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1. 发明申请

US20060008460A1 Monoclonal antibody MR1 and uses thereof 失效
标题翻译：单克隆抗体MR1及其用途
公开(公告)号：US20060008460A1
公开(公告)日：2006-01-12
申请号：US11127046
申请日：2005-05-10
申请人： Randolph Noelle
发明人： Randolph Noelle
IPC分类号： A61K39/395 , C12N5/06
CPC分类号： C07K16/2875 , A61K38/00 , A61K2039/505 , C07K14/70575 , C07K2317/73 , C07K2317/76 , Y10S514/885 , Y10S530/866 , Y10S530/868
摘要： The present invention relates to a counter-receptor, termed CD40CR, for the CD40 B-cell antigen, and to soluble ligands for this receptor, including fusion molecules comprising at least a portion of CD40 protein. It is based, at least in part, on the discovery that a soluble CD40/immunoglobulin fusion protein was able to inhibit helper T-cell mediated B-cell activation by binding to a novel 39 kD protein receptor on helper T-cell membranes. The present invention provides for a substantially purified CD40CR receptor; for soluble ligands of CD40CR, including antibodies as well as fusion molecules comprising at least a portion of CD40 protein; and for methods of controlling B-cell activation which may be especially useful in the treatment of allergy or autoimmune disease.
摘要翻译：本发明涉及用于CD40B细胞抗原的称为CD40CR的反受体，以及该受体的可溶性配体，包括至少包含一部分CD40蛋白的融合分子。至少部分基于这样一个发现，即可溶性CD40 /免疫球蛋白融合蛋白能够通过结合辅助性T细胞膜上的新型39kD蛋白受体来抑制辅助T细胞介导的B细胞活化。本发明提供了基本纯化的CD40CR受体; 用于CD40CR的可溶性配体，包括抗体以及包含至少一部分CD40蛋白的融合分子; 以及用于控制B细胞活化的方法，其可能特别可用于治疗过敏或自身免疫性疾病。

2. 发明申请

US20050152897A1 Methods for inducing T cell tolerance to a tissue or organ graft 失效
标题翻译：诱导T细胞对组织或器官移植物耐受的方法
公开(公告)号：US20050152897A1
公开(公告)日：2005-07-14
申请号：US10962033
申请日：2004-10-07
申请人： Randolph Noelle , Fiona Durie , David Parker , Michael Appel , Nancy Phillips , John Mordes , Dale Grenier , Aldo Rossini
发明人： Randolph Noelle , Fiona Durie , David Parker , Michael Appel , Nancy Phillips , John Mordes , Dale Grenier , Aldo 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 , A61K48/00
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。

3. 发明授权

US08802098B2 Methods of promoting antitumor immunity by administering CD40 agonists and alpha-galactosyl ceramide 有权
标题翻译：通过施用CD40激动剂和α-半乳糖苷神经酰胺来促进抗肿瘤免疫的方法
公开(公告)号：US08802098B2
公开(公告)日：2014-08-12
申请号：US12597615
申请日：2008-04-25
申请人： Cory Ahonen , Randolph Noelle
发明人： Cory Ahonen , Randolph Noelle
IPC分类号： A61K39/395 , A61K31/70 , C07K14/435
CPC分类号： A61K39/39 , A61K31/7032 , A61K39/29 , A61K39/39541 , A61K39/3955 , A61K45/06 , A61K2039/505 , A61K2039/55511 , A61K2039/55516 , A61K2039/57 , C07K16/2878 , C07K16/468 , C07K2317/21 , C07K2317/24 , C07K2317/31 , C07K2317/74 , C07K2317/75 , C07K2317/76 , A61K2300/00
摘要： Adjuvant combinations comprising at least one NKT activator, such as alpha-galactosylceramide (α-Gal-Cer) or iGb3, a CD40 agonist and optionally an antigen are disclosed. The use of these immune adjuvants for treatment of various chronic diseases such as cancers is also provided.
摘要翻译：公开了包含至少一种NKT活化剂，例如α-半乳糖神经酰胺（α-Gal-Cer）或iGb3，CD40激动剂和任选的抗原的佐剂组合。还提供了这些免疫佐剂用于治疗各种慢性疾病如癌症的用途。

