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1. 发明申请

US20180092961A1 EXTRACELLULAR HISTONES AS BIOMARKERS FOR PROGNOSIS AND MOLECULAR TARGETS FOR THERAPY 审中-公开
公开(公告)号：US20180092961A1
公开(公告)日：2018-04-05
申请号：US15838639
申请日：2017-12-12
申请人： OKLAHOMA MEDICAL RESEARCH FOUNDATION
发明人： Charles T. ESMON , Jun XU , Xiaomei ZHANG
IPC分类号： A61K38/10 , A61K39/395 , A61K38/48 , C07K7/08 , A61K45/06 , C07K16/18 , A61K31/727 , A61K38/17
CPC分类号： A61K38/10 , A61K31/727 , A61K38/1709 , A61K38/36 , A61K38/4833 , A61K38/4846 , A61K38/4866 , A61K39/3955 , A61K45/06 , A61K2039/505 , C07K7/08 , C07K16/18 , C07K16/40 , C07K2317/76 , C12Y304/21005 , C12Y304/21006 , C12Y304/21069 , G01N33/6875 , A61K2300/00
摘要： Hyper-inflammatory responses can lead to a variety of diseases including sepsis. It is now shown that extracellular histones released in response to inflammatory challenge are mediators contributing to endothelial dysfunction, organ failure and death during sepsis. As such, they can be targeted pharmacologically by inhibitors, as well as used as biomarkers for prognosis of sepsis and other diseases.

2. 发明授权

US09649366B2 Manufacturing and purification processes of Complex protein found in Fraction IV to make a separated Apo, Transferrin, and Alpha 1 Antitrypsin (A1AT) or a combined Transferrin/Apo/Human Albumin/A1AT and all new found proteins 有权
公开(公告)号：US09649366B2
公开(公告)日：2017-05-16
申请号：US14056363
申请日：2013-10-17
申请人： Kieu Hoang
发明人： Kieu Hoang
IPC分类号： A61K38/00 , A61K38/57 , A61K38/17 , A61K38/38 , A61K38/40 , A61K38/36 , A61K38/37 , A61K38/39 , A61K38/48 , C07K14/775
CPC分类号： A61K38/57 , A61K38/1709 , A61K38/363 , A61K38/37 , A61K38/38 , A61K38/39 , A61K38/40 , A61K38/4833 , A61K38/4866 , C07K14/775 , A61K2300/00
摘要： Manufacturing and purification processes of complex protein found in Fraction IV to make a separated Apo, Transferrin, and Alpha-1 Antitrypsin (A1AT) or a combined Transferrin/Apo/Human Albumin/A1AT and all new found proteins. A complex of all proteins found currently in plasma, cryoprecipitate, Fraction III and many newly found proteins now being identified or any substances which are known proteins or unknown proteins which contain healthy cells and the combination of any of these known or unknown proteins which contain any one of these healthy cells: neutrophil, lymphocyte, eosinophil, basophil, and macrophage, and their potential applications for treating a wide variety of diseases and other physical conditions and disorders, and for maintaining health.

3. 发明申请

US20160354477A1 CONJUGATES OF TUMOR NECROSIS FACTOR INHIBITORS TO FUNCTIONALIZED POLYMERS 有权
标题翻译：肿瘤坏死因子抑制剂功能化聚合物的结合
公开(公告)号：US20160354477A1
公开(公告)日：2016-12-08
申请号：US14980322
申请日：2015-12-28
申请人： QuiaPEG Pharmaceuticals AB
发明人： Marek Kwiatkowski
IPC分类号： A61K47/48 , C07K16/42 , A61K38/47 , A61K38/28 , C07K14/62 , C12N9/96 , C07K14/705 , C07K16/00 , C07K1/107 , C07K19/00 , C12N9/36 , A61K39/395 , A61K38/17
CPC分类号： A61K47/68 , A61K38/1793 , A61K38/1816 , A61K38/28 , A61K38/36 , A61K38/37 , A61K38/47 , A61K38/4846 , A61K38/4866 , A61K39/395 , A61K39/39566 , A61K47/60 , A61K2039/505 , C07K1/1077 , C07K14/62 , C07K14/70578 , C07K16/00 , C07K16/4291 , C07K19/00 , C07K2319/30 , C12N9/2462 , C12N9/96 , C12Y302/01017
摘要： This document relates to conjugates of TNF inhibitors or derivatives thereof and functionalized (e.g., mono- or bi-functional) polymers (e.g., polyethylene glycol and related polymers) as well as methods and materials for making and using such conjugates.
摘要翻译：本文件涉及TNF抑制剂或其衍生物和官能化（例如单 - 或双功能）聚合物（例如聚乙二醇和相关聚合物）的缀合物以及用于制备和使用这种缀合物的方法和材料。

