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61. 发明申请

WO2018106998A1 COMPOSITIONS AND RELATED METHODS FOR TARGETED DRUG DELIVERY 审中-公开
公开(公告)号：WO2018106998A1
公开(公告)日：2018-06-14
申请号：PCT/US2017/065262
申请日：2017-12-08
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , THE BRIGHAM AND WOMEN'S HOSPITAL, INC.
发明人： TRAVERSO, Carlo, Giovanni , KAKKAR, Ashok , KORZENIK, Joshua , LANGER, Robert, S. , ZHANG, Sufeng
IPC分类号： A61K47/69 , C08F120/56
CPC分类号： C08F220/56 , A61K9/0024 , A61K9/5169 , A61K31/58 , A61K38/193 , A61K47/34 , A61K47/54 , A61K47/58 , C08F220/54 , C08F224/00 , C08F220/06 , A61K2300/00
摘要： Compositions, articles, and methods for targeted drug delivery, such as thermoresponsive hydrogel polymers, are generally provided. In one aspect, the compositions and articles comprise a thermoresponsive hydrogel polymer comprising a releasable therapeutic agent. In some cases, the compositions described herein have advantageous combinations of properties including mechanical strength, biocompatibility, tunable charge densities, thermal responsiveness, drug loading, and/or configurations for targeted drug delivery. In one embodiment, the composition comprises a solution comprising a thermoresponsive polymer including one or more ligands attached to the polymer, wherein the solution is configured to undergo a sol-to-gel transition under physiological conditions. In another embodiment, the composition comprises a plurality of nanoparticles e.g., associated with the thermoresponsive polymer. In yet another embodiment, the composition comprises a therapeutic agent e.g., associated with the nanoparticles and/or thermoresponsive polymer.

62. 发明申请

WO2018053264A2 KLRG1 DEPLETION THERAPY 审中-公开
标题翻译： KLRG1消毒治疗
公开(公告)号：WO2018053264A2
公开(公告)日：2018-03-22
申请号：PCT/US2017/051776
申请日：2017-09-15
申请人： THE BRIGHAM AND WOMEN'S HOSPITAL, INC. , CHILDREN'S MEDICAL CENTER CORPORATION
发明人： GREENBERG, Steven , GULLA, Stefano, Vincenzo , THOMPSON, Kenneth, Evan
IPC分类号： A61K39/395
摘要： A method of treating a subject can comprise administering to a subject in need thereof an effective amount of a killer cell lectin-like receptor G1 (KLRG1) depleting agent, thereby depleting CD8+ cytotoxic T and/or NK cells in vivo. A method of treating a subject can comprise administering to a subject in need thereof an effective amount of a KLRG1 depleting agent with effector killing function. A composition, for example an anti-KLRG1 antibody, can comprise a KLRG1 depleting agent. The methods and compositions can be used for various diseases in which KLRG1 is overexpressed, for example autoimmune diseases, transplant rejection, hematologic malignancies, and solid tumors.
摘要翻译：治疗受试者的方法可包括向有需要的受试者施用有效量的杀伤细胞凝集素样受体G1（KLRG1）消耗剂，由此耗尽CD8 +细胞毒性T和/或NK 细胞在体内。治疗受试者的方法可以包括向有需要的受试者施用有效量的具有效应物杀伤功能的KLRG1消耗剂。组合物（例如抗KLRG1抗体）可以包含KLRG1消耗剂。该方法和组合物可用于KLRG1过度表达的各种疾病，例如自身免疫疾病，移植排斥，血液恶性肿瘤和实体瘤。

