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1. 发明授权

US07501124B2 Methods of inducing T-cell non-responsiveness with anti-gp39 24-31 antibodies 失效
标题翻译：用抗gp39 24-31抗体诱导T细胞非反应性的方法
公开(公告)号：US07501124B2
公开(公告)日：2009-03-10
申请号：US10962033
申请日：2004-10-07
申请人： Randolph J. Noelle , Fiona H. Durie , David C. Parker , Michael C. Appel , Nancy E. Phillips , John P. Mordes , Dale L. Grenier , Aldo A. Rossini
发明人： Randolph J. Noelle , Fiona H. Durie , David C. Parker , Michael C. Appel , Nancy E. Phillips , John P. Mordes , Dale L. Grenier , Aldo A. Rossini
IPC分类号： A61K39/395 , A61K35/26 , A61K35/28 , C07K16/28
CPC分类号： A61K39/001 , A61K35/17 , A61K35/39 , A61K38/00 , A61K2039/505 , C07K14/705 , C07K16/2875 , C07K2317/73 , Y10S514/885 , A61K2300/00
摘要： Methods for inducing T cell tolerance to a tissue or organ graft in a transplant recipeint are disclosed. The methods involve administering to a subject: 1) an allogeneic or xenogeneic cell which expresses donor antigens and which has a ligand on the cell surface which interacts with a receptor on the surface of a recipient T cell which mediates contact-dependent helper effector function; and 2) an antagonist of the receptor which inhibits interaction of the ligand with the receptor. In a preferred embodiment, the allogeneic or xenogeneic cell is a B cell, preferably a resting B cell, and the molecule on the surface of the T cell which mediates contact-dependent helper effector function is gp39. A preferred gp39 antagonist is an anti-gp39 antibody. The allogeneic or xenogeneic cell and the gp39 antagonist are typically administered to a transplant recipient prior to transplantation of the tissue or organ. The methods of the invention can be used to induce T cell tolerance to transplants such as liver, kidney, heart, lung, skin, muscle, neuronal tissue, stomach and intestine. A method for treating diabetes comprising administering to a subject allogeneic or xenogeneic cells expressing donor antigens, a gp39 antagonist and pancreatic islets is also disclosed.
摘要翻译：公开了在移植食谱中诱导T细胞对组织或器官移植物的耐受性的方法。所述方法包括对受试者施用：1）同种异体或异种细胞，其表达供体抗原，并且其在细胞表面上具有与介导接触依赖性辅助效应子功能的受体T细胞表面上的受体相互作用的配体; 和2）抑制配体与受体相互作用的受体拮抗剂。在一个优选的实施方案中，同种异体或异种细胞是B细胞，优选静止的B细胞，并且介导接触依赖性辅助效应子功能的T细胞表面上的分子是gp39。优选的gp39拮抗剂是抗gp39抗体。同种异体或异种细胞和gp39拮抗剂通常在移植组织或器官之前给予移植受体。本发明的方法可用于诱导移植物如肝，肾，心脏，肺，皮肤，肌肉，神经元组织，胃和肠的T细胞耐受性。还公开了一种用于治疗糖尿病的方法，其包括向受试者施用表达供体抗原的同种异体或异种细胞，gp39拮抗剂和胰岛。

