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1. 发明申请

WO2019145413A1 ANTAGONISTS OF IL-33 FOR USE IN METHODS FOR PREVENTING ISCHEMIA REPERFUSION INJURY IN AN ORGAN 审中-公开
公开(公告)号：WO2019145413A1
公开(公告)日：2019-08-01
申请号：PCT/EP2019/051738
申请日：2019-01-24
申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) , UNIVERSITÉ DE POITIERS , CENTRE HOSPITALIER UNIVERSITAIRE DE POITIERS , CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS)
发明人： HERBELIN, André , GOMBERT, Jean-Marc , FERHAT, Maroua , THIERRY, Antoine , GIRARD, Jean-Philippe
IPC分类号： A61K38/20 , A61K39/395 , A61K38/17 , A61P9/10
CPC分类号： A61K38/2006 , A61K38/1793 , A61P9/10
摘要： Inflammation is a prominent feature of ischemia-reperfusion injury (IRI) characterized by leukocyte infiltration and renal tubular injury. However, the signals that initiate these events remain poorly understood. The inventors identify the nuclear alarmin interleukin (IL)-33 as an initiation factor of tissue injury and also as a major amplification factor of the innate immune response triggered by experimental kidney ischemia-reperfusion in mice. In mice lacking IL-33, IRI is reduced, as attested by early decreased tubular cell injury, and by subsequent decreased infiltration of IFN- γ /IL-17A-producing neutrophils and preservation of renal functions. These findings led the inventors to propose that endogenous IL-33 contributes to kidney IRI by promoting iNKT cell recruitment and cytokine production, resulting in neutrophil infiltration and activation at the injury site. Accordingly, the present invention relates to antagonists of IL-33 for use in methods for preventing ischemia reperfusion injury in an organ.

2. 发明申请

WO2017175229A1 POLYSACCHARIDE COMPOSITIONS AND USES THEREOF 审中-公开
标题翻译：多糖组合物及其用途
公开(公告)号：WO2017175229A1
公开(公告)日：2017-10-12
申请号：PCT/IL2017/050423
申请日：2017-04-06
申请人： B.G. NEGEV TECHNOLOGIES AND APPLICATIONS LTD.
发明人： PEARLMAN, Andrew , COHEN, Smadar , RUVINOV, Emil
IPC分类号： A61B17/56 , A61L27/52 , A61K38/18 , A61K47/36
CPC分类号： A61K35/28 , A61K35/16 , A61K38/1793 , A61K38/1841 , A61K38/1875 , A61L27/20 , A61L27/3616 , A61L27/446 , A61L27/46 , A61L27/52 , A61L27/54 , A61L27/56 , A61L2300/414 , A61L2430/02 , A61L2430/06 , C08L5/08 , C08L5/04
摘要： The present invention provides compositions comprising alginate, sulfated alginate, or hyaluronan sulfate for repairing or regenerating damaged tissue and in particular, joint tissue. The invention also provides a multi-layer hydrogel comprising alginate, sulfated alginate, or hyaluronan sulfate in which one of the layers is affinity-bound to one or more bioactive polypeptides and another one of the layers does not comprise a bioactive polypeptide. The present invention also provides compositions comprising a non-biological additive such as hydroxyapatite, calcium phosphate, mannitol beads, and/or magnesium ions; a biological additive such as platelet rich plasma (PRP) and/or bone marrow aspirate; an interleukin-1 receptor antagonist (IL-1RA), or such composition cross-linked using calcium phosphate as a source of calcium ions.
摘要翻译：本发明提供了用于修复或再生受损组织，特别是关节组织的包含藻酸盐，硫酸化海藻酸盐或透明质酸硫酸盐的组合物。本发明还提供了包含藻酸盐，硫酸化海藻酸盐或硫酸透明质酸的多层水凝胶，其中一层与一种或多种生物活性多肽亲和结合，另一层不含生物活性多肽。本发明还提供包含非生物添加剂如羟基磷灰石，磷酸钙，甘露糖醇珠和/或镁离子的组合物; 生物添加剂如富血小板血浆（PRP）和/或骨髓抽吸物; 白细胞介素-1受体拮抗剂（IL-1RA）或使用磷酸钙作为钙离子源交联的此类组合物。