4. 发明申请

US20120238623A1 Inflammation and Autoimmune Disorder Treatment using RARa Selective Agonists 审中-公开
标题翻译：使用RARa选择性激动剂的炎症和自身免疫性疾病治疗
公开(公告)号：US20120238623A1
公开(公告)日：2012-09-20
申请号：US13420067
申请日：2012-03-14
申请人： Roshantha A. Chandraratna , Elizabeth Nowak , Randolph Noelle
发明人： Roshantha A. Chandraratna , Elizabeth Nowak , Randolph Noelle
IPC分类号： A61K31/196 , A61P29/00 , A61P11/00 , A61P25/22 , A61P25/24 , A61P3/08 , A61K31/24 , A61P1/00
CPC分类号： A61K31/196 , A61K31/24 , Y02A50/414
摘要： The present specification provides compounds, compositions and methods using such compounds and compositions to treat an autoimmune disorder, inflammation and/or a transplant rejection.
摘要翻译：本说明书提供了使用这些化合物和组合物治疗自身免疫性疾病，炎症和/或移植排斥的化合物，组合物和方法。

5. 发明申请

US20110182847A1 USE OF TLR AGONISTS AND/OR TYPE 1 INTERFERONS TO ALLEVIATE TOXICITY OF TNF-R AGONIST THERAPEUTIC REGIMENS 审中-公开
标题翻译： TLR激动剂和/或1型干扰素对TNF-α激动剂治疗方案的致敏性的使用
公开(公告)号：US20110182847A1
公开(公告)日：2011-07-28
申请号：US12664921
申请日：2008-06-16
申请人： Randolph Noelle , Ross Kedl , Cory Ahonen
发明人： Randolph Noelle , Ross Kedl , Cory Ahonen
IPC分类号： A61K38/21 , A61K39/395 , A61K35/74 , A61K35/66 , A61K39/00 , A61K39/12 , A61K39/02 , A61K39/002 , A61K39/112 , A61K39/21 , A61K39/125 , A61K39/193 , A61K39/29 , A61K39/205 , A61K39/275 , A61K39/285 , A61K39/25 , A61K39/245 , A61K39/145 , A61K39/108 , A61K39/08 , A61K39/07 , A61K39/106 , A61K39/05 , A61K39/09 , A61K39/015 , A61K39/005 , A61K39/018 , A61K39/012 , A61P31/04 , A61P31/10 , A61P31/12 , A61P31/14 , A61P31/16 , A61P31/18 , A61P31/20 , A61P31/22 , A61P33/00 , A61P33/02 , A61P33/06 , A61P33/10 , A61P37/04
CPC分类号： A61K39/3955 , A61K31/135 , A61K35/74 , A61K36/06 , A61K38/191 , A61K38/21 , A61K39/00 , A61K39/0002 , A61K39/0005 , A61K39/0011 , A61K39/002 , A61K39/02 , A61K39/12 , A61K45/06 , A61K47/6881 , C07K14/555 , A61K2300/00
摘要： Improved (safer and more effective) methods of therapy using TNF-R agonists, e.g., CD40 agonists are provided. These methods provide for the addition of an amount of a type 1 interferon and/or a TLR agonist that is effective to prevent or reduce the toxicity (liver toxicity) that may otherwise result in some patients of the TNF-R agonist is used as a monotherapy (without the type 1 interferon and/r TLR agonist).
摘要翻译：提供使用TNF-R激动剂（例如CD40激动剂）的改进（更安全和更有效的）治疗方法。这些方法提供了一定量的1型干扰素和/或TLR激动剂的量，其有效预防或降低可能导致TNF-R激动剂的一些患者的毒性（肝毒性）单一疗法（不含1型干扰素和/ r TLR激动剂）。

6. 发明申请

US20060222649A1 Methods for inducing antigen-specific T cell tolerance 审中-公开
标题翻译：诱导抗原特异性T细胞耐受的方法
公开(公告)号：US20060222649A1
公开(公告)日：2006-10-05
申请号：US11405876
申请日：2006-04-17
申请人： Randolph Noelle , Teresa Foy , Fiona Durie
发明人： Randolph Noelle , Teresa Foy , Fiona Durie
IPC分类号： A61K39/395
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。