2. 发明授权

US5683693A Method for inducing T cell unresponsiveness to a tissue or organ graft with anti-CD40 ligand antibody or soluble CD40 失效
标题翻译：用抗CD40配体抗体或可溶性CD40诱导T细胞对组织或器官移植物无反应的方法
公开(公告)号：US5683693A
公开(公告)日：1997-11-04
申请号：US234987
申请日：1994-04-25
申请人： Randolph J. Noelle , Fiona H. Durie , David C. Parker , Michael C. Appel , Nancy E. Phillips , John P. Mordes , Dale L. Grenier , Aldo A. Rossini
发明人： Randolph J. Noelle , Fiona H. Durie , David C. Parker , Michael C. Appel , Nancy E. Phillips , John P. Mordes , Dale L. Grenier , Aldo A. Rossini
IPC分类号： C12N15/02 , A61K31/00 , A61K35/14 , A61K35/38 , A61K38/00 , A61K38/17 , A61K39/00 , A61K39/395 , A61P3/00 , A61P3/10 , A61P37/00 , A61P37/06 , C07K14/705 , C07K16/28 , C12P21/08 , C12R1/91
CPC分类号： A61K39/001 , A61K35/17 , A61K35/39 , C07K14/705 , C07K16/2875 , A61K2039/505 , A61K38/00 , C07K2317/73 , Y10S514/885
摘要： Methods for inducing T cell unresponsiveness to a tissue or organ graft in a transplant recipeint are disclosed. The methods involve administering to a subject: 1) an allogeneic or xenogeneic cell which expresses donor antigens and which has a ligand on the cell surface which interacts with a receptor on the surface of a recipient T cell which mediates contact-dependent helper effector function; and 2) an antagonist of the receptor which inhibits interaction of the ligand with the receptor. In a preferred embodiment, the allogeneic or xenogeneic cell is a B cell, preferably a resting B cell, and the molecule on the surface of the T cell which mediates contact-dependent helper effector function is gp39. A preferred gp39 antagonist is an anti-gp39 antibody. The allogeneic or xenogeneic cell and the gp39 antagonist are typically administered to a transplant recipient prior to transplantation of the tissue or organ. The methods of the invention can be used to induce T cell unresponsiveness to transplants such as liver, kidney, heart, lung, skin, muscle, neuronal tissue, stomach and intestine. A method for treating diabetes comprising administering to a subject allogeneic or xenogeneic cells expressing donor antigens, a gp39 antagonist and pancreatic islets is also disclosed.
摘要翻译：公开了在移植食谱中诱导T细胞对组织或器官移植物无反应的方法。所述方法包括对受试者施用：1）同种异体或异种细胞，其表达供体抗原，并且其在细胞表面上具有与介导接触依赖性辅助效应子功能的受体T细胞表面上的受体相互作用的配体; 和2）抑制配体与受体相互作用的受体拮抗剂。在一个优选的实施方案中，同种异体或异种细胞是B细胞，优选静止的B细胞，并且介导接触依赖性辅助效应子功能的T细胞表面上的分子是gp39。优选的gp39拮抗剂是抗gp39抗体。同种异体或异种细胞和gp39拮抗剂通常在移植组织或器官之前给予移植受体。本发明的方法可用于诱导T细胞对肝脏，肾脏，心脏，肺，皮肤，肌肉，神经元组织，胃和肠等移植物的反应。还公开了一种用于治疗糖尿病的方法，其包括向受试者施用表达供体抗原的同种异体或异种细胞，gp39拮抗剂和胰岛。

