , FREEMAN GORDON J
IPC分类号： G01N33/53
CPC分类号： C07K16/2863 , A61K31/7105 , A61K39/3955 , A61K45/06 , A61K2039/505 , C07K16/22 , C07K16/2803 , C07K2317/565 , C07K2317/76 , C12N15/1138 , C12N15/115 , C12N2310/11 , C12N2310/14 , C12N2310/16 , C12N2320/31 , G01N33/566 , G01N2333/715 , G01N2500/04
摘要： The present invention relates to compositions and methods for the modulation RGMb-Neogenin-BMP signaling.
摘要翻译：本发明涉及用于调节RGMb-Neogenin-BMP信号传导的组合物和方法。

2. 发明申请

WO9640915A3 NOVEL CTLA4/CD28 LIGANDS AND USES THEREFOR 审中-公开
标题翻译：新CTLA4 / CD28配对及其用途
公开(公告)号：WO9640915A3
公开(公告)日：1997-01-23
申请号：PCT/US9609052
申请日：1996-06-06
申请人： DANA FARBER CANCER INST INC , REPLIGEN CORP
发明人： FREEMAN GORDON J , NADLER LEE M , GRAY GARY S
IPC分类号： C12N15/09 , A61K31/00 , A61K38/00 , A61K39/395 , A61P37/00 , A61P37/08 , C07K14/705 , C07K16/28 , C07K19/00 , C12N15/12 , C12N15/85 , A61K38/17 , A61K47/48 , C07K17/14 , C12N5/10 , C12N15/62 , G01N33/545
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 B7-2 fusion protein, comprising a first peptide having a B7-2 activity and a second peptide corresponding to a moiety that alters the solubility, binding affinity or valency of the first peptide, such as an immunoglobulin constant region. Preferably, the nucleic acid is a DNA molecule comprising at least a portion of a nucleotide sequence shown in Figure 8, SEQ ID NO:1 or Figure 14, SEQ ID NO:22. 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.

3. 发明申请

WO0114557B1 PD-1, A RECEPTOR FOR B7-4, AND USES THEREFOR 审中-公开
标题翻译： PD-1，B7-4的受体及其用途
公开(公告)号：WO0114557B1
公开(公告)日：2001-04-19
申请号：PCT/US0023347
申请日：2000-08-23
申请人： DANA FARBER CANCER INST INC , GENETICS INST
发明人： WOOD CLIVE , FREEMAN GORDON J
IPC分类号： G01N33/50 , A61K38/00 , A61K39/00 , A61K39/395 , A61K45/00 , A61K45/06 , A61P1/16 , A61P3/10 , A61P9/00 , A61P9/10 , A61P15/06 , A61P19/02 , A61P21/04 , A61P25/00 , A61P25/28 , A61P29/00 , A61P31/06 , A61P31/12 , A61P31/16 , A61P31/18 , A61P31/20 , A61P31/22 , A61P33/06 , A61P33/12 , A61P35/00 , A61P37/02 , A61P37/04 , A61P37/06 , A61P37/08 , A61P41/00 , C07K14/705 , C07K16/28 , C12N15/09 , C12N15/12 , C12Q1/02 , G01N33/15 , G01N33/566 , A61K38/17
CPC分类号： C07K14/70532 , A61K38/00 , A61K39/00 , A61K39/395 , A61K45/06 , A61K2039/55516 , C07K14/70503 , C07K16/2803 , C07K16/2827 , C07K2317/21 , C07K2317/622 , C07K2317/73 , C07K2317/74 , C07K2317/76 , C07K2319/00 , C07K2319/30 , G01N2333/70503 , G01N2500/04 , A61K2300/00
摘要： The invention identifies PD-1 as a receptor for B7-4. B7-4 can inhibit immune cell activation upon binding to an inhibitory receptor on an immune cell. Accordingly, the invention provides agents for modulating PD-1, B7-4, and the interaction between B7-4 and PD-1 in order to modulate a costimulatory or an inhibitory signal in an immune cell resulting in modulation of the immune response.
摘要翻译：本发明将PD-1鉴定为B7-4的受体。 B7-4可以在结合免疫细胞上的抑制性受体时抑制免疫细胞活化。因此，本发明提供用于调节PD-1，B7-4以及B7-4和PD-1之间的相互作用的试剂，以调节免疫细胞中的共刺激或抑制性信号，从而导致免疫应答的调节。