3. 发明申请

WO2017062456A3 BIOMARKERS RELATED TO INTERLEUKIN-33 (IL-33)-MEDIATED DISEASES AND USES THEREOF 审中-公开
标题翻译：与白介素-33（IL-33）介导的疾病有关的生物标记及其用途
公开(公告)号：WO2017062456A3
公开(公告)日：2017-05-18
申请号：PCT/US2016055502
申请日：2016-10-05
申请人： REGENERON PHARMA
发明人： ORENGO JAMIE M , ALLINNE JEANNE , FURY WEN , BAI YU
IPC分类号： C07K16/24 , C07K14/715 , G01N33/50
CPC分类号： C07K16/244 , A61K38/1793 , A61K39/3955 , A61K45/06 , A61K2039/505 , C07K14/57527 , C07K14/7155 , C07K2317/21 , C07K2317/24 , C07K2317/56 , C07K2317/76 , C07K2319/30 , G01N33/6893 , G01N2333/54 , G01N2333/585
摘要： The present invention relates to the identification of certain biomarkers for use in identifying patients who have, or are likely to develop an IL-33 mediated disease or disorder and who are more likely to respond to therapy with an IL-33 antagonist. The invention also relates to methods of treatment of an IL-33-mediated disease or disorder in a patient by administering an IL-33 antagonist to the patient in need thereof and monitoring the effectiveness of therapy using the biomarkers described herein. Also provided are methods for decreasing the level of at least one biomarker in a subject suffering from an IL-33-mediated disease or disorder, and methods for treating such diseases or disorders according to the expression levels of one or more biomarkers. The methods of the present invention comprise administering to a subject in need thereof a pharmaceutical composition comprising an interleukin-33 antagonist.
摘要翻译：本发明涉及鉴定用于鉴定患有或可能发展IL-33介导的疾病或病症并且更可能对用IL-33拮抗剂治疗有反应的患者的某些生物标记。本发明还涉及通过向有需要的患者施用IL-33拮抗剂并且使用本文所述的生物标志物监测治疗的有效性来治疗患者中IL-33介导的疾病或病症的方法。还提供了用于降低患有IL-33介导的疾病或病症的受试者中至少一种生物标志物的水平的方法，以及根据一种或多种生物标志物的表达水平治疗此类疾病或病症的方法。本发明的方法包括向有需要的受试者施用包含白细胞介素-33拮抗剂的药物组合物。