7. 发明授权

US06472510B1 CD40 receptor ligands 失效
标题翻译： CD40受体配体
公开(公告)号：US06472510B1
公开(公告)日：2002-10-29
申请号：US08338975
申请日：1994-11-14
申请人： Alejandro A. Aruffo , Jeffrey A. Ledbetter , Ivan Stamenkovic , Randolph Noelle
发明人： Alejandro A. Aruffo , Jeffrey A. Ledbetter , Ivan Stamenkovic , Randolph Noelle
IPC分类号： C07K14705
CPC分类号： C07K16/2875 , A61K38/00 , A61K2039/505 , C07K14/70578 , C07K2317/73 , C07K2319/00 , C07K2319/30 , Y10S530/866
摘要： The present invention relates to a counter-receptor, termed CD40CR, for the CD40 B-cell antigen, and to soluble ligands for this receptor, including fusion molecules comprising at least a portion of CD40 protein. It is based, at least in part, on the discovery that a soluble CD40/immunoglobulin fusion protein was able to inhibit helper T-cell mediated B-cell activation by binding to a novel 39 kD protein receptor on helper T-cell membranes. The present invention provides for a substantially purified CD40CR receptor; for soluble ligands of CD40CR, including antibodies as well as fusion molecules comprising at least a portion of CD40 protein; and for methods of controlling B-cell activation which may be especially useful in the treatment of allergy or autoimmune disease.
摘要翻译：本发明涉及用于CD40B细胞抗原的称为CD40CR的反受体，以及该受体的可溶性配体，包括至少包含一部分CD40蛋白的融合分子。至少部分基于这样一个发现，即可溶性CD40 /免疫球蛋白融合蛋白能够通过结合辅助性T细胞膜上的新型39kD蛋白受体来抑制辅助T细胞介导的B细胞活化。本发明提供了基本纯化的CD40CR受体; 用于CD40CR的可溶性配体，包括抗体以及包含至少一部分CD40蛋白的融合分子; 以及用于控制B细胞活化的方法，其可能特别可用于治疗过敏或自身免疫性疾病。

8. 发明申请

US20100247537A1 ADJUVANT COMBINATIONS OF NKT ACTIVATOR, CD40 AGONIST, AND OPTIONAL ANTIGEN, THE USE THROUGH INDUCING SYNERGISTIC CELLULAR IMMUNITY 有权
标题翻译： NKT激活剂，CD40激动剂和可选抗原的补充剂组合，通过诱导协同细胞免疫的用途
公开(公告)号：US20100247537A1
公开(公告)日：2010-09-30
申请号：US12597615
申请日：2008-04-25
申请人： Cory Ahonen , Randolph Noelle
发明人： Cory Ahonen , Randolph Noelle
IPC分类号： A61K39/39 , A61K39/395 , A61K39/00 , A61K39/12 , A61K39/21 , A61K39/155 , A61K39/165 , A61K39/125 , A61K39/20 , A61K39/215 , A61K39/205 , A61K39/245 , A61K39/25 , A61K39/275 , A61K39/02 , A61K39/09 , A61K39/05 , A61K39/07 , A61K39/08 , A61K39/102 , A61K39/108 , A61K39/112 , A61K39/104 , A61K39/106 , A61K39/005 , A61K39/015 , A61K39/002 , C12N1/00
CPC分类号： A61K39/39 , A61K31/7032 , A61K39/29 , A61K39/39541 , A61K39/3955 , A61K45/06 , A61K2039/505 , A61K2039/55511 , A61K2039/55516 , A61K2039/57 , C07K16/2878 , C07K16/468 , C07K2317/21 , C07K2317/24 , C07K2317/31 , C07K2317/74 , C07K2317/75 , C07K2317/76 , A61K2300/00
摘要： Adjuvant combinations comprising at least one NKT activator, such as alpha-galactosylceramide (α-Gal-Cer) or iGb3, a CD40 agonist and optionally an antigen are disclosed. The use of these immune adjuvants for treatment of various chronic diseases such as cancers is also provided.
摘要翻译：公开了包含至少一种NKT活化剂，例如α-半乳糖神经酰胺（α-Gal-Cer）或iGb3，CD40激动剂和任选的抗原的佐剂组合。还提供了这些免疫佐剂用于治疗各种慢性疾病如癌症的用途。