63. 发明申请

WO2018053069A1 BLOCKADE OF ALPHAFETOPROTEIN (AFP) INTERACTIONS WITH BETA2-MICROGLOBULIN ASSOCIATED MOLECULES 审中-公开
标题翻译： Aβ与β2-微球蛋白相关分子相互作用的阻断
公开(公告)号：WO2018053069A1
公开(公告)日：2018-03-22
申请号：PCT/US2017/051462
申请日：2017-09-14
申请人： THE BRIGHAM AND WOMEN'S HOSPITAL, INC. , UNIVERSITY OF OSLO
发明人： BLUMBERG, Richard, S. , PYZIK, Michal , GANDHI, Amit , SANDLIE, Inger , SAND, Kine, Marita, Knudsen , ANDERSEN, Jan, Terje
IPC分类号： A61K39/395 , A61K38/38 , A61P37/06 , C12P21/02 , C07K14/47 , C07K14/76 , C07K14/765 , C07K14/74
摘要： Provided herein, in some aspects, are compositions and methods to inhibit AFP interactions with β2Μ and/or Class I-related molecule interactions in diseases or disorders where elevated AFP levels are associated with immunosuppression. Also provided herein, in some aspects, are compositions and methods to enhance or potentiate AFP interactions with β2Μ and/or Class I-related molecule in diseases or disorders with decreased AFP levels or diseases or disorders where increasing AFP levels is desired to increase immunosuppression or enhance organ regeneration.
摘要翻译：本文提供了一些组合物和方法，用于抑制AFP与Aβ水平升高与免疫抑制相关的疾病或病症中AFP与β2M和/或I类相关分子相互作用的相互作用。在一些方面，本文还提供了增强或加强AFP与β2M和/或I类相关分子在具有降低的AFP水平的疾病或病症中的相互作用的组合物和方法，或期望增加AFP水平以增加免疫抑制的疾病或病症增强器官再生。

64. 发明申请

WO2017213695A1 COMPOSITIONS AND METHODS RELATING TO T PERIPHERAL HELPER CELLS IN AUTOANTIBODY-ASSOCIATED CONDITIONS 审中-公开
标题翻译：在与自体动物相关的条件下与T外周有害细胞相关的组合物和方法
公开(公告)号：WO2017213695A1
公开(公告)日：2017-12-14
申请号：PCT/US2016/065107
申请日：2016-12-06
申请人： THE BRIGHAM AND WOMEN'S HOSPITAL, INC.
发明人： BRENNER, Michael, B. , RAO, Deepak, A.
IPC分类号： A61K47/68 , A61P19/02
摘要： This disclosure provides methods and compositions for detecting Tph cells and/or reducing the number (or frequency) and/or activity of such cells in order to provide therapeutic benefit to a subject having or at risk of developing an autoantibody-associated condition such as an autoantibody-associated autoimmune disease.
摘要翻译：本公开提供了用于检测Tph细胞和/或降低这些细胞的数量（或频率）和/或活性以便为患有或有风险发展的受试者提供治疗益处的方法和组合物自身抗体相关的病症，如自身抗体相关的自身免疫性疾病。

65. 发明申请

WO2017173453A1 STIMULI-RESPONSIVE NANOPARTICLES FOR BIOMEDICAL APPLICATIONS 审中-公开
标题翻译：用于生物医学应用的刺激性纳米颗粒
公开(公告)号：WO2017173453A1
公开(公告)日：2017-10-05
申请号：PCT/US2017/025772
申请日：2017-04-03
申请人： THE BRIGHAM AND WOMEN'S HOSPITAL, INC.
发明人： XU, Xiaoding , SHI, Jinjun , FAROKHZAD, Omid C.
IPC分类号： A61K9/127 , A61K9/51 , C08G75/14 , A61K47/58 , C08F293/00 , A61K47/60 , A61K47/64 , A61K49/12
摘要： Stimuli-responsive NPs with excellent stability, high loading efficiency, encapsulation of multiple agents, targeting to certain cells, tissues or organs of the body, can be used as delivery tools. These NPs contain a hydrophobic inner core and hydrophilic outer shell, which endows them with high stability and the ability to load therapeutic agents with high encapsulation efficiency. The NPs are preferably formed from amphiphilic stimulus-responsive polymers or a mixture of amphiphilic and hydrophobic polymers or compounds, at least one type of which is stimuli-responsive. These NPs can be made so that their cargo is released primarily within target certain cells, tissues or organs of the body, upon exposure to endogenous or exogenous stimuli. The rate of release can be controlled so that it may be a burst, sustained, delayed, or a combination thereof. The NPs have utility as research tools or for clinical applications including diagnostics, therapeutics, or combination of both.
摘要翻译：可以将刺激响应性NPs用作递送工具，其具有优异的稳定性，高加载效率，多种药物的包封，靶向身体的某些细胞，组织或器官。这些纳米粒子含有疏水性内核和亲水性外壳，赋予它们高度的稳定性，并且能够载入具有高包封率的治疗剂。 NPs优选由两亲性刺激响应性聚合物或两亲性和疏水性聚合物或化合物的混合物形成，其至少一种类型是刺激响应性的。这些纳米颗粒可以制成使得它们的货物在暴露于内源性或外源性刺激下时主要释放到身体目标特定的细胞，组织或器官内。可以控制释放速率，使其可以是爆发，持续，延迟或其组合。 NPs可用作研究工具或用于临床应用，包括诊断，治疗或两者的组合。