4. 发明授权

US09220789B2 Conjugates of tumor necrosis factor inhibitors to functionalized polymers 有权
标题翻译：肿瘤坏死因子抑制剂与官能化聚合物的结合
公开(公告)号：US09220789B2
公开(公告)日：2015-12-29
申请号：US13916251
申请日：2013-06-12
申请人： QuiaPEG AB
发明人： Marek Kwiatkowski
IPC分类号： A61K47/48 , C07K14/62 , C07K1/107 , A61K38/17 , A61K38/18 , A61K38/28 , A61K38/36 , A61K38/37 , A61K38/48 , A61K39/395 , C12N9/96 , A61K39/00
CPC分类号： A61K47/68 , A61K38/1793 , A61K38/1816 , A61K38/28 , A61K38/36 , A61K38/37 , A61K38/47 , A61K38/4846 , A61K38/4866 , A61K39/395 , A61K39/39566 , A61K47/60 , A61K2039/505 , C07K1/1077 , C07K14/62 , C07K14/70578 , C07K16/00 , C07K16/4291 , C07K19/00 , C07K2319/30 , C12N9/2462 , C12N9/96 , C12Y302/01017
摘要： This document relates to conjugates of TNF inhibitors or derivatives thereof and functionalized (e.g., mono- or bi-functional) polymers (e.g., polyethylene glycol and related polymers) as well as methods and materials for making and using such conjugates.
摘要翻译：本文件涉及TNF抑制剂或其衍生物和官能化（例如单 - 或双功能）聚合物（例如聚乙二醇和相关聚合物）的缀合物以及用于制备和使用这种缀合物的方法和材料。

5. 发明申请

US20150344556A1 EXTRACELLULAR HISTONES AS BIOMARKERS FOR PROGNOSIS AND MOLECULAR TARGETS FOR THERAPY 审中-公开
公开(公告)号：US20150344556A1
公开(公告)日：2015-12-03
申请号：US14734238
申请日：2015-06-09
申请人： OKLAHOMA MEDICAL RESEARCH FOUNDATION
发明人： Charles T. ESMON , Jun XU , Xiaomei ZHANG
IPC分类号： C07K16/18 , A61K39/395 , A61K38/10 , A61K45/06 , A61K38/48
CPC分类号： A61K38/10 , A61K31/727 , A61K38/1709 , A61K38/36 , A61K38/4833 , A61K38/4846 , A61K38/4866 , A61K39/3955 , A61K45/06 , A61K2039/505 , C07K7/08 , C07K16/18 , C07K16/40 , C07K2317/76 , C12Y304/21005 , C12Y304/21006 , C12Y304/21069 , G01N33/6875 , A61K2300/00
摘要： Hyper-inflammatory responses can lead to a variety of diseases including sepsis. It is now shown that extracellular histones released in response to inflammatory challenge are mediators contributing to endothelial dysfunction, organ failure and death during sepsis. As such, they can be targeted pharmacologically by inhibitors, as well as used as biomarkers for prognosis of sepsis and other diseases.

6. 发明授权

US09192657B2 Activated protein C variants with normal cytoprotective activity but reduced anticoagulant activity 有权
标题翻译：具有正常细胞保护活性但具有降低的抗凝血活性的活化蛋白C变体
公开(公告)号：US09192657B2
公开(公告)日：2015-11-24
申请号：US11589371
申请日：2006-10-30
申请人： John H. Griffin , Laurent O. Mosnier , Andrew J. Gale
发明人： John H. Griffin , Laurent O. Mosnier , Andrew J. Gale
IPC分类号： A61K38/48 , C12N9/64
CPC分类号： A61K38/4866 , C12N9/6464 , C12Y304/21069
摘要： Variants (mutants) of recombinant activated protein C (APC) or recombinant protein C (prodrug, capable of being converted to APC) that have substantial reductions in anticoagulant activity but that retain normal levels of anti-apoptotic activity are provided. Three examples of such recombinant APC mutants are KKK191-193AAA-APC, RR229/230AA-APC, and RR229/230AA plus KKK191-193AAA-APC. APC variants and prodrugs of the invention have the desirable property of being cytoprotective (anti-apoptotic effects), while having significantly reduced risk of bleeding. The invention also provides a method of using the APC variants or prodrugs of the invention to treat subjects who will benefit from APC's cytoprotective activities that are independent of APC's anticoagulant activity. These subjects include patients at risk of damage to blood vessels or tissue in various organs caused, at least in part, by apoptosis. At risk patients include, for example, those suffering (severe) sepsis, ischemia/reperfusion injury, ischemic stroke, acute myocardial infarction, acute or chronic neurodegenerative diseases, or those undergoing organ transplantation or chemotherapy, among other conditions. Methods of screening for variants of recombinant protein C or APC that are useful in accordance with the invention are also provided.
摘要翻译：提供重组活化蛋白C（APC）或重组蛋白C（前体药物，能够转化为APC）的变体（突变体），其具有显着降低抗凝血活性，但保持正常水平的抗凋亡活性。这些重组APC突变体的三个实例是KKK191-193AAA-APC，RR229 / 230AA-APC和RR229 / 230AA加上KKK191-193AAA-APC。本发明的APC变体和前药具有细胞保护性（抗凋亡作用）的期望性质，同时具有显着降低的出血风险。本发明还提供了使用本发明的APC变体或前药来治疗受益于APC的细胞保护活性而不受APC抗凝活性影响的受试者的方法。这些受试者包括至少部分地通过细胞凋亡而导致各种器官的血管损伤或组织损伤风险的患者。在危险中，患者包括例如患有（严重）败血症，缺血/再灌注损伤，缺血性卒中，急性心肌梗死，急性或慢性神经变性疾病或经历器官移植或化疗的患者等。还提供了筛选根据本发明有用的重组蛋白C或APC的变体的方法。