3. 发明授权

US5902585A Methods of inducing T cell unresponsiveness to donor tissue or organ in a recipient with GP39 antagonists 失效
标题翻译：在GP39拮抗剂的受体中诱导T细胞对供体组织或器官的反应性的方法
公开(公告)号：US5902585A
公开(公告)日：1999-05-11
申请号：US906332
申请日：1997-08-05
申请人： Randolph J. Noelle , Fiona H. Durie , David C. Parker , Michael C. Appel , Nancy E. Phillips , John P. Mordes , Dale L. Grenier , Aldo A. Rossini
发明人： Randolph J. Noelle , Fiona H. Durie , David C. Parker , Michael C. Appel , Nancy E. Phillips , John P. Mordes , Dale L. Grenier , Aldo A. Rossini
IPC分类号： C12N15/02 , A61K31/00 , A61K35/14 , A61K35/38 , A61K38/00 , A61K38/17 , A61K39/00 , A61K39/395 , A61P3/00 , A61P3/10 , A61P37/00 , A61P37/06 , C07K14/705 , C07K16/28 , C12P21/08 , C12R1/91 , A61K35/26 , C07K14/435
CPC分类号： A61K39/001 , A61K35/17 , A61K35/39 , C07K14/705 , C07K16/2875 , A61K2039/505 , A61K38/00 , C07K2317/73 , Y10S514/885
摘要： Methods for inducing T cell tolerance to a tissue or organ graft in a transplant recipeint are disclosed. The methods involve administering to a subject: 1) an allogeneic or xenogeneic cell which expresses donor antigens and which has a ligand on the cell surface which interacts with a receptor on the surface of a recipient T cell which mediates contact-dependent helper effector function; and 2) an antagonist of the receptor which inhibits interaction of the ligand with the receptor. In a preferred embodiment, the allogeneic or xenogeneic cell is a B cell, preferably a resting B cell, and the molecule on the surface of the T cell which mediates contact-dependent helper effector function is gp39. A preferred gp39 antagonist is an anti-gp39 antibody. The allogeneic or xenogeneic cell and the gp39 antagonist are typically administered to a transplant recipient prior to transplantation of the tissue or organ. The methods of the invention can be used to induce T cell tolerance to transplants such as liver, kidney, heart, lung, sklin, muscle, neuronal tissue, stomach and intestine. A method for treating diabetes comprising administering to a subject allogeneic or xenogeneic cells expressing donor antigens, a gp39 antagonist and pancreatic islets is also disclosed.
摘要翻译：公开了在移植食谱中诱导T细胞对组织或器官移植物的耐受性的方法。所述方法包括对受试者施用：1）同种异体或异种细胞，其表达供体抗原，并且其在细胞表面上具有与介导接触依赖性辅助效应子功能的受体T细胞表面上的受体相互作用的配体; 和2）抑制配体与受体相互作用的受体拮抗剂。在一个优选的实施方案中，同种异体或异种细胞是B细胞，优选静止的B细胞，并且介导接触依赖性辅助效应子功能的T细胞表面上的分子是gp39。优选的gp39拮抗剂是抗gp39抗体。同种异体或异种细胞和gp39拮抗剂通常在移植组织或器官之前给予移植受体。本发明的方法可用于诱导移植物如肝，肾，心脏，肺，肌肉，肌肉，神经元组织，胃和肠的T细胞耐受性。还公开了一种用于治疗糖尿病的方法，其包括向受试者施用表达供体抗原的同种异体或异种细胞，gp39拮抗剂和胰岛。

4. 发明授权

US5869049A Methods of inducing T cell unresponsiveness to bone marrow with gp39 antagonists 失效
标题翻译：用gp39拮抗剂诱导T细胞对骨髓无反应的方法
公开(公告)号：US5869049A
公开(公告)日：1999-02-09
申请号：US232929
申请日：1994-04-25
申请人： Randolph J. Noelle , Teresa M. Foy , Fiona H. Durie , David C. Parker , Dale L. Greiner , Aldo A. Rossini , John P. Mordes
发明人： Randolph J. Noelle , Teresa M. Foy , Fiona H. Durie , David C. Parker , Dale L. Greiner , Aldo A. Rossini , John P. Mordes
IPC分类号： A61K35/14 , A61K35/28 , A61K38/00 , A61P37/06 , C07K14/705 , C07K16/28 , C07K19/00 , G01N33/68 , A61K39/395 , A61K38/16
CPC分类号： C07K14/70578 , A61K35/28 , C07K16/2875 , C07K19/00 , G01N33/6854 , A61K2039/57 , A61K38/00 , C07K2317/24 , C07K2317/73 , C07K2319/00
摘要： Methods for inducing antigen-specific T cell tolerance are disclosed. The methods involve contacting a T cell with: 1) a cell which presents antigen to the T cell, wherein a ligand on the cell interacts with a receptor on the surface of the T cell which mediates contact-dependent helper effector function; and 2) an antagonist of the receptor on the surface of the T cell which inhibits interaction of the ligand on the antigen presenting cell with the receptor on the T cell. In a preferred embodiment, the cell which presents antigen to the T cell is a B cell and the receptor on the surface of the T cell which mediates contact-dependent helper effector function is gp39. Preferably, the antagonist is an anti-gp39 antibody or a soluble gp39 ligand (e.g., soluble CD40). The methods of the invention can be used to induce T cell tolerance to a soluble antigen or to an allogeneic cell. The methods of the invention can also be used to induce tolerance in cases of bone marrow transplantation and other organ transplants and to inhibit graft-versus-host disease.
摘要翻译：公开了诱导抗原特异性T细胞耐受性的方法。所述方法包括使T细胞接触：1）向T细胞呈递抗原的细胞，其中细胞上的配体与介导接触依赖性辅助效应子功能的T细胞表面上的受体相互作用; 和2）T细胞表面上的受体拮抗剂，其抑制抗原呈递细胞上的配体与T细胞上的受体的相互作用。在优选的实施方案中，向T细胞呈递抗原的细胞是B细胞，介导接触依赖性辅助效应子功能的T细胞表面上的受体是gp39。优选地，拮抗剂是抗gp39抗体或可溶性gp39配体（例如可溶性CD40）。本发明的方法可用于诱导对可溶性抗原或同种异体细胞的T细胞耐受性。本发明的方法还可用于在骨髓移植和其他器官移植的情况下诱导耐受性并抑制移植物抗宿主病。