66. 发明申请

WO2017165766A3 BIOMARKERS OF PROTEOPATHIES AND USES THEREOF 审中-公开
公开(公告)号：WO2017165766A3
公开(公告)日：2017-09-28
申请号：PCT/US2017/024012
申请日：2017-03-24
申请人： GENZYME CORPORATION , THE BRIGHAM AND WOMEN'S HOSPITAL, INC.
发明人： SARDI, Sergio Pablo , SCHERZER, Clemens
IPC分类号： G01N33/92
摘要： Provided herein are methods of determining the efficacy of a treatment for a proteopathy, diagnosing a proteopathy in a subject, determining a subject's risk of developing a proteopathy, determining the stage of a proteopathy in a subject, monitoring a proteopathy in a subject, selecting a treatment for a proteopathy for a subject, and selecting a subject for a clinical trial that include determining a level of at least one sphingolipid in a sample including a biological fluid from the subject.

67. 发明申请

WO2017147087A1 TREATMENT METHODS FOR FIBROSIS TARGETING SMOC2 审中-公开
标题翻译：纤维化靶向SMOC2的治疗方法
公开(公告)号：WO2017147087A1
公开(公告)日：2017-08-31
申请号：PCT/US2017/018753
申请日：2017-02-21
申请人： THE BRIGHAM AND WOMEN'S HOSPITAL, INC.
发明人： VAIDYA, Vishal S. , GERARDUZZI, Casimiro
IPC分类号： A61K39/395 , C07K16/00 , C12P21/08
CPC分类号： A61P43/00 , A61P13/12 , C07K16/18 , C07K16/2842 , C07K2317/76 , C12N15/113 , C12N2310/14
摘要： Described herein are methods for treating fibrosis, e.g., kidney fibrosis, using agents that target Secreted Modular Calcium-binding protein 2 (SMOC2).
摘要翻译：本文描述了使用靶向分泌性模块钙结合蛋白2（SMOC2）的试剂治疗纤维化（例如肾纤维化）的方法。

68. 发明申请

WO2017120543A1 PRODUCTION OF DIFFERENTIATED ENTEROENDOCRINE CELLS AND INSULIN PRODUCING CELLS 审中-公开
标题翻译：产生分化的肠道腺苷细胞和胰岛素生产细胞
公开(公告)号：WO2017120543A1
公开(公告)日：2017-07-13
申请号：PCT/US2017/012631
申请日：2017-01-06
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , THE BRIGHAM AND WOMEN'S HOSPITAL, INC.
发明人： KARP, Jeffrey, Michael , LANGER, Robert, Samuel , YIN, Xiaolei
IPC分类号： C12N5/071
CPC分类号： C12N5/0678 , C12N5/0613 , C12N5/0679 , C12N2500/38 , C12N2500/62 , C12N2501/01 , C12N2501/065 , C12N2501/11 , C12N2501/119 , C12N2501/13 , C12N2501/15 , C12N2501/155 , C12N2501/335 , C12N2501/395 , C12N2501/415 , C12N2501/42 , C12N2501/71 , C12N2501/72 , C12N2501/727 , C12N2501/999 , C12N2502/23 , C12N2533/90 , G01N33/5008
摘要： A population of enteroendocrine cells (EEC) is obtained from a mammalian post-natal cell population, such as a population including post-natal stem cells, by treating the population with a plurality of small molecules that upregulate ChgA and promote differentiation of the cells to form the enteroendocrine cells. The upregulation of ChgA is such that the fraction of cells expressing CGA in the obtained cell population, as measured by a ChgA Immunostaining Assay, is at least about 1.5%. Small molecules that can be used to differentiate the post-natal cells into the enteroendocrine cells can include at least one of a Wnt activator, a Notch inhibitor, a Wnt inhibitor, a MEK/ERK inhibitor, a growth factor, a HDAC inhibitor, a Histone Methylation Inhibitor, a Tgf-β inhibitor, and a NeuroD1 activator. Also, the insulin expression of a population of mammalian cells is increased by treating the population with a plurality of small molecules that increase the insulin expression.
摘要翻译：通过用多种上调的小分子处理群体，从哺乳动物产后细胞群体（例如包括产后干细胞的群体）获得肠内分泌细胞群体（EEC） ChgA并促进细胞分化形成肠内分泌细胞。 ChgA的上调使得在获得的细胞群中表达CGA的细胞部分（如通过ChgA免疫染色测定法测量的）为至少约1.5％。可用于将产后细胞分化成肠内分泌细胞的小分子可包括Wnt激活剂，Notch抑制剂，Wnt抑制剂，MEK / ERK抑制剂，生长因子，HDAC抑制剂，组蛋白甲基化抑制剂，Tgf-β抑制剂和NeuroD1激活剂。而且，哺乳动物细胞群体的胰岛素表达通过用增加胰岛素表达的多个小分子处理群体而增加。