9. 发明申请

US20050163780A1 Method for prolonged suppression of humoral immune response to a thymus-dependent antigen 失效
标题翻译：延长抑制对胸腺依赖性抗原的体液免疫应答的方法
公开(公告)号：US20050163780A1
公开(公告)日：2005-07-28
申请号：US11029868
申请日：2005-01-04
申请人： Randolph Noelle , Teresa Foy
发明人： Randolph Noelle , Teresa Foy
IPC分类号： A61K35/14 , A61K35/28 , A61K38/00 , A61K38/17 , A61P37/06 , C07K14/705 , C07K16/28 , C07K19/00 , G01N33/68 , A61K39/395
CPC分类号： C07K14/70575 , A61K38/00 , A61K2039/505 , A61K2039/57 , C07K14/70578 , C07K16/2875 , C07K19/00 , C07K2317/24 , C07K2319/00 , G01N33/6854 , Y10S514/885
摘要： Methods of suppressing a humoral immune response to a thymus-dependent (TD) antigen are disclosed. The methods involve administering to a subject a TD antigen with an antagonist of a molecule which mediates contact-dependent helper effector functions. In a preferred embodiment, the antagonist is an antagonist of gp39. Primary and secondary humoral immune responses can be suppressed and suppression is prolonged.
摘要翻译：公开了抑制对胸腺依赖（TD）抗原的体液免疫应答的方法。所述方法包括用受体介导接触依赖性辅助效应子功能的分子的拮抗剂向受试者施用TD抗原。在优选的实施方案中，拮抗剂是gp39的拮抗剂。初级和次级体液免疫应答可以被抑制并且抑制被延长。

10. 发明授权

US06376459B1 Inhibiting B cell activation with soluble CD40 or fusion proteins thereof 失效
标题翻译：用可溶性CD40或其融合蛋白抑制B细胞活化
公开(公告)号：US06376459B1
公开(公告)日：2002-04-23
申请号：US08114944
申请日：1993-08-31
申请人： Alejandro A. Aruffo , Jeffrey A. Ledbetter , Ivan Stamenkovic , Randolph Noelle
发明人： Alejandro A. Aruffo , Jeffrey A. Ledbetter , Ivan Stamenkovic , Randolph Noelle
IPC分类号： A61K3802
CPC分类号： C07K16/2875 , A61K38/00 , A61K2039/505 , C07K14/70575 , C07K2317/73 , C07K2317/76 , Y10S514/885 , Y10S530/866 , Y10S530/868
摘要： The present invention relates to a counter-receptor, termed CD40CR, for the CD40 B-cell antigen, and to soluble ligands for this receptor, including fusion molecules comprising at least a portion of CD40 protein. It is based, at least in part, on the discovery that a soluble CD40/immunoglobulin fusion protein or antibody specific for gp39 on T cells was able to inhibit helper T-cell mediated B-cell activation by binding to a novel 39 kD protein receptor on helper T-cell membranes. The present invention provides for a substantially purified CD40CR receptor; for soluble ligands of CD40CR, including antibodies as well as fusion molecules comprising at least a portion of CD40 protein; and for methods of controlling B-cell activation which may be especially useful in the treatment of allergy or autoimmune disease, including graft-versus-host disease and rheumatoid arthritis.
摘要翻译：本发明涉及用于CD40B细胞抗原的称为CD40CR的反受体，以及该受体的可溶性配体，包括至少包含一部分CD40蛋白的融合分子。至少部分基于以下发现：T细胞上gp39特异性的可溶性CD40 /免疫球蛋白融合蛋白或抗体能够通过结合新的39kD蛋白受体来抑制辅助T细胞介导的B细胞活化在辅助T细胞膜上。本发明提供了基本纯化的CD40CR受体; 用于CD40CR的可溶性配体，包括抗体以及包含至少一部分CD40蛋白的融合分子; 以及用于控制B细胞活化的方法，其可特别用于治疗过敏或自身免疫疾病，包括移植物抗宿主病和类风湿性关节炎。

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