5. 发明授权

US07722874B2 Methods for reducing T cell responsiveness to an autoantigen with anti-gp39 antibodies and antigen presenting cells 有权
标题翻译：用抗Gp39抗体和抗原呈递细胞降低T细胞对自身抗原反应性的方法
公开(公告)号：US07722874B2
公开(公告)日：2010-05-25
申请号：US09164568
申请日：1998-10-01
申请人： Randolph J. Noelle , Teresa M. Foy , Fiona H. Durie
发明人： Randolph J. Noelle , Teresa M. Foy , Fiona H. Durie
IPC分类号： A61K39/395 , A61K35/26 , A61K35/28
CPC分类号： C07K14/70578 , A61K38/00 , A61K2039/505 , A61K2039/57 , C07K16/2875 , C07K19/00 , C07K2317/24 , C07K2317/73 , C07K2319/00 , G01N33/6854
摘要： Methods for inducing antigen-specific T cell tolerance are disclosed. The methods involve contacting a T cell with: 1) a cell which presents antigen to the T cell, wherein a ligand on the cell interacts with a receptor on the surface of the T cell which mediates contact-dependent helper effector function; and 2) an antagonist of the receptor on the surface of the T cell which inhibits interaction of the ligand on the antigen presenting cell with the receptor on the T cell. In a preferred embodiment, the cell which presents antigen to the T cell is a B cell and the receptor on the surface of the T cell which mediates contact-dependent helper effector function is gp39. Preferably, the antagonist is an anti-gp39 antibody or a soluble gp39 ligand (e.g., soluble CD40). The methods of the invention can be used to induce T cell tolerance to a soluble antigen or to an allogeneic cell. The methods of the invention can also be used to induce tolerance in cases of bone marrow transplantation and other organ transplants and to inhibit graft-versus-host disease.
摘要翻译：公开了诱导抗原特异性T细胞耐受性的方法。所述方法包括使T细胞接触：1）向T细胞呈递抗原的细胞，其中细胞上的配体与介导接触依赖性辅助效应子功能的T细胞表面上的受体相互作用; 和2）T细胞表面上的受体拮抗剂，其抑制抗原呈递细胞上的配体与T细胞上的受体的相互作用。在优选的实施方案中，向T细胞呈递抗原的细胞是B细胞，介导接触依赖性辅助效应子功能的T细胞表面上的受体是gp39。优选地，拮抗剂是抗gp39抗体或可溶性gp39配体（例如可溶性CD40）。本发明的方法可用于诱导对可溶性抗原或同种异体细胞的T细胞耐受性。本发明的方法还可用于在骨髓移植和其他器官移植的情况下诱导耐受性并抑制移植物抗宿主病。