4. 发明申请

WO2015157399A9 TRANSGENE GENETIC TAGS AND METHODS OF USE 审中-公开
标题翻译：转基因遗传标签及其使用方法
公开(公告)号：WO2015157399A9
公开(公告)日：2016-11-24
申请号：PCT/US2015024895
申请日：2015-04-08
申请人： SEATTLE CHILDREN'S HOSPITAL (DBA SEATTLE CHILDREN'S RES INSTITUTE)
发明人： JENSEN MICHAEL C , JOHNSON ADAM
IPC分类号： C07K16/28 , A61K39/39
CPC分类号： C07K14/71 , A61K35/17 , A61K35/28 , A61K38/1774 , A61K38/179 , A61K38/1793 , A61K39/3955 , A61K2035/124 , A61K2039/505 , A61K2039/5156 , A61K2039/5158 , A61K2039/572 , C07K14/7051 , C07K14/70517 , C07K14/70521 , C07K14/70578 , C07K14/7151 , C07K16/2803 , C07K16/2818 , C07K16/32 , C07K2317/14 , C07K2317/524 , C07K2317/526 , C07K2317/53 , C07K2317/622 , C07K2317/73 , C07K2319/02 , C07K2319/03 , C07K2319/33 , C12N5/0636 , C12N9/12 , C12N15/85 , C12N2510/00 , C12N2800/90 , C12Y207/10001
摘要： The present invention provides genetic tags operably linked to transgenes. The expression of the genetic tag allows identification, detection, selection, and ablation of cells expressing the transgene and the genetic tag. In some alternatives the genetically modified host cell comprises a transgene comprising a polynucleotide coding for a chimeric antigen receptor comprising a ligand binding domain, a polynucleotide comprising a spacer region, a polynucleotide comprising a transmembrane domain, and a polynucleotide comprising an intracellular signaling domain and a polynucleotide coding for a genetic tag. In some alternatives the genetically modified host cell comprises a transgene comprising a polynucleotide coding for a chimeric antigen receptor comprising a ligand binding domain, a polynucleotide comprising a spacer region, a polynucleotide comprising a transmembrane domain, and a polynucleotide comprising an intracellular signaling domain and a polynucleotide coding for a genetic tag, and wherein the polypeptide further comprises a flexible linker comprising amino acids GGGSGGGS (SEQ ID NO: 45). Pharmaceutical formulations produced by the method, and methods of using the same, are also described.
摘要翻译：本发明提供可操作地连接到转基因的遗传标签。遗传标签的表达允许识别，检测，选择和消除表达转基因和遗传标签的细胞。在一些替代方案中，遗传修饰的宿主细胞包含转基因，其包含编码嵌合抗原受体的多核苷酸，其包含配体结合结构域，包含间隔区的多核苷酸，包含跨膜结构域的多核苷酸以及包含细胞内信号转导结构域和编码遗传标签的多核苷酸。在一些替代方案中，遗传修饰的宿主细胞包含转基因，其包含编码嵌合抗原受体的多核苷酸，其包含配体结合结构域，包含间隔区的多核苷酸，包含跨膜结构域的多核苷酸以及包含细胞内信号转导结构域和编码遗传标签的多核苷酸，并且其中所述多肽还包含包含氨基酸GGGSGGGS（SEQ ID NO：45）的柔性接头。还描述了通过该方法制备的药物制剂及其使用方法。

5. 发明申请

WO2016122806A1 COMPOSITIONS AND METHODS OF USING A SOLUBLE TNF-ALPHA RECEPTOR MODIFIED FOR INCREASED HALF-LIFE 审中-公开
标题翻译：使用可溶性TNF-ALPHA受体修饰的增加的半衰期的组合物和方法
公开(公告)号：WO2016122806A1
公开(公告)日：2016-08-04
申请号：PCT/US2015/067055
申请日：2015-12-21
申请人： DNX BIOTECH, LLC
发明人： DATAR, Rajiv , EDWARDS, Carl, K.
IPC分类号： A61K38/16 , C07K14/475 , C07K14/525
CPC分类号： A61K38/191 , A61K38/1712 , A61K38/177 , A61K38/179 , A61K38/1793 , A61K47/26 , A61K47/60 , C07K14/525 , C07K14/7151 , C08B37/0081 , C12N15/85
摘要： Methods and pharmaceutical compositions for preventing and/or treating acute and chronic inflammation and autoimmune diseases are provided herein. Tumor necrosis factor-α (TNFα) promotes an inflammatory response, which causes clinical problems associated with inflammation and autoimmune disorders such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriasis, hidradenitis suppurativa, and refractory asthma. TNFα is also implicated in promoting pathogenesis of diabetic retinopathy leading to loss of retinal microvascular cells. Methods herein contain the step of administering a prophylactic and/or therapeutic formulation of a pharmaceutical composition containing a recombinant soluble human TNF receptor or portions thereof which are TNFα inhibitors. These pharmaceutic compositions have been modified by conjugating natural amino acids such as proline and alanine, and/or serine (PA/S) via PASylation ® to create a linear polypeptide that possesses fewer of the processing, preparation, formulation, cost, and other long-term issues of administering PEGylated drugs.
摘要翻译：本文提供了用于预防和/或治疗急性和慢性炎症和自身免疫疾病的方法和药物组合物。肿瘤坏死因子-α（TNFα）促进炎症反应，其引起与炎症和自身免疫性疾病如类风湿性关节炎，强直性脊柱炎，炎性肠病，牛皮癣，化脓性贫血和难治性哮喘相关的临床问题。 TNFα也涉及促进导致视网膜微血管细胞丧失的糖尿病性视网膜病变的发病机制。本文的方法包含施用包含TNFα抑制剂的重组可溶性人TNF受体或其部分的药物组合物的预防和/或治疗制剂的步骤。这些药物组合物已经通过使天然氨基酸例如脯氨酸和丙氨酸和/或丝氨酸（PA / S）通过PASylation？缀合来产生线性多肽，其具有较少的加工，制备，配方，成本和其它长 - 治疗聚乙二醇化药物的问题。