4. 发明申请

WO03042402A2 AGENTS THAT MODULATE IMMUNE CELL ACTIVATION AND METHODS OF USE THEREOF 审中-公开
标题翻译：调节免疫细胞活化的试剂及其使用方法
公开(公告)号：WO03042402A2
公开(公告)日：2003-05-22
申请号：PCT/US0236518
申请日：2002-11-12
申请人： DANA FARBER CANCER INST INC , BRIGHAM & WOMENS HOSPITAL
发明人： FREEMAN GORDON J , SHARPE ARLENE H , BUHLMAN JANET , MANDELBROT DIDIER
IPC分类号： A61K38/17 , C07K14/705 , C07K16/28 , C12N15/09 , C12Q1/02 , G01N33/15 , G01N33/50 , G01N33/566 , G01N33/68 , C12Q
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多肽之间的相互作用的试剂，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。

5. 发明申请

WO9523859A3 NOVEL FORMS OF T CELLS COSTIMULATORY MOLECULES AND USES THEREFOR 审中-公开
标题翻译： T细胞的新形式成本分子及其用途
公开(公告)号：WO9523859A3
公开(公告)日：1995-10-05
申请号：PCT/US9502576
申请日：1995-03-02
申请人： BRIGHAM & WOMENS HOSPITAL , DANA FARBER CANCER INST INC , SHARPE ARLENE H , BORRIELLO FRANCESCOPAOLO , FREEMAN GORDON J , NADLER LEE M
发明人： SHARPE ARLENE H , BORRIELLO FRANCESCOPAOLO , FREEMAN GORDON J , NADLER LEE M
IPC分类号： C12N15/09 , C07K14/47 , C07K14/705 , C07K14/725 , C07K16/18 , C12N5/10 , C12N15/12 , C12P21/02 , C12P21/08 , C12R1/91 , C07K16/28
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-occuring 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. 00000
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。 00000

6. 发明申请

WO03063792A8 COMPOSITIONS AND METHODS RELATED TO TIM-3, A TH1-SPECIFIC CELL SURFACE MOLECULE 审中-公开
标题翻译：与TIM-3相关的组成和方法，TH1特异性细胞表面分子
公开(公告)号：WO03063792A8
公开(公告)日：2003-10-16
申请号：PCT/US0302919
申请日：2003-01-30
申请人： BRIGHAM & WOMENS HOSPITAL , DANA FARBER CANCER INST INC
发明人： KUCHROO VIJAY K , MONNEY LAURENT , GREEFIELD EDWARD A , GAGLIA JASON L , FREEMAN GORDON J , WALDNER HANSPETER
IPC分类号： C12N15/09 , A61K38/00 , A61K39/395 , A61K45/00 , A61P31/04 , A61P35/00 , A61P43/00 , C07K16/28 , C12N5/06 , C12N15/00 , A61K
CPC分类号： A61K39/3955 , A61K9/0019 , A61K45/06 , A61K2039/505 , C07K16/18 , C07K16/28 , C07K2317/34 , C07K2317/50
摘要： The present invention provides compositions and methods useful for promoting or reducing T-cell trafficking to a target tissue. Also provided are compositions and methods useful for promoting or inhibiting antigen-presenting cell (APC) activation. The invention is related to discovery of functional characteristics of TIM-3, a molecule that is preferentially expressed on the surface of Th1 cells. The methods are useful for treating disorders including cancer, infectious disease, allergy, asthma, and autoimmune disease.
摘要翻译：本发明提供了可用于促进或减少T细胞运送到靶组织的组合物和方法。还提供了可用于促进或抑制抗原呈递细胞（APC）活化的组合物和方法。本发明涉及TIM-3功能特征的发现，TIM-3是优先在Th1细胞表面表达的分子。该方法可用于治疗包括癌症，感染性疾病，变态反应，哮喘和自身免疫性疾病的疾病。

7. 发明申请

WO9821314A3 Method of promoting B-cell proliferation and activation and of modulating the immune system 审中-公开
标题翻译：促进B细胞增殖和激活和调节免疫系统的方法
公开(公告)号：WO9821314A3
公开(公告)日：1998-10-01
申请号：PCT/US9721858
申请日：1997-11-12
申请人： SCHULTZE JOACHIM L , FREEMAN GORDON J , GRIBBEN JOHN G , NADLER LEE M , DANA FARBER CANCER INST INC
发明人： SCHULTZE JOACHIM L , FREEMAN GORDON J , GRIBBEN JOHN G , NADLER LEE M
IPC分类号： A61K38/00 , C12N5/0781 , C12N5/08 , A61K35/14
CPC分类号： C12N5/0635 , A61K38/00 , 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 be expanded up to 1 x 103 to 1 x 104 fold in 2 weeks or 1 x 105 to 1 x 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-1O and TGFβ.

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