7. 发明申请

US20150147345A1 CONJUGATES OF BIOLOGICALLY ACTIVE MOLECULES TO FUNCTIONALIZED POLYMERS 有权
标题翻译：生物活性分子与功能化聚合物的结合
公开(公告)号：US20150147345A1
公开(公告)日：2015-05-28
申请号：US14407580
申请日：2013-06-12
申请人： QuiaPEG AB
发明人： Marek Kwiatkowski
IPC分类号： A61K47/48 , A61K38/28 , A61K38/18 , C12N9/96 , A61K38/37 , A61K38/36 , A61K38/48 , C07K1/107 , A61K39/395 , A61K38/17
CPC分类号： A61K47/68 , A61K38/1793 , A61K38/1816 , A61K38/28 , A61K38/36 , A61K38/37 , A61K38/47 , A61K38/4846 , A61K38/4866 , A61K39/395 , A61K39/39566 , A61K47/60 , A61K2039/505 , C07K1/1077 , C07K14/62 , C07K14/70578 , C07K16/00 , C07K16/4291 , C07K19/00 , C07K2319/30 , C12N9/2462 , C12N9/96 , C12Y302/01017
摘要： This document relates to conjugates of a biologically active molecule or a derivative thereof and functionalized (e.g., mono- or bi-functional) polymers (e.g., polyethylene glycol and related polymers) as well as methods and materials for making and using such conjugates.
摘要翻译：本文件涉及生物活性分子或其衍生物和官能化（例如单 - 或双功能）聚合物（例如聚乙二醇和相关聚合物）的缀合物以及用于制备和使用这种缀合物的方法和材料。

8. 发明申请

US20140142284A1 Manufacturing and Purification Processes of Complex Protein found in Fraction IV to make a separated Apo, Transferrin, and Alpha 1 Anti strepsin (A1AT) or A combined Transferrin/Apo/Human Albumin/A1AT and all new found proteins 审中-公开
标题翻译：在分数IV中发现的复合蛋白质的制备和纯化过程以制备分离的Apo，转铁蛋白和α1抗粘蛋白酶（A1AT）或A组合的转铁蛋白/ Apo /人白蛋白/ A1AT和所有新发现的蛋白质
公开(公告)号：US20140142284A1
公开(公告)日：2014-05-22
申请号：US14056363
申请日：2013-10-17
申请人： Kieu Hoang
发明人： Kieu Hoang
IPC分类号： C07K14/775
CPC分类号： A61K38/57 , A61K38/1709 , A61K38/363 , A61K38/37 , A61K38/38 , A61K38/39 , A61K38/40 , A61K38/4833 , A61K38/4866 , C07K14/775 , A61K2300/00
摘要： Manufacturing and Purification Processes of Complex Protein found in Fraction IV to make a separated Apo, Transferrin, and Alpha 1 Antitrypsin (A1AT) or a combined Transferrin/Apo/Human Albumin/A1AT and all new found proteins. A complex of all proteins found currently in Plasma, Cryoprecipitate, Fraction III and many newly found proteins now being identified or any substances which are known proteins or unknown proteins which contain good healthy cells and the combination of any of these known or unknown proteins which contain any one of these good healthy cells: Neutrophil, Lymphocyte, Eosinophil, Basophil, and Macrophage, and their potential applications for treating a wide variety of diseases and other physical conditions and disorders, and for maintaining health.
摘要翻译：在分数IV中发现的复合蛋白的制备和纯化过程，以制备分离的Apo，转铁蛋白和α1抗胰蛋白酶（A1AT）或组合的转铁蛋白/ Apo /人白蛋白/ A1AT和所有新发现的蛋白质。目前正在鉴定的等离子体，冷沉淀物，级分III和许多新发现的蛋白质中发现的所有蛋白质的复合物或已知蛋白质或任何含有良好健康细胞的蛋白质或未知蛋白质的任何物质以及任何这些已知或未知蛋白质的组合，其含有这些良好的健康细胞中的任何一种：中性粒细胞，淋巴细胞，嗜酸性粒细胞，嗜碱性粒细胞和巨噬细胞，以及它们用于治疗各种疾病和其他身体状况和障碍以及维持健康的潜在应用。