6. 发明申请

WO2016029043A1 TUMOR NECROSIS FACTOR SUPERFAMILY AND TNF-LIKE LIGAND MUTEINS AND METHODS OF PREPARING AND USING THE SAME 审中-公开
标题翻译：肿瘤坏死因子超家族和类TNF类似配体的制剂及其制备和使用方法
公开(公告)号：WO2016029043A1
公开(公告)日：2016-02-25
申请号：PCT/US2015/046152
申请日：2015-08-20
申请人： THE GENERAL HOSPITAL CORPORATION
发明人： FAUSTMAN, Denise, L. , VANAMEE, Eva
IPC分类号： A61K45/00 , C07K1/00
CPC分类号： C07K14/525 , A61K38/00 , A61K38/1793 , A61K38/191 , A61K38/22 , A61K45/06 , C07K14/5255 , C07K14/575 , C07K14/70575 , C07K14/70578
摘要： The invention features homo-multimers, e.g., homo-trimers, of TNFSF or TNF-like ligand muteins in which each TNFSF ligand or TNF-like ligand mutein monomer contains at least one cysteine residue substitution or insertion that promotes the formation of a disulfide bond with a cysteine residue on a neighboring TNFSF or TNF-like ligand mutein monomer. The invention features methods of producing such TNFSF and TNF-like ligand muteins, pharmaceutical compositions containing such muteins, and methods of using such muteins in cancer immunotherapy, in treating autoimmune and neurological diseases, and in reducing or eliminating the complications and risks of rejection in organ transplantation or tissue or organ repair or regeneration.
摘要翻译：本发明具有TNFSF或TNF-样配体突变蛋白的同型多聚体，例如同三聚体，其中每个TNFSF配体或TNF-样配体突变蛋白单体含有至少一个促进二硫键形成的半胱氨酸残基取代或插入在相邻的TNFSF或TNF-样配体突变蛋白单体上具有半胱氨酸残基。本发明的特征在于制备这种TNFSF和TNF-样配体突变蛋白的方法，含有此类突变蛋白的药物组合物，以及在癌症免疫治疗中使用这种突变蛋白的方法，用于治疗自身免疫性和神经性疾病，以及减少或消除并发症和排斥风险器官移植或组织或器官修复或再生。

7. 发明申请

WO2016009222A1 THERAPEUTIC USE OF P75NTR NEUROTROPHIN BINDING PROTEIN 审中-公开
标题翻译： P75NTR神经营养蛋白结合蛋白的治疗应用
公开(公告)号：WO2016009222A1
公开(公告)日：2016-01-21
申请号：PCT/GB2015/052083
申请日：2015-07-17
申请人： LEVICEPT LIMITED
发明人： WESTBROOK, Simon
IPC分类号： A61K38/16 , A61P19/02 , C12N15/00 , C12N15/62 , C12N15/82
CPC分类号： C07K14/70571 , A61K38/1793 , A61K45/06 , A61K47/60 , A61K47/643 , A61K47/644 , C07K2319/30 , A61K2300/00
摘要： The present invention relates to a new therapeutic use of a p75NTR neurotrophin binding protein and related molecules in the treatment of osteoarthritis.
摘要翻译：本发明涉及p75NTR神经营养因子结合蛋白和相关分子在治疗骨关节炎中的新的治疗用途。

