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1. 发明申请

WO2013049362A8 METHOD OF TREATING MULTIPLE SCLEROSIS BY INTRATHECAL DEPLETION OF B CELLS AND BIOMARKERS TO SELECT PATIENTS WITH PROGRESSIVE MULTIPLE SCLEROSIS 审中-公开
标题翻译：通过B细胞和生物标志物的内分泌治疗多发性硬化的方法选择患有进行性多发性硬化症的患者
公开(公告)号：WO2013049362A8
公开(公告)日：2014-04-24
申请号：PCT/US2012057583
申请日：2012-09-27
申请人： US HEALTH
发明人： BIELEKOVA BIBIANA , HERMAN MATTHEW L
IPC分类号： C07K16/28 , A61P25/00 , A61P37/06 , G01N33/53
CPC分类号： C07K16/2887 , A61K9/0085 , A61K2039/505 , A61K2039/54 , A61K2039/545 , G01N33/6863 , G01N33/6869 , G01N33/6893 , G01N2333/521 , G01N2333/5434 , G01N2800/285 , G01N2800/52
摘要： Described herein are methods of treating multiple sclerosis (MS), such as secondary progressive MS (SPMS), by intrathecally administering a B cell depleting agent, such as rituximab, alone or in combination with intravenous administration of a B cell depleting agent. Also described is the use of IL-12p40, CXCL13, or both as CSF biomarkers for selecting a patient with progressive MS as a candidate for treatment with an intrathecal immunomodulatory therapy, and for identifying a progressive MS patient as having meningeal inflammation. The present disclosure also describes a method of evaluating the effectiveness of a therapy for treating progressive MS by measuring the level of IL-12p40, CXCL13, or both in the CSF of the patient before and after treatment. A decrease in the level of IL-12p40, CXCL13, or both after treatment indicates the therapy is effective for treating progressive MS.
摘要翻译：本文描述的是通过鞘内施用B细胞消耗剂（例如利妥昔单抗）单独或与静脉内施用B细胞消耗剂组合来治疗多发性硬化（MS），例如继发性进行性MS（SPMS）的方法。还描述了使用IL-12p40，CXCL13或两者作为CSF生物标志物，用于选择进行性MS的患者作为用鞘内免疫调节治疗治疗的候选者，以及用于鉴定进行性MS患者具有脑膜炎症。本公开还描述了通过测量治疗前后患者的CSF中的IL-12p40，CXCL13或两者的水平来评估治疗进行性MS的疗法的有效性的方法。治疗后IL-12p40，CXCL13或两者均降低，说明治疗对于进行性MS有效。

2. 发明申请

WO2016028699A8 BIOMARKERS FOR DIAGNOSIS AND MANAGEMENT OF NEURO-IMMUNOLOGICAL DISEASES 审中-公开
标题翻译：生物标志物用于神经免疫疾病的诊断和管理
公开(公告)号：WO2016028699A8
公开(公告)日：2016-11-17
申请号：PCT/US2015045549
申请日：2015-08-17
申请人： US HEALTH , MONTANA STATE UNIV
发明人： BIELEKOVA BIBIANA , KOMORI MIKA , KOSA PETER , GREENWOOD MARK C , BARBOUR CHRISTOPHER
IPC分类号： G01N33/68
CPC分类号： G01N33/6896 , G01N2333/705 , G01N2800/285 , G01N2800/52 , G01N2800/60
摘要： Biomarkers associated with neuroimmunological disease are described. The disclosed biomarkers are secreted proteins identified in cerebral spinal fluid (CSF) samples of patients with neurological disease. The disclosed biomarkers identify patients with intrathecal inflammation, distinguish multiple sclerosis (MS) patients from patients with other types of inflammatory neurological diseases and from subjects without MS, distinguish progressive MS patients from patients with relapsing-remitting MS, identify subjects with non-MS inflammatory neurological diseases, differentiate healthy subjects from patients with any type of neurological disease, and/or identify subjects with increased disability, CNS tissue damage and/or neurodegeneration. Process-specific biomarkers that can be used in place of a brain biopsy to identify immune cell infiltration and/or activation in the CNS are also described. Methods of treating subject with neurological disease, and methods of evaluating the efficacy of particular treatments, based on detection of the disclosed biomarkers are also described.
摘要翻译：描述了与神经免疫疾病相关的生物标志物。所公开的生物标记是在患有神经疾病的患者的脑脊液（CSF）样品中鉴定的分泌蛋白。所公开的生物标志物鉴定患有鞘内炎症的患者，区分多发性硬化症（MS）患者与其他类型炎症性神经疾病患者以及无MS患者，将进行性MS患者与具有复发缓解MS的患者区分开来，鉴别患有非MS炎性神经疾病，将健康受试者与任何类型的神经疾病患者区分开，和/或鉴定残疾增加，CNS组织损伤和/或神经变性的受试者。还描述了可用于代替脑活检以鉴定CNS中免疫细胞浸润和/或活化的过程特异性生物标志物。还描述了基于检测所公开的生物标志物来治疗患有神经疾病的受试者的方法以及评估特定治疗的功效的方法。