69. 发明申请

WO2017075478A2 COMPOSITIONS AND METHODS FOR EVALUATING AND MODULATING IMMUNE RESPONSES BY USE OF IMMUNE CELL GENE SIGNATURES 审中-公开
标题翻译：使用免疫细胞基因签名评估和调节免疫应答的组合物和方法
公开(公告)号：WO2017075478A2
公开(公告)日：2017-05-04
申请号：PCT/US2016/059507
申请日：2016-10-28
申请人： THE BROAD INSTITUTE INC. , MASSACHUSETTS INSTITUTE OF TECHNOLOGY , THE BRIGHAM AND WOMEN'S HOSPITAL, INC. , REGEV, Aviv , ANDERSON, Ana, Carrizosa , CONG, Le , KUCHROO, Vijay, K. , SINGER, Meromit , WANG, Chao
发明人： REGEV, Aviv , ANDERSON, Ana, Carrizosa , CONG, Le , KUCHROO, Vijay, K. , SINGER, Meromit , WANG, Chao
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12N5/0636 , C12N2510/00 , C12Q1/6881 , C12Q2600/158
摘要： The present invention provides markers, marker signatures and molecular targets that correlate with dysfunction of immune cells and are advantageously independent of the immune cell activation status. The present markers, marker signatures and molecular targets provide for new ways to evaluate and modulate immune responses. Therapeutic methods are also provided to treat a patient in need thereof who would benefit from an increased immune response.
摘要翻译：本发明提供了与免疫细胞功能障碍相关的标志物，标志物标志和分子靶点，并且有利地不依赖于免疫细胞活化状态。目前的标记，标记特征和分子靶标提供了评估和调节免疫应答的新方法。还提供了治疗方法来治疗有需要的患者，这些患者将从增加的免疫应答中获益。

70. 发明申请

WO2017075465A1 COMPOSITIONS AND METHODS FOR EVALUATING AND MODULATING IMMUNE RESPONSES BY DETECTING AND TARGETING GATA3 审中-公开
标题翻译：通过检测和靶向GATA3评估和调节免疫应答的组合物和方法
公开(公告)号：WO2017075465A1
公开(公告)日：2017-05-04
申请号：PCT/US2016/059487
申请日：2016-10-28
申请人： THE BROAD INSTITUTE INC. , MASSACHUSETTS INSTITUTE OF TECHNOLOGY , THE BRIGHAM AND WOMEN'S HOSPITAL, INC. , REGEV, Aviv , ANDERSON, Ana Carrizosa , CONG, Le , KUCHROO, Vijay, K. , SINGER, Meromit , WANG, Chao
发明人： REGEV, Aviv , ANDERSON, Ana Carrizosa , CONG, Le , KUCHROO, Vijay, K. , SINGER, Meromit , WANG, Chao
IPC分类号： A61K39/00 , A61K35/17 , C12N5/0783 , G01N33/50
CPC分类号： G01N33/5023 , A61K35/17 , A61K39/0011 , C12N5/0636 , G01N33/505 , G01N2333/4703 , G01N2800/52
摘要： The present invention provides markers, marker signatures and molecular targets that correlate with dysfunction of immune cells and are advantageously independent of the immune cell activation status. The present markers, marker signatures and molecular targets provide for new ways to evaluate and modulate immune responses. Specifically, GATA3 and/or FOXOl modulation are provided for use as markers, marker signatures and molecular targets. Therapeutic methods are also provided to treat a patient in need thereof who would benefit from an increased immune response.
摘要翻译：本发明提供了与免疫细胞功能障碍相关的标志物，标志物标志和分子靶点，并且有利地不依赖于免疫细胞活化状态。目前的标记，标记特征和分子靶标提供了评估和调节免疫应答的新方法。具体而言，提供GATA3和/或FOXO1调节作为标志物，标志物标志和分子靶标使用。还提供了治疗方法来治疗有需要的患者，这些患者将从增加的免疫应答中获益。

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