6. 发明授权

US06375950B1 Methods for inducing T cell unresponsiveness to donor tissue or organ in a recipient with gp39 antagonists 有权
标题翻译：用gp39拮抗剂诱导T细胞对受体中供体组织或器官不起反应的方法
公开(公告)号：US06375950B1
公开(公告)日：2002-04-23
申请号：US09227081
申请日：1999-01-05
申请人： Randolph J. Noelle , Fiona H. Durie
发明人： Randolph J. Noelle , Fiona H. Durie
IPC分类号： A61K39395
CPC分类号： A61K39/001 , A61K35/17 , A61K35/39 , A61K38/00 , A61K2039/505 , C07K14/705 , C07K16/2875 , C07K2317/73 , Y10S514/885 , A61K2300/00
摘要： Methods for inducing T cell tolerance to a tissue or organ graft in a transplant recipeint are disclosed. The methods involve administering to a subject: 1) an allogeneic or xenogeneic cell which expresses donor antigens and which has a ligand on the cell surface which interacts with a receptor on the surface of a recipient T cell which mediates contact-dependent helper effector function; and 2) an antagonist of the receptor which inhibits interaction of the ligand with the receptor. In a preferred embodiment, the allogeneic or xenogeneic cell is a B cell, preferably a resting B cell, and the molecule on the surface of the T cell which mediates contact-dependent helper effector function is gp39. A preferred gp39 antagonist is an anti-gp39 antibody. The allogeneic or xenogeneic cell and the gp39 antagonist are typically administered to a transplant recipient prior to transplantation of the tissue or organ. The methods of the invention can be used to induce T cell tolerance to transplants such as liver, kidney, heart, lung, skin, muscle, neuronal tissue, stomach and intestine. A method for treating diabetes comprising administering to a subject allogeneic or xenogeneic cells expressing donor antigens, a gp39 antagonist and pancreatic islets is also disclosed.
摘要翻译：公开了在移植食谱中诱导T细胞对组织或器官移植物的耐受性的方法。所述方法包括对受试者施用：1）同种异体或异种细胞，其表达供体抗原，并且其在细胞表面上具有与介导接触依赖性辅助效应子功能的受体T细胞表面上的受体相互作用的配体; 和2）抑制配体与受体相互作用的受体拮抗剂。在一个优选的实施方案中，同种异体或异种细胞是B细胞，优选静止的B细胞，并且介导接触依赖性辅助效应子功能的T细胞表面上的分子是gp39。优选的gp39拮抗剂是抗gp39抗体。同种异体或异种细胞和gp39拮抗剂通常在移植组织或器官之前给予移植受体。本发明的方法可用于诱导移植物如肝，肾，心脏，肺，皮肤，肌肉，神经元组织，胃和肠的T细胞耐受性。还公开了一种用于治疗糖尿病的方法，其包括向受试者施用表达供体抗原的同种异体或异种细胞，gp39拮抗剂和胰岛。

7. 发明授权

US08501915B2 Regulatory T cell mediator proteins and uses thereof 有权
标题翻译：调节性T细胞介质蛋白及其用途
公开(公告)号：US08501915B2
公开(公告)日：2013-08-06
申请号：US13546098
申请日：2012-07-11
申请人： Randolph J. Noelle , Li Wang
发明人： Randolph J. Noelle , Li Wang
IPC分类号： C07K16/00
CPC分类号： C07K16/2827 , A61K38/00 , A61K2039/505 , C07K14/70596 , C07K2319/00 , C07K2319/30 , G01N33/505 , Y02A50/412 , Y02A50/423
摘要： The present invention relates to novel regulatory T cell proteins. One protein, designated PD-L3, resembles members of the PD-L1 family, and co-stimulates αCD3 proliferation of T cells in vitro. A second, TNF-like, protein has also been identified as being upregulated upon αCD3/αGITR stimulation. This protein has been designated Treg-sTNF. Proteins, antibodies, activated T cells and methods for using the same are disclosed.In particular methods of using these proteins and compounds, preferably antibodies, which bind or modulate (agonize or antagonize) the activity of these proteins, as immune modulators and for the treatment of cancer, autoimmune disease, allergy, infection and inflammatory conditions, e.g. multiple sclerosis is disclosed.
摘要翻译：本发明涉及新型调节性T细胞蛋白。称为PD-L3的一种蛋白质类似于PD-L1家族的成员，并且在体外共同刺激T细胞的αCD3增殖。第二种TNF样蛋白也被鉴定为在αCD3/αGITR刺激下上调。该蛋白质已被命名为Treg-sTNF。公开了蛋白质，抗体，活化的T细胞及其使用方法。特别是使用这些蛋白质和化合物（优选抗体）的方法，其结合或调节（激动或拮抗）这些蛋白质的活性，作为免疫调节剂和用于治疗癌症，自身免疫疾病，变态反应，感染和炎性病症，例如，公开了多发性硬化。