3. 发明申请

WO2010068923A3 AGENTS THAT SELECTIVELY INHIBIT CD25 ON DENDRITIC CELLS OR T CELLS AND THEIR USE 审中-公开
标题翻译：选择性抑制CD25对细胞或细胞的作用及其使用
公开(公告)号：WO2010068923A3
公开(公告)日：2010-12-02
申请号：PCT/US2009067755
申请日：2009-12-11
申请人： US HEALTH , BIELEKOVA BIBIANA , EDWAN JEHAD , MARTIN JAYNE
发明人： BIELEKOVA BIBIANA , EDWAN JEHAD , MARTIN JAYNE
IPC分类号： A61K39/395 , A61P35/00 , C07K16/18 , C12N5/0784
CPC分类号： C07K16/2866 , A61K2039/505 , C07K2317/24 , C07K2317/73 , C07K2317/76
摘要： Agent that selectively inhibit CD25 on dendritic cells on T cells are disclosed herein. Methods are provided for treating a subject with an immune mediated disease. These methods include administering to the subject a therapeutically effective amount of an agent that selectively inhibits CD25 on dendritic cells, thereby treating the immune mediated disorder in the subject. In other embodiments, methods are provided for treating a subject with a tumor. The methods include administering to the subject a therapeutically effective amount of an agent that selectively inhibits CD25 on T cells, thereby treating the tumor in the subject. Compositions are disclosed that include a composite molecule and a carrier, wherein the composite molecule comprises an agent that selectively binds dendritic cells or an agent that selectively binds T cells, wherein the agent is covalently bound to a CD25 antagonist. Methods for selecting an agent of use in treating an immune mediated disorder are also disclosed.
摘要翻译：本文公开了在T细胞上树突状细胞上选择性抑制CD25的药剂。提供了用免疫介导的疾病治疗受试者的方法。这些方法包括向受试者施用治疗有效量的选择性抑制树突状细胞上的CD25的试剂，从而治疗受试者的免疫介导的病症。在其它实施方案中，提供了用于用肿瘤治疗受试者的方法。所述方法包括向受试者施用治疗有效量的选择性抑制T细胞上的CD25的药剂，从而治疗受试者的肿瘤。公开了包含复合分子和载体的组合物，其中所述复合分子包含选择性结合树突状细胞的试剂或选择性结合T细胞的试剂，其中所述试剂与CD25拮抗剂共价结合。还公开了用于选择用于治疗免疫介导的病症的药剂的方法。