8. 发明申请

WO2015108912A1 TARGETED NANOCARRIERS FOR THE ADMINISTRATION OF IMMUNOSUPPRESSIVE AGENTS 审中-公开
标题翻译：用于管理免疫抑制剂的目标纳米颗粒
公开(公告)号：WO2015108912A1
公开(公告)日：2015-07-23
申请号：PCT/US2015/011310
申请日：2015-01-14
申请人： MUSC FOUNDATION FOR RESEARCH AND DEVELOPMENT
发明人： BROOME, Ann-Marie , DIXIT, Suraj , NADIG, Satish , ATKINSON, Carl
IPC分类号： A61K9/127 , A61K47/48
CPC分类号： A61K47/488 , A61K31/365 , A61K31/395 , A61K31/436 , A61K31/713 , A61K35/17 , A61K38/13 , A61K38/1793 , A61K38/2013 , A61K47/62 , A61K47/6909 , A61K2035/124 , C12N15/111 , C12N15/117 , C12N2310/14 , C12N2310/17 , C12N2320/32
摘要： Disclosed is a nanocarrier-containing immunosuppressive agent that is targeted to C3 breakdown products, integrin, or a combination thereof, to reduce the deleterious systemic effects of the immunosuppressive agent. Also disclosed is a method for suppressing an allo-immune response in a subject, such as one that can occur after an allograft transplantation.
摘要翻译：公开了一种靶向C3分解产物，整联蛋白或其组合的纳米载体免疫抑制剂，以减少免疫抑制剂的有害全身效应。还公开了抑制受试者中同种异体免疫应答的方法，例如可以在同种异体移植后发生的同种异体免疫应答。

9. 发明申请

WO2015103928A1 IL-15异源二聚体蛋白及其用途审中-公开
公开(公告)号：WO2015103928A1
公开(公告)日：2015-07-16
申请号：PCT/CN2014/094947
申请日：2014-12-25
申请人：上海恒瑞医药有限公司 , 江苏恒瑞医药股份有限公司
发明人：屈向东 , 叶鑫 , 袁纪军 , 张蕾 , 陈侃 , 张连山 , 曹国庆 , 许志宾 , 陶维康
IPC分类号： C07K19/00 , C12N15/62 , C12N15/63 , A61P35/00 , A61K38/20 , A61K39/395
CPC分类号： A61K38/2086 , A61K38/00 , A61K38/1793 , A61K45/06 , C07K14/5443 , C07K14/7155 , C07K2319/30
摘要：公开了一种IL-15异源二聚体蛋白及其用途。所述IL-15异源二聚体蛋白包含蛋白(Ⅰ)和蛋白(Ⅱ)，其中蛋白(Ⅰ)由IL-15或其变体和第一Fc变体重组而成；蛋白(Ⅱ)是第二Fc变体，或由IL-15Rα或其变体和第二Fc变体重组而成；第一Fc变体和第二Fc变体间以Knob-into-Hole形式连接。所述IL-15异源二聚体蛋白具有明显的抑瘤活性，比单一IL-15分子具有更好的生物活性及延长的体内半衰期。

10. 发明申请

WO2015031673A3 CNS-TARGETEDCONJUGATES OF ANTIBODIES 审中-公开
标题翻译：抗体的中枢神经系统药物
公开(公告)号：WO2015031673A3
公开(公告)日：2015-07-16
申请号：PCT/US2014053257
申请日：2014-08-28
申请人： BIOASIS TECHNOLOGIES INC
发明人： JEFFERIES WILFRED
IPC分类号： A61K47/48 , A61P35/00
CPC分类号： A61K47/483 , A61K38/1793 , A61K47/64 , A61K47/644
摘要： Provided are central nervous system (CNS)-targeted antibody or therapeutic Fc-fusion polypeptide conjugates having modified Fc regions, and related methods of use thereof, for instance, to facilitate delivery of therapeutic and/or diagnostic polypeptides across the blood-brain barrier (BBB), and thereby treat and/or diagnose conditions associated with the CNS, including cancer, pain, and various neuropathologies, such as neuroinflammatory, auto-immune, and/or neurodegenerative disorders.
摘要翻译：提供了具有修饰的Fc区的中枢神经系统（CNS）靶向抗体或治疗性Fc-融合多肽缀合物及其相关使用方法，例如促进治疗和/或诊断多肽跨越血脑屏障的递送（ BBB），从而治疗和/或诊断与CNS相关的病症，包括癌症，疼痛和各种神经病理学，例如神经炎症，自身免疫和/或神经变性疾病。

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