9. 发明授权

US08716218B2 Extracellular histones as biomarkers for prognosis and molecular targets for therapy 有权
标题翻译：细胞外组蛋白作为预后的生物标志物和治疗的分子靶标
公开(公告)号：US08716218B2
公开(公告)日：2014-05-06
申请号：US12266336
申请日：2008-11-06
申请人： Charles T. Esmon , Jun Xu , Xiaomei Zhang
发明人： Charles T. Esmon , Jun Xu , Xiaomei Zhang
IPC分类号： A61K38/10
CPC分类号： A61K38/10 , A61K31/727 , A61K38/1709 , A61K38/36 , A61K38/4833 , A61K38/4846 , A61K38/4866 , A61K39/3955 , A61K45/06 , A61K2039/505 , C07K7/08 , C07K16/18 , C07K16/40 , C07K2317/76 , C12Y304/21005 , C12Y304/21006 , C12Y304/21069 , G01N33/6875 , A61K2300/00
摘要： Hyper-inflammatory responses can lead to a variety of diseases including sepsis. It is now shown that extracellular histones released in response to inflammatory challenge are mediators contributing to endothelial dysfunction, organ failure and death during sepsis. As such, they can be targeted pharmacologically by inhibitors, as well as used as biomarkers for prognosis of sepsis and other diseases.
摘要翻译：高发炎反应可导致多种疾病，包括败血症。现在显示出响应于炎性攻击而释放的细胞外组蛋白是介导脓毒血症的内皮功能障碍，器官衰竭和死亡的介质。因此，它们可以通过抑制剂药理靶向，并且用作脓毒症和其他疾病的预后的生物标志物。

10. 发明申请

US20130123473A1 BISPECIFIC ANTIBODY TARGETING A COMPLEMENT FACTOR OR COMPLEMENT REGULATORY PROTEIN 审中-公开
标题翻译：补充因子或补充调节蛋白的双重抗体
公开(公告)号：US20130123473A1
公开(公告)日：2013-05-16
申请号：US13717230
申请日：2012-12-17
申请人： Immunomedics, Inc.
发明人： David M. GOLDENBERG , Hans J. HANSEN
IPC分类号： A61K39/395
CPC分类号： A61K39/3955 , A61K31/513 , A61K38/193 , A61K38/2013 , A61K38/4866 , A61K39/40 , A61K45/06 , A61K49/0002 , A61K2039/505 , A61K2039/507 , C07K16/1203 , C07K16/24 , C07K16/241 , C07K16/248 , C07K16/2803 , C07K16/2896 , C07K16/30 , C07K2317/24 , C07K2317/31 , C07K2317/734
摘要： A multispecific antagonist is disclosed that reacts specifically with at least two different targets. The targets are (A) proinflammatory effectors of the innate immune system, (B) coagulation factors, (C) complement factors and complement regulatory proteins, and (D) targets specifically associated with an inflammatory or immune-dysregulatory disorder or with a pathologic angiogenesis or cancer, wherein this latter target is not (A), (B) or (C). At least one of the targets is (C), and when the multispecific antagonist comprises a single multispecific antibody, then CD74 is excluded as a target of said antagonist. When the multispecific antagonist comprises a combination of separate antibodies, combinations are excluded where one of said antibodies targets a B-cell antigen and the other antibody targets a T-cell, plasma cell, macrophage or inflammatory cytokine and combinations are also excluded where one of said antibodies targets CD20 and the other antibody targets C3b or CD40.
摘要翻译：公开了与至少两个不同靶物特异性反应的多特异性拮抗剂。目标是（A）先天免疫系统的促炎效应物，（B）凝血因子，（C）补体因子和补体调节蛋白，以及（D）与炎症或免疫调节障碍或病理血管发生特异性相关的靶标或癌症，其中后一靶标不是（A），（B）或（C）。至少一个目标是（C），并且当多特异性拮抗剂包含单个多特异性抗体时，则排除CD74作为所述拮抗剂的靶标。当多特异性拮抗剂包含单独的抗体的组合时，除了其中一种所述抗体靶向B细胞抗原并且另一种抗体靶向T细胞，浆细胞，巨噬细胞或炎性细胞因子的组合之外，并且组合也被排除在其中之一所述抗体靶向CD20，其他抗体靶标为C3b或CD40。

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