4. 发明申请

WO2016028699A2 BIOMARKERS FOR DIAGNOSIS AND MANAGEMENT OF NEURO-IMMUNOLOGICAL DISEASES 审中-公开
标题翻译：生物标志物诊断和管理神经免疫缺陷病毒
公开(公告)号：WO2016028699A2
公开(公告)日：2016-02-25
申请号：PCT/US2015045549
申请日：2015-08-17
申请人： US HEALTH , UNIV MONTANA STATE
发明人： BIELEKOVA BIBIANA , KOMORI MIKA , KOSA PETER , GREENWOOD MARK C , BARBOUT CHRISTOPHER
IPC分类号： G01N33/68
CPC分类号： G01N33/6896 , G01N2333/705 , G01N2800/285 , G01N2800/52 , G01N2800/60
摘要： Biomarkers associated with neuroimmunological disease are described. The disclosed biomarkers are secreted proteins identified in cerebral spinal fluid (CSF) samples of patients with neurological disease. The disclosed biomarkers identify patients with intrathecal inflammation, distinguish multiple sclerosis (MS) patients from patients with other types of inflammatory neurological diseases and from subjects without MS, distinguish progressive MS patients from patients with relapsing-remitting MS, identify subjects with non-MS inflammatory neurological diseases, differentiate healthy subjects from patients with any type of neurological disease, and/or identify subjects with increased disability, CNS tissue damage and/or neurodegeneration. Process-specific biomarkers that can be used in place of a brain biopsy to identify immune cell infiltration and/or activation in the CNS are also described. Methods of treating subject with neurological disease, and methods of evaluating the efficacy of particular treatments, based on detection of the disclosed biomarkers are also described.
摘要翻译：描述了与神经免疫疾病相关的生物标志物。所公开的生物标志物是在具有神经疾病的患者的脑脊髓液（CSF）样品中鉴定的分泌蛋白质。所公开的生物标志物识别患有鞘内炎症的患者，区分多发性硬化（MS）患者与患有其他类型炎症性神经疾病的患者和来自不具有MS的受试者，区分进行性MS患者与复发缓解MS患者，鉴定具有非MS炎性的受试者神经疾病，将健康受试者与患有任何类型的神经疾病的患者区分开来，和/或识别残疾增加，CNS组织损伤和/或神经变性的受试者。还描述了可用于代替脑活检以鉴定CNS中的免疫细胞浸润和/或激活的过程特异性生物标志物。还描述了基于所公开的生物标志物的检测来治疗患有神经疾病的受试者的方法和评估特定治疗的功效的方法。

5. 发明申请

WO2013049362A3 METHOD OF TREATING MULTIPLE SCLEROSIS BY INTRATHECAL DEPLETION OF B CELLS AND BIOMARKERS TO SELECT PATIENTS WITH PROGRESSIVE MULTIPLE SCLEROSIS 审中-公开
标题翻译：通过B细胞和生物标志物的内分泌治疗多发性硬化的方法选择患有进行性多发性硬化症的患者
公开(公告)号：WO2013049362A3
公开(公告)日：2013-07-04
申请号：PCT/US2012057583
申请日：2012-09-27
申请人： US HEALTH
发明人： BIELEKOVA BIBIANA , HERMAN MATTHEW L
IPC分类号： C07K16/28 , A61P25/00 , A61P37/06 , G01N33/53
CPC分类号： C07K16/2887 , A61K9/0085 , A61K2039/505 , A61K2039/54 , A61K2039/545 , G01N33/6863 , G01N33/6869 , G01N33/6893 , G01N2333/521 , G01N2333/5434 , G01N2800/285 , G01N2800/52
摘要： Described herein are methods of treating multiple sclerosis (MS), such as secondary progressive MS (SPMS), by intrathecally administering a B cell depleting agent, such as rituximab, alone or in combination with intravenous administration of a B cell depleting agent. Also described is the use of IL-12p40, CXCL13, or both as CSF biomarkers for selecting a patient with progressive MS as a candidate for treatment with an intrathecal immunomodulatory therapy, and for identifying a progressive MS patient as having meningeal inflammation. The present disclosure also describes a method of evaluating the effectiveness of a therapy for treating progressive MS by measuring the level of IL-12p40, CXCL13, or both in the CSF of the patient before and after treatment. A decrease in the level of IL-12p40, CXCL13, or both after treatment indicates the therapy is effective for treating progressive MS.
摘要翻译：本文描述的是通过鞘内施用B细胞消耗剂（例如利妥昔单抗）单独或与静脉内施用B细胞消耗剂组合来治疗多发性硬化（MS），例如继发性进行性MS（SPMS）的方法。还描述了使用IL-12p40，CXCL13或两者作为CSF生物标志物，用于选择进行性MS的患者作为用鞘内免疫调节治疗治疗的候选者，以及用于鉴定进行性MS患者具有脑膜炎症。本公开还描述了通过测量治疗前后患者的CSF中的IL-12p40，CXCL13或两者的水平来评估治疗进行性MS的疗法的有效性的方法。治疗后IL-12p40，CXCL13或两者均降低，说明治疗对于进行性MS有效。

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