8. 发明申请

US20130136734A1 ANTI-CD154 ANTIBODIES HAVING IMPAIRED FcR BINDING AND/OR COMPLEMENT BINDING PROPERTIES AND RELATED THERAPIES 有权
标题翻译：具有有害FcR结合和/或补体结合特性的抗CD154抗体及相关治疗
公开(公告)号：US20130136734A1
公开(公告)日：2013-05-30
申请号：US13648808
申请日：2012-10-10
申请人： Randolph J. Noelle
发明人： Randolph J. Noelle
IPC分类号： C07K16/18
CPC分类号： C07K16/2875 , A61K2039/505 , C07K16/18 , C07K2317/24 , C07K2317/41 , C07K2317/52 , C07K2317/565 , C07K2317/71 , C07K2317/732
摘要： Improved anti-CD154 antibodies are provided herein which have ablated FcR binding and/or complement binding/activation. The use of these antibodies for inducing tolerance and treating immune diseases including autoimmunity, inflammation and allergic disorders is disclosed herein.
摘要翻译：本文提供了已经消除了FcR结合和/或补体结合/活化的抗CD154抗体。本文公开了这些抗体用于诱导耐受性和治疗包括自身免疫，炎症和过敏性疾病的免疫疾病的用途。

9. 发明授权

US08415154B2 Compositions and methods for producing adaptive regulatory T cells 有权
标题翻译：用于生产适应性调节性T细胞的组合物和方法
公开(公告)号：US08415154B2
公开(公告)日：2013-04-09
申请号：US12601682
申请日：2008-05-29
申请人： Randolph J. Noelle
发明人： Randolph J. Noelle
IPC分类号： C12N5/00
CPC分类号： C12N5/0637 , A61K39/001 , A61K2035/122 , C12N5/0636 , C12N2501/385
摘要： The present invention relates to a method for producing adaptive regulatory T cells from effector T cells by contacting the effector T cells with retinoic acid. Adaptive regulatory T cells produced by this method are Foxp3+, home to the gut, and are refractory to reversion in vivo. As such, such cells find application in the treatment of autoimmune disease and facilitating transplantation tolerance.
摘要翻译：本发明涉及通过使效应T细胞与视黄酸接触来从效应T细胞产生适应性调节性T细胞的方法。通过该方法产生的适应性调节性T细胞是肠道归巢的Foxp3 +，并且在体内不可逆转。因此，这样的细胞可用于治疗自身免疫性疾病并促进移植耐受。

10. 发明授权

US08231872B2 Regulatory T cell mediator proteins and uses thereof 有权
标题翻译：调节性T细胞介质蛋白及其用途
公开(公告)号：US08231872B2
公开(公告)日：2012-07-31
申请号：US12732371
申请日：2010-03-26
申请人： Randolph J. Noelle , Li Wang
发明人： Randolph J. Noelle , Li Wang
IPC分类号： A61K39/395
CPC分类号： C07K16/2827 , A61K38/00 , A61K2039/505 , C07K14/70596 , C07K2319/00 , C07K2319/30 , G01N33/505 , Y02A50/412 , Y02A50/423
摘要： The present invention relates to novel regulatory T cell proteins. One protein, designated PD-L3, resembles members of the PD-L1 family, and co-stimulates αCD3 proliferation of T cells in vitro. A second, TNF-like, protein has also been identified as being upregulated upon αCD3/αGITR stimulation. This protein has been designated Treg-sTNF. Proteins, antibodies, activated T cells and methods for using the same are disclosed.In particular methods of using these proteins and compounds, preferably antibodies, which bind or modulate (agonize or antagonize) the activity of these proteins, as immune modulators and for the treatment of cancer, autoimmune disease, allergy, infection and inflammatory conditions, e.g. multiple sclerosis is disclosed.
摘要翻译：本发明涉及新型调节性T细胞蛋白。称为PD-L3的一种蛋白质类似于PD-L1家族的成员，并且在体外共同刺激T细胞的αCD3增殖。第二种TNF样蛋白也被鉴定为在αCD3/αGITR刺激下上调。该蛋白质已被命名为Treg-sTNF。公开了蛋白质，抗体，活化的T细胞和使用它们的方法。特别是使用这些蛋白质和化合物（优选抗体）的方法，其结合或调节（激动或拮抗）这些蛋白质的活性，作为免疫调节剂和用于治疗癌症，自身免疫疾病，变态反应，感染和炎性病症，例如，公开了多发性硬化。

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